Microstructural white matter abnormality and frontal cognitive dysfunctions in juvenile myoclonic epilepsy

Purpose: Previous neuroimaging studies provide growing evidence that patients with juvenile myoclonic epilepsy (JME) have both structural and functional abnormalities of the thalamus and frontal lobe gray matter. However, limited data are available regarding the issue of white matter (WM) involvement, making the microstructural WM changes in JME largely unknown. In the present study we investigated changes of WM integrity in patients with JME, and their relationships with cognitive functions and epilepsy-specific clinical factors. Methods: We performed diffusion tensor imaging (DTI) and neuropsychological assessment in 25 patients with JME and 30 control subjects matched for age, gender, and education level. Between-group comparisons of fractional anisotropy (FA) and mean diffusivity (MD) were carried out in a whole-brain voxel-wise manner by using tract-based spatial statistics (TBSS). In addition, both FA and MD were correlated with cognitive performance and epilepsy-specific clinical variables to investigate the influence of these clinical and cognitive factors on WM integrity changes. Key Findings: Neuropsychological evaluation revealed that patients with JME had poorer performance than control subjects on most of the frontal function tests. TBSS demonstrated that, compared to controls, patients with JME had significantly reduced FA and increased MD in bilateral anterior and superior corona radiata, genu and body of corpus callosum, and multiple frontal WM tracts. Disease severity, as assessed by the number of generalized tonic-clonic seizures in given years, was negatively correlated with FA and positively correlated with MD extracted from regions of significant differences between patients and controls in TBSS. Significance: Our findings of widespread disturbance of microstructural WM integrity in the frontal lobe and corpus callosum that interconnects frontal cortices could further support the pathophysiologic hypothesis of thalamofrontal network abnormality in JME. These WM abnormalities may implicate frontal cognitive dysfunctions and disease progression in JME.     

Atlas-based white matter analysis in individuals with velo-cardio-facial syndrome (22q11.2 deletion syndrome) and unaffected siblings

ABSTRACT: BACKGROUND: Velo-cardio-facial syndrome (VCFS, MIM#192430) is a genetic disorder caused by a deletion of about 40 genes at the q11.2 band of one copy of chromosome 22. Individuals with VCFS present with deficits in cognition and social functioning, high risk of psychiatric disorders, volumetric reductions in gray and white matter (WM) and some alterations of the WM microstructure. The goal of the current study was to characterize the WM microstructural differences in adolescents with VCFS and unaffected siblings, and the correlation of WM microstructure with neuropsychological performance. We hypothesized that individuals with VCFS would have decreased photometric indices of WM microstructure (FA, AD and RD), particularly in WM tracts to the frontal lobe, and that these measures that would be correlated with cognitive functioning. METHODS: For the current study, thirty-three individuals with VCFS (21 female) and 16 unaffected siblings (8 female) participated in DTI scanning and neuropsychological testing. We performed an atlas-based analysis, extracted FA, AD, and RD measures for 54 WM tracts (27 in each hemisphere) for each subject, and used MANOVAs to compare individuals with VCFS to siblings. For WM tracts that were statistically significantly different between VCFS and siblings (pFDR<0.05), we assessed the correlations of FA, AD, and RD with neuropsychological measures. RESULTS: In VCFS individuals as compared to unaffected siblings, we found decreased FA in the uncinate fasciculus, decreased RD in the right posterior corona radiata, and decreased AD in multiple WM tracts (bilateral superior and posterior corona radiata, dorsal cingulum, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, superior cerebellar peduncle, posterior thalamic radiation, and left anterior corona radiata, retrolenticular part of internal capsule, external capsule, sagittal stratum). We also found significant correlations of AD and RD with measures of executive function, IQ, working memory, and/or social cognition. CONCLUSIONS: Our results suggest that adolescents with VCFS display abnormal WM connectivity from/to frontal lobe, as well as temporal, parietal, occipital areas and the cerebellum. Future studies could focus on the developmental trajectory of WM in VCFS, the association of WM alterations with psychiatric disorders, and the effects of candidate genes within the 22q11.2 region on WM anomalies.     

