RESUMO
The insula is an integral component of sensory, motor, limbic, and executive functions, and insular dysfunction is associated with numerous human neuropsychiatric disorders. Insular afferents project widely, but insulo-striate projections are especially numerous. The targets of these insulo-striate projections are organized into tissue compartments, the striosome and matrix. These striatal compartments have distinct embryologic origins, afferent and efferent connectivity, dopamine pharmacology, and susceptibility to injury. Striosome and matrix appear to occupy separate sets of cortico-striato-thalamo-cortical loops, so a bias in insulo-striate projections towards one compartment may also embed an insular subregion in distinct regulatory and functional networks. Compartment-specific mapping of insulo-striate structural connectivity is sparse; the insular subregions are largely unmapped for compartment-specific projections. In 100 healthy adults, we utilized probabilistic diffusion tractography to map and quantify structural connectivity between 19 structurally-defined insular subregions and each striatal compartment. Insulo-striate streamlines that reached striosome-like and matrix-like voxels were concentrated in distinct insular zones (striosome: rostro- and caudoventral; matrix: caudodorsal) and followed different paths to reach the striatum. Though tractography was generated independently in each hemisphere, the spatial distribution and relative bias of striosome-like and matrix-like streamlines were highly similar in the left and right insula. 16 insular subregions were significantly biased towards one compartment: seven toward striosome-like voxels and nine toward matrix-like voxels. Striosome-favoring bundles had significantly higher streamline density, especially from rostroventral insular subregions. The biases in insulo-striate structural connectivity we identified mirrored the compartment-specific biases identified in prior studies that utilized injected tract tracers, cytoarchitecture, or functional MRI. Segregating insulo-striate structural connectivity through either striosome or matrix may be an anatomic substrate for functional specialization among the insular subregions.
RESUMO
The mammalian striatum is comprised of intermingled tissue compartments, matrix and striosome. Though indistinguishable by routine histological techniques, matrix and striosome have distinct embryologic origins, afferent/efferent connections, surface protein expression, intra-striatal location, susceptibilities to injury, and functional roles in a range of animal behaviors. Distinguishing the compartments previously required post-mortem tissue and/or genetic manipulation; we aimed to identify matrix/striosome non-invasively in living humans. We used diffusion MRI (probabilistic tractography) to identify human striatal voxels with connectivity biased towards matrix-favoring or striosome-favoring regions (determined by prior animal tract-tracing studies). Segmented striatal compartments replicated the topological segregation and somatotopic organization identified in animal matrix/striosome studies. Of brain regions mapped in prior studies, our human brain data confirmed 93% of the compartment-selective structural connectivity demonstrated in animals. Test-retest assessment on repeat scans found a voxel classification error rate of 0.14%. Fractional anisotropy was significantly higher in matrix-like voxels, while mean diffusivity did not differ between the compartments. As mapped by the Talairach human brain atlas, 460 regions were significantly biased towards either matrix or striosome. Our method allows the study of striatal compartments in human health and disease, in vivo, for the first time.