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1.  Evaluation of white matter myelin water fraction in chronic stroke☆ 
NeuroImage : Clinical  2013;2:569-580.
Multi-component T2 relaxation imaging (MCRI) provides specific in vivo measurement of myelin water content and tissue water environments through myelin water fraction (MWF), intra/extra-cellular water fraction (I/EWF) and intra/extracellular and global geometric mean T2 (GMT2) times. Quantitative MCRI assessment of tissue water environments has provided new insights into the progression and underlying white matter pathology in neural disorders such as multiple sclerosis. It has not previously been applied to investigate changes in white matter in the stroke-affected brain. Thus, the purposes of this study were to 1) use MCRI to index myelin water content and tissue water environments in the brain after stroke 2) evaluate relationships between MWF and diffusion behavior indexed by diffusion tensor imaging-based metrics and 3) examine the relationship between white matter status (MWF and fractional anisotropy) and motor behavior in the chronic phase of stroke recovery. Twenty individuals with ischemic stroke and 12 matched healthy controls participated. Excellent to good test/re-test and inter-rater reliability was observed for region of interest-based voxelwise MWF data. Reduced MWF was observed in whole-cerebrum white matter (p < 0.001) and in the ipsilesional (p = 0.017) and contralesional (p = 0.037) posterior limb of internal capsule (PLIC) after stroke compared to whole-cerebrum and bilateral PLIC MWF in healthy controls. The stroke group also demonstrated increased I/EWF, I/E GMT2 and global GMT2 times for whole-cerebrum white matter. Measures of diffusion behavior were also significantly different in the stroke group across each region investigated (p < 0.001). MWF was not significantly correlated with specific tensor-based measures of diffusion in the PLIC for either group. Fractional anisotropy in the ipsilesional PLIC correlated with motor behavior in chronic stroke. These results provide novel insights into tissue-specific changes within white matter after stroke that may have important applications for the understanding of the neuropathology of stroke.
•Changes in structural properties of white matter may occur after stroke.•In vivo magnetic resonance techniques used to quantify brain myelin water fraction.•The imaging approach used showed excellent test/re-test and inter-rater reliability.•Local and global reductions in brain myelin water fraction shown in chronic stroke.•First report of in vivo changes in brain myelin in humans following stroke.
PMCID: PMC3777839  PMID: 24179808
Stroke; Myelin water fraction; T2 relaxation; Motor recovery; White matter
2.  White Matter Microstructure Alterations: A Study of Alcoholics with and without Post-Traumatic Stress Disorder 
PLoS ONE  2013;8(11):e80952.
Many brain imaging studies have demonstrated reductions in gray and white matter volumes in alcoholism, with fewer investigators using diffusion tensor imaging (DTI) to examine the integrity of white matter pathways. Among various medical conditions, alcoholism and post-traumatic stress disorder (PTSD) are two comorbid diseases that have similar degenerative effects on the white matter integrity. Therefore, understanding and differentiating these effects would be very important in characterizing alcoholism and PTSD. Alcoholics are known to have neurocognitive deficits in decision-making, particularly in decisions related to emotionally-motivated behavior, while individuals with PTSD have deficits in emotional regulation and enhanced fear response. It is widely believed that these types of abnormalities in both alcoholism and PTSD are related to fronto-limbic dysfunction. In addition, previous studies have shown cortico-limbic fiber degradation through fiber tracking in alcoholism. DTI was used to measure white matter fractional anisotropy (FA), which provides information about tissue microstructure, possibly indicating white matter integrity. We quantitatively investigated the microstructure of white matter through whole brain DTI analysis in healthy volunteers (HV) and alcohol dependent subjects without PTSD (ALC) and with PTSD (ALC+PTSD). These data show significant differences in FA between alcoholics and non-alcoholic HVs, with no significant differences in FA between ALC and ALC+PTSD in any white matter structure. We performed a post-hoc region of interest analysis that allowed us to incorporate multiple covariates into the analysis and found similar results. HV had higher FA in several areas implicated in the reward circuit, emotion, and executive functioning, suggesting that there may be microstructural abnormalities in white matter pathways that contribute to neurocognitive and executive functioning deficits observed in alcoholics. Furthermore, our data do not reveal any differences between ALC and ALC+PTSD, suggesting that the effect of alcohol on white matter microstructure may be more significant than any effect caused by PTSD.
PMCID: PMC3832443  PMID: 24260518
3.  Both projection and commissural pathways are disrupted in individuals with chronic stroke: investigating microstructural white matter correlates of motor recovery 
BMC Neuroscience  2012;13:107.
Complete recovery of motor function after stroke is rare with deficits persisting into the chronic phase of recovery. Diffusion tensor imaging (DTI) can evaluate relationships between white matter microstructure and motor function after stroke. The objective of this investigation was to characterize microstructural fiber integrity of motor and sensory regions of the corpus callosum (CC) and descending motor outputs of the posterior limb of the internal capsule (PLIC) in individuals with chronic stroke and evaluate the relationships between white matter integrity and motor function.
Standardized measures of upper extremity motor function were measured in thirteen individuals with chronic stroke. Manual dexterity was assessed in thirteen healthy age-matched control participants. DTI scans were completed for each participant. Fractional anisotropy (FA) of a cross-section of sensory and motor regions of the CC and the PLIC bilaterally were quantified. Multivariate analysis of variance evaluated differences between stroke and healthy groups. Correlational analyses were conducted for measures of motor function and FA. The stroke group exhibited reduced FA in the sensory (p = 0.001) region of the CC, contra- (p = 0.032) and ipsilesional (p = 0.001) PLIC, but not the motor region of the CC (p = 0.236). In the stroke group, significant correlations between contralesional PLIC FA and level of physical impairment (p = 0.005), grip strength (p = 0.006) and hand dexterity (p = 0.036) were observed.
Microstructural status of the sensory region of the CC is reduced in chronic stroke. Future work is needed to explore relationships between callosal sensorimotor fiber integrity and interhemispheric interactions post-stroke. In addition, contralesional primary motor output tract integrity is uniquely and closely associated with multiple dimensions of motor recovery in the chronic phase of stroke suggesting it may be an important biomarker of overall motor recovery.
PMCID: PMC3547772  PMID: 22931454
Diffusion tensor imaging; Stroke; Motor recovery; White matter; Integrity; Corpus callosum; Internal capsule
4.  Parietofrontal integrity determines neural modulation associated with grasping imagery after stroke 
Brain  2012;135(2):596-614.
