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Brain Injury, March 2012; 26(3): 201–210
Diffusion tensor imaging and volumetric analysis of the ventral
striatum in adults with traumatic brain injury
SANJEEV SHAH
1,2
, RAGINI YALLAMPALLI
2,3
, TRICIA L. MERKLEY
2,4
, STEPHEN
R. MCCAULEY
2,3,5
, ERIN D. BIGLER
4,6,7
, MARIANNE MACLEOD
2
, ZILI CHU
8,9
,
XIAOQI LI
2
, MAYA TROYANSKAYA
2,3
, JILL V. HUNTER
8,9
, HARVEY S. LEVIN
2,3,5
,
& ELISABETH A. WILDE
2,3,5,8
1
University of Texas Southwestern Medical Center, Dallas, TX, USA,
2
Physical Medicine and Rehabilitation Alliance,
Baylor College of Medicine and the University of Texas-Houston Medical School, Houston, TX, USA,
3
Michael E.
DeBakey Veterans Affairs Medical Center, Houston, TX, USA,
4
Department of Psychology, Brigham Young
University, Provo, UT, USA,
5
Department of Neurology, Baylor College of Medicine, Houston, TX, USA,
6
Department of Neuroscience, Brigham Young University, Provo, UT, USA,
7
Department of Psychiatry and the Utah
Brain Institute, University of Utah, Salt Lake City, UT, USA,
8
Department of Radiology, Baylor College of Medicine,
Houston, TX, USA, and
9
Department of Pediatric Radiology, Texas Children’s Hospital, Houston, TX, USA
(Received 29 July 2011; revised 11 December 2011; accepted 2 January 2012)
Abstract
Objectives: The aim was to determine if there are changes in the integrity and volume of the ventral striatum following severe
traumatic brain injury (TBI) and if these changes relate to executive functioning.
Methods: This study recruited 14 participants with severe TBI (mean age: 22 years) and 15 demographically-matched
controls. All participants underwent magnetic resonance imaging with diffusion tensor imaging (DTI) and volumetric
analysis at 6 months post-injury. Participants with TBI underwent neuropsychological testing and the relation between
imaging data and cognitive performance was examined.
Results: Differences in DTI parameters (fractional anisotropy (FA) and apparent diffusion coefficient (ADC)) were found
between participants with TBI and controls. Correlations between right and left ventral striatum ADC and the executive
functioning factor of the Neurobehavioural Rating Scale-Revised (NRS-R) were found. Correlations between right ventral
striatum FA and the Controlled Oral Word Association Test, Trails Making Test Part B (TMT-B) time and NRS-R
executive functioning factor were also found. Volumetric analysis showed a difference only in left nucleus accumbens
between TBI and control groups.
Conclusions: The integrity of the ventral striatum is affected following severe TBI. Decreases in executive functioning are
related to damage to the ventral striatum and its associated structures.
Keywords: Neuroimaging, MRI, DTI, TBI, executive functioning
Introduction
Each year in the US, at least 1.7 million people sustain
a traumatic brain injury (TBI). Of them, 52 000 die,
275 000 are hospitalized and the remainder (almost
80%) are treated in an emergency department and
released [1]. Those who survive their injuries may
display short- or long-term changes in language,
cognition or behaviour.
A key brain region involved in cognition and
behaviour is the ventral striatum, but this region’s
Correspondence: Elisabeth A. Wilde, PhD, Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, 1709 Dryden Road, Suite 1200,
Houston, TX 77030, USA. E-mail: ewilde@bcm.edu
ISSN 0269–9052 print/ISSN 1362–301X online ß2012 Informa UK Ltd.
