In vivo studies of human and rat brain using functional magnetic resonance imaging and spectroscopy

Nuclear Magnetic Resonance techniques were implemented to study function in the human auditory cortex and metabolism in the rat cortex. (1) To investigate the auditory cortex response to speech, six human subjects were asked to listen to English nouns presented at various rates ranging from 0 words per minute (wpm) to 130 wpm while functional magnetic resonance images of their brain were acquired. Localized grey matter activation was consistently observed in all subjects in the transverse temporal gyrus, the transverse temporal sulcus, and the posterior superior aspect of the superior temporal gyrus. The total activated volume and the integrated signal response in bilateral primary and posterior superior secondary auditory cortices increased with increasing word presentation rate peaking at 90 wpm with a subsequent fall at 130 wpm (p {dollar}<{dollar} 0.05). (2) The cerebral tricarboxylic acid cycle rate (V{dollar}rmsb{lcub}TCA{rcub}{dollar}) and the flux from glutamate to glutamine (V{dollar}rmsb{lcub}GLN{rcub}{dollar}) were measured using {dollar}sp{lcub}13{rcub}{dollar}C NMR spectroscopy in: (a) control rats ({dollar}alpha{dollar}-chloralose sedation), (b) rats under hyperammonemic conditions, and (c) rats under high-dose pentobarbital anesthesia.; In each, a (1-{dollar}sp{lcub}13{rcub}{dollar}C) glucose infusion was initiated and {dollar}sp{lcub}13{rcub}{dollar}C NMR spectra were acquired continuously to monitor {dollar}sp{lcub}13{rcub}{dollar}C labeling of key cerebral metabolites. The time courses of glutamate and glutamine C-4 labeling were fitted with a mathematical model to yield V{dollar}rmsb{lcub}TCA{rcub}{dollar} and V{dollar}rmsb{lcub}GLN{rcub}{dollar}.; The measured rates of V{dollar}rmsb{lcub}TCA{rcub}{dollar} and V{dollar}rmsb{lcub}GLN{rcub}{dollar} were used to develop a novel model of glutamate neurotransmitter metabolism and cycling. It was calculated that under basal conditions, the majority of the glutamine synthetase flux results from neurotransmitter substrate cycling between neurons and glia. Under hyperammonemic conditions, an increase in the rate of glutamine synthesis, resulting directly from the increased substrate ammonia pool, is superimposed on the neurotransmitter cycling. During pentobarbital sedation, a reduction in the rate of glutamine synthesis results directly from inhibition of neurotransmitter release and, therefore, of cycling.; These studies demonstrate the feasibility of using in vivo NMR techniques to investigate function, metabolism and neurotransmitter cycling in the brain. Furthermore, the {dollar}sp{lcub}13{rcub}{dollar}C NMR data provide the first in vivo measurement of a glutamate-glutamine neurotransmitter cycle in the brain.