T96. Ketamine Induced Changes in Regional Cerebral Blood Flow, Metabolic Connectivity, and Glutamate Metabolism
Year: 2019
Type: conference-abstract
Abstract: Several neuroimaging studies have attempted to characterize the contribution of glutamatergic dysfunction to functional dysconnectivity of large-scale brain networks using ketamine models. However, findings from blood oxygen level dependent signal (BOLD) imaging studies have been conflicting, in part because the signal stems from a complex interaction between blood flow, blood volume, and oxygen consumption. We obtained multimodal neuroimaging in a group of healthy volunteers (n= 15) during a saline and during a ketamine infusion (0.27mg/kg bolus over 10 minutes, followed by a continuous infusion of 0.25mg/kg/hour for 50 minutes). We acquired 2D pCASL scans (TR/ TE= 5230/ 53ms, excitation flip angle= 90°, in-plane resolution= 3.75× 3.75mm2, matrix= 64× 64, slice thickness= 6mm, label time 1s, delay time 1s, labeling offset 8cm) with 30 pairs of labeled and unlabeled images to measure regional cerebral blood flow (rCBF) and MR spectroscopy scans in the left hippocampus (TR/TE= 2000/80ms; 1200 Hz spectral bandwidth; 1024 points; 640 averages, and 8 averages without water suppression, voxel size: 2.7x 1.5x 1cm) to measure glx (glutamate+glutamine). We examined changes in rCBF and metabolic connectivity, as well as their associations with clinical symptom severity (measured with the Brief Psychiatric Rating Scale [BPRS]) and glx levels. Voxelwise analysis comparing rCBF during a saline infusion and ketamine challenge demonstrated regionally selective increases in the prefrontal, orbitofrontal and cingulate cortices as well as the insula, angular gyrus, caudate, putamen, thalamus and hippocampus. No areas showed a decrease in rCBF. Metabolic connectivity analyses revealed a complex pattern of ketamine related rCBF changes. Positive correlations between the anterior cingulate/ frontal pole and insula decreased. Negative correlations between the hippocampus and the dorsolateral prefrontal cortex as well as the putamen decreased. We also found that the increase in rCBF in the bilateral putamen and left hippocampus was positively correlated with psychosis severity during the ketamine challenge while change in anterior cingulate cortex rCBF was negatively correlated with change in hippocampal Glx. Here we find regionally selective patterns of rCBF changes, and metabolic connectivity changes at the level of large-scale brain networks that are thought to be central to the schizophrenia psychopathology. Our study adds to the efforts to confirm putative links between an imbalance in glutamate metabolism and dysconnectivity of large-scale brain networks. Development of glutamatergic compounds that alleviate disease burden, possibly through normalizing glutamate excess related increased rCBF, are direly needed.
Source: Schizophrenia Bulletin
Authors: Edward Bryant, Michael Froelich, Steve Tran, Meredith Reid, Adrienne Lahti, Nina Kraguljac
Institutions: University of Alabama at Birmingham, Auburn University
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2936240977