White Matter Integrity In Patients Research Articles

White matter damage is related to ataxia severity in SCA3

Spinocerebellar ataxia type 3 (SCA3) is the most frequent inherited cerebellar ataxia in Europe, the US and Japan, leading to disability and death through motor complications. Although the affected protein ataxin-3 is found ubiquitously in the brain, grey matter atrophy is predominant in the cerebellum and the brainstem. White matter pathology is generally less severe and thought to occur in the brainstem, spinal cord, and cerebellar white matter. Here, we investigated both grey and white matter pathology in a group of 12 SCA3 patients and matched controls. We used voxel-based morphometry for analysis of tissue loss, and tract-based spatial statistics (TBSS) on diffusion magnetic resonance imaging to investigate microstructural pathology. We analysed correlations between microstructural properties of the brain and ataxia severity, as measured by the Scale for the Assessment and Rating of Ataxia (SARA) score. SCA3 patients exhibited significant loss of both grey and white matter in the cerebellar hemispheres, brainstem including pons and in lateral thalamus. On between-group analysis, TBSS detected widespread microstructural white matter pathology in the cerebellum, brainstem, and bilaterally in thalamus and the cerebral hemispheres. Furthermore, fractional anisotropy in a white matter network comprising frontal, thalamic, brainstem and left cerebellar white matter strongly and negatively correlated with SARA ataxia scores. Tractography identified the thalamic white matter thus implicated as belonging to ventrolateral thalamus. Disruption of white matter integrity in patients suffering from SCA3 is more widespread than previously thought. Moreover, our data provide evidence that microstructural white matter changes in SCA3 are strongly related to the clinical severity of ataxia symptoms.

Cortical thickness, cortical and subcortical volume, and white matter integrity in patients with their first episode of major depression

BackgroundThe uncertainty over the true morphological changes in brains with major depressive disorder (MDD) underlines the necessity of comprehensive studies with multimodal structural brain imaging analyses. This study aimed to evaluate the differences in cortical thickness, cortical and subcortical volume, and white matter integrity between first episode, medication-naïve MDD patients and healthy controls. MethodsSubjects with their first episode of MDD whose illness duration had not exceeded 6 months (n=20) were enrolled in this study and were compared to age-, sex-, and education level-matched healthy controls (n=22). All participants were subjected to T1-weighted structural magnetic resonance imaging (MRI). We used an automated procedure of FreeSurfer and Tract-based spatial statistics (TBSS) to analyze differences in cortical thickness, cortical and subcortical volume, and white matter integrity between two groups. ResultsThe patients with first episode MDD exhibited significantly reduced cortical volume in the caudal anterior cingulate gyrus (P<0.0015) compared to healthy controls. We also observed altered white matter integrity in the body of the corpus callosum (P<0.01), reduced cortical volume of the caudal middle frontal gyrus and medial orbitofrontal gyrus, and enlarged hippocampal volume in the first episode MDD patients. LimitationsWe relied on a relatively small sample size and cortical volume reduction in several brain regions was not replicated in the analysis of cortical thickness. ConclusionsUsing multimodal imaging analyses on medication-naïve first episode MDD patients, we demonstrated fundamental structural alteration of brain gray and white matter, such as reduced cortical volume of the caudal ACC and white matter integrity in the body of the corpus callosum.

Diffusion Measures Indicate Fight Exposure-Related Damage to Cerebral White Matter in Boxers and Mixed Martial Arts Fighters

Traumatic brain injury is common in fighting athletes such as boxers, given the frequency of blows to the head. Because DTI is sensitive to microstructural changes in white matter, this technique is often used to investigate white matter integrity in patients with traumatic brain injury. We hypothesized that previous fight exposure would predict DTI abnormalities in fighting athletes after controlling for individual variation. A total of 74 boxers and 81 mixed martial arts fighters were included in the analysis and scanned by use of DTI. Individual information and data on fight exposures, including number of fights and knockouts, were collected. A multiple hierarchical linear regression model was used in region-of-interest analysis to test the hypothesis that fight-related exposure could predict DTI values separately in boxers and mixed martial arts fighters. Age, weight, and years of education were controlled to ensure that these factors would not account for the hypothesized effects. We found that the number of knockouts among boxers predicted increased longitudinal diffusivity and transversal diffusivity in white matter and subcortical gray matter regions, including corpus callosum, isthmus cingulate, pericalcarine, precuneus, and amygdala, leading to increased mean diffusivity and decreased fractional anisotropy in the corresponding regions. The mixed martial arts fighters had increased transversal diffusivity in the posterior cingulate. The number of fights did not predict any DTI measures in either group. These findings suggest that the history of fight exposure in a fighter population can be used to predict microstructural brain damage.

