Accelerated aging of selective brain structures in human immunodeficiency virus infection: a controlled, longitudinal magnetic resonance imaging study.

Advances in treatment have transformed human immunodeficiency virus (HIV) infection from an inexorable march to severe morbidity and premature death to a manageable chronic condition, often marked by good health. Thus, infected individuals are living long enough that there is a potential for interaction with normal senescence effects on various organ systems, including the brain. To examine this interaction, the brains of 51 individuals with HIV infection and 65 uninfected controls were studied using 351 magnetic resonance imaging and a battery of neuropsychological tests collected 2 or more times over follow-up periods ranging from 6 months to 8 years. Brain tissue regions of interest showed expected age-related decrease in volume; cerebrospinal fluid-filled spaces showed increase in volume for both groups. Although HIV-infected individuals were in good general health, and free of clinically-detectable dementia, several brain regions supporting higher-order cognition and integration of functions showed acceleration of the normal aging trajectory, including neocortex, which extended from the frontal and temporal poles to the parietal lobe, and the thalamus. Beyond an anticipated increase in lateral ventricle and Sylvian fissure volumes and decrease in tissue volumes (specifically, the frontal and sensorimotor neocortices, thalamus, and hippocampus) with longer duration of illness, most regions also showed accelerated disease progression. This accelerated loss of cortical tissue may represent a risk factor for premature cognitive and motor compromise if not dementia. On a more promising note, HIV-infected patients with increasing CD4 counts exhibited slower expansion of Sylvian fissure volume and slower declines of frontal and temporoparietal cortices, insula, and hippocampus tissue volumes. Thus, attenuated shrinkage of these brain regions, likely with adequate pharmacologic treatment and control of further infection, has the potential of abating decline in associated higher-order functions, notably, explicit memory, executive functions, self-regulation, and visuospatial abilities.

Thalamic volume deficit contributes to procedural and explicit memory impairment in HIV infection with primary alcoholism comorbidity.

Component cognitive and motor processes contributing to diminished visuomotor procedural learning in HIV infection with comorbid chronic alcoholism (HIV+ALC) include problems with attention and explicit memory processes. The neural correlates associated with this constellation of cognitive and motor processes in HIV infection and alcoholism have yet to be delineated. Frontostriatal regions are affected in HIV infection, frontothalamocerebellar regions are affected in chronic alcoholism, and frontolimbic regions are likely affected in both; all three of these systems have the potential of contributing to both visuomotor procedural learning and explicit memory processes. Here, we examined the neural correlates of implicit memory, explicit memory, attention, and motor tests in 26 HIV+ALC (5 with comorbidity for nonalcohol drug abuse/dependence) and 19 age-range matched healthy control men. Parcellated brain volumes, including cortical, subcortical, and allocortical regions, as well as cortical sulci and ventricles, were derived using the SRI24 brain atlas. Results indicated that smaller thalamic volumes were associated with poorer performance on tests of explicit (immediate and delayed) and implicit (visuomotor procedural) memory in HIV+ALC. By contrast, smaller hippocampal volumes were associated with lower scores on explicit, but not implicit memory. Multiple regression analyses revealed that volumes of both the thalamus and the hippocampus were each unique independent predictors of explicit memory scores. This study provides evidence of a dissociation between implicit and explicit memory tasks in HIV+ALC, with selective relationships observed between hippocampal volume and explicit but not implicit memory, and highlights the relevance of the thalamus to mnemonic processes.

White matter microstructural recovery with abstinence and decline with relapse in alcohol dependence interacts with normal ageing: a controlled longitudinal DTI study.

