Track-based Spatial Statistics Research Articles

Disturbed white matter integrity on diffusion tensor imaging in young children with epilepsy

To evaluate whether abnormalities in white matter (WM) integrity are present in young children with epilepsy. Twelve children (3-6 years old) with epilepsy and six matched healthy controls were recruited for brain diffusion tensor imaging (DTI). Track-based spatial statistics (TBSS) was used to analyse and compare DTI indices of mean diffusivity (MD), fractional anisotropy (FA), axial and radial diffusivity (AD/RD) between patients and controls, and correlations between clinical variables and DTI parameters were analysed. Compared with controls, patients showed increased FA in the left superior corona radiata and increased AD in the bilateral superior corona radiata. In children with generalised epilepsy, FA was increased in the left external capsule, while AD was decreased in the body of the corpus callosum, the left external capsule and the left superior longitudinal fasciculus. In those with focal epilepsy, FA was increased in the genu and body of the corpus callosum, and RD was decreased in the genu of the corpus callosum and left external capsule. Compared with partial epilepsy, generalised epilepsy was associated with increased FA in the right anterior corona radiata and decreased RD in the right anterior corona radiata and the genu and body of the corpus callosum. No significant correlations were observed between clinical variables and DTI parameters. The results of this study indicate that the microstructure of the white matter is disturbed by epileptic discharges and a compensatory response occurs during early brain development.

Diffusion Tensor Imaging in Parenchymal Neuro-Behçet's Disease.

Parenchymal Neuro-Behçet's disease (p-NBD) usually presents with a characteristic lesion in the mesodiencephalic region. However, there is a lack of information regarding the axonal integrity of normal-appearing white matter in p-NBD. Diffusion tensor imaging (DTI) is based on the properties of diffusivity and anisotropy that indicate the integrity of axons. The primary objective of the study was to compare p-NBD patients to healthy controls using diffusion tensor magnetic resonance imaging (DTI-MRI). The study enrolled parenchymal p-NBD patients who maintained stable disease status for 12 months. Healthy controls were chosen from a population with a similar age and gender distribution. Axial DTI was acquired using single-shot echo-planar imaging. Group analyses were carried out using the track-based spatial statistics tool of FMRIB software library (FSL). Correlations between DTI parameters and clinical outcomes were analyzed in the patient group. We recruited 12 patients with p-NBD and 12 healthy individuals. We found significant fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) differences in the superior longitudinal fasciculus, superior corona radiata, anterior corona radiata, body and genu of the corpus callosum, external capsule, and anterior limb of the internal capsule, mainly in the frontal white matter. Patients with p-NBD exhibit significant DTI alterations in the otherwise normal-appearing frontal association tracts. This study may contribute to a better understanding of the neuropsychological impairment pattern in patients with p-NBD, which is often associated with frontal cognitive networks.

White matter microstructure and cognitive functioning across healthy older adults with different APOE alleles

AbstractBackgroundAPOE alleles play an important neurobiological role in the development of Alzheimer’s Disease (AD), including modifying structure of white matter in the brain and cognitive decline (Gold et al., 2012; Reas et al., 2019). However, certain alleles (i.e., APOE‐e4) have be studied more than others (i.e., APOE‐e2 & e3), and have been primarily studied in individuals already diagnosed with AD, rather than in healthy older adults. While APOE‐e4 is well establish risk factor for AD, APOE‐e2 may play a role in protective mechanisms against AD, and APOE‐e3 may be neutral, yet their underlying neural mechanisms and association with cognitive functioning in the healthy aging brain are equivocal (Suri et al., 2013). Thus, the current study aimed to investigate the influence of different APOE alleles on white matter microstructure and cognition in healthy older adults.MethodWhite matter microstructure, memory, and executive functioning (EF) were compared between cognitively normal older adults with either APOE‐e2+ (n= 16, mean age= 76), APOE e3e3 (n= 64, mean age= 74), or APOE‐e4+ (n=35, mean age=73). White matter microstructure was compared using Diffusion Tensor Imaging (DTI) Track‐based spatial statistics (TBSS) methods to derive fractional anisotropy (FA). Whole‐brain mean FA was compared first between e3e3 and e2+ and then between e3e3 and e4+ groups. Memory and executive functioning composite scores were compared, including covariates of age, sex, and education levels, using multivariate analysis of covariance (MANCOVA). All data were retrieved from the Alzheimer’s Disease Neuroimaging Initiative (ADNI).ResultNo significant differences in white matter microstructure (FA; p> 0.05, corrected) were observed. Further, groups were not significantly different in memory, EF, age, sex, or education levels (p=0.59).ConclusionThese results indicate that white matter microstructure, memory, and EF changes are not evident in the healthy brain as a function of APOE allele presence. DTI may not be sensitive to APOE‐related changes in the healthy brain; nonetheless, future investigations should evaluate whether other structural (e.g., grey matter volume) and functional (e.g., fMRI) differences are evident across different APOE alleles in this population, as well as examine other cognitive domains.

