Fractional Anisotropy In Patients Research Articles

Machine learning based on functional and structural connectivity in mild cognitive impairment

ObjectiveAlzheimer's disease (AD) is a chronic, degenerative neurological disorder characterized by progressive cognitive decline and mental behavioral abnormalities. Mild cognitive impairment (MCI) is regarded as a transitional stage in the progression from normal elderly individuals to patients with AD. While studies have identified abnormalities in brain connectivity in patients with MCI, including functional and structural connectivity, accurately identifying patients with MCI in clinical screening remains challenging. We hypothesized that utilizing machine learning (ML) based on both functional and structural connectivity could yield meaningful results in distinguishing between patients with MCI and normal elderly individuals, so as to provide valuable information for early diagnosis and precise evaluation of patients with MCI. MethodsFollowing clinical criteria, we recruited 32 patients with MCI for the patient group, and 32 normal elderly individuals for the control group. All subjects underwent examinations for resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI). Subsequently, significant functional and structural connectivity features were selected and combined with a support vector machine for classification of the patient and control groups. ResultsWe observed significantly different functional connectivity in the frontal lobe and putamen between the MCI group and normal controls. The results based on functional connectivity features demonstrated a classification accuracy of 71.88% and an area under the curve (AUC) value of 0.78. In terms of structural connectivity, we found that decreased fractional anisotropy in patients with MCI was significantly associated with Montreal Cognitive Assessment scores, specifically in regions such as the precuneus and cingulate gyrus. The classification results using the structural connectivity feature yielded an accuracy of 92.19% and an AUC value of 0.99. Lastly, combining functional and structural connectivity features resulted in a classification accuracy and AUC value of 93.75% and 0.99, respectively. ConclusionsIn this study, we demonstrated a high classification performance, underscoring the potential of both brain functional and structural connectivity in distinguishing patients with MCI from normal elderly individuals. Furthermore, the integration of functional connectivity and structural connectivity features indicated that utilizing rs-fMRI and DTI could enhance the accuracy and specificity of identifying patients with MCI compared with relying on a single neuroimaging technique.

Outcome Prediction by Combining Corticospinal Tract Lesion Load with Diffusion-tensor Fractional Anisotropy in Patients after Hemorrhagic Stroke.

The objective of this study was to evaluate the predictive precision of combining the corticospinal tract lesion load (CST-LL) with the diffusion-tensor fractional anisotropy of the corticospinal tract (CST-FA) in the lesioned hemispheres regarding motor outcomes. Patients with putaminal and/or thalamic hemorrhage who had undergone computed tomography (CT) soon after onset in our hospital were retrospectively enrolled. The CST-LL was calculated after registration of the CT images to a standard brain. Diffusion-tensor imaging was performed during the second week after onset. Standardized automated tractography was employed to calculate the CST-FA. Outcomes were assessed at discharge from our affiliated rehabilitation facility using total scores of the motor component of the Stroke Impairment Assessment Set (SIAS-motor total; null to full, 0 to 25). Multivariate regression analysis was performed with CST-LL and CST-FA as explanatory variables and SIAS-motor total as a target value. Twenty-five patients participated in this study. SIAS-motor total ranged from 0 to 25 (median, 17). CST-LL ranged from 0.298 to 7.595 (median, 2.522) mL, and the lesion-side CST-FA ranged from 0.211 to 0.530 (median, 0.409). Analysis revealed that both explanatory variables were detected as statistically significant contributory factors. The estimated t values indicated that the contributions of these two variables were almost equal. The obtained regression model accounted for 63.9% of the variability of the target value. Incorporation of the CST-LL with the lesion-side CST-FA enhances the precision of the stroke outcome prediction model.

The shared white matter developmental trajectory anomalies of attention-deficit/hyperactivity disorder and autism spectrum disorders: A meta-analysis of diffusion tensor imaging studies

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) show common brain area abnormalities, which may contribute to the high shared co-occurrence symptoms and comorbidity of the two disorders. However, neuroanatomic anomalies in neurodevelopmental disorders may change over the course of development, and the developmental variation of these two disorders is unclear. Our study conducted a systematic literature search of PubMed, Web of Science, and EMBASE databases to identify disorder-shared abnormalities of white matter (WM) from childhood to adulthood in ADHD and ASD. 28 ADHD and 23 ASD datasets were included in this meta-analysis and were analysed by AES-SDM to detect differences in fractional anisotropy in patients compared to typically developing individuals. Our main findings reveal the variable WM developmental trajectories in ADHD and ASD respectively, and the two disorders showed overlapping corpus callosum tract abnormalities in their development from children to adults. Furthermore, the overlapping abnormalities of the corpus callosum tract increased with age, which may be related to their gradually increasing shared symptoms and comorbidity in these two disorders.

