White matter microstructure in bipolar disorder is influenced by the serotonin transporter gene polymorphism 5‐HTTLPR

Bipolar disorder (BD) is associated with signs of widespread disruption of white matter (WM) integrity. A polymorphism in the promoter of the serotonin transporter (5‐HTTLPR) influenced functional cortico‐limbic connectivity in healthy subjects and course of illness in BD, with the short (s) allele being associated with lower functional connectivity, and with earlier onset of illness and poor response to treatment. We tested the effects of 5‐HTTLPR on diffusion tensor imaging (DTI) measures of WM microstructure in 140 inpatients, affected by a major depressive episode in course of BD, of Italian descent. We used whole brain tract‐based spatial statistics in the WM skeleton with threshold‐free cluster enhancement of DTI measures of WM microstructure: axial, radial and mean diffusivity and fractional anisotropy. Compared with l/l homozygotes, 5‐HTTLPR*s carriers showed significantly increased radial and mean diffusivity in several brain WM tracts, including corpus callosum, cingulum bundle, uncinate fasciculus, corona radiata, thalamic radiation, inferior and superior longitudinal fasciculus and inferior fronto‐occipital fasciculus. An increase of mean and radial diffusivity, perpendicular to the main axis of the WM tract, is thought to signify increased space between fibers, thus suggesting demyelination or dysmyelination, or loss of bundle coherence. The effects of 5‐HTTLPR on the anomalous emotional processing in BD might be mediated by changes of WM microstructure in key WM tracts contributing to the functional integrity of the brain.     

White matter integrity and vulnerability to Alzheimer's disease: Preliminary findings and future directions

Neuroimaging biomarkers that precede cognitive decline have the potential to aid early diagnosis of Alzheimer's disease (AD). A body of diffusion tensor imaging (DTI) work has demonstrated declines in white matter (WM) microstructure in AD and its typical prodromal state, amnestic mild cognitive impairment. The present review summarizes recent evidence suggesting that WM integrity declines are present in individuals at high AD-risk, prior to cognitive decline. The available data suggest that AD-risk is associated with WM integrity declines in a subset of tracts showing decline in symptomatic AD. Specifically, AD-risk has been associated with WM integrity declines in tracts that connect gray matter structures associated with memory function. These tracts include parahippocampal WM, the cingulum, the inferior fronto-occipital fasciculus, and the splenium of the corpus callosum. Preliminary evidence suggests that some AD-risk declines are characterized by increases of radial diffusivity, raising the possibility that a myelin-related pathology may contribute to AD onset. These findings justify future research aimed at a more complete understanding of the neurobiological bases of DTI-based declines in AD. With continued refinement of imaging methods, DTI holds promise as a method to aid identification of presymptomatic AD. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

White matter integrity and vulnerability to Alzheimer's disease: preliminary findings and future directions

Neuroimaging biomarkers that precede cognitive decline have the potential to aid early diagnosis of Alzheimer's disease (AD). A body of diffusion tensor imaging (DTI) work has demonstrated declines in white matter (WM) microstructure in AD and its typical prodromal state, amnestic mild cognitive impairment. The present review summarizes recent evidence suggesting that WM integrity declines are present in individuals at high AD-risk, prior to cognitive decline. The available data suggest that AD-risk is associated with WM integrity declines in a subset of tracts showing decline in symptomatic AD. Specifically, AD-risk has been associated with WM integrity declines in tracts that connect gray matter structures associated with memory function. These tracts include parahippocampal WM, the cingulum, the inferior fronto-occipital fasciculus, and the splenium of the corpus callosum. Preliminary evidence suggests that some AD-risk declines are characterized by increases of radial diffusivity, raising the possibility that a myelin-related pathology may contribute to AD onset. These findings justify future research aimed at a more complete understanding of the neurobiological bases of DTI-based declines in AD. With continued refinement of imaging methods, DTI holds promise as a method to aid identification of presymptomatic AD. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