Association between frontal cortico-limbic white-matter microstructure and risk for pediatric depression

This study aimed to identify white-matter microstructural characteristics associated with risk for pediatric major depressive disorder (MDD) measured by the Child Behavior Checklist (CBCL) Anxiety/Depression scores. Children (N = 32) of both sexes, aged 6–12, underwent T1-weighted whole-head anatomical and diffusion-weighted imaging. Each participant's mean diffusion measure image was generated and thinned to create an alignment-invariant tract representation. Voxel-wise analysis on the resulting map was carried out in Track Based Spatial Statistics (TBSS) using general linear models by regressing the CBCL-Anxiety/Depression score against measures of diffusion tensor imaging (DTI). We also compared these results with prior DTI findings from the same children associated with CBCL-Emotion Dysregulation profile, an indicator for bipolar disorder. TBSS voxel-wise analysis showed a significant negative correlation between fractional anisotropy (FA) and CBCL-Anxiety/Depression scores localized in the right anterior cingulum and connected corpus callosal region. The negative FA correlations in these regions were greater in CBCL-Anxiety/ Depression scores compared to CBCL-Emotional Dysregulation scores. Reduced white-matter connectivity in the anterior cingulum and connected corpus callosal region may represent a biomarker of risk for pediatric MDD. These results may help identify brain differences associated with the development of MDD, and assist with earlier clinical identification of pediatric MDD.

Progressive brain microstructural damage in patients with multiple sclerosis but not in patients with neuromyelitis optica spectrum disorder: A cross-sectional and follow-up tract-based spatial statistics study

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) may sometimes be misdiagnosed as multiple sclerosis (MS) because both disorders have similar clinical presentations and commonly show white matter damage in the brain. Diffusion tensor imaging (DTI) is an advanced MRI technique to assess the microstructural organization of white matter and provides greater pathological specificity than conventional MRI. In the present combined cross-sectional and longitudinal study, the novel DTI technique of Track-Based Spatial Statistics (TBSS) was used to investigate the difference of DTI parameter abnormalities between NMOSD and MS. MethodsA total of 42 patients with NMOSD, 51 patients with MS and 56 health controls (HC) were recruited and of these 14 patients with NMOSD and 13 patients with MS were also studied at follow-up after an average interval of approximately one year. Measurements of fractional anisotropy (FA), mean diffusion (MD), axial diffusivity (AD) and radial diffusivity (RD) were compared at baseline and follow-up in patients with NMOSD and MS. ResultsSignificant reduction in FA, increase in MD, AD and RD were observed in patients with MS (p < 0.05) and reduced FA was shown in NMOSD (p < 0.05) compared to HC, with all the effects, together with lesion load on T1WI and T2WI, being greater in patients with MS than in patients with NMOSD (p < 0.05). There was no significant difference in the time interval to follow-up in patients with MS (1.37 years) and NMOSD (1.25 years) (p > 0.05), during which there were significant changes in EDSS score between baseline and follow-up in NMOSD and MS patients (p < 0.05). There was a significantly reduced FA, and increased MD and RD in patients with MS (p < 0.05), but no significant changes in patients with NMOSD (p > 0.05). ConclusionsBoth MS and NMOSD have microstructure damage in white matter, while the progressive change in brain microstructural properties is observed in patients with MS but may not in patients with NMOSD in a short-term follow-up.