Chronic stroke patients with heterogeneous lesions, but no direct damage to the primary sensorimotor cortex, are capable of longitudinally acquiring the ability to modulate sensorimotor rhythms using grasping imagery of the affected hand. Volitional modulation of neural activity can be used to drive grasping functions of the paralyzed hand through a brain–computer interface. The neural substrates underlying this skill are not known. Here, we investigated the impact of individual patient's lesion pathology on functional and structural network integrity related to this volitional skill. Magnetoencephalography data acquired throughout training was used to derive functional networks. Structural network models and local estimates of extralesional white matter microstructure were constructed using T1-weighted and diffusion-weighted magnetic resonance imaging data. We employed a graph theoretical approach to characterize emergent properties of distributed interactions between nodal brain regions of these networks. We report that interindividual variability in patients’ lesions led to differential impairment of functional and structural network characteristics related to successful post-training sensorimotor rhythm modulation skill. Patients displaying greater magnetoencephalography global cost-efficiency, a measure of information integration within the distributed functional network, achieved greater levels of skill. Analysis of lesion damage to structural network connectivity revealed that the impact on nodal betweenness centrality of the ipsilesional primary motor cortex, a measure that characterizes the importance of a brain region for integrating visuomotor information between frontal and parietal cortical regions and related thalamic nuclei, correlated with skill. Edge betweenness centrality, an analogous measure, which assesses the role of specific white matter fibre pathways in network integration, showed a similar relationship between skill and a portion of the ipsilesional superior longitudinal fascicle connecting premotor and posterior parietal visuomotor regions known to be crucially involved in normal grasping behaviour. Finally, estimated white matter microstructure integrity in regions of the contralesional superior longitudinal fascicle adjacent to primary sensorimotor and posterior parietal cortex, as well as grey matter volume co-localized to these specific regions, positively correlated with sensorimotor rhythm modulation leading to successful brain–computer interface control. Thus, volitional modulation of ipsilesional neural activity leading to control of paralyzed hand grasping function through a brain–computer interface after longitudinal training relies on structural and functional connectivity in both ipsilesional and contralesional parietofrontal pathways involved in visuomotor information processing. Extant integrity of this structural network may serve as a future predictor of response to longitudinal therapeutic interventions geared towards training sensorimotor rhythms in the lesioned brain, secondarily improving grasping function through brain–computer interface applications.
PMCID: PMC3286199  PMID: 22232595
motor learning; skill; stroke; rehabilitation; brain–computer interface; imagery
5.  White matter structural connectivity is associated with sensorimotor function in stroke survivors☆ 
NeuroImage : Clinical  2013;2:767-781.
Diffusion tensor imaging (DTI) provides functionally relevant information about white matter structure. Local anatomical connectivity information combined with fractional anisotropy (FA) and mean diffusivity (MD) may predict functional outcomes in stroke survivors. Imaging methods for predicting functional outcomes in stroke survivors are not well established. This work uses DTI to objectively assess the effects of a stroke lesion on white matter structure and sensorimotor function.
A voxel-based approach is introduced to assess a stroke lesion's global impact on motor function. Anatomical T1-weighted and diffusion tensor images of the brain were acquired for nineteen subjects (10 post-stroke and 9 age-matched controls). A manually selected volume of interest was used to alleviate the effects of stroke lesions on image registration. Images from all subjects were registered to the images of the control subject that was anatomically closest to Talairach space. Each subject's transformed image was uniformly seeded for DTI tractography. Each seed was inversely transformed into the individual subject space, where DTI tractography was conducted and then the results were transformed back to the reference space. A voxel-wise connectivity matrix was constructed from the fibers, which was then used to calculate the number of directly and indirectly connected neighbors of each voxel. A novel voxel-wise indirect structural connectivity (VISC) index was computed as the average number of direct connections to a voxel's indirect neighbors. Voxel-based analyses (VBA) were performed to compare VISC, FA, and MD for the detection of lesion-induced changes in sensorimotor function. For each voxel, a t-value was computed from the differences between each stroke brain and the 9 controls. A series of linear regressions was performed between Fugl-Meyer (FM) assessment scores of sensorimotor impairment and each DTI metric's log number of voxels that differed from the control group.
Correlation between the logarithm of the number of significant voxels in the ipsilesional hemisphere and total Fugl-Meyer score was moderate for MD (R2 = 0.512), and greater for VISC (R2 = 0.796) and FA (R2 = 0.674). The slopes of FA (p = 0.0036), VISC (p = 0.0005), and MD (p = 0.0199) versus the total FM score were significant. However, these correlations were driven by the upper extremity motor component of the FM score (VISC: R2 = 0.879) with little influence of the lower extremity motor component (FA: R2 = 0.177).
The results suggest that a voxel-wise metric based on DTI tractography can predict upper extremity sensorimotor function of stroke survivors, and that supraspinal intraconnectivity may have a less dominant role in lower extremity function.
•An intrinsic voxel-based structural connectivity metric is proposed.•The metric enhances the impact of stroke lesions on the distant voxels.•Whole-brain extralesional anatomical connectivity predicts functional outcome.•Functional impact of a lesion is determined by residual anatomical connectivity.•Connectivity to the posterior parietal cortex is a key to sensorimotor function.
PMCID: PMC3777792  PMID: 24179827
DTI, diffusion tensor imaging; FA, fractional anisotropy; FOV, field of view; FM, Fugl-Meyer; LDV, log difference volume; LE, lower extremity; MD, mean diffusivity; TE, echo time; TFIRE, Tactful Functional Imaging Research Environment; TR, repetition time; UE, upper extremity; VISC, voxel-wise indirect structural connectivity; Voxel-wise structural connectivity; Tractography; Diffusion tensor imaging; Stroke; Sensorimotor function; Lesion analysis
6.  Associations Between White Matter Microstructure and Infants’ Working Memory 
NeuroImage  2012;64:10.1016/j.neuroimage.2012.09.021.
Working memory emerges in infancy and plays a privileged role in subsequent adaptive cognitive development. The neural networks important for the development of working memory during infancy remain unknown. We used diffusion tensor imaging (DTI) and deterministic fiber tracking to characterize the microstructure of white matter fiber bundles hypothesized to support working memory in 12-month-old infants (n=73). Here we show robust associations between infants’ visuospatial working memory performance and microstructural characteristics of widespread white matter. Significant associations were found for white matter tracts that connect brain regions known to support working memory in older children and adults (genu, anterior and superior thalamic radiations, anterior cingulum, arcuate fasciculus, and the temporal-parietal segment). Better working memory scores were associated with higher FA and lower RD values in these selected white matter tracts. These tract-specific brain-behavior relationships accounted for a significant amount of individual variation above and beyond infants’ gestational age and developmental level, as measured with the Mullen Scales of Early Learning. Working memory was not associated with global measures of brain volume, as expected, and few associations were found between working memory and control white matter tracts. To our knowledge, this study is among the first demonstrations of brain-behavior associations in infants using quantitative tractography. The ability to characterize subtle individual differences in infant brain development associated with complex cognitive functions holds promise for improving our understanding of normative development, biomarkers of risk, experience-dependent learning and neuro-cognitive periods of developmental plasticity.