White matter abnormalities in children with and at risk for bipolar disorder

OBJECTIVES: Diffusion tensor magnetic resonance imaging (DT-MRI) assesses the integrity of white matter (WM) tracts in the brain. Children with bipolar disorder (BPD) may have WM abnormalities that precede illness onset. To more fully examine this possibility, we scanned children with DSM-IV BPD and compared them to healthy peers and children at risk for BPD (AR-BPD), defined as having a first-degree relative with the disorder. METHODS: Ten children with BPD, eight healthy controls (HC), and seven AR-BPD, similar in age, had MRI scans on a 1.5 Tesla GE scanner, including a standard DT-MRI sequence (T2-EPI) with 25 axial slices. Fractional anisotropy (FA) values were compared between groups to determine regions of significant difference (p < 0.05). RESULTS: Compared to HC, children with BPD had decreased FA in right and left superior frontal tracts, including the superior longitudinal fasciculus I (SLF I) and the cingulate-paracingulate WM (CG-PAC(WM)). In addition, the BPD group had reduced FA in left orbital frontal WM and the right corpus callosum body. Compared to AR-BPD, children with BPD showed reduced FA in the right and left CG-PAC(WM). Both the BPD and AR-BPD groups showed reduced FA relative to HC in bilateral SLF I. CONCLUSIONS: The bilateral SLF I finding in both the BPD and AR-BPD groups may represent a trait-based marker or endophenotype of the disorder. The finding of decreased FA in the right and left CG-PAC(WM) in children with BPD compared to the other two groups may represent a disease-state related finding.     

White matter integrity alterations in post‐traumatic stress disorder

Post‐traumatic stress disorder (PTSD) is a debilitating condition which can develop after exposure to traumatic stressors. Seventy‐five adults were recruited from the community, 25 diagnosed with PTSD along with 25 healthy and 25 trauma‐exposed age‐ and gender‐matched controls. Participants underwent clinical assessment and magnetic resonance imaging. A previous voxel based morphometry (VBM) study using the same subject cohort identified decreased grey matter (GM) volumes within frontal/subcortical brain regions including the hippocampus, amygdala, and anterior cingulate cortex (ACC). This study examines the microstructural integrity of white matter (WM) tracts connecting the aforementioned regions/structures. Using diffusion tensor imaging, we investigated the integrity of frontal/subcortical WM tracts between all three subject groups. Trauma exposed subjects with and without PTSD diagnosis were identified to have significant disruption in WM integrity as indexed by decreased fractional anisotropy (FA) in the uncinate fasciculus (UF), cingulum cingulate gyrus (CCG), and corpus callosum (CC), when compared with healthy non‐trauma‐exposed controls. Significant negative correlations were found between total Clinician Administered PTSD scale (CAPS) lifetime clinical subscores and FA values of PTSD subjects in the right UF, CCG, CC body, and right superior longitudinal fasciculus (SLF). An analysis between UF and SLF FA values and VBM determined rostral ACC GM values found a negative correlation in PTSD subjects. Findings suggest that compromised WM integrity in important tracts connecting limbic structures such as the amygdala to frontal regions including the ACC (i.e., the UF and CCG) may contribute to impairments in threat/fear processing associated with PTSD.     

The anatomy of the callosal and visual-association pathways in high-functioning autism: A DTI tractography study

There is increasing recognition that many of the core behavioral impairments that characterize autism potentially emerge from poor neural synchronization across nodes comprising dispersed cortical networks. A likely candidate for the source of this atypical functional connectivity in autism is an alteration in the structural integrity of intra- and inter-hemispheric white matter (WM) tracts that form large-scale cortical networks. To test this hypothesis, in a group of adults with high-functioning autism (HFA) and matched control participants, we used diffusion tensor tractography to compare the structural integrity of three intra-hemispheric visual-association WM tracts, the inferior longitudinal fasciculus (ILF), the inferior fronto-occipito fasciculus (IFOF) and the uncinate fasciculus (UF), with the integrity of three sub-portions of the major inter-hemispheric fiber tract, the corpus callosum. Compared with the control group, the HFA group evinced an increase in the volume of the intra-hemispheric fibers, particularly in the left hemisphere, and a reduction in the volume of the forceps minor (F-Mi) and body of the corpus callosum. The reduction in the volume of the F-Mi also correlated with an increase in repetitive and stereotypical behavior as measured by the Autism Diagnostic Interview. These findings suggest that the abnormalities in the integrity of key inter- and intra-hemispheric WM tracts may underlie the atypical information processing observed in these individuals.     

