Alteration of fractional anisotropy and apparent diffusion coefficient in obsessive-compulsive disorder: a diffusion tensor imaging study

BACKGROUND: Abnormalities of fractional anisotropy (FA) have been reported in previous diffusion tensor imaging (DTI) studies in patients with obsessive-compulsive disorder (OCD). However, there are some inconsistencies in the results and the apparent diffusion coefficient (ADC) has not been investigated. The goal of this study was to investigate white matter abnormalities and water diffusivity, as reflected by FA and ADC, using DTI in patients with OCD. METHODS: Fifteen patients with OCD and 15 healthy volunteers underwent DTI. Voxelwise analysis was used to compare FA in white matter and ADC in gray matter/white matter of the two groups. RESULTS: Compared with healthy volunteers, the patients had higher FA in the bilateral semioval center extending to the subinsular white matter; and a higher ADC in the left medial frontal cortex. There were no areas with a significantly lower FA or ADC in patients compared with healthy volunteers. CONCLUSIONS: A significantly higher FA was found in regions associated with the emotion of disgust and a trend for a higher ADC was found in a region associated with the regulation of emotions. These findings suggest that neurocircuits involved in disgust processing may play an important role in the pathophysiology of OCD.     

常规磁共振与弥散性磁共振检查对多发性硬化的诊断价值

目的：比较常规磁共振（MRI）检查和弥散磁共振（MR－DWI）检查技术对判定脑内多发性硬化（MS）的价值。方法：经临床表现与实验室检查明确MS的病例有26例行MRI扫描,T1,T2加权及质子密度像,MRDWI用平面回波成像技术,将两者所见进行比较,同时使用软件进行MRI－DWI的弥散系数（apparent diffusion coefficient ADC)值及影像分析。结果：MRI扫描在T2W1像上可见明确T2高信号及高质子密度者占25／26,脑室旁白质为主占病灶总数的83％,T1W1表现为低信号者占16／26,可见急性期发作的病灶均有不同程度的强化,96．5％是多病灶的,MR－DWI示发病早期12例可见高信号,ADC值高于脑缺血但低于脑肿瘤,结论：使用多种MRI技术可以明确判定脑内白质区的MS病灶是急性期还是非急性期。同时应用MR－DWI,ADC图检查对判断病灶是脑缺血性病灶或肿瘤有较大帮助,是诊断MS等脱髓鞘疾病的有效影像学方法。     

Tenascin-R and C in multiple sclerosis lesions: relevance to extracellular matrix remodelling

In the present study the distribution of the inhibitory extracellular molecules tenascin-R (TN-R) and tenascin- C (TN-C) was examined by immunocytochemistry during evolution of the multiple sclerosis (MS) lesion, in which astrogliosis is a prominent feature. Sections were cut from five control cases and from 22 blocks containing lesions representing different pathological stages in 18 cases of secondary progressive MS. Widespread expression of TN-R was found in the normal human central nervous system (CNS), while that of TN-C was in general restricted to white matter. In acute MS plaques however, there was a similar striking loss of both TN-R and TN-C up to the edge of the lesion, where the macrophage density is greatest, extending into the apparently normal white matter. In subacute lesions a TN-C and/or TN-R-immunopositive reactive astrocyte subpopulation was prominent, reflecting synthesis of extracellular matrix molecules. Both tenascins were expressed throughout chronic MS plaques at levels similar to those seen in adjacent white matter. The loss of TN-R and TN-C in acute plaques is indicative of enzyme-mediated breakdown of the matrix which may be a marker of blood-brain barrier breakdown and leucocyte extravasation. Subsequent production of tenascins by reactive astrocytes may result in glial scar formation impeding remyelination and axonal repair in MS lesions.     

Age-related white matter lesions are associated with reduction of the apparent diffusion coefficient in the cerebellum

