Anjali Deshmukh

Cerebellar volume decline in normal aging, alcoholism, and Korsakoff's syndrome: Relation to ataxia.

The authors used magnetic resonance imaging to measure gray and white matter volumes in cerebellar hemispheres and 4 vermian regions in 61 normal control (NC) men aged 23-72 years, 25 men with uncomplicated alcoholism (ALC), and 8 men and 1 woman with alcoholic Korsakoff s syndrome (KS). NC and ALC took quantitative gait and balance tests. Gray but not white matter volume declined with normal age in both hemispheres and anterior-superior vermis. ALC had gray but not white matter cerebellar hemisphere volume deficits, whereas KS had deficits in both tissue types. ALC and KS had gray and white matter volume deficits in anterior superior but not posterior inferior vermis. ALC had a 1 SD ataxia deficit, significantly and selectively correlated with white matter volume in anterior superior vermis. Regional distribution but not severity of cerebellar volume deficits is similar in alcoholic individuals whether or not complicated by KS and relates to ataxia.

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.

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.

Regional striatal volume abnormalities in schizophrenia: Effects of comorbidity for alcoholism, recency of alcoholic drinking, and antipsychotic medication type

Striatal structures form critical nodes of multiple circuits that are implicated in the pathophysiology of schizophrenia and alcoholism. Here, we examined the separate and combined effects of schizophrenia and alcoholism and effects of medication type and drinking recency on striatal volumes. Accordingly, we measured caudate nucleus, putamen, and nucleus accumbens in 27 schizophrenic, 25 alcohol-dependent, 19 comorbid (schizophrenia and alcohol dependence or abuse), and 51 age-matched control men. Schizophrenics were classified by antipsychotic medication (typical or atypical), and alcoholics were classified by recency of sobriety. All measured structures were smaller in the patient groups than the control group. The caudate deficit was comparable across groups, whereas putamen and nucleus accumbens deficits were greater in schizophrenia than alcoholism; comorbids fell between these groups. Schizophrenic patients treated with atypical medication showed greater volume deficits in the putamen than those treated with typical medication. Recently sober (<3 weeks) alcoholics had greater deficits in nucleus accumbens than longer sober drinkers. In conclusion, caudate, putamen, and nucleus accumbens exhibited different patterns of volume deficit in patients with alcoholism and schizophrenia alone, with no evidence for compounded deficits in comorbid patients. Further, these cross-sectional data provide indirect support for at least partial recovery of nucleus accumbens volume with sobriety in alcoholics, regardless of schizophrenia comorbidity.

Quantification of cerebellar structures with MRI

Methodological issues have limited neuroimaging studies of cerebellar structures. In this article we describe a method that addresses some of these limitations and phantom studies that examine the validity of the image manipulations. We compared volumes derived from 3D Spoiled Gradient Recalled Acquisition MR images sliced with respect to three different alignment methods: one based on cerebellar landmarks, another on cerebral landmarks and a third on the plane of acquisition. Examination of coefficients of variation, coefficients of error and convergent validity suggests that although regional cerebellar volumes based on cerebellar landmarks provide the best estimates of the true volumes, observed differences between volume measurements from alignments based on cerebellar or cerebral landmarks were generally not significant and were inconsequential. In this case, the measure was improved with alignment along local, relevant cerebellar landmarks. A set of phantom experiments showed that realignment, reslicing and interpolation in 3-dimensional image processing exerted, at most, trivial distortion on the estimates of actual object volumes.

123. Cerebellar gray matter volume deficits in schizophrenia and alcoholism

Sensorimotor gating of the startle reflex, measured by PPI, is impaired in humans with specific neuropsychiatric disorders, and is disrupted in humans and rats by dopamine (DA) agonists. Animal models are clarifying the genetics of PPI and its sensitivity to neurochemical regulation. Differences in sensitivity to the PPI-disruptive effects of APO across rat strains (eg. Sprague Dawley (SD) vs. Wistar (W)), and within strains, across suppliers (eg. Harlan [“H”] vs. Bantin-Kingman [“BK”]) must reflect relatively subtle genetic drift, which might be manipulated by pharmacogenetic strategies and serve as targets for QTL or other approaches for understanding the genetics of complex phenotypes. We assessed the scope and development of PPI APO sensitivity differences in SD vs. W rats (H and BK). Findings confirmed significant SDH . WH sensitivity to the PPI-disruptive effects of APO in adults and d18 pups; an SDH3 WH F1 exhibited the WH parental phenotype. Both BK rat strains were less sensitive than SDH rats to the PPI-disruptive effects of APO; in SDBKs, APO effects on PPI interacted with changes in startle magnitude. SDH. SDBK sensitivity was also noted in the PPI-disruptive effects of the D1 agonist SKF82958, but not the D2 agonist quinpirole. Substrain differences in PPI drug sensitivity are DA receptor subtypespecific. SDH. WH APO sensitivity in d18 pups suggests that genetic differences in DAergic sensitivity are expressed early in development; for this substrate, efficient phenotype screening can be completed in pups.