The functional MRI group of CBDB consists of multidisciplinary specialists with expertise in neurology, psychiatry, physics, biology and MRI techniques. This group pursues a variety of research agendas involving study of brain function and metabolism in normals and patients with neuropsychiatric disorders particularly schizophrenia, senile dementia of the Alzheimer's type, movement disorders and cerebrovascular disorders. The lion's share of the effort of this group over the last year has been in the implementation of whole brain studies of cognitive activation during neuropsychiatric tasks and imaging of brain metabolites (N acetyl aspartate, choline and creatine) using magnetic resonance specroscopic imaging (MRSI) in normal individuals, patients with neuropsychiatric disorders and in animal models of schizophrenia. Several interesting findings have emerged from these studies: 1) there is a capacity constraint in the key nodes of the putative network underlying working memory, 2) patients with schizophrenia reach this capacity sooner, but within their capacity constraints show normal physiological relationships, 3) ketamine, a non- competitive N-methyl-D-Aspartate receptor antagonist, induces changes in the working memory circuitry of normal subjects similar to those seen in patients with schizophrenia i.e. reaching the working memory capacity sooner than when the subjects were on placebo, 4) dextroamphetamine causes cognitively specific signal augmentation, 5) ipsilateral cortical motor areas are recruited during both dominant and non- dominant hand movements, but this appears to be more so in less familiar and less automatic tasks regardless of the hand or hemisphere involved. 6) patients with schizophrenia and their siblings had significant reductions in hippocampal NAA as compared with controls. Such a pattern of neurochemical abnormality may represent a brain 'phenotype' associated with schizophrenia. 7) lower relative NAA concentrations in the dorsolateral prefrontal cortex predict a higher D-2 binding potential in the basal ganglia of patients with schizophrenia, 8) in patients with schizophrenia, NAA measures in dorsolateral prefrontal cortex strongly correlate with activation of the entire working memory network, including prefrontal, parietal, temporal, and cingulate cortices 9) neuronal integrity of prefrontal cortex as measured by NAA, correlates with working memory impairment in HIV positive adults treated with IL2. Studies in the upcoming years will continue in the realm of clinical testing and optimization of imaging protocols with improved spatial and temporal resolution, of brain studies of cognitive activation during neuropsychiatric tasks with pharmacological manipulations, and mapping brain function and metabolism in family members who are at risk for neuropsychiatric illnesses such as schizophrenia, Alzheimer's disease, etc. It is conceivable that a genetic risk marker, possibly of use in linkage studies, could be identified.
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