WM Abnormalities Research Articles

Are white matter abnormalities a cause of “unexplained dizziness”?: A retrospective bi-centre study

Introduction Although cerebral small vessel disease is a significant contributor to the development of imbalance and falls in the elderly, whether it also contributes to the development of dizziness is not known. Methods A retrospective case analysis was conducted for 125 dizzy patients referred to two neuro-otology tertiary centres in London and Pisa. Specific search criteria of “white matter disease” was applied to databases and patients were divided into ‘explained’ causes of dizziness (ie benign positional vertigo, orthostatic hypotension, cerebellar ataxias) and ‘unexplained’ causes of dizziness. White matter hyperintensities (WMH) in MRI (T2 weighted and FLAIR) were blindly rated according to the Fazekas scale. Results 61 patients (mean age=72SD=7.95 years) in the ‘unexplained’ group and 64 (mean age=72.01SD=8.28 years) in the ‘explained’ group were recruited. The overall frequency of lesions (Fazekas 1–3) differed between the groups (p=0.015). The frequency of severe lesions (Fazekas 3) was significantly higher in the unexplained group (21%) than in the explained group (5%; p=0.005). Conclusion Increased severity of WM abnormalities in cases of unexplained dizziness suggests that such abnormalities are contributory to the development of dizziness. WM lesions may induce dizziness either because patients perceive a degree of objective unsteadiness or by a cortical-subcortical disconnection syndrome.

White Matter Development is Potentially Influenced in Adolescents with Vertically Transmitted HIV Infections: A Tract-Based Spatial Statistics Study.

Convergent evidence indicates that HIV is associated with abnormal WM microstructure in adults. However, little is known about whether HIV affects WM development in adolescents. In this study, we used DTI to investigate the integrity of WM microstructure in adolescents with vertically transmitted HIV infections. Fifteen HIV-positive adolescents with vertically transmitted infections and 26 HIV-negative controls participated in this study. Whole-brain analysis of fractional anisotropy was performed by Tract-Based Spatial Statistics to localize abnormal WM regions between groups. VOI analysis was further performed to explore the changes in diffusivity indices in the regions with fractional anisotropy alterations. Correlation analyses were used to assess the relationship between fractional anisotropy alterations and clinical measures within the HIV-positive group. Relative to HIV-negative controls, HIV-positive adolescents demonstrated significantly reduced fractional anisotropy in the corpus callosum, superior and posterior corona radiata, frontal and parietal WM, pre-/postcentral gyrus, and superior longitudinal fasciculus. In the affected regions, fractional anisotropy reductions were caused by an increase in radial diffusivity, and no changes were observed in axial diffusivity. Moreover, fractional anisotropy values in the bilateral frontal WM were negatively correlated with the duration of highly active antiretroviral therapy and were positively associated with the age at onset of highly active antiretroviral therapy. These findings suggest that early HIV infections may affect WM development, especially in the frontal WM, corpus callosum, and corona radiata in adolescents, which may be associated with hypomyelination and demyelination. Moreover, WM integrity may serve as a potential new treatment target.

Long-Term Blood-Brain Barrier Permeability Changes in Binswanger Disease.

The blood-brain barrier (BBB) is disrupted in small vessel disease patients with lacunes and white matter hyperintensities (WMHs). The relationship of WMHs and regional BBB permeability changes has not been studied. We hypothesized that BBB disruption occurs in normal appearing WM and regions near the WMHs. To test the hypothesis, we repeated BBB permeability measurements in patients with extensive WMHs related to Binswanger disease. We selected a subset of 22 Binswanger disease subjects from a well-characterized larger prospective vascular cognitive impairment cohort. We used 16 age-matched controls for comparison. The abnormal WM permeability (WMP) was measured twice for several years using dynamic contrast-enhanced magnetic resonance imaging. WMP maps were constructed from voxels above a predetermined threshold. Scans from first and second visits were coregistered. WM was divided into 3 regions: normal appearing WM, WMH ring, and WMH core. The ring was defined as 2 mm on each side of the WMH border. WMP was calculated in each of the 3 specific regions. We used paired t test, ANOVA, and Fisher exact test to compare individual changes. WMP was significantly higher in subjects than in controls (P<0.001). There was no correlation between WMH load and WMP. High permeability regions had minimal overlap between first and second scans. Nine percent of WMP was within the WMHs, 49% within the normal appearing WM, and 52% within the WMH ring (P<0.001; ANOVA). Increased BBB permeability in normal appearing WM and close to the WMH borders supports a relationship between BBB disruption and the development of WMHs.