Thalamic structural connectivity profiles in blepharospam/Meige’s syndrome

BackgroundBlepharospasm is a debilitating focal dystonia characterized by involuntary eyelid spasms that can be accompanied by oromandibular muscle involvement (Meige’s syndrome). Frequently observed abnormality in functional neuroimaging hints at an important position of the thalamus, that relays involved cortico-basal ganglia-cortical and cortico-cerebello-cortical circuits, within the abnormal network in blepharospasm. ObjectiveTo characterize abnormal cortico-thalamic structural/streamline connectivity (SC) patterns in the disease, as well as their potential co-occurrence with abnormal subcortico-thalamo-cortical projections using diffusion tractography. MethodsDiffusion imaging was obtained in 17 patients with blepharospasm (5 with mild lower facial involvement) and 17 healthy controls. Probabilistic tractography was used for quantification of SC between six cortical regions and thalamus, and voxel-level thalamic SC mapping as well as evaluation of the thalamic SC distributions’ topography by center-of-gravity analysis was performed. Post-hoc, correlations of SC with clinical parameters were evaluated. Further, white matter integrity was investigated within representative segments of the dentato-thalamo-cortical and pallido-thalamo-cortical tract. ResultsConnectivity mapping showed significant reduction of right (pre)motor- and left occipital-thalamic SC, as well as a topographic shift of the left occipital-thalamic SC distribution in patients. Significant positive correlation of occipital-thalamic SC with disease severity was found. Post-hoc analysis revealed significantly reduced mean fractional anisotropy in patients within the dentato-thalamo-cortical trajectory connecting to right (pre)motor and left occipital cortex. ConclusionAbnormal occipital/motor SC provides evidence for dysfunction of the thalamus-relayed visual and motor network as a key aspect in the disease. Concurrent impairment of microstructural integrity within the dentato-thalamic trajectories targeting those cortices hints at cerebellar contribution.

Uncinate Fasciculus in Temporal Lobe Epilepsy

Background and purpose: Temporal lobe epilepsy is the most common focal intractable epilepsy. Uncinate fasciculus is a white fiber bundle that connects the orbitofrontal cortex with the anterior temporal lobe, and is implicated in most of the superior mental functions. There is evidence of uncinate fasciculus as a propagation pathway of seizures from temporal lobe. The aim of the study is to determine uncinate fasciculus alterations in patients with temporal lobe epilepsy, through fractional anisotropy. Methods: Thirty-three patients with temporal lobe epilepsy (10 right and 23 left) were studied. All of them were right-handed and had left hemisphere dominance for language. A 1.5 T MR imaging scanner was used to obtain diffusion tensor imaging (DTI). Fractional anisotropy of uncinate fasciculus was calculated through TBSS (Tract Based Spatial Statistics). Statistical analysis was done using IBM SPSS (v. 25). Results: Fractional anisotropy was higher in right uncinate fasciculus, regardless of epilepsy side. Right uncinate fasciculus, at the insula level, showed lower fractional anisotropy in patients with right temporal lobe epilepsy. Conclusions: Results support the evidence of uncinate fasciculus as a pathway of propagation in temporal lobe epilepsy, specially at insular level.

Cerebrospinal fluid biomarkers predict frontotemporal dementia trajectory.

