Hippocampus-Centered Network Is Associated With Positive Symptom Alleviation in Patients With First-Episode Psychosis

Jussi Alho*, Juha M. Lahnakoski, Jonatan M. Panula, Eva Rikandi, Teemu Mäntylä, Maija Lindgren, Tuula Kieseppä, Jaana Suvisaari, Mikko Sams, Tuukka T. Raij*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

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Background: Previous functional magnetic resonance imaging studies have reported widespread brain functional connectivity alterations in patients with psychosis. These studies have mostly used either resting-state or simple-task paradigms, thereby compromising experimental control or ecological validity, respectively. Additionally, in a conventional functional magnetic resonance imaging intrasubject functional connectivity analysis, it is difficult to identify which connections relate to extrinsic (stimulus-induced) and which connections relate to intrinsic (non–stimulus-related) neural processes. Methods: To mitigate these limitations, we used intersubject functional connectivity (ISFC) to analyze longitudinal functional magnetic resonance imaging data collected while 36 individuals with first-episode psychosis (FEP) and 29 age- and sex-matched population control participants watched scenes from the fantasy movie Alice in Wonderland at baseline and again at 1-year follow-up. Furthermore, to allow unconfounded comparison and to overcome possible circularity of ISFC, we introduced a novel approach wherein ISFC in both the FEP and population control groups was calculated with respect to an independent group of participants (not included in the analyses). Results: Using this independent-reference ISFC approach, we found an interaction effect wherein the independent-reference ISFC in individuals with FEP, but not in the control group participants, was significantly stronger at baseline than at follow-up in a network centered in the hippocampus and involving thalamic, striatal, and cortical regions, such as the orbitofrontal cortex. Alleviation of positive symptoms, particularly delusions, from baseline to follow-up was correlated with decreased network connectivity in patients with FEP. Conclusions: These findings link deviation of naturalistic information processing in the hippocampus-centered network to positive symptoms.

Original languageEnglish
Pages (from-to)1197-1206
Number of pages10
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
Issue number12
Early online date2023
Publication statusPublished - Dec 2023
MoE publication typeA1 Journal article-refereed


  • Functional connectivity
  • Functional magnetic resonance imaging (fMRI)
  • Hippocampus
  • Movie
  • Positive symptoms
  • Psychosis


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