DTI Detection of Longitudinal WM Abnormalities Due to Accumulated Head Impacts

Longitudinal evaluation using diffusion-weighted imaging and collision event monitoring was performed on high school athletes who participate in American football. Observed changes in white matter health were suggestive of injury and found to be correlated with accumulation of head collision events during practices and games.

Abnormal white matter integrity in chronic users of codeine-containing cough syrups: a tract-based spatial statistics study.

Codeine-containing cough syrups have become one of the most popular drugs of abuse in young people in the world. Chronic codeine-containing cough syrup abuse is related to impairments in a broad range of cognitive functions. However, the potential brain white matter impairment caused by chronic codeine-containing cough syrup abuse has not been reported previously. Our aim was to investigate abnormalities in the microstructure of brain white matter in chronic users of codeine-containing syrups and to determine whether these WM abnormalities are related to the duration of the use these syrups and clinical impulsivity. Thirty chronic codeine-containing syrup users and 30 matched controls were evaluated. Diffusion tensor imaging was performed by using a single-shot spin-echo-planar sequence. Whole-brain voxelwise analysis of fractional anisotropy was performed by using tract-based spatial statistics to localize abnormal WM regions. The Barratt Impulsiveness Scale 11 was surveyed to assess participants' impulsivity. Volume-of-interest analysis was used to detect changes of diffusivity indices in regions with fractional anisotropy abnormalities. Abnormal fractional anisotropy was extracted and correlated with clinical impulsivity and the duration of codeine-containing syrup use. Chronic codeine-containing syrup users had significantly lower fractional anisotropy in the inferior fronto-occipital fasciculus of the bilateral temporo-occipital regions, right frontal region, and the right corona radiata WM than controls. There were significant negative correlations among fractional anisotropy values of the right frontal region of the inferior fronto-occipital fasciculus and the right superior corona radiata WM and Barratt Impulsiveness Scale total scores, and between the right frontal region of the inferior fronto-occipital fasciculus and nonplan impulsivity scores in chronic codeine-containing syrup users. There was also a significant negative correlation between fractional anisotropy values of the right frontal region of the inferior fronto-occipital fasciculus and the duration of codeine-containing syrup use in chronic users. Chronic codeine-containing syrup abuse may be associated with disruptions in brain WM integrity. These WM microstructural deficits may be linked to higher impulsivity in chronic codeine-containing syrup users.

Correction

HomeCirculationVol. 129, No. 13Correction Free AccessCorrectionPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCorrectionPDF/EPUBCorrection Originally published1 Apr 2014https://doi.org/10.1161/CIR.0000000000000036Circulation. 2014;129:e429This article corrects the followingPrognostic Value of High-Dose Dipyridamole Stress Myocardial Contrast Perfusion EchocardiographyIn the article by Gaibazzi et al, “Prognostic Value of High-Dose Dipyridamole Stress Myocardial Contrast Perfusion Echocardiography,” which was published in the September 4, 2012 issue of the journal (Circulation. 2012;126:1217–1224), the legend within Figure 1 incorrectly noted “Only WM abnormalities” instead of “Only MP abnormalities.”The current online version of the article has been corrected. The authors regret the error. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesPrognostic Value of High-Dose Dipyridamole Stress Myocardial Contrast Perfusion EchocardiographyNicola Gaibazzi, et al. Circulation. 2012;126:1217-1224 April 1, 2014Vol 129, Issue 13 Advertisement Article InformationMetrics © 2014 American Heart Association, Inc.https://doi.org/10.1161/CIR.0000000000000036 Originally publishedApril 1, 2014 PDF download Advertisement

