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 disorder. The lion’s share of the effort of this group over the last year has continued to be in studies of cognitive activation during neuropsychiatric tasks and imaging of brain metabolites [N acetyl aspartate (NAA), choline and creatine] using magnetic resonance spectroscopic imaging (MRSI) in normal individuals, patients with schizophrenia and their unaffected siblings, animal models of schizophrenia, and in patients with Parkinson’s disease. 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. Patients with schizophrenia reach this capacity sooner, but within their capacity constraints show normal physiological relationships. Beyond capacity they become paradoxically hyper-frontal while controls decreased dorsolateral prefrontal cortical (DLPFC) activity 2) In a double blinded placebo controlled study, the effect of dextroamphetamine on performance and prefrontal cortical activation was heterogeneous across the group. It improved performance only in those subjects who had relatively low working memory capacity at baseline, whereas in subjects that had relatively high working memory capacity at baseline it worsened performance. In subjects whose performance deteriorated, signal change was relatively greater than in subjects who had an improvement in performance. These heterogeneic effects of dextroamphetamine may be explained by genetic variations that interact with the effects of dextroamphetamine. Further studies are in progress to explore this hypothesis. 3) 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. 4) Preliminary analysis of data from patients with schizophrenia and their siblings show that they have significantly reduced functional lateralization of the sensorimotor cortex when compared with controls. A larger database is being collected to evaluate if this phenomenon represents a brain ‘phenotype’ associated with schizophrenia. 5) Lower relative NAA concentrations in the dorsolateral prefrontal cortex predict a higher D-2 binding potential in the basal ganglia of patients with schizophrenia, 6) Patients with bipolar disorder show a selective reduction of NAA measures in the hippocampal region suggesting a neuronal pathology in this cortical area and adding further evidence for hippocampal involvement in the pathophysiology of bipolar disorder. 7) Neonatal lesions of the hippocampus of rats produced post pubertal emergence of specific neuronal deficits in the prefrontal cortex as evidenced by reduced NAA levels. Since previous studies in rodents have reported that neonatal lesions of the hippocampus induce biochemical and behavioral abnormalities consistent with the phenomenology of schizophrenia, these findings provide further evidence that aberrant development of the hippocampal and prefrontal systems could play a role in the pathophysiology of schizophrenia. 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, Parkinsons disease, etc. It is conceivable that a genetic risk marker, possibly of use in linkage studies, could be identified. - Brain function, MRI, Schizophrenia, neuropsychiatric disorders, cognition - Human Subjects
Showing the most recent 10 out of 76 publications
