SlideShare a Scribd company logo
1 of 118
Rubric Detail
A rubric lists grading criteria that instructors use to evaluate
student work. Your instructor linked a rubric to this item and
made it available to you. Select Grid View or List View to
change the rubric's layout.
Content
https%3A%2F%2Fkeiseruniversity.blackboard.com%2Fwebapps
%2Frubric%2FWEB-
INF%2Fjsp%2Fcourse%2FrubricGradingPopup.jsp%3Fmode%3
Dgrid%26isPopup%3Dtrue%26rubricCount%3D1%26prefix%3D
_7714706_1%26course_id%3D_411476_1%26maxValue%3D10
0.0%26rubricId%3D_345993_1%26viewOnly%3Dtrue%26displa
yGrades%3Dfalse%26type%3Dgrading%26rubricAssoId%3D_60
5243_1
Name: Week 7 Video Presentation
Description: Up to 10% deduction may be implemented for not
following APA style standards (e.g., references and in-text
citations).
Grid ViewList View
Poor
Satisfactory
Good
Excellent
Introduction
Points:
Points Range:
0 (0.00%) - 10.35 (10.35%)
One of the following components are included in the
presentation: (1) Student introduces the article topic, tells the
reader what to expect. (2) rough background of literature (3)
Student describes significance of the problem, (4)researcher's
question(s) and hypothesis introduces the article topic, tells the
reader what to expect. Student describes significance of the
problem, researcher's hypothesis, and rough background of
literature.
Feedback:
Points:
Points Range:
10.5 (10.50%) - 11.85 (11.85%)
Two of the following components are included in the
presentation: (1) Student introduces the article topic, tells the
reader what to expect. (2) rough background of literature (3)
Student describes significance of the problem, (4)researcher's
question(s) and hypothesis what to expect. Student describes
significance of the problem, researcher's hypothesis, and rough
background of literature.
Feedback:
Points:
Points Range:
12 (12.00%) - 13.35 (13.35%)
Three of the following components are included in the
presentation: (1) Student introduces the article topic, tells the
reader what to expect. (2) rough background of literature (3)
Student describes significance of the problem, (4)researcher's
question(s) and hypothesis
Feedback:
Points:
Points Range:
13.5 (13.50%) - 15 (15.00%)
All of the following components are included in the
presentation: (1) Student introduces the article topic, tells the
reader what to expect. (2) rough background of literature (3)
Student describes significance of the problem, (4)researcher's
question(s) and hypothesis
Feedback:
Methods
Points:
Points Range:
0 (0.00%) - 10.35 (10.35%)
One of the following are demonstrated: (1) Student accurately
and thoroughly explains the research design, (2) includes
sampling, (3) identification and measurement of variables, (4)
procedures, and data collection.
Feedback:
Points:
Points Range:
10.5 (10.50%) - 11.85 (11.85%)
Two of the following are demonstrated: (1) Student accurately
and thoroughly explains the research design, (2) includes
sampling, (3) identification and measurement of variables, (4)
procedures, and data collection.
Feedback:
Points:
Points Range:
12 (12.00%) - 13.35 (13.35%)
Three of the following are demonstrated: (1) Student
accurately and thoroughly explains the research design, (2)
includes sampling, (3) identification and measurement of
variables, (4) procedures, and data collection.
Feedback:
Points:
Points Range:
13.5 (13.50%) - 15 (15.00%)
Four of the following are demonstrated: (1) Student accurately
and thoroughly explains the research design, (2) includes
sampling, (3) identification and measurement of variables, (4)
procedures, and data collection.
Feedback:
Results
Points:
Points Range:
0 (0.00%) - 10.35 (10.35%)
None of the following are
demonstrated: (1) the results
of the study are presented; (2)
the interpretation of results
are clearly and concisely
described (3) the connection to the researchers'
questions/hypotheses are made
Feedback:
Points:
Points Range:
10.5 (10.50%) - 11.85 (11.85%)
One of the following are
demonstrated: (1) the results
of the study are presented; (2)
the interpretation of results
are clearly and concisely
described (3) the connection to the researchers'
questions/hypotheses are made
Feedback:
Points:
Points Range:
12 (12.00%) - 13.35 (13.35%)
Two of the following are
demonstrated: (1) the results
of the study are presented; (2)
the interpretation of results
are clearly and concisely
described (3) the connection to the researchers'
questions/hypotheses are made
Feedback:
Points:
Points Range:
13.5 (13.50%) - 15 (15.00%)
Three of the following are
demonstrated: (1) the results
of the study are presented; (2)
the interpretation of results
are clearly and concisely
described (3) the connection to the researchers'
questions/hypotheses are made
Feedback:
Critique
Points:
Points Range:
0 (0.00%) - 13.8 (13.80%)
One of the following are
demonstrated: (1) Critique addresses strengths and
weaknesses of the study (2) Student applies higher-level
thinking skills about possible flaws in the study prior to making
recommendations (3) Critiques are have a clear connection to
the design of the study and information provided; (4)
generalizability of the study is discussed in a clear and logical
manner.
Feedback:
Points:
Points Range:
14 (14.00%) - 15.8 (15.80%)
Two of the following are
demonstrated: (1) Critique addresses strengths and
weaknesses of the study (2) Student applies higher-level
thinking skills about possible flaws in the study prior to making
recommendations (3) Critiques are have a clear connection to
the design of the study and information provided; (4)
generalizability of the study is discussed in a clear and logical
manner.
Feedback:
Points:
Points Range:
16 (16.00%) - 17.8 (17.80%)
Three of the following are
demonstrated: (1) Critique addresses strengths and
weaknesses of the study (2) Student applies higher-level
thinking skills about possible flaws in the study prior to making
recommendations (3) Critiques are have a clear connection to
the design of the study and information provided; (4)
generalizability of the study is discussed in a clear and logical
manner.
Feedback:
Points:
Points Range:
18 (18.00%) - 20 (20.00%)
Four of the following are
demonstrated: (1) Critique addresses strengths and
weaknesses of the study (2) Student applies higher-level
thinking skills about possible flaws in the study prior to making
recommendations (3) Critiques are have a clear connection to
the design of the study and information provided; (4)
generalizability of the study is discussed in a clear and logical
manner.
Feedback:
Creative Thinking
Points:
Points Range:
0 (0.00%) - 6.9 (6.90%)
Recommendations for future research does not include the
following: (1) understanding of research design (2) gaps or
flaws in the study reviewed (3) original thinking.
Feedback:
Points:
Points Range:
7 (7.00%) - 7.9 (7.90%)
Recommendations for future research demonstrates one of the
following: (1) understanding of research design (2) gaps or
flaws in the study reviewed (3) original thinking.
Feedback:
Points:
Points Range:
8 (8.00%) - 8.9 (8.90%)
Recommendations for future research demonstrates two of the
following: (1) understanding of research design (2) gaps or
flaws in the study reviewed (3) original thinking.
Feedback:
Points:
Points Range:
9 (9.00%) - 10 (10.00%)
Recommendations for future research demonstrates three of
the following: (1) understanding of research design (2) gaps or
flaws in the study reviewed (3) original thinking.
Feedback:
Organization
Points:
Points Range:
0 (0.00%) - 3.45 (3.45%)
Presentation is vague or uninteresting. Lacks supporting points
and related details. Information lacks connection to the
presentation topic. Information is not organized.
Feedback:
Points:
Points Range:
3.5 (3.50%) - 3.95 (3.95%)
Presentation is general, and at times uninteresting. Content is
not clear and lack significant detail. Some information is linked
to the presentation topic. Information is loosely organized.
Feedback:
Points:
Points Range:
4 (4.00%) - 4.45 (4.45%)
Presentation is general, but still interesting. Content is
somewhat clear but could use more detail. Most information is
linked to the presentation topic. Information is organized.
Feedback:
Points:
Points Range:
4.5 (4.50%) - 5 (5.00%)
Presentation is thorough and interesting. Content is very clear
and very detailed. Information is directly linked to presentation
topic. Information is very organized.
Feedback:
Verbal Communication
Points:
Points Range:
0 (0.00%) - 3.45 (3.45%)
Speaker's voice is consistently too weak or too strong. Speaker
fails to use inflections to emphasize key points and create
interest or speaker often uses inflections inappropriately.
Speaker's talking pace is consistently too slow or too fast.
Feedback:
Points:
Points Range:
3.5 (3.50%) - 3.95 (3.95%)
Speaker's voice is frequently too weak or too strong. Speaker
rarely uses inflections to emphasize key points and create
interest or speaker sometimes uses inflections inappropriately.
Speaker's talking pace is often too slow or too fast.
Feedback:
Points:
Points Range:
4 (4.00%) - 4.45 (4.45%)
Speaker's voice is generally steady, strong, and clear. Speaker
sometimes uses inflections to emphasize key points and create
interest. Speaker's talking pace is appropriate.
Feedback:
Points:
Points Range:
4.5 (4.50%) - 5 (5.00%)
Speaker's voice is very confident, steady, strong, and clear.
Speaker consistently uses inflections to emphasize key points or
to create interest. Speaker's talking pace is consistently
appropriate.
Feedback:
Mechanics
Points:
Points Range:
0 (0.00%) - 0 (0.00%)
Presentation is less than 11 minutes long.
Feedback:
Points:
Points Range:
3 (3.00%) - 3 (3.00%)
Presentation is 11-12 minutes long.
Feedback:
Points:
Points Range:
4 (4.00%) - 4 (4.00%)
Presentation is 13-14 minutes long.
Feedback:
Points:
Points Range:
5 (5.00%) - 5 (5.00%)
Presentation is at least 15 minutes long.
Feedback:
Article Submission
Points:
Points Range:
0 (0.00%) - 0 (0.00%)
Did not submit a full version of the article
Feedback:
Points:
Points Range:
0 (0.00%) - 0 (0.00%)
Feedback:
Points:
Points Range:
0 (0.00%) - 0 (0.00%)
Feedback:
Points:
Points Range:
5 (5.00%) - 5 (5.00%)
Submitted the a full version of the article
Feedback:
Visual Tools
Points:
Points Range:
0 (0.00%) - 3.45 (3.45%)
Visual aids demonstrate no creativity or clarity and are often
difficult to read. Contains numerous errors and lack of detail.
Little care taken in production. Presentation is weakened by the
visual tools.
Feedback:
Points:
Points Range:
3.5 (3.50%) - 3.95 (3.95%)
Visual aids have limited creativity or clarity or are sometimes
difficult to read. May have some errors and show some detail.
Some care has been taken in production. Presentation is not
enhanced by the visual tools.
Feedback:
Points:
Points Range:
4 (4.00%) - 4.45 (4.45%)
Visual aids are reasonably creative, clear, and easy to read.
Evident that presentation shows a general attention to detail and
accuracy. General care has been taken in production.
Presentation is sometimes enhanced by the visual tools.
Feedback:
Points:
Points Range:
4.5 (4.50%) - 5 (5.00%)
Visual aids are very creative, clear, and easy to read. Clearly
evident that presentation is well constructed, accurate, and
shows attention to detail. Extra care has been taken in the
production. Presentation is enhanced by the visual tools.
Feedback:
Show Descriptions
Show Feedback
Introduction--
Levels of Achievement:
Poor
0 (0.00%) - 10.35 (10.35%)
One of the following components are included in the
presentation: (1) Student introduces the article topic, tells the
reader what to expect. (2) rough background of literature (3)
Student describes significance of the problem, (4)researcher's
question(s) and hypothesis introduces the article topic, tells the
reader what to expect. Student describes significance of the
problem, researcher's hypothesis, and rough background of
literature.
Satisfactory
10.5 (10.50%) - 11.85 (11.85%)
Two of the following components are included in the
presentation: (1) Student introduces the article topic, tells the
reader what to expect. (2) rough background of literature (3)
Student describes significance of the problem, (4)researcher's
question(s) and hypothesis what to expect. Student describes
significance of the problem, researcher's hypothesis, and rough
background of literature.
Good
12 (12.00%) - 13.35 (13.35%)
Three of the following components are included in the
presentation: (1) Student introduces the article topic, tells the
reader what to expect. (2) rough background of literature (3)
Student describes significance of the problem, (4)researcher's
question(s) and hypothesis
Excellent
13.5 (13.50%) - 15 (15.00%)
All of the following components are included in the
presentation: (1) Student introduces the article topic, tells the
reader what to expect. (2) rough background of literature (3)
Student describes significance of the problem, (4)researcher's
question(s) and hypothesis
Feedback:
Methods--
Levels of Achievement:
Poor
0 (0.00%) - 10.35 (10.35%)
One of the following are demonstrated: (1) Student accurately
and thoroughly explains the research design, (2) includes
sampling, (3) identification and measurement of variables, (4)
procedures, and data collection.
Satisfactory
10.5 (10.50%) - 11.85 (11.85%)
Two of the following are demonstrated: (1) Student accurately
and thoroughly explains the research design, (2) includes
sampling, (3) identification and measurement of variables, (4)
procedures, and data collection.
Good
12 (12.00%) - 13.35 (13.35%)
Three of the following are demonstrated: (1) Student accurately
and thoroughly explains the research design, (2) includes
sampling, (3) identification and measurement of variables, (4)
procedures, and data collection.
Excellent
13.5 (13.50%) - 15 (15.00%)
Four of the following are demonstrated: (1) Student accurately
and thoroughly explains the research design, (2) includes
sampling, (3) identification and measurement of variables, (4)
procedures, and data collection.
Feedback:
Results--
Levels of Achievement:
Poor
0 (0.00%) - 10.35 (10.35%)
None of the following are
demonstrated: (1) the results
of the study are presented; (2)
the interpretation of results
are clearly and concisely
described (3) the connection to the researchers'
questions/hypotheses are made
Satisfactory
10.5 (10.50%) - 11.85 (11.85%)
One of the following are
demonstrated: (1) the results
of the study are presented; (2)
the interpretation of results
are clearly and concisely
described (3) the connection to the researchers'
questions/hypotheses are made
Good
12 (12.00%) - 13.35 (13.35%)
Two of the following are
demonstrated: (1) the results
of the study are presented; (2)
the interpretation of results
are clearly and concisely
described (3) the connection to the researchers'
questions/hypotheses are made
Excellent
13.5 (13.50%) - 15 (15.00%)
Three of the following are
demonstrated: (1) the results
of the study are presented; (2)
the interpretation of results
are clearly and concisely
described (3) the connection to the researchers'
questions/hypotheses are made
Feedback:
Critique--
Levels of Achievement:
Poor
0 (0.00%) - 13.8 (13.80%)
One of the following are
demonstrated: (1) Critique addresses strengths and
weaknesses of the study (2) Student applies higher-level
thinking skills about possible flaws in the study prior to making
recommendations (3) Critiques are have a clear connection to
the design of the study and information provided; (4)
generalizability of the study is discussed in a clear and logical
manner.
Satisfactory
14 (14.00%) - 15.8 (15.80%)
Two of the following are
demonstrated: (1) Critique addresses strengths and
weaknesses of the study (2) Student applies higher-level
thinking skills about possible flaws in the study prior to making
recommendations (3) Critiques are have a clear connection to
the design of the study and information provided; (4)
generalizability of the study is discussed in a clear and logical
manner.
Good
16 (16.00%) - 17.8 (17.80%)
Three of the following are
demonstrated: (1) Critique addresses strengths and
weaknesses of the study (2) Student applies higher-level
thinking skills about possible flaws in the study prior to making
recommendations (3) Critiques are have a clear connection to
the design of the study and information provided; (4)
generalizability of the study is discussed in a clear and logical
manner.
Excellent
18 (18.00%) - 20 (20.00%)
Four of the following are
demonstrated: (1) Critique addresses strengths and
weaknesses of the study (2) Student applies higher-level
thinking skills about possible flaws in the study prior to making
recommendations (3) Critiques are have a clear connection to
the design of the study and information provided; (4)
generalizability of the study is discussed in a clear and logical
manner.
Feedback:
Creative Thinking--
Levels of Achievement:
Poor
0 (0.00%) - 6.9 (6.90%)
Recommendations for future research does not include the
following: (1) understanding of research design (2) gaps or
flaws in the study reviewed (3) original thinking.
Satisfactory
7 (7.00%) - 7.9 (7.90%)
Recommendations for future research demonstrates one of the
following: (1) understanding of research design (2) gaps or
flaws in the study reviewed (3) original thinking.
Good
8 (8.00%) - 8.9 (8.90%)
Recommendations for future research demonstrates two of the
following: (1) understanding of research design (2) gaps or
flaws in the study reviewed (3) original thinking.
Excellent
9 (9.00%) - 10 (10.00%)
Recommendations for future research demonstrates three of the
following: (1) understanding of research design (2) gaps or
flaws in the study reviewed (3) original thinking.
Feedback:
Organization--
Levels of Achievement:
Poor
0 (0.00%) - 3.45 (3.45%)
Presentation is vague or uninteresting. Lacks supporting points
and related details. Information lacks connection to the
presentation topic. Information is not organized.
Satisfactory
3.5 (3.50%) - 3.95 (3.95%)
Presentation is general, and at times uninteresting. Content is
not clear and lack significant detail. Some information is linked
to the presentation topic. Information is loosely organized.
Good
4 (4.00%) - 4.45 (4.45%)
Presentation is general, but still interesting. Content is
somewhat clear but could use more detail. Most information is
linked to the presentation topic. Information is organized.
Excellent
4.5 (4.50%) - 5 (5.00%)
Presentation is thorough and interesting. Content is very clear
and very detailed. Information is directly linked to presentation
topic. Information is very organized.
Feedback:
Verbal Communication--
Levels of Achievement:
Poor
0 (0.00%) - 3.45 (3.45%)
Speaker's voice is consistently too weak or too strong. Speaker
fails to use inflections to emphasize key points and create
interest or speaker often uses inflections inappropriately.
Speaker's talking pace is consistently too slow or too fast.
Satisfactory
3.5 (3.50%) - 3.95 (3.95%)
Speaker's voice is frequently too weak or too strong. Speaker
rarely uses inflections to emphasize key points and create
interest or speaker sometimes uses inflections inappropriately.
Speaker's talking pace is often too slow or too fast.
Good
4 (4.00%) - 4.45 (4.45%)
Speaker's voice is generally steady, strong, and clear. Speaker
sometimes uses inflections to emphasize key points and create
interest. Speaker's talking pace is appropriate.
Excellent
4.5 (4.50%) - 5 (5.00%)
Speaker's voice is very confident, steady, strong, and clear.
Speaker consistently uses inflections to emphasize key points or
to create interest. Speaker's talking pace is consistently
appropriate.
Feedback:
Mechanics--
Levels of Achievement:
Poor
0 (0.00%) - 0 (0.00%)
Presentation is less than 11 minutes long.
Satisfactory
3 (3.00%) - 3 (3.00%)
Presentation is 11-12 minutes long.
Good
4 (4.00%) - 4 (4.00%)
Presentation is 13-14 minutes long.
Excellent
5 (5.00%) - 5 (5.00%)
Presentation is at least 15 minutes long.
Feedback:
Article Submission--
Levels of Achievement:
Poor
0 (0.00%) - 0 (0.00%)
Did not submit a full version of the article
Satisfactory
0 (0.00%) - 0 (0.00%)
Good
0 (0.00%) - 0 (0.00%)
Excellent
5 (5.00%) - 5 (5.00%)
Submitted the a full version of the article
Feedback:
Visual Tools--
Levels of Achievement:
Poor
0 (0.00%) - 3.45 (3.45%)
Visual aids demonstrate no creativity or clarity and are often
difficult to read. Contains numerous errors and lack of detail.
Little care taken in production. Presentation is weakened by the
visual tools.
Satisfactory
3.5 (3.50%) - 3.95 (3.95%)
Visual aids have limited creativity or clarity or are sometimes
difficult to read. May have some errors and show some detail.
Some care has been taken in production. Presentation is not
enhanced by the visual tools.
Good
4 (4.00%) - 4.45 (4.45%)
Visual aids are reasonably creative, clear, and easy to read.
Evident that presentation shows a general attention to detail and
accuracy. General care has been taken in production.
Presentation is sometimes enhanced by the visual tools.
Excellent
4.5 (4.50%) - 5 (5.00%)
Visual aids are very creative, clear, and easy to read. Clearly
evident that presentation is well constructed, accurate, and
shows attention to detail. Extra care has been taken in the
production. Presentation is enhanced by the visual tools.
Feedback:
Name:Week 7 Video Presentation
Description:Up to 10% deduction may be implemented for not
following APA style standards (e.g., references and in-text
citations).
Accepted Manuscript
Title: Brain alterations in children/adolescents with ADHD
revisited: a neuroimaging meta-analysis of 96 structural and
functional studies
Authors: Fateme Samea, Solmaz Soluki, Vahid Nejati,
Mojtaba Zarei, Samuele Cortese, Simon B. Eickhoff, Masoud
Tahmasian, Claudia R. Eickhoff
PII: S0149-7634(18)30662-6
DOI: https://doi.org/10.1016/j.neubiorev.2019.02.011
Reference: NBR 3351
To appear in:
Received date: 31 August 2018
Revised date: 21 January 2019
Accepted date: 16 February 2019
Please cite this article as: Samea F, Soluki S, Nejati V, Zarei M,
Cortese S,
Eickhoff SB, Tahmasian M, Eickhoff CR, Brain alterations in
children/adolescents
with ADHD revisited: a neuroimaging meta-analysis of 96
structural
and functional studies, Neuroscience and Biobehavioral
Reviews (2019),
https://doi.org/10.1016/j.neubiorev.2019.02.011
This is a PDF file of an unedited manuscript that has been
accepted for publication.
As a service to our customers we are providing this early
version of the manuscript.
The manuscript will undergo copyediting, typesetting, and
review of the resulting proof
before it is published in its final form. Please note that during
the production process
errors may be discovered which could affect the content, and all
legal disclaimers that
apply to the journal pertain.
https://doi.org/10.1016/j.neubiorev.2019.02.011
https://doi.org/10.1016/j.neubiorev.2019.02.011
1
Brain alterations in children/adolescents with ADHD revisited:
a neuroimaging meta-
analysis of 96 structural and functional studies
Fateme Samea1 M.Sc., Solmaz Soluki1 M.Sc., Vahid Nejati1,2≠
Ph.D., Mojtaba Zarei3 MD., Ph.D.,
Samuele Cortese4,5,6,7 M.D., Ph.D., Simon B. Eickhoff8,9
M.D., Masoud Tahmasian3*≠ M.D., Ph.D.,
Claudia R. Eickhoff9,10,11 M.D.
1 Institute for Cognitive and Brain Sciences, Shahid Beheshti
University, Tehran, Iran.
2 Department of Psychology, Shahid Beheshti University,
Tehran, Iran.
3 Institute of Medical Science and Technology, Shahid Beheshti
University, Tehran, Iran.
4 Center for Innovation in Mental Health, Academic Unit of
Psychology, University of Southampton,
Southampton, UK.
5 Faculty of Medicine, Clinical and Experimental Sciences
(CNS and Psychiatry), University of
Southampton, Southampton, UK.
6 Division of Psychiatry and Applied Psychology, School of
Medicine, University of Nottingham,
Nottingham, UK.
7 Department of Child and Adolescent Psychiatry, NYU
Langone Medical Center, New York, USA.
8 Institute for Systems Neuroscience, Medical Faculty,
Heinrich-Heine University Düsseldorf, Germany.
9 Institute of Neuroscience and Medicine (INM-1; INM-7),
Research Center Jülich, Jülich, Germany.
10 Institute of Clinical Neuroscience and Medical Psychology,
Heinrich Heine University Düsseldorf,
Düsseldorf, Germany.
11 Department of Psychiatry, Psychotherapy, and
Psychosomatics, RWTH Aachen University, Aachen,
Germany.
≠ V.N. & M.T. contributed equally to this study.
* Corresponding author: Masoud Tahmasian M.D., Ph.D.,
Institute of Medical Science and
Technology, Shahid Beheshti University, Daneshjou Boulevard,
Velenjak, P.O. Box
1983969411, Tehran, Iran. Telephone: +98-21-29905803; Fax:
+98-21-29902650;
Email: [email protected]
Running title: Brain alterations in children/adolescents with
ADHD
Count: Title (16), Abstract (168), Text (4787), References (49),
Figure (3), Table (1),
Supplement file (1).
Highlights
ACCEPTED M
ANUSCRIP
T
2
with Attention-
Deficit/Hyperactivity Disorder (ADHD), and those of meta-
analyses provide mixed
conclusions. Here, we conducted the largest meta-analysis
including both
structural and functional MRI, using state of the art procedures
and following
recently established consensus guidelines for neuroimaging
meta-analyses, to
address this inconsistency.
