Biomedical subjects

Adolf Pfefferbaum

Publications and source records attributed to Adolf Pfefferbaum.

At least 55 records · Page 3Linked to original sources

PubMed2003

Compounded brain volume deficits in schizophrenia-alcoholism comorbidity.

BACKGROUND: Schizophrenia and alcoholism are characterized by brain volume abnormalities. Despite the frequent comorbidity of these conditions, the potentially compounded effects of comorbidity on brain structure have seldom been rigorously assessed. METHODS: To determine the compounding effect of schizophrenia and alcoholism on regional brain volumes, we performed retrospective quantitative analysis of magnetic resonance images from men who participated in research protocols at the Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif. Participants were selected on the basis of diagnostic criteria, yielding 4 comparison groups: 35 men comorbid for DSM-III-R schizophrenia or schizoaffective disorder and lifetime alcohol abuse or dependence; 64 men with DSM-III-R schizophrenia or schizoaffective disorder; 62 men with Research Diagnostic Criteria alcoholism; and 62 healthy men screened to exclude any Axis I diagnosis or heavy alcohol use. The comorbid group matched the schizophrenia group on age and illness severity but was younger and drank 5 times less alcohol in their lifetimes than the alcoholism group. Gray and white matter volumes from 6 cortical regions were expressed as age- and head size-corrected z scores and were subjected to multivariate profile analyses. RESULTS: Gray matter volume deficits were present in all 3 patient groups but were greatest in the comorbid group. In the comorbid group, the most prominent volume deficits were in the prefrontal and anterior superior temporal regions. CONCLUSIONS: Despite lower alcohol exposure than in pure alcoholism, the comorbidity of schizophrenia with alcoholism has a particularly profound effect on prefrontal gray matter volume, compounding the prominent prefrontal deficits present independently in schizophrenia and alcoholism.

Adult↗

PubMed2003

Replicability of diffusion tensor imaging measurements of fractional anisotropy and trace in brain.

PURPOSE: To evaluate within-scanner and between-scanner reliability of fractional anisotropy (FA) and trace (sum of the diagonal elements of the diffusion tensor) as measured by diffusion tensor imaging (DTI). MATERIALS AND METHODS: Ten young healthy adults were scanned on three separate days, on two different systems made by the same manufacturer. One scan was acquired at one site, and two scans were acquired on two different occasions on another scanner at another site. Three levels of analysis were used to compare the DTI metrics: 1) a voxel-by-voxel analysis of all supratentorial brain (gray matter + white matter + cerebrospinal fluid) and of supratentorial white matter; 2) a slice-by-slice analysis of supratentorial white matter; and 3) a single-region analysis of the corpus callosum. RESULTS: The voxel-by-voxel analysis of all supratentorial brain found that FA and trace measures and correlations were equivalently and significantly higher within than across scanners. For supratentorial white matter, FA was similar within and across scanners, whereas trace demonstrated across-scanner bias. A similar pattern was observed for the slice-by-slice comparison. For the single-region analysis of the corpus callosum, within-scanner FA and trace measures were highly reproducible for FA (CV = 1.9%) and trace (CV = 2.6%), but both DTI measures showed a systematic mean bias across scanners (CV = 4.5% for FA and CV = 7.5% for trace). CONCLUSION: These estimates of measurement variation and scanner bias can be used to predict effect sizes for longitudinal and multisite studies using diffusion tensor imaging.

Adult↗

PubMed2003

Increased brain white matter diffusivity in normal adult aging: relationship to anisotropy and partial voluming.

Diffusion tensor imaging (DTI) was used to examine 1) age-related changes in genu, splenium, and centrum semiovale white matter diffusivity in 64 healthy men and women (age 23-85 years); 2) the relationship between diffusivity (trace) and fractional anisotropy (FA) across and within individuals; and 3) the role of macrostructural and microstructural partial voluming effects on the DTI metrics. Regional differences were greater in FA (approximately 43%) than in trace (approximately 16%). Depending on the region of interest, trace increased with age (r = 0.24 to 0.58) and FA decreased with age (r = -0.29 to -0.79). FA was inversely correlated with trace, even when controlling for age. Histogram analysis of trace and FA following systematic expansion and dilation of the white matter regions demonstrated greater susceptibility of FA than trace to error arising from macrostructural partial voluming, i.e., erroneous inclusion of primarily nonwhite-matter voxels. Three-phase ellipsoid shape analysis revealed that after morphometric erosion the spherical component remained greater in older than younger subjects in the splenium and centrum, suggesting that age-related reduction in FA arises from intravoxel increased interstitial fluid. Reducing the size of the white matter samples to control for macrostructural partial voluming attenuated but did not negate effects, indicating that observed changes in white matter with aging can reflect real microstructural alterations rather than sampling artifact. Morphological dilation of white matter regions of interest resulting in purposeful inclusion of non-white matter pixels significantly reduced mean FA, suggesting that reports of FA values below 0.25 in healthy adults may reflect partial voluming rather than actual changes in white matter coherence.