PMCID: PMC3838303  PMID: 22989623
infant; working memory; white matter; diffusion tensor imaging; brain development
7.  White matter integrity of premotor–motor connections is associated with motor output in chronic stroke patients 
NeuroImage : Clinical  2014;7:82-86.
Corticocortical functional interactions between the primary motor cortex (M1) and secondary motor areas, such as the dorsal (PMd) and ventral (PMv) premotor cortices and the supplementary motor area (SMA) are relevant for residual motor output after subcortical stroke. We hypothesized that the microstructural integrity of the underlying white matter tracts also plays a role in preserved motor output. Using diffusion-tensor imaging we aimed at (i) reconstructing individual probable intrahemispheric connections between M1 and the three secondary areas (PMd, PMv, SMA) and (ii) examining the extent to which the tract-related microstructural integrity correlates with residual motor output. The microstructural integrity of the tract connecting ipsilesional M1 and PMd was significantly associated with motor output (R = 0.78, P = 0.02). The present results support the view that ipsilesional secondary motor areas such as the PMd might support M1 via corticocortical connections to generate motor output after stroke.
•Cortico-cortical functional interactions in the motor network are relevant for residual motor output after subcortical stroke.•Microstructural integrity of the underlying white matter tracts might play a significant role in preserved motor functions.•Diffusion-tensor imaging (DTI) was used in stroke patients to reconstruct individual intrahemispheric connections between M1 and three secondary motor areas (PMd, PMv, SMA).•The extent to which the tract related microstructural integrity correlates with residual motor function was determined.•Microstructural integrity of intrahemispheric corticocortical tracts can be determined in stroke patients.•Data support the view that the microstructural integrity of the tract connecting ipsilesional M1 and PMd is significantly associated with recovered motor output in stroke patients.
PMCID: PMC4299958  PMID: 25610769
Fractional anisotropy; Cortical; Diffusion; Recovery; Structural
8.  Compensatory Neural Reorganization in Tourette Syndrome 
Current Biology  2011;21(7):580-585.
Children with neurological disorders may follow unique developmental trajectories whereby they undergo compensatory neuroplastic changes in brain structure and function that help them gain control over their symptoms [1–6]. We used behavioral and brain imaging techniques to investigate this conjecture in children with Tourette syndrome (TS). Using a behavioral task that induces high levels of intermanual conflict, we show that individuals with TS exhibit enhanced control of motor output. Then, using structural (diffusion-weighted imaging) brain imaging techniques, we demonstrate widespread differences in the white matter (WM) microstructure of the TS brain that include alterations in the corpus callosum and forceps minor (FM) WM that significantly predict tic severity in TS. Most importantly, we show that task performance for the TS group (but not for controls) is strongly predicted by the WM microstructure of the FM pathways that lead to the prefrontal cortex and by the functional magnetic resonance imaging blood oxygen level-dependent response in prefrontal areas connected by these tracts. These results provide evidence for compensatory brain reorganization that may underlie the increased self-regulation mechanisms that have been hypothesized to bring about the control of tics during adolescence.
► We combine behavioral studies with structural and functional neuroimaging ► We report enhanced cognitive control in children with Tourette syndrome ► Frontal lobe white-matter microstructure predicts tic severity in Tourette syndrome ► Frontal lobe white-matter and fMRI BOLD predict cognitive control in Tourette syndrome
PMCID: PMC3076629  PMID: 21439830
9.  MRI investigation of the sensorimotor cortex and the corticospinal tract after acute spinal cord injury: a prospective longitudinal study 
Lancet Neurology  2013;12(9):873-881.
In patients with chronic spinal cord injury, imaging of the spinal cord and brain above the level of the lesion provides evidence of neural degeneration; however, the spatial and temporal patterns of progression and their relation to clinical outcomes are uncertain. New interventions targeting acute spinal cord injury have entered clinical trials but neuroimaging outcomes as responsive markers of treatment have yet to be established. We aimed to use MRI to assess neuronal degeneration above the level of the lesion after acute spinal cord injury.
In our prospective longitudinal study, we enrolled patients with acute traumatic spinal cord injury and healthy controls. We assessed patients clinically and by MRI at baseline, 2 months, 6 months, and 12 months, and controls by MRI at the same timepoints. We assessed atrophy in white matter in the cranial corticospinal tracts and grey matter in sensorimotor cortices by tensor-based analyses of T1-weighted MRI data. We used cross-sectional spinal cord area measurements to assess atrophy at cervical level C2/C3. We used myelin-sensitive magnetisation transfer (MT) and longitudinal relaxation rate (R1) maps to assess microstructural changes associated with myelin. We also assessed associations between MRI parameters and clinical improvement. All analyses of brain scans done with statistical parametric mapping were corrected for family-wise error.
Between Sept 17, 2010, and Dec 31, 2012, we recruited 13 patients and 18 controls. In the 12 months from baseline, patients recovered by a mean of 5·27 points per log month (95% CI 1·91–8·63) on the international standards for the neurological classification of spinal cord injury (ISNCSCI) motor score (p=0·002) and by 10·93 points per log month (6·20–15·66) on the spinal cord independence measure (SCIM) score (p<0·0001). Compared with controls, patients showed a rapid decline in cross-sectional spinal cord area (patients declined by 0·46 mm per month compared with a stable cord area in controls; p<0·0001). Patients had faster rates than controls of volume decline of white matter in the cranial corticospinal tracts at the level of the internal capsule (right Z score 5·21, p=0·0081; left Z score 4·12, p=0·0004) and right cerebral peduncle (Z score 3·89, p=0·0302) and of grey matter in the left primary motor cortex (Z score 4·23, p=0·041). Volume changes were paralleled by significant reductions of MT and R1 in the same areas and beyond. Improvements in SCIM scores at 12 months were associated with a reduced loss in cross-sectional spinal cord area over 12 months (Pearson's correlation 0·77, p=0·004) and reduced white matter volume of the corticospinal tracts at the level of the right internal capsule (Z score 4·30, p=0·0021), the left internal capsule (Z score 4·27, p=0·0278), and left cerebral peduncle (Z score 4·05, p=0·0316). Improvements in ISNCSCI motor scores were associated with less white matter volume change encompassing the corticospinal tract at the level of the right internal capsule (Z score 4·01, p<0·0001).
