Longitudinal Brain Correlates of Cognitive Performance in Early Psychosis
- 1Vanderbilt University Medical Center
Abstract
BackgroundCognitive impairment is the leading cause of disability in schizophrenia with limited treatments. A major barrier to treatment development is the absence of reproducible, mechanistically grounded neural targets. Cross-sectional studies have identified dorsomedial prefrontal cortex (DMPFC)-somatomotor connectivity as a neural marker of cognitive performance on the Auditory Continuous performance task (ACPT), a measure of attention. To test the stability of this marker, we tested the relationship between DMPFC-somatomotor connectivity and ACPT performance in a longitudinal psychosis sample.
MethodsIndividuals with early psychosis (n=251) and matched controls (n=90) were enrolled and underwent resting-state neuroimaging and neurocognitive assessment. A subset completed longitudinal assessments over 2-4 years. We calculated DMPFC-somatomotor resting-state functional connectivity using a previously identified DMPFC region and a seed in the somatomotor cortex. We performed linear mixed effects models to predict ACPT performance based on connectivity, time, psychosis type, and their interaction.
ResultsIn the psychosis sample, time (p=.0037) and affective psychosis diagnosis (p<.0001) predicted better ACPT performance. In a model predicting ACPT performance, we observed a significant interaction effect of DMPFC-somatomotor connectivity*psychosis subtype (p=.0079) such that DMPFC-somatomotor connectivity predicted ACPT performance only in individuals with non-affective psychosis (p=.0051). We then tested the specificity of this connectivity-cognitive performance relationship. In a model predicting DMPFC-somatomotor connectivity, only ACPT performance (p=.017), but not fluid cognition, was a significant predictor.
ConclusionsDMPFC-somatomotor connectivity is longitudinally associated with cognitive performance in early psychosis. This relationship is strongest in nonaffective psychosis, suggesting a novel, reliable target for intervention for cognitive deficits in early psychosis.
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BibTeX
@misc{mignondje2026longitudinal,
title = {{Longitudinal Brain Correlates of Cognitive Performance in Early Psychosis}},
author = {K. A. Mignondje and J. G. Connolly and A. Beermann and E. Crabtree and S. Vandekar and M. J. Roeske and K. Biernacki and M. J. Coleman and M. E. Shenton and R. O. Brady and K. E. Lewandowski and H. B. Ward},
howpublished = {medRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.28.26361680},
url = {https://www.medrxiv.org/content/10.64898/2026.08.28.26361680v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Longitudinal Brain Correlates of Cognitive Performance in Early Psychosis
AU - K. A. Mignondje
AU - J. G. Connolly
AU - A. Beermann
AU - E. Crabtree
AU - S. Vandekar
AU - M. J. Roeske
AU - K. Biernacki
AU - M. J. Coleman
AU - M. E. Shenton
AU - R. O. Brady
AU - K. E. Lewandowski
AU - H. B. Ward
PY - 2026
DA - 2026/08/28
PB - medRxiv
DO - 10.64898/2026.08.28.26361680
UR - https://www.medrxiv.org/content/10.64898/2026.08.28.26361680v1
AB - BackgroundCognitive impairment is the leading cause of disability in schizophrenia with limited treatments. A major barrier to treatment development is the absence of reproducible, mechanistically grounded neural targets. Cross-sectional studies have identified dorsomedial prefrontal cortex (DMPFC)-somatomotor connectivity as a neural marker of cognitive performance on the Auditory Continuous performance task (ACPT), a measure of attention. To test the stability of this marker, we tested the relationship between DMPFC-somatomotor connectivity and ACPT performance in a longitudinal psychosis sample. MethodsIndividuals with early psychosis (n=251) and matched controls (n=90) were enrolled and underwent resting-state neuroimaging and neurocognitive assessment. A subset completed longitudinal assessments over 2-4 years. We calculated DMPFC-somatomotor resting-state functional connectivity using a previously identified DMPFC region and a seed in the somatomotor cortex. We performed linear mixed effects models to predict ACPT performance based on connectivity, time, psychosis type, and their interaction. ResultsIn the psychosis sample, time (p=.0037) and affective psychosis diagnosis (p<.0001) predicted better ACPT performance. In a model predicting ACPT performance, we observed a significant interaction effect of DMPFC-somatomotor connectivity*psychosis subtype (p=.0079) such that DMPFC-somatomotor connectivity predicted ACPT performance only in individuals with non-affective psychosis (p=.0051). We then tested the specificity of this connectivity-cognitive performance relationship. In a model predicting DMPFC-somatomotor connectivity, only ACPT performance (p=.017), but not fluid cognition, was a significant predictor. ConclusionsDMPFC-somatomotor connectivity is longitudinally associated with cognitive performance in early psychosis. This relationship is strongest in nonaffective psychosis, suggesting a novel, reliable target for intervention for cognitive deficits in early psychosis.
ER -