Diffusion Tensor Imaging Detects Acute Pathology-Specific Changes in the P301L Tauopathy Mouse Model Following Traumatic Brain Injury

Traumatic brain injury (TBI) has been linked with tauopathy. However, imaging methods that can non-invasively detect tau-protein abnormalities following TBI need further investigation. This study aimed to investigate the potential of diffusion tensor imaging (DTI) to detect tauopathy following TBI in P301L mutant-tau-transgenic-pR5-mice. A total of 24 9-month-old pR5 mice were randomly assigned to sham and TBI groups. Controlled cortical injuries/craniotomies were performed for TBI/sham groups followed by DTI data acquisition on days 1 and 7 post-injury. DTI data were analyzed by using voxelwise analysis and track-based spatial statistics for gray matter and white matter. Further, immunohistochemistry was performed for total-tau and phosphorylated-tau, astrocytes, and microglia. To detect the association of DTI with these pathological markers, a correlation analysis was performed between DTI and histology findings. At day 1 post-TBI, DTI revealed a widespread reduction in fractional anisotropy (FA) and axial diffusivity (AxD) in the TBI group compared to shams. On day 7, further reduction in FA, AxD, and mean diffusivity and increased radial diffusivity were observed. FA was significantly increased in the amygdala and cortex. Correlation results showed that in the ipsilateral hemisphere FA reduction was associated with increased phosphorylated-tau and glial-immunoreactivity, whereas in the contralateral regions, the FA increase was associated with increased immunostaining for astrocytes. This study is the first to exploit DTI to investigate the effect of TBI in tau-transgenic mice. We show that alterations in the DTI signal were associated with glial activity following TBI and would most likely reflect changes that co-occur with/without phosphorylated-tau. In addition, FA may be a promising measure to identify discrete pathological processes such as increased astroglia activation, tau-hyperphosphorylation or both in the brain following TBI.

Loss of white matter connections after severe traumatic brain injury (TBI) and its relationship to social cognition

Adults with severe traumatic brain injury (TBI) often suffer poor social cognition. Social cognition is complex, requiring verbal, non-verbal, auditory, visual and affective input and integration. While damage to focal temporal and frontal areas has been implicated in disorders of social cognition after TBI, the role of white matter pathology has not been examined. In this study 17 adults with chronic, severe TBI and 17 control participants underwent structural MRI scans and Diffusion Tensor Imaging. The Awareness of Social Inference Test (TASIT) was used to assess their ability to understand emotional states, thoughts, intentions and conversational meaning in everyday exchanges. Track-based spatial statistics were used to perform voxelwise analysis of Fractional Anisotropy (FA) and Mean Diffusivity (MD) of white matter tracts associated with poor social cognitive performance. FA suggested a wide range of tracts were implicated in poor TASIT performance including tracts known to mediate, auditory localisation (planum temporale) communication between nonverbal and verbal processes in general (corpus callosum) and in memory in particular (fornix) as well as tracts and structures associated with semantics and verbal recall (left temporal lobe and hippocampus), multimodal processing and integration (thalamus, external capsule, cerebellum) and with social cognition (orbitofrontal cortex, frontopolar cortex, right temporal lobe). Even when controlling for non-social cognition, the corpus callosum, fornix, bilateral thalamus, right external capsule and right temporal lobe remained significant contributors to social cognitive performance. This study highlights the importance of loss of white matter connectivity in producing complex social information processing deficits after TBI.

Changes to white matter microstructure in transient ischemic attack: A longitudinal diffusion tensor imaging study

Transient ischemic attack (TIA) is associated with localized ischemic changes, identifiable by diffusion-weighted imaging. Past research has not considered whether TIA is also associated with diffuse changes to white matter microstructure; further past work has not tracked changes longitudinally. Here we examine whole-brain changes in fractional anisotropy (FA) in individuals with TIA presenting with sensorimotor symptoms. Twenty individuals with a recent (within 30 days) TIA and 12 healthy older adults were recruited. Participants underwent 3.0T diffusion MRI at baseline; scans were repeated for the TIA group 90 days post-TIA. Track-based spatial statistics (TBSS) was used to conduct a voxel-wise analysis of FA between groups. FA was significantly lower in the TIA group relative to healthy controls, primarily in anterior white matter tracts including: forceps minor, anterior thalamic radiations, cingulum, inferior fronto-occipital fasciculus, and corticospinal tract. TBSS results informed an ROI-based longitudinal examination of FA in the TIA group. There were no changes to TBSS-identified clusters, forceps minor, or the corticospinal tract over time. There was lower FA in the anterior thalamic radiations in the TIA-affected hemisphere at baseline, but no difference between hemispheres at 90days. In summary, individuals with TIA presenting with sensorimotor symptoms have decreased FA in tracts that are also implicated in sensorimotor function, which outlast the clinical symptoms associated with TIA. This suggests a more profound type of brain damage associated with TIA than has been typically described in past work. Diffusion tensor imaging may have utility as a marker of TIA-associated changes to white matter pathways. Hum Brain Mapp 38:5795-5803, 2017. © 2017 Wiley Periodicals, Inc.