Extensive upstream atrophic and microstructural changes of corticospinal axons and sensorimotor cortical areas occur in the first months after spinal cord injury, with faster degenerative changes relating to poorer recovery. Structural volumetric and microstructural MRI protocols remote from the site of spinal cord injury could serve as neuroimaging biomarkers in acute spinal cord injury.
SRH Holding, Swiss National Science Foundation, Clinical Research Priority Program “NeuroRehab” University of Zurich, Wellcome Trust.
PMCID: PMC3744750  PMID: 23827394
10.  Motor recovery and microstructural change in rubro-spinal tract in subcortical stroke☆ 
NeuroImage : Clinical  2013;4:201-208.
The mechanism of motor recovery after stroke may involve reorganization of the surviving networks. However, details of adaptive changes in structural connectivity are not well understood. Here, we show long-term changes in white matter microstructure that relate to motor recovery in stroke patients. We studied ten subcortical ischemic stroke patients who showed motor hemiparesis at the initial clinical examination and an infarcted lesion centered in the posterior limb of internal capsule of the unilateral hemisphere at the initial diffusion-weighted magnetic resonance imaging scan. The participants underwent serial diffusion tensor imaging and motor function assessments at three consecutive time points; within 2 weeks, and at 1 and 3 months after the onset. Fractional anisotropy (FA) was analyzed for regional differences between hemispheres and time points, as well as for correlation with motor recovery using a tract-based spatial statistics analysis. The results showed significantly increased FA in the red nucleus and dorsal pons in the ipsi-lesional side at 3 months, and significantly decreased FA in the ipsi-lesional internal capsule at all time points, and in the cerebral peduncle, corona radiata, and corpus callosum at 3 months. In the correlation analysis, FA values of clusters in the red nucleus, dorsal pons, midbody of corpus callosum, and cingulum were positively correlated with recovery of motor function. Our study suggests that changes in white matter microstructure in alternative descending motor tracts including the rubro-spinal pathway, and interhemispheric callosal connections may play a key role in compensating for motor impairment after subcortical stroke.
•Subcortical stroke patients showed motor hemiparesis followed by gradual recovery.•Lesion overlap was located with its center in the posterior limb of internal capsule.•Fractional anisotropy (FA) gradually increased in the red nucleus in three months.•FA in the red nucleus was positively correlated with recovery of motor paresis.•FA in the middle part of corpus callosum was also correlated with motor recovery.
PMCID: PMC3891492  PMID: 24432247
CC, Corpus callosum; CP, Cerebral peduncle; CR, Corona radiata; DTI, Diffusion tensor imaging; EPT, Extrapyramidal tract; FA, Fractional Anisotropy; FMMS, Fugl-Meyer Motor Scale; PLIC, Posterior limb of internal capsule; PT, Pyramidal tract; TBSS, Tract-based spatial statistics; Motor recovery; Subcortical stroke; Reorganization; Diffusion tensor image; Tract-based spatial statistics
11.  Diffusion Tensor Imaging in Autism Spectrum Disorder: A Review 
Lay Abstract
White matter tracts are like the “highways” of the brain, allowing for fast and efficient communication among diverse brain regions. The purpose of this paper is to review the results of autism studies that have used Diffusion Tensor Imaging (DTI), which is a neuroimaging method that allows us to examine the structure and integrity of these white matter tracts. From the 48 studies we reviewed, persons with ASD tended to have decreased white matter integrity spanning across many regions of the brain but most consistently in regions such as the corpus callosum (connecting the left and right hemispheres and associated with motor skill and complex information processing), the cingulum bundles (connecting regions along the middle-line of the brain with important frontal projections and associated with executive function), and white matter tracts that pass through the temporal lobe (connecting temporal lobe regions with other brain regions and associated with social functioning). The pattern of results in these studies suggests that the white matter tracts may be atypical in persons with ASD. Additionally, the review suggests that people with ASD may not exhibit the typical left-greater-than-right-brain asymmetry in white matter integrity compared to people with typical development. White matter alterations in persons with ASD are a target of emerging interventions and may help identify the brain basis of individual differences in this population.
Scientific Abstract
White matter tracts of the brain allow neurons and neuronal networks to communicate and function with high efficiency. The aim of this review is to briefly introduce Diffusion Tensor Imaging (DTI) methods that examine white matter tracts and then to give an overview of the studies that have investigated white matter integrity in the brains of individuals with Autism Spectrum Disorder (ASD). From the 48 studies we reviewed, persons with ASD tended to have decreased fractional anisotropy and increased mean diffusivity in white matter tracts spanning many regions of the brain but most consistently in regions such as the corpus callosum, cingulum, and aspects of the temporal lobe. This decrease in fractional anisotropy was often accompanied by increased radial diffusivity. Additionally, the review suggests possible atypical lateralization in some white matter tracts of the brain and a possible atypical developmental trajectory of white matter microstructure in persons with ASD. Clinical implications and future research directions are discussed.
PMCID: PMC3474893  PMID: 22786754
Diffusion Tensor Imaging; Neuroimaging; Autism; White Matter
12.  Abnormal Anatomical Connectivity between the Amygdala and Orbitofrontal Cortex in Conduct Disorder 
PLoS ONE  2012;7(11):e48789.
Previous research suggested that structural and functional abnormalities within the amygdala and orbitofrontal cortex contribute to the pathophysiology of Conduct Disorder (CD). Here, we investigated whether the integrity of the white-matter pathways connecting these regions is abnormal and thus may represent a putative neurobiological marker for CD.
Diffusion Tensor Imaging (DTI) was used to investigate white-matter microstructural integrity in male adolescents with childhood-onset CD, compared with healthy controls matched in age, sex, intelligence, and socioeconomic status. Two approaches were employed to analyze DTI data: voxel-based morphometry of fractional anisotropy (FA), an index of white-matter integrity, and virtual dissection of white-matter pathways using tractography.
Adolescents with CD displayed higher FA within the right external capsule relative to controls (T = 6.08, P<0.05, Family-Wise Error, whole-brain correction). Tractography analyses showed that FA values within the uncinate fascicle (connecting the amygdala and orbitofrontal cortex) were abnormally increased in individuals with CD relative to controls. This was in contrast with the inferior frontal-occipital fascicle, which showed no significant group differences in FA. The finding of increased FA in the uncinate fascicle remained significant when factoring out the contribution of attention-deficit/hyperactivity disorder symptoms. There were no group differences in the number of streamlines in either of these anatomical tracts.