alterations in ADHD in
the main analysis. Among several different sub-analyses, we
only observed the
convergence dysfunction for task-fMRI experiments (using
neutral stimuli) in the
left pallidum/putamen and decreased activity (using male
subjects) in the left
inferior frontal gyrus.
brain alterations
across patients or a more distributed, network-based pathology
lacking a
consistent expression at any particular location, which might be
due to
heterogeneous clinical populations, in-/exclusion criteria,
various experimental
design, preprocessing, statistical procedures in individual
publications.
homogenous clinical
samples assessing regional structural and functional alterations,
as well as
connectivity in parallel to unravel the relation between
abnormal regional effects
and disturbed integration in children/adolescents with ADHD.
Abstract
The findings of neuroimaging studies in children/adolescents
with ADHD, and even those of previous
meta-analyses, are divergent. Here, Activation Likelihood
Estimation meta-analysis, following the current
best-practice guidelines, was conducted. We searched multiple
databases and traced the references up to
June 2018. Then, we extracted the reported coordinates
reflecting group comparison between ADHD and
healthy subjects from 96 eligible studies, containing 1914
unique participants. The analysis of pooled
ACCEPTED M
ANUSCRIP
T
3
structural and functional, sub-analyses restricted to modality,
and in-/decreased contrast did not yield any
significant findings. However, further sub-analyses in the task-
fMRI experiments (neutral stimuli only) led
to aberrant activity in the left pallidum/putamen and decreased
activity (male subjects only) in the left
inferior frontal gyrus. The overall findings indicate a lack of
regional convergence in children/adolescents
with ADHD, which might be due to heterogeneous clinical
populations, various experimental design,
preprocessing, statistical procedures in individual publications.
Our results highlight the need for further
high-powered investigations, but may also indicate ADHD
pathophysiology might rest in network
interactions rather than just regional abnormality.
Key words: ADHD; Activation likelihood estimation;
Coordinate-based meta-analysis; fMRI;
VBM.
ACCEPTED M
ANUSCRIP
T
4
1. Introduction
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent
neurodevelopmental condition characterized by
age-inappropriate and impairing inattention and/or
impulsiveness-hyperactivity based on Diagnostic and
Statistical Manual of Mental Disorders, fifth edition (DSM-5)
and International Classification of Diseases (ICD-
10)(American Psychiatric Association, 2013). ADHD is
commonly associated with school/academic,
occupational, and social dysfunction (Biederman, 2005; Caye et
al., 2016). Furthermore, deficit in several
cognitive domains has been demonstrated in individuals with
ADHD by neuropsychological studies (Sonuga-
Barke et al., 2010) In addition to neuropsychological, genetics
and neurochemical studies investigating the
pathophysiology of ADHD (Caye et al., 2016), a large number
of neuroimaging studies have been published
over the last three decades to elucidate potential structural or
functional alterations of ADHD (Hoogman et al.,
2017; Konrad and Eickhoff, 2010). However, their findings are
often inconsistent or conflicting. Hence, based
on these individual studies, the neural correlates of ADHD
remain elusive.
Coordinate based meta-analysis (CBMA) of neuroimaging
experiments can overcome these issues by
providing a synoptic view of findings across studies, hereby
consolidating the existing literature (Eickhoff et al.,
2012; Turkeltaub et al., 2002). CBMA uses the reported peak
coordinates to identify “if” and “where” the
convergence between reported coordinates is higher than
expected by chance (Eickhoff et al., 2012). Previous
meta-analyses on neuroimaging studies in ADHD have focused
on structural imaging (Ellison-Wright et al.,
2008; Frodl and Skokauskas, 2012; Nakao et al., 2011; Valera et
al., 2007) or task-based functional imaging
only (Cortese et al., 2012; Dickstein et al., 2006; Hart et al.,
2012; Hart et al., 2013; Lei et al., 2015; McCarthy
et al., 2014) (Supplemental Table S1). In addition of being
outdated, however, they also yielded inconsistent
findings. Meta-analyses of structural imaging studies suggested
regional gray matter volume reductions in
various cortical regions and also the basal ganglia and
cerebellum, but showed limited agreement across
analyses (Ellison-Wright et al., 2008; Frodl and Skokauskas,
2012; Nakao et al., 2011; Valera et al., 2007).
Likewise, meta-analyses of activation studies heterogeneously
indicated aberrations in a wide number of
regions covering different cerebral lobes and systems as well as
the basal ganglia, thalamus and cerebellum
(Cortese et al., 2012; Dickstein et al., 2006; Hart et al., 2012;
Hart et al., 2013; Lei et al., 2015; McCarthy et al.,
2014).
Divergence across previous meta-analyses may in part reflects
rather low number of included studies,
ACCEPTED M
ANUSCRIP
T
5
different in-/exclusion criteria, (too) liberal statistical
thresholding in search for positive findings (Muller et al.,
2018; Tahmasian M, 2018). Moreover, heterogeneity in the
examined hypotheses, the assessed clinical
populations (e.g. subtype or severity of patients), the applied
statistical approaches, and last but not least,
different practices in reporting negative findings related to the
included individual studies are important factors
too (Muller et al., 2018; Tahmasian M, 2018). To address the
heterogeneity and statistical power issues of the
previous meta-analyses, we conducted a large scale structural
and functional meta-analysis, following recently
established consensus guidelines for neuroimaging meta-
analyses suggested by the developers of all major
software packages (Muller et al., 2018). The current meta-
analysis is based on the largest number of original
ADHD findings, strict adherence to best-practice protocols and
stringent thresholding. The first aim of the
current study was to find spatially consistent brain
abnormalities in patients with ADHD compared to healthy
comparisons. Hence, we pooled all the structural and functional
studies, to provide a comprehensive overview
of grey matter and functional alterations in ADHD. This
approach has been applied previously to other
neuropsychiatric disorder (Radua et al., 2012; Raschle et al.,
2015; Sacher et al., 2012; Tahmasian et al.,
2016; Tahmasian M, 2018; Zakzanis et al., 2003). Moreover,
with regard to heterogeneity issues, we
conducted several sub-analyses, clustered by extracted factors
representing potential heterogeneity sources
(i.e. modality, medication status, gender or behavioral subtype
ADHD patients as well as specific cognitive
domains and stimuli type of the tasks used in task-fMRI
studies). By revisiting the issue of neuroimaging
findings in ADHD, we thus aim to settle the ongoing dispute on
the presence and localization of structural
and/or functional brain alterations in children and adolescents
with ADHD.
2. Methods
2.1. Search strategy and selection criteria
Based on the Preferred Reporting Items for Systematic Reviews
and Meta-Analyses(Moher et al.) and
current consensus guidelines for neuroimaging meta-analyses
(Muller et al., 2018), we searched PubMed,
OVID (EMBASE, ERIC and Medline), Web of Knowledge,and
Scopus up to June 1,2018,for neuroimaging
studies on ADHD using the following search terms: (ADHD OR
attention-deficit hyperactivity disorder)
AND ("functional magnetic resonance imaging" OR fMRI OR
"voxel-based morphometry" OR VBM) AND
(children OR adolescents). In addition, we identified further
papers by reference tracing and consulting
ACCEPTED M
ANUSCRIP
T
6
review articles. Next, two authors (FS and SS) independently
screened all the identified abstracts. Case-
reports, letters to editors, reviews, meta-analyses,
methodological studies and reports based on < 10
subjects per group were excluded as suggested previously
(Muller et al., 2018; Tahmasian et al., 2017;
Tahmasian et al., 2016). Furthermore, we excluded all studies
using region of interest (ROI) analysis, as
the null distribution in CBMA reflects a random spatial
association between findings across the entire
brain. The assumption that each voxel has a priori the same
chance for being reported, however, is
violated by ROI analyses, creating a sizable bias and inflated
significance for the respective regions
(Muller et al., 2018; Muller et al., 2017).
Diagnosis of ADHD patients in the included papers had to be
based on DSM-IV-TR, or DSM-5, or
ICD-10 criteria. The other criteria include the mean age < 18
year old, no neurological or psychiatric
comorbidities (such as depression, anxiety, autism, learning
disorder, and epilepsy) or IQ > 70. We only
included the experiments performing a group comparison
between patients with ADHD and healthy
controls (i.e., no within-group contrasts or contrasts of patients
with ADHD versus patients with other
disorders). We did not exclude reports on medicated ADHD
patients in order to reflect the fact that these
represent the bulk of the current literature. However, all
included patients were off-medicated during the
image acquisition. As suggested (Muller et al., 2018; Muller et
al., 2017), studies reporting the effects of
pharmacologic or psychological treatment were only included in
case the authors reported between-group
differences at baseline or main effects of diagnosis.
2.2. Organization of Coordinates
Extracted data included bibliographic information, age, gender
& number of subjects, imaging modality,
subtype and medication status of patients with ADHD, and the
peak coordinates of group comparisons in
Montreal Neurological Institute (MNI) (A.C. Evans, 1993) or
Talairach (Talairach and Tournoux, 1988)
space with the latter being subsequently transformed into MNI
space.(Lancaster et al., 2007) Of note, in
neuroimaging meta-analyses, “study” refers to a single
scientific publication while “experiment” denotes a
particular comparison, i.e., a contrast yielding a distinct set of
coordinates.
Given that the samples of several studies (partially) overlapped,
including such experiments may
yield spurious convergence. Thus, we followed the
recommended approach to organize data by subjects
ACCEPTED M
ANUSCRIP
T
7
rather than experiments, avoiding undue influence of a patient
cohort (Turkeltaub et al., 2012).
Specifically, we combined experiments in the same direction
(in-/decreases) for a given set of patients,
yielding a maximum of two “experiments” per sample
consisting of all extracted coordinates for this set of
patients (i.e., one for ADHD > Control contrast, one for Control
> ADHD contrast). Of note, the
experiments were merged regardless of whether separate
experiments were reported in one or different
papers whenever identity of the subjects could be established
(Turkeltaub et al., 2012).
2.3. Activation likelihood estimation
We used the revised version of the Activation Likelihood
Estimation (ALE) algorithm (Eickhoff et al., 2012)
to test significant convergence between activation foci relative
to a null-hypothesis of random spatial
association between experiments. Firstly, the reported foci were
modeled as center peaks of 3D Gaussian
probability distributions representing the spatial uncertainty
associated with these arising from both
sampling effects and methodological differences in data
processing and analysis. Importantly, the
modeled uncertainty is scaled by the number of subjects in the
smaller group to accommodate higher
uncertainty of findings from smaller samples. The ensuing per-
experiment “modeled activation” maps were
then combined into an ALE map by computing their union
across experiments (Eickhoff et al., 2012;
Turkeltaub et al., 2012). Subsequently, an analytical approach
based on non-linear histogram integration
was conducted to test against the null hypothesis of random
spatial association (Eickhoff et al., 2012;
Turkeltaub et al., 2012), followed by cluster-level family-wise
error (cFWE) correction at p < 0.05 (cluster-
forming threshold of p < 0·001 on the voxel level) based on
Monte-Carlo simulation (Eickhoff et al., 2017;
Muller et al., 2018).
2.4. Performed analyses
We first performed an ALE analysis across all identified
experiments in order to probe for abnormalities
independently of direction and neuroimaging modality. Next,
we performed three separate sets of
analyses assessing increases, decreases or aberrations (pooling
in-/decreases) in structural (VBM) and
functional (fMRI) imaging, respectively. As recommended,
separate analyses were performed only for
those combinations of direction and modality yielding at least
17 experiments, given consideration on
ACCEPTED M
ANUSCRIP
T
8
robustness and power (Eickhoff et al., 2016). Hence, specific
analysis of rs-fMRI studies was not possible
due to low number of experiments. Relatedly, we also split the
available experiments by medication
status, gender or behavioral subtype ADHD patients, noting that
the number of experiments for female
patients as well as isolated inattentive or hyperactive subtypes
was insufficient for analysis.
Furthermore, we probed for convergence among task-fMRI
studies when focusing only on specific
cognitive domains and found a sufficient number of experiments
(i.e., > 17) (Eickhoff et al., 2016) for
inhibitory and attention, but also performed a joint analyses on
the remaining cognitive tasks (memory,
timing, reasoning). Number of experiments on reward
processing tasks, were not sufficient to analyze.
Finally, the available studies were also categorized by stimulus
type (emotion, reward, neutral), but only
field a sufficient number for a sub-analysis of neutral stimuli.
Finally, for significant convergent findings, related to
subgroups of experiments e.g. subgroup of all
fMRI experiments representing male only, we checked the
number of studies, contributed to the
convergent cluster. The question was whether the contribution
rate represents the proportion of all related
experiments in the database. For example, if X out of P fMRI
experiments with mail only contribute to a
convergent cluster, we evaluated that how likely it is that, this
contribution rate represent proportion of P
fMRI experiments across all available experiments (96) in the
database. We tested this for each significant
finding separately, using binomial test in SPSS (v22). Wherever
the contribution rate of a subgroup of
experiments represents the proportion of their experiments
across all experiments in the database, one
could infer that the convergent finding may be driven by the
effects of main indicator (e.g. male only) of the
subgroup.
Results
From a pool of 1586 retrieved publications, 205 potentially
eligible studies were identified. Among them,
109 were subsequently excluded due to reasons including ROI
analyses, no reported contrast between
ADHD and healthy subjects, or reporting of longitudinal effects
without baseline. In case the study met all
the criteria except reporting the peak coordinates for group
comparisons, we contacted the authors to
obtain the relevant information. In total, 96 studies were finally
eligible for the current meta-analyses
(Figure 1, Supplemental Table S2) reporting a total of 130
individual experiments (92 task-fMRI, 32 VBM
ACCEPTED M
ANUSCRIP
T
9
and 6 rs-fMRI; Supplement) based on 1914 unique subjects. Of
these, 62.7% reported decreases in
ADHD patients compared to controls (54 task-fMRI, 25 VBM
and 3 rs-fMRI; Supplement).
2.5. Meta-analyses of neuroimaging findings in ADHD
Overall, we conducted several separate ALE meta-analyses.
When pooling in-/decreases experiments
(Figure 2), the results yielded p= 0.129 (across structural and
functional findings), p= 0.452 (for VBM
only), and p= 0.212 (for fMRI, pooling across task and resting
state). Also a restriction to task-fMRI
experiments did not provide a significance finding (p= 0.062).
Similarly, restricting meta-analyses to in-
/decreases in ADHD, lead to non-significant findings
(decreased: all p= 0.195, VBM p= 0.341, fMRI p=
0.138, task-fMRI only p= 0.329; increased: all p= 0.175; fMRI
p= 0.153, task-fMRI p= 0.668; Table 1A). Of
note, repeating all analyses with an alternative, potentially more
liberal statistical threshold (i.e., threshold-
free cluster enhancement, TFCE (Smith and Nichols, 2009)),
fully corroborated these results and likewise
reveal non-significant convergence (Table 1A).
2.6. Follow-up sub-analyses on task fMRI findings
Of the 68 task-fMRI studies, 33% investigated inhibitory
control, 29% attention, 25% other cognitive
domains and 13% reward processing (Supplement). With respect
to stimulus type, 70% used neutral, 12%
emotional and 17% rewarding stimuli (Supplement). Again, no
significant convergence (Table 1B) was
found in any of the more restricted and hence specific sub-
analyses for which a sufficient number of
experiments was available (inhibitory control p= 0.302,
attention p= 0.847, all other cognitive domains p=
0.520), even though we noted a trend towards significance when
specifically analyzing the convergence of
decreased activity for inhibitory control (p= 0.052). Repeating
all analyses with TFCE threshold, the latter
result did pass statistical significance at p= 0.040 (Table 1B).
We also conducted separate analyses on in-/decreases and their
pooled effect for only those experiments
using neutral stimuli and found significant aberrant convergence
in the left pallidum/putamen (local
maximum: -18, 4, -4 in MNI space, 109 voxels, 69.7% left
Pallidum, 12.7% left Putamen) when looking at
ACCEPTED M
ANUSCRIP
T
10
the pooled in-/decreased activation experiments in ADHD (p=
0.036), but not for either direction
individually (decrease p= 0.244, increase p= 0.110 (Figure 3A,
Table 1C).
Finally, we also repeated all main and follow-up analyses
including only medication-naïve, male or
combined-type ADHD patients, respectively, yielding a single
(marginally significant) convergence for
decreased fMRI (task-fMRI and rs-fMRI) in male subjects on
the left inferior frontal gyrus (IFG) (local
maximum: -38, 26, -16 in MNI space, 93 voxels, 83% in frontal
orbital cortex) (p=0.049, Figure 3B,
Supplement). Moreover, we used binomial test on the
contribution-rate (i.e. 0.13 (4 out of 30) of
decreased fMRI experiments with male only and their main
proportion in the database (i.e.52% (30 out of
57 decreased fMRI experiments). The result indicated that
observed contribution-rate significantly is less
than the chance probability (observed-prob= 0.13, test-prob=
0.52, p-value= 0.001). Regarding the left
Putamen-Pallidum, 11 out of 41 task-fMRI experiments with
neutral stimuli, contributed to this convergent
finding, while the proportion of task-fMRI experiments with
neutral stimuli in the database was 0.44 (41out
of 92 task-fMRI experiments). The result of binomial test was
not significant (observed-prob= 0.37, test-
prob= 0.44, p-value= 0.268).
Discussion
The current study provides the largest and most comprehensive
meta-analytic summary of neuroimaging
findings in children and adolescents with ADHD across several
imaging modalities, following the current
best-practice recommendations (Muller et al., 2018). The pooled
structural and functional assessment and
the additional sub-analyses focusing on homogeneous subsets of
experiments (in terms of modality and
direction) yielded no significant convergence across the
available ADHD literature. Reasons of this
heterogeneity may be accounted for several issues including
clinical heterogeneity and variations in
experimental design and analysis. We discuss further this
heterogeneity in the next section. Moreover, we
also restricted all the experiments by medication-status, gender,
ADHD sub-types, as well as task-fMRI by
specific cognitive domains and stimulus types, and observed
convergence aberrant finding in the task-
ACCEPTED M
ANUSCRIP
T
11
fMRI experiments (using neutral stimuli) in the left
pallidum/putamen and decreased activity (in male
subjects only) in the left IFG. Dysfunction of the
pallidum/putamen and IFG has been reported in ADHD
previously (Castellanos and Proal, 2012; Cortese et al., 2012;
Hart et al., 2012; Hart et al., 2013; Konrad
and Eickhoff, 2010; Rubia, 2011), which is in line with the
fronto-striatal pathway dysfunction model of
ADHD. The dopamine-rich ventral putamen receives fibers from
the medial orbitofrontal cortex and IFG
and it has been shown that their abnormality is linked with
hyperactivity, impulsivity, disinhibition, and
inattention symptoms of ADHD (Itami and Uno, 2002; Max et
al., 2002; Rubia, 2011).
2.7. Neuroimaging in ADHD: A heterogeneous field
The heterogeneity in experimental design and procedure across
the task-based fMRI experiments, which
containing 70% of our included studies, might be one of the
potential sources of inconsistent results. Most
available tasks were often aimed at probing various functional
impairments in children/adolescents with
ADHD (Arnsten and Rubia, 2012). The paradigms of included
tasks varied widely (i.e. Go/No-Go, Stroop,
Stop signal, timing, reward processing, memory and attention
tasks), but each of them applied in less than
10 studies. In addition to the paradigm diversity, there is
flexibility in each paradigm regarding to the type
of stimuli, presentation of stimuli and type of trials. Due to
these inconsistencies, the cognitive operations
performed by the subjects when engaging in the respective tasks
should vary widely. From the overall
inconsistent results of the current study, we conclude that there
is limited convergent regional abnormality
that was tapped into by the structural and functional
experiments that have been used to study ADHD, to
date. Additionally, across cognitive domains, there is no
convergence in the neurobiological aberrations
underlying ADHD. Worthy of note, in the structural imaging
studies (i.e. VBM), experimental or design
flexibility is absent, but analytical heterogeneity still plays a
major role (e.g., various statistical thresholds
or spatial transformation of the images). Finally, the included
rs-fMRI analytical approaches were likewise
vastly different. This methodological multiplicity may have
contributed a lot of variance to the current
literature beyond what could already be expected given the
heterogeneity of the clinical presentation in
ADHD.
Our divergent results on structural and functional experiments
support the view that ADHD is a
multi-faceted disorder, which affects several functional and
behavioral domains. We would hence side with
ACCEPTED M
ANUSCRIP
T
12
the hypothesis, that ADHD may be primarily reflecting a
dysconnectivity disorder, i.e., that the various
cognitive and affective affections in ADHD patients may stem
from impaired communication and
integration between the brain regions/networks rather than from
regional abnormalities only (Castellanos
and Proal, 2012; Konrad and Eickhoff, 2010). Of note, here we
could not test the network alterations due
to low number of available rs-fMRI experiment. Also, as
recommended, we did not include the ROI-based
functional connectivity publications (Muller et al., 2018). In
particular, such distributed network pathology
would explain both the lack of convergence in either structural
or functional imaging findings, as well as
the heterogeneous expression of the core and associated
symptoms across patients. The latter is
particularly important, as ADHD is clinically described as a
heterogeneous disorder, which includes
impairment on several cognitive and emotional domains
(Wahlstedt et al., 2009). These deficits have
differential influence on neuropsychological functioning of
patients and lead to various clinical
presentations (Wahlstedt et al., 2009). Although ADHD is often
classified into three different presentations,
they have considerable overlap (Wahlstedt et al., 2009). A
recent neuroimaging study also found no
common brain abnormalities in all ADHD subgroups, suggesting
that ADHD is a collection of discrete
disorders (Stevens et al., 2018). It is worth mentioning that
most of the included studies either recruited
patients from different presentations or did not specify the
clinical presentation of ADHD that was
investigated, even though diagnostic validity of such
presentation classification is questionable per se
(Bernfeld, 2012). Moreover, most studies retained in the present
meta-analysis included participants with
high rates of comorbidities, which increases the clinical
heterogeneity of the samples (Elia et al., 2008).
Thus, even though all patients were labeled as ADHD, they may
have presented quite differently, both
within each and across samples, potentially featuring different
underlying pathologies and hereby further
contributing to the lack of convergence using combination of
structural and functional experiments. We
discuss now key methodological issue form the body of research
that we included.
2.8. Methodological issues
A main advantage of the ALE meta-analysis approach is
integration of a large number of findings to
establish consensus on the spatial locations of regional