Short-Term Internet-Search Training Is Associated with Increased Fractional Anisotropy in the Superior Longitudinal Fasciculus in the Parietal Lobe.

The Internet search engine has become an indispensable tool for many people, yet the ways in which Internet searching may alter brain structure and function is poorly understood. In this study, we investigated the influence of short-term Internet-search “training” on white matter microstructure using diffusion tensor imaging (DTI). Fifty-nine valid subjects (Experimental group, 43; Control group, 16) completed the whole procedure: pre- DTI scan, 6-day's training and post- DTI scan. Using track-based spatial statistics, we found increased fractional anisotropy in the right superior longitudinal fasciculus at post-test as compared to pre-test in experimental group. Within the identified region of the right superior longitudinal fasciculus, decreased radial diffusivity (RD), and unchanged axial diffusivity (AD) were observed. These results suggest that short-term Internet-search training may increase white-matter integrity in the right superior longitudinal fasciculus. A possible mechanism for the observed FA change may involve increased myelination after training, although this possibility warrants additional investigation.

White matter microstructural abnormalities and their association with anticipatory anhedonia in depression

Anhedonia is associated with dysfunction of the neural circuitry of reward in patients with major depressive disorder (MDD). However, its neurobiological basis is not fully understood. The present study examined the association between anhedonia and white matter (WM) characteristics in patients with first-episode MDD. We recruited 30 patients with first-episode drug-naive MDD and 28 healthy controls (HC) to undergo diffusion weighted imaging. We examined specifically the correlation between WM characteristics and anhedonia measured with the Temporal Experience of Pleasure Scale (TEPS) in MDD patients. Using Track-Based Spatial Statistics (TBSS), we found that MDD patients exhibited reduced fractional anisotropy (FA) in the left cingulum and the forceps minor. These patients also exhibited increased radial diffusivity (RD) in several major tracts including the bilateral anterior thalamic radiation, the corticospinal tract, the superior longitudinal fasciculus and the uncinate fasciculus in the left hemisphere. Correlational analysis showed that increased RD was significantly correlated with anticipatory anhedonia in the MDD group, while reduced mean FA was correlated with consummatory anhedonia in HC. These preliminary findings suggest that left-sided WM tracts abnormalities may contribute to the development of anhedonia in MDD patients.

Increased Water Diffusion in the Parcellated Cortical Regions from the Patients with Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

Background: The loss of cortical neuron environment integrity is the hallmark of neurodegeneration diseases such as Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). To reveal the microenvironment changes in cerebral cortex, the current study aimed to examine the changes of mean diffusivity (MD) in parcellated brain among AD, aMCI patients and normal controls (NC).Methods: Diffusion tensor imaging data with the whole brain coverage were acquired from 28 AD (aged 69.4 ± 8.2 year old), 41 aMCI patients (aged 68.2 ± 6.4 year old) and 40 NC subjects (aged 65.7 ± 6.4 year old). Subsequently, the MD values were parcellated according to the standard automatic anatomic labeling (AAL) template. Only the 90 regions located in the cerebral cortex were used in the final analysis. The mean values of MD from each brain region were extracted and compared among the participant groups. The integrity of the white matter tracts and gray matter atrophy was analyzed using the track-based spatial statistics and voxel-based morphometry approaches, respectively.Results: Significant differences of MD were noticed both in aMCI and AD patients, in terms of the affected regions and the amount of increase. The hippocampus, parahippocampal gyrus and cingulum were the most significantly affected regions in AD patients. From all the 90 cerebral cortex regions, significant increase of MD in the AD patients was found in 40 regions, compared to only one (fusiform gyrus on the right) in aMCI patients. In the disease affected regions, the MD from aMCI patients is in state between NC and AD patients.Conclusions: Increased MD in the specific regions of the brain shows the feasibility of MD as an indicator of the early stage cortical degeneration in aMCI and AD patients.