These results provide evidence that CD is associated with white-matter microstructural abnormalities in the anatomical tract that connects the amygdala and orbitofrontal cortex, the uncinate fascicle. These results implicate abnormal maturation of white-matter pathways which are fundamental in the regulation of emotional behavior in CD.
PMCID: PMC3492256  PMID: 23144970
13.  Probing white-matter microstructure with higher-order diffusion tensors and susceptibility tensor MRI 
Diffusion MRI has become an invaluable tool for studying white matter microstructure and brain connectivity. The emergence of quantitative susceptibility mapping and susceptibility tensor imaging (STI) has provided another unique tool for assessing the structure of white matter. In the highly ordered white matter structure, diffusion MRI measures hindered water mobility induced by various tissue and cell membranes, while susceptibility sensitizes to the molecular composition and axonal arrangement. Integrating these two methods may produce new insights into the complex physiology of white matter. In this study, we investigated the relationship between diffusion and magnetic susceptibility in the white matter. Experiments were conducted on phantoms and human brains in vivo. Diffusion properties were quantified with the diffusion tensor model and also with the higher order tensor model based on the cumulant expansion. Frequency shift and susceptibility tensor were measured with quantitative susceptibility mapping and susceptibility tensor imaging. These diffusion and susceptibility quantities were compared and correlated in regions of single fiber bundles and regions of multiple fiber orientations. Relationships were established with similarities and differences identified. It is believed that diffusion MRI and susceptibility MRI provide complementary information of the microstructure of white matter. Together, they allow a more complete assessment of healthy and diseased brains.
PMCID: PMC3589706  PMID: 23507987
MRI; white matter; diffusion tensor imaging; generalized diffusion tensor imaging; susceptibility tensor imaging; higher order tensor; cumulant; kurtosis
14.  Characterizing relationships of DTI, fMRI, and motor recovery in stroke rehabilitation utilizing brain-computer interface technology 
The relationship of the structural integrity of white matter tracts and cortical activity to motor functional outcomes in stroke patients is of particular interest in understanding mechanisms of brain structural and functional changes while recovering from stroke. This study aims to probe these underlying mechanisms using diffusion tensor imaging (DTI) and fMRI measures. We examined the structural integrity of the posterior limb of the internal capsule (PLIC) using DTI and corticomotor activity using motor-task fMRI in stroke patients who completed up to 15 sessions of rehabilitation therapy using Brain-Computer Interface (BCI) technology. We hypothesized that (1) the structural integrity of PLIC and corticomotor activity are affected by stroke; (2) changes in structural integrity and corticomotor activity following BCI intervention are related to motor recovery; (3) there is a potential relationship between structural integrity and corticomotor activity. We found that (1) the ipsilesional PLIC showed significantly decreased fractional anisotropy (FA) values when compared to the contralesional PLIC; (2) lower ipsilesional PLIC-FA values were significantly associated with worse motor outcomes (i.e., ipsilesional PLIC-FA and motor outcomes were positively correlated.); (3) lower ipsilesional PLIC-FA values were significantly associated with greater ipsilesional corticomotor activity during impaired-finger-tapping-task fMRI (i.e., ipsilesional PLIC-FA and ipsilesional corticomotor activity were negatively correlated), with an overall bilateral pattern of corticomotor activity observed; and (4) baseline FA values predicted motor recovery assessed after BCI intervention. These findings suggest that (1) greater vs. lesser microstructural integrity of the ipsilesional PLIC may contribute toward better vs. poor motor recovery respectively in the stroke-affected limb and demand lesser vs. greater cortical activity respectively from the ipsilesional motor cortex; and that (2) PLIC-FA is a promising biomarker in tracking and predicting motor functional recovery in stroke patients receiving BCI intervention.
PMCID: PMC4114288  PMID: 25120466
DTI; FA; fMRI; motor recovery; stroke rehabilitation; BCI
15.  Transcallosal White Matter Degradation Detected With Quantitative Fiber Tracking in Alcoholic Men and Women: Selective Relations to Dissociable Functions 
Excessive alcohol consumption can adversely affect white matter fibers and disrupt transmission of neuronal signals. Here, we examined six anatomically defined transcallosal white matter fiber bundles and asked whether any bundle was specifically vulnerable to alcohol, what aspect of white matter integrity was most affected, whether women were more vulnerable than men, and whether evidence of compromise in specific bundles was associated with deficits in balance, sustained attention, associative learning, and psychomotor function, commonly affected in alcoholics.
Diffusion tensor imaging quantitative fiber tracking assessed integrity of six transcallosal white matter bundles in 87 alcoholics (59 men, 28 women) and 88 healthy controls (42 men, 46 women). Measures included orientational diffusion coherence (fractional anisotropy, FA) and magnitude of diffusion, quantified separately for axial (longitudinal; λL) and radial (transverse; λT) diffusivity. The Digit Symbol Test and a test of ataxia were also administered.
Alcoholism negatively affected callosal FA and λT of all but the sensory-motor bundle. Women showed no evidence for greater vulnerability to alcohol than men. Multiple regression analyses confirmed a double dissociation: higher diffusivity in sensory-motor and parietal bundles was associated with poorer balance but not psychomotor speed, whereas higher diffusivity in prefrontal and temporal bundles was associated with slower psychomotor speed but not balance.
This study revealed stronger alcohol effects for FA and radial diffusivity than axial diffusivity, suggesting myelin degradation, but no evidence for greater vulnerability to alcohol in women than men. The presence of brain-behavior relationships provides support for the role of alcoholism-related commissural white matter degradation as a substrate of cognitive and motor impairment. Identification of a double dissociation provides further support for the role of selective white matter integrity in specific domains of performance.
PMCID: PMC2910526  PMID: 20477772
Alcoholism; Corpus Callosum; Fiber Tracking; Sex; Ataxia; Digit Symbol Test
16.  Microstructural Correlations of White Matter Tracts in the Human Brain 
NeuroImage  2010;51(2):531-541.