Diffusion tensor imaging of cerebral white matter integrity in cognitive aging

In this article we review recent research on diffusion tensor imaging (DTI) of white matter (WM) integrity and the implications for age-related differences in cognition. Neurobiological mechanisms defined from DTI analyses suggest that a primary dimension of age-related decline in WM is a decline in the structural integrity of myelin, particularly in brain regions that myelinate later developmentally. Research integrating behavioral measures with DTI indicates that WM integrity supports the communication among cortical networks, particularly those involving executive function, perceptual speed, and memory (i.e., fluid cognition). In the absence of significant disease, age shares a substantial portion of the variance associated with the relation between WM integrity and fluid cognition. Current data are consistent with one model in which age-related decline in WM integrity contributes to a decreased efficiency of communication among networks for fluid cognitive abilities. Neurocognitive disorders for which older adults are at risk, such as depression, further modulate the relation between WM and cognition, in ways that are not as yet entirely clear. Developments in DTI technology are providing a new insight into both the neurobiological mechanisms of aging WM and the potential contribution of DTI to understanding functional measures of brain activity. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

The Microstructural Status of the Corpus Callosum Is Associated with the Degree of Motor Function and Neurological Deficit in Stroke Patients

Human neuroimaging studies and animal models have suggested that white matter damage from ischemic stroke leads to the functional and structural reorganization of perilesional and remote brain regions. However, the quantitative relationship between the transcallosal tract integrity and clinical motor performance score after stroke remains unexplored. The current study employed a tract-based spatial statistics (TBSS) analysis on diffusion tensor imaging (DTI) to investigate the relationship between white matter diffusivity changes and the clinical scores in stroke patients. Probabilistic fiber tracking was also used to identify structural connectivity patterns in the patients. Thirteen ischemic stroke patients and fifteen healthy control subjects participated in this study. TBSS analyses showed that the corpus callosum (CC) and bilateral corticospinal tracts (CST) in the stroke patients exhibited significantly decreased fractional anisotropy and increased axial and radial diffusivity compared with those of the controls. Correlation analyses revealed that the motor and neurological deficit scores in the stroke patients were associated with the value of diffusivity indices in the CC. Compared with the healthy control group, probabilistic fiber tracking analyses revealed that significant changes in the inter-hemispheric fiber connections between the left and right motor cortex in the stroke patients were primarily located in the genu and body of the CC, left anterior thalamic radiation and inferior fronto-occipital fasciculus, bilateral CST, anterior/superior corona radiate, cingulum and superior longitudinal fasciculus, strongly suggesting that ischemic induces inter-hemispheric network disturbances and disrupts the white matter fibers connecting motor regions. In conclusion, the results of the present study show that DTI-derived measures in the CC can be used to predict the severity of motor skill and neurological deficit in stroke patients. Changes in structural connectivity pattern tracking between the left and right motor areas, particularly in the body of the CC, might reflect functional reorganization and behavioral deficit.     

Associations of White Matter Microstructure with Clinical and Demographic Characteristics in Heavy Drinkers

Damage to the brain’s white matter is a signature injury of alcohol use disorders (AUDs), yet understanding of risks associated with clinical and demographic characteristics is incomplete. This study investigated alcohol problem severity, recent drinking behavior, and demographic factors in relation to white matter microstructure in heavy drinkers. Magnetic resonance imaging (MRI) scans, including diffusion tensor imaging (DTI), were collected from 324 participants (mean age = 30.9 ± 9.1 years; 30% female) who reported five or more heavy drinking episodes in the past 30 days. Drinking history and alcohol problem severity were assessed. A common white matter factor was created from fractional anisotropy (FA) values of five white matter tracts: body of corpus callosum, fornix, external capsule, superior longitudinal fasciculus, and cingulate gyrus. Previous research has implicated these tracts in heavy drinking. Structural equation modeling (SEM) analyses tested the hypothesis that, after controlling for duration of alcohol exposure, clinical and behavioral measures of alcohol use severity would be associated with lower white matter factor scores. Potential interactions with smoking status, gender, age, treatment-seeking status, and depression or anxiety symptoms also were tested. Controlling for number of years drinking, greater alcohol problem severity and recent drinking frequency were significantly associated with lower white matter factor scores. The effect of drinking frequency differed significantly for men and women, such that higher drinking frequency was linked to lower white matter factor scores in women but not in men. In conclusion, alcohol problem severity was a significant predictor of lower white matter FA in heavy drinkers, after controlling for duration of alcohol exposure. In addition, more frequent drinking contributed to lower FA in women but not men, suggesting gender-specific vulnerability to alcohol neurotoxicity.     