Diffusion tensor MRI of the corpus callosum in amyotrophic lateral sclerosis

To determine if decline in corpus callosum (CC) white matter integrity in patients with amyotrophic lateral sclerosis (ALS) is localized to motor-related areas. Twenty-one ALS patients and 21 controls participated. Diffusion tensor images (DTI) were acquired using 3 Tesla (T) MRI. Tract-based spatial statistics were used to examine whole-brain white matter damage. A segmentation schema was used to define CC volumes-of-interest (VOI). Fractional anisotropy (FA) and radial- and axial-diffusivity (RD, AD) were extracted from VOIs and compared between groups. DTI measurements in motor-related Area III were tested for correlation with symptoms and disease duration. Extracted FA values from CC VOIs were reduced in ALS patients (P≤0.0001), particularly in Areas II and III (P≤0.01). Reduced FA in Area III correlated with disease symptomology (P≤0.05) and duration (P≤0.02). Between-group whole-brain comparisons (P≤0.05, corrected) showed reduced FA and increased RD throughout white matter regions including the CC, corona radiata, and internal capsule. AD was increased in the left corona radiata and internal and external capsules. FA in motor-related regions of the CC is more affected than other CC areas in ALS patients. Microstructural pathology of transcallosal fiber tracts may represent a future component of an imaging biomarker for ALS.

Symptomatic White Matter Changes in Mild Traumatic Brain Injury Resemble Pathologic Features of Early Alzheimer Dementia

To evaluate white matter integrity in patients with mild traumatic brain injury (TBI) who did not have morphologic abnormalities at conventional magnetic resonance (MR) imaging with diffusion-tensor imaging to determine any relationship between patterns of white matter injury and severity of postconcussion symptoms. The institutional review board approved this study, with waiver of informed consent. Diffusion-tensor images from 64 consecutive patients with mild TBI obtained with conventional MR imaging were evaluated retrospectively. Fractional anisotropy (FA) maps were generated as a measure of white matter integrity. All patients underwent a neurocognitive evaluation. Correlations between skeletonized FA values in white matter, total concussion symptom score, and findings of sleep and wake disturbances were analyzed with regression analysis that used tract-based spatial statistics. Total concussion symptom scores varied from 2 to 97 (mean ± standard deviation, 32.7 ± 24.4), with 34 patients demonstrating sleep and wake disturbances. Tract-based spatial statistics showed a significant correlation between high total concussion symptom score and reduced FA at the gray matter-white matter junction (P < .05), most prominently in the auditory cortex (P < .05). FA in the parahippocampal gyri was significantly decreased in patients with sleep and wake disturbances relative to patients without such disturbances (0.26 and 0.37, respectively; P < .05). The distribution of white matter abnormalities in patients with symptomatic mild TBI is strikingly similar to the distribution of pathologic abnormalities in patients with early Alzheimer dementia, a finding that may help direct research strategies.

Plasma brain-derived neurotrophic factor and prefrontal white matter integrity in late-onset depression and normal aging

To explore the relationship between brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), cerebral deep white matter lesions (DWMLs), and measures of white matter integrity in patients with late-onset depression, with respect to vascular risk factors. We examined 22 patients with late-onset depression and 22 matched controls. Quantification of plasma BDNF and VEGF levels were performed with enzyme-linked immunosorbent assay (ELISA) kits. Measures of white matter integrity comprised apparent diffusion coefficient (ADC) and fractional anisotropy (FA), obtained by diffusion tensor imaging (DTI). Effects of DWMLs, FA, ADC, and vascular risk factors on BDNF and VEGF were assessed using multiple linear regression. The BDNF and VEGF levels did not differ significantly between groups. With pooled data for patients and controls, the BDNF level was positively associated with both number (t = 2.14, P = 0.039) and volume (t = 2.04, P = 0.048) of prefrontal DWMLs and negatively associated with FA in prefrontal normal-appearing white matter (t = -2.40, P = 0.02), adjusted for age and gender. Smoking and hypercholesterolemia was positively associated with the BDNF (t = 2.36, P = 0.023) and VEGF levels (t = 2.28, P = 0.028), respectively. Our results suggest a role for BDNF in the complex pathophysiologic mechanisms underlying DWMLs in both normal aging and late-onset depression.

