Altered dynamic functional network connectivity in levodopa‐induced dyskinesia of Parkinson's disease

Abstract

BackgroundTraditional measures of static functional connectivity may not completely re ect the dynamic neural activity of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). This study was aimed to investigate the dynamic changes of large-scale functional network connectivity in the temporal domain in PD patients with and without LID. MethodsUsing dynamic functional network connectivity (dFNC) analysis, we evaluated 41 PD patients with LID (LID group) and 34 PD patients without LID (No-LID group), on and off their levodopa medications. Group spatial independent component analysis, sliding-window approach and k-means clusters were employed. ResultsIn OFF phase, we found no differences between PD subgroups in temporal properties. In ON phase, compared than No-LID group, LID group occurred more frequently and dwelled longer in strongly connected State 1, characterized by strong connections between visual network (VIS) and other networks.When switching from OFF to ON phase, LID group occurred more frequently and dwelled longer in State 2 and occurred less frequently and dwelled shorter in State 3 (both states were strongly connected), while No-LID group occurred more frequently and dwelled longer in State 5 (weakly connected). Additionally, correlation analysis further demonstrated that the severity of dyskinesia was only associated with frequency of occurrence and dwell time in State 2, dominated by inferior frontal cortex in cognitive executive network (CEN), strongly connecting with sensorimotor network (SMN) and VIS. ConclusionsUsing dFNC analysis, we found that compared to those without LID, PD patients with LID may be involved in the superexcitation of VIS, as well as interconnections between CEN and SMN, VIS, having impact on inhibition of motor circuits. The dFNC analysis might provide new insights into the neural mechanisms of LID in PD.

Cortico–subcortical spatiotemporal dynamics in Parkinson’s disease can be modulated by transcranial alternating current stimulation

“…To investigate the individualized effects of group-average target tACS in patients with PD, our study used electric field simulation and found that the same tACS electrode placement (FC1 and FC2) can stimulate different functional networks across individuals, indicating the necessity of individual targets in noninvasive neuromodulation. This finding is similar to a previous TMS study, which reveals variabilities in individual functional brain network engagement using the same TMS coil placement [34]. In addition, theta frequency was used in this study due to its involvement in high-order cognitive functions [55] and potential efficacy in PD [23].…”

“…Therefore, this study first investigated whether the same electrode arrangement (FC1 and FC2) activated the same individual brain networks. Similar to a previous TMS study, we set the minimum activation threshold [34]. For each participant, 80% of the maximum simulated electric field was set as the minimum activation threshold and the vertices with an electric field in the range of 80%–100% of the maximum value were defined as activation zones.…”

“…Previous studies have shown that individual functional mapping can better capture brain-behavior associations than group-level functional mapping [31], characterize individualized brain dynamics in healthy aging [32], and provide candidate neuroimaging markers for clinical psychiatric symptoms across different mental disorders [33]. Although individual mapping has been emphasized in transcranial magnetic stimulation (TMS) studies [34], individual differences in the same tACS montages are unclear. In addition, cortico–subcortical coordination is not limited to transitions between different dynamic functional connectivity states but occurs continuously because cortical and subcortical regions exhibit general simultaneity of dynamical changes.…”

“…In addition, cortico-subcortical coordination is not limited to transitions between different dynamic functional connectivity states but occurs continuously because cortical and subcortical regions exhibit general simultaneity of dynamical changes. Abnormal dynamic functional connectivity states have been characterized in PD using sliding window analysis [29,35]. Their studies have revealed altered global integration [29] and sensorimotor changes [35] in brain dynamics.…”

“…Abnormal dynamic functional connectivity states have been characterized in PD using sliding window analysis [29,35]. Their studies have revealed altered global integration [29] and sensorimotor changes [35] in brain dynamics. However, the focus in PD has remained primarily on group-level functional brain mapping and sliding window dynamic analysis, with less work focused on the contributions of cortical and subcortical dynamic states at the individual level.…”