Functional Connectivity of Human Striatum: A Resting State fMRI Study

Abstract

Classically regarded as motor structures, the basal ganglia subserve a wide range of functions, including motor, cognitive, motivational, and emotional processes. Consistent with this broad-reaching involvement in brain function, basal ganglia dysfunction has been implicated in numerous neurological and psychiatric disorders. Despite recent advances in human neuroimaging, models of basal ganglia circuitry continue to rely primarily upon inference from animal studies. Here, we provide a comprehensive functional connectivity analysis of basal ganglia circuitry in humans through a functional magnetic resonance imaging examination during rest. Voxelwise regression analyses substantiated the hypothesized motor, cognitive, and affective divisions among striatal subregions, and provided in vivo evidence of a functional organization consistent with parallel and integrative loop models described in animals. Our findings also revealed subtler distinctions within striatal subregions not previously appreciated by task-based imaging approaches. For instance, the inferior ventral striatum is functionally connected with medial portions of orbitofrontal cortex, whereas a more superior ventral striatal seed is associated with medial and lateral portions. The ability to map multiple distinct striatal circuits in a single study in humans, as opposed to relying on meta-analyses of multiple studies, is a principal strength of resting state functional magnetic resonance imaging. This approach holds promise for studying basal ganglia dysfunction in clinical disorders.

Striatal subdivisions that coherently interact with multiple cerebrocortical networks

“…Supporting Information Figure S4a shows group average maps of the SSCs that were most strongly connected with the PCG, MFG, OFG, or inferior parietal lobule, based on the atlas by Desikan et al (2006). Consistent with previous studies (Barnes et al, 2010; Choi et al, 2012; Di Martino et al, 2008; Draganski et al, 2008; Garcia‐Garcia et al, 2018; Janssen et al, 2015; Jaspers et al, 2017; Jung et al, 2014), the middle part of the putamen was most strongly connected with the PCG, the caudate nucleus was most strongly connected with the MFG, and the caudate nucleus extending to ventral striatum was most strongly connected with the OFG.…”

“…Previous studies of striatal functional architecture have revealed a well‐organized relationship for cerebrocortical‐striatal connectivity (Barnes et al, 2010; Choi et al, 2012; Di Martino et al, 2008; Draganski et al, 2008; Garcia‐Garcia et al, 2018; Janssen et al, 2015; Jaspers et al, 2017; Jung et al, 2014). We confirmed, as a positive control, that the larger‐scale observations could be replicated using the present data set.…”

The acute brain response to levodopa heralds dyskinesias in Parkinson disease

“…Given our a priori hypothesis that PD22 and dyskinesias23 would be associated with abnormal activity of the putamen, we defined the bilateral dorsocaudal putamen as a region of interest (ROI) and applied small volume correction (SVC) using a sphere 10mm in radius on the Montreal Neurologic Institute coordinates ±28, 2, 2 (x, y, z) 24…”

Dysfunctional Striatal Systems in Treatment-Resistant Schizophrenia

“…Striato-cortico-striatal loops predominantly involving prefrontal cortex (PFC) projections have been delineated in nonhuman primates (Alexander et al, 1986), and confirmed in humans with diffusion tensor imaging (Leh et al, 2007;Lehericy et al, 2004) and resting-state functional magnetic resonance imaging (rs-fMRI) (Di Martino et al, 2008). These loops include: a ventral circuit anchored in the inferior limbic subdivision of the striatum and comprising connections with orbitofrontal cortex (OFC), ventromedial PFC, medial thalamus, and limbic regions that is fundamental to associative learning and reward-mediated decision making (Knutson and Cooper, 2005); and a dorsal circuit, including the associative subdivision of the striatum, dorsolateral PFC and mediodorsal and ventroanterior thalamus that maintains information relating to reward outcomes (O' Doherty et al, 2004).…”

“…Seeds were defined in both hemispheres as 3.5 mm radius spheres at the following stereotaxic coordinates: dorsal caudate (DC; x = ± 13, y = 15, z = 9); ventral striatum/nucleus accumbens (VS; x = ± 9, y = 9, z = − 8); dorsal-caudal putamen (dcP; x = ± 28, y = 1, z = 3); and ventral-rostral putamen (vrP; x = ± 20, y = 12, z = − 3) (Dandash et al, 2014). To complement the original investigation of Di Martino et al (2008), effects were additionally modeled in relation to their remaining two seeds, but as per previous work (Dandash et al, 2014), experimental focus was placed upon the former four seeds. Component-based correction (CompCor) of temporal confounds relating to head movement and physiological noise was performed using the CONN toolbox (v.14) (Whitfield-Gabrieli and Nieto-Castanon, 2012).…”