Cerebellum-ventral tegmental connectivity as a mechanism-informed target for apathy in schizophrenia

Overview

1. Neuroimaging and Translational Psychiatry Lab, Department of Psychiatry, University of Geneva; Geneva, 1202, Switzerland
2. Synapsy Center for Neuroscience and Mental Health Research, University of Geneva; Geneva, 1202, Switzerland
3. Institute of Behavioral Science, Feinstein Institutes for Medical Research; Manhasset, New York, 11030, United States of America
4. Division of Psychiatry Research, Zucker Hillside Hospital; Glen Oaks, 11004, New York
5. Department of Psychiatry, Zucker School of Medicine at Hofstra/Northwell, Hempstead, 11549, New York
6. Neuro-X Institute, École Polytechnique Fédérale de Lausanne; Geneva, 1202, Switzerland
7. Department of Radiology and Medical Informatics, University of Geneva; Geneva, 1202, Switzerland
8. Clinical and Experimental Psychopathology Laboratory, Department of Psychiatry, University of Geneva; Geneva, 1205, Switzerland
9. Adult Psychiatry Division, Department of Psychiatry, University Hospitals of Geneva; Geneva, 1205, Switzerland

Abstract

Apathy is a leading driver of functional disability in schizophrenia, yet effective mechanism-based therapies are lacking. We evaluated whether cerebellum–ventral tegmental area functional connectivity (CB-VTA FC) meets the criteria for clinical translation as a therapeutic neuromodulation target. Using resting-state fMRI in three independent repeated-imaging cohorts (healthy controls, early psychosis or chronic schizophrenia patients, minutes–months inter-scan intervals), CB-VTA FC was always stable and individual-specific (stability r=0.52–0.69; differential identifiability Δr=0.21–0.35; all p<10− L). In paravermal cerebellar territories, it tracked apathy severity in two patient cohorts (early psychosis, Crus I/II: n=99; rLL=0.36, p=2.65·10−L; chronic schizophrenia, Lobules VIIB/VIIIA: n=87 scans [65 patients]; tLL=4.06, p=1.1·10−L). In a meta-analysis of 39 randomized controlled transcranial magnetic stimulation trials (n=1,624; 867 active), connectivity of neighboring areas to stimulation site predicted negative symptoms improvement. CB-VTA FC thus emerges as a stable, individual-specific, and symptom-related therapeutically relevant circuit, constituting a mechanism-informed precision neuromodulation target in schizophrenia, ready for prospective clinical trials.

Reproduced under the paper's license (CC0), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

The paper's code and data availability statement is in the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

• humanconnectome.org/storage/app, at Human Connectome Project; found in the text, “Dataset 1 (Human Connectome Project Young…”

Software and data availability

Unless otherwise specified, all the analyses were performed using MATLAB (The MathWorks, Inc., California, United States of America; version 2024a).

Data from Datasets 1 and 2 can be accessed by accredited experimenters. Data from Dataset 3 are available upon reasonable request, subject to data-sharing agreements and within the limits of laboratory resources.

Reproduced under the paper's license (CC0), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

• Authors: added Indrit Bègue (0000-0001-5350-4454); removed Indrit Bègue

Version 1, 28 September 2026: the first record

Recorded: type, journal, dates, 7 authors, 5 funders, 57 references.

Cite

This paper

Bolton, T. A., Sinanaj, L., Velioglu, H. A., Van De Ville, D., Kaiser, S., Cao, H., & Bègue, I. (2026). Cerebellum-ventral tegmental connectivity as a mechanism-informed target for apathy in schizophrenia. medRxiv (preprint). https://doi.org/10.64898/2026.05.20.26353653

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1002/hbm.70533 [code]

Trait-Relevant Tasks Improve Personality Prediction From Structural-Functional Brain Network Coupling.

Journal: Human brain mapping

In common: humanconnectome.org/storage/app, 2 references

[2] doi:10.1038/s41380-026-03547-x [code]

Multiscale characterization of cortical signatures in positive and negative schizotypy: a worldwide ENIGMA study.

Journal: Molecular psychiatry

In common: schizophrenia / psychosis, author Indrit Bègue

[3] doi:10.1038/s41467-026-72940-5 [code]

Cerebellar growth is associated with domain-specific cerebral maturation and socio-linguistic behavior.

Journal: Nature communications

In common: humanconnectome.org/storage/app, 1 reference

[4] doi:10.21203/rs.3.rs-9326213/v1 [code]

Multi-task fMRI outperforms resting-state fMRI for revealing task-invariant organization of the human brain

Journal: Research Square (preprint)

In common: 5 references

[5] doi:10.64898/2026.03.09.710558 [code]

Multi-task fMRI outperforms resting-state fMRI for revealing task-invariant organization of the human brain

Journal: bioRxiv (preprint)

In common: 5 references

[6] doi:10.1007/s11682-026-01167-1

Estradiol modulated brain connectivity in females during midlife performing an episodic memory task.

Journal: Brain imaging and behavior

In common: humanconnectome.org/storage/app, 1 reference

[7] doi:10.1162/imag.a.1222 [code]

Network-based near-scalp personalized brain stimulation targets.

Journal: Imaging neuroscience (Cambridge, Mass.)

In common: 4 references

[8] doi:10.1038/s42003-026-10066-6 [code]

Morphological and anatomical variations in subcortical anatomy between humans and chimpanzees associated with heritability patterns related to human behavioral traits.

Journal: Communications biology

In common: humanconnectome.org/storage/app, 1 reference

[9] doi:10.1038/s41467-026-75371-4 [code]

Cerebellar neural populations orchestrate dopamine reward signaling with single-trial precision.

Journal: Nature communications

In common: 3 references

[10] doi:10.1007/s00429-026-03114-8

Asymmetry of the sulcal pattern of the anterior cingulate cortex modulates delay discounting.

Journal: Brain structure & function

In common: humanconnectome.org/storage/app

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.