“Early to bed, early to rise”: Diffusion tensor imaging identifies chronotype-specificity

Sleep and wakefulness are crucial prerequisites for cognitive efficiency, the disturbances of which severely impact performance and mood as present e.g. after time zone traveling, in shift workers or patients with sleep or affective disorders. Based on their individual disposition to sleep and wakefulness, humans can be categorized as early (EC), late (LC) or intermediate (IC) chronotypes. While ECs tend to wake up early in the morning and find it difficult to remain awake beyond their usual bedtime, LCs go to bed late and have difficulties getting up. Beyond sleep/wake timings, chronotypes show distinct patterns of cognitive performance, gene expression, endocrinology and lifestyle. However, little is known about brain structural characteristics potentially underlying differences. Specifically, white matter (WM) integrity is crucial for intact brain function and has been related to various lifestyle habits, suggesting differences between chronotypes. Hence, the present study draws on Diffusion Tensor Imaging as a powerful tool to non-invasively probe WM architecture in 16 ECs, 23 LCs and 20 ICs. Track-based spatial statistics highlight that LCs were characterized by WM differences in the frontal and temporal lobes, cingulate gyrus and corpus callosum. Results are discussed in terms of findings reporting late chronotypes to exhibit a chronic form of jet lag accompanied with sleep disturbances, vulnerability to depression and higher consumption of nicotine and alcohol. This study has far-reaching implications for health and the economy. Ideally, work schedules should fit in with chronotype-specificity whenever possible.

Fatigue-related brain white matter changes in granulomatosis with polyangiitis

To determine the association between brain white matter (WM) damage and persistent fatigue among patients with granulomatosis with polyangiitis (GPA). A case-control MRI study was conducted. Both cases, defined as GPA patients with chronic fatigue, and controls, defined as GPA patients without fatigue, underwent MRI brain scanning. Standard T1, T2 and FLAIR images were acquired and Scheltens white matter hyperintensity scores (SWMHS) reported in order to quantify macroscopic damage. In addition, diffusion tensor imaging (DTI) data were analysed using track-based spatial statistics to measure structural integrity and thus microscopic damage. No statistically significant differences in macroscopic damage were observed between cases (n = 14) and controls (n = 14) (median SWMHS 6, interquartile range 3-7 vs median SWMHS 3.5, interquartile range 3-8; P = 0.52). Compared with controls, there were no regions of WM where cases recorded reduced structural integrity; however, significantly greater structural integrity was registered in the regions of the fornix and cingulum nerve bundles of cases (P < 0.05, corrected for multiple comparisons). This study found no evidence to suggest that GPA-related fatigue is associated with either macroscopic or microscopic damage of the WM. On the contrary, regions of significantly greater structural integrity were observed among fatigued cases, which may reflect sustained activation secondary to chronic fatigue exposure.

Diffusion Tensor Imaging in Episodic Cluster Headache

Cluster headache (CH) is a rare headache disorder with severe unilateral headache bouts and autonomic symptoms. The pathophysiology of CH is not completely understood. Using a voxel-based morphometric paradigm or functional imaging, a key role of the hypothalamus and the pain matrix could be demonstrated during CH episodes. However, there are no diffusion tensor imaging (DTI) data investigating the white matter microstructure of the brain in patients with CH. Therefore, we used DTI to delineate microstructural changes in patients with CH in a headache-free state. Seven male patients with episodic CH and 7 healthy subjects were included and examined with a routine 1.5 T magnetic resonance imaging scanner. Whole-head DTI scans measuring fractional anisotropy were analyzed without a priori hypotheses using track-based spatial statistics. We found significant microstructural brain tissue changes bilaterally in the white matter of the brainstem, the frontal lobe, the temporal lobe, the occipital lobe, the internal capsule, and on the right side of thalamus and cerebellum. There were further lesions in the basal frontal lobe that were part of the olfactory system. Alterations of fractional anisotropy in the brainstem might indicate changes of the medial lemniscus and central sympathetic pathways. Patients with episodic CH have microstructural brain changes in regions that belong to the pain matrix. Furthermore, we were able to detect structural changes suggesting an involvement of the olfactory system as well as lesions in the brainstem indicating an involvement of trigeminal and sympathetic systems.