Executive dysfunction in frontotemporal dementia is related to abnormalities in frontal white matter tracts

Cognitive deficits in behavioral-variant frontotemporal dementia (bvFTD) and AD are linked to frontal and temporal lobe gray matter (GM) pathology. The aim of this study was to assess the relative contribution of white (WM) and GM abnormalities to cognitive dysfunction in bvFTD and AD. Fractional anisotropy (FA) for the corpus callosum, cingulum (Cg), and uncinate fasciculus (Unc) was determined in 17 bvFTD and 10 AD patients who underwent neuropsychological testing. Regressions were performed to assess the relative contribution of WM and GM abnormalities to cognitive deficits. Multiple regression analysis revealed that in bvFTD, the left anterior Cg FA was related to executive function, the right anterior Cg FA to visual-spatial attention and working memory, the right posterior Cg to visual-constructional abilities and the left Unc FA to Modified Trails Errors. After adding corresponding GM volumes, the left anterior Cg FA, the right anterior cingulate FA, the right posterior cingulate FA and the left uncinate FA remained significant predictors of the cognitive tasks. In the AD group, the left posterior Cg FA and right descending Cg FA were related to visual recall performance but did not remain significant predictors when GM volumes were added to the regression. These results suggest that reduced integrity of specific WM tracts contribute to cognitive deficits observed in bvFTD after accounting for GM atrophy. In AD, memory impairment was related to WM tract injury but this relationship was no longer observed when GM volumes were included.     

Genetic contributions to changes of fiber tracts of ventral visual stream in 22q11.2 deletion syndrome

Patients with 22q11.2 deletion syndrome (22q11.2DS) represent a population at high risk for developing schizophrenia, as well as learning disabilities. Deficits in visuo-spatial memory are thought to underlie some of the cognitive disabilities. Neuronal substrates of visuo-spatial memory include the inferior fronto-occipital fasciculus (IFOF) and the inferior longitudinal fasciculus (ILF), two tracts that comprise the ventral visual stream. Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) is an established method to evaluate white matter (WM) connections in vivo. DT-MRI scans of nine 22q11.2DS young adults and nine matched healthy subjects were acquired. Tractography of the IFOF and the ILF was performed. DT-MRI indices, including Fractional anisotropy (FA, measure of WM changes), axial diffusivity (AD, measure of axonal changes) and radial diffusivity (RD, measure of myelin changes) of each of the tracts and each group were measured and compared. The 22q11.2DS group showed statistically significant reductions of FA in IFOF in the left hemisphere. Additionally, reductions of AD were found in the IFOF and the ILF in both hemispheres. These findings might be the consequence of axonal changes, which is possibly due to fewer, thinner, or less organized fibers. No changes in RD were detected in any of the tracts delineated, which is in contrast to findings in schizophrenia patients where increases in RD are believed to be indicative of demyelination. We conclude that reduced axonal changes may be key to understanding the underlying pathology of WM leading to the visuo-spatial phenotype in 22q11.2DS.     

Assessment of whole brain white matter integrity in youths and young adults with a family history of substance‐use disorders

Individuals with a family history of substance use disorders (FH+) are at a greater risk of developing substance use disorders than their peers with no such family histories (FH?) and this vulnerability is proportional to the number of affected relatives (FH density). The risk for developing substance use disorders peaks during adolescence to early adulthood in the general population, and that is thought to be related to delayed maturation of frontocortical and frontostriatal functional circuits. We hypothesized that FH+ youth and young adults have impaired myelination of frontocortical and frontostriatal white matter tracts. We examined fractional anisotropy (FA) data in 80 FH+ and 34 FH? youths (12.9 ± 1.0 years) and in 25 FH+ and 30 FH? young adults (24.3 ± 3.4 years). FH+ youths had lower FA values in both frontocortical and frontostriatal tracts as well as parietocortical tracts including the anterior, superior and posterior corona radiata and the superior frontal‐occipital fasciculus. Moreover, FA values in these tracts were negatively correlated with FH density. FH+ adults had lower FA values in two frontocortical tracts: the genu of the corpus callosum and anterior corona radiata and also significant negative correlations between FA and FH density in these same tracts. In both groups, lower FA values corresponded to higher radial diffusivity suggesting reduced axonal myelination. We interpreted our findings as evidence for impaired myelination of frontal white matter that was proportional to FH density. Our data suggest that deficits may partially resolve with age, paralleling an age‐related decline in risk for developing substance use disorders. Hum Brain Mapp 35:5401–5413, 2014. © 2014 Wiley Periodicals, Inc .     