Apathy and White Matter Integrity in Alzheimer’s Disease: A Whole Brain Analysis with Tract-Based Spatial Statistics

The aim of this study was to investigate the microstructural alterations of white matter (WM) in Alzheimer’s disease (AD) patients with apathy and to observe the relationships with the severity of apathy. Sixty drug-naïve subjects took part in this study (30 apathetic and 30 nonapathetic subjects with AD). The loss of integrity in WM was compared in AD patients with and without apathy through measurement of fractional anisotropy (FA) using by tract-based spatial statistics (TBSS). In addition, we explored the correlation pattern between FA values and the severity of apathy in AD patients with apathy. The apathy group had significantly reduced FA values (p_corrected<0.05) in the genu of the corpus callosum compared to the nonapathy group. The severity of apathy was negatively correlated with FA values of the left anterior and posterior cingulum, right superior longitudinal fasciculus, splenium, body and genu of the corpus callosum and bilateral uncinate fasciculusin the apathy group (p_corrected<0.05). This study was the first to explore FA values in whole brain WM in AD patients with apathy. The findings of these microstructural alterations of WM may be the key to the understanding of underlying neurobiological mechanism and clinical significances of apathy in AD.     

Cognitive Processing Speed in Older Adults: Relationship with White Matter Integrity

Cognitive processing slows with age. We sought to determine the importance of white matter integrity, assessed by diffusion tensor imaging (DTI), at influencing cognitive processing speed among normal older adults, assessed using a novel battery of computerized, non-verbal, choice reaction time tasks. We studied 131 cognitively normal adults aged 55–87 using a cross-sectional design. Each participant underwent our test battery, as well as MRI with DTI. We carried out cross-subject comparisons using tract-based spatial statistics. As expected, reaction time slowed significantly with age. In diffuse areas of frontal and parietal white matter, especially the anterior corpus callosum, fractional anisotropy values correlated negatively with reaction time. The genu and body of the corpus callosum, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus were among the areas most involved. This relationship was not explained by gray or white matter atrophy or by white matter lesion volume. In a statistical mediation analysis, loss of white matter integrity mediated the relationship between age and cognitive processing speed.     

Exploratory analysis of diffusion tensor imaging in children with attention deficit hyperactivity disorder: evidence of abnormal white matter structure

Abnormalities in the white matter microstructure of the attentional system have been implicated in the aetiology of attention deficit hyperactivity disorder (ADHD). Diffusion tensor imaging (DTI) is a promising magnetic resonance imaging (MRI) technology that has increasingly been used in studies of white matter microstructure in the brain. The main objective of this work was to perform an exploratory analysis of white matter tracts in a sample of children with ADHD versus typically developing children (TDC). For this purpose, 13 drug-naive children with ADHD of both genders underwent MRI using DTI acquisition methodology and tract-based spatial statistics. The results were compared to those of a sample of 14 age- and gender-matched TDC. Lower fractional anisotropy was observed in the splenium of the corpus callosum, right superior longitudinal fasciculus, bilateral retrolenticular part of the internal capsule, bilateral inferior fronto-occipital fasciculus, left external capsule and posterior thalamic radiation (including right optic radiation). We conclude that white matter tracts in attentional and motor control systems exhibited signs of abnormal microstructure in this sample of drug-naive children with ADHD.     