Adult↗

PubMed2003

Diffusion tensor imaging in normal aging and neuropsychiatric disorders.

The application of diffusion imaging to the quantitative study of the effects of normal aging and neuropsychiatric diseases on brain tissue microstructure has witnessed its greatest development just over the last few years. Measures derived from diffusion imaging have already been shown to have great utility in identifying age- and disease-related degradation of regional microstructure, particularly of white matter. Investigations comparing diagnoses hold promise for contribution to differential diagnosis. Correlations with cognitive and motor performance provide evidence for functional ramifications of these diffusion measures.

Adult↗

PubMed2003

Increased frontocerebellar activation in alcoholics during verbal working memory: an fMRI study.

Although there is clear evidence of alcoholism-related damage to the frontal lobes and cerebellum from neuroimaging, neuropathological, and neuropsychological studies, the functional role of the cerebellum and cerebrocerebellar circuits related to verbal working memory deficits of alcoholics have not been well studied. Alcoholic and nonalcoholic subjects performed a Sternberg verbal working memory task while receiving an fMRI scan in a 3T magnet. This task has been found in previous studies to reliably activate the articulatory control and phonological storage components of the phonological loop (left frontal, left temporal/parietal structures, right superior cerebellar regions) in young healthy controls. We hypothesized that the alcoholics would show a different pattern of activation from the controls, based on the regions of interest (ROIs) identified from a previous study of healthy subjects. Behavioral results showed the alcoholics to be performing at a comparable level to the matched controls in terms of accuracy and median reaction time, with no statistically significant differences. However, analysis of the functional data revealed that the alcoholics exhibited greater activation in the left frontal (BA44/45) and right superior cerebellum (HVI) regions relative to the matched controls. These findings suggest that brain activation in left frontal and right cerebellar regions that support the articulatory control system of verbal working memory may require a compensatory increase in alcoholics in order to maintain the same level of performance as controls.

Adult↗

PubMed2003

Disruption of frontocerebellar circuitry and function in alcoholism.

This article represents a symposium of the 2002 joint meeting of RSA and ISBRA held in San Francisco. Presentations were Neuropathology of alcohol-related cerebellar damage in humans, by Antony J. Harding; Neuropathological evidence of cerebellar damage in an animal model of alcoholism, by Roberta Pentney and Cynthia Dlugos; Understanding cortical-cerebellar circuits through neuroimaging study of chronic alcoholics, by Peter R. Martin and Mitchell H. Parks; and Functional reorganization of the brain in alcoholism: neuroimaging evidence, by John E. Desmond, S.H. Annabel Chen, Michelle R. Pryor, Eve De Rosa, Adolf Pfefferbaum, and Edith V. Sullivan.

Alcohol-Induced Disorders, Nervous System↗

PubMed2003

How important are brain banks for alcohol research?

This article contains the proceedings of a symposium at the 2002 RSA/ISBRA Meeting in San Francisco, organized and chaired by Clive Harper and co-chaired by Izuru Matsumoto. The presentations were (1) Introduction, by Clive Harper; (2) The quality of tissue-a critical issue, by Therese Garrick; (3) The first systematic brain tissue donor program in Japan, by Izuru Matsumoto; (4) Brain scans after death-really! by Adolf Pfefferbaum, Elfar Adalsteinsson, and Edith Sullivan; (5) Capture that (genial) expression, by Joanne Lewohl and Peter Dodd; and (6) Neurochemical/pharmacological studies: experimental design and limitations, by Roger Butterworth.

Alcohol-Induced Disorders, Nervous System↗

PubMed2003

Effects of alcohol dependence comorbidity and antipsychotic medication on volumes of the thalamus and pons in schizophrenia.