BACKGROUND: Alcohol dependence exacts a toll on brain white matter microstructure, which has the potential of repair with prolonged sobriety. Diffusion tensor imaging (DTI) enables in-vivo quantification of tissue constituents and localisation of tracts potentially affected in alcohol dependence and its recovery. We did an extended longitudinal study of alcoholism's trajectory of effect on selective fibre bundles with sustained sobriety or decline with relapse. METHODS: Participants were drawn from a longitudinal, 1·5T DTI database of 841 scans of individuals with various medical or neuropsychiatric conditions and normal ageing. Participants diagnosed with alcohol dependence had to meet the criteria from DSM-IV for alcohol dependence. Controls were screened and free of any DSM-IV axis I diagnosis, including being without history of alcohol or drug abuse or dependence. Tract-based spatial statistics (TBSS) quantified white matter integrity throughout the brain in 47 alcohol-dependent individuals and 56 controls examined 2-5 times over 1-8 year intervals. We identified regions showing group differences with a white matter atlas. For macrostructural comparison, we measured corpus callosum and centrum semiovale volumes on MRI. FINDINGS: This study took place in the USA, between June 23, 2000, and Sept 6, 2011. TBSS identified a large cluster (threshold p<0·001), where controls showed significant fractional anisotropy (FA) decrease with ageing and alcohol-dependent individuals had significantly lower FA than controls regardless of age. Over the examination interval, 27 (57%) alcohol-dependent individuals abstained, ten (21%) relapsed into light drinking, and ten (21%) relapsed into heavy drinking (>5 kg of alcohol/year). Despite abnormally low FA, age trajectories of the abstainers were positive and progressing toward normality, whereas those of the relapsers and controls were negative. Axial diffusivity (lower values indexing myelin integrity) was abnormally high in the total alcohol-dependent group; however, the abstainers' slopes paralleled those of controls, whereas the heavy-drinking relapsers' slopes showed accelerated ageing. Callosal genu and body microstructure but not macrostructure showed untoward alcohol-related effects. Affected projection and association tracts had an anterior and superior neuroanatomical distribution. INTERPRETATION: Return to heavy drinking resulted in accelerating microstructural white matter damage. Despite evidence for damage, alcohol-dependent individuals maintaining sobriety over extended periods showed improvement in brain fibre tract integrity reflective of fibre reorganisation and myelin restoration, indicative of a neural mechanism explaining recovery. FUNDING: US National Institute on Alcohol Abuse and Alcoholism (AA012388, AA017168, AA005965, AA013521-INIA).

Variation in longitudinal trajectories of regional brain volumes of healthy men and women (ages 10 to 85 years) measured with atlas-based parcellation of MRI.

Numerous cross-sectional MRI studies have characterized age-related differences in regional brain volumes that differ with structure and tissue type. The extent to which cross-sectional assumptions about change are accurate depictions of actual longitudinal measurement remains controversial. Even longitudinal studies can be limited by the age range of participants, sex distribution of the samples, and scan intervals. To address these issues, we calculated trajectories of regional brain volume changes from T1-weighted (SPGR) MRI data, quantified with our automated, unsupervised SRI24 atlas-based registration and parcellation method. Longitudinal MRIs were acquired at 3T in 17 boys and 12 girls, age 10 to 14 years, and 41 men and 41 women, age 20 to 85 years at first scan. Application of a regression-based correction function permitted merging of data acquired at 3T field strength with data acquired at 1.5T from additional subjects, thereby expanding the sample to a total of 55 men and 67 women, age 20 to 85 years at first scan. Adjustment for individual supratentorial volume removed regional volume differences between men and women due to sex-related differences in head size. Individual trajectories were computed from data collected on 2 to 6 MRIs at a single field strength over a ~1 to 8 year interval. Using linear mixed-effects models, the pattern of trajectories over age indicated: rises in ventricular and Sylvian fissure volumes, with older individuals showing faster increases than younger ones; declines in selective cortical volumes with faster tissue shrinkage in older than younger individuals; little effect of aging on volume of the corpus callosum; more rapid expansion of CSF-filled spaces in men than women after age 60 years; and evidence for continued growth in central white matter through early adulthood with accelerated decline in senescence greater in men than women.

Differential effect of alcoholism and HIV infection on visuomotor procedural learning and retention.

