Shared Fine-Scale Functional Organization in the Human Subcortex Revealed by Connectivity Hyperalignment
- 1Dartmouth College
Abstract
Subcortical structures are central to cognition, emotion, and social processing, and their dysfunction underlies a wide range of neurological and psychiatric conditions. Yet subcortical fine-scale functional organization has remained largely inaccessible to group-level fMRI analysis: nuclei are small and low-SNR, and their functional topography varies idiosyncratically across individuals in ways that anatomical alignment cannot resolve. This idiosyncrasy carries real stakes. For example, deep brain stimulation targets with more variable functional connectivity across individuals show correspondingly less consistent clinical outcomes. Here we show that this seemingly idiosyncratic subcortical organization in fact reflects shared, fine-grained structure that can be recovered by modeling each individual's connectivity in a common functional space (connectivity hyperalignment, CHA), rather than relying on anatomical correspondence. Applying CHA to fMRI data collected during naturalistic movie viewing, we found that aligning subcortical voxels by their cortical connectivity, rather than their anatomical location, sharply increased cross-subject correspondence in both stimulus-evoked response and connectivity profiles. Critically, this alignment sharpened rather than blurred local structure: neighboring voxels became more functionally distinct from one another, and cortical connectivity targets became substantially more decodable across subjects. These results indicate that human subcortical nuclei possess a common fine-scale functional architecture that is masked by anatomical variability but recoverable at the individual level. This reframes a central methodological constraint in subcortical neuroimaging: rather than trading spatial resolution for signal quality via smoothing, group-level analyses can achieve voxel-level precision by aligning function rather than anatomy, opening a path to studying cortical-subcortical circuit organization in greater detail.
Related
- Spatial organization of neural responses to physical and agentive movement dynamics is reflected in intrinsic functional connectivity
- Insula functional connectivity development follows a canonical antero-posterior axis of organization
- Functional organization and natural scene responses across mouse visual cortical areas revealed with encoding manifolds
- Topographic and somatotopic organization of functional connectivity between the intraparietal sulcus and primary somatosensory cortex in macaque monkeys
- Coordinated spatial organization of basal ganglia structures revealed by dopamine subtype projectome mapping
BibTeX
@misc{tu2026shared,
title = {{Shared Fine-Scale Functional Organization in the Human Subcortex Revealed by Connectivity Hyperalignment}},
author = {J. C. Tu and M. Feilong and Y. Zhang and M. I. Gobbini and J. V. Haxby},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.29.755436},
url = {https://www.biorxiv.org/content/10.64898/2026.09.29.755436v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Shared Fine-Scale Functional Organization in the Human Subcortex Revealed by Connectivity Hyperalignment
AU - J. C. Tu
AU - M. Feilong
AU - Y. Zhang
AU - M. I. Gobbini
AU - J. V. Haxby
PY - 2026
DA - 2026/09/29
PB - bioRxiv
DO - 10.64898/2026.09.29.755436
UR - https://www.biorxiv.org/content/10.64898/2026.09.29.755436v1
AB - Subcortical structures are central to cognition, emotion, and social processing, and their dysfunction underlies a wide range of neurological and psychiatric conditions. Yet subcortical fine-scale functional organization has remained largely inaccessible to group-level fMRI analysis: nuclei are small and low-SNR, and their functional topography varies idiosyncratically across individuals in ways that anatomical alignment cannot resolve. This idiosyncrasy carries real stakes. For example, deep brain stimulation targets with more variable functional connectivity across individuals show correspondingly less consistent clinical outcomes. Here we show that this seemingly idiosyncratic subcortical organization in fact reflects shared, fine-grained structure that can be recovered by modeling each individual's connectivity in a common functional space (connectivity hyperalignment, CHA), rather than relying on anatomical correspondence. Applying CHA to fMRI data collected during naturalistic movie viewing, we found that aligning subcortical voxels by their cortical connectivity, rather than their anatomical location, sharply increased cross-subject correspondence in both stimulus-evoked response and connectivity profiles. Critically, this alignment sharpened rather than blurred local structure: neighboring voxels became more functionally distinct from one another, and cortical connectivity targets became substantially more decodable across subjects. These results indicate that human subcortical nuclei possess a common fine-scale functional architecture that is masked by anatomical variability but recoverable at the individual level. This reframes a central methodological constraint in subcortical neuroimaging: rather than trading spatial resolution for signal quality via smoothing, group-level analyses can achieve voxel-level precision by aligning function rather than anatomy, opening a path to studying cortical-subcortical circuit organization in greater detail.
ER -