Relating Glutamate, Conditioned, and Clinical Hallucinations via 1H-MR Spectroscopy.

Abstract

Hallucinations may be driven by an excessive influence of prior expectations on current experience. Initial work has supported that contention and implicated the anterior insula in the weighting of prior beliefs. Here we induce hallucinated tones by associating tones with the presentation of a visual cue. We find that people with schizophrenia who hear voices are more prone to the effect and using computational modeling we show they overweight their prior beliefs. In the same participants, we also measured glutamate levels in anterior insula, anterior cingulate, dorsolateral prefrontal, and auditory cortices, using magnetic resonance spectroscopy. We found a negative relationship between prior-overweighting and glutamate levels in the insula that was not present for any of the other voxels or parameters. Through computational psychiatry, we bridge a pathophysiological theory of psychosis (glutamate hypofunction) with a cognitive model of hallucinations (prior-overweighting) with implications for the development of new treatments for hallucinations.