BACKGROUND: Selective declarative memory processes are differentially compromised in chronic alcoholism (ALC) and HIV infection (HIV) and likely reflect neuropathology associated with each condition: frontocerebellar dysfunction in ALC and frontostriatal dysfunction in HIV infection. Evidence for disease overlap derives from observed exacerbated impairments in these declarative memory processes in ALC-HIV comorbidity. Less is known about nondeclarative memory processes in these disease conditions. Examination of visuomotor learning in chronic ALC and HIV infection could provide insight into the differential and combined contribution of selective disease-related injury to visuomotor procedural memory processes. METHODS: We examined component processes of visuomotor learning and retention on the rotary pursuit task in 29 ALC, 23 HIV, 28 ALC + HIV, and 20 control subjects. Participants were given 4 rotary pursuit learning sessions over 2 testing days, typically separated by 1 week, to assess visuomotor learning and retention patterns. Ancillary measures of simple motor, psychomotor, explicit memory, and balance abilities were administered to test which component processes independently predicted visuomotor learning. RESULTS: All clinical groups showed visuomotor learning across rotary pursuit testing sessions, despite impairment in visuomotor speed in the HIV groups and impairment in explicit memory and psychomotor speed in the alcohol groups. The 2 alcoholic groups showed retention and consolidation over time (i.e., improved performance without further training), whereas the HIV-infected group showed learning and retention but no consolidation effect. The comorbid group shared impairments associated with the ALC-only group (explicit memory and psychomotor speed) and the HIV-only group (visuomotor speed), although there was no clear compounded effect of alcohol and HIV infection on visuomotor learning performance. CONCLUSIONS: This study supports the hypothesis that ALC and HIV infection exert differential effects on components of visuomotor procedural learning. Further, the results provide behavioral evidence for dissociable influences of frontocerebellar and frontostriatal disruption to visuomotor procedural learning and retention.

Selective neurocognitive deficits and poor life functioning are associated with significant depressive symptoms in alcoholism-HIV infection comorbidity.

Alcoholism, HIV, and depressive symptoms frequently co-occur and are associated with impairment in cognition and life function. We administered the Beck Depression Inventory-II (BDI-II), measures of life function, and neurocognitive tests to 67 alcoholics, 56 HIV+ patients, 63 HIV+ alcoholics, and 64 controls to examine whether current depressive symptom level (significant, BDI-II>14 vs. minimal, BDI-II<14) was associated with poorer cognitive or psychosocial function in alcoholism-HIV comorbidity. Participants with significant depressive symptoms demonstrated slower manual motor speed and poorer visuospatial memory than those with minimal depressive symptoms. HIV patients with depressive symptoms showed impaired manual motor speed. Alcoholics with depressive symptoms showed impaired visuospatial memory. HIV+ alcoholics with depressive symptoms reported the poorest quality of life; alcoholics with depressive symptoms, irrespective of HIV status, had poorest life functioning. Thus, significant depressive symptoms were associated with poorer selective cognitive and life functioning in alcoholism and in HIV infection, even though depressive symptoms had neither synergistic nor additive effects on cognition in alcoholism-HIV comorbidity. The results suggest the relevance of assessing and treating current depressive symptoms to reduce cognitive compromise and functional disability in HIV infection, alcoholism, and their comorbidity.

Regional brain structural dysmorphology in human immunodeficiency virus infection: effects of acquired immune deficiency syndrome, alcoholism, and age.

BACKGROUND: Human immunodeficiency virus (HIV) infection and alcoholism each carries liability for disruption of brain structure and function integrity. Despite considerable prevalence of HIV-alcoholism comorbidity, few studies examined the potentially heightened burden of disease comorbidity. METHODS: Participants were 342 men and women: 110 alcoholics, 59 with HIV infection, 65 with HIV infection and alcoholism, and 108 healthy control subjects. This design enabled examination of independent and combined effects of HIV infection and alcoholism along with other factors (acquired immune deficiency syndrome [AIDS]-defining events, hepatitis C infection, age) on regional brain volumes derived from T1-weighted magnetic resonance images. RESULTS: Brain volumes, expressed as Z scores corrected for intracranial volume and age, were measured in 20 tissue and 5 ventricular and sulcal regions. The most profound and consistent volume deficits occurred with alcohol use disorders, notable in the cortical mantle, insular and anterior cingulate cortices, thalamus, corpus callosum, and frontal sulci. The HIV-only group had smaller thalamic and larger frontal sulcal volumes than control subjects. HIV disease-related factors associated with greater volume abnormalities included CD4 cell count nadir, clinical staging, history of AIDS-defining events, infection age, and current age. Longer sobriety and less lifetime alcohol consumption were predictive of attenuated brain volume abnormalities in both alcohol groups. CONCLUSIONS: Having HIV infection with alcoholism and AIDS had an especially poor outcome on brain structures. That longer periods of sobriety and less lifetime alcohol consumption were predictive of attenuated brain volume abnormalities encourages the inclusion of alcohol recovery efforts in HIV/AIDS therapeutic settings.

