Functional parcellation of human and macaque striatum reveals human-specific connectivity in the dorsal caudate

Xiaojin Liu,Simon B Eickhoff,Svenja Caspers,Jianxiao Wu,Sarah Genon,Felix Hoffstaedter,Rogier B Mars,Iris E Sommer,Claudia R Eickhoff,Ji Chen,Renaud Jardri,Kathrin Reetz,Imis Dogan,André Aleman,Lydia Kogler,Oliver Gruber,Julian Caspers,Christian Mathys,Kaustubh R Patil

doi:10.1016/j.neuroimage.2021.118006

Abstract

A wide homology between human and macaque striatum is often assumed as in both the striatum is involved in cognition, emotion and executive functions. However, differences in functional and structural organization between human and macaque striatum may reveal evolutionary divergence and shed light on human vulnerability to neuropsychiatric diseases. For instance, dopaminergic dysfunction of the human striatum is considered to be a pathophysiological underpinning of different disorders, such as Parkinson's disease (PD) and schizophrenia (SCZ). Previous investigations have found a wide similarity in structural connectivity of the striatum between human and macaque, leaving the cross-species comparison of its functional organization unknown. In this study, resting-state functional connectivity (RSFC) derived striatal parcels were compared based on their homologous cortico-striatal connectivity. The goal here was to identify striatal parcels whose connectivity is human-specific compared to macaque parcels. Functional parcellation revealed that the human striatum was split into dorsal, dorsomedial, and rostral caudate and ventral, central, and caudal putamen, while the macaque striatum was divided into dorsal, and rostral caudate and rostral, and caudal putamen. Cross-species comparison indicated dissimilar cortico-striatal RSFC of the topographically similar dorsal caudate. We probed clinical relevance of the striatal clusters by examining differences in their cortico-striatal RSFC and gray matter (GM) volume between patients (with PD and SCZ) and healthy controls. We found abnormal RSFC not only between dorsal caudate, but also between rostral caudate, ventral, central and caudal putamen and widespread cortical regions for both PD and SCZ patients. Also, we observed significant structural atrophy in rostral caudate, ventral and central putamen for both PD and SCZ while atrophy in the dorsal caudate was specific to PD. Taken together, our cross-species comparative results revealed shared and human-specific RSFC of different striatal clusters reinforcing the complex organization and function of the striatum. In addition, we provided a testable hypothesis that abnormalities in a region with human-specific connectivity, i.e., dorsal caudate, might be associated with neuropsychiatric disorders.

Highlights

Animal models provide important perspectives on neural functions, structures and disease, with several studies reporting an overall functional and structural similarity between non-human primates and humans (Goulas et al, 2014; Mars et al, 2011, 2018; MirandaDominguez et al, 2014; van den Heuvel et al, 2019)
Functional parcellation revealed that the human striatum was split into dorsal, dorsomedial, and rostral caudate and ventral, central, and caudal putamen, while the macaque striatum was divided into dorsal, and rostral caudate and rostral, and caudal putamen
Our findings showed dissimilar cortico-striatal resting-state functional connectivity (RSFC) of dorsal caudate relating to relevant reward and decision-making functions can be detected in cross-species comparison supplementing previous studies

Summary

Introduction

Animal models provide important perspectives on neural functions, structures and disease, with several studies reporting an overall functional and structural similarity between non-human primates and humans (Goulas et al, 2014; Mars et al, 2011, 2018; MirandaDominguez et al, 2014; van den Heuvel et al, 2019). Projections from anteromedial prefrontal cortex to dorsoanterior striatum mediates learning processes related to reward-related actions, while projections from sensorimotor cortex to dorsoposterior striatum mediated processes related to acquisition of habits (Balleine et al, 2007) These projections route the information flow through substantia nigra pars reticularis (SNr) and globus pallidus internal segment (GPi) and back to the cerebral cortex. This prior knowledge from non-human primates and subsequent in-vivo neuroimaging findings in humans suggests that the human striatum is potentially divided into several structural and functional subregions (i.e. parcels) based on their involvement in multiple cortico-striatal circuits (Choi et al, 2012; Leh et al, 2007; Tziortzi et al, 2014)

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