White matter microstructural abnormalities in families multiply affected with bipolar I disorder: a diffusion tensor tractography study

White matter (WM) abnormalities are proposed as potential endophenotypic markers of bipolar disorder (BD). In a diffusion tensor imaging (DTI) voxel-based analysis (VBA) study of families multiply affected with BD, we previously reported that widespread abnormalities of fractional anisotropy (FA) are associated with both BD and genetic liability for illness. In the present study, we further investigated the endophenotypic potential of WM abnormalities by applying DTI tractography to specifically investigate tracts implicated in the pathophysiology of BD. Diffusion magnetic resonance imaging (MRI) data were acquired from 19 patients with BD type I from multiply affected families, 21 of their unaffected first-degree relatives and 18 healthy volunteers. DTI tractography was used to identify the cingulum, uncinate fasciculus (UF), arcuate portion of the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), corpus callosum, and the anterior limb of the internal capsule (ALIC). Regression analyses were conducted to investigate the effect of participant group and genetic liability on FA and radial diffusivity (RD) in each tract. We detected a significant effect of group on both FA and RD in the cingulum, SLF, callosal splenium and ILF driven by reduced FA and increased RD in patients compared to controls and relatives. Increasing genetic liability was associated with decreased FA and increased RD in the UF, and decreased FA in the SLF, among patients. WM microstructural abnormalities in limbic, temporal and callosal pathways represent microstructural abnormalities associated with BD whereas alterations in the SLF and UF may represent potential markers of endophenotypic risk.

Concordance of white matter and gray matter abnormalities in autism spectrum disorders: A voxel‐based meta‐analysis study

There are at least two fundamental unanswered questions in the literature on autism spectrum disorders (ASD): Are abnormalities in white (WM) and gray matter (GM) consistent with one another? Are WM morphometric alterations consistent with alterations in the GM of regions connected by these abnormal WM bundles and vice versa? The aim of this work is to bridge this gap. After selecting voxel-based morphometry and diffusion tensor imaging studies comparing autistic and normally developing groups of subjects, we conducted an activation likelihood estimation (ALE) meta-analysis to estimate consistent brain alterations in ASD. Multidimensional scaling was used to test the similarity of the results. The ALE results were then analyzed to identify the regions of concordance between GM and WM areas. We found statistically significant topological relationships between GM and WM abnormalities in ASD. The most numerous were negative concordances, found bilaterally but with a higher prevalence in the right hemisphere. Positive concordances were found in the left hemisphere. Discordances reflected the spatial distribution of negative concordances. Thus, a different hemispheric contribution emerged, possibly related to pathogenetic factors affecting the right hemisphere during early developmental stages. Besides, WM fiber tracts linking the brain structures involved in social cognition showed abnormalities, and most of them had a negative concordance with the connected GM regions. We interpreted the results in terms of altered brain networks and their role in the pervasive symptoms dramatically impairing communication and social skills in ASD patients.

