Cingulate Bundle Research Articles

Diffusion tensor imaging and tractography of the white matter in normal aging: The rate-of-change differs between segments within tracts

Knowledge concerning the normal aging of cerebral white matter will improve our understanding of abnormal changes in neurodegenerative diseases. The microstructural basis of white matter maturation and aging can be investigated using diffusion tensor imaging (DTI). Generally, diffusion anisotropy increases during childhood and adolescence followed by a decline in middle age. However, this process is subject to spatial variations between tracts. The aim of this study was to investigate to what extent age-related variations also occur within tracts. DTI parameters were compared between segments of two white matter tracts, the cingulate bundle (CB) and the inferior fronto-occipital fasciculus (IFO), in 257 healthy individuals between 13 and 84years of age. Segments of the CB and the IFO were extracted and parameters for each segment were averaged across the hemispheres. The data was analysed as a function of age. Results show that age-related changes differ both between and within individual tracts. Different age trajectories were observed in all segments of the analysed tracts for all DTI parameters. In conclusion, aging does not affect white matter tracts uniformly but is regionally specific; both between and within white matter tracts.

White matter microstructure of patients with neurofibromatosis type 1 and its relation to inhibitory control

Neurofibromatosis Type 1 (NF1) is commonly associated with deficits in executive functions such as working memory and inhibitory control. A valid biomarker to describe the pathological basis of these deficits in NF1 is not available. The aim of this study was to investigate whether any abnormalities in white matter integrity of the executive function related anterior thalamic radiation (ATR), cingulate bundle (CB), and superior longitudinal fasciculus (SLF) may be regarded as a pathological basis for inhibitory control deficits in adolescents with NF1. Sixteen NF1 patients and 32 healthy controls underwent 3 T DTI MRI scanning. Whole brain-, ATR-, CB-, and SLF-white matter integrity were studied using fractional anisotropy, mean (MD), radial, and axial (DA) diffusivity. Correlation analyses between white matter metrics and inhibitory control (as measured with a computerized task) were performed. Also, verbal and performance abilities (IQ-estimates) were assessed and correlated with white matter metrics. Patients showed significant whole brain- and local microstructural pathology when compared to healthy controls in all measures. In NF1-patients, whole-brain (MD: r = .646 and DA: r = .673) and ATR- (r-range: −.405–.771), but not the CB- (r-range: −.307–.472) and SLF- (r-range: −.187–.406) white matter integrity, were correlated with inhibitory control. Verbal and performance abilities were not associated with white matter pathology. In NF1, white matter abnormalities are observed throughout the brain, but damage to the ATR seems specifically, or at least most strongly related to inhibitory control. Future studies should examine whether reduced white matter integrity in other brain regions or tracts is (more strongly) associated with different aspects of the cognitive-behavioral phenotype associated with NF1.

Associations between brain white matter integrity and disease severity in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway blockage, with continued diaphragmatic efforts to breathe during sleep. Brain structural changes in OSA appear in various regions, including white matter sites that mediate autonomic, mood, cognitive, and respiratory control. However, the relationships between brain white matter changes and disease severity in OSA are unclear. This study examines associations between an index of tissue integrity, magnetization transfer (MT) ratio values (which show MT between free and proton pools associated with tissue membranes and macromolecules), and disease severity (apnea-hypopnea index [AHI]) in OSA subjects. We collected whole-brain MT imaging data from 19 newly diagnosed, treatment-naïve OSA subjects (50.4 ± 8.6 years of age, 13 males, AHI 39.7 ± 24.3 events/hr], using a 3.0-Tesla MRI scanner. With these data, whole-brain MT ratio maps were calculated, normalized to common space, smoothed, and correlated with AHI scores by using partial correlation analyses (covariates, age and gender; P < 0.005). Multiple brain sites in OSA subjects, including superior and inferior frontal regions, ventral medial prefrontal cortex and nearby white matter, midfrontal white matter, insula, cingulate and cingulum bundle, internal and external capsules, caudate nuclei and putamen, basal forebrain, hypothalamus, corpus callosum, and temporal regions, showed principally lateralized negative correlations (P < 0.005). These regions showed significant correlations even with correction for multiple comparisons (cluster-level, family-wise error, P < 0.05), except for a few superior frontal areas. Predominantly negative correlations emerged between local MT values and OSA disease severity, indicating potential usefulness of MT imaging for examining the OSA condition. These findings indicate that OSA severity plays a significant role in white matter injury. © 2016 Wiley Periodicals, Inc.

