Biomedical subjects

Edith V Sullivan

Publications and source records attributed to Edith V Sullivan.

At least 37 records · Page 2Linked to original sources

PubMed2005

A dissociation in attentional control: evidence from methamphetamine dependence.

BACKGROUND: Selective attention comprises multiple, dissociable component processes, including task shifting and selective inhibition. The goal of this study was to test whether task-shifting, selective inhibition, or both processes were impaired in long-term but currently abstinent methamphetamine-dependent individuals. METHODS: Participants were 34 methamphetamine-dependent subjects and 20 nonsubstance abusing controls who were tested on an alternating-runs switch task with conflict sequences that required subjects to switch tasks on every second trial (AABBAABB). RESULTS: Methamphetamine-dependent individuals committed more errors on trials that required inhibition of distracting information compared with controls (methamphetamine = 17%; controls = 13%; p = .02). By contrast, error rates did not differ between the groups on switch trials (methamphetamine = 7%; controls = 6%; p = .68). CONCLUSIONS: These results indicate that selective inhibition, but not task switching, is selectively compromised by methamphetamine.

Adult↗

PubMed2005

Differential effect of HIV infection and alcoholism on conflict processing, attentional allocation, and perceptual load: evidence from a Stroop Match-to-Sample task.

BACKGROUND: Alcoholism and human immunodeficiency virus (HIV) infection each can impair components of selective attention, probably through disruption of the integrity of the frontoparietal neural systems that underlie conflict processing, attentional allocation, and perceptual load. METHODS: We studied 18 patients with alcoholism (ALC) alone, 19 with HIV infection alone (HIV), 20 with both disorders (H+A), and 19 healthy control subjects (CTL). We used a novel paradigm (Stroop Match-to-Sample tasks), in which subjects saw either a valid or invalid color cue before a target word, printed in a color that was either congruent or incongruent with the word's meaning. RESULTS: All groups showed a significant Stroop effect, cue-target color Match effect, and interaction between Match and Stroop, with an exaggerated Stroop effect for the Match condition. The HIV patients were comparable to CTL, whereas ALC showed mild delays, with further delays associated with comorbidity with HIV. Although H+A profited from a valid match to Stroop stimuli, they were compromised in disengaging attention from the invalidly cued color. CONCLUSIONS: Impairment in conflict processing and attentional allocation in alcoholism suggests disruption of frontal-parietal attentional systems. Although HIV alone did not demonstrate detectable impairment in performance, HIV conferred liability on attentional processes when combined with alcohol abuse.

Adult↗

PubMed2005

Disruption of brain white matter microstructure by excessive intracellular and extracellular fluid in alcoholism: evidence from diffusion tensor imaging.

Magnetic resonance diffusion tensor imaging (DTI) has revealed the disruption of brain white matter microstructure in normal aging and alcoholism undetectable with conventional structural MR imaging. The metrics of DTI can be useful in establishing the nature of the observed microstructural aberrations. Abnormally low fractional anisotropy (FA), a measure of diffusion orientation and coherence, may result from increased intracellular or extracellular fluid, which would be reflected in complementary high apparent diffusion coefficients (bulk mean diffusivity) and low FA, or from disorganization of fiber structure, which would be reflected in low FA but with a lack of the inverse FA and diffusivity relationship. To test these competing possibilities, we examined 15 alcoholic men and 31 control men with DTI to quantify diffusivity in the genu and splenium of the corpus callosum and centrum semiovale. In addition to the previously observed FA deficits in all the three brain regions, the alcoholics had abnormally high white matter diffusivity values in the genu and centrum. Further, inverse correlations between FA and diffusivity were significant in the genu (r=-0.52, p<0.05) and centrum (r=-0.92, p=0.0001). Multiple regression analyses examining diffusivity and age as predictors of FA identified diffusivity as a significant unique contributor to FA in both regions. These results suggest that decreased orientational coherence of brain white matter in alcoholism is attributable, at least in part, to the accumulation of intracellular and extracellular fluid in excess of that occurring in aging, and that the differential influence of these fluid compartments can vary across brain regions.

Adult↗

PubMed2005

Cortical NAA deficits in HIV infection without dementia: influence of alcoholism comorbidity.