Increases in brain white matter abnormalities and subcortical gray matter are linked to CD4 recovery in HIV infection

MRI alterations in the cerebral white (WM) and gray matter (GM) are common in HIV infection, even during successful combination antiretroviral therapy (CART), and their pathophysiology and clinical significance are unclear. We evaluated the association of these alterations with recovery of CD4+ T cells. Seventy-five HIV-infected (HIV+) volunteers in the CNS HIV Anti-Retroviral Therapy Effects Research study underwent brain MRI at two visits. Multi-channel morphometry yielded volumes of total cerebral WM, abnormal WM, cortical and subcortical GM, and ventricular and sulcal CSF. Multivariable linear regressions were used to predict volumetric changes with change in current CD4 and detectable HIV RNA. On average, the cohort (79% initially on CART) demonstrated loss of total cerebral WM alongside increases in abnormal WM and ventricular volumes. A greater extent of CD4 recovery was associated with increases in abnormal WM and subcortical GM volumes. Virologic suppression was associated with increased subcortical GM volume, independent of CD4 recovery. These findings suggest a possible link between brain alterations and immune recovery, distinct from the influence of virologic suppression. The association of increasing abnormal WM and subcortical GM volumes with CD4+ T cell recovery suggests that neuroinflammation may be one mechanism in CNS pathogenesis.

Progressive White Matter Microstructure Damage in Male Chronic Heroin Dependent Individuals: A DTI and TBSS Study

BackgroundTo investigate the WM microstructure deficits in heroin dependent individuals (HDIs) with different length of heroin dependence, and to investigate whether these WM deficits can be related to the duration of heroin use and to decision-making deficits in HDIs.Methodology/Principal FindingsThirty-six HDIs [including eighteen sHDIs (duration of heroin dependent is less than 10 years) and eighteen lHDIs (duration of dependent is between 10∼20 years)] and sixteen healthy controls participated in this study. Whole brain voxel-wise analysis of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da) and radial diffusivity (Dr) were performed by tract-based spatial statistics (TBSS) to localize abnormal WM regions among groups. TBSS demonstrated that sHDIs had significantly lower FA than controls in right orbito-frontal WM, bilateral temporal WM and right parietal WM. The lHDIs had significantly lower FA throughout the brain compared with the controls and sHDIs. The lHDIs had significantly lower Da than controls in bilateral inferior frontaloccipital fasciculus, bilateral splenium of corpus callosum, left inferior longitudinal fasciculus, and had significantly higher Dr than controls in bilateral uncinatus fasciculus, bilateral inferior frontaloccipital fasciculus and bilateral cortical spinal fasciculus. Volume-of-interest (VOI) analyses detect the changes of diffusivity indices in the regions with FA abnormalities revealed by control vs sHDIs. In most VOIs, FA reductions were caused by the increase in Dr as well as the decrease in Da. Correlation analysis was used to assess the relationship between FA and behavioral measures in HDIs and controls available. Significantly positively correlations were found between the FA values in the right orbital-frontal WM, right parietal WM and IGT performance.ConclusionsThe extent and severity of WM integrity deficits in HDIs was associated with the length of heroin dependent. Furthermore, abnormal WM microstructure may correlate with decision-making impairments in HDIs.

DTI Values in Key White Matter Tracts from Infancy through Adolescence

DTI is an advanced neuroimaging technique that allows in vivo quantification of water diffusion properties as surrogate markers of the integrity of WM microstructure. In our study, we investigated normative data from a large number of pediatric and adolescent participants to examine the developmental trends in DTI during this conspicuous WM maturation period. DTI data in 202 healthy pediatric and adolescent participants were analyzed retrospectively. Fractional anisotropy and mean diffusivity values in the corpus callosum and internal capsule were fitted to an exponential regression model to delineate age-dependent maturational changes across the WM structures. The DTI metrics demonstrated characteristic exponential patterns of progression during development and conspicuous age-dependent changes in the first 36 months, with rostral WM tracts experiencing the highest slope of the exponential function. In contrast, the highest final FA and lowest MD values were detected in the splenium of the corpus callosum and the posterior limb of the internal capsule. Our analysis shows that the more caudal portions of the corpus callosum and internal capsule begin the maturation process earlier than the rostral regions, but the rostral regions develop at a more accelerated pace, which may suggest that rostral regions rely on development of more caudal brain regions to instigate their development. Our normative DTI can be used as a reference to study normal spatiotemporal developmental profiles in the WM and help identify abnormal WM structures in patient populations.