DOI: 10.3109/02699052.2012.654591
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specific susceptibility to injury and the role that it
may play in TBI has been mostly inferred rather than
directly examined as a region of interest (ROI)
[2, 3]. One of the challenges to studying this region
is that many of the boundary distinctions of the
ventral striatum are histologically based and are
rather ill-defined, even with advanced in vivo
contemporary neuroimaging methods. Part of the
problem is that, when using images derived from
magnetic resonance imaging (MRI), the ventral
aspect of the basal ganglia merges with gray matter
structures of the basal forebrain, including the
extended amygdala emerging upward from the
medial temporal lobe. One neuroimaging approach
has utilized a voxel-based morphological analysis as
a method to show reductions in the amount of gray
matter pixels in the general region of the ventral
striatum [4]. Recently, with improvements in seg-
mentation, parcellation, and MRI classification of
this region by software such as FreeSurfer, two
regions of the ventral striatum can now be reliably
quantified—the nucleus accumbens and the ventral
diencephalon. This now permits an automated
approach for obtaining volumetric data for two
specific ROIs involving the ventral striatum and
directly measuring whether TBI results in atrophic
changes of this area of the brain.
This study used diffusion tensor imaging (DTI)-
based fibre tractography to analyse the white matter
pathways through the ventral striatum along with
volumetric changes in the nucleus accumbens and
ventral diencephalon in young adults with severe
TBI. The DTI technique has successfully been
utilized in the past to create three-dimensional
reconstructions of cortical and subcortical white
matter pathways in the human brain in studies of
TBI [5, 6]. DTI is a promising tool for use in
both healthy and brain-injured individuals, due to its
ability to detect pathologies in white matter resulting
from diffuse axonal injury, which may not be seen
using conventional MRI. DTI allows for measure-
ment of white matter fibre integrity using fractional
anisotropy (FA) and apparent diffusion coefficient
(ADC; mean diffusivity) [7, 8].
Structurally, the ventral striatum consists of the
nucleus accumbens, ventromedial parts of the cau-
date nucleus and putamen and the olfactory tubercle
[9], anatomically juxtaposed with and connected
to the basal forebrain [10]. The ventral striatum is
characterized by inputs from components of the
limbic system (basolateral amygdala, hippocampus
and midline thalamus) as well as the orbital and
medial prefrontal cortices [11]. As part of the limbic
system and due to its connections to the prefrontal
cortex and basolateral amygdala, the ventral
striatum has been implicated in the emotional
and motivational aspects of decision-making and
behaviour [12]. The ventral striatum also receives
substantial dopaminergic inputs from the ventral
tegmental area (VTA) of the mid-brain [13, 14].
These inputs contribute to its role in reward and
positive reinforcement [12]. While it has been well
established that the base of the frontal lobe, includ-
ing the basal forebrain, is a particularly susceptible
region of injury in TBI [15], whether selective
damage occurs to the ventral striatum and its
relationship to neuropsychological outcome has not
been specifically examined.
A rich inter-connectivity of the ventral striatum
from the anterior part of the cerebrum inferiorly to
the brainstem has long been established [10]. This
path likely makes it susceptible to rotational injury
[16] where, if traumatic axonal injury damages these
neural connections, DTI should be sensitive enough
to detect pathology at the ventral striatal level.
To the authors’ knowledge, this is the first time DTI
has been used to specifically view the ventral striatal
region in adults who have sustained severe TBI.
It was hypothesized that: (I) group differences in FA
and ADC values in the right and left ventral striatal
region between individuals with and without TBI
will be present; and (II) there will be group differ-
ences in a volumetric composite of white matter
regions comprising the ventral striatum pathway;
and (III) these quantitative differences correlate with
changes in executive functioning.
Methods
Participants
The TBI group in this study consisted of 14 partic-
ipants (12 males, two females) with severe TBI
resulting mainly from motor vehicle injuries. Post-
resuscitation Glasgow Coma Scale scores of these
participants (GCS) [17] upon admission to the
emergency department (ED) ranged from
3–7 (mean of 5.29). MRI for DTI and volumetrics
and neuropsychological assessment were per-
formed 6 months post-injury (range of 5.60–6.90
months). A control group of 15 neurologically-intact
individuals (13 males, two females) recruited from
the community via advertisement or word of mouth
was used for comparison. Where possible, controls
were matched to participants based on age, race and
ethnicity. In both the TBI and the control groups, all
participants were right-hand dominant. Previous
history of brain injury, history of major psychiatric
or neurological illness, psychotropic medication that
would alter neuropsychological testing or diagnosed
learning disability were used as exclusion criteria.