Is depression a disconnection syndrome? Meta- analysis of diffusion tensor imaging studies in patients with MDD

Many studies using diffusion tensor imaging (DTI) have demonstrated impaired white matter integrity in patients with major depressive disorder (MDD), with significant results found in diverse brain regions. We sought to identify whether there are consistent changes of regional white matter integrity in patients with MDD, as shown by decreased fractional anisotropy in DTI. A systematic search strategy was used to identify relevant whole brain voxel-based DTI studies of patients with MDD in relation to comparison groups. Relevant databases were searched for studies published between January 1994 and February 2011 using combinations of the terms "DTI" or "diffusion tensor;" "whole brain" or "voxel-based;" and "depress*." Using the studies that met our inclusion criteria, we performed a meta-analysis of the coordinates of decreased fractional anisotropy using the activation likelihood estimation (ALE) method, which detects 3-dimensional conjunctions of coordinates from multiple studies, weighted by sample size. We then used DTIquery software for fibre tracking to locate the fascicles involved in each region. We included 11 studies with a combined sample of 231 patients with MDD and 261 comparison participants, providing 50 coordinates of decreased fractional anisotropy. Our meta-analysis identified 4 consistent locations of decreased fractional anisotropy in patients with MDD: white matter in the right frontal lobe, right fusiform gyrus, left frontal lobe and right occipital lobe. Fibre tracking showed that the main fascicles involved were the right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, right posterior thalamic radiation and interhemispheric fibres running through the genu and body of the corpus callosum. The number of studies included was relatively small, and the DTI data acquisition and analysis techniques were heterogeneous. The ALE method cannot handle studies with no significant group differences. Voxel-based analysis of DTI studies of patients with MDD consistently identified decreased fractional anisotropy in the white matter fascicles connecting the prefrontal cortex within cortical (frontal, temporal and occipital lobes) and subcortical areas (amygdala and hippocampus). This isstrong evidence for the involvement of these neural circuits in the pathology of MDD.

Right lateralized white matter abnormalities in first-episode, drug-naive paranoid schizophrenia

Numerous studies in first-episode schizophrenia suggest the involvement of white matter (WM) abnormalities in multiple regions underlying the pathogenesis of this condition. However, there has never been a neuroimaging study in patients with first-episode, drug-naive paranoid schizophrenia by using tract-based spatial statistics (TBSS) method. Here, we used diffusion tensor imaging (DTI) with TBSS method to investigate the brain WM integrity in patients with first-episode, drug-naive paranoid schizophrenia. Twenty patients with first-episode, drug-naive paranoid schizophrenia and 26 healthy subjects matched with age, gender, and education level were scanned with DTI. An automated TBSS approach was employed to analyze the data. Voxel-wise statistics revealed that patients with paranoid schizophrenia had decreased fractional anisotropy (FA) values in the right superior longitudinal fasciculus (SLF) II, the right fornix, the right internal capsule, and the right external capsule compared to healthy subjects. Patients did not have increased FA values in any brain regions compared to healthy subjects. There was no correlation between the FA values in any brain regions and patient demographics and the severity of illness. Our findings suggest right-sided alterations of WM integrity in the WM tracts of cortical and subcortical regions may play an important role in the pathogenesis of paranoid schizophrenia.

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

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. 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. 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. 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.

Poster #47 WHITE MATTER ALTERATIONS IN SCHIZOPHRENIA: A DIFFUSION TRACTOGRAPHY STUDY OF CINGULUM BUNDLE

Integrity of brain white matter (WM) tracts in adulthood could be detrimentally affected by exposure to adverse childhood experiences (ACE). Changes of diffusion tensor imaging (DTI) measures suggesting WM disruption have been reported in patients with schizophrenia together with a history of childhood maltreatment. We therefore hypothesized that ACE could be associated with altered DTI measures of WM integrity in patients with schizophrenia. We tested this hypothesis in 83 schizophrenia patients using whole brain tract-based spatial statistics in the WM skeleton with threshold-free cluster enhancement of DTI measures of WM microstructure: axial, radial, and mean diffusivity (MD), and fractional anisotropy (FA). We observed an inverse correlation between severity of ACE and DTI measures of FA, and a positive correlation with MD in several WM tracts including corona radiata, thalamic radiations, corpus callosum, cingulum bundle, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus. Lower FA and higher MD are indexes of a reduction in fibre coherence and integrity. The association of ACE to reduced FA and increased MD in key WM tracts contributing to the functional integrity of the brain suggests that ACE might contribute to the pathophysiology of schizophrenia through a detrimental action on structural connectivity in critical cortico-limbic networks.