无先兆偏头痛患者大脑结构和功能异常的MRI研究

目的研究无先兆偏头痛患者大脑结构和功能异常的MRI表现。方法选取30例无先兆偏头痛患者作为观察组,同期25例健康志愿者作为对照组。Signa Excite 3.0 T磁共振扫描仪,采用平面回波成像序列采集对象静息态功能MRI图像,采用单次激发回波平面成像序列采集脑白质DTI图像。采用肯德尔系数评估静息态局部一致性,采用基于纤维束追踪空间统计分析技术(TBSS)分析脑白质纤维的分数各项异性(FA)、平行弥散系数(RD)、轴向弥散系数(AD)、以及平均弥散系数(MD)。结果与对照组比较,观察组患者多个脑区存在局部一致性降低,包括左侧前后扣带回、左侧颞下回、左侧梭状回、右侧中央前后回、右侧额中回、右侧舌回局部一致性减弱(FEW校正,P0.05)。观察组患者双侧大脑脚、双侧内囊后肢、右侧内囊前肢、右侧上纵束、右侧胼胝体体部和压部、右侧上放射冠和后放射冠、左侧扣带的FA值显著降低(FEW校正,P0.05);双侧上放射冠和后放射冠、双侧扣带、双侧丘脑后辐射、双侧上纵束、右侧大脑脚、右侧内囊前后肢以及右侧胼胝体体部和压部的RD值显著升高(FEW校正,P0.05);胼胝体体部和压部,右侧上放射冠和后放射冠,以及右侧上纵束的MD值显著升高(FEW校正,P0.05);两组各脑区的AD值无显著性差异(FEW校正,P0.05)。结论无先兆偏头痛患者大脑静息态局部一致性和脑白质纤维束存在改变,且明显区别于健康志愿者。     

The temporal stem in traumatic brain injury: preliminary findings

The temporal stem (TS) of the temporal lobe is a major white matter (WM) region containing several major pathways that connect the temporal lobe with the rest of the brain. Because of its location, it may be particularly vulnerable to shear-strain effects resulting from traumatic brain injury (TBI). A case vignette is presented in a patient with severe brain injury and focal TS pathology. Also, 12 severe TBI subjects unselected for TS pathology were compared to demographically matched, neurologically-intact controls using diffusion tensor imaging (DTI) to examine white matter tracts associated with the TS, including the inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), arcuate fasciculus (AF), cingulum bundle (CB) and the uncinate fasciculus (UF). For each tract, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed and compared between the two groups and also examined in relationship to memory performance in the TBI subjects. Significant FA and ADC differences were observed in all tracts in the TBI patients compared to controls, with several relationships with memory outcome noted in the IFOF, ILF and AF. Based on these preliminary findings, the potential role of TBI-induced WM disconnection involving the TS is discussed as well as the relationship of TS damage to neurobehavioral outcome. The need for future studies specifically examining the role of TS injury in TBI is emphasized.     

Disrupted white matter integrity of corticopontine-cerebellar circuitry in schizophrenia

Evidence for white matter abnormalities in patients with schizophrenia is increasing. Decreased fractional anisotropy (FA) in interhemispheric commissural fibers as well as long-ranging fronto-parietal association fibers belongs to the most frequent findings. The present study used tract-based spatial statistics to investigate white matter integrity in 35 patients with schizophrenia and 35 healthy volunteers. We found that patients exhibited significantly decreased FA relative to healthy subjects in the corpus callosum, the cerebral peduncle, the left inferior fronto-occipital fasciculus, the anterior thalamic radiation, the right posterior corona radiata, the middle cerebellar peduncle, and the right superior longitudinal fasciculus. Increased FA was detectable in the inferior sections of the corticopontine-cerebellar circuit. Present data indicate extended cortical-subcortical alterations of white matter integrity in schizophrenia using advanced data analysis strategies. They corroborate preceding findings of white matter structural deficits in mainly long-ranging association fibers and provide first evidence for neuroplastic changes in terms of an increased directionality in more inferior fiber tracts.     