Aside from one Spanish-speaking individual, English
was the primary language spoken by all participants.
This individual was administered all standardized
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tests in Spanish by a Spanish-speaking examiner.
Written informed consent was obtained from all
participants and the study was approved by the
Institutional Review Board.
Magnetic imaging resonance acquisition
Both TBI and control participants underwent MRI
(without sedation) on a Philips 3.0 T Intera scanner
(Philips, Cleveland, OH). Volumetric measures for
the right hemisphere for one participant with TBI
were not used in the analysis due to the presence of
artifact on the T1-weighted imaging. DTI measures
for one TBI patient were not attainable due to the
severity of damage.
T1-weighted 3D sagittal acquisition parameters
included 8.6 milliseconds repetition time (TR), 3.9
milliseconds echo time (TE), 1.0 mm slices, 0 mm
gap. Transverse multi-slice spin echo, single shot,
echoplanar imaging (EPI) sequences were applied
(6318.0 milliseconds TR, 51 milliseconds TE,
2.0 mm slices, 0 mm gap) for DTI acquisition.
Diffusivities were measured along 30 directions
[18] using a low b-value of 0 and a high b-value of
1000 sec mm
2
. Each acquisition was comprised
of 70 slices, taking 5 minutes. To attain a better
signal-to-noise ratio, two acquisitions were per-
formed and were later combined by using the
Philips diffusion affine registration programme.
Eddy current distortion and head motion artifacts
were corrected during the merging process and co-
registration was done on the two datasets before they
were averaged to produce one DTI dataset. FA map
calculations and fibre tracking were performed with
the Philips fibre tracking 4.1 V3 Beta 2 software.
Diffusion tensor imaging analysis
Regions of interest (ROIs) were chosen on the right
and left coronal and axial slices using the protocols
described below. An automated Philips three-
dimensional fibre tracking tool was used to deter-
mine fibre tracts based on the selected ROIs. For the
ventral striatum, mean FA and ADC were used as
the quantitative DTI measures.
Regions of interest
A multiple ROI approach was used to focus the
identification of the tract and produce reliable
measurements. ROIs were traced in the coronal
and axial planes using one slice per plane. The ROI
from the coronal slice was selected just anterior to
the genu of the corpus callosum. The ROI from the
axial slice was selected at the level of the brainstem
where the VTA resides. This slice was chosen due to
the extensive inputs of the VTA to the ventral
striatum. ROI placement is shown in Figure 1 and
the resulting tractography of the ventral striatum
is displayed in Figure 2.
Intra-operator and inter-operator reliability
To evaluate intra-operator reliability of the DTI
protocol, two trials were performed for each struc-
ture by the primary rater. To evaluate inter-operator
reliability of the DTI protocol, another experienced
rater independently measured the study data in a
sub-set of two participants with TBI and three
controls. Shrout-Fleiss reliability statistics were used
to calculate intra-class correlation coefficients
(ICCs) in order to establish intra-rater and inter-
rater reliability. All resulting ICCs were greater
than 0.97.
Volumetric analysis
Volumetric segmentation and cortical reconstruction
of the T1-weighted MR images were carried
out using the FreeSurfer image analysis suite
(http://surfer.nmr.mgh.harvard.edu/), as previously
described [19, 20]. Regional WM was parcellated
as defined by the cortical regions overlying them,
with a constrained depth of 5 mm [21]. The post-
processing outputs for each subject were examined
visually to ensure processing accuracy and image
quality. To optimize the accuracy of the results,
minimal manual editing was done and only where
necessary. Nucleus accumbens and ventral dien-
cephalon volumes were derived from the results
of automated subcortical labelling. The ventral
diencephalon region includes structures such as the
hypothalamus, mammillary body, subthalamic
nuclei, substantia nigra, red nucleus, lateral genicu-
late nucleus, medial geniculate nucleus and cerebral
peduncle. Composite white matter (WM) volume of
the frontal lobe was calculated as the sum of the WM
parcellated regions associated with the regional
cortex parcellations including: caudal middle frontal,
lateral orbitofrontal, medial orbitofrontal, pars oper-
cularis, pars orbitalis, pars triangularis, rostral
middle frontal, superior frontal and frontal pole.
