Multimodal characterization of the human nucleus accumbens

Cartmell, Samuel; Tian, Qiyuan; Thio, Brandon J.; Leuze, Christoph; Li, Ye; Williams, Nolan; Yang, Grant; Ben-Dor, Gabriel A.; Deisseroth, Karl; Grill, Warren M.; McNab, Jennifer A.; Halpern, Casey H.

doi:10.1016/j.neuroimage.2019.05.019

Cited by 38 publications

(34 citation statements)

References 78 publications

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“…Therefore, the volume atrophy of the globus pallidus and accumbens could also be related to this. In fact, the human nucleus accumbens is an important structure in maintaining normal cognition, motivation, and emotional processes and is involved in some neuropsychiatric disorders (Cartmell et al, 2019 ). There was also a negative correlation between cognitive function and accumbens volume (Mavridis et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Volumetric and Diffusion Abnormalities in Subcortical Nuclei of Older Adults With Cognitive Frailty

Wan

Xia

Lin

et al. 2020

Front. Aging Neurosci.

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Background: Cognitive frailty (CF) is defined as the simultaneous presence of physical frailty and cognitive impairment among older adults without dementia. Previous studies have revealed that neuropathological changes may contribute to the degeneration of subcortical nuclei in the process of cognitive impairment. However, it is unclear in CF. The aim of this study is to investigate the changes in subcortical nuclei in older adults with CF and their relationship with cognitive decline and physical frailty. Methods: A total of 26 older adults with CF and 26 matched healthy subjects were enrolled. Cognitive function and physical frailty were assessed with the Montreal Cognitive Assessment (MoCA) scale (Fuzhou version) and the Chinese version of the Edmonton Frailty Scale (EFS). Volumetric and diffusion tensor imaging (DTI) parameters of subcortical nuclei were measured with structural and DTI brain magnetic resonance imaging (MRI) and compared between groups. Partial correlation analysis was conducted between subcortical nuclei volumes, MoCA scores, and physical frailty indexes. Results: Significant volume reductions were found in five subcortical nuclei, including the bilateral thalami, left caudate, right pallidum, and accumbens area, in older adults with CF (P < 0.05), and the bilateral thalami was most obvious. Decreased fractional anisotropy and relative anisotropy values were observed only in the left thalamus in the CF group (P < 0.05). No group differences were found in apparent diffusion coefficient (ADC) values. The MoCA scores were positively correlated with the volumes of the bilateral thalami, right pallidum, and accumbens area (P < 0.05). Negative correlations were found between the physical frailty index and the volumes of the bilateral thalami, caudate, pallidum, and right accumbens area (P < 0.05). Conclusion: Microstructural changes occur in the subcortical nuclei of older adults with CF, and these changes are correlated with cognitive decline and physical frailty. Therefore, microstructural atrophy of the subcortical nuclei may be involved in the pathological progression of CF.

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Section: Discussionmentioning

confidence: 99%

Volumetric and Diffusion Abnormalities in Subcortical Nuclei of Older Adults With Cognitive Frailty

Wan

Xia

Lin

et al. 2020

Front. Aging Neurosci.

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“…Therefore, the ability to reconstruct a whole brain distribution of a given microscopic biomarker from a set of smaller samples is crucial to build multimodal, multi-scale maps of the human brain. We highlighted in the previous section how previous studies have focused either on major portions of the brain using a large-scale microtome 4,5,51,52 or on specific ROIs using a standard microtome 10,13,[28][29][30][31][32][33][34][35] . There is currently no clear approach to target a large part of the brain (e.g.…”

Section: Contributionmentioning

confidence: 99%

“…The sampling strategy for mounting and staining sections for each tissue block was tailored to the presence of structures of interest for post-mortem neuropathology. In line with previous studies 10, [30][31][32][33][34][35] , a more dense sampling scheme was used for blocks that included subcortical structures in the forebrain, medial structures of the cerebellum and brainstem structures. Specifically, for such blocks, we mount on glass slides and stain two consecutive sections every 10 sections (i.e., every 250 μm) with two routine histological stains: hematoxylin and eosin (H&E) and Luxol Fast Blue (LFB).…”

Section: Staining and Digitizationmentioning

confidence: 99%

“…Recent studies have proposed ROI-based approaches to better understand the microscopic substrate of pathologies such as amyotrophic lateral sclerosis 28 , epilepsy 13 and Alzheimer’s disease 29 . The main targets mostly include subcortical structures, including thalamus 30 , 31 , hippocampus 32 , 33 , nucleus accumbens 34 , and pedunculopontine nucleus 35 , among others 10 . In addition to the practical advantage of dealing with well-defined structures, the focus on the subcortex is due mainly to its implications in neurological diseases and psychiatric disorders.…”