Grey and white matter abnormalities in temporal lobe epilepsy with and without mesial temporal sclerosis

Temporal lobe epilepsy with (TLE-mts) and without (TLE-no) mesial temporal sclerosis display different patterns of cortical neuronal loss, suggesting that the distribution of white matter damage may also differ between the sub-groups. The purpose of this study was to examine patterns of white matter damage in TLE-mts and TLE-no and to determine if identified changes are related to neuronal loss at the presumed seizure focus. The 4 T diffusion tensor imaging (DTI) and T1-weighted data were acquired for 22 TLE-mts, 21 TLE-no and 31 healthy controls. Tract-based spatial statistics (TBSS) was used to compare fractional anisotropy (FA) maps and voxel-based morphometry (VBM) was used to identify grey matter (GM) volume atrophy. Correlation analysis was conducted between the FA maps and neuronal loss at the presumed seizure focus. In TLE-mts, reduced FA was identified in the genu, body and splenium of the corpus callosum, bilateral corona radiata, cingulum, external capsule, ipsilateral internal capsule and uncinate fasciculus. In TLE-no, FA decreases were identified in the genu, the body of the corpus callosum and ipsilateral anterior corona radiata. The FA positively correlated with ipsilateral hippocampal volume. Widespread extra-focal GM atrophy was associated with both sub-groups. Despite widespread and extensive GM atrophy displaying different anatomical patterns in both sub-groups, TLE-mts demonstrated more extensive FA abnormalities than TLE-no. The microstructural organization in the corpus callosum was related to hippocampal volume in both patients and healthy subjects demonstrating the association of these distal regions.     

White matter tracts associated with set-shifting in healthy aging

Attentional set-shifting ability, commonly assessed with the Trail Making Test (TMT), decreases with increasing age in adults. Since set-shifting performance relies on activity in widespread brain regions, deterioration of the white matter tracts that connect these regions may underlie the age-related decrease in performance. We used an automated fiber tracking method to investigate the relationship between white matter integrity in several cortical association tracts and TMT performance in a sample of 24 healthy adults, 21–80 years. Diffusion tensor images were used to compute average fractional anisotropy (FA) for five cortical association tracts, the corpus callosum (CC), and the corticospinal tract (CST), which served as a control. Results showed that advancing age was associated with declines in set-shifting performance and with decreased FA in the CC and in association tracts that connect frontal cortex to more posterior brain regions, including the inferior fronto-occipital fasciculus (IFOF), uncinate fasciculus (UF), and superior longitudinal fasciculus (SLF). Declines in average FA in these tracts, and in average FA of the right inferior longitudinal fasciculus (ILF), were associated with increased time to completion on the set-shifting subtask of the TMT but not with the simple sequencing subtask. FA values in these tracts were strong mediators of the effect of age on set-shifting performance. Automated tractography methods can enhance our understanding of the fiber systems involved in performance of specific cognitive tasks and of the functional consequences of age-related changes in those systems.     

Diffusion tensor imaging in early Alzheimer's disease

Our aim was to investigate the extent of white matter tissue damage in patients with early Alzheimer disease (AD) using diffusion tensor magnetic resonance imaging (DTI). Although AD pathology mainly affects cortical grey matter, previous magnetic resonance imaging (MRI) studies showed that changes also exist in the white matter (WM). However, the nature of AD-associated WM damage is still unclear. Conventional and DTI examinations (b=1000 s/mm(2), 25 directions) were obtained from 12 patients with early AD (Mini Mental State Examination [MMSE] score=27, Grober and Buschke test score=33.2, digit span score=5.6) and 12 sex- and age-matched volunteers. The right and left mean diffusivity (MD) and fractional anisotropy (FA) of several WM regions were pooled in each patient and control, and compared between the two groups. Volumes of the whole brain and degree of atrophy of the temporal lobe were compared between the two groups. In AD, MD was increased in the splenium of the corpus callosum and in the WM in the frontal and parietal lobes. FA was bilaterally decreased in the WM of the temporal lobe, the frontal lobe and the splenium compared with corresponding regions in controls. Values in other areas (occipital area, superior temporal area, cingulum, internal capsule, and genu of the corpus callosum) were not different between patients and controls. No correlations were found between the MMSE score and the anisotropy indices. Findings of DTI reveal abnormalities in the frontal and temporal WM in early AD patients. These changes are compatible with early temporal-to-frontal disconnections.     