Figure 3 depicts the frontal composite, the nucleus
accumbens and the ventral diencephalon volumes.
Neuropsychological testing
Participants with TBI were given the Controlled
Oral Word Association Test (COWAT) and the
Trail Making Test Part B (TMT-B). The COWAT
is a verbal fluency test based on a phonemic cue.
Higher scores indicate better performance. The
TMT-B test requires the participant to alternately
connect a consecutive series of letters and numbers
together in a desired order (i.e. 1 !A!2!B...).
This test is used to evaluate scanning and searching
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ability, mental flexibility, processing speed and
executive functioning. The Neurobehavioural
Rating Scale-Revised (NRS-R) is a 27-item clinical
assessment used to measure neurobehavioural
disturbances in patients with TBI. Higher scores
indicated greater behavioural disturbance [22]. The
executive functioning components of this assessment
were used in this study [23].
Statistical analysis
Between-group differences on demographic charac-
teristics were analysed using the independent sample
t-test (age and education) and Fisher’s exact test
(gender, ethnicity and race distribution). Since
assumptions for normality were not violated, para-
metric statistics were applied in the subsequent
analyses. Independent sample t-tests were conducted
to compare diffusion parameters for the ventral
striatum (FA and ADC) between the TBI and
control groups. Analyses of covariance (ANCOVA)
were used to test group effects on WM frontal,
nucleus accumbens and ventral diencephalon volu-
metric data, separately for the left and the right
hemisphere. Total intracranial volume (TICV) was
included as a covariate to account for the potential
effects of cranial vault size on brain volume. Pearson
product-moment correlations were also used to
examine the relation between DTI parameters
Figure 1. Regions of interest in DTI as shown on B ¼0(a,c) and FA colour map (b,d). The first ROI in this multi-ROI protocol was
all hemispheric frontal white matter outlined in the coronal plane using the slice just anterior to the genu of the corpus callosum (a,b).
The second ROI included the ventral tegmental area outlined in the axial plane at the level of the cerebral peduncles.
Figure 2. DTI fibre tractography of the ventral striatum super-
imposed upon B ¼0 slices used for ROIs in an uninjured
participant. Consistent with convention, green colour indicates
fibres coursing in an anterior-to-posterior direction and blue
colour indicates fibres coursing in a superior-to-inferior direction.
204 S. Shah et al.
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in the right and the left ventral striatum and the
COWAT, NRS-R and TMT-B in the TBI group
only. One patient was missing cognitive testing data
for COWAT and TMT-B, thus 13 participants
were used in the correlational analyses. Partial
correlations (TICV as a covariate) were additionally
conducted to examine the relation between volu-
metric data and cognitive scores. Statistical analyses
were performed with SPSS (v.17.0) software and
the threshold for statistical significance was set
at p<0.05. The Bonferroni procedure was used to
correct for multiple comparisons for testing of group
differences on DTI and volumetric data.
Results
Demographic characteristics
Demographic and clinical characteristics of all
participants are listed in Table I. There was no
significant difference in age or education between
TBI and control groups (p>0.05). Furthermore,
there were no significant differences found for
distributions of gender, ethnicity and race (p>0.05).
Group differences in ventral striatum diffusion
parameters
Table II presents the ventral striatum diffusion
parameters for the right and the left hemispheres
for both TBI and control participants. Compared to
the control group, the TBI group had significantly
higher ADCs in both right [t(26) ¼4.99;
p<0.0001] and left [t(26) ¼4.28; p¼0.002] ven-
tral striatum as well as significantly lower FAs
in both right [t(26) ¼3.44; p¼0.002] and left
[t(26) ¼2.93; p¼0.007] ventral striatum after
Bonferroni correction for multiple comparisons
(p<0.0125).
