GABA, Glutamate dynamics and BOLD observed during cognitive processing in psychosis patients with hallucinatory traits

Abstract

The perception of a voice in the absence of an external auditory source - an auditory verbal hallucination - is a characteristic symptom of schizophrenia. To better understand this phenomenon requires integration of findings across behavioural, functional, and neurochemical levels. We address this with a locally adapted MEGA-PRESS sequence incorporating interleaved unsuppressed water acquisitions, allowing concurrent assessment of behaviour, blood-oxygenation-level-dependent (BOLD) functional changes, Glutamate+Glutamine (Glx), and GABA, synchronised with a cognitive (flanker) task. We acquired data from the anterior cingulate cortex (ACC) of 51 patients with psychosis (predominantly schizophrenia spectrum disorder) and hallucinations, matched to healthy controls. Consistent with the notion of an excitatory/inhibitory imbalance, we hypothesized differential effects for Glx and GABA between groups, and aberrant dynamics in response to task. Results showed impaired task performance, lower baseline Glx and positive association between Glx and BOLD in patients, contrasting a negative correlation in healthy controls. Task-related increases in Glx were observed in both groups, with no significant difference between groups. No significant effects were observed for GABA. These findings suggest that a putative excitatory/inhibitory imbalance affecting inhibitory control in the ACC is primarily observed as tonic, baseline glutamate differences, rather than GABAergic effects or aberrant dynamics in relation to a task. HighlightsO_LIIn-vivo, GABA-edited functional 1H-MRS data were collected from 51 patients with hallucinations and a similar number of matched healthy controls C_LIO_LIReduced Glutamate+Glutamine (Glx) levels were observed in the patient group. C_LIO_LIBOLD association to baseline Glutamate+Glutamine (Glx) differed between patients and controls C_LIO_LIRobust task-related increases in measured Glx were observed in the Anterior Cingulate Cortex (ACC) C_LIO_LITask-related changes in measured Glx did not differ between patients and controls C_LI