Combining atlas-based parcellation of regional brain data acquired across scanners at 1.5 T and 3.0 T field strengths.

Longitudinal brain morphometric studies designed for data acquisition at a single MRI field strength can be seriously limited by system replacements from lower to higher field strength. Merging data across field strengths has not been endorsed for a variety of reasons, yet the ability to combine such data would broaden longitudinal investigations. To determine whether structural T1-weighted MRI data acquired across MR field strengths could be merged, parcellations of archival SPGR data acquired in 114 individuals at 1.5 T and at 3.0 T within 3 weeks of each other were compared. The first set of analyses examined 1) the correspondence between regional tissue volumes derived from data collected at 1.5 T and 3.0 T and 2) whether there were systematic differences for which a correction factor could be determined and applied to improve measurement agreement. Comparability of regional volume determination at 1.5 T and 3.0 T was assessed with intraclass correlation (ICC) computed on volumes derived from the automated and unsupervised SRI24 atlas registration and parcellation method. A second set of analyses measured the reliability of the registration and quantification using the same approach on longitudinal data acquired in 69 healthy adults at a single field strength, 1.5 T, at an interval < 2 years. The mainstay of the analyses was based on the SRI24 method; to examine the potential of merging data across field strengths and across image analysis packages, a secondary set of analyses used FreeSurfer instead of the SRI24 method. For both methods, a regression-based linear correction function significantly improved correspondence. The results indicated high correspondence between most selected cortical, subcortical, and CSF-filled spaces; correspondence was lowest in the globus pallidus, a region rich in iron, which in turn has a considerable field-dependent effect on signal intensity. Thus, the application of a regression-based correction function that improved the correspondence in regional volume estimations argues well for the proposition that selected T1-weighted regional anatomical brain data can be reliably combined across 1.5 T and 3.0 T field strengths with the application of an appropriate correction procedure.

Remote semantic memory for public figures in HIV infection, alcoholism, and their comorbidity.

BACKGROUND: Impairments in component processes of working and episodic memory mark both HIV infection and chronic alcoholism, with compounded deficits often observed in individuals comorbid for these conditions. Remote semantic memory processes, however, have only seldom been studied in these diagnostic groups. Examination of remote semantic memory could provide insight into the underlying processes associated with storage and retrieval of learned information over extended time periods while elucidating spared and impaired cognitive functions in these clinical groups. METHODS: We examined component processes of remote semantic memory in HIV infection and chronic alcoholism in 4 subject groups (HIV, ALC, HIV + ALC, and age-matched healthy adults) using a modified version of the Presidents Test. Free recall, recognition, and sequencing of presidential candidates and election dates were assessed. In addition, component processes of working, episodic, and semantic memory were assessed with ancillary cognitive tests. RESULTS: The comorbid group (HIV + ALC) was significantly impaired on sequencing of remote semantic information compared with age-matched healthy adults. Free recall of remote semantic information was also modestly impaired in the HIV + ALC group, but normal performance for recognition of this information was observed. Few differences were observed between the single diagnosis groups (HIV, ALC) and healthy adults, although examination of the component processes underlying remote semantic memory scores elicited differences between the HIV and ALC groups. Selective remote memory processes were related to lifetime alcohol consumption in the ALC group and to viral load and depression level in the HIV group. Hepatitis C diagnosis was associated with lower remote semantic memory scores in all 3 clinical groups. Education level did not account for group differences reported. CONCLUSIONS: This study provides behavioral support for the existence of adverse effects associated with the comorbidity of HIV infection and chronic alcoholism on selective component processes of memory function, with untoward effects exacerbated by Hepatitis C infection. The pattern of remote semantic memory function in HIV + ALC is consistent with those observed in neurological conditions primarily affecting frontostriatal pathways and suggests that remote memory dysfunction in HIV + ALC may be a result of impaired retrieval processes rather than loss of remote semantic information per se.