Serum S100B Protein is Specifically Related to White Matter Changes in Schizophrenia.

Background: Schizophrenia can be conceptualized as a form of dysconnectivity between brain regions.To investigate the neurobiological foundation of dysconnectivity, one approach is to analyze white matter structures, such as the pathology of fiber tracks. S100B is considered a marker protein for glial cells, in particular oligodendrocytes and astroglia, that passes the blood brain barrier and is detectable in peripheral blood. Earlier Studies have consistently reported increased S100B levels in schizophrenia. In this study, we aim to investigate associations between S100B and structural white matter abnormalities.Methods: We analyzed data of 17 unmedicated schizophrenic patients (first and recurrent episode) and 22 controls. We used voxel based morphometry (VBM) to detect group differences of white matter structures as obtained from T1-weighted MR-images and considered S100B serum levels as a regressor in an age-corrected interaction analysis.Results: S100B was increased in both patient subgroups. Using VBM, we found clusters indicating significant differences of the association between S100B concentration and white matter. Involved anatomical structures are the posterior cingulate bundle and temporal white matter structures assigned to the superior longitudinal fasciculus.Conclusions: S100B-associated alterations of white matter are shown to be existent already at time of first manifestation of psychosis and are distinct from findings in recurrent episode patients. This suggests involvement of S100B in an ongoing and dynamic process associated with structural brain changes in schizophrenia. However, it remains elusive whether increased S100B serum concentrations in psychotic patients represent a protective response to a continuous pathogenic process or if elevated S100B levels are actively involved in promoting structural brain damage.

Non-Gaussian diffusion alterations on diffusion kurtosis imaging in patients with early Alzheimer’s disease

ObjectiveTo evaluate non-Gaussian diffusion changes of the whole-brain and its correlation with cognitive performance in patients with early Alzheimer's disease (AD), using diffusion kurtosis imaging (DKI). MethodsTwenty-six patients with early AD and twenty-six normal controls underwent diffusion imaging. Seven parametric maps were calculated from multiple b-value diffusion data, including mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD). Voxel-based analyses were performed to evaluate the group difference between the AD patients and normal controls. Then correlation between the diffusion parameters (MK, FA and MD) and cognitive performance were analyzed in AD patients. ResultsFor AD patients, increased MD, AxD and RD were found in white matter (WM), including the genu of corpus callosum, bilateral cingulate bundle, bilateral temporal and frontal WM, and were also found in gray matter (GM), including the bilateral temporal GM, parahippocampal gyrus, hippocampus, cingulate gyrus, thalamus, and amygdala. These regions were partially overlapped with those showing decreased FA, MK, AK and RK. However, only kurtosis indices could detect the significant differences in the lentiform nucleus between AD patients and health control. DKI indices in AD patients significantly correlated with the clinical scores in genu of CC, cingulate bundle, temporal and frontal lobe, while the voxel number showing significant correlation with MK was more than that with FA and MD. ConclusionsEarly AD patients already have microstructural changes in both WM and GM. DKI can provide supplementary information in reflecting these changes and may be sensitive in diagnosing early AD.

Neuroimaging of cognitive-affective disorders in Parkinson’s disease

About one third of PD patients experience significant depression and apathy, and cognitive difficulties are even more frequent. The etiology of cognitive-affective symptoms in PD is multifocal: a reaction to disability, monoaminergic as well as cholinergic dysfunction and white matter lesions (WML) could all be contributors. Our results of WML (60 patients) and voxel-based morphometry (VBM) MRI changes (40 patients) associated with depression will be presented and literature data of cognitive-affective symptoms in PD are reviewed. PD patients with depression (PD-Dep) had a significantly higher score for periventricular regions WML comparing with both patients without depression (PD-NDep) and controls. Multivariate analyses showed that periventricular WML total score explaining the 39% of the variance in the depressive score. VBM analysis showed that PD-Dep vs PD-NDep patients exhibit white matter loss in the right anterior cingulate bundle and inferior orbitofrontal (OF) region, and depression score correlated with WM loss in the right inferior OF region. Taken together, these findings suggest dysfunction of basal ganglia circuits projecting to the inferior frontal lobe may cause aberrant regulation of mood. Literature data show some discordance between the development of functional MRI changes in PD with cognitive difficulties and Braak staging hypothesis.