Alcoholism comorbidity is highly prevalent in individuals infected with human immunodeficiency virus (HIV). Each condition is known to affect brain structure, function, and metabolism, but the combined effects on the brain have only recently been considered. Single-voxel, proton MR spectroscopy (MRS) has yielded sensitive measures of early brain deterioration in the progression of HIV, but has limited coverage of neocortex, whereas MRS imaging (MRSI) can simultaneously interrogate large regions of cortex. Included were 15 men with HIV+alcoholism, nine men with HIV alone, eight men with alcoholism alone (abstinent for 3-17 months), and 23 controls. The two HIV groups were matched in T-cell count and were not demented; the two alcoholism groups were relatively matched in lifetime alcohol consumption. We used MRSI with a variable-density spiral sequence to quantify major proton metabolites--N-acetylaspartate (NAA), creatine (Cr), and choline (Cho)-in the superior parietal-occipital cortex. Metabolites were expressed in absolute units and as the NAA/Cr ratio. Significant group effects were present for NAA and Cr. Only the HIV+alcoholism group was significantly affected, exhibiting a 0.8 SD deficit in NAA and a 1.0 SD deficit in Cr. The deficits were not related to highly active antiretroviral therapy (HAART) status. Neither HIV infection nor alcoholism independently resulted in parietal-occipital cortical metabolite abnormalities, yet each disease carried a liability that put affected individuals at a heightened risk of neuronal compromise when the diseases were compounded. Further, the use of absolute measures revealed deficits in NAA and Cr that would have gone undetected if these metabolites were expressed as a ratio.

Adult↗

PubMed2005

Differentiating pathologic delta from healthy physiologic delta in patients with Alzheimer disease.

STUDY OBJECTIVE: In patients with Alzheimer disease, the electroencephalogram during wakefulness shows pathologic signs of abundant, diffuse, large-amplitude delta activity. The carryover of this abnormal delta activity into non-rapid eye movement sleep raises the question of whether the observed delta electroencephalographic activity during sleep in Alzheimer disease in any way reflects normal physiologic delta activity slow-wave sleep. The objective of the study was to compare patients with Alzheimer disease with age-matched controls using an experimentally controlled procedure that can test the capacity of the nervous system to generate physiologic delta-frequency responses during sleep. SETTING: Research sleep laboratory. PARTICIPANTS: Seven ambulatory patients with Alzheimer disease (mean age = 70.0 +/- 5.77 years) meeting the National Institute of Neurological and Communicative Diseases and Stroke and Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer disease and 8 controls (mean age = 69.25 +/- 4.95 years), underwent at least 1 night of evoked-potential recordings. MEASUREMENT AND RESULTS: Data were collected during stage 2 sleep. Responses to stimuli were classified based on whether they produced a K-complex. Averages of K-complex responses were calculated, latencies and amplitudes of components evaluated, and K-complex incidence was determined. Relative to controls, subjects with Alzheimer disease produced significantly fewer evoked K-complexes (P < .001) and had substantially smaller N550 amplitudes than controls (P < .05). A lower probability of eliciting a K-complex correlated with greater dementia severity, as measured by the Mini Mental State Examination and Dementia Rating Scale. CONCLUSIONS: Despite observed increases in pathologic delta-frequency electroencephalographic activity, patients with Alzheimer disease have an impaired capacity to generate normal physiologic delta responses during non-rapid eye movement sleep.

Acoustic Stimulation↗

PubMed2005

Neuroimaging of rodent and primate models of alcoholism: initial reports from the integrative neuroscience initiative on alcoholism.

Neuroimaging of animal models of alcoholism offers a unique path for translational research to the human condition. Animal models permit manipulation of variables that are uncontrollable in clinical, human investigation. This symposium, which took place at the annual meeting of the Research Society on Alcoholism in Vancouver, British Columbia, Canada, on June 29th, 2004, presented initial findings based on neuroimaging studies from the two centers of the Integrative Neuroscience Initiative on Alcoholism funded by the National Institute on Alcohol Abuse and Alcoholism. Effects of alcohol exposure were assessed with in vitro glucose metabolic imaging of rat brain, in vitro receptor imaging of monkey brain, in vivo magnetic resonance imaging of monkey brain, and in vivo magnetic resonance spectroscopic quantification of alcohol metabolism kinetics in rat brain.

Alcoholism↗

PubMed2005

Alcoholic neurobiology: changes in dependence and recovery.