Cerebellar apparent diffusion coefficient (ADC) was found to be increased after acute cerebral hemispheric stroke. There are no data on cerebellar ADC changes in patients with chronic, age-related white matter lesions (ARWML). We aimed to determine longitudinal ADC variations on cerebral hemispheric and cerebellar white matter regions of patients with ARWML in order to study relations between ADC changes in both regions. ADC was measured serially (1-year interval) on lesioned periventricular frontal white matter, frontal and parietoccipital normal appearing white matter and middle cerebellar peduncles, on 19 aged patients with ARWML, which also underwent gait assessment. We compared regional ADC at 0 and 1 year and calculated variation percentages for each region. Correlation analysis was made between ADC variation in cerebellar regions and in contralateral hemispheric regions and between cerebellar ADC at 1 year and walking speed. After 1 year, ADC was higher on lesioned periventricular frontal white matter and lower on cerebellar regions. ADC variations on these regions were negatively correlated. Cerebellar ADC measured after 1 year was positively correlated with walking speed. This suggests a link between vascular disease progression inside frontal lesions and ADC reduction in contralateral cerebellar peduncles. Chronic ischemia in frontal white matter could have interrupted frontal-cerebellar circuits, producing hypometabolism in cerebellar regions (and worse performance on motor tasks), decreased perfusion and hence ADC reduction.     

Changes within the "normal" cerebral white matter of multiple sclerosis patients during acute attacks and during high-dose cortisone therapy assessed by means of quantitative MRI.

Changes in the apparently unaffected cerebral white matter of multiple sclerosis (MS) patients were studied during acute attacks as well as during high-dose prednisolone therapy. Serial MR scans of patients with a clinically definite diagnosis were performed on four defined occasions: before an episode, within three days after its onset, after 10 days of therapy as well as four weeks later. Thirteen patients agreed to cooperate in forming a MRI data base and to be rescanned immediately after the onset of an acute relapse. Within one year, six patients had such episodes, one of them had a second bout. Both T1 and T2 relaxation times within the apparently normal white matter were significantly prolonged in all cerebral lobes compared to a control group of healthy volunteers. During the acute attacks as well as during therapy the T1 values remained as before. The T2 values were elevated only in two out of six cases during the episode. After therapy a considerable clinical improvement was seen in all cases, but a significant T2 decrease as a possible effect of cortisone was noted in only one case. We conclude that the prolonged relaxation times T1 and T2 within the apparently normal cerebral white matter of MS patients are the result of a number of molecular events differing considerably among individual patients and that serial measurements of these relaxation times do not consistently change during an acute relapse and do not reflect clinical improvement after high dose prednisolone therapy.     

White matter abnormalities in first-episode schizophrenia or schizoaffective disorder: a diffusion tensor imaging study

OBJECTIVE: The goal of this study was to investigate brain white matter abnormalities by using diffusion tensor imaging in patients with schizophrenia or schizoaffective disorder close to illness onset. METHOD: Ten patients experiencing a first episode of schizophrenia or schizoaffective disorder and 13 healthy volunteers received diffusion tensor imaging and structural magnetic resonance imaging examinations. Voxel-wise analysis was used to compare fractional anisotropy maps in the white matter of the two groups following intersubject registration to Talairach space. RESULTS: Compared with healthy volunteers, patients demonstrated lower fractional anisotropy in the left internal capsule and left-hemisphere white matter of the middle frontal gyrus and posterior superior temporal gyrus. There were no areas of significantly higher fractional anisotropy in patients compared with healthy volunteers. CONCLUSIONS: These findings suggest that white matter pathology is present early in the course of schizophrenia and may be less pronounced than has been found in previous diffusion tensor imaging studies of patients with chronic illness. Further, these data are consistent with hypotheses regarding frontotemporal dysfunction and the failure of left-hemisphere lateralization in the pathophysiology of schizophrenia.     

多发性硬化患者MRI扩散张量成像脑白质束示踪的三维仿真定量研究

目的 研究多发性硬化(MS)患者脑白质束示踪的三维仿真影像表现,评价其定量结果与残疾状态扩展评分(EDSS)的相关性. 方法 对28例MS患者(MS组)和28名健康自愿者(对照组)通过MRI扩散张量成像扫描进行脑白质束示踪,测量示踪纤维数和示踪纤维密度,并应用配对t检验比较两组间差异;对MS组脱髓鞘斑块、正常表现脑白质和对照组感兴趣区的ADC值和FA值进行方差分析,使用线性回归模型计算MS组脑白质束示踪的定量结果与EDSS评分的相关性. 结果 在MS组脑白质束示踪三维仿真图像中可直接观察到脑白质束的受损和减少.MS组的示踪纤维数(2220±100)和示踪纤维密度(0.75±0.04)明显低予对照组(2750±70、0.93±0.02),差异有统计学意义(P＜0.05).MS组脱髓鞘斑块、正常表现脑白质和对照组感兴趣区的ADC值依次下降,分别为(1.23 ±0.13)× 10-3 mm2/s、(0.76±0.09)× 10-3 mm2/s、(0.63 ±0.10)×10-3 mm2/s; FA值依次升高,分别为0.24±0.04、0.42±0.07、0.48±0.06,差异均有统计学意义(P＜0.05).MS组示踪纤维数和示踪纤维密度都与EDSS评分呈负相关关系(r=-0.782,P=0.000;r=-0.771,P=0.000). 结论 通过MRI扩散张量成像扫描进行脑白质束示踪可以发现MS患者脑白质束的受损情况,其较常规MRI能提供更多的空间信息.     

