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Walker_POE presentation 7-23-2015_revision
1. Novel Applications & Considerations of
Neurocognitive Research using Functional
Magnetic Resonance Imaging (fMRI)
Breya Walker, B.A.
Department of Psychology
St. Jude Children’s Research Hospital
P.O.E. Talk July 28th 2015
2. What is fMRI?
• Indirect measure of cognitive functioning
– A task is given that requires a response
– neuronal activation increased regional oxygen
http://www.sandiegouniontribune.com
/news/2015/apr/02/brain-graphics-
imaging-map/
http://www-
psychology.concordia.ca/fac/penhu
ne/photos-experiments.html
3. fMRI is advantageous
• Non-invasive
• No exposure to radiation
• Identify neural networks associated with cognition
• Clarify the impact of disease and treatment on brain
development
• Measure brain changes in response to intervention
http://www.tru.ca/distance/partnerships/current-partners/about-camrt.html
5. Working memory
• Holding, processing, and manipulating new information (e.g.
mental sketchpad)
• Predict functional outcomes (e.g., reading, math)
• Well-defined neuroanatomical network
• Developmental perspective vulnerable in children with
early brain insult
http://usablealgebra.landmark.edu/instru
ctor-training/working-memory-attention-
executive-function/
6. Measuring working memory
• Performance-based measures
• Rater-based measures
BUT working memory can be difficult to measure in
research settings, including fMRI
7. Considerations for fMRI research
Task Design Response modality Vision/motor
impairment
Age/developmental
limitations
Capability to
complete task
Movement
8. Healthy Adults 18-30 years old (N=25)
Total
N = 25
Gender (% male) 48
Race (% Caucasian) 96
Age at assessment 25.42 ± 3.71
Full Scale IQ 120.12 ± 7.32
• Exclusions
– History of CNS injury/disease
– Cognitive limitations (self-report history of special education)
– Substance use
– MR compatibility issues
9. Self ordered search (SOS) task
Adopted: Conklin INS presentation 2012
First attempt
11. fMRI of Working Memory
• Aim: Investigate the utility of a self-ordered search task
– Effect of task difficulty?
– Is performance reliable?
– Expected pattern of brain activation?
• Implications
– Establish neural activation patterns for comparison with patient
populations
– Establish performance reliability inside and outside scanner
12. Effect of task difficulty
N = 25 18-30 years of age
0
20
40
60
80
100
120
140
5 8 11
MeanReactionTime(s)
Difficulty Level
0
0.1
0.2
0.3
0.4
0.5
0.6
5 8 11
MeanErrorRate(E)
Difficulty Level
18. Effect of task difficulty? YES
o Increased difficulty more errors, slower reaction time
Is performance reliable? NO
o Inconsistent performance inside and outside scanner
Pattern of neural activation? YES
o Neural activation in well-defined brain regions
SOS task is useful in MR but modification is needed
Application of laterality findings (e.g., surgical planning)
Aim: Investigate the utility of the SOS task
19. Study Limitations
Sample representativeness
Total
N = 25
Gender (% male) 48
Race (% Caucasian) 96
Age at assessment 25.42 ± 3.71
Full Scale IQ 120.12 ± 7.32
21. Department of Psychology
Lisa Jacola, PhD
Heather Conklin, PhD
Jason Ashford, MS, CCRP
Division of Radiological Sciences
Matt Scoggins, PhD
Robert Ogg, PhD
POE Program
Dr. Gronemeyer and James Marmion
Editor's Notes
My name is Breya Walker and I am a second 2nd master’s student at the University of Memphis with the department of psychology, and this summer I worked with the department of psychology here at St. Jude on the project entitled….
What is fMRI?
fMRI is as an indirect measure of neural activity that is based on local changes in oxygenated and deoxygenated blood.
Changes in neuronal activity can be associated with tasks measuring cognitive functioning
When a participant has to complete a cognitive task in the scanner that requires a response.
Responding results in an influx of regional oxygen in specific areas of the brain.
So this tapping is associated with the area of activity and an increase in local Oxygenated blood which is time locked and picked up by the MR. So you can say that those regions of activity are thought to be task dependent
fMRI has its advantages for a number of reasons.
It is non invasive
There is no exposure to radiation like in PET and CT scans
It can be used to clarify the impact of disease and treatment on brain development( e.g. fMRI can measure brain changes due to medication or treatment in a patient)
The summer project I worked on involved measuring the cognitive process called working memory with fMRI
WM is a cognitive process that can and has been assessed using fMRI.
WM is responsible for holding processing and manipulating information. A great example of this would be being told a new phone number, recalling this phone number without writing it down and being able to dial the number properly.
WM is important because predicts a number of outcomes such as achievement in math and reading.
Furthermore, WM has a defined neural network and we can use that to assess effects of treatment, for example.
WM ability increases over the lifespan, which makes this cognitive ability particularly vulnerable to early insult from disease or treatment.
WM can be measured in the clinical setting with the use of performance based measures and rater based measures. A performance based measure, such as being told a list of numbers and repeating them backwards, is an example of a tool used. Also, self reports asking about everyday working memory, such as do you have problems finishing a task, or how well do you stay on task without being reminded?
Although we have clinical measures to assess WM, we need research measures for assessing WM and this can be challenging for a number of reasons that I’ll get into in a bit.
When designing cognitive tasks to be used in fMRI there are a few things that should be considered.
Response modality – motor response without a lot of movement, may not hear speech
Patient populations (brain tumors) consider the possibility of visual or motor impairment
When designing tasks in children or in patients with cognitive limitations, consider
Children may have difficulty sitting still and understanding tasks, limit age for studies
Patients with cognitive limitations may have difficulties regardless of age
You also, have to consider the cohort that is studied.