Cognitive demands during quiet standing elicit truncal tremor in two frequency bands: differential relations to tissue integrity of corticospinal tracts and cortical targets.

The ability to stand quietly is disturbed by degradation of cerebellar systems. Given the complexity of sensorimotor integration invoked to maintain upright posture, the integrity of supratentorial brain structures may also contribute to quiet standing and consequently be vulnerable to interference from cognitive challenges. As cerebellar system disruption is a common concomitant of alcoholism, we examined 46 alcoholics and 43 controls with a force platform to derive physiological indices of quiet standing during cognitive (solving simple, mental arithmetic problems) and visual (eyes closed) challenges. Also tested were relations between tremor velocity and regional gray matter and white matter tissue quality measured with the diffusion tensor imaging (DTI) metric of mean diffusivity (MD), indexing disorganized microstructure. Spectral analysis of sway revealed greater tremor in alcoholic men than alcoholic women or controls. Cognitive dual-tasking elicited excessive tremor in two frequency bands, each related to DTI signs of degradation in separate brain systems: tremor velocity at a low frequency (2–5 Hz/0–2 Hz) correlated with higher MD in the cerebellar hemispheres and superior cingulate bundles, whereas tremor velocity at a higher frequency (5–7 Hz) correlated with higher MD in the motor cortex and internal capsule. These brain sites may represent “tremorgenic networks” that, when disturbed by disease and exacerbated by cognitive dual-tasking, contribute to postural instability, putting affected individuals at heightened risk for falling.

Brain structural abnormalities in behavior therapy-resistant obsessive-compulsive disorder revealed by voxel-based morphometry.

BackgroundAlthough several functional imaging studies have demonstrated that behavior therapy (BT) modifies the neural circuits involved in the pathogenesis of obsessive-compulsive disorder (OCD), the structural abnormalities underlying BT-resistant OCD remain unknown.MethodsIn this study, we examined the existence of regional structural abnormalities in both the gray matter and the white matter of patients with OCD at baseline using voxel-based morphometry in responders (n=24) and nonresponders (n=15) to subsequent BT. Three-dimensional T1-weighted magnetic resonance imaging was performed before the completion of 12 weeks of BT.ResultsRelative to the responders, the nonresponders exhibited significantly smaller gray matter volumes in the right ventromedial prefrontal cortex, the right orbitofrontal cortex, the right precentral gyrus, and the left anterior cingulate cortex. In addition, relative to the responders, the nonresponders exhibited significantly smaller white matter volumes in the left cingulate bundle and the left superior frontal white matter.ConclusionThese results suggest that the brain structures in several areas, including the orbitofrontal cortex, anterior cingulate cortex, and cingulate bundles, are related to the lack of a response to BT in patients with OCD. The use of a voxel-based morphometry approach may be advantageous to understanding differences in brain abnormalities between responders and nonresponders to BT.

Diffusion tensor imaging predictors of treatment outcomes in major depressive disorder.