Lower Orbital Frontal White Matter Integrity in Adolescents With Bipolar I Disorder

ObjectiveTo examine white matter microstructure, as assessed via diffusion tensor imaging (DTI), in adolescents with bipolar I disorder compared with control volunteers.MethodTwenty-six (12 male and 14 female subjects) adolescents (mean age, 16.0 years) with bipolar I disorder and 26 (14 male and 12 female subjects) control volunteers (mean age, 15.3 years) completed structural and DTI examinations. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) maps were compared between groups in the brain white matter using a voxelwise analysis after intersubject registration to Talairach space. Exploratory analyses were performed to assess structure-function correlations in a subgroup of 11 patients with available neuropsychological measures.ResultsCompared with the control volunteers, the patients demonstrated abnormalities in white matter regions predicted to differ a priori between groups, including lower FA in the right orbital frontal lobe and higher ADC in the right and left subgenual region (p < .005, uncorrected; cluster size ≥ 100). There were no areas of higher FA or lower ADC in patients compared with control volunteers. Lower FA across regions that differed significantly between groups correlated significantly with slower visuomotor speed among patients with bipolar disorder.ConclusionsAbnormalities involving the orbital frontal and subgenual white matter in adolescents with bipolar disorder are consistent with neurobiological models that implicate dysregulation of affective systems and impulsivity in the pathophysiology of the disorder. Preliminary findings suggest that white matter abnormalities in pediatric bipolar disorder have functional correlates and may be useful in constructing neurobiological models of the disorder.     

Diffusion-weighted imaging in multiple sclerosis

Diffusion-weighted imaging (DWI) provides a unique form of magnetic resonance (MR) contrast that enables the diffusional motion of water molecules to be quantitatively measured. As a consequence, DWI provides information about the orientation, size and geometry of brain structures. Cellular structures in the central nervous system restrict water molecular motion, and the apparent diffusion coefficient (ADC) is reduced compared to diffusion in bulk water. Pathological processes that modify tissue integrity, thus removing some of the “restricting” barriers, can result in increased ADC. Preliminary studies in multiple sclerosis (MS) using DWI showed that the ADC is higher in macroscopic lesions than in the normal appearing white matter (NAWM). The ADC is also dependent on the direction in which diffusion is measured, thus making comparison of ADC values meaningless without taking into account the measurement direction. One measurement of diffusion that is independent of the orientation of structures is provided by measuring the ADC in three orthogonal directions, and then averaging the results to form the mean diffusivity, \({\overline D}\). We obtained DW scans from 35 patients with relapsing-remitting MS and 24 healthy volunteers. \({\overline D}\) was measured inside T2-visible lesions and regions located in different areas of the NAWM. \({\overline D}\) histograms from a large portion of the brain were created. MS lesions had a significantly higher \({\overline D}\) than NAWM. T1-hypointense lesions had the highest diffusion values, consistent with more severe tissue disruption. \({\overline D}\)was higher in the NAWM from patients than in the white matter from healthy controls. We also found significant differences between \({\overline D}\) histogram-derived measures from patients and controls, confirming the presence of diffuse damage in the brain of patients with MS.     

Abnormal ubiquitination of axons in normally myelinated white matter in multiple sclerosis brain