OBJECTIVE: Postmortem and in vivo brain imaging studies have identified abnormalities in the thalamus and the pons in both schizophrenia and alcoholism. The authors sought to determine whether patients with both schizophrenia and alcohol dependence would manifest exaggerated volume deficits in either structure. METHOD: Volumetric measures of the left and right thalamus and the pons were derived from magnetic resonance imaging scans obtained from 27 patients with schizophrenia, 19 patients with schizophrenia and comorbid alcohol dependence, 25 patients with alcohol dependence without comorbid axis I disorders, and 51 healthy comparison subjects. RESULTS: The alcohol-dependent patients had significant volume deficits in both the thalamus and the pons. Among patients with schizophrenia, there were no differences in thalamus volumes between those with and without comorbid alcohol dependence. However, patients with schizophrenia who were taking atypical antipsychotic medications had bilateral thalamic deficits, whereas those taking typical neuroleptics did not. Patients with schizophrenia and comorbid alcohol dependence had deficits in the pons. CONCLUSIONS: Patients with schizophrenia and comorbid alcohol dependence are at risk for alcohol-related reduction of pontine structures that are not necessarily affected by schizophrenia per se. The effect of alcohol dependence on the thalamus in schizophrenic patients may be mitigated by the type of neuroleptic medication they receive.

Adult↗

PubMed2003

Alcoholic men endorse more DSM-IV withdrawal symptoms than alcoholic women matched in drinking history.

OBJECTIVE: Given gender differences in alcohol metabolism, drinking patterns and alcohol-related problems, we asked whether men and women recruited for research protocols from treatment programs would meet different subsets of alcohol dependence or withdrawal criteria or differ in current level of functioning. METHOD: The subjects were 66 men and 62 women meeting DSM-III-R or DSM-IV criteria for alcohol dependence. Gender differences were tested infrequency counts of criteria endorsed and Global Assessment of Functioning (GAF) scores. RESULTS: All seven alcohol dependence criteria were endorsed by 50% of the sample. There were no significant gender differences in frequency of individual criteria endorsed. However, more men than women tended to endorse the withdrawal criterion for alcohol dependence and the tremor criterion for alcohol withdrawal, whereas women had higher GAF scores. When subgroups of men and women were matched on alcohol consumption variables, significantly more men than women endorsed the withdrawal criterion for alcohol dependence and the anxiety criterion for alcohol withdrawal, and women still had significantly higher GAF scores than men. CONCLUSIONS: DSM criteria provide a similar characterization of alcohol dependence in male and female research volunteers. Despite this similarity, the DSM criteria were sensitive to gender differences, which can now be challenged with rigorous testing.

Adult↗

PubMed2003

Using magnetic resonance imaging and diffusion tensor imaging to assess brain damage in alcoholics.

Brain imaging using conventional magnetic resonance imaging (MRI) has revealed that several brain structures in people with a history of chronic alcohol dependence are smaller in volume than the same brain structures in nonalcoholic control subjects. Areas that are particularly affected are the frontal lobes, which are involved in reasoning, judgment, and problem solving. Older people are especially vulnerable to the damaging effects of alcohol. It is unclear whether women show consistently more vulnerability to these changes in the brain than men do. In general, alcoholics evaluated before and after a period of abstinence show some recovery of tissue volume, whereas alcoholics evaluated again after continued drinking show further reductions in brain tissue volume. A new MR technique called diffusion tensor imaging (DTI) can aid in detecting the degradation of fibers (i.e., white matter) that carry information between brain cells (i.e., gray matter). With DTI, researchers studying alcoholics have been able to detect abnormalities in white matter not visible with conventional MRI. Ultimately DTI may be useful in elucidating the mechanisms that underlie macrostructural and functional brain changes seen with abstinence and relapse.

Alcoholism↗

PubMed2002

Low N-acetyl-aspartate and high choline in the anterior cingulum of recently abstinent methamphetamine-dependent subjects: a preliminary proton MRS study. Magnetic resonance spectroscopy.

Studies based on animal models report that methamphetamine (MA) abuse diminishes dopamine (DA) and serotonin innervation in frontal brain regions. In this in vivo human study, we used proton magnetic resonance spectroscopy (MRS), which yields measures of N-acetyl-aspartate (NAA), a marker of living neurons, to examine frontal brain regions possibly affected by methamphetamine dependence (MD). We tested the hypothesis that MD subjects would exhibit abnormally low levels of NAA, referenced to creatine (Cr), in anterior cingulate gray matter. We further hypothesized that the primary visual cortex, which receives relatively less DA innervation than the frontal brain regions, would show normal NAA/Cr ratios in MD subjects. Subjects included nine MD men (mean+/-standard deviation (S.D.)=32.5+/-6.4 years) and nine age-matched control men (mean+/-S.D.=32.7+/-6.8 years). The MD subjects were MA-free for 4-13 weeks. Proton MRS metabolites were expressed as ratios of creatine; the absolute values of which did not distinguish controls and MD subjects. With regard to metabolite ratios, the MD men had significantly lower NAA/Cr in the cingulum (mean+/-standard error (S.E.): control=1.46+/-0.03; MD=1.30+/-0.03; Mann-Whitney P=0.01) but not in the visual cortex (mean+/-S.E.: control=1.64+/-0.06; MD=1.69+/-11; Mann-Whitney P=0.52) relative to controls. These results provide evidence for NAA/Cr deficit that is selective to the anterior cingulum, at least with respect to visual cortex, in MD subjects. The neuronal compromise that these changes reflect may contribute to the attentional deficits and dampened reward system in MD.