Functional neuroimaging studies implicate anterior cingulate and limbic dysfunction in major depressive disorder (MDD) and responsiveness to antidepressants. Diffusion tensor imaging (DTI) enables characterisation of white matter tracts that relate to these regions. To examine whether DTI measures of anterior cingulate and limbic white matter are useful prognostic biomarkers for MDD. Of the 102 MDD out-patients from the International Study to Predict Optimized Treatment for Depression (iSPOT-D) who provided baseline magnetic resonance imaging (MRI) data, 74 completed an 8-week course of antidepressant medication (randomised to escitalopram, sertraline or extended-release venlafaxine) and were included in the present analyses. Thirty-four matched controls also provided DTI data. Fractional anisotropy was measured for five anterior cingulate-limbic white matter tracts: cingulum cingulate and hippocampus bundle, fornix, stria terminalis and uncinate fasciculus. (Trial registered at ClinicalTrials.gov: NCT00693849.) A cross-validated logistic regression model demonstrated that altered connectivity for the cingulum part of the cingulate and stria terminalis tracts significantly predicted remission independent of demographic and clinical measures with 62% accuracy. Prediction improved to 74% when age was added to this model. Anterior cingulate-limbic white matter is a useful predictor of antidepressant treatment outcome in MDD.

Cingulum bundle alterations underlie subjective fatigue in multiple sclerosis

Objective: To evaluate the neural basis of subjective fatigue in subjects with multiple sclerosis (MS) using a connectionist framework. Methods: Seventy seven subjects with relapsing–remitting MS were recruited in the study and underwent subjective fatigue evaluations and a diffusion MRI scan. Firstly, local white matter Fractional Anisotropy values were correlated with subjective fatigue scores using a voxel-wise approach. The long-range loss of connectivity due to structural damage in the white matter voxels thus associated with subjective fatigue was then assessed using the Network Modification (NeMo) package. Results: A voxel-wise regression analysis with fatigue scores revealed a significant association between structural damage and fatigue levels in two discrete white matter clusters, both included in the left cingulate bundle. The connectivity analysis revealed that damage in these clusters was associated with loss of structural connectivity in the anterior and medial cingulate cortices, dorsolateral prefrontal areas and in the left caudate. Discussion: Our data point to the cingulum bundle and its projections as the key network involved in subjective fatigue perception in MS. More generally, these results suggest the potential of the connectionist framework to generate coherent models of the neural basis of complex symptomatology in MS.

Effect of clozapine on white matter integrity in patients with schizophrenia: A diffusion tensor imaging study

Several diffusion tensor imaging (DTI) studies have reported disturbed white matter integrity in various brain regions in patients with schizophrenia, whereas only a few studied the effect of antipsychotics on DTI measures. The aim of this study was to investigate the effect of 12 weeks of clozapine treatment on DTI findings in patients with schizophrenia, and to compare the findings with those in unaffected controls. The study included 16 patients with schizophrenia who were assessed with the Positive and Negative Syndrome Scale, a neurocognitive test battery, and DTI at baseline and 12 weeks after the initiation of clozapine treatment. Eight unaffected controls were assessed once with the neurocognitive test battery and DTI. Voxel-wise analysis of DTI data was performed via tract-based spatial statistics (TBSS). Compared with the control group, the patient group exhibited lower fractional anisotropy (FA) in 16 brain regions, including the bilateral superior longitudinal fasciculi, inferior fronto-occipital fasciculi, superior and inferior parietal lobules, cingulate bundles, cerebellum, middle cerebellar peduncles, and left inferior longitudinal fasciculus, whereas the patients had higher FA in six regions, including the right parahippocampus, left anterior thalamic radiation, and right posterior limb of the internal capsule before clozapine treatment. After 12 weeks of treatment with clozapine, white matter FA was increased in widespread brain regions. In two of the regions where FA had initially been lower in patients compared with controls (left inferior fronto-occipital fasciculus and superior parietal lobule), clozapine appeared to increase FA. An improvement in semantic fluency was correlated with the increase in FA value in the left inferior fronto-occipital fasciculus. An increase in FA following 12 weeks of treatment with clozapine suggests that this treatment alters white matter microstructural integrity in patients with schizophrenia previously treated with typical and/or atypical antipsychotics and, in some locations, reverses a previous deficit.

