This document discusses a proposed study to investigate differences in motor function and response to therapies between cerebral palsy (CP) patient subgroups based on injury timing (pre-, peri-, and post-natal). The study aims to 1) use transcranial direct current stimulation (tDCS) to identify the influence of each motor cortex hemisphere on the affected limb for each subgroup and 2) determine how targeted therapies differentially enhance motor control for each subgroup. The significance is that current treatments do not consider injury timing, but recent evidence suggests differences in motor pathways between subgroups that could inform more tailored therapies. The innovation is applying tDCS and targeted therapies known to benefit stroke patients to CP subgroups to exploit pathway differences identified through tDCS.

1. Identification of the effect of injury timing on cerebral palsy
using transcranial direct current stimulation and targeted
therapies
BME 463 Neuropathophysiology
Thomas Curran, Andrew Dragunas, Janeen Wiliiams
March 15, 2015

2. Introduction
We would like to thank our reviewers for their constructive and informative comments. Concerns were
raised that our significance was that identification of the pathways involved in neural control of the three
injury timing categories were not discussed at length. Throughout the proposed grant, we specified how
functional differences in timing categories were due to the development and pruning of different
pathways. In particular, we highlighted that neurological development continues to occur after birth and
the differences between pre-, peri-, and post-natal subgroups are a result of differences in neurological
development. This clarification also addressed the concern for why pre-, peri- and post-natal subgroups
were chosen. We also added how these different subgroups were identified through imaging techniques.
Subsequent additions, highlighted how the change in treatment options can affect the quality of life.
In light of concerns from our innovation section, we stressed that we were not developing novel
techniques, nor using tDCS as a therapy, but providing novelty in the application of current therapeutic
techniques. Additionally, our innovation stems from tailoring therapy to the time of injury. We further
clarified that stroke therapies are not currently being used in CP patients. These therapies would be
beneficial to post-natal CP patients. With regards to the comment that we should focus more on the novel
results instead of the differences, our novelty stems from the use of differences between the CP
subgroups to tailor existing therapies to the subgroups rather than applying the same therapy to all of
them.
A weakness presented in the approach was that coincidental stimulation would produce a linearized sum
of the individual results. This however, is not a weakness. We intend to use coincident stimulation to
further highlight differences in motor function as a result of hemispheric and pathway contributions. We
addressed why tDCS was chosen, due to its ability to isolate hemispheric contributions, as well as its
proven efficacy in children. We chose tDCS over other methods because it has not been done before
since it was only recently shown to be safe and effective in children with CP. A schematic was added to
highlight the differences in CS pathways between pre- and post-natal CP. And in response to comments,
a timeline was also added for aim 2.
While there are a variety of therapies available, it is not realistic or feasible to test all of them
concurrently. We highlighted the functional outcomes and goals of the therapies we chose, and how they
relate to the deficits experienced by patients with CP. We also addressed how these therapies relate to
the functional deficits of the hypothesized pathways being used. With regards to reviewer feedback, we
clarified our language so it is clear we are only looking at joint torques. We also clarified how the EMG
and joint torque data would be used to support our hypotheses.
Aim 2 previously used joint torque and EMG to categorize therapy efficacy. Concerns addressing this
method resulted in changing our method of quantifying efficacy. Each therapy targets separate functional
goals, we deemed it inappropriate to compare the two treatments with the same quantifiers. Instead, each
subgroups response to the treatment will be quantified. Further details of this change can be found in the
Approach section of Aim 2.
Solid black lines were added in the left hand margin to indicate these changes in the proposal.