disruptions in neuropsychiatric disorders (Eickhoff
et al., 2012; Goodkind et al., 2015; Muller et al., 2017;
Tahmasian et al., 2017; Tahmasian et al., 2018;
ACCEPTED M
ANUSCRIP
T
13
Tahmasian et al., 2016). Thus, ALE allows synthesizing the
multitude of single studies in an unbiased
fashion and consolidates the available literature, overcoming
problems associated with individual
neuroimaging experiments (Eickhoff et al., 2012; Muller et al.,
2018). Here, we followed the recently
developed best-practice protocols of neuroimaging meta-
analysis (Muller et al., 2018). In particular, we
performed multiple-comparison correction using the cluster-
level FWE correction, which should be
preferred over the liberal but previously popular false discovery
rate (FDR) to provide maximum statistical
rigor (Eickhoff et al., 2017; Eickhoff et al., 2016).
In addition, it has been suggested to include at least 17
experiments into an ALE meta-analysis to
achieve 80% power for at least moderate to strong effects
(Eickhoff et al., 2016). To explore the potential
moderators that might influence on our results, we first
identified all eligible experiments and
subsequently, categorized them by available variety sources
including imaging modality, medication
status, gender or behavioral subtype ADHD patients. However,
the number of experiments of most of the
categories (including rs-fMRI, as well as female patients and
isolated inattentive or hyperactive subtypes)
were insufficient for a valid analysis. Given that ALE analyses
with very few sets of experiments have
been shown to be unstable and potentially driven by individual
studies, we could not perform the initially
planned set of assessments for the effects of most potential
moderators. Indeed, exploring moderators is
not feasible unless each subgroup yields enough experiments for
a separate meta-analysis. Furthermore,
by splitting the task-fMRI experiments with specific cognitive
domains and also stimulus type of the tasks,
the issue was the same, as sufficient number of experiments
were not supplied for all subgroups.
Accordingly, we could only perform separate meta-analyses for
individual subgroups of experiments,
categorized by inhibitory, attention, and also joint of the
remaining cognitive tasks (memory, timing, and
reasoning), as well as neutral stimuli, to probe for convergent
functional abnormalities in children and
adolescents with ADHD. However, the results were significant
only for two subgroups of experiments, i.e
task-fMRI experiments with neutral stimuli and decreased fMRI
experiments with male only. According to
the result of binomial test for neutral stimuli experiments, the
contribution-rate of experiments represents
the main proportion of the experiments with neutral stimuli in
the database. Hence, the convergent finding
of task-fMRI experiments may be driven by the effects of using
tasks with neutral stimuli. Moreover,
regarding the decreased fMRI experiments with male only, the
result of the binomial test indicated that
ACCEPTED M
ANUSCRIP
T
14
observed contribution-rate significantly is less than the chance
probability. Hence, the contribution-rate of
experiments with male only is likely an under-representation of
the expected proportion in the database.
Moreover, we carefully excluded studies with ROI analysis to
avoid inflating significance for the
particular regions (Muller et al., 2018). Importantly, we
organized our dataset based on the recommended
approach, which has been introduced to minimize within-group
effects (Turkeltaub et al., 2012) We
discuss now our findings in the light of previous ADHD meta-
analyses.
2.9. Divergence of previous mega- and meta-analyses findings
Previous ADHD meta-analyses focusing on structural imaging
(Ellison-Wright et al., 2008; Frodl and
Skokauskas, 2012; Nakao et al., 2011; Valera et al., 2007) and
task-based fMRI (Cortese et al., 2012;
Dickstein et al., 2006; Hart et al., 2012; Hart et al., 2013; Lei et
al., 2015; McCarthy et al., 2014) found
significant brain abnormalities in variety of brain regions
(Supplemental Table S1). Hence, not only
individual studies, but also previous meta-analyses in
children/adolescents with ADHD have yielded
inconsistent findings. This might be due to the fact that those
meta-analyses were not following the current
best-practice guideline, which is developed recently (Muller et
al., 2018). Results of such meta-analyses
may be in part driven by small sample size, liberal thresholding
and other methodological choices that
should be considered non-optimal currently. For example, three
meta-analyses on task fMRI (Cortese et
al., 2012; Dickstein et al., 2006; Lei et al., 2015) and one on
VBM studies (Ellison-Wright et al., 2008)
used a version of GingerALE, which was later discovered to
have a bug leading to inadequately liberal
thresholds that were substantially different from the requested
level and did not control for multiple
comparisons (Eickhoff et al., 2017). In turn, two fMRI meta-
analyses focusing on timing (Hart et al., 2012)
and inhibition/attention (Hart et al., 2013), as well as two VBM
meta-analyses applied the Signed
Differential Mapping (SDM) method (Frodl and Skokauskas,
2012; Nakao et al., 2011), which by design
are being more liberal, i.e., to err on the side of false positives
rather than negatives. Last but not least,
previous meta-analyses assessed substantially smaller samples
of experiments, which entail a high
likelihood (formally) significant convergence might be often
driven by few experiments and dominates the
regional effects of those studies (Muller et al., 2018). Given the
current growth of the literature, however,
we were able to apply more stringent in-/exclusion criteria and
still analyze an unprecedentedly large
ACCEPTED M
ANUSCRIP
T
15
number of individual experiments. Our included studies are
overlapping with those of previous meta-
analyses in various degrees. We excluded the ones that did not
meet our inclusion criteria (Supplemental
Table S1).
Although there are many available CBMA with significant
consistent results in various
neuropsychiatric disorders (Cortese et al., 2016; Cortese et al.,
2012; Goodkind et al., 2015; Herz et al.,
2014; Radua et al., 2012; Tahmasian et al., 2017; Tahmasian et
al., 2016; Wegbreit et al., 2014) , some
previous meta-analyses in unipolar depression (Muller et al.,
2017) and insomnia disorder (Tahmasian et
al., 2018; Tahmasian M, 2018) investigated a large body of
literature and followed the best-practice
guideline (i.e. rigorous in-/exclusion criteria and statistical
threshold), but still observed a lack of
convergence across their sub-analyses. The authors suggested
that small samples of participants, clinical
variability, various experimental design, flexibility in
preprocessing, and statistical approaches could be the
possible reasons of observed heterogeneity in such disorder
(Muller et al., 2017; Tahmasian et al., 2018).
Recently, a study comprising 1713 participants with ADHD and
1529 controls from 23
sites applied FreeSurfer and found that volume of the
accumbens, amygdala, caudate, hippocampus,
putamen, and intracranial volume were smaller in subjects with
ADHD compared with controls (9). We did
not include this paper, as they focused on particular subcortical
ROIs, which could affect the whole brain
results. In the present study, we included 28 structural
experiments which yielded no significant volume
alterations. Of note, the mentioned study has a unified analysis
protocol and therefore has less
experimental and analytical noise and hence is more likely to
find the regional abnormality. However, it is
not clear whether the findings are just reflecting their particular
regional choices or are robust across
studies, which can be tested by neuroimaging meta-analyses.
2.10. Future directions
Technical problems and clinical heterogeneity aside, we would
argue that one of the major obstacles in
neuroimaging research is the strong bias towards publishing
positive results, combined with low sample
size and high preprocessing and analytical flexibility (garden of
forking paths) in (f)MRI analyses. It stands
to reason that this combination provides the wrong incentives to
analyze data in various ways until
significant results emerge, which are often spurious and not
replicable or convergent. Coupled with the
ACCEPTED M
ANUSCRIP
T
16
fact that direct replication studies are still rare, we would thus
worry that a large body of the imaging
literature contains inflated reports of regional effects which
only becomes apparent once well-powered and
robust (through their size) meta-analyses as the current are
performed. To us, this indicates a need for
change at several levels including higher-powered original
studies, homogenous clinical populations, pre-
registration of analysis plans, a better standardization of
processing pipelines (also from the level of
replicability), large scale open data sharing, and maybe most
importantly a cultural shift away from the
current bias towards more likely publication of positive findings
as well-powered inconsistent findings may
be as important to move the entire field forward.
3. Conclusion
To the best of our knowledge, this study is the largest meta-
analysis of structural and functional
neuroimaging experiments in children/adolescents with ADHD.
We found no significant convergent across
structural and functional regional alterations in ADHD, which
might be attributable to clinical heterogeneity,
experimental and analytical flexibility and positive publication
bias, but could also point towards a more
distributed, network-based pathology lacking a consistent
expression at any particular location. Among
many different sub-analyses, we only observed the convergence
dysfunction for task-fMRI experiments
(using neutral stimuli) in the left pallidum/putamen and
decreased activity (using male subjects) in the left
IFG. This study highlights the need for further exploration
assessing regional structural and functional
maladaptation, as well as connectivity in parallel to unravel the
relation between abnormal regional effects
and disturbed integration in ADHD.
Conflict of interest
The authors declare that the research was conducted in the
absence of any commercial or financial
relationships that could be construed as a potential conflict of
interest.
Acknowledgements
SBE is supported by the Deutsche Forschungsgemeinschaft DFG
(EI 816/11-1), the National Institute of
Mental Health (R01-MH074457), the Helmholtz Portfolio
Theme "Supercomputing and Modeling for the
ACCEPTED M
ANUSCRIP
T
17
Human Brain" and the European Union’s Horizon 2020
Research and Innovation Programme under Grant
Agreement No. 785907 (HBP SGA2).
ACCEPTED M
ANUSCRIP
T
18
References
A.C. Evans, D.L.C., S.R Mills, E.D. Brown, R.L. Kelly, T.M.
Peters, 1993. 3D statistical neuroanatomical models
from 305 MRI volumes. Nuclear Science Symposium and
Medical Imaging Conference, IEEE Conference
Record, 1813–1817.
American Psychiatric Association, 2013. Diagnostic and
Statistical Manual of Mental Disorders, 5th ed,
Washington, DC.
Arnsten, A.F., Rubia, K., 2012. Neurobiological circuits
regulating attention, cognitive control, motivation, and
emotion: disruptions in neurodevelopmental psychiatric
disorders. J Am Acad Child Adolesc Psychiatry 51,
356-367.
Bernfeld, J., 2012. ADHD and factor analysis: are there really
three distinct subtypes of ADHD? Appl
Neuropsychol Child 1, 100-104.
Biederman, J., 2005. Attention-deficit/hyperactivity disorder: a
selective overview. Biol Psychiatry 57, 1215-
1220.
Castellanos, F.X., Proal, E., 2012. Large-scale brain systems in
ADHD: beyond the prefrontal-striatal model.
Trends Cogn Sci 16, 17-26.
Caye, A., Rocha, T.B., Anselmi, L., Murray, J., Menezes, A.M.,
Barros, F.C., Goncalves, H., Wehrmeister, F., Jensen,
C.M., Steinhausen, H.C., Swanson, J.M., Kieling, C., Rohde,
L.A., 2016. Attention-Deficit/Hyperactivity Disorder
Trajectories From Childhood to Young Adulthood: Evidence
From a Birth Cohort Supporting a Late-Onset
Syndrome. JAMA Psychiatry 73, 705-712.
Cortese, S., Castellanos, F.X., Eickhoff, C.R., D'Acunto, G.,
Masi, G., Fox, P.T., Laird, A.R., Eickhoff, S.B., 2016.
Functional Decoding and Meta-analytic Connectivity Modeling
in Adult Attention-Deficit/Hyperactivity
Disorder. Biol Psychiatry 80, 896-904.
Cortese, S., Kelly, C., Chabernaud, C., Proal, E., Di Martino,
A., Milham, M.P., Castellanos, F.X., 2012. Toward
systems neuroscience of ADHD: a meta-analysis of 55 fMRI
studies. Am J Psychiatry 169, 1038-1055.
Dickstein, S.G., Bannon, K., Castellanos, F.X., Milham, M.P.,
2006. The neural correlates of attention deficit
hyperactivity disorder: an ALE meta-analysis. J Child Psychol
Psychiatry 47, 1051-1062.
Eickhoff, S.B., Bzdok, D., Laird, A.R., Kurth, F., Fox, P.T.,
2012. Activation likelihood estimation meta-analysis
revisited. Neuroimage 59, 2349-2361.
Eickhoff, S.B., Laird, A.R., Fox, P.M., Lancaster, J.L., Fox,
P.T., 2017. Implementation errors in the GingerALE
Software: Description and recommendations. Hum Brain Mapp
38, 7-11.
Eickhoff, S.B., Nichols, T.E., Laird, A.R., Hoffstaedter, F.,
Amunts, K., Fox, P.T., Bzdok, D., Eickhoff, C.R., 2016.
Behavior, sensitivity, and power of activation likelihood
estimation characterized by massive empirical
simulation. Neuroimage 137, 70-85.
Elia, J., Ambrosini, P., Berrettini, W., 2008. ADHD
characteristics: I. Concurrent co-morbidity patterns in
children & adolescents. Child Adolesc Psychiatry Ment Health
2, 15.
Ellison-Wright, I., Ellison-Wright, Z., Bullmore, E., 2008.
Structural brain change in Attention Deficit
Hyperactivity Disorder identified by meta-analysis. BMC
psychiatry 8, 51.
ACCEPTED M
ANUSCRIP
T
19
Frodl, T., Skokauskas, N., 2012. Meta-analysis of structural
MRI studies in children and adults with attention
deficit hyperactivity disorder indicates treatment effects. Acta
psychiatrica Scandinavica 125, 114-126.
Goodkind, M., Eickhoff, S.B., Oathes, D.J., Jiang, Y., Chang,
A., Jones-Hagata, L.B., Ortega, B.N., Zaiko, Y.V., Roach,
E.L., Korgaonkar, M.S., Grieve, S.M., Galatzer-Levy, I., Fox,
P.T., Etkin, A., 2015. Identification of a common
neurobiological substrate for mental illness. JAMA Psychiatry
72, 305-315.
Hart, H., Radua, J., Mataix-Cols, D., Rubia, K., 2012. Meta-
analysis of fMRI studies of timing in attention-deficit
hyperactivity disorder (ADHD). Neurosci Biobehav Rev 36,
2248-2256.
Hart, H., Radua, J., Nakao, T., Mataix-Cols, D., Rubia, K.,
2013. Meta-analysis of functional magnetic resonance
imaging studies of inhibition and attention in attention-
deficit/hyperactivity disorder: exploring task-specific,
stimulant medication, and age effects. JAMA Psychiatry 70,
185-198.
Herz, D.M., Eickhoff, S.B., Lokkegaard, A., Siebner, H.R.,
2014. Functional neuroimaging of motor control in
Parkinson's disease: a meta-analysis. Hum Brain Mapp 35,
3227-3237.
Hoogman, M., Bralten, J., Hibar, D.P., Mennes, M., Zwiers,
M.P., Schweren, L.S.J., van Hulzen, K.J.E., Medland, S.E.,
Shumskaya, E., Jahanshad, N., Zeeuw, P., Szekely, E., Sudre,
G., Wolfers, T., Onnink, A.M.H., Dammers, J.T.,
Mostert, J.C., Vives-Gilabert, Y., Kohls, G., Oberwelland, E.,
Seitz, J., Schulte-Ruther, M., Ambrosino, S., Doyle,
A.E., Hovik, M.F., Dramsdahl, M., Tamm, L., van Erp, T.G.M.,
Dale, A., Schork, A., Conzelmann, A., Zierhut, K.,
Baur, R., McCarthy, H., Yoncheva, Y.N., Cubillo, A.,
Chantiluke, K., Mehta, M.A., Paloyelis, Y., Hohmann, S.,
Baumeister, S., Bramati, I., Mattos, P., Tovar-Moll, F.,
Douglas, P., Banaschewski, T., Brandeis, D., Kuntsi, J.,
Asherson, P., Rubia, K., Kelly, C., Martino, A.D., Milham,
M.P., Castellanos, F.X., Frodl, T., Zentis, M., Lesch, K.P.,
Reif, A., Pauli, P., Jernigan, T.L., Haavik, J., Plessen, K.J.,
Lundervold, A.J., Hugdahl, K., Seidman, L.J., Biederman, J.,
Rommelse, N., Heslenfeld, D.J., Hartman, C.A., Hoekstra, P.J.,
Oosterlaan, J., Polier, G.V., Konrad, K., Vilarroya, O.,
Ramos-Quiroga, J.A., Soliva, J.C., Durston, S., Buitelaar, J.K.,
Faraone, S.V., Shaw, P., Thompson, P.M., Franke, B.,
2017. Subcortical brain volume differences in participants with
attention deficit hyperactivity disorder in
children and adults: a cross-sectional mega-analysis. Lancet
Psychiatry 4, 310-319.
Itami, S., Uno, H., 2002. Orbitofrontal cortex dysfunction in
attention-deficit hyperactivity disorder revealed by
reversal and extinction tasks. Neuroreport 13, 2453-2457.
Konrad, K., Eickhoff, S.B., 2010. Is the ADHD brain wired
differently? A review on structural and functional
connectivity in attention deficit hyperactivity disorder. Hum
Brain Mapp 31, 904-916.
Lancaster, J.L., Tordesillas-Gutierrez, D., Martinez, M.,
Salinas, F., Evans, A., ZilleS, K., Mazziotta, J.C., Fox, P.T.,
2007. Bias between MNI and talairach coordinates analyzed
using the ICBM-152 brain template. Human Brain
Mapping 28, 1194-1205.
Lei, D., Du, M., Wu, M., Chen, T., Huang, X., Du, X., Bi, F.,
Kemp, G.J., Gong, Q., 2015. Functional MRI reveals
different response inhibition between adults and children with
ADHD. Neuropsychology 29, 874-881.
Max, J.E., Fox, P.T., Lancaster, J.L., Kochunov, P., Mathews,
K., Manes, F.F., Robertson, B.A., Arndt, S., Robin, D.A.,
Lansing, A.E., 2002. Putamen lesions and the development of
attention-deficit/hyperactivity symptomatology.
J Am Acad Child Adolesc Psychiatry 41, 563-571.
McCarthy, H., Skokauskas, N., Frodl, T., 2014. Identifying a
consistent pattern of neural function in attention
deficit hyperactivity disorder: a meta-analysis. Psychol Med 44,
869-880.
Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G., Group, P.,
2009. Preferred reporting items for systematic
reviews and meta-analyses: the PRISMA statement. PLoS Med
6, e1000097.
ACCEPTED M
ANUSCRIP
T
20
Muller, V.I., Cieslik, E.C., Laird, A.R., Fox, P.T., Radua, J.,
Mataix-Cols, D., Tench, C.R., Yarkoni, T., Nichols, T.E.,
Turkeltaub, P.E., Wager, T.D., Eickhoff, S.B., 2018. Ten simple
rules for neuroimaging meta-analysis. Neurosci
Biobehav Rev 84, 151-161.
Muller, V.I., Cieslik, E.C., Serbanescu, I., Laird, A.R., Fox,
P.T., Eickhoff, S.B., 2017. Altered Brain Activity in
Unipolar Depression Revisited: Meta-analyses of Neuroimaging
Studies. JAMA Psychiatry 74, 47-55.
Nakao, T., Radua, J., Rubia, K., Mataix-Cols, D., 2011. Gray
matter volume abnormalities in ADHD: voxel-based
meta-analysis exploring the effects of age and stimulant
medication. Am J Psychiatry 168, 1154-1163.
Radua, J., Borgwardt, S., Crescini, A., Mataix-Cols, D., Meyer-
Lindenberg, A., McGuire, P.K., Fusar-Poli, P., 2012.
Multimodal meta-analysis of structural and functional brain
changes in first episode psychosis and the effects
of antipsychotic medication. Neurosci Biobehav Rev 36, 2325-
2333.
Raschle, N.M., Menks, W.M., Fehlbaum, L.V., Tshomba, E.,
Stadler, C., 2015. Structural and Functional
Alterations in Right Dorsomedial Prefrontal and Left Insular
Cortex Co-Localize in Adolescents with
Aggressive Behaviour: An ALE Meta-Analysis. PLoS One 10,
e0136553.
Rubia, K., 2011. "Cool" inferior frontostriatal dysfunction in
attention-deficit/hyperactivity disorder versus
"hot" ventromedial orbitofrontal-limbic dysfunction in conduct
disorder: a review. Biol Psychiatry 69, e69-87.
Sacher, J., Neumann, J., Funfstuck, T., Soliman, A., Villringer,
A., Schroeter, M.L., 2012. Mapping the depressed
brain: a meta-analysis of structural and functional alterations in
major depressive disorder. J Affect Disord
140, 142-148.
Smith, S.M., Nichols, T.E., 2009. Threshold-free cluster
enhancement: Addressing problems of smoothing,
threshold dependence and localisation in cluster inference.
Neuroimage 44, 83-98.
Sonuga-Barke, E., Bitsakou, P., Thompson, M., 2010. Beyond
the dual pathway model: evidence for the
dissociation of timing, inhibitory, and delay-related
impairments in attention-deficit/hyperactivity disorder. J
Am Acad Child Adolesc Psychiatry 49, 345-355.
Stevens, M.C., Pearlson, G.D., Calhoun, V.D., Bessette, K.L.,
2018. Functional Neuroimaging Evidence for Distinct
Neurobiological Pathways in Attention-Deficit/Hyperactivity
Disorder. Biol Psychiatry Cogn Neurosci
Neuroimaging 3, 675-685.
Tahmasian, M., Eickhoff, S.B., Giehl, K., Schwartz, F., Herz,
D.M., Drzezga, A., van Eimeren, T., Laird, A.R., Fox,
P.T., Khazaie, H., Zarei, M., Eggers, C., Eickhoff, C.R., 2017.
Resting-state functional reorganization in
Parkinson's disease: An activation likelihood estimation meta-
analysis. Cortex 92, 119-138.
Tahmasian M, N.K., Samea F, Zarei M, Spiegelhalder K,
Eickhoff SB, Van Someren E, Khazaie H, Eickhoff CR.,
2018. Reply to Hua Liu, HaiCun Shi and PingLei Pan:
Coordinate based meta-analyses in a medium sized
literature: considerations, limitations and road ahead. Sleep
Medicine Reviews.
Tahmasian, M., Noori, K., Samea, F., Zarei, M., Spiegelhalder,
K., Eickhoff, S.B., van Someren, E., Khazaie, H.,
Eickhoff, C.R., 2018. A Lack of consistent brain alterations in
insomnia disorder: an activation likelihood
estimation meta-analysis. Sleep Medicine Reviews.
Tahmasian, M., Rosenzweig, I., Eickhoff, S.B., Sepehry, A.A.,
Laird, A.R., Fox, P.T., Morrell, M.J., Khazaie, H.,
Eickhoff, C.R., 2016. Structural and functional neural
adaptations in obstructive sleep apnea: an activation
likelihood estimation meta-analysis. Neurosci Biobehav Rev.
Talairach, J., Tournoux, P., 1988. Co-planar stereotaxic atlas of
the human brain : 3-dimensional proportional
system : an approach to cerebral imaging. Georg Thieme,
Stuttgart ; New York.
ACCEPTED M
ANUSCRIP
T
21
Turkeltaub, P.E., Eden, G.F., Jones, K.M., Zeffiro, T.A., 2002.
Meta-analysis of the functional neuroanatomy of
single-word reading: method and validation. Neuroimage 16,
765-780.
Turkeltaub, P.E., Eickhoff, S.B., Laird, A.R., Fox, M., Wiener,
M., Fox, P., 2012. Minimizing within-experiment and
within-group effects in Activation Likelihood Estimation meta-
analyses. Hum Brain Mapp 33, 1-13.
Valera, E.M., Faraone, S.V., Murray, K.E., Seidman, L.J., 2007.
Meta-analysis of structural imaging findings in
attention-deficit/hyperactivity disorder. Biol Psychiatry 61,
1361-1369.
Wahlstedt, C., Thorell, L.B., Bohlin, G., 2009. Heterogeneity in
ADHD: neuropsychological pathways,
comorbidity and symptom domains. J Abnorm Child Psychol 37,
551-564.
Wegbreit, E., Cushman, G.K., Puzia, M.E., Weissman, A.B.,
Kim, K.L., Laird, A.R., Dickstein, D.P., 2014.
Developmental meta-analyses of the functional neural correlates
of bipolar disorder. JAMA Psychiatry 71,
926-935.
Zakzanis, K.K., Graham, S.J., Campbell, Z., 2003. A meta-
analysis of structural and functional brain imaging in
dementia of the Alzheimer's type: a neuroimaging profile.
Neuropsychol Rev 13, 1-18.
ACCEPTED M
ANUSCRIP
T
22
Figures’ legends
Figure 1. Study selection strategy flow chart. ROI: region of
Interest, task-fMRI: task-based functional
magnetic resonance imaging, rs-fMRI: resting-state functional
magnetic resonance imaging, VBM: voxel-
based morphometry, ADHD: attention-deficit/hyperactivity
disorder.
ACCEPTED M
ANUSCRIP
T
23
Figure 2. Distribution of the included coordinates in the current
study. Included coordinates
reflecting structural/functional alterations in
children/adolescents with ADHD compared to healthy
ACCEPTED M
ANUSCRIP
T
24
subjects. Rs-fMRI: resting-state functional magnetic resonance
imaging; task-fMRI: task-based functional
magnetic resonance imaging; VBM: voxel-based morphometry.
Figure 3. Convergent findings of sub-analyses. A. Aberrant
activity (green) in the left pallidum/putamen
(-18, 4, -4 MNI, 109 voxels, p= 0.036), based on task-based
fMRI experiments (using neutral stimuli only);
B. Decreased activity (blue) in the left inferior frontal gyrus (-
38, 26, -16 MNI, 93 voxels, p =0.049 based
on fMRI (task-fMRI & rs-fMRI) experiments (using male
patients only).
ACCEPTED M
ANUSCRIP
T
25
ACCEPTED M
ANUSCRIP
T
26
Table 1: Results of conducted meta-analyses in
children/adolescent with ADHD compared to
healthy subjects
A. Modality
Number of
Experiments
Modalities Contrasts
P-value
TFCE cFWE
1 130 VBM, task-fMRI, rs-fMRI - 0·170 0·129
2 81 VBM, task-fMRI, rs-fMRI Control > ADHD 0·087 0·195
3 48 VBM, task-fMRI, rs-fMRI ADHD > Control 0·104 0·175
4 98
fMRI
(combination of task- and rs-fMRI)
- 0·151 0·212
5 57
fMRI
(combination of task- and rs-fMRI)
Control > ADHD 0·061 0·138
6 1
fMRI
(combination of task- and rs-fMRI)
ADHD > Control 0·063 0·153
7 92 task-fMRI - 0·064 0·062
8 54 task-fMRI Control > ADHD 0·103 0·329
9 38 task-fMRI ADHD > Control 0·248 0·668
10 32 VBM - 0·817 0·452
11 25 VBM Control > ADHD 0·630 0·341
B· Cognitive domain
Number of
Experiments
Domain Contrasts
P-value
TFCE cFWE
12 31 Inhibitory control - 0·405 0·302
13 18 Inhibitory control Control > ADHD 0·040 0·052
15 27 Attention - 0·447 0·847
18 23 Other cognitive domains - 0·440 0·520
C· Stimulus type
Number of
Experiments
Stimulus Type Contrasts
P-value
TFCE cFWE
21 65 Neutral - 0·079 0·036
22 41 Neutral Control > ADHD 0·048 0·244
23 24 Neutral ADHD > Control 0·104 0·110
rs-fMRI: resting-state functional magnetic resonance imaging;
task-fMRI: task-based functional
magnetic resonance imaging; VBM: voxel-based morphometry;
TFCE: threshold-free cluster
enhancement; cFWE: cluster-level family-wise error.
ACCEPTED M
ANUSCRIP
T