This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism (ISBRA) in Mannheim, Germany, in October, 2004. Chronic alcoholism follows a fluctuating course, which provides a naturalistic experiment in vulnerability, resilience, and recovery of human neural systems in response to presence, absence, and history of the neurotoxic effects of alcoholism. Alcohol dependence is a progressive chronic disease that is associated with changes in neuroanatomy, neurophysiology, neural gene expression, psychology, and behavior. Specifically, alcohol dependence is characterized by a neuropsychological profile of mild to moderate impairment in executive functions, visuospatial abilities, and postural stability, together with relative sparing of declarative memory, language skills, and primary motor and perceptual abilities. Recovery from alcoholism is associated with a partial reversal of CNS deficits that occur in alcoholism. The reversal of deficits during recovery from alcoholism indicates that brain structure is capable of repair and restructuring in response to insult in adulthood. Indirect support of this repair model derives from studies of selective neuropsychological processes, structural and functional neuroimaging studies, and preclinical studies on degeneration and regeneration during the development of alcohol dependence and recovery form dependence. Genetics and brain regional specificity contribute to unique changes in neuropsychology and neuroanatomy in alcoholism and recovery. This symposium includes state-of-the-art presentations on changes that occur during active alcoholism as well as those that may occur during recovery-abstinence from alcohol dependence. Included are human neuroimaging and neuropsychological assessments, changes in human brain gene expression, allelic combinations of genes associated with alcohol dependence and preclinical studies investigating mechanisms of alcohol induced neurotoxicity, and neuroprogenetor cell expansion during recovery from alcohol dependence.

Adult↗

PubMed2005

Persistent cognitive deficits in community-treated alcoholic men and women volunteering for research: limited contribution from psychiatric comorbidity.

OBJECTIVE: The contribution of psychiatric comorbidity to cognitive status was assessed in a sample of treatment-seeking alcoholics who met criteria to participate in studies of effects of chronic alcohol misuse on brain structure and cognition. METHOD: Alcoholic men (n = 43) and women (n = 21) who responded to notices about a research study were screened, clinically assessed and administered Wechsler Memory and Intelligence tests after 3 months of sobriety, on average. Cognitive performance was compared with that of an age-matched sample of healthy controls (n = 51). RESULTS: As a group, the alcoholics achieved significantly lower scores than controls on summary indices of the Wechsler Memory and Adult Intelligence Scales and showed greater decline from estimated premorbid intelligence levels than controls. Almost 60% of the alcoholics had at least one additional psychiatric (mood or anxiety) or past substance-dependence comorbidity. There were no marked sex differences in patterns of comorbidity. Comorbid alcoholics were younger, had consumed less alcohol over their lifetime and performed between noncomorbid alcoholics and controls on all tests. CONCLUSIONS: Mood and anxiety comorbidity did not necessarily compound poor cognitive test performance associated with chronic alcohol misuse. While unexpected, this finding suggests that, in this sample, poorer cognitive performance was more a function of alcoholism per se than nonalcoholic comorbidity.

Alcoholism↗

PubMed2004

Preservation of hippocampal volume throughout adulthood in healthy men and women.

To address controversies regarding the effect of age on the hippocampus, volumes of hippocampus and a comparison structure, temporal cortex, were measured on magnetic resonance imaging (MRI) in 84 healthy men and 44 healthy women (20-85 years). Neither men nor women showed significant correlations between hippocampal volumes and age, despite significant age-related decline in temporal volumes. Absence of hippocampus age relationships endured when restricting analyses to older individuals (> or =50 years) and considering menopause and hormone replacement therapy.

Adult↗

PubMed2004

The human basal forebrain integrates the old and the new.

Acquisition of new learning is challenged by the phenomenon of proactive interference (PI), which occurs when previous learning disrupts later learning. Whereas human neuroimaging studies have focused on the cortical contributions to interference resolution, animal studies demonstrate that efficient resolution of PI depends on cholinergic modulation from basal forebrain (BF). Whether the BF promotes PI resolution in humans is unknown. Here, we adapted a PI paradigm from animal studies for use in a functional MRI experiment. During PI resolution, neurologically intact subjects recruited a BF network that included afferent anterior and posterior cortical sites associated with efficient memory acquisition and perceptual processing. Despite normal performance, nonamnesic patients with alcoholism, which is known to disrupt BF function, did not activate a BF network but instead invoked anterior cortical sites traditionally associated with executive function. These results provide evidence for parallel neural systems, each with the potential to resolve interference in the face of competing information.

Adult↗

PubMed2004

In vivo structural imaging of the rat brain with a 3-T clinical human scanner.