ObjectiveThe prognostic value of cerebrospinal fluid neurofilament light chain, total tau, phosphorylated tau181, and amyloid beta1‐42 was examined in frontotemporal dementia subtypes.MethodsWe compared baseline biomarkers between 49 controls, 40 patients with behavioral variant frontotemporal dementia, 24 with semantic variant primary progressive aphasia, and 26 with nonfluent variant primary progressive aphasia. Linear mixed effect models were used to assess the value of baseline biomarkers in predicting clinical and radiographic change in patient cohorts over multiple yearly follow up visits.ResultsNeurofilament light chain concentrations were lowest in controls. Elevated baseline neurofilament light chain predicted faster worsening in clinical severity, frontotemporal volume and frontotemporal fractional anisotropy in patients with behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. High total tau similarly predicted faster progression in nonfluent variant primary progressive aphasia. In behavioral variant frontotemporal dementia, higher phosphorylated tau181 predicted faster clinical progression whereas lower amyloid beta1‐42 predicted faster volumetric and fractional anisotropy reduction. Neurofilament light chain and phosphorylated tau181 were of greater predictive value in patients with tau pathology as compared to TDP‐43 pathology. Baseline neurofilament light chain correlated with baseline clinical severity and frontotemporal volume in behavioral variant frontotemporal dementia. Baseline total tau correlated with baseline clinical severity in semantic variant primary progressive aphasia.InterpretationHigh cerebrospinal fluid neurofilament light chain predicts more aggressive disease in behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. Total tau, phosphorylated tau181, and amyloid beta1‐42 also predict some measures of disease aggressiveness in frontotemporal dementia.

Microstructural white matter abnormalities in patients with COL6A3 mutations (DYT27 dystonia)

IntroductionRecently, mutations in the collagen gene COL6A3 have been reported in patients with autosomal-recessive, isolated dystonia (DYT27). Zebrafish models of COL6A3 mutations showed deficits in axonal targeting mechanisms. Therefore, COL6A3 mutations have been considered to contribute to irregular sensorimotor circuit formation. To test this hypothesis, we examined structural abnormalities in cerebral fiber tracts of dystonia patients with COL6A3 mutations using diffusion tensor imaging. MethodsWe performed a voxel-wise statistical analysis to compare fractional anisotropy within whole-brain white matter in four of the previously reported dystonia patients with COL6A3 mutations and 12 healthy controls. Region of interests-based probabilistic tractography was performed as a post-hoc-analysis. ResultsDystonia patients with COL6A3 mutations showed significantly decreased fractional anisotropy bilaterally in midbrain, pons, cerebellar peduncles, thalamus, internal capsule and in frontal and parietal subcortical regions compared to healthy controls. Tractography revealed a decreased fractional anisotropy in patients with COL6A3-associated dystonia between bilateral dentate nucleus and thalamus. ConclusionDiffusion tensor imaging demonstrates an altered white matter structure especially in various parts of the cerebello-thalamo-cortical network in dystonia patients with COL6A3 mutations. This suggests that COL6A3 mutations could contribute to abnormal circuit formation as potential basis of dystonia.

Gray matter abnormalities of the dorsal posterior cingulate in sleep walking

ObjectiveThis study aimed to determine whether voxel-based analysis of T1 weighted magnetic resonance imaging (MRI) and diffusion tensor imaging is able to detect alterations of gray and white matter morphometry as well as measures of mean diffusivity and fractional anisotropy in patients with non-rapid eye movement parasomnia. Methods3 Tesla MRI was performed in 14 drug-free, polysomnography-confirmed adult patients with non-rapid eye movement parasomnia (age: 29 ± 4.2 years; disease duration 19.2 ± 7.7 years) and 14 healthy subjects, matched for age and gender. Statistical parametric mapping was applied to objectively identify focal changes of MRI parameters throughout the entire brain volume. ResultsStatistical parametric mapping localized significant decreases of gray matter volume in the left dorsal posterior cingulate cortex (BA23) and posterior midcingulate cortex (BA24) in patients with non-rapid eye movement parasomnias compared to the control group (p < 0.001, corrected for multiple comparisons). No significant differences of mean diffusivity and fractional anisotropy measures were found between the non-rapid eye movement parasomnia group and the healthy control group. ConclusionsRecently, the simultaneous co-existence of arousal or wakefulness originating from the motor and cingulate cortices and persistent sleep in associative cortical regions was suggested as a functional framework of somnambulism. Gray matter volume decline in the dorsal posterior and posterior midcingulate cortex reported in this study might represent the neuroanatomical substrate for this condition.

Reduced fractional anisotropy in patients with major depressive disorder and associations with vascular stiffness.