Pontocerebellar contribution to postural instability and psychomotor slowing in HIV infection without dementia.

Postural instability occurs in HIV infection, but quantitative balance tests in conjunction with neuroimaging are lacking. We examined whether infratentorial brain tissue volume would be deficient in nondemented HIV-infected individuals and whether selective tissue deficits would be related to postural stability and psychomotor speed performance. The 123 participants included 28 men and 12 women with HIV infection without dementia or alcohol use disorders, and 40 men and 43 women without medical or psychiatric conditions. Participants completed quantitative balance testing, Digit Symbol test, and a test of finger movement speed and dexterity. An infratentorial brain region, supratentorial ventricular system, and corpus callosum were quantified with MRI-derived atlas-based parcellation, and together with archival DTI-derived fiber tracking of pontocerebellar and internal and external capsule fiber systems, brain measures were correlated with test performance. The tissue ratio of the infratentorium was ~3% smaller in the HIV than control group. The HIV group exhibited performance deficits in balancing on one foot, walking toe-to-heel, Digit Symbol substitution task, and time to complete all Digit Symbol grid boxes. Total infratentorial tissue ratio was a significant predictor of balance and Digit Symbol scores. Balance scores did not correlate significantly with ventricular volumes, callosal size, or internal or external capsule fiber integrity but did so with indices of pontocerebellar tract integrity. HIV-infected individuals specifically recruited to be without complications from alcohol use disorders had pontocerebellar tissue volume deficits with functional ramifications. Postural stability and psychomotor speed were impaired and attributable, at least in part, to compromised infratentorial brain systems.

Signs of preclinical Wernicke's encephalopathy and thiamine levels as predictors of neuropsychological deficits in alcoholism without Korsakoff's syndrome.

The purpose of this study was to determine whether meeting historical criteria for unsuspected Wernicke's encephalopathy (WE), largely under-diagnosed in vivo, explains why some alcoholics have severe neuropsychological deficits, whereas others, with a similar drinking history, exhibit preserved performance. Demographic, clinical, alcohol related, and neuropsychological measures were collected in 56 abstinent alcoholics and 38 non-alcohol-dependent volunteers. Alcoholics were classified using the clinical criteria established by Caine et al (1997) and validated in their neuropathological study of alcoholic cases. Our alcoholics who met a single criterion were considered 'at risk for WE' and those with two or more criteria with 'signs of WE'. Whole blood thiamine was also measured in 22 of the comparison group and 28 alcoholics. Of the alcoholics examined, 27% met no criteria, 57% were at risk for WE, and 16% had signs of WE. Neuropsychological performance of the alcoholic subgroups was graded, with those meeting zero criteria not differing from controls, those meeting one criterion presenting mild-to-moderate deficits on some of the functional domains, and those meeting two or more criteria having the most severe deficits on each of the domains examined. Thiamine levels were selectively related to memory performance in the alcoholics. Preclinical signs of WE can be diagnosed in vivo, enabling the identification of ostensibly 'uncomplicated' alcoholics who are at risk for neuropsychological complications. The graded effects in neuropsychological performance suggest that the presence of signs of WE explains, at least partially, the heterogeneity of alcoholism-related cognitive and motor deficits.

Age-related reorganization of functional networks for successful conflict resolution: a combined functional and structural MRI study.

Aging has readily observable effects on the ability to resolve conflict between competing stimulus attributes that are likely related to selective structural and functional brain changes. To identify age-related differences in neural circuits subserving conflict processing, we combined structural and functional MRI and a Stroop Match-to-Sample task involving perceptual cueing and repetition to modulate resources in healthy young and older adults. In our Stroop Match-to-Sample task, older adults handled conflict by activating a frontoparietal attention system more than young adults and engaged a visuomotor network more than young adults when processing repetitive conflict and when processing conflict following valid perceptual cueing. By contrast, young adults activated frontal regions more than older adults when processing conflict with perceptual cueing. These differential activation patterns were not correlated with regional gray matter volume despite smaller volumes in older than young adults. Given comparable performance in speed and accuracy of responding between both groups, these data suggest that successful aging is associated with functional reorganization of neural systems to accommodate functionally increasing task demands on perceptual and attentional operations.