3. Specific Aims
Cerebral palsy (CP) is the leading cause of motor disabilities in children; in the US, 1 in 323 children were
diagnosed with CP in 2008 (CDC), 36% of children with CP have hemiplegia (Sakzewski et al, 2009). CP
can be divided into three subgroups depending upon injury timing: pre- (in utero), peri- (beginning of third
trimester to 2 months post birth), or post-natal (>2 months post birth). Studies suggest that these timing
differences lead to different motor function in unilateral hemiparesis due to altered corticospinal (CS) and
reticulospinal (RS) pathways between the subgroups (Sukal-Moulton et al, 2013). During development,
there are bilateral CS pathways and that these ipsilateral CS projections are pruned shortly after birth due
to disuse. This pruning leads to difference between the subgroups based on injury timing. Currently, there
is no difference in treatment to target the unique motor deficits between the three subgroups (Pagliano,
2001). Therapeutic transcranial direct current stimulation (tDCS), a non-invasive method that promotes
(anodal) or inhibits (cathodal) excitability of the cortex, is a promising technique to restore motor function
following hemiparesis. It is currently unclear how electrical stimulation or targeted therapies respond to the
pathway and hemisphere differences between the subgroups. Understanding how therapy effectiveness is
influenced by injury timing is an important problem because it will allow us to develop targeted treatment
techniques for CP patients that focus on the unique deficits affecting each subgroup.
Our long-term goal is to develop a distinct rehabilitation program for CP children based on injury timing.
The overall objective is to identify the role and motor response of the different pathways through tDCS
and targeted therapy. Our central hypothesis is that tDCS and targeted therapy will affect the three groups
uniquely due to the presence of alternative pathways. The rationale that underlies the proposed research
is that there is greater potential for improved motor function that is not being taken advantage of currently.
Supporting our rationale are studies which highlight differences amongst subgroups of CP patients that
require targeted therapy (Sukal-Moulton et al. 2013a, 2013b, 2013c).
We plan to test our central hypothesis while accomplishing the objective of this application by pursuing the
following two specific aims:
1. Identify the influence of transcranial stimulation on the affected limb for pre-, peri- and post-
natal injuries.
Our working hypothesis is that anodal tDCS will have different changes in paretic limb strength and
coupling for pre-natal subjects compared to post-natal subjects, with peri-natal subjects representing a
continuum between them due to differences in ipsilateral and contralateral pathways present between
these groups.
2. Determine how targeted therapy enhances motor control for each subgroup.
Our working hypothesis is that the pre- and peri- natal subjects will benefit more from bimanual intensive
therapy than post-natal subjects due to persistence of abnormal ipsilateral CS projections. Post-natal
subjects will show greater improvements of motor control with progressive shoulder abduction loading
training than pre- and peri-natal subjects.
With respect to expected outcomes, we anticipate that transcranial stimulation and targeted therapy will
affect pre-natal CP patients uniquely from post-natal CP patients, with peri-natal subjects being in
between the two groups, due to the differences in ipsilateral pruning. Achievement of these objectives will
have an important positive impact, because these results are highly likely to lead to the development of
new therapeutic techniques for functional recovery in addition to fundamentally advancing the
understanding of neural plasticity, as will now be detailed in the following section.

4. Significance:
Clinical metrics currently are unable to differentiate among the three subgroups of hemiparetic CP
patients (Sukal-Moulton et al, 2013a). However, recent studies have shown variable symptoms that are
time-dependent on when the injury occurred, pre-, peri-, or post-natally. These symptoms include
differences in joint torque and muscle activation about the elbow joint of the paretic arm causing
differences in distal control (Sukal-Moulton et al, 2013a, 2013b, 2013c). Differences in coupling of
muscles between the paretic and non-paretic arm occurred predominantly in the pre-natal population
during elbow flexion. This is theorized to be due to preservation of ipsilateral projections of CS tracts that
are normally pruned in the third trimester of gestation (Eyre et al, 2007). In contrast, the post-natal group
has shoulder and elbow torque coupling patterns which resemble adult stroke subjects (Sukal-Moulton et
al, 2013b). These differences are due to the timing of injury which indicates the amount of pruning that
has taken place. In utero, bilateral CS pathways exist. In normal development the ipsilateral pathways are
pruned due to disuse after birth. These ipsilateral CS pathways allow for greater fine motor control, but
result in mirroring movements due to motor commands for both limbs originating from the same
hemisphere. For control when CS pathways are unavailable, the RS tract is often used. The RS
pathways does not have the same motor control that the CS pathways do, which results in a loss of
independent joint control and coupled limb movements. Excitation and inhibition of the ipsilateral and
contralateral hemisphere through the use of tDCS will provide a more substantial understanding of the
differences in pathways between the subgroups.