Poster #M55 DURATION OF ILLNESS ASSOCIATED WITH CORTICAL THICKNESS CHANGE IN SCHIZOPHRENIA: A LONGITUDINAL MRI STUDY

Several diffusion tensor imaging (DTI) studies have reported disturbed white matter integrity in various brain regions in patients with schizophrenia, whereas only a few studied the effect of antipsychotics on DTI measures. The aim of this study was to investigate the effect of 12 weeks of clozapine treatment on DTI findings in patients with schizophrenia, and to compare the findings with those in unaffected controls. The study included 16 patients with schizophrenia who were assessed with the Positive and Negative Syndrome Scale, a neurocognitive test battery, and DTI at baseline and 12 weeks after the initiation of clozapine treatment. Eight unaffected controls were assessed once with the neurocognitive test battery and DTI. Voxel-wise analysis of DTI data was performed via tract-based spatial statistics (TBSS). Compared with the control group, the patient group exhibited lower fractional anisotropy (FA) in 16 brain regions, including the bilateral superior longitudinal fasciculi, inferior fronto-occipital fasciculi, superior and inferior parietal lobules, cingulate bundles, cerebellum, middle cerebellar peduncles, and left inferior longitudinal fasciculus, whereas the patients had higher FA in six regions, including the right parahippocampus, left anterior thalamic radiation, and right posterior limb of the internal capsule before clozapine treatment. After 12 weeks of treatment with clozapine, white matter FA was increased in widespread brain regions. In two of the regions where FA had initially been lower in patients compared with controls (left inferior fronto-occipital fasciculus and superior parietal lobule), clozapine appeared to increase FA. An improvement in semantic fluency was correlated with the increase in FA value in the left inferior fronto-occipital fasciculus. An increase in FA following 12 weeks of treatment with clozapine suggests that this treatment alters white matter microstructural integrity in patients with schizophrenia previously treated with typical and/or atypical antipsychotics and, in some locations, reverses a previous deficit.

Exploratory meta-analysis on deep brain stimulation in treatment-resistant depression.

Deep brain stimulation is currently an experimental treatment for major depressive disorder. Information is lacking, however, on how sham responding may affect efficacy. This article applies exploratory meta-analysis to address that topic. Data on benefits of deep brain electrical stimulation come from a recent review. Stimulated brain regions included subgenual cingulate, capsular interna, nucleus accumbens, and medial forebrain bundle. Expert opinion plus random number software was used to generate hypothetical values for sham responding. An effect size of 1.71 (95% CI: 1.47-1.96) was obtained for deep brain stimulation versus sham treatment in patients suffering from long-term treatment-resistant depression. Preliminary findings on deep brain electrical stimulation suggest that the procedure may be 71% more effective than sham treatment. Expressing these findings as patients-needed-to-treat, deep brain electrical stimulation is required by 2.9 patients with long-term treatment-resistant depression in order for one of them to benefit.

Progressive levels of physical dependence to tobacco coincide with changes in the anterior cingulum bundle microstructure.

BackgroundThe tobacco withdrawal syndrome indicates the development of neurophysiologic dependence. Clinical evidence indicates that neurophysiologic dependence develops through a set sequence of symptom presentation that can be assessed with a new 3-item survey measure of wanting, craving, and needing tobacco, the Level of Physical Dependence (PD). This study sought to determine if advancing neurophysiologic dependence as measured by the Level of PD correlates with characteristics of white matter structure measured by Fractional Anisotropy (FA).MethodsDiffusion-MRI based FA and diffusion tensor imaging probabilistic tractography were used to evaluate 11 smokers and 10 nonsmokers. FA was also examined in relation to two additional measures of dependence severity, the Hooked on Nicotine Checklist (HONC), and the Fagerström Test for Nicotine Dependence (FTND).ResultsAmong smokers, FA in the left anterior cingulate bundle (ACb) correlated negatively with the Level of PD (r = −0.68, p = 0.02) and HONC scores (r = −0.65, p = 0.03), but the correlation for the FTND did not reach statistical significance (r = −49, p = 0.12). With advancing Levels of PD, the density of streamlines between the ACb and precuneus increased (r = −0.67, p<0.05) and those between the ACb and white matter projecting to the superior-frontal cortex (r = −0.86, p = 0.0006) decreased significantly.ConclusionsThe correlations between neural structure and both the clinical Level of PD survey measure and the HONC suggest that the Level of PD and the HONC may reflect the microstructural integrity of white matter, as influenced by tobacco abuse. Given that the Level of PD is measuring a sequence of symptoms of neurophysiologic dependence that develops over time, the correlation between the Level of PD and neural structure suggests that these features might represent neuroplastic changes that develop over time to support the development of neurophysiologic dependence.