Section: Introductionmentioning

confidence: 99%

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A multimodal computational pipeline for 3D histology of the human brain

Mancini

Casamitjana

Peter

et al. 2020

Sci Rep

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Ex vivo imaging enables analysis of the human brain at a level of detail that is not possible in vivo with MRI. In particular, histology can be used to study brain tissue at the microscopic level, using a wide array of different stains that highlight different microanatomical features. Complementing MRI with histology has important applications in ex vivo atlas building and in modeling the link between microstructure and macroscopic MR signal. However, histology requires sectioning tissue, hence distorting its 3D structure, particularly in larger human samples. Here, we present an open-source computational pipeline to produce 3D consistent histology reconstructions of the human brain. The pipeline relies on a volumetric MRI scan that serves as undistorted reference, and on an intermediate imaging modality (blockface photography) that bridges the gap between MRI and histology. We present results on 3D histology reconstruction of whole human hemispheres from two donors. Motivation. One of the major challenges in the quest to understand the human brain as a complex system is characterizing its multiscale organization. From a macroscopic anatomical perspective, the brain is subdivided into distinct structures and presents well-defined landmarks, for instance its gyri and sulci. At a much finer scale, neurons are interconnected to form complex circuits. These circuits give rise to features at coarser scales, e.g., the laminar organization of the cortex 1. Although these distinct levels of organization may seem separate, they are, in fact, deeply linked and mutually influential. One clear example is given by Alzheimer's disease, which can be described by the interactions between proteinopathy at the microscale and distributed, network-level disruptions at the macroscale 2. Understanding these multi-scale mechanisms requires a multi-scale map of the brain. However, the current concept of brain mapping is closely linked to the specific tool used to construct cartographic representations, and thus to the spatial scale of the tool. As a result, the different organizational principles can only be observed in a scale-specific fashion with dedicated tools 3. Multi-scale imaging of the human brain is therefore necessarily multimodal, as different modalities are needed to study different scales. While a macroscopic anatomical picture of the brain is easily acquired non invasively or ex vivo with magnetic resonance imaging (MRI), finer characterization requires histological procedures and microscopy. Histology and MRI are highly complementary modalities: histology produces excellent contrast at the microscopic scale using dedicated stains that target different microanatomical or cytoarchitectural features, but it is a 2D modality that also inevitably introduces distortions in the tissue during blocking and sectioning. MRI does not yield microscopic resolution, but produces undistorted 3D volumes. Therefore, the combination of these two modalities offers a solution to the problem of imaging the human brain at high resolution in 3D.

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“…Situated at the interface between cortical and subcortical structures, the NAc integrates limbic, affective, and cognitive inputs in order to drive reward-guided behaviors. It is a crucial structure in reward valuation and action selection under conditions of uncertainty [38,71,72,73,74]. In this section, we provide an overview of the single-neuron and LFP studies investigating the neural processing of reward-guided behaviors in the human NAc, as well as a critical perspective on these electrophysiological contributions to our understanding of NAc reward-related signals.…”

Section: Reward Driven Behavior: Nacmentioning

confidence: 99%

Neural Circuit and Clinical Insights from Intraoperative Recordings During Deep Brain Stimulation Surgery

et al. 2019

Self Cite

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Observations using invasive neural recordings from patient populations undergoing neurosurgical interventions have led to critical breakthroughs in our understanding of human neural circuit function and malfunction. The opportunity to interact with patients during neurophysiological mapping allowed for early insights in functional localization to improve surgical outcomes, but has since expanded into exploring fundamental aspects of human cognition including reward processing, language, the storage and retrieval of memory, decision-making, as well as sensory and motor processing. The increasing use of chronic neuromodulation, via deep brain stimulation, for a spectrum of neurological and psychiatric conditions has in tandem led to increased opportunity for linking theories of cognitive processing and neural circuit function. Our purpose here is to motivate the neuroscience and neurosurgical community to capitalize on the opportunities that this next decade will bring. To this end, we will highlight recent studies that have successfully leveraged invasive recordings during deep brain stimulation surgery to advance our understanding of human cognition with an emphasis on reward processing, improving clinical outcomes, and informing advances in neuromodulatory interventions.

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Multimodal characterization of the human nucleus accumbens

Cited by 38 publications

References 78 publications

Volumetric and Diffusion Abnormalities in Subcortical Nuclei of Older Adults With Cognitive Frailty

Volumetric and Diffusion Abnormalities in Subcortical Nuclei of Older Adults With Cognitive Frailty

A multimodal computational pipeline for 3D histology of the human brain

Neural Circuit and Clinical Insights from Intraoperative Recordings During Deep Brain Stimulation Surgery

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