The hallmark of the lesions in multiple sclerosis (MS) is inflammatory demyelination with sparing of axons. Recent neuropathological and neuroradiological investigations show that structural changes of the axons occur, both in plaques and in the normal appearing white matter. A better understanding of the axonal damage in MS is important, since this may be responsible for permanent disability. We have investigated the immunoreactivity for ubiquitin, a sensitive method to detect axonal dystrophy and accumulation of abnormal proteins in pathological conditions of the nervous system, in the brains of six cases of MS (age range 39-66 years). Tissue blocks were fixed in formalin and embedded in paraffin. A panel of antibodies was used: anti-ubiquitin, anti-neurofilament (SMI-31 + SMI-32), anti-amyloid precursor protein and anti-PGP9.5. We focused our attention on chronic plaques, recognized by the absence of Luxol Fast Blue B-positive inclusions in macrophages. SMI-31 + SMI-32 showed the presence of a variable amount of axons within the plaques; the axonal network within the plaques was looser than outside. No ubiquitin reactivity was present in chronic plaques. In the normally myelinated white matter surrounding the plaques, a dense granular ubiquitin immunoreactivity was found both near and far from the plaque edge. No similar staining was found in control brains. Ubiquitination is the first step of a non-lysosomal degradation pathway of proteins. The present findings suggest a derangement of this proteolytic pathway in the axons outside the plaques, possibly as a consequence of chronic absence of myelin in the axonal segment inside the plaque. The spectrum of axonal changes in MS appears to be wider than expected and involves the apparently normal white matter.     

A magnetization transfer imaging study of the brain in patients with migraine

The authors evaluated the magnetization transfer ratio (MTR) of T2 lesions, normal-appearing white matter (NAWM), and brain from 39 migraineurs, 17 healthy volunteers, and 22 patients with MS. Migraineurs had NAWM and brain MTR values similar to those of normal subjects but significantly higher than those of MS patients. Average lesion MTR values also were significantly lower in MS patients than in migraineurs. In patients with migraine, other etiologies should be considered in the presence of tissue damage beyond that seen on T2-weighted scans.     

Cognitive function correlates with frontal white matter apparent diffusion coefficients in patients with leukoaraiosis

Background and aims Diffusion weighted imaging (DWI) displays a high sensitivity to white matter changes, even in areas where no lesions are visible. Correlation with vascular risk factors and cognitive dysfunction seems to be feasible using this technique. We aimed to test relations between age, blood pressure and cognitive function,with lesion load and average Apparent Diffusion Coefficient (ADC) values in lesioned (LWM) and in normal appearing white matter (NAWM), in patients with age related white matter lesions (ARWML). Methods Subjects were 29 patients (mean age 72.6 ± 5.2 years) with different severity of ARWML on MRI and no (or mild) disability assessed by the Instrumental Activities of Daily Living Scale. Imaging lesion load was quantified in bilateral frontal, temporal, parieto-occipital, basal ganglia and infratentorial regions, using a simple visual rating scale; ADC was measured bilaterally in Regions of Interest in parieto-occipital and frontal NAWM, and in frontal periventricular LWM. Neuropsychological examination consisted of Raven Colored Progressive Matrices, Rey’s Complex Figure, Digit Canceling. Symbol digit Substitution, Inverse Digit Repetition and Verbal Fluency tests. Results Visual scales scores and ADC were significantly higher in frontal and parieto-occipital regions. Both were significantly correlated to age and blood pressure, in frontal (visual scale scores and ADC) and parieto-occipital regions (ADC). Attention skills were negatively correlated to ADC in LWM and NAWM in frontal regions and with frontal region visual scale scores. Conclusion Our findings suggest that severity of white matter ischemic changes is correlated with worse cognitive function, as well as advanced age and higher blood pressure.A higher vulnerability of frontal white matter to vascular disease seems to play an important role in executive dysfunction, mainly determined by impairment of attentional skills.DWI results suggest this could be true even for NAWM.     

Magnetic resonance spectroscopy of memory and frontal brain region in early multiple sclerosis

In vivo proton magnetic resonance spectroscopy (1H-MRS) has been used to assess biochemical changes that occur in demyelinating lesions and in normal appearing white matter (NAWM) in multiple sclerosis (MS) patients. N-acetylaspartate (NAA) levels in MS patients may indicate neural viability. In early stages of MS, patients may suffer from slight cognitive impairment. The objective of this study was to investigate memory function in relation to biochemical properties of frontal brain areas of MS patients. Twenty-one patients with relapsing-remitting MS and 21 healthy comparison subjects were examined psychometrically using the Wechsler Memory Scale (WMS) and the Multiple Sclerosis Functional Composite (MSFC) scale, and (1H-MRS) was used to examine frontal deep white matter (left hemisphere) and the frontal cingulate gyrus (Brodmann areas 24/32, bihemispheric). A significant reduction of the NAA/Creatine (Cr) ratio in the frontal cingulate gyrus among the MS patient group was detected when compared to healthy subjects. A significant decrease in the NAA/Cr ratio was also found in volumes of cerebral deep white matter, including plaques, in the MS patients. No NAA/Cr ratio changes were found in NAWM. Differences in MSFC results did not reach statistical significance, but the WMS general memory score showed a significant statistical difference between the patient group and healthy subjects. Regression analysis showed the gray matter NAA/Cr ratio of the frontal cingulate gyrus to be significantly related to distinct memory functions. The authors conclude that (1H-MRS) of gray matter in early stages of MS may be pertinent in the detections of early metabolic disturbances, particularly in subjects with or without minor neurological impairment. Findings suggest a general relationship between the metabolic status of the frontal cortices and memory function.     