A qualitative and quantitative review of diffusion tensor imaging studies in reading and dyslexia

In this review paper we address whether deficits in reading (i.e. developmental dyslexia) are rooted in neurobiological anomalies in white matter tracts. Diffusion tensor imaging (DTI) offers an index of the connections between brain regions (via tractography) and of the white matter properties of these connections (via fractional anisotropy, FA). The reported studies generally show that lower FA values in left temporoparietal and frontal areas are indicative of poorer reading ability or dyslexia. Second, most studies have indicated that these regions coincide with the left arcuate fasciculus and corona radiata, with fewer studies suggesting a role for the posterior part of the corpus callosum or for more ventral tracts such as the inferior longitudinal fasciculus or the inferior fronto-occipital fasciculus. Finally, a quantitative activation likelihood estimation (ALE) meta-analysis on all reported studies that used a voxel-based approach reveals a cluster located close to the left temporoparietal region (x=-29, y=-17, z=26). Fibertracking through this cluster demonstrates that this region hosts both the left arcuate fasciculus and the left corona radiata.     

Reduced white matter integrity and verbal fluency impairment in young adults with bipolar disorder: A diffusion tensor imaging study

BackgroundClinical evidence shows that bipolar disorder (BD) is characterized by white matter (WM) microstructural abnormalities. However, little is known about the biological mechanisms associated with these abnormalities and their relationship with cognitive functioning.Methods49 adult BD patients ((M ± SD): 29.27 ± 7.92 years; 17 males, 32 females; 34 BD-I, 10 BD-II, and 5 BD-NOS) and 28 age-matched normal subjects ((M ± SD): 29.19 ± 7.35 years; 10 males and 18 females) underwent diffusion tensor imaging (DTI) imaging. DTI metrics were computed using whole-brain tract-based spatial statistics (TBSS) as part of the FMRIB Software Library. Measures of WM coherence (fractional anisotropy - FA) and axonal structure (mean, axial and radial diffusivity – MD, AD and RD) were employed to characterize the microstructural alterations in the limbic, commissural, association and projection fiber tracts. All participants performed the Brief Assessment of Cognition for Affective disorders (BAC-A).ResultsBD patients performed poorly on verbal fluency tasks and exhibited large clusters of altered FA, RD and MD values within the retrolenticular part of the internal capsule, the superior and anterior corona radiata, and the corpus callosum. Increased FA values in the left IFOF and the forceps minor correlated positively with verbal fluency scores. Altered RD parameters in the corticospinal tract and the forceps minor were associated with reduced visuomotor abilities.ConclusionsThe reported verbal fluency deficits and FA, RD and MD alterations in WM structures are potential cognitive and neural markers of BD. Abnormal RD values may be associated with progressive demyelination.     

Evidence of frontotemporal structural hypoconnectivity in social anxiety disorder: A quantitative fiber tractography study

Investigation of the brain's white matter fiber tracts in social anxiety disorder (SAD) may provide insight into the underlying pathophysiology. Because models of pathological anxiety posit altered frontolimbic interactions, the uncinate fasciculus (UF) connecting (orbito‐) frontal and temporal areas including the amygdala is of particular interest. Microstructural alterations in parts of the UF have been reported previously, whereas examination of the UF as discrete fiber tract with regard to more large‐scale properties is still lacking. Diffusion tensor imaging was applied in 25 patients with generalized SAD and 25 healthy control subjects matched by age and gender. By means of fiber tractography, the UF was reconstructed for each participant. The inferior fronto‐occipital fasciculus (IFOF), originating from the frontal cortex similarly to the UF, was additionally included as control tract. Volume and fractional anisotropy (FA) were compared between the groups for both tracts. Volume of left and right UF was reduced in patients with SAD, reaching statistical significance for the left UF. Bilateral IFOF volume was not different between groups. A similar pattern was observed for FA. Reduced volume of the left UF in SAD fits well into pathophysiological models of anxiety, as it suggests deficient structural connectivity between higher‐level control areas in the orbitofrontal cortex and more basal limbic areas like the amygdala. The results point to a specific role of the left UF with regard to altered white matter volume in SAD. However, results should be replicated and functional correlates of altered UF volume be determined in future studies. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

DTI tractography and white matter fiber tract characteristics in euthymic bipolar I patients and healthy control subjects