Central nervous system abnormalities in patients with PMP22 gene mutations: a prospective study

BackgroundMutations of the peripheral myelin protein-22 (PMP22) gene are the most common cause of inherited disease of the peripheral nervous system (PNS), with its deletion resulting in hereditary neuropathy with...

White matter abnormalities correlate with neurocognitive performance in patients with HBV-related cirrhosis

BackgroundWhite matter (WM) abnormalities are common in cirrhotic patients and possibly contribute to hepatic encephalopathy (HE), a frequent neuropsychiatric complication of cirrhosis. However, little is known about these WM abnormalities and their relationship to neurocognitive deficits in patients with HBV-related cirrhosis. MethodsThree-dimensional T1-weighted magnetic resonance imaging and diffusion tensor imaging (DTI) scans were obtained from 67 patients with HBV-related cirrhosis and 40 controls. Voxel-based morphometry and voxel-based DTI were performed to detect macroscopic atrophy and damage to the microstructural integrity of the WM, respectively. Correlation analyses were performed to investigate the relationships between WM abnormalities and neurocognitive performances. ResultsPatients with cirrhosis exhibited significantly decreased WM volume and fractional anisotropy (FA) values, especially in the corpus callosum, thalamus, extra-nuclear area, sensorimotor area, fusiform gyrus, lingual gyrus, and frontal lobes. These abnormalities were more severe with increasing Child–Pugh stage, minimal HE, and previous overt HE. Changes in the corpus callosum, frontal lobe, sensorimotor area, internal capsule, and temporal–occipital lobes were correlated with poor neurocognitive performance. Also, the significantly decreased global WM volume and mean FA value were correlated with poor neurocognitive performances. ConclusionsDiffuse WM abnormalities are common in patients with HBV-related cirrhosis. Advanced liver disease and episodes of HE are two factors associated with WM abnormalities. The correlation between poor neurocognitive performance and WM abnormalities suggests that WM abnormalities may be one of mechanisms underlying neurocognitive deficits in patients with HBV-related cirrhosis.

The Integration of the Glutamatergic and the White Matter Hypotheses of Schizophrenias Etiology

Background:schizophrenia's endophenotipic profile is not only generally complex, but often varies from case to case. The perspective of trying to define specific anatomic correlates of the syndrome has led to disappointing results. In that context, neurophysiologic hypotheses (e.g. glutamatergic hypothesis) and connectivity hypotheses became prominent. Nevertheless, despite their commitment to the principle of denying 'localist' views and approaching the syndrome's endophenotype from a whole brain perspective, efforts to integrate both have not flourished at this moment in time. Objectives:This paper aims to introduce a new etiological model that integrates the glutamatergic and the WM (WM) hypotheses of schizophrenia’s etiology. This model proposes to serve as a framework in order to relate to patterns of brain abnormalities from the onset of the syndrome to stages of advanced chronification.Highlights:Neurotransmitter abnormalities forego noticeable WM abnormalities. The former, chiefly represented by NMDAR hypo-function and associated molecular cascades, is related to the first signs of cell loss. This process is both directly and indirectly integrated to the underpinning of WM structural abnormalities; not only is the excess of glutamate toxic to the WM, but its disruption is associated to the expression of known genetic risk factors (e.g., NRG-1). A second level of the model develops the idea that abnormal neurotransmission within specific neural populations ('motifs') impair particular cognitive abilities, while subsequent WM structural abnormalities impair the integration of brain functions and multimodality. As a result of this two-stage dynamic, the affected individual progresses from experiencing specific cognitive and psychological deficits, to a condition of cognitive and existential fragmentation, linked to hardly reversible decreases in psychosocial functioning.