The purpose of this study is to investigate whether specific patterns of correlation exist in diffusion tensor imaging (DTI) parameters across white matter tracts in the normal human brain, and whether the relative strengths of these putative microstructural correlations might reflect phylogenetic and functional similarities between tracts. We performed quantitative DTI fiber tracking on 44 healthy adult volunteers to obtain tract-based measures of mean diffusivity (MD), fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) from four homologous pairs of neocortical association pathways (arcuate fasciculi, inferior fronto-occipital fasciculi, inferior longitudinal fasciculi, and uncinate fasciculi bilaterally), a homologous pair of limbic association pathways (left and right dorsal cingulum bundles), and a homologous pair of cortical-subcortical projection pathways (left and right corticospinal tracts). From the resulting inter-tract correlation matrices, we show that there are statistically significant correlations of DTI parameters between tracts, and that there are statistically significant variations among these inter-tract correlations. Furthermore, we observe that many, but by no means all, of the strongest correlations were between homologous tracts in the left and right hemispheres. Even among homologous pairs of tracts, there were wide variations in the degree of coupling. Finally, we generate a data-driven hierarchical clustering of the fiber pathways based on pairwise FA correlations to demonstrate that the neocortical association pathways tended to group separately from the limbic pathways at trend-level statistical significance, and that the projection pathways of the left and right corticospinal tracts comprise the most distant outgroup with high confidence (p<0.01). Hence, specific patterns of microstructural correlation exist between tracts and may reflect phylogenetic and functional similarities between tracts. The study of these microstructural relationships between white matter pathways might aid research on the genetic basis and on the behavioral effects of axonal connectivity, as well as provide a revealing new perspective with which to investigate neurological and psychiatric disorders.
PMCID: PMC2856800  PMID: 20206699
Behavior; Brain; Cognition; Diffusion Tensor Imaging (DTI); Human; Hierarchical Clustering; Fiber Tractography; Language; White Matter
17.  Abnormal functional connectivity during visuospatial processing is associated with disrupted organisation of white matter in autism 
Disruption of structural and functional neural connectivity has been widely reported in Autism Spectrum Disorder (ASD) but there is a striking lack of research attempting to integrate analysis of functional and structural connectivity in the same study population, an approach that may provide key insights into the specific neurobiological underpinnings of altered functional connectivity in autism. The aims of this study were (1) to determine whether functional connectivity abnormalities were associated with structural abnormalities of white matter (WM) in ASD and (2) to examine the relationships between aberrant neural connectivity and behavior in ASD. Twenty-two individuals with ASD and 22 age, IQ-matched controls completed a high-angular-resolution diffusion MRI scan. Structural connectivity was analysed using constrained spherical deconvolution (CSD) based tractography. Regions for tractography were generated from the results of a previous study, in which 10 pairs of brain regions showed abnormal functional connectivity during visuospatial processing in ASD. WM tracts directly connected 5 of the 10 region pairs that showed abnormal functional connectivity; linking a region in the left occipital lobe (left BA19) and five paired regions: left caudate head, left caudate body, left uncus, left thalamus, and left cuneus. Measures of WM microstructural organization were extracted from these tracts. Fractional anisotropy (FA) reductions in the ASD group relative to controls were significant for WM connecting left BA19 to left caudate head and left BA19 to left thalamus. Using a multimodal imaging approach, this study has revealed aberrant WM microstructure in tracts that directly connect brain regions that are abnormally functionally connected in ASD. These results provide novel evidence to suggest that structural brain pathology may contribute (1) to abnormal functional connectivity and (2) to atypical visuospatial processing in ASD.
PMCID: PMC3783945  PMID: 24133425
neuroimaging; autism spectrum disorders; functional connectivity; diffusion tractography; constrained spherical deconvolution; visuospatial processing; structural connectivity; mental rotation
18.  Microstructural Status of Ipsilesional and Contralesional Corticospinal Tract Correlates with Motor Skill in Chronic Stroke Patients 
Human brain mapping  2009;30(11):3461-3474.
Greater loss in structural integrity of the ipsilesional corticospinal tract (CST) is associated with poorer motor outcome in hemiparetic stroke patients. Animal models of stroke have demonstrated that structural remodeling of white matter in the ipsilesional and contralesional hemispheres is associated with improved motor recovery. Accordingly, motor recovery in stroke patients may relate to the relative strength of CST degeneration and remodeling. This study examined the relationship between microstructural status of brain white matter tracts, indexed by the fractional anisotropy (FA) metric derived from diffusion tensor imaging (DTI) data, and motor skill of the stroke-affected hand in chronic stroke patients. Voxelwise analysis revealed that motor skill significantly and positively correlated with FA of the ipsilesional and contralesional CST in the patients. Additional voxelwise analyses showed that patients with poorer motor skill had reduced FA of bilateral CST compared to normal control subjects whereas patients with better motor skill had elevated FA of bilateral CST compared to controls. These findings were confirmed using a DTI-tractography method applied to the CST in both hemispheres. The results of this study suggest that the level of motor skill recovery achieved in hemiparetic stroke patients relates to microstructural status of the CST in both the ipsilesional and contralesional hemispheres, which may reflect the net effect of degeneration and remodeling of bilateral CST.
PMCID: PMC2780023  PMID: 19370766
diffusion tensor imaging; anisotropy; stroke recovery; hemiparesis; tractography; white matter
19.  Delay Discounting and Frontostriatal Fiber Tracts: A Combined DTI and MTR Study on Impulsive Choices in Healthy Young Adults 
Cerebral Cortex (New York, NY)  2012;23(7):1695-1702.
Delay discounting, a measure of impulsive choice, has been associated with decreased control of the prefrontal cortex over striatum responses. The anatomical connectivity between both brain regions in delaying gratification remains unknown. Here, we investigate whether the quality of frontostriatal (FS) white matter tracts can predict individual differences in delay-discounting behavior. We use tract-based diffusion tensor imaging and magnetization transfer imaging to measure the microstructural properties of FS fiber tracts in 40 healthy young adults (from 18 to 25 years). We additionally explored whether internal sex hormone levels affect the integrity of FS tracts, based on the hypothesis that sex hormones modulate axonal density within prefrontal dopaminergic circuits. We calculated fractional anisotropy (FA), mean diffusivity (MD), longitudinal diffusivity, radial diffusivity (RD), and magnetization transfer ratio (MTR), a putative measure of myelination, for the FS tract. Results showed that lower integrity within the FS tract (higher MD and RD and lower FA), predicts faster discounting in both sexes. MTR was unrelated to delay-discounting performance. In addition, testosterone levels in males were associated with a lower integrity (higher RD) within the FS tract. Our study provides support for the hypothesis that enhanced structural integrity of white matter fiber bundles between prefrontal and striatal brain areas is associated with better impulse control.
PMCID: PMC3673180  PMID: 22693341
delay discounting; DTI; frontostriatal tracts; impulsivity; testosterone
20.  Anatomical Alterations of the Visual Motion Processing Network in Migraine with and without Aura 
PLoS Medicine  2006;3(10):e402.
Patients suffering from migraine with aura (MWA) and migraine without aura (MWoA) show abnormalities in visual motion perception during and between attacks. Whether this represents the consequences of structural changes in motion-processing networks in migraineurs is unknown. Moreover, the diagnosis of migraine relies on patient's history, and finding differences in the brain of migraineurs might help to contribute to basic research aimed at better understanding the pathophysiology of migraine.