Group differences in WM frontal lobe volumetric data,
nucleus accumbens and ventral diencephalon
The TBI group showed significantly decreased
volume in the left nucleus accumbens [F(1, 22) ¼
12.78; p¼0.002], but no significant difference in
the right nucleus accumbens compared to control
participants after controlling for TICV. There were
no significant differences in left or right frontal
subcortical composite volume, left or right frontal
Figure 3. Frontal composite (peach), nucleus accumbens (green) and ventral diencephalon (blue) volumetric regions superimposed upon
a T1-weighted image in an uninjured participant. (A) Sagittal view; (B) Axial view.
Table I. Demographic and clinical characteristics of TBI and control groups.
Group characteristics TBI, M(SD) (n¼14) Control, M(SD) (n¼15) Statistics
Age (years) 21.98 (4.62) 22.20 (5.93) t(27) ¼0.11; p¼0.912
Gender (M/F) 12/2 13/2 p¼1.000*
Ethnicity (N/H) 10/4 11/4 p¼1.000*
Race (C/A/AA) 11/2/1 13/2/0 p¼0.791*
Education (years) 12.3 (1.5) 12.8 (1.9) t(27) ¼0.81; p¼0.426
GCS 5.29 (1.54) N/A N/A
Post-injury interval (days) 197.43 (11.75) N/A N/A
TBI, traumatic brain injury; GCS, Glasgow Coma Scale score at admission; N/A, data not applicable; SD, standard
deviation. For gender, M, male; F, female. For ethnicity, N, Non-Hispanic; H, Hispanic. For race, C, Caucasian;
A, Asian; AA, African-American. For handedness, R, right; L, left.
*Fisher’s exact test was used.
DTI and volume of ventral striatum in TBI 205
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composite WM volume or left or right ventral
diencephalon volumes of participants with TBI
compared to controls. Table III summarizes the
results for the frontal subcortical composite, frontal
WM composite, nucleus accumbens and ventral
diencephalon volumes for both TBI and control
groups.
TBI group executive functioning performance
Executive functioning was examined using the exec-
utive function factor of the NRS-R (NRS-R EF), the
COWAT and the TMT-B. The TBI group had a
mean NRS-R EF score of 13.50 4.68. The mean
COWAT score was 24.31 14.19 and the mean
time (in seconds) taken to complete the TMT-B was
122.46 73.87.
Correlations between executive functioning and ventral
striatum diffusion parameters and volumetric data within
the TBI group
In the TBI group, the FA of the right ventral
striatum correlated with the NRS-R EF (r¼0.72;
p¼0.006) such that higher FA was related to report
of lower executive dysfunction. However, there was
no relation with the left ventral striatum (r¼0.26;
p¼0.393). A correlation was found between FA of
the right ventral striatum and the COWAT (r¼0.74;
p¼0.006) such that higher FA was related to better
performance, but the same result was not seen
in the left ventral striatum (r¼0.19; p¼0.549).
Furthermore, a correlation was seen between FA of
the right ventral striatum and the time to complete
TMT-B (r¼0.70; p¼0.011) such that higher FA
was related to decreased time to complete, but the
same was not observed in the left ventral striatum
(r¼0.13; p¼0.697). Scatter plots of the signifi-
cant correlations are demonstrated in Figures 4–6.
With respect to the ADC values, correlations were
found between the NRS-R EF and the ADCs of
the right (r¼0.64; p¼0.019) and left (r¼0.51;
p¼0.072) ventral striatum such that higher ADC
was related to increased number or severity of
symptoms related to executive dysfunction.
However, no correlations were found between the
ADCs of the left or right ventral striatum and the
Table III. WM total composite, WM frontal composite, nucleus accumbens and ventral diencephalon volumes (LSM SE) for TBI and
control groups, adjusted for TICV.