Diffusion Tensor Imaging of Parkinson’s Disease,Multiple System Atrophy and Progressive Supranuclear Palsy: A Tract-Based Spatial Statistics Study

Although often clinically indistinguishable in the early stages, Parkinson’s disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) have distinct neuropathological changes. The aim of the current study was to identify white matter tract neurodegeneration characteristic of each of the three syndromes. Tract-based spatial statistics (TBSS) was used to perform a whole-brain automated analysis of diffusion tensor imaging (DTI) data to compare differences in fractional anisotropy (FA) and mean diffusivity (MD) between the three clinical groups and healthy control subjects. Further analyses were conducted to assess the relationship between these putative indices of white matter microstructure and clinical measures of disease severity and symptoms. In PSP, relative to controls, changes in DTI indices consistent with white matter tract degeneration were identified in the corpus callosum, corona radiata, corticospinal tract, superior longitudinal fasciculus, anterior thalamic radiation, superior cerebellar peduncle, medial lemniscus, retrolenticular and anterior limb of the internal capsule, cerebral peduncle and external capsule bilaterally, as well as the left posterior limb of the internal capsule and the right posterior thalamic radiation. MSA patients also displayed differences in the body of the corpus callosum corticospinal tract, cerebellar peduncle, medial lemniscus, anterior and superior corona radiata, posterior limb of the internal capsule external capsule and cerebral peduncle bilaterally, as well as the left anterior limb of the internal capsule and the left anterior thalamic radiation. No significant white matter abnormalities were observed in the PD group. Across groups, MD correlated positively with disease severity in all major white matter tracts. These results show widespread changes in white matter tracts in both PSP and MSA patients, even at a mid-point in the disease process, which are not found in patients with PD.     

Age-related white matter microstructural differences partly mediate age-related decline in processing speed but not cognition

Aging is associated with declining cognitive performance as well as structural changes in brain gray and white matter (WM). The WM deterioration contributes to a disconnection among distributed brain networks and may thus mediate age-related cognitive decline. The present diffusion tensor imaging (DTI) study investigated age-related differences in WM microstructure and their relation to cognition (episodic memory, visuospatial processing, fluency, and speed) in a large group of healthy subjects (n = 287) covering 6 decades of the human life span. Age related decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were observed across the entire WM skeleton as well as in specific WM tracts, supporting the WM degeneration hypothesis. The anterior section of the corpus callosum was more susceptible to aging compared to the posterior section, lending support to the anterior-posterior gradient of WM integrity in the corpus callosum. Finally, and of critical interest, WM integrity differences were found to mediate age-related reductions in processing speed but no significant mediation was found for episodic memory, visuospatial ability, or fluency. These findings suggest that compromised WM integrity is not a major contributing factor to declining cognitive performance in normal aging. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

Elevated Hair Cortisol Levels among Heroin Addicts on Current Methadone Maintenance Compared to Controls

Whether methadone maintenance treatment (MMT) can improve the basal function of the hypothalamic–pituitary–adrenal (HPA) axis, which is suppressed by long-term heroin consumption, is a matter of debate. The stress state and depression and anxiety symptoms may affect the basal activity of the HPA axis in MMT patients. However, the effect of psychological factors on HPA activity was not simultaneously controlled in previous studies. This study investigated differences in HPA basal activity between MMT patients and controls using psychological variables as covariates. The participants included 52 MMT patients and 41 age-matched, non-heroin-dependent controls. Psychological states were self-reported with the Perceived Stress Scale, Self-Rating Depression Scale and Self-Rating Anxiety Scale. The hair cortisol level was adopted as a biomarker of HPA basal activity and was determined with liquid chromatography tandem mass spectrometry. The results revealed that MMT patients had significantly higher hair cortisol levels than the controls (p<0.05), but the difference was not significant (p>0.05) when the perceived stress, depression and anxiety scores were used as covariates. We concluded that patients with long-term MMT showed higher basal activity of the HPA axis. The high chronic stress state and increase in depression and anxiety symptoms may mask the suppression effect of methadone on the HPA activity.     

