Biology subjects

Sadiq, A.

Publications and source records attributed to Sadiq, A..

4 recordsLinked to original sources

bioRxiv2026

Dissociation of Striosome and Matrix Activation in the Human Striatum During the Cue and Execution Phases of Working Memory

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. In animal studies, the striosome has been linked to reward evaluation, emotional learning, and decision-making under conflict, whereas the matrix is more closely associated with sensorimotor integration and task execution. However, evidence for compartment-specific function in humans is limited and indirect. Using probabilistic tractography, we identified voxels with striosome-like and matrix-like patterns of structural connectivity in healthy adults. We then examined how these compartment-like voxels responded to task demands during an fMRI n-back working-memory paradigm that visually presented four stimulus categories (body part, face, place, or tool). We assessed activation in a low-load condition (0-back, remembering a just-viewed stimulus) vs. a high-load condition (2-back, remembering a stimulus viewed two prior). Functional activation was temporally segregated and matched our prior findings in motor tasks: striosome-like voxels were preferentially engaged during the cue and initial preparation phases, whereas matrix-like voxels dominated during task execution. Trial accuracy strongly modulated striatal activation, with both compartments showing significantly greater responses during "correct" than in "error" trials. Notably, the accuracy-related increase in activation was larger in striosome-like voxels, consistent with a prominent role for striosomal processing in performance evaluation. Both striosome- and matrix-like voxels significantly increased activation from 0-back to 2-back, indicating sensitivity to working-memory load, with larger increases for matrix-like than for striosome-like voxels. Category-selective responses also differed by compartment and cognitive load. Under low working-memory load (0-back), stimulus-category effects were modest and broadly similar between compartments. Under higher load (2-back), activation in striosome-like voxels remained selective for specific stimulus categories, while matrix-like voxels lost category specificity. Together, these findings suggest that the striosome-matrix distinction generalizes from motor to cognitive domains, reflecting a conserved division between preparatory and execution-related processes that varies systematically with task demands, memory category, and performance accuracy. This convergence of compartment-specific responses across domains points to a core organizational principle of the human striatum with potential implications for neuropsychiatric diseases. Key PointsO_LIStriatal medium spiny neurons are organized into two interdigitated compartments, the striosome and matrix, which are embryologically, pharmacologically, and anatomically distinct. Compartment-specific functions have been demonstrated in animals, but their roles in human cognition are unexplored. C_LIO_LIWe found that in humans, striosome-like voxels preferentially activated during memory cues, while matrix-like voxels preferentially activated during recall and memory maintenance. In both compartments, activation scaled with task difficulty. C_LIO_LIActivation in striosome-like voxels scaled more strongly with task accuracy and difficulty, suggesting a striosome-selective role in vigilance and/or motivation. C_LI

neuroscience↗

bioRxiv2025

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

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

neuroscience↗

bioRxiv2024

The striatal compartments, striosome and matrix, are embedded in largely distinct resting state functional networks

The striatum is divided into two interdigitated tissue compartments, the striosome and matrix. These compartments exhibit distinct anatomical, neurochemical, and pharmacological characteristics and have separable roles in motor and mood functions. Little is known about the functions of these compartments in humans. While compartment-specific roles in neuropsychiatric diseases have been hypothesized, they have yet to be directly tested. Investigating compartment-specific functions is crucial for understanding the symptoms produced by striatal injury, and to elucidating the roles of each compartment in healthy human skills and behaviors. We mapped the functional networks of striosome and matrix in humans in vivo. We utilized a diverse cohort of 674 healthy adults, derived from the Human Connectome Project, including all subjects with complete diffusion and functional MRI data and excluding subjects with substance use disorders. We identified striatal voxels with striosome-like and matrix-like structural connectivity using probabilistic diffusion tractography. We then investigated resting state functional connectivity (rsFC) using these compartment-like voxels as seeds. We found widespread differences in rsFC between striosome-like and matrix-like seeds (p < 0.05, FWE corrected for multiple comparisons), suggesting that striosome and matrix occupy distinct functional networks. Slightly shifting seed voxel locations (<4 mm) eliminated these rsFC differences, underscoring the anatomic precision of these networks. Striosome-seeded networks exhibited ipsilateral dominance; matrix-seeded networks had contralateral dominance. Next, we assessed compartment-specific engagement with the triple-network model (default mode, salience, and frontoparietal networks). Striosome-like voxels dominated rsFC with the default mode network bilaterally. The anterior insula (a primary node in the salience network) had higher rsFC with striosome-like voxels. The inferior and middle frontal cortices (primary nodes, frontoparietal network) had stronger rsFC with matrix-like voxels on the left, and striosome-like voxels on the right. Since striosome-like and matrix-like voxels occupy highly segregated rsFC networks, striosome-selective injury may produce different motor, cognitive, and behavioral symptoms than matrix-selective injury. Moreover, compartment-specific rsFC abnormalities may be identifiable before disease-related structural injuries are evident. Localizing rsFC differences provides an anatomic substrate for understanding how the tissue-level organization of the striatum underpins complex brain networks, and how compartment-specific injury may contribute to the symptoms of specific neuropsychiatric disorders.

neuroscience↗

bioRxiv2024

Nicotinamide riboside activates renal metabolism and protects the kidney in a model of Alport syndrome

Chronic kidney disease (CKD) is associated with renal metabolic disturbances, including impaired fatty acid oxidation (FAO). Nicotinamide adenine dinucleotide (NAD+) is a small molecule that participates in hundreds of metabolism-related reactions. NAD+ levels are decreased in CKD, and NAD+ supplementation is protective. However, both the mechanism of how NAD+ supplementation protects from CKD, as well as the cell types involved, are poorly understood. Using a mouse model of Alport syndrome, we show that nicotinamide riboside (NR), an NAD+ precursor, stimulates renal peroxisome proliferator-activated receptor alpha signaling and restores FAO in the proximal tubules, thereby protecting from CKD in both sexes. Bulk RNA-sequencing shows that renal metabolic pathways are impaired in Alport mice and activated by NR in both sexes. These transcriptional changes are confirmed by orthogonal imaging techniques and biochemical assays. Single nuclei RNA-sequencing and spatial transcriptomics, both the first of their kind from Alport mice, show that NAD+ supplementation restores FAO in proximal tubule cells. Finally, we also report, for the first time, sex differences at the transcriptional level in this Alport model. In summary, we identify a nephroprotective mechanism of NAD+ supplementation in CKD, and we demonstrate that the proximal tubule cells substantially contribute to this benefit.

molecular biology↗