Variables
Groups LSM (SE) Statistics
TBI Control p-value Cohen f
Frontal subcortical composite*
Right 61 411.24 (1236.82) 63 976.59 (954.03) 0.118 0.36
Left 60 805.13 (1365.97) 63 688.05 (1110.50) 0.119 0.35
WM frontal composite
Right 56 495.55 (1175.01) 58 785.94 (906.35) 0.141 0.33
Left 55 904.63 (1335.19) 58 573.65 (1085.48) 0.139 0.33
Nucleus accumbens
Right 632.17 (35.25) 681.70 (27.19) 0.282 0.24
Left 515.99 (22.94) 622.74 (18.65) 0.002 0.76
Ventral diencephalon
Right 4 283.52 (140.74) 4 508.95 (108.56) 0.222 0.27
Left 4 384.51 (109.36) 4 491.66 (88.91) 0.460 0.16
WM, white matter; TBI, traumatic brain injury; TICV, total intracranial volume; LSM, least squares mean; SE, standard error.
Volumes are expressed as mm
3
. Italicized p-values showed significant difference after Bonferroni correction for multiple comparisons
(alpha ¼0.05/8 ¼0.006).
Cohen’s fare reported where the convention for interpretation of small, medium and large effect sizes is defined at the 0.1, 0.25 and 0.40
levels, respectively (Cohen, 1988).
*Includes frontal WM composite regions, nucleus accumbens and ventral diencephalon.
Table II. Mean FA and ADC in the right and left ventral
striatum for TBI and control groups.
Variables
Groups Statistics
TBI
(n¼13*)
Control
(n¼15) p-value Cohen’s d
FA
Right 0.40 (0.03) 0.43 (0.02) 0.002 1.30
Left 0.41 (0.03) 0.44 (0.03) 0.007 1.11
ADC
Right 0.81 (0.05) 0.74 (0.03) <0.001 1.89
Left 0.81 (0.05) 0.74 (0.03) <0.001 1.62
FA and ADC values are expressed as mean (standard error). TBI,
traumatic brain injury; FA, fractional anisotropy; ADC, apparent
diffusion coefficient. Cohen’s d0.80 indicates a large effect
size; 0.50–0.79 indicates a moderate effect size (Cohen, 1988).
For ADC, measures are expressed as 10
3
mm
2
s
1
.p-values
showed significant difference after Bonferroni correction for
multiple comparisons (alpha ¼0.05/4 ¼0.0125).
*For one data set, DTI fibre tracking was unable to be performed
due to the severity of the damage.
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COWAT (right [r¼0.35; p¼0.264], left
[r¼0.39; p¼0.216]) or time measure of the
TMT-B (right [r¼0.36; p¼0.245], left [r¼0.31;
p¼0.319]). No significant correlations were found
between volumetric data and cognitive measures,
as detailed in Table IV.
Discussion
The chief goal of this study was to analyse changes
in the ventral striatum on participants with severe
TBI using DTI and volumetric analysis and to
determine its influence in various aspects of cogni-
tion. This study was able to demonstrate significant
increases in ADC and significant reductions in FA
in participants with severe TBI at a chronic stage as
compared to a demographically-matched control
group. In the TBI group, correlations were found
between the FA of the right ventral striatum and
several measures of executive functioning (executive
functioning component of NRS-R, Trails B time and
COWAT), suggesting that reduced white matter
integrity is related to poorer executive functioning.
Correlations were also found between the ADC of
the left and right ventral striatum and the executive
functioning component of the NRS-R. Volumetric
analysis showed a significant decrease in volume
in the left nucleus accumbens of the TBI group
compared to controls.
As mentioned before, the ventral striatum is
interconnected with the VTA [13, 14] as well as
medial and orbital prefrontal cortices and limbic
structures such as the hippocampus, basolateral
amygdala and mid-line thalamus [11]. The inter-
connections between the medial and orbital prefron-
tal cortices and the ventral striatum have further
been confirmed through DTI imaging analysis [24].