Adult↗

PubMed2002

Clinical signs of cerebellar dysfunction in schizophrenia, alcoholism, and their comorbidity.

Abnormalities of cerebellar structure and function, long recognized as a hallmark of chronic alcohol abuse, have also occasionally been noted in patients with schizophrenia. We used a four-point rating scale to assess clinical signs of cerebellar dysfunction in men meeting DSM-IV criteria for schizophrenia (N=34) and alcohol dependence (N=15) as well as normal control subjects (N=28). Compared to controls, alcoholics had impaired ratings of gait ataxia and instability of stance with eyes closed, and schizophrenics had impaired ratings of stance with eyes closed. The incidence of dysdiadochokinesia was greater in schizophrenics, but not alcoholics, than controls. The incidence of gait and stance abnormalities was higher in both patient groups relative to controls: within the schizophrenic group, 50-70% of those with positive signs for gait or stance impairment were comorbid for alcoholism, while only 25% of those with positive signs for dysdiadochokinesia were comorbid for alcoholism. The presence of dysdiadochokinesia in the schizophrenic group suggests cerebellar dysfunction that is independent of the effects of alcohol. By contrast, clinical signs of cerebellar dysfunction of gait and stance in patients with schizophrenia may be secondary to the effects of alcohol on the cerebellum.

Adult↗

PubMed2002

Preliminary evidence of reduced cognitive inhibition in methamphetamine-dependent individuals.

Chronic methamphetamine abuse is associated with disruption of frontostriatal function involving serotonin and dopamine circuitry. Clinically, methamphetamine-dependent (MD) individuals are highly distractible and have difficulty focussing. Here, we used a computerized single-trial version of the Stroop Test to examine selective attention and priming in MD. Subject groups comprised eight MD men (31.7+/-7.2 years of age), who had used methamphetamine for 15.75+/-8.4 years but were currently abstinent for 2-4 months, and 12 controls (35.7+9.7 years of age). Compared with the control group, the MD group exhibited significantly greater interference (P<0.05) despite intact priming. Error rates did not differ between the groups. This preliminary finding of reduced cognitive inhibition in MD individuals is consistent with the distractibility they show clinically. Furthermore, the dissociation between explicit attentional performance and priming effects suggests that some attentional functions are not as affected by long-term methamphetamine use as others.

Adult↗

PubMed2002

Microstructural but not macrostructural disruption of white matter in women with chronic alcoholism.

The results of in vivo neuroimaging studies assessing whether and where brain white matter damage occurs in alcoholic women is controversial. To address this controversy, we examined regional white matter macrostructure and microstructure, the latter of which may be more sensitive to the detection of subtle fiber disruption than gross measures of size. Accordingly, we used conventional magnetic resonance imaging (MRI) to quantify regional callosal size and diffusion tensor imaging (DTI) to examine intravoxel coherence (fractional anisotropy, FA) and intervoxel coherence (C) of white matter of the genu and splenium of the corpus callosum and of the centrum semiovale in 12 detoxified alcoholic women and 18 control women. Additional analyses examined sex differences in FA and C in alcoholic women compared with alcoholic men. Despite absence of group differences in regional areas of callosal macrostructure, the alcoholic women had lower FA and C in genu and centrum semiovale than the control group of women. These measures also correlated with total lifetime consumption of alcohol and performance on a test of visual search in the alcoholic women. Sex comparisons revealed similar extents of FA abnormality in the genu and centrum semiovale in alcoholic men and women and differential effects in other DTI measures, with abnormalities present in splenium FA and C in the men and abnormalities present in centrum C in the women. These results provide in vivo evidence for disruption of white matter microstructure in alcoholic women not necessarily detectable with coarser measures of white matter mass and perhaps antedating its appearance.

Adult↗

PubMed2002

A profile of neuropsychological deficits in alcoholic women.