Executive Dysfunction in MCI: Subtype or Early Symptom

Mild cognitive impairment (MCI) may take several forms, and amnestic MCI (aMCI) has been recognized as an early stage of Alzheimer's Disease (AD). Impairment in executive functions including attention (eMCI) may be indicative of several neurodegenerative conditions. Executive impairment is frequently found in aMCI, it is significant for prognosis, and patients with eMCI may go on to develop AD. Recent studies have found changes in white matter integrity in patients with eMCI to be more sensitive than measures of cortical atrophy. Studies of genetic high-risk groups using sensitive cognitive neuroscience paradigms indicate that changes in executive function may be a cognitive marker useful for tracking development in an AD pathophysiological process.

P-796 - Assessment of alteration in white matter integrity in schizophrenia following administration of clozapine: tract-based spatial statistics of diffusion tensor imaging

Several diffusion tensor imaging (DTI) studies have shown disturbed white matter integrity in various brain areas in schizophrenia patients compared to controls, while studies investigating the effects of antipsychotics on white matter integrity is scarce, and the effect of clozapine on DTI measures have not yet been studied. The purpose of this study was to investigate the influence of clozapine on white matter integrity in patients with chronic schizophrenia by using Tract-Based-Spatial-Statistics (TBSS). DTI of sixteen patients with schizophrenia (M/F: 10/6) were performed before the initiation, and at 3rd month of clozapine treatment using a 1.5 T MR scanner (Magnetom TIM, Siemens, Germany). A voxelwise statistical analysis of fractional anisotropy (FA) maps was carried out using TBSS, part of the FSL software package. Voxelwise statistics on the skeletonised FA data was computed at a threshold level of p < 0.05. White matter structures with significant group differences in FA were extracted as ROIs, registered to and overlaid onto an anatomical template and labelled using the MRI Atlas of Human White Matter. TBSS-DTI revealed significant increases in FA after 3 months of clozapine administration in bilateral, but predominantly right hippocampus, genu and splenium of the corpus callosum, fornices, frontal, parietal and temporal white matter. To our knowledge this is the first study to show that clozapine treatment resulted in a widespread increase in FA, indicative of improved white matter integrity. Clozapine may exert its effects by improving intra- and interhemispheric connectivity among cortical and subcortical regions.

Evaluation of White Matter Abnormality in Mild Alzheimer Disease and Mild Cognitive Impairment Using Diffusion Tensor Imaging: A Comparison of Tract-Based Spatial Statistics with Voxel-Based Morphometry

Purpose : To evaluate white matter abnormalities on diffusion tensor imaging (DTI) in patients with mild Alzheimer disease (AD) and mild cognitive impairment (MCI), using tract-based spatial statistics (TBSS) and voxel-based morphometry (VBM). Materials and Methods: DTI was performed in 21 patients with mild AD, in 13 with MCI and in 16 old healthy subjects. A fractional anisotropy (FA) map was generated for each participant and processed for voxel-based comparisons among the three groups using TBSS. For comparison, DTI data was processed using the VBM method, also. Results: TBSS showed that FA was significantly lower in the AD than in the old healthy group in the bilateral anterior and right posterior corona radiata, the posterior thalamic radiation, the right superior longitudinal fasciculus, the body of the corpus callosum, and the right precuneus gyrus. VBM identified additional areas of reduced FA, including both uncinates, the left parahippocampal white matter, and the right cingulum. There were no significant differences in FA between the AD and MCI groups, or between the MCI and old healthy groups. Conclusion: TBSS showed multifocal abnormalities in white matter integrity in patients with AD compared with old healthy group. VBM could detect more white matter lesions than TBSS, but with increased artifacts.

Assessment of white matter abnormalities in paranoid schizophrenia and bipolar mania patients