Metabolic and structural connectivity within the default mode network relates to working memory performance in young healthy adults

Studies of functional connectivity suggest that the default mode network (DMN) might be relevant for cognitive functions. Here, we examined metabolic and structural connectivity between major DMN nodes, the posterior cingulate (PCC) and medial prefrontal cortex (MPFC), in relation to normal working memory (WM). DMN was captured using independent component analysis of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) data from 35 young healthy adults (27.1 ± 5.1 years). Metabolic connectivity, a correlation between FDG uptake in PCC and MPFC, was examined in groups of subjects with (relative to median) low (n=18) and high (n=17) performance on digit span backward test as an index of verbal WM. In addition, fiber tractography based on PCC and MPFC nodes as way points was performed in a subset of subjects. FDG uptake in the DMN nodes did not differ between high and low performers. However, significantly (p=0.01) lower metabolic connectivity was found in the group of low performers. Furthermore, as compared to high performers, low performers showed lower density of the left superior cingulate bundle. Verbal WM performance is related to metabolic and structural connectivity within the DMN in young healthy adults. Metabolic connectivity as quantified with FDG-PET might be a sensitive marker of the normal variability in some cognitive functions.

The structural connectome of the human brain in agenesis of the corpus callosum

Adopting a network perspective, the structural connectome reveals the large-scale white matter connectivity of the human brain, yielding insights into cerebral organization otherwise inaccessible to researchers and clinicians. Connectomics has great potential for elucidating abnormal connectivity in congenital brain malformations, especially axonal pathfinding disorders. Agenesis of the corpus callosum (AgCC) is one of the most common brain malformations and can also be considered a prototypical genetic disorder of axonal guidance in humans. In this exploratory study, the structural connectome of AgCC is mapped and compared to that of the normal human brain. Multiple levels of granularity of the AgCC connectome are investigated, including summary network metrics, modularity analysis, and network consistency measures, with comparison to the normal structural connectome after simulated removal of all callosal connections ("virtual callostomy"). These investigations reveal four major findings. First, global connectivity is abnormally reduced in AgCC, but local connectivity is increased. Second, the network topology of AgCC is more variable than that of the normal human connectome, contradicting the predictions of the virtual callostomy model. Third, modularity analysis reveals that many of the tracts that comprise the structural core of the cerebral cortex have relatively weak connectivity in AgCC, especially the cingulate bundles bilaterally. Finally, virtual lesions of the Probst bundles in the AgCC connectome demonstrate that there is consistency across subjects in many of the connections generated by these ectopic white matter tracts, and that they are a mixture of cortical and subcortical fibers. These results go beyond prior diffusion tractography studies to provide a systems-level perspective on anomalous connectivity in AgCC. Furthermore, this work offers a proof of principle for the utility of the connectome framework in neurodevelopmental disorders.

P2‐214: Multi‐center DTI tractography of the cingulate bundle in Alzheimer's disease: A study of accuracy and comparability

P2‐214: Multi‐center DTI tractography of the cingulate bundle in Alzheimer's disease: A study of accuracy and comparability

Diminished performance on neuropsychological testing in late life depression is correlated with microstructural white matter abnormalities