Methods and Findings
To investigate a common potential anatomical basis for these disturbances, we used high-resolution cortical thickness measurement and diffusion tensor imaging (DTI) to examine the motion-processing network in 24 migraine patients (12 with MWA and 12 MWoA) and 15 age-matched healthy controls (HCs). We found increased cortical thickness of motion-processing visual areas MT+ and V3A in migraineurs compared to HCs. Cortical thickness increases were accompanied by abnormalities of the subjacent white matter. In addition, DTI revealed that migraineurs have alterations in superior colliculus and the lateral geniculate nucleus, which are also involved in visual processing.
A structural abnormality in the network of motion-processing areas could account for, or be the result of, the cortical hyperexcitability observed in migraineurs. The finding in patients with both MWA and MWoA of thickness abnormalities in area V3A, previously described as a source in spreading changes involved in visual aura, raises the question as to whether a “silent” cortical spreading depression develops as well in MWoA. In addition, these experimental data may provide clinicians and researchers with a noninvasively acquirable migraine biomarker.
A structural abnormality in the network of motion-processing areas could account for, or be the result of, the cortical hyperexcitability seen in people who have migraine.
Editors' Summary
Migraine is a disabling brain disorder that affects more than one in ten people during their lifetimes. It is characterized by severe, recurrent headaches, often accompanied by nausea, vomiting, and light sensitivity. In some migraineurs (people who have migraines), the headaches are preceded by neurological disturbances known as “aura.” These usually affect vision, causing illusions of flashing lights, zig-zag lines, or blind spots. There are many triggers for migraine attacks—including some foods, stress, and bright lights—and every migraineur has to learn what triggers his or her attacks. There is no cure for migraine, although over-the-counter painkillers can ease the symptoms and doctors can prescribe stronger remedies or drugs to reduce the frequency of attacks. Exactly what causes migraine is unclear but scientists think that, for some reason, the brains of migraineurs are hyperexcitable. That is, some nerve cells in their brains overreact when they receive electrical messages from the body. This triggers a local disturbance of brain function called “cortical spreading depression,” which, in turn, causes aura, headache, and the other symptoms of migraine.
Why Was This Study Done?
Researchers need to know more about what causes migraine to find better treatments. One clue comes from the observation that motion perception is abnormal in migraineurs, even between attacks—they can be very sensitive to visually induced motion sickness, for example. Another clue is that aura are usually visual. So could brain regions that process visual information be abnormal in people who have migraines? In this study, the researchers investigated the structure of the motion processing parts of the brain in people who have migraine with aura, in people who have migraine without aura, and in unaffected individuals to see whether there were any differences that might help them understand migraine.
What Did the Researchers Do and Find?
The researchers used two forms of magnetic resonance imaging—a noninvasive way to produce pictures of internal organs—to examine the brains of migraineurs (when they weren't having a migraine) and healthy controls. They concentrated on two brain regions involved in motion processing known as the MT+ and V3A areas and first measured the cortical thickness of these areas—the cortex is the wrinkled layer of gray matter on the outside of the brain that processes information sent from the body. They found that the cortical thickness was increased in both of these areas in migraineurs when compared to healthy controls. There was no difference in cortical thickness between migraineurs who had aura and those who did not, but the area of cortical thickening in V3A corresponded to the source of cortical spreading depression previously identified in a person who had migraine with aura. The researchers also found differences between the white matter (the part of the brain that transfers information between different regions of the gray matter) immediately below the V3A and MT+ areas in the migraineurs and the controls but again not between the two groups of migraineurs.
What Do These Findings Mean?
This study provides new information about migraine. First, it identifies structural changes in the brains of people who have migraines. Until now, it has been thought that abnormal brain function causes migraine but that migraineurs have a normal brain structure. The observed structural differences might either account for or be caused by the hyperexcitability that triggers migraines. Because migraine runs in families, examining the brains of children of migraineurs as they grow up might indicate which of these options is correct, although it is possible that abnormalities in brain areas not examined here actually trigger migraines. Second, the study addresses a controversial question about migraine: Is migraine with aura the same as migraine without aura? The similar brain changes in both types of migraine suggest that they are one disorder. Third, the abnormalities in areas MT+ and V3A could help to explain why migraineurs have problems with visual processing even in between attacks. Finally, this study suggests that it might be possible to develop a noninvasive test to help doctors diagnose migraine.
Additional Information.
Please access these Web sites via the online version of this summary at
The MedlinePlus encyclopedia has several pages on migraine
The US National Institute of Neurological Disorders and Stroke offers patient information on migraine and other headaches
The NHS Direct Online contains patient information on migraine from the UK National Health Service
MAGNUM provides information from The US National Migraine Association
The Migraine Trust is a UK charity that supports research and provides support for patients
The Migraine Aura Foundation is a site about aura that includes a section on art and aura
PMCID: PMC1609120  PMID: 17048979
21.  MRI Signatures of Brain Macrostructural Atrophy and Microstructural Degradation in Frontotemporal Lobar Degeneration Subtypes 
Brain magnetic resonance imaging (MRI) studies have demonstrated regional patterns of brain macrostructural atrophy and white matter microstructural alterations separately in the three major subtypes of frontotemporal lobar degeneration (FTLD), which includes behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). This study was to investigate to what extent the pattern of white matter microstructural alterations in FTLD subtypes mirrors the pattern of brain atrophy, and to compare the ability of various diffusion tensor imaging (DTI) indices in characterizing FTLD patients, as well as to determine whether DTI measures provide greater classification power for FTLD than measuring brain atrophy. Twenty-five patients with FTLD (13 with bvFTD, 6 with SD, and 6 with PNFA) and 19 healthy age-matched control subjects underwent both structural MRI and DTI scans. Measurements of regional brain atrophy were based on T1-weighted MRI data and voxel-based morphometry. Measurements of regional white matter degradation were based on voxelwise as well as regions-of-interest tests of DTI variations, expressed as fractional anisotropy, axial diffusivity, and radial diffusivity. Compared to controls, bvFTD, SD, and PNFA patients each exhibited characteristic regional patterns of brain atrophy and white matter damage. DTI overall provided significantly greater accuracy for FTLD classification than brain atrophy. Moreover, radial diffusivity was more sensitive in assessing white matter damage in FTLD than other DTI indices. The findings suggest that DTI in general and radial diffusivity in particular are more powerful measures for the classification of FTLD patients from controls than brain atrophy.
