Cerebral Perfusion Differences in the Visual Cortex and Fusiform Subregions Across the Psychosis Spectrum

Jothini Sritharan^1,2,3,4Victor Zeng^3,4Jan Petr⁵Henk-Jan Mutsaerts^6,7Dung Hoang^3,4Nicolas Bolo^4,8Elena Ivleva⁹Weiying Dai¹⁰Elliot Gershon¹¹Sarah Keedy¹¹David Parker¹²Rebekah Trotti^3,4Jennifer E. McDowell¹²Brett A Clementz¹²Carol A Tamminga⁹Godfrey Pearlson^13,14Matcheri S Keshavan^4,8Paulo Lizano^3,4,8*

• ¹Advanced Imaging Research, Swiss Paraplegic Research, Nottwil, Switzerland
• ²ETH Zürich, Zurich, Zürich, Switzerland
• ³Division of Translational Neuroscience, Beth Israel Deaconess Medical Center, Boston, United States
• ⁴Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, United States
• ⁵Institute for Radiopharmaceutical Cancer Research, Helmholtz Center Dresden-Rossendorf, Helmholtz Association of German Research Centers (HZ), Dresden, Lower Saxony, Germany
• ⁶Department of Radiology and Nuclear Medicine, VU Medical Center, Amsterdam, Netherlands, Netherlands
• ⁷Amsterdam Neuroscience, Brain Imaging, Amsterdam, Netherlands
• ⁸Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, United States
• ⁹Department of Psychiatry, Medical School, University of Texas Southwestern Medical Center, Dallas, Texas, United States
• ¹⁰Binghamton University, Binghamton, New York, United States
• ¹¹Department of Psychiatry, University of Chicago, Chicago, Illinois, United States
• ¹²Departments of Psychology and Neuroscience, BioImaging Research Center, University of Georgia, Athens, United States
• ¹³Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut, United States
• ¹⁴Departments of Psychiatry and Neuroscience, Yale University, New Haven, United States

Background: Approximately 50% of individuals with psychosis spectrum disorders (PSD) experience visual hallucinations and deficits in visual processing. Cerebral blood flow (CBF) alterations have been identified in the occipital lobe (OL) and fusiform gyrus (FG) in PSD.However, prior studies neither report on cytoarchitectonic subregions of the OL or FG, nor their correlations with cognition. Moreover, perfusion differences across neurobiologically defined psychosis Biotypes in these regions are not investigated yet.Methods: ExploreASL and FreeSurfer were used to extract perfusion measures from pseudocontinuous arterial spin labeling scans of visual (hOc1-hOc3v, middle temporal area (MT)) and fusiform (FG2-FG4) subregions in 122 bipolar disorder with psychosis (BP), 179 schizoaffective disorder (SAD), 203 schizophrenia (SZ), and 350 healthy controls (NC), as well as psychosis Biotypes (BT1-3). The data was adjusted for scanner effects using ComBat.Analyses were co-varied for total gray matter CBF. We used R to perform statistical comparisons across PSD and NC and across Biotypes. Partial Spearman correlation was performed between CBF and cognitive measures. Benjamini & Hochberg correction was used to correct for multiple comparisons.Results: PSD exhibited greater perfusion in MT and FG2 compared to NC. Perfusion significantly differed across psychosis Biotypes in hOc1 but not across diagnostic groups.Higher MT and FG4 perfusion in PSD were associated with worse overall cognitive performance.Conclusions: Visual and fusiform subregions demonstrate significant perfusion alterations which may indicate neurovascular deficits in PSD. Moreover, these perfusion alterations may contribute to cognitive impairments and visual abnormalities in psychosis.