Dissociation of striosome and matrix activation in the human striatum during the cue and execution phases of working memory: A probabilistic tractography and task fMRI assessment.

The striatum comprises two neurochemically and anatomically distinct tissue compartments, the striosome and matrix, that are hypothesized to support different aspects of cognition and action. Animal studies link striosome to reward evaluation, emotional learning, and decision-making under conflict, whereas matrix is associated with sensorimotor integration and task execution. However, evidence for compartment-specific function in humans remains limited, in part because the gold standard for identifying striosome and matrix, immunohistochemistry, requires ex vivo tissue sections. We instead utilized an inferential method, probabilistic tractography guided by prior histologic assessments, to identify voxels with striosome-like and matrix-like patterns of structural connectivity in healthy adults. Striosome-like and matrix-like voxels identified through this probabilistic method are highly reliable (test-retest error: 0.14%) and match the spatial distribution, extra-striate connectivity, tendency for separation vs. clustering, and relative abundance of striosome and matrix in tissue. Using these inferential compartment-like voxels, we then examined compartment-like responses during an fMRI n-back working-memory task using four visual stimulus categories (body part, face, place, and tool), comparing low (0-back) and high (2-back) working-memory load. Functional activation was temporally segregated, consistent with prior motor-task findings: striosome-like voxels were preferentially engaged during cue and preparatory phases, whereas matrix-like voxels dominated during task execution. Trial accuracy strongly modulated striatal responses, with both compartments activating more during correct than error trials (+71% in striosome-like voxels, +29% in matrix-like voxels). However, accuracy-related modulation did not significantly differ between the compartments. Both compartments showed increased activation from 0-back to 2-back, indicating sensitivity to working-memory load, with larger load-related increases in matrix-like voxels. Category-selective responses differed by compartment and load. Under low load, stimulus-category effects were modest and similar between compartments. Under high load, striosome-like voxels retained category selectivity, whereas matrix-like voxels showed reduced specificity. Together, these findings suggest that striosome-matrix specialization extends beyond motor functions to cognitive domains, reflecting a conserved division between preparatory and execution-related processes that varies systematically with task demands, stimulus category, and performance accuracy.