Bimanual intensive therapy is a clinical technique utilized to improve bilateral motor control in patients with
hemiparesis. A 2007 study found that hand-arm bimanual intensive therapy (HABIT) was effective in
improving bimanual hand use for a select group of children with mild to moderate hemiplegic CP (Gordon
et al). Constraint induced movement therapy, another clinical technique utilized to improve bilateral motor
function in hemiplegic individuals, was found to only be effective in certain populations of CP subjects
(Kuhnke et al, 2008). It is currently unknown which therapies will lead to a significant improvement in
motor function for CP subgroups based on injury timing.
The contribution of the proposed research is expected to be the identification of distinctive pathways
underlying motor control in subgroups of CP patients. This contribution will be significant because it
furthers our understanding of mechanistic differences in CP populations. Furthermore, this understanding
will contribute to the development of therapeutic techniques that specifically address the challenges faced
by each subgroup. A deeper comprehension of the challenges faced by different subsets of CP patients
will provide more pragmatic, specified, and beneficial treatment options leading to improved motor
function and improved quality of life.
Achievement of the described aims will provide evidence to solidify hypotheses regarding the
reorganization of motor tracts and the development of deficit-specific treatment options in different CP
populations. These results can be translated to other subject populations suffering from unilateral brain
injury, such as adult stroke. Furthermore, these experiments will lead to better understanding of
developmental neurobiology.
Innovation:
The current standard of care is to treat all hemiparetic CP patients the same regardless of the timing of
injury. However, recent studies have identified that the deficits experienced by hemiparetic CP patients is
dependent on the time of injury (Sukal-Moulton et al, 2013). That study hypothesized that the functional
differences are due to changes in the motor pathways present in each of these groups. In addition, the
use of tDCS to improve motor function in stroke patients is well documented; however, only as recently as
2014 has efficacy and safety been shown for the use of tDCS in patients with CP (Grecco et al,
2014). Studies have only looked at the use of tDCS to improve gait in diparetic CP patients, but not the
effect of tDCS in hemiparetic CP. One study found that hemiparetic CP patients who responded
differently to transcranial magnetic stimulation (TMS) did not respond the same to physical therapy
(Kuhnke et al, 2008). These differences, however were not identified by the timing of their injury (pre-,peri-

5. Figure 1: Schematic difference in CS pathways between
post-natal CP (left) and pre-natal CP (right). Pathways of peri-
natal subjects fall between these two subgroups.Figure
adapted from Kuhnke et al, 2008.
, or post-natal). Even though it has been shown that not all hemiparetic CP patients respond the same to
therapy, as of now treatment and rehabilitation plans are not specifically tailored towards patients based
on the timing of their injury. The proposed research is innovative, in our opinion, because it will use
electrical stimulation to identify differences in motor pathways between the subgroups of hemiparetic CP
patients and lead to the application of targeted therapeutic strategies to improve motor function based on
the timing of injury. The results from these studies will lead to the development of novel therapeutic
techniques which target the motor pathways of CP subgroups. Specifically, the use of therapies common
for stroke patients can be applied to treatment of post-natal CP patients, who more closely resemble
stroke patients than pre-natal CP patients.
Aim 1: Identify the influence of transcranial stimulation on the affected limb for pre-, peri- and post-
natal injuries.
CP can be etiologically grouped based on injury timing. If the gestational age at birth is less than 36
weeks and there was evidence of a bleed at birth through imaging or if imaging reveals a periventricular
leukomalacia after 36 weeks, then the child is classified as pre-natal CP; if the gestational age is greater
than 36 weeks and imaging shows a middle cerebral artery infarct or early neurological difficulties, then
the child is classified as peri-natal CP; and if there was a clear brain injury after 6 months of age, then the
child is classified as post-natal CP. These difference in injury timing result in varied functional ability.
