Faculty Bibliography

A progressive dementing illness, the AIDS dementia complex (ADC) is the most frequent neurological complication of the acquired immunodeficiency syndrome. Characteristic alterations in regional cerebral metabolic rate for glucose (rCMRGlc), associated with the presence or progression of ADC, were demonstrated by [18F]fluorodeoxyglucose/positron emission tomography in 9 of 12 patients with ADC compared with 18 normal volunteer subjects. In these 9 patients, two distinct patterns of regional metabolic activity were highly correlated with intersubject gray matter rCMRGlc variation and with disease severity as assessed by neuropsychological testing. Relative subcortical (thalamus and basal ganglia) hypermetabolism was characteristic of early ADC, and disease progression was accompanied by cortical and subcortical gray matter hypometabolism

Positron emission tomographic studies of regional cerebral metabolic rate for glucose (rCMRGlc) and cerebral blood flow were performed in 7 vegetative and 3 locked-in patients to determine objectively the level of brain function underlying these clinical states. Cortical gray rCMRGlc in the vegetative patients was 2.73 +/- 0.13 (mean +/- SEM) mg/100 gm/min, less than half the normal value of 6.82 +/- 0.23 (p less than 0.001). Cerebral blood flow exhibited similar but more variable reductions. By contrast, cortical rCMRGlc in the locked-in patients was 5.08 +/- 0.69, a 25% reduction (p less than 0.02) from normal. The massive reduction in vegetative rCMRGlc involved not only the cerebral cortex but also the basal nuclei and cerebellum. Such metabolic hypoactivity has precedent only in deep anesthesia and supports clinical evidence that cerebral cognitive function is lost in the vegetative state, leaving a body that can no longer think or experience pain

The data obtained from measurements of regional rCMRglu using [18F]fluorodeoxyglucose (FDG)/positron emission tomographic (PET) data contain more structure than can be identified with group mean rCMRglu profiles or regional correlation coefficients. This additional structure is revealed by a novel mathematical-statistical model of regional metabolic interactions that explicitly represents rCMRglu profiles as a combination of region-independent global effects, a group mean pattern and a mosaic of interacting networks. In its application to FDG/PET data, this model removes global subject effects [global scaling factors (GSFs)] and a group mean pattern (profile) so as to maximize statistical power for the detection and simultaneous discovery of all networks of two or more regions that form a significant and consistent linearly covarying pattern. The model approach presented here was applied to the combined rCMRglu data from 12 demented AIDS patients and 18 normal controls: Two significant metabolic covariance pattern descriptors that together accounted for 71 to 96% of the rCMRglu/GSF variation across subjects for 22/28 regions in the AIDS group were extracted. Each descriptor was found to be highly correlated with performance on several neuropsychological tests, providing independent validation of the analysis technique as a means of discovering and describing behaviorally related components of group rCMRglu profiles

Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for 82Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity

Tested 43 right-handed children on dichotic complex-pitch and speech discrimination tests. For each age group (7 to 8 yrs, 9 to 10 yrs, and 11 to 12 yrs), adult patterns of perceptual asymmetries were observed: There was a right-ear advantage for speech and a left-ear advantage for complex-pitch, without significant changes either in the magnitude of perceptual asymmetries or in the frequency of occurrence of particular patterns of asymmetry as a function of age. For overall accuracy, a significant increase with age was found for speech but not for pitch discrimination. It is suggested that, despite the absences of significant age-related changes in perceptual asymmetries in these 2 tasks, they may undergo different developmental courses. Implications for cerebral specialization, cerebral lateralization, and perceptual asymmetry are noted.

A 48-year-old woman with a stimulating electrode implanted in the right thalamic nucleus ventralis posterolateralis developed compulsive self-stimulation associated with erotic sensations and changes in autonomic and neurologic function. Stimulation effects were evaluated by neuropsychologic testing, endocrine studies, positron emission tomographic measurements of regional cerebral metabolic rate for glucose, EEG and evoked potentials. During stimulation, vital signs and pupillary diameter increased and a left hemiparesis and left hemisensory loss developed. Verbal functions deteriorated and visuospatial processing improved. Plasma growth hormone concentrations decreased, and adrenocorticotrophic hormone and cortisol levels rose. With stimulation, glucose metabolism increased in both thalami and both hemispheres, reversing baseline right-sided hypometabolism and right-left asymmetries. EEG and both somatosensory and brain-stem auditory evoked potentials remained unchanged during stimulation, while visual evoked potentials revealed evidence of anterior visual pathway dysfunction in the left eye. This case establishes the potential for addiction to deep brain stimulation and demonstrates that widespread behavioral and physiological changes, with concomitant alteration in the regional cerebral metabolic rate for glucose, may accompany unilateral thalamic stimulation

Responds to I. Dennis's (see record 1984-19673-001) comments on the present author's (see record 1983-09879-001) suggestion that the discrepancy between the proportion of right-handed Ss exhibiting a right-ear advantage wth dichotic speech stimuli and the greater proportion found to have left-hemisphere language lateralization in clincial studies can be explained by the presence in some individuals of asymmetry in the contralateral auditory pathways. Dennis suggested that some aspects of these data may be artifacts of statistical procedures. The present author reviews his data and model of dichotic listening. (2 ref)

In patients who have undergone complete section of the corpus callosum for intractable epilepsy, lateralized presentation of visual nonverbal stimulation showed that the coordination of motor acts by either hand is controlled exclusively by the contralateral hemisphere. When two patients had serial operations consisting of an initial division of the splenium and posterior 3 cm, followed by complete callosal division, an opportunity arose to test the explicit cortical pathways involved in ipsilateral control. Between operations, these patients could not coordinate movements of the hand ipsilateral to the hemisphere receiving the command. This suggested that for visual nonverbal stimulation, the posterior 3 cm of corpus callosum is necessary for control of the ipsilateral hand; the rostral callosum cannot transfer sensorimotor commands. Also, contrary to current views, each hemisphere can carry out sequentially dependent motor activity

The covert interhemispheric transfer of linguistic information was demonstrated in a commissurotomy patient with bilateral language organization. It was found that under conditions of unilateral stimulation, a verbal association established in one hemisphere was available to the untrained hemisphere as well. Such interhemispheric transfer was observed only for phonetically codable information. Moreover, transfer was not observed under conditions of simultaneous bilateral stimulation. These results suggest that the point of convergence between the left and right hemisphere language systems allows for the paracallosal transfer of linguistic information