White Matter Abnormalities in Patients with Focal Cortical Dysplasia Revealed by Diffusion Tensor Imaging Analysis in a Voxelwise Approach

Background: Diffusion tensor imaging (DTI) allows the analysis of changes in microstructure, through the quantification of the spread and direction of water molecules in tissues. We used fractional anisotropy (FA) maps to compare the integrity of WM between patients and controls. The objective of the present study was to investigate WM abnormalities in patients with frontal lobe epilepsy secondary to focal cortical dysplasia (FCD). Materials and Methods: We included 31 controls (12 women, 33.1 ± 9.6 years, mean ± SD) and 22 patients (11 women, 30.4 ± 10.0 years), recruited from our outpatient clinic. They had clinical and EEG diagnosis of frontal lobe epilepsy, secondary to FCD detected on MRI. Patients and controls underwent 3T MRI, including the DTI sequence, obtained in 32 directions and b value of 1000 s/mm2. To process the DTI we used the following softwares: MRIcroN and FSL/TBSS (tract-based spatial statistics). We used a threshold-free cluster enhancement with significance at p < 0.05, fully corrected for multiple comparisons across space. Results: Areas with FA reduction in patients were identified in both hemispheres, mainly in the frontal lobes, cingulum, and forceps minor (p = 0.014), caudate e anterior thalamic radiation (p = 0.034), superior longitudinal fasciculus (p = 0.044), uncinate fasciculus, and inferior fronto-occipital fasciculus (p = 0.042). Conclusion: Our results showed a widespread pattern of WM microstructural abnormalities extending beyond the main lesion seen on MRI (frontal lobe), which may be related to frequent seizures or to the extent of MRI-invisible portion of FCD.

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.

Microstructural white matter abnormalities in type 2 diabetes mellitus: A diffusion tensor imaging study

This study investigated whether diffusion tensor imaging (DTI) could identify potential abnormalities in type 2 diabetes mellitus (T2DM) patients without cognitive complaints compared to healthy controls. In addition, the existence of associations between diffusion measures and clinical parameters was examined. Forty T2DM patients and 97 non-diabetic controls completed a clinical and biochemistry examination. Structural MRI scans (DTI, T1, T2, FLAIR) were subsequently acquired with a 1.5 Tesla scanner. In addition to a global DTI analysis, voxel-based analysis was performed on the fractional anisotropy (FA), mean diffusivity (MD), and axial (AD) and transverse (TD) diffusivity maps to investigate regions that exhibit (i) WM differences between patients and controls; and (ii) associations between clinical measurements and these DTI indices. There were no significant differences in age, gender, and WM hyperintensity scores derived by the conventional MRI scans between controls and T2DM patients. For the T2DM patients, however, the MD of the brain parenchyma was significantly increased compared to controls and was positively correlated with disease duration. The voxel based analyses revealed (i) a significantly decreased FA in the bilateral frontal WM compared to controls which was mainly caused by an increased TD and not a decreased AD within these regions; (ii) a significant association between disease duration and microstructural properties in several brain regions including bilateral cerebellum, temporal lobe WM, right caudate, bilateral cingulate gyrus, pons, and parahippocampal gyrus. Our findings indicate that microstructural WM abnormalities and associations with clinical measurements can be detected with DTI in T2DM patients.

P03-111 - Does antipsychotic medication affect white matter in schizophrenia and bipolar disorder? a review of diffusion tensor imaging literature

