Macrostructural abnormalities in Korsakoff syndrome compared with uncomplicated alcoholism.

OBJECTIVE: To distinguish, in patients with Korsakoff syndrome (KS), the structural brain abnormalities shared with alcoholic patients without KS (AL), from those specific to KS. METHODS: MRI data were collected in 11 alcoholic patients with KS, 34 alcoholic patients without KS, and 25 healthy control subjects (CS). Gray and white matter volumes were compared in the 3 groups using a voxel-based approach. RESULTS: A conjunction analysis indicated a large pattern of shared gray and white matter volume deficits in AL and KS. There were graded effects of volume deficits (KS < AL < CS) in the medial portion of the thalami, hypothalamus (mammillary bodies), left insula, and genu of the corpus callosum. Abnormalities in the left thalamic radiation were observed only in KS. CONCLUSIONS: Our results indicate considerable similarities in the pattern of gray and white matter damage in AL and KS. This finding confirms the widespread neurotoxic effect of chronic alcohol consumption. Only a few cerebral regions, including the medial thalami, mammillary bodies, and corpus callosum, were more severely damaged in KS than in AL. The continuum of macrostructural damage from AL to KS is therefore restricted to key brain structures. Longitudinal investigations are required to determine whether alcoholic patients with medial thalamic volumes that are comparable to those of patients with KS are at increased risk of developing KS.

Voxel-based mapping of brain hypometabolism in permanent amnesia with PET.

In this study, we used voxel-based mapping methods to compare the resting cerebral metabolic rate of glucose (CMRglc) measured with PET in five patients with permanent amnesia (three with chronic Wernicke-Korsakoff and two with postanoxia syndrome) to that of nine healthy age-matched subjects. We assessed (i) a group pattern of relative hypometabolism; and (ii) the consistency of this group pattern, if any, in individual subjects, according to etiology. The results from the group analysis documented that permanent amnesia is associated with hypometabolism in the thalamus, posterior cingulate cortex, and mesial prefrontal cortex (near the anterior cingulate gyrus), bilaterally, as well as in the left supramarginal and middle temporal gyri. The individual analysis showed that this group pattern was found in essentially each patient, regardless of the cause of amnesia. Thus, permanent amnesia is subtended by dysfunction in structures belonging to Papez/limbic circuits as well as in left-hemisphere areas typically concerned with verbal functions, probably through a mechanism of thalamo-cortical disconnection and possibly involved in retrograde amnesia. The use of a voxel-based method allowed us to map a common network of synaptic dysfunction in a neuropsychological syndrome regardless of etiology. Our results indicate that this should be a powerful method in functional neuropsychology.

High temporal resolution dynamic mapping of instantaneous EEG amplitude modulation after tone-burst auditory stimulation.

A new method of instantaneous EEG analysis based on amplitude modulation (AM-EEG) was applied to analyze the AM-EEG changes in the alpha frequency band (8.20-12.89 Hz) for successive 5 ms epochs. Repeated auditory tone-burst stimuli (of 220 ms duration) were presented at fixed 2.56 second intervals to 12 attending right-handed young female volunteers, who were EEG-recorded over 19 EEG channels at 200 Hz sampling frequency. The time-course of functional activation was characterized in terms of percent decrease in instantaneous amplitude modulation, as compared to baseline, in analogy with the classical event-related desynchronization paradigm. A dynamic sequence of the successive 122 AM-EEG maps obtained for the 610 ms from beginning of tone-burst was stored and later animated on PC microcomputer. Topological changes among successive maps were extracted into 40 specific AM-EEG maps. Early left temporal and centro-temporal activation was observed, followed first by strong bilateral frontal, and then by left temporal activation. These changes induced by a warning tone-burst are discussed in terms of functional neurophysiology. The present method therefore allows an improved time-resolution for functional brain activation paradigms.

The structural components of music perception. A functional anatomical study.

This work explores the cerebral structures involved in the appreciation of music. We studied six young healthy subjects (right handed, French, without musical talent), using a high resolution PET device (CTI 953B) and 15O-labelled water. In three tasks, we studied the effects of selective attention to pitch, timbre and rhythm; a final task studied semantic familiarity with tunes (considered as divided attention for pitch and rhythm). These four tasks were performed on the same material (a tape consisting of 30 randomly arranged sequences of notes). We selected a paradigm, without a reference task, to compare the activations produced by attention to different parameters of the same stimulus. We expected that the activations recorded during each task would differ according to the differences in cognitive operations. We found activations preferentially in the left hemisphere for familiarity, pitch tasks and rhythm, and in the right hemisphere for the timbre task. The familiarity task activated the left inferior frontal gyrus, Brodmann area (BA) 47, and superior temporal gyrus (in its anterior part, BA 22). These activations presumably represent lexico-semantic access to melodic representations. In the pitch task, activations were observed in the left cuneus/precuneus (BA 18/19). These results were unexpected and we interpret them as reflecting a visual mental imagery strategy employed to carry out this task. The rhythm task activated left inferior Broca's area (BA 44/6), with extention into the neighbouring insula, suggesting a role for this cerebral region in the processing of sequential sounds.

Healthy aging, memory subsystems and regional cerebral oxygen consumption.

The present study was designed to search for concomitant age-related changes in memory subsystems, defined according to current structural theories, and resting oxygen consumption in selected brain regions. We have investigated a sample of subjects between 20 and 68 years of age and strictly screened for their good health. We applied in the same subjects a battery of neuropsychological tests selected to investigate several memory subsystems, and high-resolution positron imaging with stereotaxic localization to study a purposely limited number of cerebral structures, selected on a priori hypotheses to match the different memory subsystems. Our results showed significant age-related changes in performance on some tests, consistent with the literature, including an increase in semantic memory and a decrease in both working memory (central executive system) and verbal episodic and explicit memory. There was also an age-related linear decrease in global brain oxygen consumption which regionally reached statistical significance for the neocortical areas and the left thalamus. There was a limited number of significant, age-independent correlations between the raw psychometric test scores and resting regional oxidative metabolism. Consistent with our present understanding of the functional anatomy of memory, the Associate Learning scores (verbal episodic and explicit memory) were positively correlated with left hippocampal and thalamic metabolism. The positive relationships found between right hippocampal metabolism and performance in the Associate Learning and the Brown-Peterson tests were less expected but would be consistent with findings from recent PET activation studies. The results from this investigation are discussed in the light of current knowledge concerning the neuropsychology and the neurobiology of both aging and memory.