BackgroundTraditional T2 weighted MR imaging results are non-specific for the extent of underlying white matter structural abnormalities present in late life depression (LLD). Diffusion tensor imaging provides a unique opportunity to investigate the extent and nature of structural injury, but has been limited by examining only a subset of regions of interest (ROI) and by confounds common to the study of an elderly population, including comorbid vascular pathology. Furthermore, comprehensive correlation of diffusion tensor imaging (DTI) measurements, including axial and radial diffusivity measurements, has not been demonstrated in the late life depression population. Methods51 depressed and 16 non-depressed, age- and cerebrovascular risk factor-matched elderly subjects underwent traditional anatomic T1 and T2 weight imaging, as well as DTI. The DTI data were skeletonized using tract based spatial statistics (TBSS), and both regional and global analyses were performed. ResultsWidespread structural abnormalities within white matter were detected in the LLD group, accounting for age, gender and education and matched for cerebrovascular risk factors and global T2 white matter hyperintensities (T2WMH). Regional differences were most prominent in uncinate and cingulate white matter and were generally characterized by an increase in radial diffusivity. Age-related changes particularly in the cingulate bundle were more advanced in individuals with LLD relative to controls. Regression analysis demonstrated significant correlations of regional fractional anisotropy and radial diffusivity with five different neuropsychological factor scores. TBSS analysis demonstrated a greater extent of white matter abnormalities in LLD not responsive to treatment, as compared to controls. ConclusionsWhite matter integrity is compromised in late life depression, largely manifested by increased radial diffusivity in specific regions, suggesting underlying myelin injury. A possible mechanism for underlying myelin injury is chronic white matter ischemia related to intrinsic cerebrovascular disease. In some regions such as the cingulate bundle, the white matter injury related to late life depression appears to be independent of and compounded by age-related changes. The correlations with neuropsychological testing indicate the essential effects of white matter injury on functional status. Lastly, response to treatment may depend on the extent of white matter injury, suggesting a need for intact functional networks.

Automated tractography of the cingulate bundle in Alzheimer's disease: A multicenter DTI study

To evaluate the feasibility of multicenter tractography of the cingulate bundle (CB) in Alzheimer's disease (AD). Automated deterministic tractography of the CB was applied to scans of 45 patients with probable AD and 58 healthy controls (HC) acquired with Siemens Sonata (1.5T; 60 gradients), Trio (3T; 61 gradients), and Avanto (1.5T; 30 gradients). Diagnosis and center effects on the tracking indices fractional anisotropy (FA), mean diffusivity (MD), track density, and volume were estimated with analysis of variance. The multicenter coefficients of variance (CVs) in HC and AD patients were 7% and 7% for FA, 10% and 8% for MD, 18% and 20% for density, and 21% and 21% for volume. Multicenter and single-center CVs were within a similar range. Significant center effects declined in the order MD > FA > density > volume. After adjustment for center and age, the AD group showed significantly higher MD (P < 0.001) and lower FA (P < 0.05) as compared with the HC group. Despite strong center effects, we detected significantly altered microstructural integrity of the CB in AD patients. Diffusion-tensor imaging indices of the CB as obtained by automated tractography might qualify as a biologically sustained surrogate marker for diagnostic and monitoring purposes in multicenter AD trials.

P-805 - Diffusion tensor imaging (DTI) findings in schizophrenia: what's new?

Diffusion tensor imaging (DTI) is a magnetic resonance imaging technique that have increasingly being used for the non-invasive evaluation of brain white matter (WM) abnormalities.Several studies suggest that the normal integration of cerebral function may be compromised in schizophrenia. Abnormalities in WM tracts may be directly relevant for the neuropathology of schizophrenia The purpose of this review was to discuss recent DTI findings in schizophrenia and a methodologic analysis. The literature search was performed with the search engine PubMed of the U.S. National Library of Medicine.Search strategy used was based on the Cochrane review technique, limited to the period between 1998 (first report on DTI and schizophrenia) and October 2011. And limited to ‘Title/Abstract’..The reference lists of these studies were used to identify additional studies. There is a striking amount of heterogeneity in findings, probably by methodologic problems.Brain regions such as the cingulate bundle,corpus callosum, and regions within frontal and temporal WM have a proportionally larger number of positive findings across the studies.In addition,WM tracts as The superior longitudinal fasciculus, fronto-occipital longitudinal fasciculi, uncinate fasciculi,frontal longitudinal fasciculus and the arcuate fasciculus have also positive findings in patients with schizophrenia. Other brain structures as the cerebellar peduncles,the fornix,the hippocampus and parahippocampal gyrus, the thalamic and optic radiations have been evaluated and shown positive findings. However, these findings are not present in all studies.DTI abnormalities in first-episode patients are less robust than in chronic patients. Recent DTI findings seem to support the hypothesis of structural dysconnectivity in schizophrenia.