Previous studies revealed several alterations of the cerebral white matter in patients with major depressive disorder. However, it is unknown if these alterations are associated with vascular changes in the brain and other body parts. We compared diffusion tensor imaging derived fractional anisotropy in a well characterized sample of middle-aged patients with major depressive disorder (n = 290) and never-depressed controls (n = 346) by the method of tract-based spatial statistics. Subsequently, the potential role of pulse wave velocity as a mediator of depression- and age-related changes in extracted estimates of fractional anisotropy were analyzed.The results of the tract-based analysis revealed significantly reduced fractional anisotropy in the left posterior thalamic radiation associated with depression. Analyses of extracted data indicated additional reductions of fractional anisotropy bilaterally in the posterior thalamic radiation and in the left sagittal stratum. The analyses of indirect effects did not show any significant mediation of depression-related effects on fractional anisotropy via pulse wave velocity. However, age-related effects on fractional anisotropy were partially mediated by pulse wave velocity.In conclusion, major depressive disorder is associated with detrimental effects on cerebral white matter microstructure properties which are independent of vascular changes, as measured by pulse wave velocity. However, a portion of age-related detrimental effects on white matter is explained by vascular changes. Longitudinal studies are required for investigating changes in white matter and vascular parameters over time and their association with incident depression.

Intrinsic functional connectivity of fronto-temporal networks in adolescents with early psychosis.

Adults with psychotic disorders have abnormal connectivity of fronto-temporal networks. However, whether these abnormalities are present in adolescents with early psychosis has not been fully assessed. One-hundred and thirty-nine adolescents aged 12-18 underwent resting-state functional magnetic resonance imaging and diffusion tensor imaging. Following motion correction, data were available for 44 participants with a psychosis risk syndrome, 34 patients with a first episode psychosis (FEP) and 35 healthy controls. Independent component analysis was performed to assess functional networks showing a fronto-temporal scope; this identified a language and a salience network. Mean fractional anisotropy was measured in clusters showing between-group differences in intrinsic functional connectivity (iFC). For the language network, there was a group effect within the right middle/inferior frontal gyrus, explained by reduced iFC in patients with an FEP relative to healthy controls, while in participants with a psychosis risk syndrome values of iFC were intermediate. In this region, values of iFC were positively correlated with mean fractional anisotropy in patients with an FEP. No group differences were observed in the salience network. Reduced iFC of the language network, in association with disrupted white matter microstructure, may characterize FEP during adolescence.

Fractional anisotropy in patients with disproportionately enlarged subarachnoid space hydrocephalus.

Disproportionately enlarged subarachnoid space hydrocephalus (DESH) findings on MRI were described as a prognostic factor for responsiveness to the treatment of idiopathic normal pressure hydrocephalus (iNPH). Our premise is that DESH could be associated with compression of the cerebral white matter. Microstructural changes can be identified using diffusion tensor imaging (DTI), specifically fractional anisotropy (FA). The aim of this study is to compare FA in iNPH patients with and without DESH and healthy controls. We analysed 1.5-T MRI scans of patients fulfilling the criteria of probable or possible iNPH and positive supplementary tests before and after surgery (ventriculo-peritoneal shunt). FA was measured in the anterior and posterior limb of the internal capsule (PLIC) and in the corpus callosum. Patients were divided into the DESH and non-DESH group. These data were also compared to FA values in the control group. Twenty-seven patients and 24 healthy controls were enrolled. DESH was present in 15 patients and lacking in 12. Twenty-three iNPH patients were shunt responders (85.2%), and 4 were non-responders (14.8%). All patients in the DESH group were shunt responders. In the non-DESH group, eight patients were responders (66.7%). A significant difference between the DESH and non-DESH group was found in the FA of the PLIC. The mean value of FA in the PLIC was 0.72 in the DESH group and 0.66 in the non-DESH group. After the surgery FA decreased in both groups. In the DESH iNPH group FA PLIC decreased to 0.65 and in the non-DESH iNPH group to 0.60. In the healthy controls, the mean FA in the PLIC was 0.58. DESH on MRI scans is related to a higher FA in the PLIC with a decrease after the surgery. It reflects a more severe compression of the white matter than in non-DESH patients or healthy volunteers. DESH patients had better outcome than non-DESH patients. This study confirmed the importance of DESH as a supportive sign for iNPH.

Longitudinal evidence for anterograde trans-synaptic degeneration after optic neuritis.

