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.

Contribution of alcohol abuse to cerebellar volume deficits in men with schizophrenia.

BACKGROUND: It is controversial whether cerebellar tissue volume deficits occur in schizophrenia and, if so, what regions and tissue types are affected. Complicating such investigations is the high incidence of alcoholism comorbidity in patients with schizophrenia that itself can contribute to cerebellar abnormalities. METHOD: We studied 61 healthy men (control subjects), 25 men with alcoholism, 27 men with schizophrenia, and 19 men comorbid for schizophrenia and alcoholism with the use of magnetic resonance imaging. Cerebellar structures were outlined manually, tissue classification was determined statistically, and regional volumes were corrected for normal variation in head size and age. RESULTS: Patients with schizophrenia alone had enlarged fourth ventricles (1.5 SD relative to controls) but showed no cerebellar tissue volume deficits. The alcoholic group had gray and white matter vermian deficits (-0.5 SD), most prominent in anterior superior lobules, and gray matter hemisphere deficits (-0.8 SD), but not fourth ventricle enlargement. The comorbid group had cerebellar hemisphere (-1.3 SD) and vermian gray matter volume deficits (-0.7 SD) and fourth ventricular enlargement (1.6 SD); these abnormalities were greater than in either single-diagnosis group, despite significantly lower levels of alcohol consumption compared with the alcoholic group. Gray matter volume in the anterior superior vermis correlated with lifetime alcohol consumption in the schizophrenic and comorbid groups when combined. CONCLUSIONS: Cerebellar tissue volume deficits were detected in schizophrenia only when accompanied by alcoholism. By contrast, fourth ventricular enlargement occurred in schizophrenia even without alcoholism, although it was exacerbated by alcoholism. These findings support a model of cerebellar supersensitivity to alcohol-related tissue volume deficits in schizophrenia.

Pattern of motor and cognitive deficits in detoxified alcoholic men.

BACKGROUND: Chronic excessive consumption of alcohol produces marked deficits in cognitive and motor abilities, although not all functions are affected to the same extent. Furthermore, although the occurrence of neuropsychological deficits in recently detoxified alcoholics is firmly established, the relative severity of these deficits, the specific neural systems that underlie the deficits, and their relationship to age and alcohol consumption variables either are less established or have proven elusive altogether. METHODS: We administered an extensive battery of neuropsychological tests, chosen for their known sensitivity to brain lesions in specific locations, to 71 recently (1 month) detoxified alcoholic men and 74 healthy controls who spanned the adult age range. Test scores were standardized to the controls for age and grouped a priori into composites that reflected performance in six functional domains: executive functions, short-term memory, upper limb motor ability, declarative memory, visuospatial abilities, and gait and balance. Analogous verbal and nonverbal materials and left- and right-hand upper limb motor tasks were used to test whether alcohol-related deficits were greater for left or right hemisphere. RESULTS: Compared with controls, the alcoholics were impaired on executive functions, visuospatial abilities, and gait and balance even after we accounted for group differences in estimated premorbid IQ and education. Within the alcoholic group, the most salient deficits were in gait and balance and visuospatial abilities. No consistent lateralized deficit was observed across the four domains tested. Unlike the cognitive composites, the upper limb motor ability and gait and balance composites both showed increasing vulnerability to age, with an independent contribution to the gait and balance dysfunction from the amount of alcohol consumed over a lifetime. CONCLUSIONS: The pattern of functional deficits implicates at least two principal neural systems: the cerebellar-frontal system and the corticocortical system between the prefrontal and parietal cortices. In addition, age and amount of alcohol consumption were better predictors of motor than cognitive impairments.

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.

In vivo mammillary body volume deficits in amnesic and nonamnesic alcoholics.

