Margaret J. Rosenbloom

Longitudinal changes in cognition, gait, and balance in abstinent and relapsed alcoholic men: relationships to changes in brain structure.

Chronic alcoholism is associated with cognitive and motor deficits, and there is evidence for reversibility with sobriety. Alcoholic men were examined after 1 month of sobriety and 2 to 12 months later with cognitive and motor tests and magnetic resonance imaging. In this naturalistic study, 20 alcoholic participants had abstained and 22 had resumed drinking at retesting. Abstainers sustained greater improvement than relapsers on tests of delayed recall of drawings, visuospatial function, attention, gait, and balance. Shrinkage in 3rd ventricle volume across all participants significantly correlated with improvement in nonverbal short-term memory. Additional brain structure-function relationships, most involving short-term memory, were observed when analyses were restricted to alcoholic men who had maintained complete abstinence, were light relapsers for at least 3 months, or had consumed no more than 10 drinks prior to follow-up testing. Thus, alcoholic men who maintain abstinence can show substantial functional improvement that is related to improvement in brain structure condition.

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.

Degradation of Association and Projection White Matter Systems in Alcoholism Detected with Quantitative Fiber Tracking

BACKGROUND Excessive alcohol use can cause macrostructural tissue shrinkage with regional preference for frontal systems. The extent and locus of alcoholisms effect on white matter microstructure is less known. METHODS Quantitative fiber tracking derived from diffusion tensor imaging (DTI) assessed the integrity of samples of 11 major white matter bundles in 87 alcoholics (59 men, 28 women) and 88 healthy control subjects (42 men, 46 women). Fiber integrity was expressed as fractional anisotropy (FA) and apparent diffusion coefficient (ADC), quantified separately for longitudinal diffusivity (lambdaL), a putative index of axonal integrity, and transverse diffusivity (lambdaT), a putative index of myelin integrity. RESULTS Alcoholism affected FA and diffusivity, particularly lambdaT, of several fiber bundles. Frontal and superior sites (frontal forceps, internal and external capsules, fornix, and superior cingulate and longitudinal fasciculi) showed greatest abnormalities in alcoholics relative to control subjects. More posterior and inferior bundles were relatively spared. Lifetime alcohol consumption correlated with regional DTI measures in alcoholic men but not women. When matched for alcohol exposure, alcoholic women showed more DTI signs of white matter degradation than alcoholic men in several fiber bundles. Among all alcoholics, poorer performance on speeded tests correlated with DTI signs of regional white matter degradation. CONCLUSIONS This survey of multiple brain fiber systems revealed a differential pattern of alcoholisms effect on regional FA and diffusivity with functional consequences attributable in part to compromised fiber microstructure with prominence in signs of myelin degradation. Sex-based differences suggest that women are at enhanced risk for alcoholism-related degradation in selective white matter systems.

Sex differences in corpus callosum size: relationship to age and intracranial size ☆

This quantitative MRI study reports measurement of corpus callosum area taken from midsagittal brain images in 51 healthy men and 41 healthy women, spanning the adult age range (22 to 71 years). Men had larger brains and corpora callosa than women, but callosal size did not correlate with age in either sex. Intracranial (i.c.) volume (ICV) and midsagittal i.c. area (ICA) of brain were used in covariate, regression, and ratio analyses to determine whether sex differences in the corpus callosum endured with statistical adjustment for sex differences in maximally attained brain size. With the exception of one ratio measure, the different statistical adjustments for the contribution of sex differences in brain size to corpus callosum size all indicated that men had larger corpora callosa than women for their brain size. A subsample of men and women selected to be matched on i.c. volume and age confirmed this statistical observation. Sexual dimorphism in the corpus callosum is not a simple artifact of sex differences in brain size and may reflect differences in connectivity necessitated by differences in brain size.

Cortical gray matter deficit in patients with bipolar disorder

BACKGROUND cortical gray matter volume deficit and ventricular enlargement are well documented in schizophrenia, but their presence in bipolar disorder is less well established. METHODS global cortical gray matter, white matter and sulcal CSF, as well as lateral and third ventricular volume measures, were derived from axial MRI brain images obtained on age-matched bipolar (n=9), schizophrenic (n=9), and control (n=16) subjects. All subjects were free of history of alcohol or other substance dependence. RESULTS relative to controls, bipolar patients had widespread volume deficits of cortical gray matter but not of cortical white matter. Schizophrenic patients had an even more severe cortical gray matter deficit and greater sulcal and lateral ventricular enlargement than the bipolar patients. CONCLUSIONS this group of patients with bipolar disorder had a widespread deficit of cortical gray matter similar to, but less pronounced than, that observed in patients with schizophrenia.