A limited number of studies have provided evidence for alternative motor pathways attributing to
differences amongst subgroups of CP (Sukal-Moulton et al, 2013, Hoon et al, 2009). By manipulating the
engagement of the primary motor cortex of each hemisphere through stimulation, we will be able to
identify the use of alternative (ipsilateral or contralateral) motor pathways on motor function. Our objective
is to use tDCS to isolate hemispheric contribution to the motor function of the paretic limb. Our working
hypothesis is that anodal tDCS will have different changes in paretic limb strength and coupling for pre-
natal subjects compared to post-natal subjects, with peri-natal subjects representing a continuum between
them due to differences in ipsilateral and contralateral pathways present between these groups. We will
obtain our objective by independently and coincidentally performing anodal and cathodal stimulation on
each hemisphere. Joint torque and EMG recordings, from activated muscles, will be used to determine
the effects of this stimulation on the paretic limb. The rationale for this aim is that hemispheric isolation is
required to evaluate the alternative role of the motor pathways on differences in motor function. At the
conclusion of the proposed experiments, we expect to identify which hemisphere has primary motor
control of the paretic limb in pre-, peri- and post-natal CP patients. Such information is fundamental
because it will isolate which motor pathways are in use and allow, for the first time, the development of
targeted therapeutic techniques.
Normal neuronal development of motor projections is
rapid and biased, resulting in increased contralateral and
decreased ipsilateral CS projections (Eyre, 2001). This
process is activity-dependent and is facilitated by the
repeated use of synaptic connections (Personius, 2000).
This normal development often results in pruning of
unemployed projections, such as the ipsilateral CS
projections and is shown in Figure 1. From in-utero
development to early childhood, this process leads to a
predominance of contralateral projections to spinal motor
circuits (Eyre et al, 2007). This process is altered in the
injured brain. Ipsilateral pathways might be retained to
aid in motor control after injury due to repeated use of
these connections. Thus, possible motor function
differences in pre-, peri- and post-natal injuries might be
a result of retaining a different amount of ipsilateral
pathways during development.

6. Motor function differences have been previously shown amongst pre-, peri- and post-natal CP patients
(Sukal-Moulton et al, 2013a, 2013b, 2013c ). Although clinical assessments did not show any significant
differences between the three categories, evaluations of joint torque and EMG showed otherwise. A
significant difference between pre-, peri- and post-natal CP patients was shown for relative weakness
ratio, relative strength ratio, timing, and muscle activation of proximal and distal muscles (Sukal-Moulton
et al, 2013c). Thus, motor function differences between these groups require further evaluation so that
these differences can be exploited for therapeutic use.
Transcranial stimulation will affect the paretic limb of CP patients as evidenced by its use in stimulating
and restoring motor function of paretic limbs in stroke patients (Schlaug et al, 2008). Previous studies
have used dual activation of tDCS, coincident anodal and cathodal stimulation, in the primary motor cortex
of each hemisphere to excite muscle activation for stroke populations (Vines et al, 2008). Stroke
populations are a relevant sample group due to their similarities with post-natal CP patients. Studies have
shown comparable paretic arm muscle weakness ratios between post-natal CP patients and adult stroke
patients (Sukal-Moulton et al, 2013c). The significance of these studies is that tDCS can be safely used in
children to increase the excitability of the hemisphere it is applied to. When changing the excitability of a
single hemisphere, the subsequent difference in motor functionality can be attributed to the pathways that
originate
from the excited hemisphere.