BACKGROUND: Neuropathological studies use the presence of mammillary body (MB) pathology as a cardinal, diagnostic feature of Wernicke's encephalopathy (WE) in neuropsychiatric diseases, most notably alcoholism. Although Korsakoffs Syndrome (KS), which is marked behaviorally by dense global amnesia, is a typical sequela of WE, it remains controversial whether these two conditions necessarily co-occur and whether MB pathology is therefore a diagnostic requisite for KS. METHODS: We investigated these issues by examining, in vivo, 24 nonamnesic alcoholics (ALC), 5 amnesic alcoholics (KS), and 51 normal controls with three-dimensional MRI and memory testing. MB volume was determined from successive, 1 mm thick slices. RESULTS: The ALC group had significantly smaller MB volumes bilaterally (mean = 54.5 +/- 22.0 mm3) than controls (mean = 66.3 +/- 17.1 mm3), and the KS group had even smaller MB volumes than the ALC group (mean = 20.7 +/- 14.8 mm3). Only 2 ALC patients met historical clinical criteria for past WE, and their MB volumes were well within range of the remaining 22 ALC patients. Although all five KS patients met historical clinical criteria for WE, three KS did not have accompanying dementia and had the same degree of MB volume loss as the ALC; the remaining two KS had accompanying dementia and MB volumes half the volume of the ALC group and of KS patients without dementia. CONCLUSIONS: These findings provide volumetric in vivo evidence that: (1) MB volume deficits do occur in alcoholics without amnesia, although these deficits are not present in ail such alcoholics; (2) greater MB volume deficits are present in alcoholics with clinically detectable amnesia or dementia; (3) MB shrinkage is related to severity of cognitive and memory dysfunction, which suggests a continuum of MB pathology in chronic alcoholism to KS; and (4) the presence of WE in all of the KS patients and in the two ALC patients with the greatest long-term declarative memory deficit supports the possibility of an additional and unique pathology distinguishing nonamnesic and amnesic alcoholism.

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.

A controlled study of cortical gray matter and ventricular changes in alcoholic men over a 5-year interval.

BACKGROUND: We report on structural brain changes during a 5-year period in healthy control and alcoholic men. METHODS: Alcoholic patients (n = 16), from an initial group of 58 who underwent brain magnetic resonance imaging scanning while in treatment, were rescanned with the same acquisition sequence approximately 5 years later. Control subjects (n = 28) spanning the same age range also were scanned twice at a comparable interval. Changes in brain volume were corrected for error due to differences in head placement between scans and expressed as slopes (cubic centimeters per year), percentage of change over baseline for the control subjects, and standardized change for the alcoholic patients. The alcoholic patients varied considerably in the percentage of time that symptoms of alcohol dependence were present and in the amount of alcohol consumed during follow-up. RESULTS: The cortical gray matter diminished in volume over time in the control subjects, most prominently in the prefrontal cortex, while the lateral and third ventricles enlarged. The alcoholic patients showed similar age-related changes with a greater rate of gray matter volume loss than the control subjects in the anterior superior temporal lobe. The amount of alcohol consumed during follow-up predicted the rate of cortical gray matter volume loss, as well as sulcal expansion. The rate of ventricular enlargement in alcoholic patients who maintained virtual sobriety was comparable to that in the control subjects. CONCLUSIONS: During a 5-year period, brain volume shrinkage is exaggerated in the prefrontal cortex in normal aging with additional loss in the anterior superior temporal cortex in alcoholism. The association of cortical gray matter volume reduction with alcohol consumption over time suggests that continued alcohol abuse results in progressive brain tissue volume shrinkage.

Proton magnetic resonance spectroscopic imaging of cortical gray and white matter in schizophrenia.