Microstructural White Matter Changes,Not Hippocampal Atrophy,Detect Early Amnestic Mild Cognitive Impairment

Background

Alzheimer’s disease (AD) is generally considered to be characterized by pathology in gray matter of the brain, but convergent evidence suggests that white matter degradation also plays a vital role in its pathogenesis. The evolution of white matter deterioration and its relationship with gray matter atrophy remains elusive in amnestic mild cognitive impairment (aMCI), a prodromal stage of AD.

Methods

We studied 155 cognitively normal (CN) and 27 ‘late’ aMCI individuals with stable diagnosis over 2 years, and 39 ‘early’ aMCI individuals who had converted from CN to aMCI at 2-year follow up. Diffusion tensor imaging (DTI) tractography was used to reconstruct six white matter tracts three limbic tracts critical for episodic memory function - the fornix, the parahippocampal cingulum, and the uncinate fasciculus; two cortico-cortical association fiber tracts - superior longitudinal fasciculus and inferior longitudinal fasciculus; and one projection fiber tract - corticospinal tract. Microstructural integrity as measured by fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AxD) was assessed for these tracts.

Results

Compared with CN, late aMCI had lower white matter integrity in the fornix, the parahippocampal cingulum, and the uncinate fasciculus, while early aMCI showed white matter damage in the fornix. In addition, fornical measures were correlated with hippocampal atrophy in late aMCI, whereas abnormality of the fornix in early aMCI occurred in the absence of hippocampal atrophy and did not correlate with hippocampal volumes.

Conclusions

Limbic white matter tracts are preferentially affected in the early stages of cognitive dysfunction. Microstructural degradation of the fornix preceding hippocampal atrophy may serve as a novel imaging marker for aMCI at an early stage.     

An Uncertain Dominion: Irish Psychiatry,Methadone, and the Treatment of Opiate Abuse

This paper investigates some productive ambiguities around the medical administration of methadone in the Republic of Ireland. The tensions surrounding methadone maintenance therapy (MMT) are outlined, as well as the sociohistorical context in which a serious heroin addiction problem in Ireland developed. Irish psychiatry intervened in this situation, during a time of institutional change, debates concerning the nature of addiction, moral panics concerning heroin addiction in Irish society and the recent boom in the Irish economy, known popularly as the Celtic Tiger. A particular history of this sort illuminates how technologies like MMT become cosmopolitan, settling into, while changing, local contexts.     

Neuroanatomical Correlates of Theory of Mind Deficit in Parkinson’s Disease: A Multimodal Imaging Study

BackgroundParkinson’s disease (PD) patients show theory of mind (ToM) deficit since the early stages of the disease, and this deficit has been associated with working memory, executive functions and quality of life impairment. To date, neuroanatomical correlates of ToM have not been assessed with magnetic resonance imaging in PD. The main objective of this study was to assess cerebral correlates of ToM deficit in PD. The second objective was to explore the relationships between ToM, working memory and executive functions, and to analyse the neural correlates of ToM, controlling for both working memory and executive functions.MethodsThirty-seven PD patients (Hoehn and Yahr median = 2.0) and 15 healthy controls underwent a neuropsychological assessment and magnetic resonance images in a 3T-scanner were acquired. T1-weighted images were analysed with voxel-based morphometry, and white matter integrity and diffusivity measures were obtained from diffusion weighted images and analysed using tract-based spatial statistics.ResultsPD patients showed impairments in ToM, working memory and executive functions; grey matter loss and white matter reduction compared to healthy controls. Grey matter volume decrease in the precentral and postcentral gyrus, middle and inferior frontal gyrus correlated with ToM deficit in PD. White matter in the superior longitudinal fasciculus (adjacent to the parietal lobe) and white matter adjacent to the frontal lobe correlated with ToM impairment in PD. After controlling for executive functions, the relationship between ToM deficit and white matter remained significant for white matter areas adjacent to the precuneus and the parietal lobe.ConclusionsFindings reinforce the existence of ToM impairment from the early Hoehn and Yahr stages in PD, and the findings suggest associations with white matter and grey matter volume decrease. This study contributes to better understand ToM deficit and its neural correlates in PD, which is a basic skill for development of healthy social relationships.     