Our approach for our first aim is to use tDCS to increase or decrease the excitability of each hemisphere
and then evaluate the changes in motor function. This will allow us to determine which cortical
hemisphere is primarily responsible for motor function in each patient. We expect changing the excitability
of the ipsilateral hemisphere will only result in differences in joint torque and muscle activation in the
paretic limb when ipsilateral CS projections are present. tDCS uses electrodes to induce either a small
positive (anodal) current to increase tissue excitability or a small negative (cathodal) current to decrease
tissue excitability. The tDCS system uses a mobile battery-operated direct current stimulator connected
with 2 electrodes. The active electrode is positioned over C3 (corresponding to the precentral gyrus), and
the reference electrode is positioned over the contralateral supraorbital region. To measure muscle
activations we will use EMG electrodes placed over the bellies of the target muscles. A six degree of
freedom load cell will be used to measure joint torque about the shoulder, elbow, and wrist. We will have
4 subject groups: age-matched controls, pre-natal, peri-natal, and post-natal hemiparetic CP
subjects. Subjects will be recruited from the Cerebral Palsy Research Registry (Hurley et al, 2012) and
recruitment to each subgroup will be balanced to the best of our efforts. Our controls will be age-matched
children that do not suffer from any neurological disorders. The number of our controls will be ascertained
by the number of hemiparetic subjects we are able to recruit. A two-way ANOVA test, with limb and
hemisphere as independent variables and joint torque and EMG activation as dependent variables, will be
used to ascertain differences between subgroups.
Each subject will experience randomized stimulation of either the contralateral hemisphere, the ipsilateral
hemisphere, or both. Thus, a single subject will experience the following stimuli: anodal stimulation of the
contralateral hemisphere, anodal stimulation of the ipsilateral hemisphere, cathodal stimulation of the
contralateral hemisphere, cathodal stimulation of the ipsilateral hemisphere, cathodal contralateral
stimulation with anodal ipsilateral stimulation, anodal contralateral stimulation with cathodal ipsilateral
stimulation, and a trial where tDCS will not be applied.
We expect tDCS will have different changes in paretic limb strength and coupling for pre-, peri-, and post-
natal subjects due to the previously mentioned altered motor pathways between the subgroups. Anodal
tDCS of the contralateral hemisphere should increase joint torque in the paretic arm in the post-natal CP
group. We expect anodal tDCS of the ipsilateral hemisphere to increase joint torque in the paretic arm for
both the pre- and peri-natal CP groups, and to increase coupling in the paretic arm for all three CP
groups. Simultaneous anodal stimulation of one hemisphere and cathodal stimulation of the opposite
should have the same effect as the sum of the effects from independent stimulation. Our results of the

7. effect of tDCS stimulation will be used to interpret the predominant pathways governing motor control in
each subject. If there is a prevalence of contralateral pathways (such as the CS tract), then an increased
joint torque would result from anodal stimulation of the contralateral hemisphere. If there is a prevalence
of ipsilateral pathways (such as the BS tract), then increased joint torque and coupling would be a result
of anodal stimulation of the ipsilateral hemisphere.
One potential problem is that electrical stimulation will not identify differences in the groups. This is
unlikely to happen because electrical stimulation has been proven to selectively activate regions of the
motor cortex which synapses with the motor pathways we are analyzing (Grecco, 2014). However, in the
unlikely event that we are unable to detect a difference between the different subgroups, other techniques
will be used to detect the pathways, such as diffusion tensor imaging (DTI), functional magnetic
resonance imaging (fMRI), or transcranial magnetic stimulation (TMS).
At the end of the study, a proposed timeline is provided in Figure 2 below, we should confirm that there
are differences in the motor pathways between pre-, peri-, and post-natal hemiparetic CP patients. To
build upon this research, we will then identify how the subgroups respond to targeted therapies that take
advantage of the pathway differences. This will lead to improved functional outcomes for all subgroups.
Figure 2: A proposed timeline to complete Aim 1, timings for Aim 2 will be added after completion of Aim
1.
CP
Start
Date
End
Date
Time Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug
Set-up 1-Apr 30-Sep 181
Subject Recruitment 1-Apr 30-Jun 90
Finalize and Test
Protocol
1-Jul 30-Sep 91
Aim 1 1-Oct 31-Aug 335
Data Collection 1-Oct 31-Dec 91
Data Analysis 1-Feb 31-Mar 59
Manuscript
Preparation
1-Apr 31-Jul 121
Publish Aim 1
Milestone
1-Aug 31-Aug 30
Aim 2: Determine how targeted therapy enhances motor control for each subgroup.
CP is the most common physical disability in children, and 36% of children with CP have hemiplegia
(Stanley et al, 2000). Currently, CP is treated broadly with a variety of different therapeutic techniques.