More Related Content

Similar to Rubric Detail A rubric lists grading criteria that instruct.docx

1. PART ONETop of FormMotivational Interviewing· Watch this
1. PART ONETop of FormMotivational Interviewing· Watch this 1. PART ONETop of FormMotivational Interviewing· Watch this
1. PART ONETop of FormMotivational Interviewing· Watch this TatianaMajor22
 
6719, 6(27 PMRubric Detail – Blackboard LearnPage 1 of 3.docx
6719, 6(27 PMRubric Detail – Blackboard LearnPage 1 of 3.docx6719, 6(27 PMRubric Detail – Blackboard LearnPage 1 of 3.docx
6719, 6(27 PMRubric Detail – Blackboard LearnPage 1 of 3.docxtroutmanboris
 
Week 3 Assignment Organizational Needs AssessmentSubmit As.docx
Week 3 Assignment Organizational Needs AssessmentSubmit As.docxWeek 3 Assignment Organizational Needs AssessmentSubmit As.docx
Week 3 Assignment Organizational Needs AssessmentSubmit As.docxendawalling
 
Man7057 Proposal Feedback FormStudent NameSanaullahStudent N.docx
Man7057 Proposal Feedback FormStudent NameSanaullahStudent N.docxMan7057 Proposal Feedback FormStudent NameSanaullahStudent N.docx
Man7057 Proposal Feedback FormStudent NameSanaullahStudent N.docxjessiehampson
 
Man7057 Proposal Feedback FormStudent NameSanaullahStudent N.docx
Man7057 Proposal Feedback FormStudent NameSanaullahStudent N.docxMan7057 Proposal Feedback FormStudent NameSanaullahStudent N.docx
Man7057 Proposal Feedback FormStudent NameSanaullahStudent N.docxtienboileau
 
Ch 6 only 1. Distinguish between a purpose statement, research p
Ch 6 only 1. Distinguish between a purpose statement, research pCh 6 only 1. Distinguish between a purpose statement, research p
Ch 6 only 1. Distinguish between a purpose statement, research pMaximaSheffield592
 
Ch 6 only 1. distinguish between a purpose statement, research p
Ch 6 only 1. distinguish between a purpose statement, research pCh 6 only 1. distinguish between a purpose statement, research p
Ch 6 only 1. distinguish between a purpose statement, research pnand15
 
Introduction to Epidemiology Course Project Detailed Article Cri.docx
Introduction to Epidemiology Course Project Detailed Article Cri.docxIntroduction to Epidemiology Course Project Detailed Article Cri.docx
Introduction to Epidemiology Course Project Detailed Article Cri.docxmariuse18nolet
 
ACC202 - Management AccountingTrimester 3 2018 GROUP ASSIGNMENT.docx
ACC202 - Management AccountingTrimester 3 2018 GROUP ASSIGNMENT.docxACC202 - Management AccountingTrimester 3 2018 GROUP ASSIGNMENT.docx
ACC202 - Management AccountingTrimester 3 2018 GROUP ASSIGNMENT.docxbartholomeocoombs
 
Rubric Detail Select Grid View or List View to change the rubric.docx
Rubric Detail Select Grid View or List View to change the rubric.docxRubric Detail Select Grid View or List View to change the rubric.docx
Rubric Detail Select Grid View or List View to change the rubric.docxtoddr4
 
BUSI 230Discussion Board Forum 1Project 2 InstructionsSta.docx
BUSI 230Discussion Board Forum 1Project 2 InstructionsSta.docxBUSI 230Discussion Board Forum 1Project 2 InstructionsSta.docx
BUSI 230Discussion Board Forum 1Project 2 InstructionsSta.docxRAHUL126667
 
Discussion # 1 Due Weds 081921Wk 8 Discussion 1 [due Thurs]D
Discussion # 1 Due Weds 081921Wk 8 Discussion 1 [due Thurs]DDiscussion # 1 Due Weds 081921Wk 8 Discussion 1 [due Thurs]D
Discussion # 1 Due Weds 081921Wk 8 Discussion 1 [due Thurs]DAlyciaGold776
 
NR449 Evidence-Based Practice RUA Evidence-Based Pract
 NR449 Evidence-Based Practice RUA Evidence-Based Pract NR449 Evidence-Based Practice RUA Evidence-Based Pract
NR449 Evidence-Based Practice RUA Evidence-Based PractTatianaMajor22
 
Rubric Detail Select Grid View or List View to change the rubric.docx
Rubric Detail Select Grid View or List View to change the rubric.docxRubric Detail Select Grid View or List View to change the rubric.docx
Rubric Detail Select Grid View or List View to change the rubric.docxhealdkathaleen
 

Similar to Rubric Detail A rubric lists grading criteria that instruct.docx (14)

1. PART ONETop of FormMotivational Interviewing· Watch this
1. PART ONETop of FormMotivational Interviewing· Watch this 1. PART ONETop of FormMotivational Interviewing· Watch this
1. PART ONETop of FormMotivational Interviewing· Watch this
 
6719, 6(27 PMRubric Detail – Blackboard LearnPage 1 of 3.docx
6719, 6(27 PMRubric Detail – Blackboard LearnPage 1 of 3.docx6719, 6(27 PMRubric Detail – Blackboard LearnPage 1 of 3.docx
6719, 6(27 PMRubric Detail – Blackboard LearnPage 1 of 3.docx
 
Week 3 Assignment Organizational Needs AssessmentSubmit As.docx
Week 3 Assignment Organizational Needs AssessmentSubmit As.docxWeek 3 Assignment Organizational Needs AssessmentSubmit As.docx
Week 3 Assignment Organizational Needs AssessmentSubmit As.docx
 
Man7057 Proposal Feedback FormStudent NameSanaullahStudent N.docx
Man7057 Proposal Feedback FormStudent NameSanaullahStudent N.docxMan7057 Proposal Feedback FormStudent NameSanaullahStudent N.docx
Man7057 Proposal Feedback FormStudent NameSanaullahStudent N.docx
 
Man7057 Proposal Feedback FormStudent NameSanaullahStudent N.docx
Man7057 Proposal Feedback FormStudent NameSanaullahStudent N.docxMan7057 Proposal Feedback FormStudent NameSanaullahStudent N.docx
Man7057 Proposal Feedback FormStudent NameSanaullahStudent N.docx
 
Ch 6 only 1. Distinguish between a purpose statement, research p
Ch 6 only 1. Distinguish between a purpose statement, research pCh 6 only 1. Distinguish between a purpose statement, research p
Ch 6 only 1. Distinguish between a purpose statement, research p
 
Ch 6 only 1. distinguish between a purpose statement, research p
Ch 6 only 1. distinguish between a purpose statement, research pCh 6 only 1. distinguish between a purpose statement, research p
Ch 6 only 1. distinguish between a purpose statement, research p
 
Introduction to Epidemiology Course Project Detailed Article Cri.docx
Introduction to Epidemiology Course Project Detailed Article Cri.docxIntroduction to Epidemiology Course Project Detailed Article Cri.docx
Introduction to Epidemiology Course Project Detailed Article Cri.docx
 
ACC202 - Management AccountingTrimester 3 2018 GROUP ASSIGNMENT.docx
ACC202 - Management AccountingTrimester 3 2018 GROUP ASSIGNMENT.docxACC202 - Management AccountingTrimester 3 2018 GROUP ASSIGNMENT.docx
ACC202 - Management AccountingTrimester 3 2018 GROUP ASSIGNMENT.docx
 
Rubric Detail Select Grid View or List View to change the rubric.docx
Rubric Detail Select Grid View or List View to change the rubric.docxRubric Detail Select Grid View or List View to change the rubric.docx
Rubric Detail Select Grid View or List View to change the rubric.docx
 
BUSI 230Discussion Board Forum 1Project 2 InstructionsSta.docx
BUSI 230Discussion Board Forum 1Project 2 InstructionsSta.docxBUSI 230Discussion Board Forum 1Project 2 InstructionsSta.docx
BUSI 230Discussion Board Forum 1Project 2 InstructionsSta.docx
 
Discussion # 1 Due Weds 081921Wk 8 Discussion 1 [due Thurs]D
Discussion # 1 Due Weds 081921Wk 8 Discussion 1 [due Thurs]DDiscussion # 1 Due Weds 081921Wk 8 Discussion 1 [due Thurs]D
Discussion # 1 Due Weds 081921Wk 8 Discussion 1 [due Thurs]D
 
NR449 Evidence-Based Practice RUA Evidence-Based Pract
 NR449 Evidence-Based Practice RUA Evidence-Based Pract NR449 Evidence-Based Practice RUA Evidence-Based Pract
NR449 Evidence-Based Practice RUA Evidence-Based Pract
 
Rubric Detail Select Grid View or List View to change the rubric.docx
Rubric Detail Select Grid View or List View to change the rubric.docxRubric Detail Select Grid View or List View to change the rubric.docx
Rubric Detail Select Grid View or List View to change the rubric.docx
 

More from robert345678

1Principles of Economics, Ninth EditionN. Gregory Mankiw.docx
1Principles of Economics, Ninth EditionN. Gregory Mankiw.docx1Principles of Economics, Ninth EditionN. Gregory Mankiw.docx
1Principles of Economics, Ninth EditionN. Gregory Mankiw.docxrobert345678
 
1IntroductionThe objective of this study plan is to evaluate.docx
1IntroductionThe objective of this study plan is to evaluate.docx1IntroductionThe objective of this study plan is to evaluate.docx
1IntroductionThe objective of this study plan is to evaluate.docxrobert345678
 
1Project One Executive SummaryCole Staats.docx
1Project One Executive SummaryCole Staats.docx1Project One Executive SummaryCole Staats.docx
1Project One Executive SummaryCole Staats.docxrobert345678
 
1Management Of CareChamberlain U.docx
1Management Of CareChamberlain U.docx1Management Of CareChamberlain U.docx
1Management Of CareChamberlain U.docxrobert345678
 
1NOTE This is a template to help you format Project Part .docx
1NOTE This is a template to help you format Project Part .docx1NOTE This is a template to help you format Project Part .docx
1NOTE This is a template to help you format Project Part .docxrobert345678
 
15Problem Orientation and Psychologica.docx
15Problem Orientation and Psychologica.docx15Problem Orientation and Psychologica.docx
15Problem Orientation and Psychologica.docxrobert345678
 
122422, 850 AMHow to successfully achieve business integrat.docx
122422, 850 AMHow to successfully achieve business integrat.docx122422, 850 AMHow to successfully achieve business integrat.docx
122422, 850 AMHow to successfully achieve business integrat.docxrobert345678
 
1PAGE 5West Chester Private School Case StudyGrand .docx
1PAGE  5West Chester Private School Case StudyGrand .docx1PAGE  5West Chester Private School Case StudyGrand .docx
1PAGE 5West Chester Private School Case StudyGrand .docxrobert345678
 
12Toxoplasmosis and Effects on Abortion, And Fetal A.docx
12Toxoplasmosis and Effects on Abortion, And Fetal A.docx12Toxoplasmosis and Effects on Abortion, And Fetal A.docx
12Toxoplasmosis and Effects on Abortion, And Fetal A.docxrobert345678
 
155Chapter 11The Frivolity of EvilTheodore Dalrymple.docx
155Chapter 11The Frivolity of EvilTheodore Dalrymple.docx155Chapter 11The Frivolity of EvilTheodore Dalrymple.docx
155Chapter 11The Frivolity of EvilTheodore Dalrymple.docxrobert345678
 
122022, 824 PM Rubric Assessment - SOC1001-Introduction to .docx
122022, 824 PM Rubric Assessment - SOC1001-Introduction to .docx122022, 824 PM Rubric Assessment - SOC1001-Introduction to .docx
122022, 824 PM Rubric Assessment - SOC1001-Introduction to .docxrobert345678
 
1.2.3.4.5.6.7.8..docx
1.2.3.4.5.6.7.8..docx1.2.3.4.5.6.7.8..docx
1.2.3.4.5.6.7.8..docxrobert345678
 
121122, 1204 AM Activities - IDS-403-H7189 Technology and S.docx
121122, 1204 AM Activities - IDS-403-H7189 Technology and S.docx121122, 1204 AM Activities - IDS-403-H7189 Technology and S.docx
121122, 1204 AM Activities - IDS-403-H7189 Technology and S.docxrobert345678
 
1. When drug prices increase at a faster rate than inflation, the .docx
1. When drug prices increase at a faster rate than inflation, the .docx1. When drug prices increase at a faster rate than inflation, the .docx
1. When drug prices increase at a faster rate than inflation, the .docxrobert345678
 
1. Which of the following sentences describe a child functioning a.docx
1. Which of the following sentences describe a child functioning a.docx1. Which of the following sentences describe a child functioning a.docx
1. Which of the following sentences describe a child functioning a.docxrobert345678
 
1. How did the case study impact your thoughts about your own fina.docx
1. How did the case study impact your thoughts about your own fina.docx1. How did the case study impact your thoughts about your own fina.docx
1. How did the case study impact your thoughts about your own fina.docxrobert345678
 
1 The Biography of Langston Hughes .docx
1  The Biography of Langston Hughes .docx1  The Biography of Langston Hughes .docx
1 The Biography of Langston Hughes .docxrobert345678
 