Striatal and forebrain nuclei volumes: Contribution to motor function and working memory deficits in alcoholism

BACKGROUND Striatal structures are involved in dopaminergic alcohol reward mechanisms and aspects of motor control. Basal forebrain structures hold cholinergic mechanisms influencing memory formation, vulnerable to chronic alcoholism; however, alcoholisms effect on volumes of these structures has seldom been considered with in vivo measurement. METHODS We measured bilateral volumes of caudate nucleus, putamen, nucleus accumbens, and medial septal/diagonal band (MS/DB) in 25 men with alcohol dependence and 51 age-matched control men. Six alcoholic subjects had been drinking recently, and 19 had been sober. RESULTS Volumes of caudate and putamen were smaller in the alcoholics than in the control subjects, regardless of length of sobriety. Recent drinkers showed greater deficits in nucleus accumbens than sober alcoholics. Putamen volume was positively correlated with grip strength; MS/DB volume was positively correlated with verbal working memory independently of the negative association between age-standardized MS/DB and age in alcoholics. CONCLUSIONS Caudate and putamen volume deficits occur and endure in chronic alcoholism. Nucleus accumbens might be especially sensitive to recent alcohol exposure. Striatal volumes should be considered in functional imaging studies of alcohol craving that target striatal brain regions. The age-alcohol interaction for MS/DB volumes is consistent with a cholinergic mechanism for the working memory impairment observed in the alcoholics.

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.

P300 reduction and prolongation with illness duration in schizophrenia

BACKGROUND The P300 component of the auditory event-related potential (ERP) is both reduced in amplitude and delayed in schizophrenia. P300 is prolonged and, less consistently, reduced with normal aging. Additional latency delays are observed in neurodegenerative disorders. We asked whether P300 is reduced and delayed with longer illness duration in schizophrenia, consistent with a neurodegenerative process. METHODS P300 amplitude and latency were recorded to infrequent auditory target stimuli from 35 men with schizophrenia (DSM-III-R) and 26 control men. Effects of current age, age of onset, and duration of illness on P300 were assessed using regression analysis. RESULTS P300 amplitude showed no age-related decrease in either group; however, among schizophrenic participants, P300 amplitude correlated positively with onset age and negatively with illness duration. P300 latency correlated positively with age in schizophrenic participants and also tended to increase with age in controls. Slopes of the latency-age relationships were significantly greater in schizophrenic participants than in control participants. Latency also correlated positively with illness duration but showed no relationship to onset age. CONCLUSIONS P300 amplitude and latency are reduced and delayed with longer illness duration in schizophrenia, consistent with a progressive pathophysiological process. Reduced P300 amplitude may also be a marker of an early onset variant of schizophrenia.

Response-monitoring dysfunction in aging and Alzheimer’s disease: an event-related potential study

Executive control is a broad-reaching function that includes response monitoring and is likely implemented in the frontal lobes. Age- and dementia-related changes in response-monitoring were assessed during a Picture-Name Verification Task, using response-synchronized event-related potential (ERP) markers of response monitoring: the centrally oriented error-related negativity (ERN); the smaller and more frontally-oriented correct-response negativity (CRN); and the positivity associated with errors (Pe), a marker of error awareness. These were recorded from 10 younger and 10 older healthy controls, as well as 12 Alzheimers disease (AD) patients. Although the older and younger controls showed equivalent accuracy, error awareness (Pe), and relative ERN>CRN amplitude, aging was associated with slower behavioral responses and decreased ERN amplitude. Although dementia was associated with decreased accuracy, decreased ERN, and a loss of relative ERN>CRN amplitude, error awareness (Pe) remained somewhat intact in AD patients. In AD patients, CRN amplitude was affected by item certainty (assessed a week earlier), being larger to items that were idiosyncratically difficult for patients to name.

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.