Imaging-Based Biomarkers of Cognitive Performance in Older Adults Constructed via High-Dimensional Pattern Regression Applied to MRI and PET

In this study, we used high-dimensional pattern regression methods based on structural (gray and white matter; GM and WM) and functional (positron emission tomography of regional cerebral blood flow; PET) brain data to identify cross-sectional imaging biomarkers of cognitive performance in cognitively normal older adults from the Baltimore Longitudinal Study of Aging (BLSA). We focused on specific components of executive and memory domains known to decline with aging, including manipulation, semantic retrieval, long-term memory (LTM), and short-term memory (STM). For each imaging modality, brain regions associated with each cognitive domain were generated by adaptive regional clustering. A relevance vector machine was adopted to model the nonlinear continuous relationship between brain regions and cognitive performance, with cross-validation to select the most informative brain regions (using recursive feature elimination) as imaging biomarkers and optimize model parameters. Predicted cognitive scores using our regression algorithm based on the resulting brain regions correlated well with actual performance. Also, regression models obtained using combined GM, WM, and PET imaging modalities outperformed models based on single modalities. Imaging biomarkers related to memory performance included the orbito-frontal and medial temporal cortical regions with LTM showing stronger correlation with the temporal lobe than STM. Brain regions predicting executive performance included orbito-frontal, and occipito-temporal areas. The PET modality had higher contribution to most cognitive domains except manipulation, which had higher WM contribution from the superior longitudinal fasciculus and the genu of the corpus callosum. These findings based on machine-learning methods demonstrate the importance of combining structural and functional imaging data in understanding complex cognitive mechanisms and also their potential usage as biomarkers that predict cognitive status.     

Improved sensitivity to cerebral white matter abnormalities in Alzheimer's disease with spherical deconvolution based tractography

Diffusion tensor imaging (DTI) based fiber tractography (FT) is the most popular approach for investigating white matter tracts in vivo, despite its inability to reconstruct fiber pathways in regions with "crossing fibers." Recently, constrained spherical deconvolution (CSD) has been developed to mitigate the adverse effects of "crossing fibers" on DTI based FT. Notwithstanding the methodological benefit, the clinical relevance of CSD based FT for the assessment of white matter abnormalities remains unclear. In this work, we evaluated the applicability of a hybrid framework, in which CSD based FT is combined with conventional DTI metrics to assess white matter abnormalities in 25 patients with early Alzheimer's disease. Both CSD and DTI based FT were used to reconstruct two white matter tracts: one with regions of "crossing fibers," i.e., the superior longitudinal fasciculus (SLF) and one which contains only one fiber orientation, i.e. the midsagittal section of the corpus callosum (CC). The DTI metrics, fractional anisotropy (FA) and mean diffusivity (MD), obtained from these tracts were related to memory function. Our results show that in the tract with "crossing fibers" the relation between FA/MD and memory was stronger with CSD than with DTI based FT. By contrast, in the fiber bundle where one fiber population predominates, the relation between FA/MD and memory was comparable between both tractography methods. Importantly, these associations were most pronounced after adjustment for the planar diffusion coefficient, a measure reflecting the degree of fiber organization complexity. These findings indicate that compared to conventionally applied DTI based FT, CSD based FT combined with DTI metrics can increase the sensitivity to detect functionally significant white matter abnormalities in tracts with complex white matter architecture.     

Correlating Function and Imaging Measures of the Medial Longitudinal Fasciculus

Objective

To test the validity of diffusion tensor imaging (DTI) measures of tissue injury by examining such measures in a white matter structure with well-defined function, the medial longitudinal fasciculus (MLF). Injury to the MLF underlies internuclear ophthalmoparesis (INO).