In multiple sclerosis, microstructural damage of normal-appearing brain tissue is an important feature of its pathology. Understanding these mechanisms is vital to help develop neuroprotective strategies. The visual pathway is a key model to study mechanisms of damage and recovery in demyelination. Anterograde trans-synaptic degeneration across the lateral geniculate nuclei has been suggested as a mechanism of tissue damage to explain optic radiation abnormalities seen in association with demyelinating disease and optic neuritis, although evidence for this has relied solely on cross-sectional studies. We therefore aimed to assess: (i) longitudinal changes in the diffusion properties of optic radiations after optic neuritis suggesting trans-synaptic degeneration; (ii) the predictive value of early optic nerve magnetic resonance imaging measures for late optic radiations changes; and (iii) the impact on visual outcome of both optic nerve and brain post-optic neuritis changes. Twenty-eight consecutive patients with acute optic neuritis and eight healthy controls were assessed visually (logMAR, colour vision, and Sloan 1.25%, 5%, 25%) and by magnetic resonance imaging, at baseline, 3, 6, and 12 months. Magnetic resonance imaging sequences performed (and metrics obtained) were: (i) optic nerve fluid-attenuated inversion-recovery (optic nerve cross-sectional area); (ii) optic nerve proton density fast spin-echo (optic nerve proton density-lesion length); (iii) optic nerve post-gadolinium T1-weighted (Gd-enhanced lesion length); and (iv) brain diffusion-weighted imaging (to derive optic radiation fractional anisotropy, radial diffusivity, and axial diffusivity). Mixed-effects and multivariate regression models were performed, adjusting for age, gender, and optic radiation lesion load. These identified changes over time and associations between early optic nerve measures and 1-year global optic radiation/clinical measures. The fractional anisotropy in patients' optic radiations decreased (P = 0.018) and radial diffusivity increased (P = 0.002) over 1 year following optic neuritis, whereas optic radiation measures were unchanged in controls. Also, smaller cross-sectional areas of affected optic nerves at 3 months post-optic neuritis predicted lower fractional anisotropy and higher radial diffusivity at 1 year (P = 0.007) in the optic radiations, whereas none of the inflammatory measures of the optic nerve predicted changes in optic radiations. Finally, greater Gd-enhanced lesion length at baseline and greater optic nerve proton density-lesion length at 1 year were associated with worse visual function at 1 year (P = 0.034 for both). Neither the cross-sectional area of the affected optic nerve after optic neuritis nor the damage in optic radiations was associated with 1-year visual outcome. Our longitudinal study shows that, after optic neuritis, there is progressive damage to the optic radiations, greater in patients with early residual optic nerve atrophy, even after adjusting for optic radiation lesions. These findings provide evidence for trans-synaptic degeneration.

POSSIBILITY OF MR TRACTOGRAPHY IN EVALUATION OF PATHWAYS AT MODERATE-COGNITIVE DISORDERS WITH CHRONIC CEREBRAL ISCHEMIA

A significant decline in the fractional anisotropy in patients with chronic cerebral ischemia with mild cognitive disorders, especially in the white matter of the frontal lobes is proof starting neurodegenerative process in the brain, which can later be transformed into one or another form of dementia. The latter may indicate a need for MR tractography in all patients with cognitive impairment, which in turn will improve the early diagnosis of various forms of dementia.

Cognitive and White Matter Tract Differences in MS and Diffuse Neuropsychiatric Systemic Lupus Erythematosus.

Multiple sclerosis and neuropsychiatric systemic lupus erythematosus are autoimmune diseases with similar CNS inflammatory and neurodegenerative characteristics. Our aim was to investigate white matter tract changes and their association with cognitive function in patients with MS and those with neuropsychiatric systemic lupus erythematosus compared with healthy controls by using diffusion tensor imaging. Thirty patients with relapsing-remitting MS and 23 patients with neuropsychiatric systemic lupus erythematosus matched for disease severity and duration and 43 healthy controls were scanned with 3T MR imaging. The DTI was postprocessed, corrected for lesions, and analyzed with tract-based spatial statistics. Cognitive assessment included examination of processing speed; visual, auditory/verbal, and visual-spatial memory; and sustained attention and executive function. Differences were considered significant at P < .05. Tract-based spatial statistics analysis revealed significantly decreased fractional anisotropy and increased mean diffusivity in patients with MS compared with healthy controls, decreased fractional anisotropy in patients with MS compared with those with neuropsychiatric systemic lupus erythematosus, and an increased mean diffusivity in patients with neuropsychiatric systemic lupus erythematosus compared with healthy controls. Patients with MS showed decreased fractional anisotropy throughout central WM pathways, including the corpus callosum and the inferior longitudinal and fronto-occipital fasciculi compared with those with neuropsychiatric systemic lupus erythematosus. Altered cognitive scores in patients with MS were significantly associated with decreased fractional anisotropy and increased mean diffusivity in all examined domains, while in patients with diffuse neuropsychiatric systemic lupus erythematosus, only decreased fractional anisotropy in the superior WM pathways showed significant association with executive function. Patients with MS and neuropsychiatric systemic lupus erythematosus showed widespread WM tract alterations outside overt lesions, though more severe changes were identified in patients with MS. The WM tract changes were associated with cognitive dysfunction in all explored domains only in patients with MS.