Typical treatments for upper limb dysfunction include: intramuscular botulinum toxin A with strength
training, constraint-induced movement therapy, hand-arm bimanual intensive training, and
neurodevelopment training. Despite the variety of options that therapists have to prescribe to children with
CP, none of these approaches have proven to be particularly effective or superior to any other
(Sakzewski, 2009). However, to date, there has been no consideration of injury timing on treatment
effectiveness. The objective of our study will be to determine how pre-, peri-, and post-natal CP children
respond differently to therapies targeted to their subgroups’ specific neurological and motor dysfunction.
Our working hypothesis is that post-natal CP subjects will respond best to shoulder abduction loading
training, and pre- and peri-natal subjects will respond best to bimanual intensive therapy. The use of
ipsilateral CS pathways causes mirror movements, which affects function in bimanual motor
tasks. Bimanual intensive therapy stresses the practice of age-appropriate, and bimanual, fine motor
activities to improve function. Using RS pathways results in loss of independent joint control. Progressive
should abduction therapy helps to decouple within limb synergies. We expect post-natal subjects to
behave most similar to post-stroke adults, where progressive shoulder abduction loading has been shown
to be crucial for upper limb rehabilitation (Ellis et al, 2009). We expect pre- and peri-natal subjects to

8. respond best to bimanual training due to the persistence of abnormal ipsilateral CS projections present in
these subjects. Previous studies (Kuhnke et al, 2008) have shown that CP patients do not respond
equally to the same type of therapy. By identifying therapy techniques which best suit each subgroup,
there will be significant improvements in motor function that was not previously achievable.
Using the same subject population as our first aim, we will group subjects according to injury timing and
randomize their assignment to one of two therapeutic techniques. There will be four subject groups: age-
matched controls, pre-natal, peri-natal, and post-natal hemiparetic CP subjects. Each of which will be
evenly, and randomly assigned to either the progressive shoulder abduction loading treatment or to
bimanual intensive therapy. We will use a robot, such as the ACT3D to perform the progressive shoulder
abduction loading treatment and adapt techniques from (Gordon et al, 2007) to develop a protocol for
bimanual intensive therapy. We will then compare how timing of injury impacts therapy efficacy. For the
robot, we will test improvement in functional work space. Clinical measures will provide insight to
bimanual intensive therapy effectiveness. A one-way ANOVA will be used to determine main effects of
treatment.
We anticipate that pre- and peri-natal subgroups will show greater improvement in bimanual therapy as
opposed to progressive shoulder abduction loading therapy, and the opposite for post-natal subjects. We
do not expect any improvements for the control group. If the pre- and peri-natal subjects respond better to
bimanual therapy, this would suggest these subgroups have retained their abnormal ipsilateral CS
projections. If the post-natal subjects do not respond to bimanual therapy, this suggests that the
underutilized projections in the ipsilateral CS tract were pruned prior to injury. Successful completion of
these experiments will allow us to identify targeted therapies that increase motor function for these
subgroups.
A potential problem of this design is that these subgroups will not show a preference to the targeted
therapies. This is unlikely to happen due to the abundant evidence that pre- and peri-natal CP children do
not resemble post-stroke adults, as the post-natal CP children do, which suggests that shoulder abduction
loading therapy will not be effective in those groups. However, if this problem did result we would try an
alternative combination of therapies to evaluate effectiveness based on injury timing.
At the conclusion of this study we will be able to identify targeted therapeutic techniques based on timing
of injury in CP patients. This will allow us to address the unique challenges of the CP subgroups and
further improve their respective motor function. A proposed timeline for this aim is included in Figure 3
below.
Figure 3: A proposed timeline to compete Aim 2.
CP Proposal
Start
Date
End
Date
Time Sep Oct Nov Dec Jan Feb Mar Apr May
Aim 2 1-Sep 31-May 273
Data
Collection
1-Sep 30-Nov 90
Data Analysis 1-Dec 31-Mar 121
Manuscript
Preparation
1-Feb 30-Apr 89
Publish Aim 1
Milestone
1-May 31-May 30

9. References
Ellis MD, Sukal-Moulton T, Dewald JP. Progressive shoulder abduction loading is a crucial element of arm
rehabilitation in chronic stroke. Neurorehabil Neural Repair. 2009;23:862-869.