White matter abnormalities have been repeatedly reported in both schizophrenia and bipolar disorder (BD) in diffusion tensor imaging (DTI) studies, but the empirical evidence about the diagnostic specificity of white matter abnormalities in these disorders is still limited. This study sought to investigate the alterations in fractional anisotropy (FA) in white matter throughout the entire brain of patients from Chengdu, China with paranoid schizophrenia and bipolar mania. For this purpose, DTI was used to assess white matter integrity in patients with paranoid schizophrenia (n=25) and psychotic bipolar mania (n=18) who had been treated with standard pharmacotherapy for fewer than 5 days at the time of study, as well as in normal controls (n=30). The differences in FA were measured by use of voxel-based analysis. The results show that reduced FA was found in the left posterior corona radiata (PCR) in patients with psychotic bipolar mania and paranoid schizophrenia compared to the controls. Patients with psychotic bipolar mania also showed a significant reduction in FA in right posterior corona radiata and in right anterior thalamic radiation (ATR). A direct comparison between the two patient groups found no significant differences in any regions, and none of the findings were associated with illness duration. Correlation analysis indicated that FA values showed a significant negative correlation with positive symptom scores on the Positive and Negative Syndrome Scale in the left frontal-parietal lobe in the paranoid schizophrenia. It was concluded that common abnormalities in the left PCR might imply an overlap in white matter pathology in the two disorders and might be related to shared risk factors for the two disorders.

Measures of spinal canal stenosis and relationship to spinal cord structure in patients with cervical spondylosis

Spinal canal stenosis is often measured on anatomical magnetic resonance imaging (MRI) to estimate the degree of spinal cord compression. This study examined whether two quantitative measures of spinal canal stenosis taken from anatomical MRI are related to spinal cord white-matter integrity in patients with cervical spondylosis measured by diffusion tensor imaging (DTI). DTI and T2-weighted MRI of the cervical spinal cord were performed in 15 patients with cervical spondylosis and ten healthy control subjects of similar age. Severity of stenosis was calculated using Pavlov's ratio and the space-available-for-cord (SAC) technique. Patients had significantly lower Pavlov's ratios and SAC (C2-C3, C4-C5 and C6-C7), lower fractional anisotropy (FA; C2-C3 and C4-C5) and higher radial diffusivity (C2-C3, C4-C5 and C6-C7) than the controls. In patients, only Pavlov's ratio correlated with mean FA (R=0.66, P=0.008). Variations in Pavlov's ratio and FA also showed a similar pattern across cervical levels. Pavlov's ratio is a better predictor of spinal cord integrity than the SAC and, therefore, may be more relevant clinically for the evaluation of stenosis in patients with cervical spondylosis.

The phobic brain: white matter integrity in patients with spider phobia

Spider phobia is characterized by excessive and unreasonable fear and avoidance-behaviour when exposed to a phobic stimulus. Previous research suggests that visually elicited phobic reactions deactivate prefrontal areas involved in cognitive control over emotion-triggering areas like the amygdala. The fear mechanisms in specific phobias could be explained by microstructural abnormalities in white matter integrity and may contribute to the understanding of the occurrence of irrational anxiety symptoms. A diffusion tensor imaging (DTI) sequence was used to acquire images in 30 patients with spider phobia and 30 matched healthy control subjects. This study assess whether spider phobic patients show abnormalities in association with white matter fiber tracts compared to healthy controls. Mean diffusivity (MD) is a directionally averaged measure of diffusion; whereas, fractional anisotropy (FA) is a measure of how much the diffusion tensor deviates from the isotropic form (diffusion occurs equally in all directions). These measures are compared to specify regions of interest and investigate structural connectivity. Combining fMRI and DTI, the neuronal activation of the fear-related brain areas are used as seed points for probabilistic fiber tractography.

P02-344 - Assessment of white matter abnormalities in paranoid schizophrenia and bipolar mania patients from Chengdu, China

IntroductionWhite matter abnormalities have been repeatedly reported in both schizophrenia and bipolar disorder (BD) diseases from diffusion tensor imaging (DTI) studies respectively, while the empirical evidences about the diagnostic specificity of white matter abnormalities in these disorders are still limited.Objectives25 patients with paranoid schizophrenia and 18 patients with bipolar mania were recruited from the in-patient unit of the Mental Health Centre, West China Hospital, China.Patients were diagnosed according to the criteria of Diagnostic and Statistical Manual of Mental Disorders-Version IV (DSM- IV). 30 healthy controls were recruited from the community by means of leaflets distributed throughout Chengdu city.AimsThis study sought to investigate the alterations in fractional anisotropy (FA) in white matter throughout the entire brain of patients from Chengdu, China with paranoid schizophrenia and bipolar mania.MethodsDiffusion tensor imaging (DTI) was used to assess white matter integrity in patients with paranoid schizophrenia and bipolar mania, as well as in normal controls. The differences in FA were measured by use of voxel-based analysis.ResultsReduced FA was found in the left posterior corona radiate (PCR) in patients with bipolar mania and paranoid schizophrenia compared to the controls. Patients with bipolar mania also showed a significant reduction in FA in right posterior corona radiate and in right anterior thalamic radiation (ATR).ConclusionsCommon abnormalities in the left PCR might imply an overlap in white matter pathology of both diseases and might be related to the shared risk factors for both disorders.