Comparing fractional anisotropy in patients with childhood-onset schizophrenia, their healthy siblings, and normal volunteers through DTI.

Diffusion tensor imaging is a neuroimaging method that quantifies white matter (WM) integrity and brain connectivity based on the diffusion of water in the brain. White matter has been hypothesized to be of great importance in the development of schizophrenia as part of the dysconnectivity model. Childhood-onset schizophrenia (COS), is a rare, severe form of the illness that resembles poor outcome adult-onset schizophrenia. We hypothesized that COS would be associated with WM abnormalities relative to a sample of controls. To evaluate WM integrity in this population 39 patients diagnosed with COS, 39 of their healthy (nonpsychotic) siblings, and 50 unrelated healthy volunteers were scanned using a diffusion tensor imaging (DTI) sequence during a 1.5 T MRI acquisition. Each DTI scan was processed via atlas-based analysis using a WM parcellation map, and diffeomorphic mapping that shapes a template atlas to each individual subject space. Fractional anisotropy (FA), a measure of WM integrity was averaged over each of the 46 regions of the atlas. Eleven WM regions were examined based on previous reports of WM growth abnormalities in COS. Of those regions, patients with COS, and their healthy siblings had significantly lower mean FA in the left and right cuneus as compared to the healthy volunteers (P < .005). Together, these findings represent the largest DTI study in COS to date, and provide evidence that WM integrity is significantly impaired in COS. Shared deficits in their healthy siblings might result from increased genetic risk.

Extensive white matter dysfunction in cognitively impaired patients with secondary-progressive multiple sclerosis.

Cognitive impairment is a common, disabling symptom of MS. We investigated the association between cognitive impairment and WM dysfunction in secondary-progressive multiple sclerosis using DTI. Cognitive performance was assessed with a standard neuropsychological battery, the Minimal Assessment of Cognitive Function in Multiple Sclerosis. Cognitive impairment was defined as scoring >1.5 standard deviations below healthy controls on ≥2 subtests. Fractional anisotropy maps were compared against cognitive status using tract-based spatial statistics with threshold-free cluster enhancement. Forty-five patients with secondary-progressive multiple sclerosis (median age: 55 years, female/male: 27/18, median Expanded Disability Status Scale Score: 6.5) were prospectively recruited. Cognitively impaired patients (25/45) displayed significantly less normalized global GM and WM volumes (P = .001, P = .024), more normalized T2-weighted and T1-weighted WM lesion volumes (P = .002, P = .006), and lower WM skeleton fractional anisotropy (P < .001) than non-impaired patients. Impaired patients also had significantly lower fractional anisotropy (p(corr) < .05) in over 50% of voxels within every major WM tract. The most extensively impinged tracts were the left posterior thalamic radiation (100.0%), corpus callosum (97.8%), and right sagittal stratum (97.5%). No WM voxels had significantly higher fractional anisotropy in patients with cognitive impairment compared with their non-impaired counterparts (p(corr) > .05). After the inclusion of confounders in a multivariate logistic regression, only fractional anisotropy remained a significant predictor of cognitive status. Cognitively impaired patients with secondary-progressive multiple sclerosis exhibited extensive WM dysfunction, though preferential involvement of WM tracts associated with cognition, such as the corpus callosum, was apparent. Multivariate analysis revealed that only WM skeleton fractional anisotropy was a significant predictor of cognitive status.