Methods

40 MS patients with chronic INO and 15 healthy controls were examined under an IRB-approved protocol. Tissue integrity of the MLF was characterized by DTI parameters: longitudinal diffusivity (LD), transverse diffusivity (TD), mean diffusivity (MD) and fractional anisotropy (FA). Severity of INO was quantified by infrared oculography to measure versional disconjugacy index (VDI).

Results

LD was significantly lower in patients than in controls in the medulla-pons region of the MLF (p < 0.03). FA was also lower in patients in the same region (p < 0.0004). LD of the medulla-pons region correlated with VDI (R = -0.28, p < 0.05) as did FA in the midbrain section (R = 0.31, p < 0.02).

Conclusions

This study demonstrates that DTI measures of brain tissue injury can detect injury to a functionally relevant white matter pathway, and that such measures correlate with clinically accepted evaluation indices for INO. The results validate DTI as a useful imaging measure of tissue integrity.     

Early microstructural white matter changes in patients with HIV: a diffusion tensor imaging study

ABSTRACT: Previous studies have reported white matter (WM) brain alterations in asymptomatic patients with human immunodeficiency virus (HIV). We compared diffusion tensor imaging (DTI) derived WM fractional anisotropy (FA) between HIV-patients with and without mild macroscopic brain lesions determined using standard magnetic resonance imaging (MRI). We furthermore investigated whether WM alterations co-occurred with neurocognitive deficits and depression. We performed structural MRI and DTI for 19 patients and 19 age-matched healthy controls. Regionally-specific WM integrity was investigated using voxel-based statistics of whole-brain FA maps and region-of-interest analysis. Each patient underwent laboratory and neuropsychological tests. Structural MRI revealed no lesions in twelve (HIV-MRN) and unspecific mild macrostructural lesions in seven patients (HIV-MRL). Both analyses revealed widespread FA-alterations in all patients. Patients with HIV-MRL had FA-alterations primarily adjacent to the observed lesions and, whilst reduced in extent, patients with HIV-MRN also exhibited FA-alterations in similar regions. Patients with evidence of depression showed FA-increase in the ventral tegmental area, pallidum and nucleus accumbens in both hemispheres, and patients with evidence of HIV-associated neurocognitive disorder showed widespread FA-reduction. These results show that patients with HIV-MRN have evidence of FA-alterations in similar regions that are lesioned in HIV-MRL patients, suggesting common neuropathological processes. Furthermore, they suggest a biological rather a reactive origin of depression in HIV-patients.     

Chronic memory impairment after cardiac arrest outside hospital.

OBJECTIVES--To evaluate the nature, prevalence, and severity of chronic memory deficit in patients resuscitated after cardiac arrest outside hospital and to determine whether such deficits are related to duration of cardiac arrest. DESIGN--Case-control study. SUBJECTS--35 survivors of cardiac arrest outside hospital and 35 controls matched for age and sex who had had acute myocardial infarction without cardiac arrest. MAIN OUTCOME MEASURES--Subjects assessed at least two months after index event for affective state (hospital anxiety and depression scale), premorbid intelligence (national adult reading test), short term recall (digit recall test), and episodic long term memory (Rivermead behavioural memory test). RESULTS--Cases and controls showed no difference in short term recall. Cases scored lower on Rivermead test than controls (mean (SD) score out of 24 points: 17.4 (5.4) v 21.8 (2.0), P < 0.001), particularly in subtests relating to verbal and spatial memory. Moderate or severe impairment was found in 37% of cases and in no controls. Severity of impairment of memory correlated significantly with measures of duration of cardiac arrest. This deficit was not significantly associated with subjects'' age, interval from index event to assessment, occupation, measures of comorbidity, social deprivation, anxiety or depression scores, or estimated premorbid intelligence. CONCLUSIONS--Clinically important impairment of memory was common after cardiac arrest outside hospital. Improvement in response times of emergency services could reduce the severity of such deficits. With an increasing numbers of people expected to survive cardiac arrest outside hospital, rehabilitation of those with memory deficit merits specific attention.