These known connections allowed a multiple region
of interest (ROI) approach in DTI to accurately
track the white matter fibres of the ventral striatum.
Moreover, the vulnerability of these associated
structures to damage in TBI point to the suscepti-
bility, in turn, of the ventral striatum to damage. The
selective vulnerability of the frontal lobes discussed
previously [25] is partially attributed to their prox-
imity to bony protuberances along with impact and
rotational forces that deform the frontal lobes during
injury [15]. It has also been suggested that changes
in haemodynamics of the anterior cerebral artery due
to increased intracranial pressure following injury
can lead to atrophy of structures it supplies, includ-
ing parts of the frontal cortices and the head of
the caudate [26]. Furthermore, volume loss due
to diffuse traumatic axonal injury has recently
been shown to be regionally selective rather than
uniformly diffuse, most dramatically affecting the
Figure 6. Scatterplot with regression line indicating the relation
between the FA of the right ventral striatum and the Executive
Function factor score of the NRS-R.
Figure 5. Scatterplot with regression line indicating the relation
between the FA of the right ventral striatum and the Controlled
Oral Word Association Test.
Figure 4. Scatterplot with regression line indicating the relation
between the FA of the right ventral striatum and the Trail Making
Test–B.
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amygdala, hippocampus, thalamus and putamen in
addition to cortical regions [27].
With respect to its functional roles, the ventral
striatum has been found to be involved in reward
and motivation [12] as well as reward-based
decision-making. Studies have shown the cognitive
and behavioural effects of focal damage to the right
or left ventral striatum. One study [28] of a patient
with a left nucleus accumbens bleed showed an
inability of the patient to acquire new verbal infor-
mation whether assessing free recall or recognition
memory. Tests of verbal memory, working memory,
language, divided or shifting attention, non-verbal
information encoding/retrieval and executive func-
tioning were normal. Strangman et al. [29] also
speculated on the role of ventral striatum damage in
TBI. Another group found that left ventral striatum
lesions due to bleeds were associated with beha-
vioural and executive functioning deficits, hyperac-
tivity and a decrease in daily activities [30].
Newcombe et al. [2] implicated trauma-induced
damage to the ventral striatum as one of the regions
involved in impaired decision-making in participants
who had sustained TBI. These findings with rela-
tion to the NRS-R EF were consistent with
the behavioural and executive functioning deficits
reported by Martinaud et al. [30] along with
Newcombe et al. [2].
As stated previously, this study primarily points
to the right ventral striatum as the side in which
damage (i.e. decreases in FA) correlates most with
decreases in executive functioning in the TBI group.
However, the ADC of the left ventral striatum in the
TBI group was also correlated with the executive
functioning component of the NRS-R. Nevertheless,
the reason for the aforementioned rightward later-
ality is not entirely clear. Clark et al. [31] showed
that participants with right frontal lesions dis-
play riskier behaviour and poorer decision-making
in the Iowa Gambling Task and do not adopt
safer decision-making over time, as those with left
lesions do [31]. Gender may also be a factor in the
rightward laterality seen in this study. Others have
reported greater involvement of the right frontal
region in men vs. women with regard to performance
on decision-making tasks [32, 33]. This is consistent
with this sample, which contains primarily men.
With this in mind, the inputs of the frontal cortices
to the ventral striatum may, in part, help explain the
findings.
Studies of executive functioning have implicated
the ventral striatum in risk taking. Matthews et al.
[34] showed activation of the nucleus accumbens in
risky decision-making. Bu
¨chel et al. [35] demon-
strated that ventral striatum as well as VTA signal
changes in fMRI predict future risky decision-
making when a subject feels they have missed an
opportunity in the recent past (i.e. as in gambling).