OBJECTIVE: To apply in vivo proton magnetic resonance spectroscopy imaging estimates of N-acetylaspartate (NAA), a neuronal marker, to clarify the relative contribution of neuronal and glial changes to the widespread volume deficit of cortical gray matter seen in patients with schizophrenia with magnetic resonance images. METHODS: Ten male veterans meeting criteria of the DSM-IV, for schizophrenia and 9 healthy age-matched men for comparison were scanned using spectroscopic, anatomical, and field-map sequences. Instrument and collection variables were standardized to allow an estimation of comparable values for NAA, choline, and creatine for all subjects. Metabolite values from each voxel on 3 upper cortical slices were regressed against the gray tissue proportion of that voxel to derive estimates of gray and white matter NAA, creatine, and choline concentrations. RESULTS: The volume of cortical gray matter was reduced in patients with schizophrenia, but NAA signal intensity from a comparable region was normal. In contrast, the volume of cortical white matter was normal in patients with schizophrenia, but NAA signal intensity from a comparable region was reduced. CONCLUSIONS: The lack of reduction in gray matter NAA signal intensity suggests that the cortical gray matter deficit in these patients involved both neuronal and glial compartments rather than a neurodegenerative process in which there is a decrease in the neuronal relative to the glial compartment. Reduced white matter NAA signal intensity without a white matter volume deficit may reflect abnormal axonal connections.

Longitudinal changes in magnetic resonance imaging brain volumes in abstinent and relapsed alcoholics.

Chronic alcoholism is associated with smaller volumes of cortical gray matter and white matter and a complementary increase in brain cerebrospinal fluid (CSF) volumes, relative to age norms. This longitudinal study quantified the extent of brain volume changes associated with abstinence and drinking at three time points in chronic alcoholics. We obtained magnetic resonance imaging (MRI) on 58 alcoholic men after an average of 12 days (MRI-1) and 32 days (MRI-2) of sobriety. In addition, 58 healthy control subjects were scanned at a comparable interval. At MRI-3, 11 controls and 39 alcoholics were rescanned, 2-12 months after MRI-2; 19 alcoholics had abstained, and 20 had resumed drinking. Axial MRI slices were segmented into cortical gray matter, white matter, and CSF and summed over seven slices; lateral and third ventricular volumes were also estimated. MRI volume changes were corrected using an estimate of interscan measurement error caused by head positioning differences, and then divided by the interval to yield rates of change (slopes). From MRI-1 to MRI-2, the alcoholic group showed declines in CSF volumes of the lateral ventricles and posterior cortical sulci, and a trend toward an increase in anterior cortical gray matter volume relative to the control group. From MRI-2 to MRI-3, third ventricular volumes decreased in the abstainers relative to the relapsers and controls; cortical white matter volume decreased in the relapsers. In the relapsers, lifetime consumption of alcohol (as of MRI-1) predicted later vulnerability to white matter volume decline and third ventricular enlargement with resumption of drinking. These data suggest that improvement in cortical gray matter, sulcal, and lateral ventricular volumes occur early in the course of abstinence, and that improvement in third ventricular volume appears later with continued abstinence.(ABSTRACT TRUNCATED AT 250 WORDS)

Increase in brain cerebrospinal fluid volume is greater in older than in younger alcoholic patients: a replication study and CT/MRI comparison.

This cross-sectional study used a semi-automated analysis technique to quantify regional brain cerebrospinal fluid (CSF) volumes derived from computed tomography (CT) in 84 healthy men ranging from 21 to 82 years of age and 28 patients meeting Research Diagnostic Criteria for alcohol dependence. The goals were to replicate an earlier CT study of an independent sample of alcoholic and control subjects (Pfefferbaum et al., 1988a; Zipursky et al., 1988) and to compare CT assessments of brain changes with magnetic resonance imaging (MRI) assessments made in the same alcoholic patients (Pfefferbaum et al., 1992). Regional brain changes associated with normal aging were derived by regression analysis, using CT data collected from the healthy control subjects. As in the earlier CT study and in the concurrent MRI study, ventricular and sulcal CSF volumes in alcoholic patients were greater than would be expected for their age. Furthermore, the present CT study replicated the previous CT and MRI findings of a positive relationship between age and CSF volume enlargement in alcoholic patients over and above the normal age-related increase in CSF volume, suggesting greater vulnerability of the aging brain to alcohol. Comparison of CT- and MRI-derived estimates of ventricular and cortical sulcal volume revealed high correlations (> 0.80). MRI and CT produced similar absolute ventricular volumes, while MRI produced larger sulcal volume estimates than did CT. The difference in sulcal volume estimate may be due to differences between CT and MRI in slice thickness and sensitivity to partial volume effects.