Diffusion Tensor Imaging in Idiopathic REM Sleep Behavior Disorder Reveals Microstructural Changes in the Brainstem, Substantia Nigra, Olfactory Region, and Other Brain Regions

Idiopathic rapid eye movement sleep behavior disorder (iRBD)--a parasomnia characterized by dream enactments--is a risk marker for the development of Parkinson disease (PD) and other alpha-synucleinopathies. The pathophysiology of iRBD is likely due to dysfunction of brainstem nuclei that regulate REM sleep. Diffusion tensor imaging (DTI) is a method for studying microstructural brain tissue integrity in vivo. We investigated whether DTI detects microstructural abnormalities in the brain of patients with iRBD--compared with age-matched control subjects--as an in vivo potential indicator for changes related to "preclinical (premotor)" neuropathology in PD. N/A. Patients with iRBD (n = 12) and age-matched healthy control subjects (n = 12) were studied. At a 1.5T MRI maschine, whole-head DTI scans of fractional anisotropy, axial diffusivity (a potential marker of neuronal loss), and radial diffusivity (a potential marker of glial pathology) were analyzed using track-based spatial statistics, and 2 types of group analysis tools (FreeSurfer and FSL). We found significant microstructural changes in the white matter of the brainstem (P < 0.0001), the right substantia nigra, the olfactory region, the left temporal lobe, the fornix, the internal capsule, the corona radiata, and the right visual stream of the patients with iRBD. Changes were identified in regions known to be involved in REM-sleep regulation and/or to exhibit neurodegenerative pathology in iRBD and/or early PD. The study findings suggest that iRBD-related microstructural abnormalities can be detected in vivo with DTI, a widely available MRI technique.

Processing speed is correlated with cerebral health markers in the frontal lobes as quantified by neuroimaging

We explored relationships between decline in cognitive processing speed (CPS) and change in frontal lobe MRI/MRS-based indices of cerebral integrity in 38 healthy adults (age 57–90 years). CPS was assessed using a battery of four timed neuropsychological tests: Grooved Pegboard, Coding, Symbol Digit Modalities Test and Category Fluency (Fruits and Furniture). The neuropsychological tests were factor analyzed to extract two components of CPS: psychomotor (PM) and psychophysical (PP). MRI-based indices of cerebral integrity included three cortical measurements per hemisphere (GM thickness, intergyral and sulcal spans) and two subcortical indices (fractional anisotropy (FA), measured using track-based spatial statistics (TBSS), and the volume of hyperintense WM (HWM)). MRS indices included levels of choline-containing compounds (GPC+PC), phosphocreatine plus creatine (PCr+Cr), and N-acetylaspartate (NAA), measured bilaterally in the frontal WM bundles. A substantial fraction of the variance in the PM-CPS (58%) was attributed to atrophic changes in frontal WM, observed as increases in sulcal span, declines in FA values and reductions in concentrations of NAA and choline-containing compounds. A smaller proportion (20%) of variance in the PP-CPS could be explained by bilateral increases in frontal sulcal span and increases in HWM volumes.

Can structural MRI indices of cerebral integrity track cognitive trends in executive control function during normal maturation and adulthood?

We explored the relationship between structural neuroimaging-based indices of cerebral integrity and executive control function (ECF) in two groups of healthy subjects: A maturing group (33 subjects; 19-29 years) and a senescing group (38 adults; 30-90 years). ECF was assessed using the Executive Interview (EXIT) battery. Cortical indices of cerebral integrity included GM thickness, intergyral span, and sulcal span, each measured for five cortical regions per hemisphere. Subcortical indices included fractional anisotropy (FA), measured using track-based-spatial-statistics (TBSS), and the volume of T2-hyperintense WM (HWM). In the maturing group, no significant relationships between neuroanatomical changes and ECF were found; however, there were hints that late-term maturation of cerebral WM influenced variability in ECF. In the senescing group, the decline in ECF corresponded to atrophic changes in cerebral WM (sulcal and intergyral span) primarily in the superior frontal and anterior cingulate regions. A large fraction of the variability in ECF (62%) can be explained by variability in the structural indices from these two regions.