Eyre, J. A. Corticospinal tract development and its plasticity after perinatal injury. Neuroscience &
Biobehavioral Reviews. 2007; 31.8: 1136-1149.
Eyre JA, Taylor JP, Villagra F, Smith M, Miller S. Evidence of activity-dependent withdrawal of
corticospinal projections during human development. Neurology. 2001;57:1543-1554.
Gordon, Andrew M., Jennifer A. Schneider, Ashley Chinnan, and Jeanne R. Charles. Efficacy of a hand–
arm bimanual intensive therapy (HABIT) in children with hemiplegic cerebral palsy: a randomized
control trial. Developmental Medicine & Child Neurology. 2007; 49.11: 830-838.
Grecco, Luanda André Collange, Mariana E. Mendonça, Natália AC Duarte, Nelci Zanon, Felipe Fregni,
and Claudia Santos Oliveira. Transcranial direct current stimulation combined with treadmill gait
training in delayed neuro-psychomotor development. Journal of physical therapy science. 2014; 26.6:
945.
Hoon, A. H. et al. Sensory and motor deficits in children with cerebral palsy born preterm correlate with
diffusion tensor imaging abnormalities in thalamocortical pathways. Dev. Med. Child Neurol. 2009; 51:
697–704.
Hurley DS, Sukal-Moulton T, Msall ME, Gaebler-Spira D, Krosschell KJ, Dewald JP. The Cerebral Palsy
Research Registry: development and progress toward national collaboration in the United States. J
Child Neurol. 2011;26:1534-1541.
Kuhnke, N., H. Juenger, M. Walther, S. Berweck, V. Mall, and M. Staudt. Do patients with congenital
hemiparesis and ipsilateral corticospinal projections respond differently to constraint‐induced
movement therapy?. Developmental Medicine & Child Neurology. 2008; 50.12: 898-903.
Pagliano, E., E. Andreucci, R. Bono, C. Semorile, L. Brollo, and E. Fedrizzi. Evolution of upper limb
function in children with congenital hemiplegia. Neurological sciences. 2001; 22. 5: 371-375.
Sakzewski, Leanne, Jenny Ziviani, and Roslyn Boyd. Systematic review and meta-analysis of therapeutic
management of upper-limb dysfunction in children with congenital hemiplegia. Pediatrics. 2009; 123.6:
e1111-e1122.
Schlaug, Gottfried, Vijay Renga, and Dinesh Nair. Transcranial direct current stimulation in stroke
recovery. Archives of neurology. 2008;65.12: 1571-1576.
Stanley, Fiona, Eve Blair, and Eva Alberman. Cerebral palsies: epidemiology and causal pathways. No.
151. Cambridge University Press, 2000.
Sukal-Moulton, Theresa, Kristin J. Krosschell, Deborah J. Gaebler-Spira, and Julius PA Dewald. Motor
Impairment Factors Related to Brain Injury Timing in Early Hemiparesis, Part I Expression of Upper-
Extremity Weakness.Neurorehabilitation and neural repair. 2013: 1545968313500564.

10. Sukal-Moulton, Theresa, Kristin J. Krosschell, Deborah J. Gaebler-Spira, and Julius PA Dewald. Motor
Impairments Related to Brain Injury Timing in Early Hemiparesis. Part II Abnormal Upper Extremity
Joint Torque Synergies. Neurorehabilitation and neural repair. 2014; 28.1: 24-35.
Sukal-Moulton, Theresa, Theresa M. Murray, and Julius PA Dewald. Loss of independent limb control in
childhood hemiparesis is related to time of brain injury onset. Experimental brain research. 2013;
225.3: 455-463.
Vines, Bradley W., Carlo Cerruti, and Gottfried Schlaug. "Dual-hemisphere tDCS facilitates greater
improvements for healthy subjects' non-dominant hand compared to uni-hemisphere stimulation."
BMC neuroscience. 2008;9.1: 103.