Evidence map›Paper›PMID 40767412›Full record

ArticleHuman brain mapping2025

The Genetics of Cerebellar Structure and Associations With Cognitive Performance: A Twin Magnetic Resonance Imaging Study.

Gretchen Lutz, Simon Smerconish, David Roalf, Michael C Neale, J Eric Schmitt

Abstract readTwin Study
In one paragraph

Article in Human brain mapping, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Gretchen LutzDepartment of Radiology, Division of Neuroradiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Simon SmerconishDepartment of Radiology, Division of Neuroradiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
David RoalfDepartment of Psychiatry, Brain Behavior Laboratory, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Michael C NealeDepartments of Psychiatry and Genetics, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, USA.
J Eric SchmittDepartment of Radiology, Division of Neuroradiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-7487-227X

Funding

Mapping the Human Connectome: Structure, Function, and HeritabilityU54MH091657 · NIMH · WASHINGTON UNIVERSITY · PI UGURBIL, KAMIL, VAN ESSEN, DAVID C · 2010 to 2014
$34.7M
Adolescent Substance Use Initiation: Disentangling neurocognitive risks from consequences using longitudinal and genetically-informed methodsU01DA041120 · NIDA · UNIVERSITY OF MINNESOTA · PI Monica Luciana, Sylia Wilson · 2015 to 2026
$34.5M
NIDA NIH HHS U01 DA041120NIH HHSNIMH NIH HHS U54 MH091657
6 · The paper itself

Abstract

The cerebellum, traditionally associated with motor control, is increasingly recognized for its involvement in higher-order cognitive functions. However, the role of cerebellar subregions in cognition remains underexplored, as are the roles of genetic factors on cerebellar structure and brain-behavioral associations. The primary goal of this study was to investigate the relationship between cerebellar subregion volumes and cognitive performance. A secondary aim was to quantify the genetic contributions to cerebellar structure and determine the degree to which any brain-behavior associations were genetically mediated. 3T anatomic MRI data from N = 932 typically developing individuals from the Human Connectome Project were used for this study. Twenty-seven cerebellar regions of interest (ROIs) were automatically parcellated using CerebNet. Three additional lobar-level ROIs were derived from smaller measures. Nine functional domains (six cognitive and three motor) related to known or suspected cerebellar function were selected. Linear regression analyses were conducted to identify correlations between cerebellar volumes and cognitive outcomes, adjusting for age, sex, and overall brain volume. Univariate and bivariate quantitative genetic modeling was then performed in OpenMx. There were numerous statistically significant phenotypic associations between cognitive measures and cerebellar lobar and lobular volumes, particularly in the IPL, AL, bilateral cortices, left lobule V, right lobule VI, vermis, and vermis lobule VIII, each meeting the threshold of p < 0.02 across at least four out of nine cognitive domains. The vermis and vermis lobule VIII were of particular note, showing even stronger associations (p < 0.0009 across three domains). Cognitive measures were modestly heritable, and cerebellar ROIs were highly heritable. Quantitative genetic models suggested that brain-behavior associations are largely driven by shared environmental factors. Our findings identify novel associations between specific cerebellar subregions and cognitive performance, highlighting the vermis as a critical structure. We also provide a detailed map of the quantitative genetics of human cerebellar structure. Future studies are warranted.

Indexed as

CerebellumCognitionAdolescentAdultChildConnectomeFemaleHumansMagnetic Resonance ImagingMaleOrgan SizeTwins, DizygoticTwins, MonozygoticYoung AdultcerebellumcognitiongeneticsMRItwin

Identifiers

PMID40767412
PMCPMC12326421

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.