1 Save Our Doughmocracy A Moophoric Voter Registratio.docx
1 Save Our Doughmocracy A Moophoric Voter Registratio.docx1 Save Our Doughmocracy A Moophoric Voter Registratio.docx
1 Save Our Doughmocracy A Moophoric Voter Registratio.docxrobert345678
 
1 MINISTRY OF EDUCATION UNIVERSITY OF HAIL .docx
1 MINISTRY OF EDUCATION UNIVERSITY OF HAIL .docx1 MINISTRY OF EDUCATION UNIVERSITY OF HAIL .docx
1 MINISTRY OF EDUCATION UNIVERSITY OF HAIL .docxrobert345678
 
1 Assessment Brief Module Code Module .docx
1     Assessment Brief  Module Code  Module .docx1     Assessment Brief  Module Code  Module .docx
1 Assessment Brief Module Code Module .docxrobert345678
 

More from robert345678 (20)

1Principles of Economics, Ninth EditionN. Gregory Mankiw.docx
1Principles of Economics, Ninth EditionN. Gregory Mankiw.docx1Principles of Economics, Ninth EditionN. Gregory Mankiw.docx
1Principles of Economics, Ninth EditionN. Gregory Mankiw.docx
 
1IntroductionThe objective of this study plan is to evaluate.docx
1IntroductionThe objective of this study plan is to evaluate.docx1IntroductionThe objective of this study plan is to evaluate.docx
1IntroductionThe objective of this study plan is to evaluate.docx
 
1Project One Executive SummaryCole Staats.docx
1Project One Executive SummaryCole Staats.docx1Project One Executive SummaryCole Staats.docx
1Project One Executive SummaryCole Staats.docx
 
1Management Of CareChamberlain U.docx
1Management Of CareChamberlain U.docx1Management Of CareChamberlain U.docx
1Management Of CareChamberlain U.docx
 
1NOTE This is a template to help you format Project Part .docx
1NOTE This is a template to help you format Project Part .docx1NOTE This is a template to help you format Project Part .docx
1NOTE This is a template to help you format Project Part .docx
 
15Problem Orientation and Psychologica.docx
15Problem Orientation and Psychologica.docx15Problem Orientation and Psychologica.docx
15Problem Orientation and Psychologica.docx
 
122422, 850 AMHow to successfully achieve business integrat.docx
122422, 850 AMHow to successfully achieve business integrat.docx122422, 850 AMHow to successfully achieve business integrat.docx
122422, 850 AMHow to successfully achieve business integrat.docx
 
1PAGE 5West Chester Private School Case StudyGrand .docx
1PAGE  5West Chester Private School Case StudyGrand .docx1PAGE  5West Chester Private School Case StudyGrand .docx
1PAGE 5West Chester Private School Case StudyGrand .docx
 
12Toxoplasmosis and Effects on Abortion, And Fetal A.docx
12Toxoplasmosis and Effects on Abortion, And Fetal A.docx12Toxoplasmosis and Effects on Abortion, And Fetal A.docx
12Toxoplasmosis and Effects on Abortion, And Fetal A.docx
 
155Chapter 11The Frivolity of EvilTheodore Dalrymple.docx
155Chapter 11The Frivolity of EvilTheodore Dalrymple.docx155Chapter 11The Frivolity of EvilTheodore Dalrymple.docx
155Chapter 11The Frivolity of EvilTheodore Dalrymple.docx
 
122022, 824 PM Rubric Assessment - SOC1001-Introduction to .docx
122022, 824 PM Rubric Assessment - SOC1001-Introduction to .docx122022, 824 PM Rubric Assessment - SOC1001-Introduction to .docx
122022, 824 PM Rubric Assessment - SOC1001-Introduction to .docx
 
1.2.3.4.5.6.7.8..docx
1.2.3.4.5.6.7.8..docx1.2.3.4.5.6.7.8..docx
1.2.3.4.5.6.7.8..docx
 
121122, 1204 AM Activities - IDS-403-H7189 Technology and S.docx
121122, 1204 AM Activities - IDS-403-H7189 Technology and S.docx121122, 1204 AM Activities - IDS-403-H7189 Technology and S.docx
121122, 1204 AM Activities - IDS-403-H7189 Technology and S.docx
 
1. When drug prices increase at a faster rate than inflation, the .docx
1. When drug prices increase at a faster rate than inflation, the .docx1. When drug prices increase at a faster rate than inflation, the .docx
1. When drug prices increase at a faster rate than inflation, the .docx
 
1. Which of the following sentences describe a child functioning a.docx
1. Which of the following sentences describe a child functioning a.docx1. Which of the following sentences describe a child functioning a.docx
1. Which of the following sentences describe a child functioning a.docx
 
1. How did the case study impact your thoughts about your own fina.docx
1. How did the case study impact your thoughts about your own fina.docx1. How did the case study impact your thoughts about your own fina.docx
1. How did the case study impact your thoughts about your own fina.docx
 
1 The Biography of Langston Hughes .docx
1  The Biography of Langston Hughes .docx1  The Biography of Langston Hughes .docx
1 The Biography of Langston Hughes .docx
 
1 Save Our Doughmocracy A Moophoric Voter Registratio.docx
1 Save Our Doughmocracy A Moophoric Voter Registratio.docx1 Save Our Doughmocracy A Moophoric Voter Registratio.docx
1 Save Our Doughmocracy A Moophoric Voter Registratio.docx
 
1 MINISTRY OF EDUCATION UNIVERSITY OF HAIL .docx
1 MINISTRY OF EDUCATION UNIVERSITY OF HAIL .docx1 MINISTRY OF EDUCATION UNIVERSITY OF HAIL .docx
1 MINISTRY OF EDUCATION UNIVERSITY OF HAIL .docx
 
1 Assessment Brief Module Code Module .docx
1     Assessment Brief  Module Code  Module .docx1     Assessment Brief  Module Code  Module .docx
1 Assessment Brief Module Code Module .docx
 

Recently uploaded

internship ppt on smartinternz platform as salesforce developer
internship ppt on smartinternz platform as salesforce developerinternship ppt on smartinternz platform as salesforce developer
internship ppt on smartinternz platform as salesforce developerunnathinaik
 
ENGLISH5 QUARTER4 MODULE1 WEEK1-3 How Visual and Multimedia Elements.pptx
ENGLISH5 QUARTER4 MODULE1 WEEK1-3 How Visual and Multimedia Elements.pptxENGLISH5 QUARTER4 MODULE1 WEEK1-3 How Visual and Multimedia Elements.pptx
ENGLISH5 QUARTER4 MODULE1 WEEK1-3 How Visual and Multimedia Elements.pptxAnaBeatriceAblay2
 
EPANDING THE CONTENT OF AN OUTLINE using notes.pptx
EPANDING THE CONTENT OF AN OUTLINE using notes.pptxEPANDING THE CONTENT OF AN OUTLINE using notes.pptx
EPANDING THE CONTENT OF AN OUTLINE using notes.pptxRaymartEstabillo3
 
Sanyam Choudhary Chemistry practical.pdf
Sanyam Choudhary Chemistry practical.pdfSanyam Choudhary Chemistry practical.pdf
Sanyam Choudhary Chemistry practical.pdfsanyamsingh5019
 
Solving Puzzles Benefits Everyone (English).pptx
Solving Puzzles Benefits Everyone (English).pptxSolving Puzzles Benefits Everyone (English).pptx
Solving Puzzles Benefits Everyone (English).pptxOH TEIK BIN
 
18-04-UA_REPORT_MEDIALITERAСY_INDEX-DM_23-1-final-eng.pdf
18-04-UA_REPORT_MEDIALITERAСY_INDEX-DM_23-1-final-eng.pdf18-04-UA_REPORT_MEDIALITERAСY_INDEX-DM_23-1-final-eng.pdf
18-04-UA_REPORT_MEDIALITERAСY_INDEX-DM_23-1-final-eng.pdfssuser54595a
 
How to Make a Pirate ship Primary Education.pptx
How to Make a Pirate ship Primary Education.pptxHow to Make a Pirate ship Primary Education.pptx
How to Make a Pirate ship Primary Education.pptxmanuelaromero2013
 
ECONOMIC CONTEXT - LONG FORM TV DRAMA - PPT
ECONOMIC CONTEXT - LONG FORM TV DRAMA - PPTECONOMIC CONTEXT - LONG FORM TV DRAMA - PPT
ECONOMIC CONTEXT - LONG FORM TV DRAMA - PPTiammrhaywood
 
call girls in Kamla Market (DELHI) 🔝 >༒9953330565🔝 genuine Escort Service 🔝✔️✔️
call girls in Kamla Market (DELHI) 🔝 >༒9953330565🔝 genuine Escort Service 🔝✔️✔️call girls in Kamla Market (DELHI) 🔝 >༒9953330565🔝 genuine Escort Service 🔝✔️✔️
call girls in Kamla Market (DELHI) 🔝 >༒9953330565🔝 genuine Escort Service 🔝✔️✔️9953056974 Low Rate Call Girls In Saket, Delhi NCR
 
Pharmacognosy Flower 3. Compositae 2023.pdf
Pharmacognosy Flower 3. Compositae 2023.pdfPharmacognosy Flower 3. Compositae 2023.pdf
Pharmacognosy Flower 3. Compositae 2023.pdfMahmoud M. Sallam
 
How to Configure Email Server in Odoo 17
How to Configure Email Server in Odoo 17How to Configure Email Server in Odoo 17
How to Configure Email Server in Odoo 17Celine George
 
Organic Name Reactions for the students and aspirants of Chemistry12th.pptx
Organic Name Reactions  for the students and aspirants of Chemistry12th.pptxOrganic Name Reactions  for the students and aspirants of Chemistry12th.pptx
Organic Name Reactions for the students and aspirants of Chemistry12th.pptxVS Mahajan Coaching Centre
 
Biting mechanism of poisonous snakes.pdf
Biting mechanism of poisonous snakes.pdfBiting mechanism of poisonous snakes.pdf
Biting mechanism of poisonous snakes.pdfadityarao40181
 
Painted Grey Ware.pptx, PGW Culture of India
Painted Grey Ware.pptx, PGW Culture of IndiaPainted Grey Ware.pptx, PGW Culture of India
Painted Grey Ware.pptx, PGW Culture of IndiaVirag Sontakke
 
History Class XII Ch. 3 Kinship, Caste and Class (1).pptx
History Class XII Ch. 3 Kinship, Caste and Class (1).pptxHistory Class XII Ch. 3 Kinship, Caste and Class (1).pptx
History Class XII Ch. 3 Kinship, Caste and Class (1).pptxsocialsciencegdgrohi
 
Introduction to AI in Higher Education_draft.pptx
Introduction to AI in Higher Education_draft.pptxIntroduction to AI in Higher Education_draft.pptx
Introduction to AI in Higher Education_draft.pptxpboyjonauth
 
BASLIQ CURRENT LOOKBOOK LOOKBOOK(1) (1).pdf
BASLIQ CURRENT LOOKBOOK  LOOKBOOK(1) (1).pdfBASLIQ CURRENT LOOKBOOK  LOOKBOOK(1) (1).pdf
BASLIQ CURRENT LOOKBOOK LOOKBOOK(1) (1).pdfSoniaTolstoy
 

Recently uploaded (20)

TataKelola dan KamSiber Kecerdasan Buatan v022.pdf
TataKelola dan KamSiber Kecerdasan Buatan v022.pdfTataKelola dan KamSiber Kecerdasan Buatan v022.pdf
TataKelola dan KamSiber Kecerdasan Buatan v022.pdf
 
internship ppt on smartinternz platform as salesforce developer
internship ppt on smartinternz platform as salesforce developerinternship ppt on smartinternz platform as salesforce developer
internship ppt on smartinternz platform as salesforce developer
 
ENGLISH5 QUARTER4 MODULE1 WEEK1-3 How Visual and Multimedia Elements.pptx
ENGLISH5 QUARTER4 MODULE1 WEEK1-3 How Visual and Multimedia Elements.pptxENGLISH5 QUARTER4 MODULE1 WEEK1-3 How Visual and Multimedia Elements.pptx
ENGLISH5 QUARTER4 MODULE1 WEEK1-3 How Visual and Multimedia Elements.pptx
 
EPANDING THE CONTENT OF AN OUTLINE using notes.pptx
EPANDING THE CONTENT OF AN OUTLINE using notes.pptxEPANDING THE CONTENT OF AN OUTLINE using notes.pptx
EPANDING THE CONTENT OF AN OUTLINE using notes.pptx
 
Sanyam Choudhary Chemistry practical.pdf
Sanyam Choudhary Chemistry practical.pdfSanyam Choudhary Chemistry practical.pdf
Sanyam Choudhary Chemistry practical.pdf
 
Solving Puzzles Benefits Everyone (English).pptx
Solving Puzzles Benefits Everyone (English).pptxSolving Puzzles Benefits Everyone (English).pptx
Solving Puzzles Benefits Everyone (English).pptx
 
Model Call Girl in Tilak Nagar Delhi reach out to us at 🔝9953056974🔝
Model Call Girl in Tilak Nagar Delhi reach out to us at 🔝9953056974🔝Model Call Girl in Tilak Nagar Delhi reach out to us at 🔝9953056974🔝
Model Call Girl in Tilak Nagar Delhi reach out to us at 🔝9953056974🔝
 
18-04-UA_REPORT_MEDIALITERAСY_INDEX-DM_23-1-final-eng.pdf
18-04-UA_REPORT_MEDIALITERAСY_INDEX-DM_23-1-final-eng.pdf18-04-UA_REPORT_MEDIALITERAСY_INDEX-DM_23-1-final-eng.pdf
18-04-UA_REPORT_MEDIALITERAСY_INDEX-DM_23-1-final-eng.pdf
 
How to Make a Pirate ship Primary Education.pptx
How to Make a Pirate ship Primary Education.pptxHow to Make a Pirate ship Primary Education.pptx
How to Make a Pirate ship Primary Education.pptx
 
Model Call Girl in Bikash Puri Delhi reach out to us at 🔝9953056974🔝
Model Call Girl in Bikash Puri  Delhi reach out to us at 🔝9953056974🔝Model Call Girl in Bikash Puri  Delhi reach out to us at 🔝9953056974🔝
Model Call Girl in Bikash Puri Delhi reach out to us at 🔝9953056974🔝
 
ECONOMIC CONTEXT - LONG FORM TV DRAMA - PPT
ECONOMIC CONTEXT - LONG FORM TV DRAMA - PPTECONOMIC CONTEXT - LONG FORM TV DRAMA - PPT
ECONOMIC CONTEXT - LONG FORM TV DRAMA - PPT
 
call girls in Kamla Market (DELHI) 🔝 >༒9953330565🔝 genuine Escort Service 🔝✔️✔️
call girls in Kamla Market (DELHI) 🔝 >༒9953330565🔝 genuine Escort Service 🔝✔️✔️call girls in Kamla Market (DELHI) 🔝 >༒9953330565🔝 genuine Escort Service 🔝✔️✔️
call girls in Kamla Market (DELHI) 🔝 >༒9953330565🔝 genuine Escort Service 🔝✔️✔️
 
Pharmacognosy Flower 3. Compositae 2023.pdf
Pharmacognosy Flower 3. Compositae 2023.pdfPharmacognosy Flower 3. Compositae 2023.pdf
Pharmacognosy Flower 3. Compositae 2023.pdf
 
How to Configure Email Server in Odoo 17
How to Configure Email Server in Odoo 17How to Configure Email Server in Odoo 17
How to Configure Email Server in Odoo 17
 
Organic Name Reactions for the students and aspirants of Chemistry12th.pptx
Organic Name Reactions  for the students and aspirants of Chemistry12th.pptxOrganic Name Reactions  for the students and aspirants of Chemistry12th.pptx
Organic Name Reactions for the students and aspirants of Chemistry12th.pptx
 
Biting mechanism of poisonous snakes.pdf
Biting mechanism of poisonous snakes.pdfBiting mechanism of poisonous snakes.pdf
Biting mechanism of poisonous snakes.pdf
 
Painted Grey Ware.pptx, PGW Culture of India
Painted Grey Ware.pptx, PGW Culture of IndiaPainted Grey Ware.pptx, PGW Culture of India
Painted Grey Ware.pptx, PGW Culture of India
 
History Class XII Ch. 3 Kinship, Caste and Class (1).pptx
History Class XII Ch. 3 Kinship, Caste and Class (1).pptxHistory Class XII Ch. 3 Kinship, Caste and Class (1).pptx
History Class XII Ch. 3 Kinship, Caste and Class (1).pptx
 
Introduction to AI in Higher Education_draft.pptx
Introduction to AI in Higher Education_draft.pptxIntroduction to AI in Higher Education_draft.pptx
Introduction to AI in Higher Education_draft.pptx
 
BASLIQ CURRENT LOOKBOOK LOOKBOOK(1) (1).pdf
BASLIQ CURRENT LOOKBOOK  LOOKBOOK(1) (1).pdfBASLIQ CURRENT LOOKBOOK  LOOKBOOK(1) (1).pdf
BASLIQ CURRENT LOOKBOOK LOOKBOOK(1) (1).pdf
 

