Non-linear variations in glutamate dynamics during a cognitive task engagement in schizophrenia

• Published in: Psychiatry research. Neuroimaging 2023-07, Vol.332, p.111640-111640, Article 111640
• Main Authors: Graham, James W.C., Jeon, Peter, Théberge, Jean, Palaniyappan, Lena
• Format: Article
• Language: English
• Subjects: Cognition; Conflict monitoring; Excitotoxicity; Glutamic Acid - metabolism; Humans; Inhibition; Interference; Magnetic Resonance Spectroscopy; NMDA; Psychotic Disorders - psychology; Schizophrenia - diagnostic imaging
• ISSN: 0925-4927; 1872-7506
• DOI: 10.1016/j.pscychresns.2023.111640

•Analysis of highly localised signals in the brain is possible through 7T-fMRS.•People with psychosis were assessed on multiple cognitive/lifestyle scales.•People with psychosis show differences in glutamate during a cognitive task.•Key time-series metrics are linked to cognitive task performance in Schizophrenia.•Proof of concept that glutamate time-series exhibits aberrant complexity in psychosis. To investigate the role of glutamate in psychosis, we employ functional magnetic resonance spectroscopy at an ultra-high magnetic field (7T) and employ fuzzy-approximate entropy (F-ApEn) and Hurst Exponent (HE) to capture time-varying nature of glutamate signaling during a cognitive task. We recruited thirty first-episode psychosis patients (FEP) with age- and gender-matched healthy controls (HC) and administered the Color-Word Stroop paradigm, providing 128 raw MRS time-points per subject over a period of 16 min. We then performed metabolite quantification of glutamate in the dorsal anterior cingulate cortex, a region reliably activated during the Stroop task. Symptoms/cognitive functioning was measured using Positive and Negative Syndrome Scale-8 score, Social and Occupational Functioning (SOFAS) score, digit symbol) coding score, and Stroop accuracy. These scores were related to the Entropy/HE data from the overall glutamate time-series. Patients with FEP had significantly higher HE compared to HC, with individuals displaying significantly higher HE having lower functional performance (SOFAS) in both HC and FEP groups. Among healthy individuals, higher HE also indicated significantly lower cognitive function through Stroop accuracy and DSST scores. F-ApEn had an inverse Pearson correlation with HE, and tracked diagnosis, cognition and function as expected, but with lower effect sizes not reaching statistical significance. We demonstrate notable diagnostic differences in the temporal course of glutamate signaling during a cognitive task in psychosis.