Transcallosal white matter degradation detected with quantitative fiber tracking in alcoholic men and women: selective relations to dissociable functions.

INTRODUCTION: Excessive alcohol consumption can adversely affect white matter fibers and disrupt transmission of neuronal signals. Here, we examined six anatomically defined transcallosal white matter fiber bundles and asked whether any bundle was specifically vulnerable to alcohol, what aspect of white matter integrity was most affected, whether women were more vulnerable than men, and whether evidence of compromise in specific bundles was associated with deficits in balance, sustained attention, associative learning, and psychomotor function, commonly affected in alcoholics. METHODS: Diffusion tensor imaging quantitative fiber tracking assessed integrity of six transcallosal white matter bundles in 87 alcoholics (59 men, 28 women) and 88 healthy controls (42 men, 46 women). Measures included orientational diffusion coherence (fractional anisotropy, FA) and magnitude of diffusion, quantified separately for axial (longitudinal; lambdaL) and radial (transverse; lambdaT) diffusivity. The Digit Symbol Test and a test of ataxia were also administered. RESULTS: Alcoholism negatively affected callosal FA and lambdaT of all but the sensory-motor bundle. Women showed no evidence for greater vulnerability to alcohol than men. Multiple regression analyses confirmed a double dissociation: higher diffusivity in sensory-motor and parietal bundles was associated with poorer balance but not psychomotor speed, whereas higher diffusivity in prefrontal and temporal bundles was associated with slower psychomotor speed but not balance. CONCLUSIONS: This study revealed stronger alcohol effects for FA and radial diffusivity than axial diffusivity, suggesting myelin degradation, but no evidence for greater vulnerability to alcohol in women than men. The presence of brain-behavior relationships provides support for the role of alcoholism-related commissural white matter degradation as a substrate of cognitive and motor impairment. Identification of a double dissociation provides further support for the role of selective white matter integrity in specific domains of performance.

Focus on the brain: HIV infection and alcoholism: comorbidity effects on brain structure and function.

Both HIV infection and alcohol abuse have negative effects on the brain, with some unique to each condition and others shared by both conditions. Investigators have used magnetic resonance imaging to study the size and integrity of various brain structures in participants with alcoholism, HIV infection, or both conditions and in healthy control subjects. In these studies, alcoholics exhibited enlarged, cerebrospinal fluid-filled spaces (i.e., ventricles) as well as tissue shrinkage in various brain regions (e.g., the corpus callosum and frontal cortex), whereas study participants with asymptomatic HIV infection showed few abnormalities. Those with both HIV infection and alcoholism also had these volume abnormalities, particularly if they had experienced an AIDS-defining event. Diffusion tensor imaging, which measures the integrity of white matter fibers, has identified abnormalities of constituents of these fibers in both diseases. Again, people with HIV infection plus alcoholism show the greatest abnormalities, particularly those with a history of an AIDS-defining event. Magnetic resonance spectroscopy, which assesses the levels of brain metabolites and selective neurotransmitters, has revealed different patterns of deficits in biochemical markers of brain integrity in individuals singly affected and a compounding of effects in individuals with both HIV infection and alcoholism. Finally, neuropsychological studies have revealed impairment in selective functions involving working memory, visuospatial abilities, and movement speed that are especially likely to occur in people with comorbid HIV infection and alcoholism. Thus, alcoholism is a major risk factor for development of neuropathology and its functional sequelae in HIV-infected people.

Callosal degradation in HIV-1 infection predicts hierarchical perception: a DTI study.