PURPOSE: To examine the feasibility of using product acquisition software on a 3-T human MRI system to acquire high-resolution structural brain images in the rat. MATERIALS AND METHODS: Three sets of dual spin-echo, high-resolution (0.234 x 0.234 mm in-plane, 0.5 mm thick) images covering the entire rat brain were collected and averaged in 66 min. The images had sufficient signal-to-noise ratio (SNR) and resolution for visual identification and manual outlining of exemplary structures, including the lateral ventricles and dorsal and ventral portions of the hippocampus. Further, the data were adequate for unsupervised, automated segmentation, permitting quantification of the dorsolateral ventricles. The images compared favorably with those collected on a 7-T system. RESULTS: Interrater reliabilities (intraclass correlations) of manual ventricular scoring were greater than 0.97, and manual vs. automated correlations were 0.97. The variability of lateral ventricular size across animals was substantially higher than that of the hippocampus. CONCLUSION: The large variability of some brain structures that can exist across even a highly selected strain of rats can readily be detected with the use of human 3-T systems for the study of small animals.

Animals↗

PubMed2004

Postmortem MR imaging of formalin-fixed human brain.

High-resolution postmortem neuroimaging of the brain can play a role in research programs by providing archival and reslicable images of brain specimens before permanent sectioning. These images can supplement evidence attained from both traditional neuropathological observations and in vivo neuroimaging. Differential brain tissue conspicuity, detectable with MRI, is determined by the density and mobility of water protons. Water content is about 70% in white matter, 80% in gray matter, and 99% in cerebrospinal fluid (CSF). To the extent that brain tissue contrast is determined by the number and microenvironment of water protons, timing parameters of MR image acquisition can interrogate this environment. Because the chemical environment of protons is different in living from dead tissue, optimal temporal imaging parameters, for example, for spin-echo imaging, commonly used for in vivo clinical and research study are different from those best for postmortem imaging. Here, we present a series of observations to identify relaxation times and optimal parameters for high-resolution structural imaging of formalin-fixed postmortem brain tissue using commercially available clinical scanners and protocols. Examples of high-resolution images and results from attempts at diffusion imaging are presented.

Aged↗

PubMed2004

Effects of age and sex on volumes of the thalamus, pons, and cortex.

Volumes of thalamus, pons, cortical gray matter, and white matter were derived from MR brain images of healthy men and women spanning the adult age range in order to delineate patterns of aging and to compare age and sex effects in thalamus and pons with such effects in cortical gray and white matter volumes. Men had larger intracranial volume (ICV) than women, but ICV did not correlate with age in either sex. Thalamic, pontine, and cortical white matter volumes did not differ between men and women once ICV differences were taken into account, but men had more cortical gray matter than women even after accounting for ICV. Volumes of pons and thalamus were associated, independent of ICV, in women but not in men. Thalamic volume declined linearly with age at a similar rate in both men and women, whereas cortical gray matter volume declined more steeply with age in men than women. Both pontine and cortical white matter volumes remained stable across the age span in both men and women.

Adult↗

PubMed2004

Morphological changes in aging brain structures are differentially affected by time-linked environmental influences despite strong genetic stability.

This longitudinal study used the full twin model to estimate change and stability of genetic contributions to morphology of two brain structures, the corpus callosum and lateral ventricles. The 142 subjects were 34 monozygotic (MZ) and 37 dizygotic (DZ) elderly male twin pairs from the National Heart, Lung, and Blood Institute (NHLBI) Twin Study who underwent brain magnetic resonance imaging twice, separated by a 4-year interval. Genetic factors accounted for a substantial portion of individual differences in the size of the corpus callosum and its substructures and of lateral ventricular size. Longitudinal genetic analyses revealed no significant change in the heritability of these structures and no evidence for new genetic variance at Time 2 not present at Time 1. However, both the callosal and ventricular measures showed evidence for new environmental variance at Time 2 not present at Time 1. Confirming a previously posed hypothesis, the phenotypic correlation between absolute change in height of the corpus callosum and absolute change in ventricular volume was significant. Bivariate genetic analysis estimated a significant genetic correlation between the changes in these two structures and the genetic variance in the change of callosal height was entirely due to genes involved in the expansion of ventricles. Genetic stability was present even in old age when brain and other morphological changes can be rapid and highly variable across individuals, inconsistent with an hypothesis that random DNA damage is the cause of aging.

Aged↗

PubMed2004

Dissociation of remote and anterograde memory impairment and neural correlates in alcoholic Korsakoff syndrome.