Rubric Detail A rubric lists grading criteria that instruct.docx

  • 1. Rubric Detail A rubric lists grading criteria that instructors use to evaluate student work. Your instructor linked a rubric to this item and made it available to you. Select Grid View or List View to change the rubric's layout. Content https%3A%2F%2Fkeiseruniversity.blackboard.com%2Fwebapps %2Frubric%2FWEB- INF%2Fjsp%2Fcourse%2FrubricGradingPopup.jsp%3Fmode%3 Dgrid%26isPopup%3Dtrue%26rubricCount%3D1%26prefix%3D _7714706_1%26course_id%3D_411476_1%26maxValue%3D10 0.0%26rubricId%3D_345993_1%26viewOnly%3Dtrue%26displa yGrades%3Dfalse%26type%3Dgrading%26rubricAssoId%3D_60 5243_1 Name: Week 7 Video Presentation Description: Up to 10% deduction may be implemented for not following APA style standards (e.g., references and in-text citations).
  • 2. Grid ViewList View Poor Satisfactory Good Excellent Introduction Points: Points Range: 0 (0.00%) - 10.35 (10.35%) One of the following components are included in the presentation: (1) Student introduces the article topic, tells the
  • 3. reader what to expect. (2) rough background of literature (3) Student describes significance of the problem, (4)researcher's question(s) and hypothesis introduces the article topic, tells the reader what to expect. Student describes significance of the problem, researcher's hypothesis, and rough background of literature. Feedback: Points: Points Range: 10.5 (10.50%) - 11.85 (11.85%)
  • 4. Two of the following components are included in the presentation: (1) Student introduces the article topic, tells the reader what to expect. (2) rough background of literature (3) Student describes significance of the problem, (4)researcher's question(s) and hypothesis what to expect. Student describes significance of the problem, researcher's hypothesis, and rough background of literature. Feedback: Points: Points Range: 12 (12.00%) - 13.35 (13.35%)
  • 5. Three of the following components are included in the presentation: (1) Student introduces the article topic, tells the reader what to expect. (2) rough background of literature (3) Student describes significance of the problem, (4)researcher's question(s) and hypothesis Feedback: Points: Points Range:
  • 6. 13.5 (13.50%) - 15 (15.00%) All of the following components are included in the presentation: (1) Student introduces the article topic, tells the reader what to expect. (2) rough background of literature (3) Student describes significance of the problem, (4)researcher's question(s) and hypothesis Feedback: Methods Points:
  • 7. Points Range: 0 (0.00%) - 10.35 (10.35%) One of the following are demonstrated: (1) Student accurately and thoroughly explains the research design, (2) includes sampling, (3) identification and measurement of variables, (4) procedures, and data collection. Feedback: Points:
  • 8. Points Range: 10.5 (10.50%) - 11.85 (11.85%) Two of the following are demonstrated: (1) Student accurately and thoroughly explains the research design, (2) includes sampling, (3) identification and measurement of variables, (4) procedures, and data collection. Feedback:
  • 9. Points: Points Range: 12 (12.00%) - 13.35 (13.35%) Three of the following are demonstrated: (1) Student accurately and thoroughly explains the research design, (2) includes sampling, (3) identification and measurement of variables, (4) procedures, and data collection. Feedback:
  • 10. Points: Points Range: 13.5 (13.50%) - 15 (15.00%) Four of the following are demonstrated: (1) Student accurately and thoroughly explains the research design, (2) includes sampling, (3) identification and measurement of variables, (4) procedures, and data collection. Feedback: Results
  • 11. Points: Points Range: 0 (0.00%) - 10.35 (10.35%) None of the following are demonstrated: (1) the results of the study are presented; (2) the interpretation of results are clearly and concisely described (3) the connection to the researchers' questions/hypotheses are made Feedback:
  • 12. Points: Points Range: 10.5 (10.50%) - 11.85 (11.85%) One of the following are demonstrated: (1) the results of the study are presented; (2) the interpretation of results are clearly and concisely described (3) the connection to the researchers' questions/hypotheses are made
  • 13. Feedback: Points: Points Range: 12 (12.00%) - 13.35 (13.35%) Two of the following are demonstrated: (1) the results of the study are presented; (2) the interpretation of results are clearly and concisely described (3) the connection to the researchers' questions/hypotheses are made
  • 14. Feedback: Points: Points Range: 13.5 (13.50%) - 15 (15.00%) Three of the following are demonstrated: (1) the results of the study are presented; (2)
  • 15. the interpretation of results are clearly and concisely described (3) the connection to the researchers' questions/hypotheses are made Feedback: Critique Points: Points Range: 0 (0.00%) - 13.8 (13.80%)
  • 16. One of the following are demonstrated: (1) Critique addresses strengths and weaknesses of the study (2) Student applies higher-level thinking skills about possible flaws in the study prior to making recommendations (3) Critiques are have a clear connection to the design of the study and information provided; (4) generalizability of the study is discussed in a clear and logical manner. Feedback: Points: Points Range:
  • 17. 14 (14.00%) - 15.8 (15.80%) Two of the following are demonstrated: (1) Critique addresses strengths and weaknesses of the study (2) Student applies higher-level thinking skills about possible flaws in the study prior to making recommendations (3) Critiques are have a clear connection to the design of the study and information provided; (4) generalizability of the study is discussed in a clear and logical manner. Feedback: Points:
  • 18. Points Range: 16 (16.00%) - 17.8 (17.80%) Three of the following are demonstrated: (1) Critique addresses strengths and weaknesses of the study (2) Student applies higher-level thinking skills about possible flaws in the study prior to making recommendations (3) Critiques are have a clear connection to the design of the study and information provided; (4) generalizability of the study is discussed in a clear and logical manner. Feedback:
  • 19. Points: Points Range: 18 (18.00%) - 20 (20.00%) Four of the following are demonstrated: (1) Critique addresses strengths and weaknesses of the study (2) Student applies higher-level thinking skills about possible flaws in the study prior to making recommendations (3) Critiques are have a clear connection to the design of the study and information provided; (4) generalizability of the study is discussed in a clear and logical manner. Feedback:
  • 20. Creative Thinking Points: Points Range: 0 (0.00%) - 6.9 (6.90%) Recommendations for future research does not include the following: (1) understanding of research design (2) gaps or flaws in the study reviewed (3) original thinking. Feedback:
  • 21. Points: Points Range: 7 (7.00%) - 7.9 (7.90%) Recommendations for future research demonstrates one of the following: (1) understanding of research design (2) gaps or flaws in the study reviewed (3) original thinking. Feedback:
  • 22. Points: Points Range: 8 (8.00%) - 8.9 (8.90%) Recommendations for future research demonstrates two of the following: (1) understanding of research design (2) gaps or flaws in the study reviewed (3) original thinking. Feedback:
  • 23. Points: Points Range: 9 (9.00%) - 10 (10.00%) Recommendations for future research demonstrates three of the following: (1) understanding of research design (2) gaps or flaws in the study reviewed (3) original thinking. Feedback:
  • 24. Organization Points: Points Range: 0 (0.00%) - 3.45 (3.45%) Presentation is vague or uninteresting. Lacks supporting points and related details. Information lacks connection to the presentation topic. Information is not organized.
  • 25. Feedback: Points: Points Range: 3.5 (3.50%) - 3.95 (3.95%) Presentation is general, and at times uninteresting. Content is not clear and lack significant detail. Some information is linked to the presentation topic. Information is loosely organized.
  • 26. Feedback: Points: Points Range: 4 (4.00%) - 4.45 (4.45%) Presentation is general, but still interesting. Content is somewhat clear but could use more detail. Most information is linked to the presentation topic. Information is organized.
  • 27. Feedback: Points: Points Range: 4.5 (4.50%) - 5 (5.00%) Presentation is thorough and interesting. Content is very clear and very detailed. Information is directly linked to presentation topic. Information is very organized.
  • 28. Feedback: Verbal Communication Points: Points Range: 0 (0.00%) - 3.45 (3.45%) Speaker's voice is consistently too weak or too strong. Speaker fails to use inflections to emphasize key points and create interest or speaker often uses inflections inappropriately.
  • 29. Speaker's talking pace is consistently too slow or too fast. Feedback: Points: Points Range: 3.5 (3.50%) - 3.95 (3.95%) Speaker's voice is frequently too weak or too strong. Speaker rarely uses inflections to emphasize key points and create
  • 30. interest or speaker sometimes uses inflections inappropriately. Speaker's talking pace is often too slow or too fast. Feedback: Points: Points Range: 4 (4.00%) - 4.45 (4.45%) Speaker's voice is generally steady, strong, and clear. Speaker
  • 31. sometimes uses inflections to emphasize key points and create interest. Speaker's talking pace is appropriate. Feedback: Points: Points Range: 4.5 (4.50%) - 5 (5.00%) Speaker's voice is very confident, steady, strong, and clear.
  • 32. Speaker consistently uses inflections to emphasize key points or to create interest. Speaker's talking pace is consistently appropriate. Feedback: Mechanics Points: Points Range: 0 (0.00%) - 0 (0.00%)
  • 33. Presentation is less than 11 minutes long. Feedback: Points: Points Range: 3 (3.00%) - 3 (3.00%)
  • 34. Presentation is 11-12 minutes long. Feedback: Points: Points Range: 4 (4.00%) - 4 (4.00%) Presentation is 13-14 minutes long.
  • 35. Feedback: Points: Points Range: 5 (5.00%) - 5 (5.00%) Presentation is at least 15 minutes long.
  • 36. Feedback: Article Submission Points: Points Range: 0 (0.00%) - 0 (0.00%) Did not submit a full version of the article
  • 38. Points: Points Range: 0 (0.00%) - 0 (0.00%) Feedback:
  • 39. Points: Points Range: 5 (5.00%) - 5 (5.00%) Submitted the a full version of the article Feedback:
  • 40. Visual Tools Points: Points Range: 0 (0.00%) - 3.45 (3.45%) Visual aids demonstrate no creativity or clarity and are often difficult to read. Contains numerous errors and lack of detail. Little care taken in production. Presentation is weakened by the visual tools. Feedback:
  • 41. Points: Points Range: 3.5 (3.50%) - 3.95 (3.95%) Visual aids have limited creativity or clarity or are sometimes difficult to read. May have some errors and show some detail. Some care has been taken in production. Presentation is not enhanced by the visual tools. Feedback:
  • 42. Points: Points Range: 4 (4.00%) - 4.45 (4.45%) Visual aids are reasonably creative, clear, and easy to read. Evident that presentation shows a general attention to detail and accuracy. General care has been taken in production. Presentation is sometimes enhanced by the visual tools. Feedback:
  • 43. Points: Points Range: 4.5 (4.50%) - 5 (5.00%) Visual aids are very creative, clear, and easy to read. Clearly evident that presentation is well constructed, accurate, and shows attention to detail. Extra care has been taken in the production. Presentation is enhanced by the visual tools.
  • 44. Feedback: Show Descriptions Show Feedback Introduction-- Levels of Achievement: Poor 0 (0.00%) - 10.35 (10.35%) One of the following components are included in the presentation: (1) Student introduces the article topic, tells the reader what to expect. (2) rough background of literature (3) Student describes significance of the problem, (4)researcher's question(s) and hypothesis introduces the article topic, tells the
  • 45. reader what to expect. Student describes significance of the problem, researcher's hypothesis, and rough background of literature. Satisfactory 10.5 (10.50%) - 11.85 (11.85%) Two of the following components are included in the presentation: (1) Student introduces the article topic, tells the reader what to expect. (2) rough background of literature (3) Student describes significance of the problem, (4)researcher's question(s) and hypothesis what to expect. Student describes significance of the problem, researcher's hypothesis, and rough background of literature. Good 12 (12.00%) - 13.35 (13.35%) Three of the following components are included in the presentation: (1) Student introduces the article topic, tells the reader what to expect. (2) rough background of literature (3) Student describes significance of the problem, (4)researcher's question(s) and hypothesis
  • 46. Excellent 13.5 (13.50%) - 15 (15.00%) All of the following components are included in the presentation: (1) Student introduces the article topic, tells the reader what to expect. (2) rough background of literature (3) Student describes significance of the problem, (4)researcher's question(s) and hypothesis Feedback: Methods-- Levels of Achievement: Poor 0 (0.00%) - 10.35 (10.35%)
  • 47. One of the following are demonstrated: (1) Student accurately and thoroughly explains the research design, (2) includes sampling, (3) identification and measurement of variables, (4) procedures, and data collection. Satisfactory 10.5 (10.50%) - 11.85 (11.85%) Two of the following are demonstrated: (1) Student accurately and thoroughly explains the research design, (2) includes sampling, (3) identification and measurement of variables, (4) procedures, and data collection. Good 12 (12.00%) - 13.35 (13.35%) Three of the following are demonstrated: (1) Student accurately and thoroughly explains the research design, (2) includes sampling, (3) identification and measurement of variables, (4) procedures, and data collection. Excellent 13.5 (13.50%) - 15 (15.00%)
  • 48. Four of the following are demonstrated: (1) Student accurately and thoroughly explains the research design, (2) includes sampling, (3) identification and measurement of variables, (4) procedures, and data collection. Feedback: Results-- Levels of Achievement: Poor 0 (0.00%) - 10.35 (10.35%) None of the following are demonstrated: (1) the results of the study are presented; (2) the interpretation of results
  • 49. are clearly and concisely described (3) the connection to the researchers' questions/hypotheses are made Satisfactory 10.5 (10.50%) - 11.85 (11.85%) One of the following are demonstrated: (1) the results of the study are presented; (2) the interpretation of results are clearly and concisely described (3) the connection to the researchers' questions/hypotheses are made Good 12 (12.00%) - 13.35 (13.35%) Two of the following are demonstrated: (1) the results of the study are presented; (2) the interpretation of results are clearly and concisely described (3) the connection to the researchers' questions/hypotheses are made
  • 50. Excellent 13.5 (13.50%) - 15 (15.00%) Three of the following are demonstrated: (1) the results of the study are presented; (2) the interpretation of results are clearly and concisely described (3) the connection to the researchers' questions/hypotheses are made Feedback: Critique-- Levels of Achievement: Poor 0 (0.00%) - 13.8 (13.80%)
  • 51. One of the following are demonstrated: (1) Critique addresses strengths and weaknesses of the study (2) Student applies higher-level thinking skills about possible flaws in the study prior to making recommendations (3) Critiques are have a clear connection to the design of the study and information provided; (4) generalizability of the study is discussed in a clear and logical manner. Satisfactory 14 (14.00%) - 15.8 (15.80%) Two of the following are demonstrated: (1) Critique addresses strengths and weaknesses of the study (2) Student applies higher-level thinking skills about possible flaws in the study prior to making recommendations (3) Critiques are have a clear connection to the design of the study and information provided; (4) generalizability of the study is discussed in a clear and logical manner. Good 16 (16.00%) - 17.8 (17.80%)
  • 52. Three of the following are demonstrated: (1) Critique addresses strengths and weaknesses of the study (2) Student applies higher-level thinking skills about possible flaws in the study prior to making recommendations (3) Critiques are have a clear connection to the design of the study and information provided; (4) generalizability of the study is discussed in a clear and logical manner. Excellent 18 (18.00%) - 20 (20.00%) Four of the following are demonstrated: (1) Critique addresses strengths and weaknesses of the study (2) Student applies higher-level thinking skills about possible flaws in the study prior to making recommendations (3) Critiques are have a clear connection to the design of the study and information provided; (4) generalizability of the study is discussed in a clear and logical manner. Feedback:
  • 53. Creative Thinking-- Levels of Achievement: Poor 0 (0.00%) - 6.9 (6.90%) Recommendations for future research does not include the following: (1) understanding of research design (2) gaps or flaws in the study reviewed (3) original thinking. Satisfactory 7 (7.00%) - 7.9 (7.90%) Recommendations for future research demonstrates one of the following: (1) understanding of research design (2) gaps or flaws in the study reviewed (3) original thinking. Good 8 (8.00%) - 8.9 (8.90%)
  • 54. Recommendations for future research demonstrates two of the following: (1) understanding of research design (2) gaps or flaws in the study reviewed (3) original thinking. Excellent 9 (9.00%) - 10 (10.00%) Recommendations for future research demonstrates three of the following: (1) understanding of research design (2) gaps or flaws in the study reviewed (3) original thinking. Feedback: Organization--
  • 55. Levels of Achievement: Poor 0 (0.00%) - 3.45 (3.45%) Presentation is vague or uninteresting. Lacks supporting points and related details. Information lacks connection to the presentation topic. Information is not organized. Satisfactory 3.5 (3.50%) - 3.95 (3.95%) Presentation is general, and at times uninteresting. Content is not clear and lack significant detail. Some information is linked to the presentation topic. Information is loosely organized. Good 4 (4.00%) - 4.45 (4.45%) Presentation is general, but still interesting. Content is somewhat clear but could use more detail. Most information is linked to the presentation topic. Information is organized.
  • 56. Excellent 4.5 (4.50%) - 5 (5.00%) Presentation is thorough and interesting. Content is very clear and very detailed. Information is directly linked to presentation topic. Information is very organized. Feedback: Verbal Communication-- Levels of Achievement: Poor 0 (0.00%) - 3.45 (3.45%)
  • 57. Speaker's voice is consistently too weak or too strong. Speaker fails to use inflections to emphasize key points and create interest or speaker often uses inflections inappropriately. Speaker's talking pace is consistently too slow or too fast. Satisfactory 3.5 (3.50%) - 3.95 (3.95%) Speaker's voice is frequently too weak or too strong. Speaker rarely uses inflections to emphasize key points and create interest or speaker sometimes uses inflections inappropriately. Speaker's talking pace is often too slow or too fast. Good 4 (4.00%) - 4.45 (4.45%) Speaker's voice is generally steady, strong, and clear. Speaker sometimes uses inflections to emphasize key points and create interest. Speaker's talking pace is appropriate. Excellent 4.5 (4.50%) - 5 (5.00%)
  • 58. Speaker's voice is very confident, steady, strong, and clear. Speaker consistently uses inflections to emphasize key points or to create interest. Speaker's talking pace is consistently appropriate. Feedback: Mechanics-- Levels of Achievement: Poor 0 (0.00%) - 0 (0.00%) Presentation is less than 11 minutes long. Satisfactory
  • 59. 3 (3.00%) - 3 (3.00%) Presentation is 11-12 minutes long. Good 4 (4.00%) - 4 (4.00%) Presentation is 13-14 minutes long. Excellent 5 (5.00%) - 5 (5.00%) Presentation is at least 15 minutes long. Feedback:
  • 60. Article Submission-- Levels of Achievement: Poor 0 (0.00%) - 0 (0.00%) Did not submit a full version of the article Satisfactory 0 (0.00%) - 0 (0.00%) Good 0 (0.00%) - 0 (0.00%)
  • 61. Excellent 5 (5.00%) - 5 (5.00%) Submitted the a full version of the article Feedback: Visual Tools-- Levels of Achievement: Poor 0 (0.00%) - 3.45 (3.45%) Visual aids demonstrate no creativity or clarity and are often
  • 62. difficult to read. Contains numerous errors and lack of detail. Little care taken in production. Presentation is weakened by the visual tools. Satisfactory 3.5 (3.50%) - 3.95 (3.95%) Visual aids have limited creativity or clarity or are sometimes difficult to read. May have some errors and show some detail. Some care has been taken in production. Presentation is not enhanced by the visual tools. Good 4 (4.00%) - 4.45 (4.45%) Visual aids are reasonably creative, clear, and easy to read. Evident that presentation shows a general attention to detail and accuracy. General care has been taken in production. Presentation is sometimes enhanced by the visual tools. Excellent 4.5 (4.50%) - 5 (5.00%)
  • 63. Visual aids are very creative, clear, and easy to read. Clearly evident that presentation is well constructed, accurate, and shows attention to detail. Extra care has been taken in the production. Presentation is enhanced by the visual tools. Feedback: Name:Week 7 Video Presentation Description:Up to 10% deduction may be implemented for not following APA style standards (e.g., references and in-text
  • 64. citations). Accepted Manuscript Title: Brain alterations in children/adolescents with ADHD revisited: a neuroimaging meta-analysis of 96 structural and functional studies Authors: Fateme Samea, Solmaz Soluki, Vahid Nejati, Mojtaba Zarei, Samuele Cortese, Simon B. Eickhoff, Masoud Tahmasian, Claudia R. Eickhoff PII: S0149-7634(18)30662-6 DOI: https://doi.org/10.1016/j.neubiorev.2019.02.011 Reference: NBR 3351 To appear in: Received date: 31 August 2018 Revised date: 21 January 2019 Accepted date: 16 February 2019 Please cite this article as: Samea F, Soluki S, Nejati V, Zarei M, Cortese S, Eickhoff SB, Tahmasian M, Eickhoff CR, Brain alterations in children/adolescents with ADHD revisited: a neuroimaging meta-analysis of 96 structural and functional studies, Neuroscience and Biobehavioral Reviews (2019), https://doi.org/10.1016/j.neubiorev.2019.02.011
  • 65. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. https://doi.org/10.1016/j.neubiorev.2019.02.011 https://doi.org/10.1016/j.neubiorev.2019.02.011 1 Brain alterations in children/adolescents with ADHD revisited: a neuroimaging meta- analysis of 96 structural and functional studies Fateme Samea1 M.Sc., Solmaz Soluki1 M.Sc., Vahid Nejati1,2≠ Ph.D., Mojtaba Zarei3 MD., Ph.D., Samuele Cortese4,5,6,7 M.D., Ph.D., Simon B. Eickhoff8,9 M.D., Masoud Tahmasian3*≠ M.D., Ph.D., Claudia R. Eickhoff9,10,11 M.D. 1 Institute for Cognitive and Brain Sciences, Shahid Beheshti
  • 66. University, Tehran, Iran. 2 Department of Psychology, Shahid Beheshti University, Tehran, Iran. 3 Institute of Medical Science and Technology, Shahid Beheshti University, Tehran, Iran. 4 Center for Innovation in Mental Health, Academic Unit of Psychology, University of Southampton, Southampton, UK. 5 Faculty of Medicine, Clinical and Experimental Sciences (CNS and Psychiatry), University of Southampton, Southampton, UK. 6 Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, UK. 7 Department of Child and Adolescent Psychiatry, NYU Langone Medical Center, New York, USA. 8 Institute for Systems Neuroscience, Medical Faculty, Heinrich-Heine University Düsseldorf, Germany. 9 Institute of Neuroscience and Medicine (INM-1; INM-7), Research Center Jülich, Jülich, Germany. 10 Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • 67. 11 Department of Psychiatry, Psychotherapy, and Psychosomatics, RWTH Aachen University, Aachen, Germany. ≠ V.N. & M.T. contributed equally to this study. * Corresponding author: Masoud Tahmasian M.D., Ph.D., Institute of Medical Science and Technology, Shahid Beheshti University, Daneshjou Boulevard, Velenjak, P.O. Box 1983969411, Tehran, Iran. Telephone: +98-21-29905803; Fax: +98-21-29902650; Email: [email protected] Running title: Brain alterations in children/adolescents with ADHD Count: Title (16), Abstract (168), Text (4787), References (49), Figure (3), Table (1), Supplement file (1). Highlights ACCEPTED M
  • 68. ANUSCRIP T 2 with Attention- Deficit/Hyperactivity Disorder (ADHD), and those of meta- analyses provide mixed conclusions. Here, we conducted the largest meta-analysis including both structural and functional MRI, using state of the art procedures and following recently established consensus guidelines for neuroimaging meta-analyses, to address this inconsistency. alterations in ADHD in the main analysis. Among several different sub-analyses, we only observed the convergence dysfunction for task-fMRI experiments (using neutral stimuli) in the
