bioRxiv Science⌕ Search

bioRxiv · 10.1101/2025.09.01.673509

In Humans, fMRI Reveals That Striosome-like and Matrix-like Striatal Voxels are Engaged in Different Phases of Movement

Abstract

IntroductionThe striatum is organized into two neurochemically and anatomically distinct compartments, the striosome and matrix, that play specialized roles in motor and cognitive functions. While extensive animal research has elucidated compartment-specific contributions to reward, learning and motor control, direct evidence for compartment specialization in humans is lacking. MethodsWe defined human striatal voxels as striosome-like or matrix-like based on biases in structural (diffusion) connectivity. Then we investigated functional activation patterns in those compartment-like voxels using task-based functional MRI (tfMRI) during pre-movement cue and five motor conditions (left/right hand, left/right foot, and tongue movements). ResultsFunctional activation was strikingly segregated: striosome-like voxels were preferentially engaged during the cue phase, while matrix-like voxels dominated activation during motor execution, especially for tongue and foot movement. Motor tasks elicited robust bilateral activation, with contralateral activation dominating during limb movements. Activation was more lateralized in matrix-like than in striosome-like voxels. Both striosome-like and matrix-like voxels exhibited strong activation at the onset of task execution (e.g., within the first few seconds post-cue). However, activation in matrix-like voxels declined modestly over the course of the movement phase, while striosomal activation dropped sharply at task termination, suggesting a role in behavioral transitions. These findings are consistent with the role of the striosome in anticipatory evaluation and dopaminergic modulation, and matrix specialization for executing automatized routines. ConclusionsThis study provides the first task-based fMRI evidence of temporally and functionally distinct striatal compartment dynamics in humans, offering novel insights into striatal microcircuitry in motivated behavior and the planning and execution of movements. Key PointsO_LIStriatal medium spiny neurons develop in two interdigitated tissue compartments, the striosome and matrix, that are embryologically, pharmacologically, and anatomically distinct. Inter-compartmental differences in function have been identified in animals, but never in humans. C_LIO_LIWe found that in humans, the compartments differed in functional activation during movement tasks: during the task cue, activation was greater in striosome-like voxels, while matrix-like activation was greater during each of five distinct types of movement. C_LIO_LIBoth compartments were active at the beginning of movement, but at the termination of movement striosome-like activation fell to below baseline, suggesting a role for the striosome in behavioral transitions. C_LI

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Sadiq, A., Waugh, J. L.. 2025-09-05. In Humans, fMRI Reveals That Striosome-like and Matrix-like Striatal Voxels are Engaged in Different Phases of Movement. https://doi.org/10.1101/2025.09.01.673509

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Neurodegeneration-inducing macromolecules exit the brain via nanovascular conduits formed by reticular fibroblasts

Accumulation of proteins such as amyloid beta (Abeta), hyperphosphorylated tau and alpha-synuclein within the brain alters neural information processing and causes neurodegeneration(1-3), but how toxic solutes are cleared from the brain remains highly controversial(4,5). Proposed exit routes include efflux across endothelial cells into the blood(6,7), and movement to the pial surface via vasomotion-induced pumping along spaces within arteriolar smooth muscle(8) or via outflow along the perivascular space of ascending venules promoted by water flux through astrocytes (the glymphatic system(9)). From the pial surface of the brain, drainage may continue to dural lymphatics, along the outer sheaths of exiting cranial nerves and across the cribriform plate(10-14). We now report the presence, in mice and humans, of 2 micron diameter conduits that remove fluorescently labelled tau and Abeta from the brain. These conduits form a spatially-organised mesh within the walls of penetrating arterioles and pial arteries, and around the surface of ascending venules and deep cerebral and pial veins. They course through the pial and arachnoid layers to span the CSF space, wrapping the brain and cranial nerves. They are formed of reticular fibroblasts, which label for VE-cadherin(15) and PDGFRalpha(16), the lymphatic markers(17) podoplanin, VEGFR3 and Prox1, and reticular fibroblast extracellular matrix components collagen I and VI(16,18-20). Parenchymal tau drains from the brain at a similar rate via arteriolar conduits and via conduits around venules, arguing against preferential removal by a glymphatic mechanism. In Alzheimer's disease model mice, Abeta is seen traversing these lymph node-like conduits. Modulation of molecular transfer via this route may accelerate or delay cognitive decline, and slowed transfer from arteriolar to pial-arachnoid conduits may initiate cerebral amyloid angiopathy.

neuroscience↗

Analysis of the influence of gradual changes in matrix sentence similarity on neural envelope tracking

Neural tracking of speech is a well-established phenomenon in neuroscience. However, for speech signals with a fixed structure, significant correlations between speech envelopes and neurophysiological representations occur even for unheard sentences. We exploit a structured speech-in-noise matrix hearing test (Oldenburger Sentence Test, OLSA) to systematically quantify the relationship between acoustic sentence similarity and neural tracking. Simultaneous magnetoencephalography (MEG) and 76-channel electroencephalography (EEG) data, including 16 channels positioned directly around the ears (ear-EEG), were recorded from 21 young adults with normal hearing during the presentation of clean-speech audiobooks and OLSA sentences at six signal-to-noise ratios. A linear decoder trained on audiobooks reconstructed OLSA sentence envelopes. Reconstruction accuracies were compared using a linear mixed model across heard (matched) and unheard (mismatched) sentences of varying acoustic similarity. Significant reconstruction accuracies were achieved across MEG, EEG, and ear-EEG for both matched and mismatched sentences. For mismatched sentences, these accuracies gradually increased with their acoustic similarity to the heard speech data. The high similarity between sentences, which is especially prominent in matrix tests, can cause significant spurious tracking for mismatched stimuli. This effect can reach levels comparable to those of matched sentences and can be mistaken for true neural tracking. Robust neural tracking across modalities further supported the established viability of ear-EEG compared to whole-head systems.

neuroscience↗

Seizures and tauopathy following neurotrauma are mediated by prion protein and metabotropic glutamate receptor 5

Traumatic brain injury (TBI) is one of the world's leading causes of death and disability and a major risk factor for dementias. The primary dementia associated with TBI is chronic traumatic encephalopathy (CTE), a neurodegenerative disease classified as a tauopathy, in which toxic tau molecules lead to disease pathologies and degeneration. The processes that lead to tauopathy and subsequent dementia after TBI remain unclear. Here, we built upon the finding that seizures after TBI may be a mechanism leading to tauopathy, by dissecting the functions of the metabotropic glutamate receptor 5 - cellular prion protein (mGluR5-PrPC) pathway. We delivered TBI to larval in a blast paradigm, and quantified aggregation of Tau via a genetically-encoded Tau-GFP fusion reporter. Zebrafish larvae lacking prp2 (homolog of mammalian cellular Prion Protein, PrPC) displayed a 168% increase in post-traumatic seizures activity after TBI. An mGluR5 agonist (CHPG) reduced post-traumatic seizures, whereas an mGluR5 antagonist (MPEP) increased post-traumatic seizures. Moreover, agonizing mGluR5 reduced tau aggregation and antagonizing mGluR5 increased tau burden. Larvae seizing from convulsants, rather than TBI, were treated with CHPG/MPEP and provided a similar pattern of outcomes, suggesting seizures may be a factor needed for mGluR5 activity to influence tau aggregation. The PrPC-mGluR5 pathway is proposed as one candidate pathomechanism linking TBI to subsequent seizures and tauopathy, and thus it warrants investigation as a target for prophylactic interventions.

neuroscience↗