Alcoholic Korsakoff's syndrome (KS) is marked by remote memory impairment together with characteristic profound anterograde memory deficits. Despite previous studies of memory processes in KS, questions remain regarding the nature and severity of these impairments and identification of brain systems that underlie these different memory impairments. This study examined remote and anterograde memory function in 5 KS patients in comparison with 8 patients with Alzheimer's disease (AD) and 24 normal control subjects (NC). In addition, relationships between memory performance and regional brain volumes were examined in the KS group. Overall, the KS group showed severe impairment on both remote and anterograde memory measures, performing at the level of the AD group on most measures. Differences were observed on the pattern of temporal gradient for verbal recognition, with KS exhibiting a more steeply graded rate of decline over the most recent period examined. Severity of the remote memory deficit in KS was not associated with severity of anterograde memory deficit. Examination of brain structure-function relationships in the KS subjects revealed that photo naming of remote historical information was related to posterior cortical white matter volumes but not hippocampal volumes; sequencing was related to prefrontal but not hippocampal volumes. By contrast, a measure of anterograde memory for nonverbal visual material showed a relationship to hippocampal but not regional cortical white matter volumes. This set of dissociations, which parallels that observed in our earlier study of AD, is now documented in KS and provides further evidence that these separate cortical and limbic brain systems are principal neural substrates of the remote and anterograde memory and sequencing deficits in KS.

Aged↗

PubMed2004

Recovery of short-term memory and psychomotor speed but not postural stability with long-term sobriety in alcoholic women.

The authors assessed effects of extended abstinence on cognitive and motor function deficits previously observed in a group of alcoholic women (n = 43) initially tested after 15 weeks of sobriety. Alcoholic women were retested 1 and 4 years later, and control women were retested 3 years later. At Year 1, 14 of 23 returners had maintained sobriety, but they did not perform significantly better than relapsers; the group as a whole continued to show deficits relative to age norms. By Year 4, 13 of 14 returners had maintained sobriety for more than 30 months; as a group, these women had returned to normal levels on tests of memory and psychomotor speed but remained impaired in standing balance.

Adult↗

PubMed2004

Perceptual learning in detoxified alcoholic men: contributions from explicit memory, executive function, and age.

BACKGROUND: Visuospatial and visuoperceptual deficits have consistently been observed in detoxified alcoholics; however, the severity of impairment varies with test and task type. Identifying the component processes and factors that underlie a particular deficit may reveal why some visuospatial and visuoperceptual tasks are more compromised than others and may lead to the specification of neural systems that are particularly vulnerable in alcoholism. METHODS: We examined visuoperception and perceptual learning with a picture fragment identification task in 51 recently detoxified nonamnesic alcoholic men (aged 29-66 years) compared with 63 normal control men (aged 21-70 years). Executive function and explicit declarative memory were also assessed. RESULTS: Despite deficits in the primary components of visuoperception and explicit memory for visuospatial stimuli, the alcoholics showed normal perceptual learning. Although the alcoholics and controls performed at comparable levels on the perceptual learning task, multiple regression analyses indicated that the factors accounting for perceptual learning variance differed between and within groups. Visuoperceptual abilities consistently predicted perceptual learning in the control subjects but not the alcoholic subjects. Explicit memory contributed to perceptual learning performance in both the alcoholic and control groups. Frontal executive ability consistently predicted perceptual learning in the alcoholic subjects, but it had predictive ability only in the control subjects as time elapsed. Age was significantly correlated with perceptual learning performance in both groups. Lifetime alcohol consumption, but not alcoholism duration, was an independent predictor of 1-hr perceptual learning. CONCLUSIONS: These correlational analyses suggest that controls invoke basic visuospatial processes to perform a perceptual learning task, whereas alcoholics invoke higher-order cognitive processes (i.e., frontal executive systems) to perform the same task at normal levels. Use of more demanding cognitive systems by the alcoholics may be less efficient and more costly to processing capacity than those invoked by controls.

Adult↗

PubMed2004

Balance and gait deficits in schizophrenia compounded by the comorbidity of alcoholism.

OBJECTIVE: Alcoholism carries a liability of balance and gait instability that persists with sobriety. Such deficits are less well documented in schizophrenia and may be compounded by comorbidity with alcoholism, which is prevalent in schizophrenia. METHOD: The authors administered quantitative ataxia tests to 10 patients comorbid for schizophrenia and alcohol dependence/abuse, 10 nonalcoholic patients with schizophrenia, 24 nonschizophrenic patients with alcohol dependence, and 27 age-matched comparison men. RESULTS: All three patient groups were impaired relative to the comparison subjects. The comorbid group was significantly more impaired than the alcoholic group on most tests and was more impaired than the schizophrenia patients, especially when tested with eyes open. CONCLUSIONS: Rigorous quantitative testing revealed gait and balance deficits in schizophrenia, even without alcohol dependence, and exacerbated deficits in schizophrenia comorbid with alcoholism. The enhancement of postural stability expected with visual information was dampened in comorbid patients, implicating compromised sensorimotor integrative abilities.

Adult↗