Dataset Information

Multimodal characterization of the human nucleus accumbens.

ABSTRACT: Dysregulation of the nucleus accumbens (NAc) is implicated in numerous neuropsychiatric disorders. Treatments targeting this area directly (e.g. deep brain stimulation) demonstrate variable efficacy, perhaps owing to non-specific targeting of a functionally heterogeneous nucleus. Here we provide support for this notion, first observing disparate behavioral effects in response to direct simulation of different locations within the NAc in a human patient. These observations motivate a segmentation of the NAc into subregions, which we produce from a diffusion-tractography based analysis of 245 young, unrelated healthy subjects. We further explore the mechanism of these stimulation-induced behavioral responses by identifying the most probable subset of axons activated using a patient-specific computational model. We validate our diffusion-based segmentation using evidence from several modalities, including MRI-based measures of function and microstructure, human post-mortem immunohistochemical staining, and cross-species comparison of cortical-NAc projections that are known to be conserved. Finally, we visualize the passage of individual axon bundles through one NAc subregion in a post-mortem human sample using CLARITY 3D histology corroborated by 7T tractography. Collectively, these findings extensively characterize human NAc subregions and provide insight into their structural and functional distinctions with implications for stereotactic treatments targeting this region.

SUBMITTER: Cartmell SC

PROVIDER: S-EPMC7341972 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Multimodal characterization of the human nucleus accumbens.

Cartmell Samuel Cd SC Tian Qiyuan Q Thio Brandon J BJ Leuze Christoph C Ye Li L Williams Nolan R NR Yang Grant G Ben-Dor Gabriel G Deisseroth Karl K Grill Warren M WM McNab Jennifer A JA Halpern Casey H CH

NeuroImage 20190508

Dysregulation of the nucleus accumbens (NAc) is implicated in numerous neuropsychiatric disorders. Treatments targeting this area directly (e.g. deep brain stimulation) demonstrate variable efficacy, perhaps owing to non-specific targeting of a functionally heterogeneous nucleus. Here we provide support for this notion, first observing disparate behavioral effects in response to direct simulation of different locations within the NAc in a human patient. These observations motivate a segmentation ...[more]

PMID: 31077843

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Project description:The nucleus accumbens (NAc) is the ventral part of the striatum and the interface between cognition, emotion, and action. It is composed of three major subnuclei: i.e., NAc core (NAcC), lateral shell (NAcLS), and medial shell (NAcMS), which exhibit functional heterogeneity. Thus, determining the synaptic inputs of the subregions of the NAc is important for understanding the circuit mechanisms involved in regulating different functions. Here, we simultaneously labeled subregions of the NAc with cholera toxin subunit B conjugated with multicolor Alexa Fluor, then imaged serial sections of the whole brain with a fully automated slide scanning system. Using the interactive WholeBrain framework, we characterized brain-wide inputs to the NAcC subdomains, including the rostral, caudal, dorsal, and ventral subdomains (i.e., rNAcC, cNAcC, dNAcC, and vNAcC, respectively) and the NAc subnuclei. We found diverse brain regions, distributed from the cerebrum to brain stem, projecting to the NAc. Of the 57 brain regions projecting to the NAcC, the anterior olfactory nucleus (AON) exhibited the greatest inputs. The input neurons of rNAcC and cNAcC are two distinct populations but share similar distribution over the same upstream brain regions, whereas the input neurons of dNAcC and vNAcC exhibit slightly different distributions over the same upstream regions. Of the 55 brain regions projecting to the NAcLS, the piriform area contributed most of the inputs. Of the 72 brain regions projecting to the NAcMS, the lateral septal nucleus contributed most of the inputs. The input neurons of NAcC and NAcLS share similar distributions, whereas the NAcMS exhibited brain-wide distinct distribution. Thus, the NAcC subdomains appeared to share the same upstream brain regions, although with distinct input neuron populations and slight differences in the input proportions, whereas the NAcMS subnuclei received distinct inputs from multiple upstream brain regions. These results lay an anatomical foundation for understanding the different functions of NAcC subdomains and NAc subnuclei.

Dataset Information

Multimodal characterization of the human nucleus accumbens.

Publications

Multimodal characterization of the human nucleus accumbens.

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