Brain gray and white matter volume loss accelerates with aging in chronic alcoholics: a quantitative MRI study.

Magnetic resonance imaging (MRI) was used to study in vivo the brains of 49 patients with chronic alcoholism, 3 to 4 weeks post-withdrawal, and 43 normal healthy controls, all right-handed male veterans between the ages of 23 and 70 years. MRI scans were analyzed using a semi-automated procedure, which allowed the subcortical regions to be segmented into cerebrospinal fluid (CSF) and brain tissue and the cortical regions to be segmented into CSF, gray matter, and white matter. An age regression model was used to examine the effects of alcohol on brain structure, over and above that expected from the normal aging process. The alcoholics exhibited decreased tissue and increased CSF after correcting for aging. In the cortex, there was significant loss of both gray matter and white matter volume. In this sample of alcoholics, no particular cortical region was preferentially affected or spared. Furthermore, brain tissue volume loss increased with advanced age in the alcoholics. In this group of alcoholics there was no relationship between length of illness and age, i.e., the younger alcoholics had as heavy alcohol use histories as did the older alcoholics. Thus, the increased brain tissue loss with advanced age is interpreted as evidence for age-related increase in brain vulnerability to chronic alcohol abuse.

A quantitative analysis of CT and cognitive measures in normal aging and Alzheimer's disease.

Patients with presumptive Alzheimer's disease (AD) and healthy community volunteers received computed tomographic (CT) brain scans and cognitive tests. The CT scans were quantitatively analyzed with a semiautomated thresholding technique to derive volumetric measures of cerebrospinal fluid (CSF)-to-tissue ratios in six regions of interest (ROIs): lateral ventricles; vertex sulci, frontal sulci, Sylvian fissures, parieto-occipital sulci, and third ventricle. Regression analysis was performed on CT data from 85 older volunteers (ages 51-82) to generate age norms for each ROI. Within this group, tissue loss, as measured by the % CSF in each ROI, was highly correlated with age, although each ROI showed different rates of change over age. For all ROIs, the AD group had significantly more tissue loss than expected in normal aging. In addition, AD patients with a presenescent onset (before age 65) tended to have greater vertex sulcal and frontal sulcal tissue reduction than AD patients with a senescent onset (age 65 or after). When regional tissue reduction, corrected for age, was correlated with cognitive test scores, two sets of double dissociations emerged within the AD group: large CT z scores (i.e., decreased tissue and increased CSF) of frontal sulci, but not of the third ventricle, correlated with low Comprehension and Boston Naming Test scores, whereas large CT z scores of the third ventricle, but not of the frontal sulci, correlated with low scores on Digit Symbol and Picture Arrangement. These results suggest that heterogeneity of structural and functional integrity exists among patients with AD.

The effects of ethanol and meperidine on auditory evoked potentials.

The effects of ethanol and meperidine on the auditory evoked potential (AEP) to stimuli of different intensities were investigated. Sixteen normal male volunteers received ethanol, 0.8 ml/kg, 100 mg meperidine, and a placebo on different days in a double-blind study. AEPs were recorded from Fz, Cz and Pz electrode placements. The stimuli were 500 msec 1000 Hz tones at 50, 60, 70 and 80 dB sound pressure level presented in a pseudo-random sequence. Meperidine had no significant effect on AEP variables. Ethanol reduced AEP activity between 24 and 250 msec but had no effect on the sustained potential measured between 300 and 450 msec.

Marihuana effects on TAT form and content.

In a double-blind study, 72 normal male subjects were given either placebo or marihuana containing 20 mg. Delta-9-tetrahydrocannabinol. Stories written to cards selected from the Thematic Apperception Test did not differ on hostile or sexual content scales between drug and placebo conditions, but 6 out of 10 scales specifically constructed to detect marihuana effects were successful at differentiating the two conditions. Under marihuana the stories had a timeless, non-narrative quality, with greater discontinuity in thought sequence and more frequent inclusion of contradictory ideas. Novelty of content was somewhat increased by marihuana, while relation to the picture, imagery, repetition, and closure were not significantly affected.