Neuropsychological deficits, most notable in executive, visuospatial, and functions of gait and balance, are detectable in alcoholic men even after a month of sobriety. Less well established are the severity and profile of persisting deficits in alcoholic women. The authors used an extensive test battery to examine cognitive and motor functions in 43 alcoholic women who were sober, on average, for 3.6 months. Functions most severely affected in alcoholic women involved visuospatial and verbal and nonverbal working memory processes as well as gait and balance. Areas of relative sparing were executive functions, declarative memory, and upper-limb strength and speed. The authors found that lifetime alcohol consumption was related to impairment severity on Block Design (Wechsler Adult Intelligence Scale-Revised, D. Wechsler, 1981) and verbal and nonverbal working memory, suggesting a dose effect of alcohol abuse. The alcohol-related deficits in working memory, visuospatial, and balance implicate disruption of prefrontal, superior parietal, and cerebellar brain systems.

Adult↗

PubMed2002

The effects of alcoholism on auditory evoked potentials during sleep.

Normal aging is associated with a reduction in the probability that an auditory stimulus will evoke a K-complex during sleep. Additional concomitants of aging are a reduction in the amplitude of the K-complex-related N550, an augmentation of the P2 component and the appearance of a long-lasting positivity (LLP) in the auditory evoked potential. Normal aging is also associated with a dramatic reduction in slow wave sleep (SWS) and a reduction in the volume of cortical gray matter, particularly in the frontal and prefrontal regions of the brain. As in aging, alcoholism is associated with reductions in both cortical gray matter and SWS. It can, therefore, be hypothesized that alcoholics would show similar evoked potential changes to those seen in aging. To test this hypothesis, we studied seven middle-aged abstinent long-term alcoholics and eight age-matched normal controls. Each subject spent one night in the laboratory. Electroencephalogram (EEG) was recorded from six midline scalp sites and auditory stimuli were presented during stage 2 non-rapid eye movement sleep. N550 amplitude in the K-complex average was lower in the alcoholics as compared with controls as was the likelihood of K-complex production. No differences were noted in either amplitude or latency of the P2 or N350 components, and both groups displayed a prominent LLP potential. The pattern of reduced K-complex production and N550 amplitude in alcoholics as compared with age-matched controls is consistent with an hypothesized association between atrophy of the frontal lobes and reductions in SWS and K-complexes. The finding also suggests that the evoked K-complex may be a relatively simple measure of the effect of alcoholism on EEG during sleep.

Alcoholism↗

PubMed2002

Alcoholism and AIDS: magnetic resonance imaging approaches for detecting interactive neuropathology.

Both alcohol abuse and human immunodeficiency virus (HIV) infection have deleterious effects on brain structure, metabolism and function. In individuals with both afflictions these effects are doubtless additive and may interact to produce synergistic adverse effects. Further, the normal processes of aging produce brain degeneration that leaves older people especially vulnerable to the untoward effects of alcohol abuse and HIV infection. Advances in in vivo brain imaging now make practical the clinical study of the interaction of alcoholism and HIV infection and the potential of increased vulnerability produced by advancing age. In addition to structural magnetic resonance imaging (MRI), which provides quantitative assessments of brain macrostructure, are diffusion tensor imaging (DTI), which assesses microstructural integrity, magnetic resonance spectroscopy (MRS), which provides assessment of brain chemical moieties related to neuronal viability, and functional magnetic resonance imaging (fMRI), which provides assessment of localized blood oxygenation state association with performance of specific cognitive or motor tasks. Here, we first review postmortem observations on patients with HIV infection and with alcoholism to identify the cell types and brain regions most affected by the end stage of the disease. We then review in vivo neuroimaging studies of brain changes associated with HIV infection, chronic alcohol use, their interaction, and the potentiating effects of age. While there are many studies of people with either HIV infection or chronic alcohol use alone currently little has been published on the interactive effects of these variables, despite the high prevalence of overlap. We conclude with a consideration of the methodological issues such studies must address.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Corpus callosum, pons, and cortical white matter in alcoholic women.

BACKGROUND: To measure the effect of alcohol abuse on white matter brain macrostructure in women with alcoholism and to determine whether observed abnormalities interact with age. METHODS: Quantitative measures of corpus callosum area, cortical white matter volume, and pons volume were derived from magnetic resonance imaging scans obtained from 34 women with DSM-III-R alcoholism (aged 28-64, mean 41 years) and 35 healthy women (aged 22-65, mean 42 years). Transverse relaxation time of the pons was also obtained. RESULTS: No significant group differences in any brain measures were observed. However, in alcoholics greater length of sobriety was associated with more cortical white matter, and higher lifetime levels of alcohol consumption were associated with smaller volumes and prolonged transverse relaxation time in the pons. CONCLUSIONS: Despite a lack of overall deficits in white matter macrostructural size in alcoholic women, certain white matter structures showed alcohol exposure vulnerability whereas others showed evidence of recovery with abstinence.

Adult↗