IntroductionWhite matter (WM) abnormalities are considered integral to the pathophysiology of Schizophrenia (SZ) and Bipolar Disorder (BD), but there is ongoing uncertainty about the contribution of medication to these findings.ObjectivesDiffusion Tensor Imaging (DTI) is a neuroimaging technique that provides quantitative indices of the structural and orientational characteristics of WM. These indices include mean diffusivity (MD), which is a directionally averaged measure of the apparent diffusion coefficient, and fractional anisotropy (FA), which summarizes the orientational dependence of diffusivity. We wanted to determine if these indices are affected by antipsychotic medication.AimsOur aim was to examine the available literature in order to differentiate antipsychotic effects from disorder-specific WM abnormalities on DTI measures.MethodsWe conducted a systematic qualitative review of the DTI literature in Bipolar Disorder (BD) and Schizophrenia (SZ), between 1998 and 2010 and included only studies where the relationship between DTI measures and antipsychotic medication was explicitly examined and reported.ResultsWe identified 40 studies in SZ and 8 in BD. All studies were cross-sectional and involved relatively small patient samples. 32 studies (80%) did not find any relationship between antipsychotic medication (dose, cumulative exposure) and FA or MD.ConclusionsCurrent evidence does not indicate a major impact of antipsychotic treatment on DTI indices of WM integrity. However, the lack of longitudinal, within-subject designs is a major gap in the current literature.

MR spectroscopy in opiate maintenance therapy: association of glutamate with the number of previous withdrawals in the anterior cingulate cortex

Pre-clinical research indicates that opioids reduce extracellular glutamate in acute opioid treatment, whereas during withdrawal, glutamatergic neurotransmission is increased and withdrawal symptoms can be blocked by glutamate receptor antagonists. The glutamate hypothesis of addiction suggests that withdrawal-associated hyperglutamatergic states destabilize the glutamatergic system chronically and contribute to relapse. magnetic resonance spectroscopy at three tesla optimized for glutamate assessment (TE 80 ms) was performed in the anterior cingulate gyrus (ACC) and frontal white matter (fWM) of 17 opiate-dependent patients during opiate maintenance therapy and 20 healthy controls. Controlling for age and gray matter content, glutamate in the ACC was positively associated with the number of previous withdrawals. For glutamate + glutamine (Glx), a significant group-age interaction was found. Whereas Glx declines with age in healthy controls, Glx increases with age in opiate-dependent patients. The number of previous withdrawals did not correlate with age. In fWM spectra, increased Cho concentrations were observed in opiate-dependent patients. Both new findings, the positive correlation of glutamate and previous withdrawals and increasing Glx with age in contrast to an age-dependent Glx decrease in controls indicate a destabilization of the glutamate system in opiate-dependent patients and support the glutamate hypothesis of addiction. Increased Cho concentrations in fWM corroborate findings of WM abnormalities in opioid-dependent subjects.

Region-specific alterations in brain development in one- to three-year-old boys with fragile X syndrome

Longitudinal neuroimaging investigation of fragile X syndrome (FXS), the most common cause of inherited intellectual disability and autism, provides an opportunity to study the influence of a specific genetic factor on neurodevelopment in the living human brain. We examined voxel-wise gray and white matter volumes (GMV, WMV) over a 2-year period in 1- to 3-year-old boys with FXS (n = 41) and compared these findings to age- and developmentally matched controls (n = 28). We found enlarged GMV in the caudate, thalamus, and fusiform gyri and reduced GMV in the cerebellar vermis in FXS at both timepoints, suggesting early, possibly prenatal, genetically mediated alterations in neurodevelopment. In contrast, regions in which initial GMV was similar, followed by an altered growth trajectory leading to increased size in FXS, such as the orbital gyri, basal forebrain, and thalamus, suggests delayed or otherwise disrupted synaptic pruning occurring postnatally. WMV of striatal-prefrontal regions was greater in FXS compared with controls, and group differences became more exaggerated over time, indicating the possibility that such WM abnormalities are the result of primary FMRP-deficiency-related axonal pathology, as opposed to secondary connectional dysregulation between morphologically atypical brain structures. Our results indicate that structural abnormalities of different brain regions in FXS evolve differently over time reflecting time-dependent effects of FMRP deficiency and provide insight into their neuropathologic underpinnings. The creation of an early and accurate human brain phenotype for FXS in humans will significantly improve our capability to detect whether new disease-specific treatments can "rescue" the FXS phenotype in affected individuals.