Biology subjects

Korponay, C.

Publications and source records attributed to Korponay, C..

3 recordsLinked to original sources

bioRxiv2022

Dissociable misconfigurations of striatal functional connectivity profiles in smokers

Corticostriatal circuits are central to reward processing and reinforcement learning functions that often become dysregulated in substance use disorder (SUD) and drive compulsive drug use. Human neuroimaging research seeking to identify how corticostriatal circuits become altered in SUD has primarily focused on evaluating connectivity between cortex-striatum node-pairs. Yet, striatal nodes receive appreciable input from many cortical nodes, and the morphological and electrophysiological properties of striatal nodes dictate that combinational features of their multivariate "connectivity profiles" shape their activity more so than any individual cortical node. Here, we introduce an approach for quantifying and statistically evaluating different types of multivariate connectivity profile configuration differences (i.e., aggregate divergence, rank order arrangement, and entropy shift) that may reflect different forms of circuit plasticity, and apply it to nicotine dependent smokers (n=46) as an exemplar SUD. Foremost, we find evidence of significant connectivity profile misconfiguration throughout much of the striatum, suggesting that prior findings of abnormal connections between individual striatal-cortical node-pairs may only represent the "tip of the iceberg" of corticostriatal circuit alteration in nicotine dependence. Moreover, we find that dorsolateral and ventromedial striatum display distinct types of connectivity profile misconfiguration. Whereas dorsolateral striatum almost exclusively displays abnormal rank order arrangement that is present in both the nicotine sated and acutely abstinent states - indicative of a "trait" misconfiguration - ventromedial striatum almost exclusively displays abnormal aggregate divergence that only manifests during acute abstinence - indicative of a "state" misconfiguration. Further, we identify a unique striatal site in the right caudal ventral putamen that displays multiple forms of connectivity profile misconfiguration, where connections with cognitive processing cortical areas overtake those with motor/premotor control cortical areas as the strongest in the connectivity profile, and acute abstinence significantly strengthens this abnormal arrangement. Moreover, the interactive magnitude of these misconfigurations during acute abstinence is significantly linked to dependence severity. Collectively, the present findings underscore the need for increased examination of connectivity profile misconfigurations as a mechanism of SUD etiology and as a potential guide for identifying therapeutic intervention targets.

neuroscience↗

bioRxiv2021

Connectivity profile laterality in corticostriatal functional circuitry: a fingerprinting approach

An abnormal magnitude of hemispheric difference (i.e. laterality) in corticostriatal circuits is a shared feature of numerous neurodevelopmental and psychiatric disorders. Detailed quantitation and regional localization of corticostriatal laterality in normative samples stands to further the understanding of hemispheric differences in healthy and disease states. Here, we used a fingerprinting approach to quantify "functional connectivity profile laterality" - the overall magnitude by which a voxels profile of connectivity with homotopic regions of the ipsilateral and contralateral cortex differs - in the striatum. Laterality magnitude heatmaps revealed "laterality hotspots" - constituting outliers in the voxel-wise distribution -in the right ventrolateral putamen and left central caudate. Findings were replicated in an independent sample, with significant (p<0.05) spatial overlap observed between the location of the laterality hotspots across samples, as measured via Dice coefficients. At both hotspots, a primary driver of overall laterality was the difference in striatal connectivity strength with the right and left pars opercularis of the inferior frontal gyrus. Right and left striatum laterality magnitude maps were found to significantly differ (p<0.05) at the hotspot locations. Moreover, using subjects left, but not right, striatum laterality magnitude maps, a support vector machine trained on a discovery sample (n=77) and tested on a replication sample (n=77) significantly predicted (r=0.25, p=0.028) subject performance on a language task, known for its lateralized nature. Laterality magnitude maps remained consistent across different cortical atlas parcellations and did not differ significantly between right-handed and left-handed individuals. In sum, meaningful variation in functional connectivity profile laterality - both spatially within the striatum and across subjects - is evident in corticostriatal circuits. Findings provide a basis to examine corticostriatal connectivity profile laterality in psychiatric illness.

neuroscience↗

bioRxiv2020

Corticostriatal Projections of Macaque Area 44

Ventrolateral frontal area 44 is implicated in inhibitory motor functions and facilitating prefrontal control over vocalization. Yet, the corticostriatal circuitry that may contribute to area 44 functions is not clear, as prior investigation of area 44 corticostriatal projections is limited. Here, we used anterograde and retrograde tracing in macaques to map the innervation zone of area 44 corticostriatal projections, quantify their strengths, and evaluate their convergence with corticostriatal projections from non-motor and motor-related frontal regions. First, terminal fields from a rostral area 44 injection site were found primarily in the central caudate nucleus, whereas those from a caudal area 44 injection site were found primarily in the ventrolateral putamen. Second, amongst sampled striatal retrograde injection sites, area 44 input as a percentage of total frontal cortical input was highest in the ventral putamen at the level of the anterior commissure. Third, area 44 projections converged with both orofacial premotor area 6VR and other motor related projections (in the putamen), and with non-motor prefrontal projections (in the caudate nucleus). These findings support the role of area 44 as an interface between motor and non-motor functional domains, possibly facilitated by rostral and caudal area 44 subregions with distinct corticostriatal connectivity profiles.

neuroscience↗