HIV-1 infection affects white matter circuits linking frontal, parietal, and subcortical regions that subserve visuospatial attention processes. Normal perception requires the integration of details, preferentially processed in the left hemisphere, and the global composition of an object or scene, preferentially processed in the right hemisphere. We tested whether HIV-related callosal white matter degradation contributes to disruption of selective lateralized visuospatial and attention processes. A hierarchical letter target detection paradigm was devised, where large (global) letters were composed of small (local) letters. Participants were required to identify target letters among distractors presented at global, local, both or neither level. Attention was directed to one (global or local) or both levels. Participants were 21 HIV-1 infected and 19 healthy control men and women who also underwent Diffusion Tensor Imaging (DTI). HIV-1 participants showed impaired hierarchical perception owing to abnormally enhanced global facilitation effects but no impairment in attentional control on local-global feature selection. DTI metrics revealed poorer fiber integrity of the corpus callosum in HIV-1 than controls that was more pronounced in posterior than anterior regions. Analysis revealed a double dissociation of anterior and posterior callosal compromise in HIV-1 infection: compromise in anterior but not posterior callosal fiber integrity predicted response conflict elicited by global targets, whereas compromise in posterior but not anterior callosal fiber integrity predicted response facilitation elicited by global targets. We conclude that component processes of visuospatial perception are compromised in HIV-1 infection attributable, at least in part, to degraded callosal microstructural integrity relevant for local-global feature integration.

Frontostriatal fiber bundle compromise in HIV infection without dementia.

BACKGROUND: Quantitative fiber tracking derived from diffusion tensor imaging (DTI) was used to determine whether white matter association, projection, or commissural tracts are affected in nondemented individuals with HIV infection and to identify the regional distribution of sparing and impairment of fiber systems. METHODS: DTI measured fractional anisotropy and diffusivity, quantified separately for longitudinal (lambdaL) diffusivity (index of axonal injury) and transverse (lambdaT) diffusivity (index of myelin injury), in 11 association and projection white matter tracts and six commissural tracts in 29 men and 13 women with HIV infection and 88 healthy, age-matched controls (42 men and 46 women). RESULTS: The total group of HIV-infected individuals had higher diffusivity (principally longitudinal) than controls in the posterior sectors of the corpus callosum, internal and external capsules, and superior cingulate bundles. High longitudinal diffusivity, indicative of axonal compromise, was especially prominent in posterior callosal sectors, fornix, and superior cingulate bundle in HIV with AIDS. Unmedicated patients had notably high transverse diffusivity, indicative of myelin compromise, in the occipital forceps, inferior cingulate bundle, and superior longitudinal fasciculus. Pontocerebellar projection fibers were resistant to HIV effects as were commissural fibers coursing through premotor and sensorimotor callosal sectors. CONCLUSION: This quantitative survey of brain fiber tract integrity indicates that even nondemented HIV patients can have neuroradiological evidence for damage to association and commissural tracts. These abnormalities were vulnerable to exacerbation with AIDS and possibly mitigated by HAART.

Working and episodic memory in HIV infection, alcoholism, and their comorbidity: baseline and 1-year follow-up examinations.

BACKGROUND: Selective memory deficits occur in individuals with human immunodeficiency virus (HIV) infection and those with chronic alcoholism, but the potential compounded effect of these conditions is seldom considered, despite the high prevalence of alcohol use disorders in HIV infection. METHODS: Here, we examined component processes of working and episodic memory in HIV infection and chronic alcoholism (ALC) in 4 subject groups (HIV, ALC, HIV + ALC, and normal controls) at baseline and 1-year follow-up. Accuracy scores, response times, and rate of information processing were assessed with subtests of the computerized neuropsychological test battery, the MicroCog. RESULTS: Although individuals with either HIV infection or alcoholism generally performed at normal levels, individuals comorbid with HIV infection and alcoholism were impaired relative to controls and to the single diagnosis groups on selective memory processes. Immediate episodic memory was impaired, whereas working memory remained intact. Ability to retain information over time was not impaired in the clinical groups. Little performance change between groups was detected over 1 year. Results could not be explained by amount of alcohol consumed over a lifetime, CD4 cell count, AIDS diagnosis, or HAART medication. CONCLUSIONS: This study provides behavioral support for adverse synergism of HIV infection and chronic alcoholism on brain function and is consistent with neuroimaging reports of compromised hippocampal and associated memory structures related to episodic memory processes in these 2 conditions.

