Abstract
Multiple studies have identified segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. It has been suggested that in PD, preferential loss of dopamine in the posterior putamen may cause a major deficit in habitual control (mediated by the sensorimotor cortical-striatal loop), and the patients may therefore be forced into a progressive reliance on the goal-directed behavior (regulated by the associative cortical-striatal loop). Functional evidence supporting this point is scarce at present. This study aims to verify the functional connectivity changes within the sensorimotor, associative, and limbic cortical-striatal loops in PD. Resting-state fMRI of 70 PD patients and 30 controls were collected. Bilateral tripartite functional territories of basal ganglia and their associated cortical structures were chosen as regions of interest, including ventral striatum and ventromedial prefrontal cortex for limbic loop; dorsomedial striatum and dorsolateral prefrontal cortex for associative loop; dorsolateral striatum and sensorimotor cortex for sensorimotor loop. Pearson's correlation coefficients for each seed pair were calculated to obtain the functional connectivity. The relationships between functional connectivity and disease severity were further investigated. Functional connectivity between dorsolateral striatum and sensorimotor cortex is decreased in PD patients, and negatively correlated with disease duration; whereas functional connectivity between dorsomedial striatum and dorsolateral prefrontal cortex is also decreased but postitively correlated with disease duration. The functional connectivity within the sensorimotor loop is pathologically decreased in PD, while the altered connectivity within the associative loop may indicate a failed attempt to compensate for the loss of connectivity within the sensorimotor loop.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disease [1]
Studies in rodents indicated that the region of dorsomedial striatum and medial prefrontal were involved in the goal-directed actions [23, 24], whereas the region of dorsolateral striatum and premotor cortex were responsible for habitual control behavior [5, 6]
We investigated the pattern of functional connectivity between the functionally segregated territories of basal ganglia and their associated functional cerebral cortex among the limbic, associative, and sensorimotor loops in PD patients, that are suggested to be associated with goal-directed and habitual control in PD patients
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disease [1]. Since the original “direct vs. indirect pathway” model of basal ganglia was introduced, it has spawned many valuable experimental studies and clinical developments in PD [2, 3]. Multiple human and animal studies have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions [4,5,6,7]. The limbic loop connecting the ventral striatum with the ventromedial prefrontal cortex (vmPFC) has been implicated in motivational and emotional processing; whereas the associative and sensorimotor networks regulate different forms of behaviors in instrumental behavior processing. The associative network connecting the dorsomedial striatum with dorsolateral prefrontal cortex (dlPFC) mainly contributes to the goal-directed behaviors [7, 9], while the sensorimotor network projecting from the dorsolateral striatum to the sensorimotor cortex is mainly responsible for the habitual control behaviors in instrumental learning [7, 9]
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