An examination of MS candidate genes identified as differentially regulated in multiple sclerosis plaque tissue, using absolute and comparative real-time Q-PCR analysis

In our laboratory, we have developed methods in real-time detection and quantitative-polymerase chain reaction (Q-PCR) to analyse the relative levels of gene expression in post mortem brain tissues. We have then applied this method to examine differences in gene activity between normal white matter (NWM) and plaque tissue from multiple sclerosis (MS) patients. Genes were selected based on their association with pathology and through identification by previously conducted global gene expression analysis. Plaque tissue was obtained from secondary progressive (SP) patients displaying chronic active, as well as acute pathologies; while NWM from the same location was obtained from age- and sex-matched controls (normal patients). In this study, we used both SYBR Green I supplementation and commercially available mixes to assess both comparative and absolute levels of gene activity. The results of both methods compared favourably for four of the five genes examined (P < 0.05, Pearsons), while differences in gene expression between chronic active and acute pathologies were also identified. For example, a >50-fold increase in osteopontin (Spp1) and inositol 1-4-5 phosphate 3 kinase B (Itpkb) levels in acute plaques contrasted with the 5-fold or less increase in chronic active plaques (P < 0.05, unpaired t test). By contrast, there was no significant difference in the levels of the MS marker and calcium-dependent protease (Calpain, Capns1) in MS plaque tissue. In summary, Q-PCR analysis using SYBR Green I has allowed us to economically obtain what may be clinically significant information from small amounts of the CNS, providing an opportunity for further clinical investigations.     

Regional differences in diffusion abnormality in cerebral white matter lesions in patients with vascular dementia of the Binswanger type and Alzheimer''s disease

We investigated changes in water diffusion in the cerebral white matter of 14 patients with vascular dementia of the Binswanger type (VDBT) and ten patients with Alzheimer's disease (AD) with periventricular hyperintensity (PVH) lesions using diffusion-weighted magnetic resonance imaging (MRI) and studied the pathophysiological differences between white matter lesions found in these two conditions. Apparent diffusion coefficients (ADCs) in the anterior and posterior white matter and the genu and splenium of the corpus callosum were significantly higher in both groups of patients than in the 12 age-matched controls, and ADC values in VDBT and AD groups were almost the same. ADC ratios, defined as diffusion restricted perpendicular to the direction of nerve fibers, were also significantly higher in the patients than in the control subjects. However, there were regional differences in ADC ratios in the two conditions, with ratios in VDBT being higher in the anterior portions of the white matter but ratios in AD were higher in the posterior portions. The diffusion-weighted MRI technique may be useful in the differential diagnosis of VDBT and AD with white matter lesions.     

Proliferating oligodendrocytes are present in both active and chronic inactive multiple sclerosis plaques

The proliferation marker Ki-67 labels cell nuclei in the G(1), S, M, and G(2) phases of the cell cycle. We used Ki-67 immunohistochemistry to quantify proliferating glial cells in brain tissue sections from twenty-four patients, comprised of multiple sclerosis, normal brains, and other neurological disease controls. Glial proliferation was greatly increased in MS lesions when compared with control brain white matter. Both actively demyelinating/early remyelinating plaques and chronic inactive plaques of long standing often displayed large numbers of glial cells in the proliferative cycle. The bulk of these proliferating cells were of oligodendroglial lineage in the MS plaques. Ki-67 positive macrophage/microglial lineage cells were largely restricted to acute lesions. The finding of increased numbers of proliferating oligodendroglia in most MS plaques, regardless of disease duration or activity state, indicates that the MS brain is capable of recruiting unexpectedly large numbers of new oligodendrocytes over long periods of time. The factors within the MS plaque microenvironment that provoke new oligodendrocyte generation and their subsequent loss still need to be identified.     