P.2.d.003 Fractional anisotropy in patients with first episode mania in late life

Background: The present analyses were designed to compare the clinical characteristics and long-term episode course of Bipolar-I and Bipolar-II patients in order to help clarify the relationship between these disorders and to test the bipolar spectrum hypothesis. Methods: The patient sample consisted of 135 definite RDC Bipolar-I (BP-I) and 71 definite RDC Bipolar-II patients who entered the NIMH Collaborative Depression Study (CDS) between 1978 and 1981; and were followed systematically for up to 20 years. Groups were compared on demographic and clinical characteristics at intake, and lifetime comorbidity of anxiety and substance use disorders. Subsets of patients were compared on the number and type of affective episodes and the duration of inter-episode well intervals observed during a 10-year period following their resolution of the intake affective episode. Results: BP-I and BP-II had similar demographic characteristics and ages of onset of their first affective episode. Both disorders had more lifetime comorbid substance abuse disorders than the general population. BP-II had a significantly higher lifetime prevalence of anxiety disorders in general, and social and simple phobias in particular, compared to BP-I. Intake episodes of BP-I were significantly more acutely severe. BP-II patietns had a substantially more chronic course, with significantly more major and minor depressive episodes and shorter inter-episode well intervals. BP-II patients were prescribed somatic treatment a substantially lower percentage of time during and between affective episodes. Limitations: BP-I patients with severe manic course are less likely to be retained in long-term follow-up, whereas the reverse might be true for BP-II patients who are significantly more prone to depression (i.e., patients with less inclination to depression and with good prognosis may have dropped out in greater proportions); this could increase the gap in long term course characteristics between the two samples. The greater chronicity of BP-II may be due, in part, to the fact that the patients were prescribed somatic treatments substantially less often both during and between affective episodes. Conclusions: The variety in severity of the affective episodes shows that bipolar disorders, similar to unipolar disorders, are expressed longitudinally during their course as a dimensional illness. The similarities of the clinical phenotypes of BP-I and BP-II, suggest that BP-I and BP-II are likely to exist in a disease spectrum. They are, however, sufficiently distinct in terms of long-term course (i.e., BP-I with more severe episodes, and BP-II more chronic with a predominantly depressive course), that they are best classified as two separate subtypes in the official classification systems.

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.

2121 – Diffusion tensor imaging in non-resistant unipolar major depression: preliminary results

Major depression is a prevalent condition which typically has a chronic and relapsing course. It is frequently accompanied by changes in brain structure and function, as well as hormonal and inflammatory markers. The relationship of these markers to response remains elusive. A growing literature documents white matter alterations in the right frontal lobe, right fusiform gyrus, left frontal lobe and right occipital lobe as revealed by lower fractional anisotropy in patients with major depression relative to healthy controls. In this pilot study we propose to explore the relationship between white matter integrity in non-resistant major depression and response to treatment. Subjects with unipolar major depression were included. Prior to initiating treatment magnetic resonance imagery was obtained. Cognitive function was evaluated with a computerized neuropsychological battery, and a blood sample for the determination of inflammatory markers was drawn. All subjects are treated with desvenlafaxine 50mg die. A possible option to increase the dose to 100mg die was available at 8 weeks. At 16 weeks the initial evaluation was repeated. We will present preliminary imaging results from the first ten patients. The data from this study may contribute to the incremental increase in evidence clarifying the neuroimmunohormonal factors characterizing depression and response to treatment.

White Matter Abnormalities in Pediatric Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) is a prevalent and often severely disabling illness with onset generally in childhood or adolescence. Although white matter deficits have been implicated in the neurobiology of OCD, few studies have been conducted in pediatric patients when the brain is still developing and have examined their functional correlates. In this study, 23 pediatric OCD patients and 23 healthy volunteers, between the ages of 9 and 17 years, matched for sex, age, handedness, and IQ, received a diffusion tensor imaging exam on a 3T GE system and a brief neuropsychological battery tapping executive functions. Patient symptom severity was assessed using the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Patients with OCD exhibited significantly greater fractional anisotropy compared to matched controls in the left dorsal cingulum bundle, splenium of the corpus callosum, right corticospinal tract, and left inferior fronto-occipital fasciculus. There were no regions of significantly lower fractional anisotropy in patients compared to controls. Higher fractional anisotropy in the splenium was significantly correlated with greater obsession severity on the CY-BOCS in the subgroup of psychotropic drug-naïve patients. Among patients, there was a significant association between greater fractional anisotropy in the dorsal cingulum bundle and better performance on measures of response inhibition and cognitive control. The overall findings suggest a pattern of greater directional coherence of white matter tracts in OCD very early in the course of illness, which may serve a compensatory mechanism, at least for response inhibition functions typically subserved by the cingulum bundle.