Joint amplitude and connectivity compensatory mechanisms in Parkinson's disease.
Neuroimaging studies in Parkinson's disease (PD) have previously demonstrated several regions of hypo- and hyper-activation during voluntary movement. How these patterns of amplitude changes at multiple discrete foci relate to changes within functional networks recruited by a given task is unclear. Changes in both amplitude and connectivity have both been individually shown within the striato-thalamo-cortical (STC) loop in PD, as well as other regions, most consistently in the cerebellum and primary motor cortex. We have previously shown overactivation of the cerebellum and motor cortex in PD subjects off medication during a visuo-motor tracking task performed at three frequencies. Here, we show that this change in activation amplitude is also accompanied by significant changes in functional connectivity between regions of interest (ROIs), with enhanced connectivity within the cerebello-thalamo-cortical (CTC) loop as well as increased inter-hemispheric communication between several basal ganglia structures. Although changes in activation amplitude were influenced by the frequency of movement performed in the tracking task, functional connectivity changes were robustly present across all three task frequencies performed, suggesting that functional connectivity analysis in PD may be a more sensitive means of detecting plastic changes which are relatively invariant to the particulars of the experimental task. Additionally, we demonstrate amplitude and connectivity changes in structures that are typically active during the resting state, or "default-mode," in PD. Unlike in STC/CTC loops, where the direction of change was the same for amplitude and connectivity, default-mode regions showed increased amplitude but decreased connectivity. Our results further support that the CTC is recruited in PD to compensate for dysfunctional basal ganglia circuits, and that this recruitment involves both amplitude and connectivity changes. The differing relationship between amplitude and connectivity changes within individual loops highlights the importance of jointly examining them in order to fully elucidate functional changes in Parkinson's disease.
Palmer SJ
，Li J
，Wang ZJ
，McKeown MJ
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Effective connectivity of brain networks during self-initiated movement in Parkinson's disease.
Patients with Parkinson's disease (PD) have difficulty in performing self-initiated movements. The neural mechanism of this deficiency remains unclear. In the current study, we used functional MRI (fMRI) and psychophysiological interaction (PPI) methods to investigate the changes in effective connectivity of the brain networks during performance of self-initiated movement in PD patients. Effective connectivity is defined as the influence one neuronal system exerts over another. fMRIs were acquired in 18 PD patients and in 18 age- and sex-matched healthy controls, when performing a self-initiated right hand tapping task. We chose the left primary motor cortex (M1), rostral supplementary motor area (pre-SMA), left premotor cortex (PMC), left putamen, and right cerebellum as index areas for PPI analysis. During the performance of self-initiated movement, connectivity between the putamen and M1, PMC, SMA, and cerebellum was decreased in PD patients compared to controls. In contrast, connections between the M1, pre-SMA, PMC, parietal cortex, and cerebellum were increased in PD patients compared to controls. In addition, the M1, pre-SMA, PMC, and cerebellum also had less connectivity with the dorsal lateral prefrontal cortex in PD. In PD patients, the effective connectivity between the putamen and M1, PMC, SMA, and cerebellum negatively correlated with the Unified Parkinson's Disease Rating Scale (UPDRS) motor scores; whereas the connectivity between the M1, pre-SMA, PMC, and cerebellum positively correlated with the UPDRS motor scores. Our findings demonstrate that the pattern of interactions of brain networks is disrupted in PD during performance of self-initiated movements. The striatum-cortical and striatum-cerebellar connections are weakened. In contrast, the connections between cortico-cerebellar motor regions are strengthened and may compensate for basal ganglia dysfunction. These altered interregional connections are more deviant when the disorder is more severe, and, therefore, our results give further insight into the explanation for the difficulty in performing self-initiated movements in PD.
Wu T
，Wang L
，Hallett M
，Chen Y
，Li K
，Chan P
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ResearchGate
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钛学术
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