In FY '97, LDRR was transferred from the Office of Director, NIH to the Clinical Center. Functional and metabolic magnetic resonance imaging (MRI) techniques have been rapidly evolving and have tremendous potential for clinical brain disorders research. Clinical activation functional magnetic resonance imaging (fMRI) studies are performed at 1.5 Tesla using the blood oxygenation level dependent (BOLD) contrast method and arterial spin tagging (AST) techniques. We have examined healthy controls, patients with schizophrenia, and their siblings using motor tasks of varying complexity and cognitive tasks of increasing working memory load. The results of these studies in over 60 patients strongly suggest that there is functional disturbance in the cortical motor circuitry of patients with schizophrenia compared with healthy controls. Patients with schizophrenia are unable to recruit as focal a response as normal subjects, even to a simple, automatic sequential finger movement task. Patients also showed greater ipsilateral activation in the primary sensorimotor and lateral premotor regions. These abnormalities were exacerbated as the complexity of the task increased.Using AST techniques, LDRR studied the activation of memory circuits in cocaine addicts as they view cocaine versus control-related cues in a single step-wise paradigm. The purpose of the study is to better understand the role environmental cues play in eliciting drug craving in addicts. No activation associated change in cerebral blood flow (CBF) was observed in volunteers, whereas six of nine cocaine addicts showed minimal (n= 4) changes in CBF. Significant increases in CBF in two cocaine addicts was observed primarily centered in the extrastriatal cortices that could be related to visual cues involving cocaine and its use.These fMRI studies and others on patients with primary brain tumors were facilitated by using a newly developed real-time analysis package for fMRI and dynamic contrast studies. This new system allows for an interactive fMRI-based Physiological Interview. The investigator can review processed and statistically evaluated activation maps within 20 to 50 seconds after the completion of the MRI acquisition, while the subject is in the scanner in order to take advantage of the experimental conditions.Multislice 1H MR Spectroscopic Imaging (1H MRSI) studies performed in schizophrenic patients have continued to show low N-Acetyl aspartate (NAA) concentrations in the dorsolateral prefrontal cortex and are predictive of higher D-2 binding potential in the basal ganglia. Patients with schizophrenia and their siblings also had significant reductions in hippocampal NAA as compared with controls. These results may suggest that this pattern of neurochemical abnormality may represent a brain OphenotypeO associated with schizophrenia. 1H MRSI was also performed in HIV-positive patients who are receiving Interleukin 2 (IL2) therapy whose side effects include decrease in cognitive function and dementia. Patients evaluated off and on IL2 showed a significant correlation between post-IL2 reductions in NAA/CRE in the prefrontal cortex and impaired performance on the mean digit span subscale. These results suggest neuronal integrity of prefrontal cortex correlates with working memory impairment in HIV-positive adults treated with IL2.