PMCID: PMC3738303  PMID: 22976075
Behavioral variant frontotemporal dementia; diffusion tensor imaging; frontotemporal lobar degeneration; multimodality MRI; progressive nonfluent aphasia; semantic dementia
22.  Diffusion tensor imaging reveals white matter microstructure correlations with auditory processing ability 
Ear and hearing  2011;32(2):156-167.
Correlation of white matter microstructure with various cognitive processing tasks and with overall intelligence has been previously demonstrated. We investigate the correlation of white matter microstructure with various higher-order auditory processing tasks, including interpretation of speech-in-noise, recognition of low-pass frequency filtered words, and interpretation of time-compressed sentences at two different values of compression. These tests are typically used to diagnose auditory processing disorder (APD) in children. Our hypothesis is that correlations between white matter microstructure in tracts connecting the temporal, frontal, and parietal lobes, as well as callosal pathways, will be seen. Previous functional imaging studies have shown correlations between activation in temporal, frontal and parietal regions from higher-order auditory processing tasks. Additionally, we hypothesize that the regions displaying correlations will vary according to the task, as each task uses a different set of skills.
Diffusion tensor imaging (DTI) data was acquired in a cohort of 17 normal-hearing children ages 9-11. Fractional anisotropy (FA), a measure of white matter fiber tract integrity and organization was computed and correlated on a voxelwise basis with performance on the auditory processing tasks, controlling for age, sex, and full-scale IQ.
Divergent correlations of white matter FA depending on the particular auditory processing task were found. Positive correlations were found between FA and speech-in-noise in white matter adjoining prefrontal areas, and between FA and filtered words in the corpus callosum. Regions exhibiting correlations with time-compressed sentences varied depending on the degree of compression: the greater degree of compression (with the greatest difficulty) resulted in correlations in white matter adjoining prefrontal (dorsal and ventral) while the smaller degree of compression (with less difficulty) resulted in correlations in white matter adjoining audio-visual association areas and the posterior cingulate. Only the time-compressed sentences with the lowest degree of compression resulted in positive correlations in the centrum semiovale; all the other tasks resulted in negative correlations.
The dependence of performance on higher-order auditory processing tasks on brain anatomical connectivity was seen in normal-hearing children ages 9-11. Results support a previously hypothesized dual-stream (dorsal and ventral) model of auditory processing, and that higher-order processing tasks rely less on the dorsal stream related to articulatory networks, and more on the ventral stream related to semantic comprehension. Results also show that the regions correlating with auditory processing vary according to the specific task, indicating that the neurological bases for the various tests used to diagnose APD in children may be partially independent.
PMCID: PMC3057932  PMID: 21063207
Auditory Processing; Auditory Processing Disorder; Children; Diffusion Tensor Imaging
23.  Structural and Functional Bases for Individual Differences in Motor Learning 
Human brain mapping  2011;32(3):494-508.
People vary in their ability to learn new motor skills. We hypothesize that between-subject variability in brain structure and function can explain differences in learning. We use brain functional and structural MRI methods to characterize such neural correlates of individual variations in motor learning. Healthy subjects applied isometric grip force of varying magnitudes with their right hands cued visually to generate smoothly-varying pressures following a regular pattern. We tested whether individual variations in motor learning were associated with anatomically colocalized variations in magnitude of functional MRI (fMRI) signal or in MRI differences related to white and grey matter microstructure. We found that individual motor learning was correlated with greater functional activation in the prefrontal, premotor, and parietal cortices, as well as in the basal ganglia and cerebellum.
Structural MRI correlates were found in the premotor cortex [for fractional anisotropy (FA)] and in the cerebellum [for both grey matter density and FA]. The cerebellar microstructural differences were anatomically colocalized with fMRI correlates of learning. This study thus suggests that variations across the population in the function and structure of specific brain regions for motor control explain some of the individual differences in skill learning. This strengthens the notion that brain structure determines some limits to cognitive function even in a healthy population. Along with evidence from pathology suggesting a role for these regions in spontaneous motor recovery, our results also highlight potential targets for therapeutic interventions designed to maximize plasticity for recovery of similar visuomotor skills after brain injury.
PMCID: PMC3674543  PMID: 20533562
24.  Individual Differences in Expert Motor Coordination Associated with White Matter Microstructure in the Cerebellum 
Cerebral Cortex (New York, NY)  2012;23(10):2282-2292.
Recent investigations into the neural basis of elite sporting performance have focused on whether cortical activity might characterize individual differences in ability. However, very little is understood about how changes in brain structure might contribute to individual differences in expert motor control. We compared the behavior and brain structure of healthy controls with a group of karate black belts, an expert group who are able to perform rapid, complex movements that require years of training. Using 3D motion tracking, we investigated whether the ability to control ballistic arm movements was associated with differences in white matter microstructure. We found that karate experts are better able than novices to coordinate the timing of inter-segmental joint velocities. Diffusion tensor imaging revealed significant differences between the groups in the microstructure of white matter in the superior cerebellar peduncles (SCPs) and primary motor cortex—brain regions that are critical to the voluntary control of movement. Motor coordination, the amount of experience, and the age at which training began were all associated with individual differences in white matter integrity in the cerebellum within the karate groups. These findings suggest a role for the white matter pathways of the SCPs in motor expertise.
PMCID: PMC3767954  PMID: 22892425
cerebellum; diffusion tensor imaging; expertise; individual differences; motor control
25.  Resting State Interhemispheric Motor Connectivity and White Matter Integrity Correlate with Motor Impairment in Chronic Stroke 
Functional and structural reorganization in the brain occurs after stroke. The ability to predict motor outcomes may depend on patterns of brain functional and structural connectivity. We tested the hypothesis that alterations in motor transcallosal and corticospinal connections correlate with motor impairment in patients with chronic stroke. Eleven ischemic stroke patients underwent the Upper Extremity Fugl-Meyer (UE-FM) assessment, resting state functional magnetic resonance imaging, and diffusion tensor imaging (DTI). Twelve healthy control subjects underwent DTI. We assessed the temporal coupling in neural activity between interhemispheric motor cortex, and white matter integrity by means of fractional anisotropy (FA), in the transcallosal motor fibers and corticospinal tract. Partial correlation analyses were performed to determine whether these connectivity measures correlate with Upper UE-FM scores. Patients compared to controls had reduced FA in common voxels of transcallosal motor and ipsilesional corticospinal fibers. Within the patient group those with higher interhemispheric motor cortex connectivity and higher FA in the transcallosal motor fibers were less impaired. The results show that markers of functional and structural motor cortex connectivity correlate with motor impairment in the chronic stage of stroke.
PMCID: PMC3819700  PMID: 24223571
corticospinal tract; transcallosal motor tract; motor recovery; resting state fMRI; DTI

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