With the introduction of diffusion tensor imaging (DTI), structural differences in white matter (WM) architecture between psychiatric populations and healthy controls can be systematically observed and measured. In particular, DTI-tractography can be used to assess WM characteristics over the entire extent of WM tracts and aggregated fiber bundles. Using 64-direction DTI scanning in 27 participants with bipolar disorder (BD) and 26 age-and-gender-matched healthy control subjects, we compared relative length, density, and fractional anisotrophy (FA) of WM tracts involved in emotion regulation or theorized to be important neural components in BD neuropathology. We interactively isolated 22 known white matter tracts using region-of-interest placement (TrackVis software program) and then computed relative tract length, density, and integrity. BD subjects demonstrated significantly shorter WM tracts in the genu, body and splenium of the corpus callosum compared to healthy controls. Additionally, bipolar subjects exhibited reduced fiber density in the genu and body of the corpus callosum, and in the inferior longitudinal fasciculus bilaterally. In the left uncinate fasciculus, however, BD subjects exhibited significantly greater fiber density than healthy controls. There were no significant differences between groups in WM tract FA for those tracts that began and ended in the brain. The significance of differences in tract length and fiber density in BD is discussed.     

White matter microstructure in 22q11 deletion syndrome: a pilot diffusion tensor imaging and voxel-based morphometry study of children and adolescents

Young people with 22q11 Deletion Syndrome (22q11DS) are at substantial risk for developing psychosis and have significant differences in white matter (WM) volume. However, there are few in vivo studies of both WM microstructural integrity (as measured using Diffusion Tensor (DT)-MRI) and WM volume in the same individual. We used DT-MRI and structural MRI (sMRI) with voxel based morphometry (VBM) to compare, respectively, the fractional anisotropy (FA) and WM volume of 11 children and adolescents with 22q11DS and 12 controls. Also, within 22q11DS we related differences in WM to severity of schizotypy, and polymorphism of the catechol-O-methyltransferase (COMT) gene. People with 22q11DS had significantly lower FA in inter-hemispheric and brainstem and frontal, parietal and temporal lobe regions after covarying for IQ. Significant WM volumetric increases were found in the internal capsule, anterior brainstem and frontal and occipital lobes. There was a significant negative correlation between increased schizotypy scores and reduced WM FA in the right posterior limb of internal capsule and the right body and left splenium of corpus callosum. Finally, the Val allele of COMT was associated with a significant reduction in both FA and volume of WM in the frontal lobes, cingulum and corpus callosum. Young people with 22q11DS have significant differences in both WM microstructure and volume. Also, there is preliminary evidence that within 22q11DS, some regional differences in FA are associated with allelic variation in COMT and may perhaps also be associated with schizotypy.     

Different patterns of association between white matter microstructure and plasma unsaturated fatty acids in those with high risk for psychosis and healthy participants

BackgroundDisrupted white matter (WM) microstructure has been commonly identified in youth at clinical high risk (CHR) for psychosis. Several lines of evidence suggest that fatty acids, especially unsaturated fatty acids (UFAs), might play a crucial role in the WM pathology of early onset psychosis. However, evidence linking UFA and WM microstructure in CHR is quite sparse.AimsWe investigated the relationship between the plasma UFA level and WM microstructure in CHR participants and healthy controls (HC).MethodsPlasma fatty acids were assessed and diffusion tensor imaging (DTI) data were performed with tract-based spatial statistics (TBSS) analysis for 66 individuals at CHR for psychosis and 70 HC.ResultsBoth the global and regional diffusion measures showed significant between-group differences, with decreased fractional anisotropy (FA) but increased mean diffusivity (MD) and radial diffusivity (RD) found in the CHR group compared with the HC group. On top of that, we found that in the HC group, plasma arachidic acid showed obvious trend-level associations with higher global FA, lower global MD and lower global RD, which regionally spread over the corpus callosum, right anterior and superior corona radiata, bilateral anterior and posterior limb of the internal capsule, and bilateral superior longitudinal fasciculus. However, there were no associations between global WM measures and any UFA in the CHR group. Conversely, we even found negative associations between arachidic acid levels and regional FA values in the right superior longitudinal fasciculus and right retrolenticular part of the internal capsule in the CHR group.ConclusionsCompared with the HC group, CHR subjects exhibited a different pattern of association between WM microstructure and plasma UFA, with a neuroprotective effect found in the HC group but not in the CHR group. Such discrepancy could be due to the excessively upregulated UFAs accumulated in the plasma of the CHR group, highlighting the role of balanced plasma-membrane fatty acids homeostasis in WM development.