Because we wanted to test a new way to measure WM in the fMRI setting, with the task we developed, we have to have a normative sample so that we can see if this new task measures working memory
The idea is that data from a normative sample can be used when we extend this task and possible findings to cancer patients.
We wanted to enroll healthy adults with typical brains and average functioning. This means that we excluded anyone with a history of CNS injury or disease or a history of cognitive or learning problems.
We also took care to screen for psychoactive medication and substance use, with a particular focus on things that are known to impact the functioning of neurons or cerebral blood flow.
Participants had to be compatible with the magnet; for example, we excluded those with metallic implants or CNS devices, because the strength of the magnet may cause these things to move or otherwise harm an individual.
Here is an example of a clinical task that has been converted into a research task. The self ordered search object task, which has another version the self ordered search verbal task, requires participants to select an object once and only once. In this case the participant looked through the matrix here and they select this object here.
Once the object is selected the matrix is rearranged and the participant is then required to select the a new object without selecting the previous object they picked.. So they have to remember that they selected the object in red without picking it again while selecting a different object.
The goal of the task it to select every object just once!
This task is pretty complex: it increases in difficulty (with 5, 8, and 11 objects that have to be picked), it requires participants to track their response using their eyes and a button press and it requires pax to complete a control task, which is just selecting an object with an asterisk over it.
Previous research has shown that this task is a valid measure of working memory outside of the scanner in healthy children and in children with brain tumors. Because it requires pax to hold information in their memory, manipulate that information in their memory in order to not select the same object twice, and it requires the pax to actively engage with the information to select a new object.
In the current study and with the given information, that being the need for investigating WM because of its importance in everyday functioning and the need for research setting tools to do this, we wanted to investigate the utility of the self ordered search task, previously shown.
We expected that with an increase in task difficulty will lead to an increase in errors made and increase in RT
We expected the performance on the tasks will be consistent inside (in the fMRI setting) and outside (in the clinical setting) the scanner
We expected that neural activation patterns will be established for this task and they will be similar to existing WM patterns reported.
We assessed all of this by creating an experimental design that used the SOS task inside the fMRI along with the SOS task outside the fMRI scanner, in the clinical environment.
We’d like to use this task, if reliable, to comparison neural activity with normative data to patient data.
The following data presented is from 25 healthy adults age 18-30
Let me orient you to the graphs. So the x axis represents the task and the varied difficulty level and the y axis shows either reaction time or error rate, with higher numbers meaning more error.
The graph on the left shows us that with an increase in task difficulty there is an increase in RT. This is what we expected. While the graph on the right shows an increase in error rates with an increase in difficulty level. This is also what we expected. So with an increase in difficulty there is an increase in RT and error in responses and the effect of load is consistent across settings.
I’m not sure if you can see the error bars but even though there is an effect of task difficulty the way in which participants responded is variable. You can see that with an increase in difficulty there is also an increase in variability
This scatterplot shows us that there is inconsistency with peoples performance inside and outside of the scanner, with some people responding slowly outside the scanner and faster inside the scanner and others responding quick outside and extremely slow inside. So there was no consistent pattern of performance across testing environments. This is not what we expected. Slow reaction time can contribute to more errors made, which will be shown next.
Here is a graph that shows the error rates inside the scanner are not equal to the error rates outside the scanner. It is shown that the group performance was not different inside and outside the scanner, just that the performance inside and outside the scanner was not consistent across testing environments resulting in this line graph showing no consistent pattern in performance from participants.
This demonstrates a limitation (limited accuracy) with response modality, so the eye tracking used in the scanner may have contributed to the lack of consistent accuracy between testing environments, which in turn impacted reaction time like I previously mentioned.
Here are the fMRI results from the current study. Let me orient you to this slide.
This is a horizontal slice with the left side representing the left and the right the right.
You can see that the frontal and parietal regions of the brain are activated when participants engage in our task
And these regions are shown to overlap…
Furthermore, the data that we found in our neural activation patterns are shown to overlap with the data collected from the use of a gold standard task used in fMRI to assess WM, the N-Back.
Which assures us that we are actually measuring WM.
Moreover, we have shown that there is laterality effects of our self ordered search tasks. With the verbal task activating the LH shown here in red and the object task activating the RH shown in green. Please note that the lateralization is not perfect here with green and red appearing on both hemispheres but the degree is stronger on each associated side. This demonstrates that our task may be more sensitive to task modality, verbal and object stimuli, than the gold standard N-Back task.
We can now use this normative data to compare to patient groups to see how behaviors and activations differ after treatment.
Thus, there was an effect of task, which is what we expected, the performance inside and outside the scanner was not reliable but we established a pattern of activation and it encompasses similar brain regions known to be associated with WM processes. The SOS task is useful in MR but the task variability has to be sorted out and laterality findings might be useful for surgical planning (similar to language mapping before surgery).
The things we controlled for are limitations in the study, such that the response modality that we used to maximum control was too much for our participants to use and it was not the best way to measure outcome, our exclusion criterion for our cohort resulted in a sample that had an above average IQ.
These are things that we have to consider as limitations, and we have to consider these things along with possible developmental limitations when utilizing this tool with children.
Future directions…
We want to establish a relationship between clinical and research measures for future assessment in populations such as cancer patients
Compare the neural findings to patients
All of which can eventually lead to tailored treatments and interventions to preserve cognitive functioning.
I’d like to thank my research team and awesome summer mentor for helping me!
