Functional organization of the primary motor cortex in psychosis and the potential role of intereffector regions in psychomotor slowing

S Sebastian Walther (University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern) F Florian Wüthrich (University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern) A Anastasia Pavlidou (University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern) N Niluja Nadesalingam (University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern) S Stephan Heckers (Department of Psychiatry and Behavioral Science, Vanderbilt University) M Melanie G. Nuoffer (University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern) V Victoria Chapellier (University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern) K Katharina Stegmayer (University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern) L Lydia V. Maderthaner (University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern) A Alexandra Kyrou (University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern) S Sofie von Känel (University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern) S Stephanie Lefebvre (University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern)

Abstract

Altered psychomotor behavior in psychosis is poorly understood. Novel insights into the physiology of the motor cortex prompted a revision of the motor homunculus. Next to core motor effector areas, the primary motor cortex (M1) contains intereffector regions with more integrative connectivity patterns, suggestive of serving psychomotor behavior. Here, we test whether patterns of connectivity differ between patients with and without psychomotor slowing and which cortical areas are associated with aberrant motor behavior in psychosis. This resting-state functional MRI study included 83 patients with psychosis and psychomotor slowing, 43 patients without psychomotor slowing, and 63 matched healthy subjects. We tested group differences in connectivity and regressed motor behavior measures with connectivity in patients with psychomotor slowing. Across subjects, we found distinct rs-fMRI connectivity profiles of the intereffector areas in M1, extending to premotor cortices and cerebellum. Patients with psychomotor slowing had stronger connectivity from the intereffectors than controls or patients without slowing. Finally, motor behavior correlated with connectivity from M1 intereffector regions in patients. Connectivity profiles of intereffectors suggest a role in planning and controlling complex behavioral repertoires. Collectively, these findings in patients with psychomotor slowing stress the importance of intereffector regions in shaping psychomotor behaviors in mental disorders.

Article Details

Volume / Issue Vol. 122, Issue 42
Published October 21, 2025
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (12)

S

Sebastian Walther

University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern

F

Florian Wüthrich

University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern

A

Anastasia Pavlidou

University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern

N

Niluja Nadesalingam

University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern

S

Stephan Heckers

Department of Psychiatry and Behavioral Science, Vanderbilt University

M

Melanie G. Nuoffer

University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern

V

Victoria Chapellier

University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern

K

Katharina Stegmayer

University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern

L

Lydia V. Maderthaner

University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern

A

Alexandra Kyrou

University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern

S

Sofie von Känel

University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern

S

Stephanie Lefebvre

University Hospital of Psychiatry and Psychotherapy Bern, Translational Research Center, University of Bern