White matter hyperintensities and changes in white matter integrity in patients with Alzheimer’s disease

White matter hyperintensities (WMHs) are a risk factor for Alzheimer's disease (AD). This study investigated the relationship between WMHs and white matter changes in AD using diffusion tensor imaging (DTI) and the sensitivity of each DTI index in distinguishing AD with WMHs. Forty-four subjects with WMHs were included. Subjects were classified into three groups based on the Scheltens rating scale: 15 AD patients with mild WMHs, 12 AD patients with severe WMHs, and 17 controls with mild WMHs. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (D(R)), and axial diffusivity (D(A)) were analyzed using the region of interest and tract-based spatial statistics methods. Sensitivity and specificity of DTI indices in distinguishing AD groups from the controls were evaluated. AD patients with mild WMHs exhibited differences from control subjects in most DTI indices in the medial temporal and frontal areas; however, differences in DTI indices from AD patients with mild WMHs and AD patients with severe WMHs were found in the parietal and occipital areas. FA and D(R) were more sensitive measurements than MD and D(A) in differentiating AD patients from controls, while MD was a more sensitive measurement in distinguishing AD patients with severe WMHs from those with mild WMHs. WMHs may contribute to the white matter changes in AD brains, specifically in temporal and frontal areas. Changes in parietal and occipital lobes may be related to the severity of WMHs. D(R) may serve as an imaging marker of myelin deficits associated with AD.

Subtle gray matter changes involving medial temporo-parietal cortex associated to cardiovascular risk factors: A possible link to Alzheimer's disease

Battery (Ganguly et al 1996), Everyday Abilities Scale for India (Fillenbaum et al 1999) was administered on subjects.Ten ml of venous blood was collected, genomic DNA extracted, and genotyping done at apolipoprotein-E locus according to standard procedure. The DTI images were obtained on the Philips 3T Archieva MRI scanner. Fractional Anisotropy (FA) maps were extracted using FSL-FDT software package. Voxel based morphometric (VBM) analysis was performed on the FA maps using study specific custom template by applying two sample t-test, at significance level of p 1⁄4 0.001 with threshold masking of 0.2 on white matter segmented FA maps using Statistical Parametric Mapping (SPM) 5 version. Results: Between patients with AD and controls the areas of significant difference was noticed in bilateral temporal lobes, bilateral limbic lobe, Left insula, uncus, amygdala & parahippocampal regions and Right posterior cingulate region. Bilateral temporal lobe and right subgyral parietal lobe area was differing between APOE e4 carrier and non-carrier AD patients. Conclusions: Patients with AD have abnormalities in white matter tracts in regions of temporal lobe compared to controls. Apo E4 carrier status is associated with structural changes in white matter integrity in patients with AD. Findings indicate the need for further study using VBM approach in white matter tracts of patients with AD and apoE4 allele.

PW01-43 - White matter integrity in social anxiety disorder - a diffusion tensor imaging study

ObjectivesSocial anxiety disorder (SAD) is characterized by anxiety in situations in which one may be evaluated or be in focus of attention by others. Functional neuroimaging studies revealed hyperactivity of the amygdala in response to social cues like faces in patients with SAD. To date, little is known about the neuroarchitecture of SAD. We hypothesized structural alterations in white matter regions projecting to or from the amygdala such as the uncinate fasciculus.MethodsDiffusion tensor imaging (DTI) was applied in 26 patients with SAD and 24 healthy controls (HC). White matter integrity was assessed by fractional anisotropy (FA), a measure of fiber coherence and integrity. In addition, individual scores of trait anxiety were correlated voxel-wise with FA values.ResultsPatients with SAD showed reduced global mean FA across the whole brain and locally in regions near the left amygdala, thalamus, cerebellum, cingulate cortex/corpus callosum, and in the corticospinal tract. Furthermore, trait anxiety correlated negatively with FA in a similar region as in the group comparison near the left amygdala, probably representing the left uncinate fasciculus.ConclusionsReduced white matter integrity in patients with SAD was found globally as well as locally in different brain regions. The region near the left amygdala/uncinate fasciculus was the only one yielding significance in both the FA group comparison and voxel-wise correlation with trait anxiety. This points to a functional role of this fiber tract in anxiety and emotion regulation, for instance in top-down inhibition of the amygdala by the frontal cortex.