Abstract
Parkinson's disease (PD) is characterized by striatal dopamine depletion, especially in the posterior putamen. The dense connectivity profile of the striatum suggests that these local impairments may propagate throughout the whole cortico-striatal network. Here we test the effect of striatal dopamine depletion on cortico-striatal network properties by comparing the functional connectivity profile of the posterior putamen, the anterior putamen, and the caudate nucleus between 41 PD patients and 36 matched controls. We used multiple regression analyses of resting-state functional magnetic resonance imaging data to quantify functional connectivity across different networks. Each region had a distinct connectivity profile that was similarly expressed in patients and controls: the posterior putamen was uniquely coupled to cortical motor areas, the anterior putamen to the pre-supplementary motor area and anterior cingulate cortex, and the caudate nucleus to the dorsal prefrontal cortex. Differences between groups were specific to the putamen: although PD patients showed decreased coupling between the posterior putamen and the inferior parietal cortex, this region showed increased functional connectivity with the anterior putamen. We conclude that dopamine depletion in PD leads to a remapping of cerebral connectivity that reduces the spatial segregation between different cortico-striatal loops. These alterations of network properties may underlie abnormal sensorimotor integration in PD.
Highlights
Parkinson’s disease (PD) is characterized by a degeneration of dopaminergic cells in the midbrain (Braak et al 2003), which leads to dopamine depletion in the striatum (Brooks and Piccini 2006)
Anterior Putamen The anterior putamen was functionally connected to the preSMA, anterior cingulate cortex (ACC), subthalamic region, and bilateral middle frontal gyrus (BA 9)
The results of this study indicate that PD patients have altered inter-regional couplings within specific cortico-striatal loops, and that these alterations follow the specific spatial pattern of dopamine depletion occurring in this disease
Summary
Parkinson’s disease (PD) is characterized by a degeneration of dopaminergic cells in the midbrain (Braak et al 2003), which leads to dopamine depletion in the striatum (Brooks and Piccini 2006) This neurochemical alteration impairs neuronal processing in the basal ganglia (Rivlin-Etzion et al 2006), which propagates, through the dense cortico-striatal connections (Houk and Wise 1995), to altered activity in other brain regions (van Eimeren and Siebner 2006). Previous neuroimaging studies in PD have described patterns of spatial covariance between different brain regions during performance of a task (Monchi et al 2004), as well as steadystate differences in brain activity during rest (Eckert et al 2007) These patterns of coactivations might suggest the presence of a functional circuit (Postuma and Dagher 2006), but networks are better defined on the basis of the structure of temporal interactions between regions (functional connectivity; He et al 2007).
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