Excessive left anterior hippocampal and caudate activation in schizophrenia underlie cognitive underperformance in a virtual navigation task

John A Zawadzki; Todd A Girard; James Samsom; George Foussias; Ishraq Siddiqui; Jason P Lerch; Cheryl Grady; Albert H C Wong

doi:10.1016/j.pscychresns.2024.111826

Excessive left anterior hippocampal and caudate activation in schizophrenia underlie cognitive underperformance in a virtual navigation task

Psychiatry Res Neuroimaging. 2024 May 6:341:111826. doi: 10.1016/j.pscychresns.2024.111826. Online ahead of print.

Authors

John A Zawadzki¹, Todd A Girard², James Samsom³, George Foussias⁴, Ishraq Siddiqui³, Jason P Lerch⁵, Cheryl Grady⁶, Albert H C Wong⁷

Affiliations

¹ Institute of Medical Science, University of Toronto, ON, Canada; Centre for Addiction & Mental Health, Campbell Family Mental Health Research Institute, Toronto, ON, Canada.
² Department of Psychology, Toronto Metropolitan University, Toronto, ON, Canada.
³ Centre for Addiction & Mental Health, Campbell Family Mental Health Research Institute, Toronto, ON, Canada.
⁴ Institute of Medical Science, University of Toronto, ON, Canada; Centre for Addiction & Mental Health, Campbell Family Mental Health Research Institute, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, ON, Canada.
⁵ Department of Medical Biophysics, University of Toronto, ON, Canada; Program in Neuroscience and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada; Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
⁶ Centre for Addiction & Mental Health, Campbell Family Mental Health Research Institute, Toronto, ON, Canada; Department of Psychology, University of Toronto, ON, Canada; Rotman Research Institute at Baycrest, Toronto, ON, Canada.
⁷ Institute of Medical Science, University of Toronto, ON, Canada; Centre for Addiction & Mental Health, Campbell Family Mental Health Research Institute, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Electronic address: albert.wong@utoronto.ca.

PMID: 38735228
DOI: 10.1016/j.pscychresns.2024.111826

Abstract

We used a virtual navigation paradigm in a city environment to assess neuroanatomical correlates of cognitive deficits in schizophrenia spectrum disorders (SSD). We studied a total of N = 36 subjects: 18 with SSD and 18 matched unaffected controls. Participants completed 10 rapid, single-trial navigation tasks within the virtual city while undergoing functional magnetic resonance imaging (fMRI). All trials tested ability to find different targets seen earlier, during the passive viewing of a path around different city blocks. SSD patients had difficulty finding previously-encountered targets, were less likely to find novel shortcuts to targets, and more likely to attempt retracing of the path observed during passive viewing. Based on a priori region-of-interest analyses, SSD participants had hyperactivation of the left hippocampus when passively viewing turns, hyperactivation of the left caudate when finding targets, and hypoactivation of a focal area of the dorsolateral prefrontal cortex when targets were initially shown during passive viewing. We propose that these brain-behaviour relations may bias or reinforce stimulus-response navigation approaches in SSD and underlie impaired performance when allocentric spatial memory is required, such as when forming efficient shortcuts. This pattern may extend to more general cognitive impairments in SSD that could be used to design remediation strategies.

Keywords: Allocentric; Caudate; Cognition; Fast thinking; Hippocampus; Map; fMRI.