  • 69. left pallidum/putamen and decreased activity (using male subjects) in the left inferior frontal gyrus. brain alterations across patients or a more distributed, network-based pathology lacking a consistent expression at any particular location, which might be due to heterogeneous clinical populations, in-/exclusion criteria, various experimental design, preprocessing, statistical procedures in individual publications. homogenous clinical samples assessing regional structural and functional alterations, as well as connectivity in parallel to unravel the relation between abnormal regional effects and disturbed integration in children/adolescents with ADHD. Abstract
  • 70. The findings of neuroimaging studies in children/adolescents with ADHD, and even those of previous meta-analyses, are divergent. Here, Activation Likelihood Estimation meta-analysis, following the current best-practice guidelines, was conducted. We searched multiple databases and traced the references up to June 2018. Then, we extracted the reported coordinates reflecting group comparison between ADHD and healthy subjects from 96 eligible studies, containing 1914 unique participants. The analysis of pooled ACCEPTED M ANUSCRIP T 3 structural and functional, sub-analyses restricted to modality, and in-/decreased contrast did not yield any significant findings. However, further sub-analyses in the task- fMRI experiments (neutral stimuli only) led to aberrant activity in the left pallidum/putamen and decreased activity (male subjects only) in the left inferior frontal gyrus. The overall findings indicate a lack of regional convergence in children/adolescents
  • 71. with ADHD, which might be due to heterogeneous clinical populations, various experimental design, preprocessing, statistical procedures in individual publications. Our results highlight the need for further high-powered investigations, but may also indicate ADHD pathophysiology might rest in network interactions rather than just regional abnormality. Key words: ADHD; Activation likelihood estimation; Coordinate-based meta-analysis; fMRI; VBM. ACCEPTED M ANUSCRIP T 4 1. Introduction Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition characterized by
  • 72. age-inappropriate and impairing inattention and/or impulsiveness-hyperactivity based on Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) and International Classification of Diseases (ICD- 10)(American Psychiatric Association, 2013). ADHD is commonly associated with school/academic, occupational, and social dysfunction (Biederman, 2005; Caye et al., 2016). Furthermore, deficit in several cognitive domains has been demonstrated in individuals with ADHD by neuropsychological studies (Sonuga- Barke et al., 2010) In addition to neuropsychological, genetics and neurochemical studies investigating the pathophysiology of ADHD (Caye et al., 2016), a large number of neuroimaging studies have been published over the last three decades to elucidate potential structural or functional alterations of ADHD (Hoogman et al., 2017; Konrad and Eickhoff, 2010). However, their findings are often inconsistent or conflicting. Hence, based on these individual studies, the neural correlates of ADHD remain elusive. Coordinate based meta-analysis (CBMA) of neuroimaging experiments can overcome these issues by providing a synoptic view of findings across studies, hereby consolidating the existing literature (Eickhoff et al.,
  • 73. 2012; Turkeltaub et al., 2002). CBMA uses the reported peak coordinates to identify “if” and “where” the convergence between reported coordinates is higher than expected by chance (Eickhoff et al., 2012). Previous meta-analyses on neuroimaging studies in ADHD have focused on structural imaging (Ellison-Wright et al., 2008; Frodl and Skokauskas, 2012; Nakao et al., 2011; Valera et al., 2007) or task-based functional imaging only (Cortese et al., 2012; Dickstein et al., 2006; Hart et al., 2012; Hart et al., 2013; Lei et al., 2015; McCarthy et al., 2014) (Supplemental Table S1). In addition of being outdated, however, they also yielded inconsistent findings. Meta-analyses of structural imaging studies suggested regional gray matter volume reductions in various cortical regions and also the basal ganglia and cerebellum, but showed limited agreement across analyses (Ellison-Wright et al., 2008; Frodl and Skokauskas, 2012; Nakao et al., 2011; Valera et al., 2007). Likewise, meta-analyses of activation studies heterogeneously indicated aberrations in a wide number of regions covering different cerebral lobes and systems as well as the basal ganglia, thalamus and cerebellum (Cortese et al., 2012; Dickstein et al., 2006; Hart et al., 2012; Hart et al., 2013; Lei et al., 2015; McCarthy et al.,
  • 74. 2014). Divergence across previous meta-analyses may in part reflects rather low number of included studies, ACCEPTED M ANUSCRIP T 5 different in-/exclusion criteria, (too) liberal statistical thresholding in search for positive findings (Muller et al., 2018; Tahmasian M, 2018). Moreover, heterogeneity in the examined hypotheses, the assessed clinical populations (e.g. subtype or severity of patients), the applied statistical approaches, and last but not least, different practices in reporting negative findings related to the included individual studies are important factors too (Muller et al., 2018; Tahmasian M, 2018). To address the heterogeneity and statistical power issues of the previous meta-analyses, we conducted a large scale structural and functional meta-analysis, following recently established consensus guidelines for neuroimaging meta- analyses suggested by the developers of all major
  • 75. software packages (Muller et al., 2018). The current meta- analysis is based on the largest number of original ADHD findings, strict adherence to best-practice protocols and stringent thresholding. The first aim of the current study was to find spatially consistent brain abnormalities in patients with ADHD compared to healthy comparisons. Hence, we pooled all the structural and functional studies, to provide a comprehensive overview of grey matter and functional alterations in ADHD. This approach has been applied previously to other neuropsychiatric disorder (Radua et al., 2012; Raschle et al., 2015; Sacher et al., 2012; Tahmasian et al., 2016; Tahmasian M, 2018; Zakzanis et al., 2003). Moreover, with regard to heterogeneity issues, we conducted several sub-analyses, clustered by extracted factors representing potential heterogeneity sources (i.e. modality, medication status, gender or behavioral subtype ADHD patients as well as specific cognitive domains and stimuli type of the tasks used in task-fMRI studies). By revisiting the issue of neuroimaging findings in ADHD, we thus aim to settle the ongoing dispute on the presence and localization of structural and/or functional brain alterations in children and adolescents with ADHD.
  • 76. 2. Methods 2.1. Search strategy and selection criteria Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(Moher et al.) and current consensus guidelines for neuroimaging meta-analyses (Muller et al., 2018), we searched PubMed, OVID (EMBASE, ERIC and Medline), Web of Knowledge,and Scopus up to June 1,2018,for neuroimaging studies on ADHD using the following search terms: (ADHD OR attention-deficit hyperactivity disorder) AND ("functional magnetic resonance imaging" OR fMRI OR "voxel-based morphometry" OR VBM) AND (children OR adolescents). In addition, we identified further papers by reference tracing and consulting ACCEPTED M ANUSCRIP T 6 review articles. Next, two authors (FS and SS) independently screened all the identified abstracts. Case-
  • 77. reports, letters to editors, reviews, meta-analyses, methodological studies and reports based on < 10 subjects per group were excluded as suggested previously (Muller et al., 2018; Tahmasian et al., 2017; Tahmasian et al., 2016). Furthermore, we excluded all studies using region of interest (ROI) analysis, as the null distribution in CBMA reflects a random spatial association between findings across the entire brain. The assumption that each voxel has a priori the same chance for being reported, however, is violated by ROI analyses, creating a sizable bias and inflated significance for the respective regions (Muller et al., 2018; Muller et al., 2017). Diagnosis of ADHD patients in the included papers had to be based on DSM-IV-TR, or DSM-5, or ICD-10 criteria. The other criteria include the mean age < 18 year old, no neurological or psychiatric comorbidities (such as depression, anxiety, autism, learning disorder, and epilepsy) or IQ > 70. We only included the experiments performing a group comparison between patients with ADHD and healthy controls (i.e., no within-group contrasts or contrasts of patients with ADHD versus patients with other
  • 78. disorders). We did not exclude reports on medicated ADHD patients in order to reflect the fact that these represent the bulk of the current literature. However, all included patients were off-medicated during the image acquisition. As suggested (Muller et al., 2018; Muller et al., 2017), studies reporting the effects of pharmacologic or psychological treatment were only included in case the authors reported between-group differences at baseline or main effects of diagnosis. 2.2. Organization of Coordinates Extracted data included bibliographic information, age, gender & number of subjects, imaging modality, subtype and medication status of patients with ADHD, and the peak coordinates of group comparisons in Montreal Neurological Institute (MNI) (A.C. Evans, 1993) or Talairach (Talairach and Tournoux, 1988) space with the latter being subsequently transformed into MNI space.(Lancaster et al., 2007) Of note, in neuroimaging meta-analyses, “study” refers to a single scientific publication while “experiment” denotes a particular comparison, i.e., a contrast yielding a distinct set of coordinates. Given that the samples of several studies (partially) overlapped,
  • 79. including such experiments may yield spurious convergence. Thus, we followed the recommended approach to organize data by subjects ACCEPTED M ANUSCRIP T 7 rather than experiments, avoiding undue influence of a patient cohort (Turkeltaub et al., 2012). Specifically, we combined experiments in the same direction (in-/decreases) for a given set of patients, yielding a maximum of two “experiments” per sample consisting of all extracted coordinates for this set of patients (i.e., one for ADHD > Control contrast, one for Control > ADHD contrast). Of note, the experiments were merged regardless of whether separate experiments were reported in one or different papers whenever identity of the subjects could be established (Turkeltaub et al., 2012). 2.3. Activation likelihood estimation
  • 80. We used the revised version of the Activation Likelihood Estimation (ALE) algorithm (Eickhoff et al., 2012) to test significant convergence between activation foci relative to a null-hypothesis of random spatial association between experiments. Firstly, the reported foci were modeled as center peaks of 3D Gaussian probability distributions representing the spatial uncertainty associated with these arising from both sampling effects and methodological differences in data processing and analysis. Importantly, the modeled uncertainty is scaled by the number of subjects in the smaller group to accommodate higher uncertainty of findings from smaller samples. The ensuing per- experiment “modeled activation” maps were then combined into an ALE map by computing their union across experiments (Eickhoff et al., 2012; Turkeltaub et al., 2012). Subsequently, an analytical approach based on non-linear histogram integration was conducted to test against the null hypothesis of random spatial association (Eickhoff et al., 2012; Turkeltaub et al., 2012), followed by cluster-level family-wise error (cFWE) correction at p < 0.05 (cluster- forming threshold of p < 0·001 on the voxel level) based on Monte-Carlo simulation (Eickhoff et al., 2017;
  • 81. Muller et al., 2018). 2.4. Performed analyses We first performed an ALE analysis across all identified experiments in order to probe for abnormalities independently of direction and neuroimaging modality. Next, we performed three separate sets of analyses assessing increases, decreases or aberrations (pooling in-/decreases) in structural (VBM) and functional (fMRI) imaging, respectively. As recommended, separate analyses were performed only for those combinations of direction and modality yielding at least 17 experiments, given consideration on ACCEPTED M ANUSCRIP T 8 robustness and power (Eickhoff et al., 2016). Hence, specific analysis of rs-fMRI studies was not possible due to low number of experiments. Relatedly, we also split the available experiments by medication
  • 82. status, gender or behavioral subtype ADHD patients, noting that the number of experiments for female patients as well as isolated inattentive or hyperactive subtypes was insufficient for analysis. Furthermore, we probed for convergence among task-fMRI studies when focusing only on specific cognitive domains and found a sufficient number of experiments (i.e., > 17) (Eickhoff et al., 2016) for inhibitory and attention, but also performed a joint analyses on the remaining cognitive tasks (memory, timing, reasoning). Number of experiments on reward processing tasks, were not sufficient to analyze. Finally, the available studies were also categorized by stimulus type (emotion, reward, neutral), but only field a sufficient number for a sub-analysis of neutral stimuli. Finally, for significant convergent findings, related to subgroups of experiments e.g. subgroup of all fMRI experiments representing male only, we checked the number of studies, contributed to the convergent cluster. The question was whether the contribution rate represents the proportion of all related experiments in the database. For example, if X out of P fMRI experiments with mail only contribute to a convergent cluster, we evaluated that how likely it is that, this
  • 83. contribution rate represent proportion of P fMRI experiments across all available experiments (96) in the database. We tested this for each significant finding separately, using binomial test in SPSS (v22). Wherever the contribution rate of a subgroup of experiments represents the proportion of their experiments across all experiments in the database, one could infer that the convergent finding may be driven by the effects of main indicator (e.g. male only) of the subgroup. Results From a pool of 1586 retrieved publications, 205 potentially eligible studies were identified. Among them, 109 were subsequently excluded due to reasons including ROI analyses, no reported contrast between ADHD and healthy subjects, or reporting of longitudinal effects without baseline. In case the study met all the criteria except reporting the peak coordinates for group comparisons, we contacted the authors to obtain the relevant information. In total, 96 studies were finally eligible for the current meta-analyses (Figure 1, Supplemental Table S2) reporting a total of 130 individual experiments (92 task-fMRI, 32 VBM
  • 84. ACCEPTED M ANUSCRIP T 9 and 6 rs-fMRI; Supplement) based on 1914 unique subjects. Of these, 62.7% reported decreases in ADHD patients compared to controls (54 task-fMRI, 25 VBM and 3 rs-fMRI; Supplement). 2.5. Meta-analyses of neuroimaging findings in ADHD Overall, we conducted several separate ALE meta-analyses. When pooling in-/decreases experiments (Figure 2), the results yielded p= 0.129 (across structural and functional findings), p= 0.452 (for VBM only), and p= 0.212 (for fMRI, pooling across task and resting state). Also a restriction to task-fMRI experiments did not provide a significance finding (p= 0.062). Similarly, restricting meta-analyses to in- /decreases in ADHD, lead to non-significant findings (decreased: all p= 0.195, VBM p= 0.341, fMRI p= 0.138, task-fMRI only p= 0.329; increased: all p= 0.175; fMRI p= 0.153, task-fMRI p= 0.668; Table 1A). Of
  • 85. note, repeating all analyses with an alternative, potentially more liberal statistical threshold (i.e., threshold- free cluster enhancement, TFCE (Smith and Nichols, 2009)), fully corroborated these results and likewise reveal non-significant convergence (Table 1A). 2.6. Follow-up sub-analyses on task fMRI findings Of the 68 task-fMRI studies, 33% investigated inhibitory control, 29% attention, 25% other cognitive domains and 13% reward processing (Supplement). With respect to stimulus type, 70% used neutral, 12% emotional and 17% rewarding stimuli (Supplement). Again, no significant convergence (Table 1B) was found in any of the more restricted and hence specific sub- analyses for which a sufficient number of experiments was available (inhibitory control p= 0.302, attention p= 0.847, all other cognitive domains p= 0.520), even though we noted a trend towards significance when specifically analyzing the convergence of decreased activity for inhibitory control (p= 0.052). Repeating all analyses with TFCE threshold, the latter result did pass statistical significance at p= 0.040 (Table 1B). We also conducted separate analyses on in-/decreases and their
  • 86. pooled effect for only those experiments using neutral stimuli and found significant aberrant convergence in the left pallidum/putamen (local maximum: -18, 4, -4 in MNI space, 109 voxels, 69.7% left Pallidum, 12.7% left Putamen) when looking at ACCEPTED M ANUSCRIP T 10 the pooled in-/decreased activation experiments in ADHD (p= 0.036), but not for either direction individually (decrease p= 0.244, increase p= 0.110 (Figure 3A, Table 1C). Finally, we also repeated all main and follow-up analyses including only medication-naïve, male or combined-type ADHD patients, respectively, yielding a single (marginally significant) convergence for decreased fMRI (task-fMRI and rs-fMRI) in male subjects on the left inferior frontal gyrus (IFG) (local maximum: -38, 26, -16 in MNI space, 93 voxels, 83% in frontal orbital cortex) (p=0.049, Figure 3B,
  • 87. Supplement). Moreover, we used binomial test on the contribution-rate (i.e. 0.13 (4 out of 30) of decreased fMRI experiments with male only and their main proportion in the database (i.e.52% (30 out of 57 decreased fMRI experiments). The result indicated that observed contribution-rate significantly is less than the chance probability (observed-prob= 0.13, test-prob= 0.52, p-value= 0.001). Regarding the left Putamen-Pallidum, 11 out of 41 task-fMRI experiments with neutral stimuli, contributed to this convergent finding, while the proportion of task-fMRI experiments with neutral stimuli in the database was 0.44 (41out of 92 task-fMRI experiments). The result of binomial test was not significant (observed-prob= 0.37, test- prob= 0.44, p-value= 0.268). Discussion The current study provides the largest and most comprehensive meta-analytic summary of neuroimaging findings in children and adolescents with ADHD across several imaging modalities, following the current best-practice recommendations (Muller et al., 2018). The pooled structural and functional assessment and the additional sub-analyses focusing on homogeneous subsets of
  • 88. experiments (in terms of modality and direction) yielded no significant convergence across the available ADHD literature. Reasons of this heterogeneity may be accounted for several issues including clinical heterogeneity and variations in experimental design and analysis. We discuss further this heterogeneity in the next section. Moreover, we also restricted all the experiments by medication-status, gender, ADHD sub-types, as well as task-fMRI by specific cognitive domains and stimulus types, and observed convergence aberrant finding in the task- ACCEPTED M ANUSCRIP T 11 fMRI experiments (using neutral stimuli) in the left pallidum/putamen and decreased activity (in male subjects only) in the left IFG. Dysfunction of the pallidum/putamen and IFG has been reported in ADHD previously (Castellanos and Proal, 2012; Cortese et al., 2012; Hart et al., 2012; Hart et al., 2013; Konrad
  • 89. and Eickhoff, 2010; Rubia, 2011), which is in line with the fronto-striatal pathway dysfunction model of ADHD. The dopamine-rich ventral putamen receives fibers from the medial orbitofrontal cortex and IFG and it has been shown that their abnormality is linked with hyperactivity, impulsivity, disinhibition, and inattention symptoms of ADHD (Itami and Uno, 2002; Max et al., 2002; Rubia, 2011). 2.7. Neuroimaging in ADHD: A heterogeneous field The heterogeneity in experimental design and procedure across the task-based fMRI experiments, which containing 70% of our included studies, might be one of the potential sources of inconsistent results. Most available tasks were often aimed at probing various functional impairments in children/adolescents with ADHD (Arnsten and Rubia, 2012). The paradigms of included tasks varied widely (i.e. Go/No-Go, Stroop, Stop signal, timing, reward processing, memory and attention tasks), but each of them applied in less than 10 studies. In addition to the paradigm diversity, there is flexibility in each paradigm regarding to the type of stimuli, presentation of stimuli and type of trials. Due to these inconsistencies, the cognitive operations
  • 90. performed by the subjects when engaging in the respective tasks should vary widely. From the overall inconsistent results of the current study, we conclude that there is limited convergent regional abnormality that was tapped into by the structural and functional experiments that have been used to study ADHD, to date. Additionally, across cognitive domains, there is no convergence in the neurobiological aberrations underlying ADHD. Worthy of note, in the structural imaging studies (i.e. VBM), experimental or design flexibility is absent, but analytical heterogeneity still plays a major role (e.g., various statistical thresholds or spatial transformation of the images). Finally, the included rs-fMRI analytical approaches were likewise vastly different. This methodological multiplicity may have contributed a lot of variance to the current literature beyond what could already be expected given the heterogeneity of the clinical presentation in ADHD. Our divergent results on structural and functional experiments support the view that ADHD is a multi-faceted disorder, which affects several functional and behavioral domains. We would hence side with ACCEPTED M
  • 91. ANUSCRIP T 12 the hypothesis, that ADHD may be primarily reflecting a dysconnectivity disorder, i.e., that the various cognitive and affective affections in ADHD patients may stem from impaired communication and integration between the brain regions/networks rather than from regional abnormalities only (Castellanos and Proal, 2012; Konrad and Eickhoff, 2010). Of note, here we could not test the network alterations due to low number of available rs-fMRI experiment. Also, as recommended, we did not include the ROI-based functional connectivity publications (Muller et al., 2018). In particular, such distributed network pathology would explain both the lack of convergence in either structural or functional imaging findings, as well as the heterogeneous expression of the core and associated symptoms across patients. The latter is particularly important, as ADHD is clinically described as a heterogeneous disorder, which includes
  • 92. impairment on several cognitive and emotional domains (Wahlstedt et al., 2009). These deficits have differential influence on neuropsychological functioning of patients and lead to various clinical presentations (Wahlstedt et al., 2009). Although ADHD is often classified into three different presentations, they have considerable overlap (Wahlstedt et al., 2009). A recent neuroimaging study also found no common brain abnormalities in all ADHD subgroups, suggesting that ADHD is a collection of discrete disorders (Stevens et al., 2018). It is worth mentioning that most of the included studies either recruited patients from different presentations or did not specify the clinical presentation of ADHD that was investigated, even though diagnostic validity of such presentation classification is questionable per se (Bernfeld, 2012). Moreover, most studies retained in the present meta-analysis included participants with high rates of comorbidities, which increases the clinical heterogeneity of the samples (Elia et al., 2008). Thus, even though all patients were labeled as ADHD, they may have presented quite differently, both within each and across samples, potentially featuring different underlying pathologies and hereby further