White matter abnormalities in early-onset schizophrenia: a voxel-based diffusion tensor imaging study

OBJECTIVE: To investigate abnormalities in the structural integrity of brain white matter as suggested by diffusion tensor imaging in adolescents with early-onset schizophrenia (onset of psychosis by age 18). METHOD: Twenty-six patients with schizophrenia and 34 age- and gender-matched healthy volunteers received diffusion tensor imaging and structural magnetic resonance imaging examinations. Fractional anisotropy maps were compared between groups in the white matter using a voxelwise analysis after intersubject registration to Talairach space. RESULTS: Compared with healthy volunteers, patients demonstrated lower fractional anisotropy values in the left anterior cingulate region in close proximity to the caudate nucleus (95% confidence interval of schizophrenic-healthy: -66 to -20). Using regression analysis, the rate of change in fractional anisotropy differed significantly between groups in this region across the age span examined (10-20 years), after adjusting for group differences in premorbid intellectual capacity and parental socioeconomic status. There were no areas of significantly higher fractional anisotropy in patients compared with healthy volunteers. CONCLUSIONS: These data suggest that early-onset schizophrenia is associated with a disruption in the structural integrity of white matter tracts in the anterior cingulate region. These structural abnormalities may contribute to the deficits in motivation, attention, memory, and higher executive functions in adolescents with schizophrenia.     

Lipocalin-type prostaglandin D synthase (beta-trace) is upregulated in the alphaB-crystallin-positive oligodendrocytes and astrocytes in the chronic multiple sclerosis

Lipocalin-type prostaglandin D synthase (L-PGDS), which is mainly synthesized in leptomeningeal cells and oligodendrocytes (OLs) in rodents and humans, is secreted into the human cerebrospinal fluid (CSF) as beta-trace. L-PGDS protects OLs and neurones against apoptosis in twitcher mice, a murine model of Krabbe's disease, and is the second only to a stress protein, alphaB-crystallin, as the most abundant gene product upregulated in the demyelinating focus of multiple sclerosis (MS). Here we report that although the CSF level of L-PGDS is not increased in MS patients, L-PGDS is increased in the white matter of MS patients, especially in the shadow plaque as compared with the normal white matter. L-PGDS immunoreactivity was intensely expressed in OLs within the shadow plaques and in hypertrophied astrocytes within the chronic plaques of MS patients. Both L-PGDS-positive OLs and astrocytes expressed a stress protein, alphaB-crystallin. These results suggest that the upregulation of L-PGDS occurs in OLs and astrocytes as a stress reaction.     

White matter abnormalities in obsessive-compulsive disorder: a diffusion tensor imaging study

CONTEXT: Several neurobiological models of obsessive-compulsive disorder (OCD) posit a primary role for dysfunction of the anterior cingulate gyrus. Both functional and structural neuroimaging studies have implicated anterior cingulate gray matter abnormalities in the pathophysiology of OCD, but there has been little investigation of the anterior cingulate white matter in this disorder. OBJECTIVE: To test the hypothesis that patients with OCD have abnormal white matter microstructure in the anterior cingulate gyrus compared with healthy volunteers as inferred from diffusion tensor imaging. Additional analyses examined group differences in white matter integrity across the entire brain. DESIGN, SETTING, AND PARTICIPANTS: Fifteen patients with a DSM-IV diagnosis of OCD and 15 healthy volunteers matched for age, sex, and handedness underwent diffusion tensor imaging and structural magnetic resonance imaging examinations. Fractional anisotropy (FA), a robust intravoxel measure of water self-diffusion, was compared between groups on a voxel-by-voxel basis in the anterior cingulate white matter after standardization in Talairach space. MAIN OUTCOME MEASURES: Clinical ratings of symptom severity (ie, Yale-Brown Obsessive-Compulsive Scale) and FA. RESULTS: Compared with healthy volunteers, patients demonstrated significantly lower FA bilaterally in 3 areas of the anterior cingulate gyrus white matter. Additional analyses conducted across the rest of the brain white matter revealed lower FA bilaterally in the parietal region (supramarginal gyri), right posterior cingulate gyrus, and left occipital lobe (lingual gyrus). No areas of significantly higher FA were observed in patients compared with healthy volunteers. Lower FA in the parietal region correlated significantly with higher Yale-Brown Obsessive-Compulsive Scale scores. CONCLUSIONS: These preliminary findings provide evidence of an abnormality that involves the anterior cingulate white matter in the pathogenesis of OCD and are consistent with neurobiological models that posit a defect in connectivity in the anterior cingulate basal ganglia-thalamocortical circuit. White matter abnormalities in other brain regions may also be implicated in the neurobiology of OCD.