Neural Circuitry of Novelty Salience Processing in Psychosis Risk Association With Clinical Outcome.pdf (5.02 MB)
Download fileNeural circuitry of novelty salience processing in psychosis risk: association with clinical outcome
journal contribution
posted on 2023-06-10, 04:57 authored by Gemma Modinos, Paul Allen, Andre Zugman, Danai Dima, Matilda Azis, Carly Samson, Ilaria Bonoldi, Beverly Quinn, George W G Gifford, Sophie E Smart, Mathilde Antoniades, Mattijis G Bossong, Matthew R Broome, Jesus Perez, Oliver D Howes, James StoneJames Stone, Anthony A Grace, Philip McGuirePsychosis has been proposed to develop from dysfunction in a hippocampal-striatal-midbrain circuit, leading to aberrant salience processing. Here, we used functional magnetic resonance imaging (fMRI) during novelty salience processing to investigate this model in people at clinical high risk (CHR) for psychosis according to their subsequent clinical outcomes. Seventy-six CHR participants as defined using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and 31 healthy controls (HC) were studied while performing a novelty salience fMRI task that engaged an a priori hippocampal-striatal-midbrain circuit of interest. The CHR sample was then followed clinically for a mean of 59.7 months (~5 y), when clinical outcomes were assessed in terms of transition (CHR-T) or non-transition (CHR-NT) to psychosis (CAARMS criteria): during this period, 13 individuals (17%) developed a psychotic disorder (CHR-T) and 63 did not. Functional activation and effective connectivity within a hippocampal-striatal-midbrain circuit were compared between groups. In CHR individuals compared to HC, hippocampal response to novel stimuli was significantly attenuated (P =. 041 family-wise error corrected). Dynamic Causal Modelling revealed that stimulus novelty modulated effective connectivity from the hippocampus to the striatum, and from the midbrain to the hippocampus, significantly more in CHR participants than in HC. Conversely, stimulus novelty modulated connectivity from the midbrain to the striatum significantly less in CHR participants than in HC, and less in CHR participants who subsequently developed psychosis than in CHR individuals who did not become psychotic. Our findings are consistent with preclinical evidence implicating hippocampal-striatal-midbrain circuit dysfunction in altered salience processing and the onset of psychosis.
History
Publication status
- Published
File Version
- Published version
Journal
Schizophrenia BulletinISSN
0586-7614Publisher
Oxford University Press (OUP)External DOI
Issue
3Volume
46Page range
670-679Event location
United StatesDepartment affiliated with
- BSMS Neuroscience Publications
Full text available
- Yes
Peer reviewed?
- Yes