  • 93. contributing to the lack of convergence using combination of structural and functional experiments. We discuss now key methodological issue form the body of research that we included. 2.8. Methodological issues A main advantage of the ALE meta-analysis approach is integration of a large number of findings to establish consensus on the spatial locations of regional disruptions in neuropsychiatric disorders (Eickhoff et al., 2012; Goodkind et al., 2015; Muller et al., 2017; Tahmasian et al., 2017; Tahmasian et al., 2018; ACCEPTED M ANUSCRIP T 13 Tahmasian et al., 2016). Thus, ALE allows synthesizing the multitude of single studies in an unbiased fashion and consolidates the available literature, overcoming problems associated with individual neuroimaging experiments (Eickhoff et al., 2012; Muller et al., 2018). Here, we followed the recently
  • 94. developed best-practice protocols of neuroimaging meta- analysis (Muller et al., 2018). In particular, we performed multiple-comparison correction using the cluster- level FWE correction, which should be preferred over the liberal but previously popular false discovery rate (FDR) to provide maximum statistical rigor (Eickhoff et al., 2017; Eickhoff et al., 2016). In addition, it has been suggested to include at least 17 experiments into an ALE meta-analysis to achieve 80% power for at least moderate to strong effects (Eickhoff et al., 2016). To explore the potential moderators that might influence on our results, we first identified all eligible experiments and subsequently, categorized them by available variety sources including imaging modality, medication status, gender or behavioral subtype ADHD patients. However, the number of experiments of most of the categories (including rs-fMRI, as well as female patients and isolated inattentive or hyperactive subtypes) were insufficient for a valid analysis. Given that ALE analyses with very few sets of experiments have been shown to be unstable and potentially driven by individual studies, we could not perform the initially
  • 95. planned set of assessments for the effects of most potential moderators. Indeed, exploring moderators is not feasible unless each subgroup yields enough experiments for a separate meta-analysis. Furthermore, by splitting the task-fMRI experiments with specific cognitive domains and also stimulus type of the tasks, the issue was the same, as sufficient number of experiments were not supplied for all subgroups. Accordingly, we could only perform separate meta-analyses for individual subgroups of experiments, categorized by inhibitory, attention, and also joint of the remaining cognitive tasks (memory, timing, and reasoning), as well as neutral stimuli, to probe for convergent functional abnormalities in children and adolescents with ADHD. However, the results were significant only for two subgroups of experiments, i.e task-fMRI experiments with neutral stimuli and decreased fMRI experiments with male only. According to the result of binomial test for neutral stimuli experiments, the contribution-rate of experiments represents the main proportion of the experiments with neutral stimuli in the database. Hence, the convergent finding of task-fMRI experiments may be driven by the effects of using tasks with neutral stimuli. Moreover,
  • 96. regarding the decreased fMRI experiments with male only, the result of the binomial test indicated that ACCEPTED M ANUSCRIP T 14 observed contribution-rate significantly is less than the chance probability. Hence, the contribution-rate of experiments with male only is likely an under-representation of the expected proportion in the database. Moreover, we carefully excluded studies with ROI analysis to avoid inflating significance for the particular regions (Muller et al., 2018). Importantly, we organized our dataset based on the recommended approach, which has been introduced to minimize within-group effects (Turkeltaub et al., 2012) We discuss now our findings in the light of previous ADHD meta- analyses. 2.9. Divergence of previous mega- and meta-analyses findings Previous ADHD meta-analyses focusing on structural imaging (Ellison-Wright et al., 2008; Frodl and
  • 97. Skokauskas, 2012; Nakao et al., 2011; Valera et al., 2007) and task-based fMRI (Cortese et al., 2012; Dickstein et al., 2006; Hart et al., 2012; Hart et al., 2013; Lei et al., 2015; McCarthy et al., 2014) found significant brain abnormalities in variety of brain regions (Supplemental Table S1). Hence, not only individual studies, but also previous meta-analyses in children/adolescents with ADHD have yielded inconsistent findings. This might be due to the fact that those meta-analyses were not following the current best-practice guideline, which is developed recently (Muller et al., 2018). Results of such meta-analyses may be in part driven by small sample size, liberal thresholding and other methodological choices that should be considered non-optimal currently. For example, three meta-analyses on task fMRI (Cortese et al., 2012; Dickstein et al., 2006; Lei et al., 2015) and one on VBM studies (Ellison-Wright et al., 2008) used a version of GingerALE, which was later discovered to have a bug leading to inadequately liberal thresholds that were substantially different from the requested level and did not control for multiple comparisons (Eickhoff et al., 2017). In turn, two fMRI meta- analyses focusing on timing (Hart et al., 2012)
  • 98. and inhibition/attention (Hart et al., 2013), as well as two VBM meta-analyses applied the Signed Differential Mapping (SDM) method (Frodl and Skokauskas, 2012; Nakao et al., 2011), which by design are being more liberal, i.e., to err on the side of false positives rather than negatives. Last but not least, previous meta-analyses assessed substantially smaller samples of experiments, which entail a high likelihood (formally) significant convergence might be often driven by few experiments and dominates the regional effects of those studies (Muller et al., 2018). Given the current growth of the literature, however, we were able to apply more stringent in-/exclusion criteria and still analyze an unprecedentedly large ACCEPTED M ANUSCRIP T 15 number of individual experiments. Our included studies are overlapping with those of previous meta- analyses in various degrees. We excluded the ones that did not
  • 99. meet our inclusion criteria (Supplemental Table S1). Although there are many available CBMA with significant consistent results in various neuropsychiatric disorders (Cortese et al., 2016; Cortese et al., 2012; Goodkind et al., 2015; Herz et al., 2014; Radua et al., 2012; Tahmasian et al., 2017; Tahmasian et al., 2016; Wegbreit et al., 2014) , some previous meta-analyses in unipolar depression (Muller et al., 2017) and insomnia disorder (Tahmasian et al., 2018; Tahmasian M, 2018) investigated a large body of literature and followed the best-practice guideline (i.e. rigorous in-/exclusion criteria and statistical threshold), but still observed a lack of convergence across their sub-analyses. The authors suggested that small samples of participants, clinical variability, various experimental design, flexibility in preprocessing, and statistical approaches could be the possible reasons of observed heterogeneity in such disorder (Muller et al., 2017; Tahmasian et al., 2018). Recently, a study comprising 1713 participants with ADHD and 1529 controls from 23 sites applied FreeSurfer and found that volume of the accumbens, amygdala, caudate, hippocampus,
  • 100. putamen, and intracranial volume were smaller in subjects with ADHD compared with controls (9). We did not include this paper, as they focused on particular subcortical ROIs, which could affect the whole brain results. In the present study, we included 28 structural experiments which yielded no significant volume alterations. Of note, the mentioned study has a unified analysis protocol and therefore has less experimental and analytical noise and hence is more likely to find the regional abnormality. However, it is not clear whether the findings are just reflecting their particular regional choices or are robust across studies, which can be tested by neuroimaging meta-analyses. 2.10. Future directions Technical problems and clinical heterogeneity aside, we would argue that one of the major obstacles in neuroimaging research is the strong bias towards publishing positive results, combined with low sample size and high preprocessing and analytical flexibility (garden of forking paths) in (f)MRI analyses. It stands to reason that this combination provides the wrong incentives to analyze data in various ways until
  • 101. significant results emerge, which are often spurious and not replicable or convergent. Coupled with the ACCEPTED M ANUSCRIP T 16 fact that direct replication studies are still rare, we would thus worry that a large body of the imaging literature contains inflated reports of regional effects which only becomes apparent once well-powered and robust (through their size) meta-analyses as the current are performed. To us, this indicates a need for change at several levels including higher-powered original studies, homogenous clinical populations, pre- registration of analysis plans, a better standardization of processing pipelines (also from the level of replicability), large scale open data sharing, and maybe most importantly a cultural shift away from the current bias towards more likely publication of positive findings as well-powered inconsistent findings may be as important to move the entire field forward.
  • 102. 3. Conclusion To the best of our knowledge, this study is the largest meta- analysis of structural and functional neuroimaging experiments in children/adolescents with ADHD. We found no significant convergent across structural and functional regional alterations in ADHD, which might be attributable to clinical heterogeneity, experimental and analytical flexibility and positive publication bias, but could also point towards a more distributed, network-based pathology lacking a consistent expression at any particular location. Among many different sub-analyses, we only observed the convergence dysfunction for task-fMRI experiments (using neutral stimuli) in the left pallidum/putamen and decreased activity (using male subjects) in the left IFG. This study highlights the need for further exploration assessing regional structural and functional maladaptation, as well as connectivity in parallel to unravel the relation between abnormal regional effects and disturbed integration in ADHD. Conflict of interest The authors declare that the research was conducted in the
  • 103. absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgements SBE is supported by the Deutsche Forschungsgemeinschaft DFG (EI 816/11-1), the National Institute of Mental Health (R01-MH074457), the Helmholtz Portfolio Theme "Supercomputing and Modeling for the ACCEPTED M ANUSCRIP T 17 Human Brain" and the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 785907 (HBP SGA2). ACCEPTED M ANUSCRIP T
  • 104. 18 References A.C. Evans, D.L.C., S.R Mills, E.D. Brown, R.L. Kelly, T.M. Peters, 1993. 3D statistical neuroanatomical models from 305 MRI volumes. Nuclear Science Symposium and Medical Imaging Conference, IEEE Conference Record, 1813–1817. American Psychiatric Association, 2013. Diagnostic and Statistical Manual of Mental Disorders, 5th ed, Washington, DC. Arnsten, A.F., Rubia, K., 2012. Neurobiological circuits regulating attention, cognitive control, motivation, and emotion: disruptions in neurodevelopmental psychiatric disorders. J Am Acad Child Adolesc Psychiatry 51, 356-367. Bernfeld, J., 2012. ADHD and factor analysis: are there really three distinct subtypes of ADHD? Appl Neuropsychol Child 1, 100-104. Biederman, J., 2005. Attention-deficit/hyperactivity disorder: a selective overview. Biol Psychiatry 57, 1215- 1220. Castellanos, F.X., Proal, E., 2012. Large-scale brain systems in ADHD: beyond the prefrontal-striatal model. Trends Cogn Sci 16, 17-26. Caye, A., Rocha, T.B., Anselmi, L., Murray, J., Menezes, A.M., Barros, F.C., Goncalves, H., Wehrmeister, F., Jensen, C.M., Steinhausen, H.C., Swanson, J.M., Kieling, C., Rohde,
  • 105. L.A., 2016. Attention-Deficit/Hyperactivity Disorder Trajectories From Childhood to Young Adulthood: Evidence From a Birth Cohort Supporting a Late-Onset Syndrome. JAMA Psychiatry 73, 705-712. Cortese, S., Castellanos, F.X., Eickhoff, C.R., D'Acunto, G., Masi, G., Fox, P.T., Laird, A.R., Eickhoff, S.B., 2016. Functional Decoding and Meta-analytic Connectivity Modeling in Adult Attention-Deficit/Hyperactivity Disorder. Biol Psychiatry 80, 896-904. Cortese, S., Kelly, C., Chabernaud, C., Proal, E., Di Martino, A., Milham, M.P., Castellanos, F.X., 2012. Toward systems neuroscience of ADHD: a meta-analysis of 55 fMRI studies. Am J Psychiatry 169, 1038-1055. Dickstein, S.G., Bannon, K., Castellanos, F.X., Milham, M.P., 2006. The neural correlates of attention deficit hyperactivity disorder: an ALE meta-analysis. J Child Psychol Psychiatry 47, 1051-1062. Eickhoff, S.B., Bzdok, D., Laird, A.R., Kurth, F., Fox, P.T., 2012. Activation likelihood estimation meta-analysis revisited. Neuroimage 59, 2349-2361. Eickhoff, S.B., Laird, A.R., Fox, P.M., Lancaster, J.L., Fox, P.T., 2017. Implementation errors in the GingerALE Software: Description and recommendations. Hum Brain Mapp 38, 7-11. Eickhoff, S.B., Nichols, T.E., Laird, A.R., Hoffstaedter, F., Amunts, K., Fox, P.T., Bzdok, D., Eickhoff, C.R., 2016. Behavior, sensitivity, and power of activation likelihood estimation characterized by massive empirical simulation. Neuroimage 137, 70-85.
  • 106. Elia, J., Ambrosini, P., Berrettini, W., 2008. ADHD characteristics: I. Concurrent co-morbidity patterns in children & adolescents. Child Adolesc Psychiatry Ment Health 2, 15. Ellison-Wright, I., Ellison-Wright, Z., Bullmore, E., 2008. Structural brain change in Attention Deficit Hyperactivity Disorder identified by meta-analysis. BMC psychiatry 8, 51. ACCEPTED M ANUSCRIP T 19 Frodl, T., Skokauskas, N., 2012. Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects. Acta psychiatrica Scandinavica 125, 114-126. Goodkind, M., Eickhoff, S.B., Oathes, D.J., Jiang, Y., Chang, A., Jones-Hagata, L.B., Ortega, B.N., Zaiko, Y.V., Roach, E.L., Korgaonkar, M.S., Grieve, S.M., Galatzer-Levy, I., Fox, P.T., Etkin, A., 2015. Identification of a common neurobiological substrate for mental illness. JAMA Psychiatry 72, 305-315. Hart, H., Radua, J., Mataix-Cols, D., Rubia, K., 2012. Meta- analysis of fMRI studies of timing in attention-deficit hyperactivity disorder (ADHD). Neurosci Biobehav Rev 36, 2248-2256.
  • 107. Hart, H., Radua, J., Nakao, T., Mataix-Cols, D., Rubia, K., 2013. Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention- deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects. JAMA Psychiatry 70, 185-198. Herz, D.M., Eickhoff, S.B., Lokkegaard, A., Siebner, H.R., 2014. Functional neuroimaging of motor control in Parkinson's disease: a meta-analysis. Hum Brain Mapp 35, 3227-3237. Hoogman, M., Bralten, J., Hibar, D.P., Mennes, M., Zwiers, M.P., Schweren, L.S.J., van Hulzen, K.J.E., Medland, S.E., Shumskaya, E., Jahanshad, N., Zeeuw, P., Szekely, E., Sudre, G., Wolfers, T., Onnink, A.M.H., Dammers, J.T., Mostert, J.C., Vives-Gilabert, Y., Kohls, G., Oberwelland, E., Seitz, J., Schulte-Ruther, M., Ambrosino, S., Doyle, A.E., Hovik, M.F., Dramsdahl, M., Tamm, L., van Erp, T.G.M., Dale, A., Schork, A., Conzelmann, A., Zierhut, K., Baur, R., McCarthy, H., Yoncheva, Y.N., Cubillo, A., Chantiluke, K., Mehta, M.A., Paloyelis, Y., Hohmann, S., Baumeister, S., Bramati, I., Mattos, P., Tovar-Moll, F., Douglas, P., Banaschewski, T., Brandeis, D., Kuntsi, J., Asherson, P., Rubia, K., Kelly, C., Martino, A.D., Milham, M.P., Castellanos, F.X., Frodl, T., Zentis, M., Lesch, K.P., Reif, A., Pauli, P., Jernigan, T.L., Haavik, J., Plessen, K.J., Lundervold, A.J., Hugdahl, K., Seidman, L.J., Biederman, J., Rommelse, N., Heslenfeld, D.J., Hartman, C.A., Hoekstra, P.J., Oosterlaan, J., Polier, G.V., Konrad, K., Vilarroya, O., Ramos-Quiroga, J.A., Soliva, J.C., Durston, S., Buitelaar, J.K., Faraone, S.V., Shaw, P., Thompson, P.M., Franke, B., 2017. Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis. Lancet
  • 108. Psychiatry 4, 310-319. Itami, S., Uno, H., 2002. Orbitofrontal cortex dysfunction in attention-deficit hyperactivity disorder revealed by reversal and extinction tasks. Neuroreport 13, 2453-2457. Konrad, K., Eickhoff, S.B., 2010. Is the ADHD brain wired differently? A review on structural and functional connectivity in attention deficit hyperactivity disorder. Hum Brain Mapp 31, 904-916. Lancaster, J.L., Tordesillas-Gutierrez, D., Martinez, M., Salinas, F., Evans, A., ZilleS, K., Mazziotta, J.C., Fox, P.T., 2007. Bias between MNI and talairach coordinates analyzed using the ICBM-152 brain template. Human Brain Mapping 28, 1194-1205. Lei, D., Du, M., Wu, M., Chen, T., Huang, X., Du, X., Bi, F., Kemp, G.J., Gong, Q., 2015. Functional MRI reveals different response inhibition between adults and children with ADHD. Neuropsychology 29, 874-881. Max, J.E., Fox, P.T., Lancaster, J.L., Kochunov, P., Mathews, K., Manes, F.F., Robertson, B.A., Arndt, S., Robin, D.A., Lansing, A.E., 2002. Putamen lesions and the development of attention-deficit/hyperactivity symptomatology. J Am Acad Child Adolesc Psychiatry 41, 563-571. McCarthy, H., Skokauskas, N., Frodl, T., 2014. Identifying a consistent pattern of neural function in attention deficit hyperactivity disorder: a meta-analysis. Psychol Med 44, 869-880. Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G., Group, P., 2009. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med
  • 109. 6, e1000097. ACCEPTED M ANUSCRIP T 20 Muller, V.I., Cieslik, E.C., Laird, A.R., Fox, P.T., Radua, J., Mataix-Cols, D., Tench, C.R., Yarkoni, T., Nichols, T.E., Turkeltaub, P.E., Wager, T.D., Eickhoff, S.B., 2018. Ten simple rules for neuroimaging meta-analysis. Neurosci Biobehav Rev 84, 151-161. Muller, V.I., Cieslik, E.C., Serbanescu, I., Laird, A.R., Fox, P.T., Eickhoff, S.B., 2017. Altered Brain Activity in Unipolar Depression Revisited: Meta-analyses of Neuroimaging Studies. JAMA Psychiatry 74, 47-55. Nakao, T., Radua, J., Rubia, K., Mataix-Cols, D., 2011. Gray matter volume abnormalities in ADHD: voxel-based meta-analysis exploring the effects of age and stimulant medication. Am J Psychiatry 168, 1154-1163. Radua, J., Borgwardt, S., Crescini, A., Mataix-Cols, D., Meyer- Lindenberg, A., McGuire, P.K., Fusar-Poli, P., 2012. Multimodal meta-analysis of structural and functional brain changes in first episode psychosis and the effects of antipsychotic medication. Neurosci Biobehav Rev 36, 2325- 2333. Raschle, N.M., Menks, W.M., Fehlbaum, L.V., Tshomba, E.,
  • 110. Stadler, C., 2015. Structural and Functional Alterations in Right Dorsomedial Prefrontal and Left Insular Cortex Co-Localize in Adolescents with Aggressive Behaviour: An ALE Meta-Analysis. PLoS One 10, e0136553. Rubia, K., 2011. "Cool" inferior frontostriatal dysfunction in attention-deficit/hyperactivity disorder versus "hot" ventromedial orbitofrontal-limbic dysfunction in conduct disorder: a review. Biol Psychiatry 69, e69-87. Sacher, J., Neumann, J., Funfstuck, T., Soliman, A., Villringer, A., Schroeter, M.L., 2012. Mapping the depressed brain: a meta-analysis of structural and functional alterations in major depressive disorder. J Affect Disord 140, 142-148. Smith, S.M., Nichols, T.E., 2009. Threshold-free cluster enhancement: Addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage 44, 83-98. Sonuga-Barke, E., Bitsakou, P., Thompson, M., 2010. Beyond the dual pathway model: evidence for the dissociation of timing, inhibitory, and delay-related impairments in attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 49, 345-355. Stevens, M.C., Pearlson, G.D., Calhoun, V.D., Bessette, K.L., 2018. Functional Neuroimaging Evidence for Distinct Neurobiological Pathways in Attention-Deficit/Hyperactivity Disorder. Biol Psychiatry Cogn Neurosci Neuroimaging 3, 675-685. Tahmasian, M., Eickhoff, S.B., Giehl, K., Schwartz, F., Herz, D.M., Drzezga, A., van Eimeren, T., Laird, A.R., Fox,
  • 111. P.T., Khazaie, H., Zarei, M., Eggers, C., Eickhoff, C.R., 2017. Resting-state functional reorganization in Parkinson's disease: An activation likelihood estimation meta- analysis. Cortex 92, 119-138. Tahmasian M, N.K., Samea F, Zarei M, Spiegelhalder K, Eickhoff SB, Van Someren E, Khazaie H, Eickhoff CR., 2018. Reply to Hua Liu, HaiCun Shi and PingLei Pan: Coordinate based meta-analyses in a medium sized literature: considerations, limitations and road ahead. Sleep Medicine Reviews. Tahmasian, M., Noori, K., Samea, F., Zarei, M., Spiegelhalder, K., Eickhoff, S.B., van Someren, E., Khazaie, H., Eickhoff, C.R., 2018. A Lack of consistent brain alterations in insomnia disorder: an activation likelihood estimation meta-analysis. Sleep Medicine Reviews. Tahmasian, M., Rosenzweig, I., Eickhoff, S.B., Sepehry, A.A., Laird, A.R., Fox, P.T., Morrell, M.J., Khazaie, H., Eickhoff, C.R., 2016. Structural and functional neural adaptations in obstructive sleep apnea: an activation likelihood estimation meta-analysis. Neurosci Biobehav Rev. Talairach, J., Tournoux, P., 1988. Co-planar stereotaxic atlas of the human brain : 3-dimensional proportional system : an approach to cerebral imaging. Georg Thieme, Stuttgart ; New York. ACCEPTED M ANUSCRIP T
  • 112. 21 Turkeltaub, P.E., Eden, G.F., Jones, K.M., Zeffiro, T.A., 2002. Meta-analysis of the functional neuroanatomy of single-word reading: method and validation. Neuroimage 16, 765-780. Turkeltaub, P.E., Eickhoff, S.B., Laird, A.R., Fox, M., Wiener, M., Fox, P., 2012. Minimizing within-experiment and within-group effects in Activation Likelihood Estimation meta- analyses. Hum Brain Mapp 33, 1-13. Valera, E.M., Faraone, S.V., Murray, K.E., Seidman, L.J., 2007. Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder. Biol Psychiatry 61, 1361-1369. Wahlstedt, C., Thorell, L.B., Bohlin, G., 2009. Heterogeneity in ADHD: neuropsychological pathways, comorbidity and symptom domains. J Abnorm Child Psychol 37, 551-564. Wegbreit, E., Cushman, G.K., Puzia, M.E., Weissman, A.B., Kim, K.L., Laird, A.R., Dickstein, D.P., 2014. Developmental meta-analyses of the functional neural correlates of bipolar disorder. JAMA Psychiatry 71, 926-935. Zakzanis, K.K., Graham, S.J., Campbell, Z., 2003. A meta- analysis of structural and functional brain imaging in dementia of the Alzheimer's type: a neuroimaging profile. Neuropsychol Rev 13, 1-18. ACCEPTED M ANUSCRIP
  • 113. T 22 Figures’ legends Figure 1. Study selection strategy flow chart. ROI: region of Interest, task-fMRI: task-based functional magnetic resonance imaging, rs-fMRI: resting-state functional magnetic resonance imaging, VBM: voxel- based morphometry, ADHD: attention-deficit/hyperactivity disorder. ACCEPTED M ANUSCRIP T 23 Figure 2. Distribution of the included coordinates in the current study. Included coordinates reflecting structural/functional alterations in children/adolescents with ADHD compared to healthy
  • 114. ACCEPTED M ANUSCRIP T 24 subjects. Rs-fMRI: resting-state functional magnetic resonance imaging; task-fMRI: task-based functional magnetic resonance imaging; VBM: voxel-based morphometry. Figure 3. Convergent findings of sub-analyses. A. Aberrant activity (green) in the left pallidum/putamen (-18, 4, -4 MNI, 109 voxels, p= 0.036), based on task-based fMRI experiments (using neutral stimuli only); B. Decreased activity (blue) in the left inferior frontal gyrus (- 38, 26, -16 MNI, 93 voxels, p =0.049 based on fMRI (task-fMRI & rs-fMRI) experiments (using male patients only). ACCEPTED M ANUSCRIP
  • 115. T 25 ACCEPTED M ANUSCRIP T 26 Table 1: Results of conducted meta-analyses in children/adolescent with ADHD compared to healthy subjects A. Modality Number of Experiments Modalities Contrasts
  • 116. P-value TFCE cFWE 1 130 VBM, task-fMRI, rs-fMRI - 0·170 0·129 2 81 VBM, task-fMRI, rs-fMRI Control > ADHD 0·087 0·195 3 48 VBM, task-fMRI, rs-fMRI ADHD > Control 0·104 0·175 4 98 fMRI (combination of task- and rs-fMRI) - 0·151 0·212 5 57 fMRI (combination of task- and rs-fMRI) Control > ADHD 0·061 0·138 6 1 fMRI (combination of task- and rs-fMRI) ADHD > Control 0·063 0·153 7 92 task-fMRI - 0·064 0·062 8 54 task-fMRI Control > ADHD 0·103 0·329 9 38 task-fMRI ADHD > Control 0·248 0·668 10 32 VBM - 0·817 0·452
  • 117. 11 25 VBM Control > ADHD 0·630 0·341 B· Cognitive domain Number of Experiments Domain Contrasts P-value TFCE cFWE 12 31 Inhibitory control - 0·405 0·302 13 18 Inhibitory control Control > ADHD 0·040 0·052 15 27 Attention - 0·447 0·847 18 23 Other cognitive domains - 0·440 0·520 C· Stimulus type Number of Experiments Stimulus Type Contrasts P-value TFCE cFWE 21 65 Neutral - 0·079 0·036
  • 118. 22 41 Neutral Control > ADHD 0·048 0·244 23 24 Neutral ADHD > Control 0·104 0·110 rs-fMRI: resting-state functional magnetic resonance imaging; task-fMRI: task-based functional magnetic resonance imaging; VBM: voxel-based morphometry; TFCE: threshold-free cluster enhancement; cFWE: cluster-level family-wise error. ACCEPTED M ANUSCRIP T