Using the Cambridge Gambling Task, Newcombe
et al. [2] found correlations between abnormal risk
adjustment and ADC (determined using DTI) of the
ventral striatum and other structures in participants
who had sustained a TBI. This study also found
that impulsivity, which can be an important aspect
of risk taking, is associated with ADC in the
orbitofrontal cortex and caudate, two key compo-
nents of the ventral striatum. Other studies have
suggested that alterations in the ventral striatum lead
to impulsivity in animals [36] as well as children
with ADHD [37]. One study of ADHD in children
demonstrated that decreased ventral striatum
volume is associated with impulsivity [38]. The
implications of these studies are discussed below.
The importance of the ventral striatum in TBI
stems from the multitude of studies, such as those
described above, which suggest ventral striatal
involvement in reward, motivation, decision-
making and other aspects of executive functioning
and behaviour. With the findings that participants
who have sustained a TBI show decreased ventral
striatum integrity and that loss of integrity in
the right (and sometimes left) ventral striatum is
Table IV. Correlations between volumetric data and cognitive measures.
Regional brain volume
Right Left
Measure Accumbens Ventral DC Frontal Accumbens Ventral DC Frontal
NRS-R r0.22 0.28 0.21 0.29 0.28 0.12
p0.541 0.442 0.564 0.410 0.431 0.736
TMT-B r0.18 0.24 0.21 0.20 0.20 0.16
p0.627 0.511 0.556 0.580 0.580 0.652
COWAT r0.19 0.26 0.26 0.11 0.21 0.24
p0.590 0.466 0.466 0.764 0.567 0.498
NRS-R, Neurobehavioural Rating Scale–Revised; TMT-B, seconds to complete on Trail-Making Test, part B;
COWAT, Controlled Oral Word Association Test; DC, diencephalon.
208 S. Shah et al.
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correlated with a reduced level of executive func-
tioning, it is believed that the ventral striatum
may have implications for substance abuse and
behaviour dysregulation in this population. The
research of others supports this possibility. In their
review, George and Koob [39] discuss the idea that
drug addiction results from a failure of various
executive systems including the ventral striatum
and prefrontal cortices. Martinez et al. [40] found
interrupted dopamine transmission in the ventral
striatum to be associated with alcohol dependence.
A PET study performed by Volkow et al. [41] shows
that regulation of the magnitude of dopamine
increases in the ventral striatum by the prefrontal
cortex modulates the value of rewards. This group
suggests that there may be disruption in this regu-
latory mechanism in addicted individuals. With the
knowledge that risky decision-making and impulsiv-
ity are rooted, at least in part, in the ventral striatum,
compromised ventral striatum integrity as a result
of TBI may promote these characteristics and lead
to substance abuse or other behavioural issues.
Limitations
There are some limitations in this study that are
important to recognize. First, with 14 participants
in the TBI group and 15 controls, the sample size is
somewhat small, although effect sizes for the relevant
statistics were generally moderate or large. Another
limitation of this study is the heterogeneity in
location, type and degree of focal injury.
Hemispheric differences with regard to degree
of damage may also be present. In one of the TBI
participants, the overall damage was so severe that
DTI fibre tracking was unable to be performed.
Lastly, the neuropsychological tasks that were used
were not very specific to the known functions of the
ventral striatum per se (e.g. decision-making). In the
future, the authors hope to try to obtain more
specific and relevant neuropsychological measures
in order to gain a more complete understanding
of the functions that are lost in TBI participants as a
result of their injuries. The automated volumetric
measures did not capture only the ventral striatum
per se and, therefore, the volumetric findings relate to
fairly general regions that include portions of the
ventral striatum.
Conclusions
TBI affects both the structural integrity of the
ventral striatum as well as the pathways intercon-
necting the upper brain with frontal and limbic
regions. Decreases in executive functioning are
related to damage to the ventral striatum and its
associated structures.
Acknowledgements
We thank Jonathan Chia, Vipulkumar Patel and
Dr. Ponnada Narayana for their assistance in the
development and implementation of the magnetic
resonance imaging sequences. Finally, we wish to
thank the participants of this study.
Declaration of Interest: The authors report no
conflicts of interest. Funding for this project
was provided by a grant from the Dana
Foundation (PI: Wilde).
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