Contribution of Regional White Matter Integrity to Visuospatial Construction Accuracy, Organizational Strategy, and Memory for a Complex Figure in Abstinent Alcoholics.

Visuospatial construction ability as used in drawing complex figures is commonly impaired in chronic alcoholics, but memory for such information can be enhanced by use of a holistic drawing strategy during encoding. We administered the Rey-Osterrieth Complex Figure Test (ROCFT) to 41 alcoholic and 38 control men and women and assessed the contribution of diffusion tensor imaging (DTI) measures of integrity of selected white matter tracts to ROCFT copy accuracy, copy strategy, and recall accuracy. Although alcoholics copied the figure less accurately than controls, a more holistic strategy at copy was associated with better recall in both groups. Greater radial diffusivity, reflecting compromised myelin integrity, in occipital forceps and external capsule was associated with poorer copy accuracy in both groups. Lower FA, reflecting compromised fiber microstructure in the inferior cingulate bundle, which links frontal and medial temporal episodic memory systems, was associated with piecemeal copy strategy and poorer immediate recall in the alcoholics. The correlations were generally modest and should be considered exploratory. To the extent that the inferior cingulate was relatively spared in alcoholics, it may have provided an alternative pathway to the compromised frontal system for successful copy strategy and, by extension, aided recall.

Frontal Callosal Fiber Integrity Selectively Predicts Coordinated Psychomotor Performance in Chronic Alcoholism.

INTRODUCTION: Quantitative fiber tracking with diffusion tensor imaging (DTI) provides a new approach for assessing deficits in the microstructural integrity of white matter circuits that may underlie cognitive deficits associated with conditions affecting white matter, including chronic alcoholism. METHODS: Alcoholic men and women (n=87) and healthy controls (n=88) performed the Digit Symbol (DS) test and underwent structural and diffusion tensor imaging. Measures of fractional anisotropy (FA) of fibers passing through genu and splenium were computed, as were size of genu and splenium fiber target regions of interest (ROI). RESULTS: Alcoholics scored lower than controls on the DS and had even greater deficits in genu than splenium fiber FA. In alcoholics, fiber FA of the genu selectively predicted DS scores after accounting for splenium FA. Neither fiber FA measure predicted incidental recall of the symbols used in the task. Size of genu and splenium ROI, although reduced in alcoholics, did not predict DS score or incidental recall. CONCLUSIONS: Quantitative tractography of frontal fibers connecting left and right hemispheres selectively predicted performance by alcoholics on a coordinated psychomotor task and provide support for frontally based systems in Digit Symbol performance, both of which are compromised in recovering alcoholics.

Magnetic resonance imaging of the living brain: evidence for brain degeneration among alcoholics and recovery with abstinence.

Magnetic resonance imaging (MRI) provides a safe, noninvasive method to examine the brain's macrostructure, microstructure, and some aspects of how the living brain functions. MRI is capable of detecting abnormalities that can occur with alcoholism as well as changes that can occur with sobriety and relapse. The brain pathology associated with chronic excessive alcohol consumption is well documented with imaging of the living body (i.e., in vivo imaging). Consistent findings include shrinkage of the frontal cortex,1 underlying white matter, and cerebellum and expansion of the ventricles. Some of these changes are reversible with abstinence, but some appear to be enduring. Research showing correlations between brain structure and quantitative neuropsychological testing demonstrates the functional consequences of the pathology. In addition, functional imaging studies provide evidence that the brain compensates for cognitive deficits. The myriad concomitants of alcoholism, the antecedents, and the consumption patterns each may influence the observed brain changes associated with alcoholism, which tend to be more deleterious with increasing age. The multifaceted nature of alcoholism presents unique challenges and opportunities to understand the mechanisms underlying alcoholism-induced neuropathology and its recovery. Longitudinal MRI studies of animal models of alcoholism, however, can address questions about the development and course of alcohol dependence and the scope and limits of in vivo degeneration and recovery of brain structure and concomitant function that may not be readily addressed in clinical studies.