Basal ganglia functional connectivity network analysis does not support the ‘noisy signal’ hypothesis of Parkinson’s disease

The ‘noisy signal’ hypothesis of basal ganglia dysfunction in Parkinson’s disease (PD) suggests that major motor symptoms of the disorder are caused by the development of abnormal basal ganglia activity patterns resulting in the propagation of ‘noisy’ signals to target systems. While such abnormal activity patterns might be useful biomarkers for the development of therapeutic interventions, correlation between specific changes in activity and PD symptoms has been inconsistently demonstrated, and raises questions concerning the accuracy of the hypothesis. Here, we tested this hypothesis by considering three nodes of the basal ganglia network, the subthalamus, globus pallidus interna, and cortex during self-paced and cued movements in patients with PD. Interactions between these regions were analyzed using measures that assess both linear and non-linear relationships. Marked changes in the network are observed with dopamine state. Specifically, we detected functional disconnection of the basal ganglia from the cortex and higher network variability in untreated PD, but various patterns of directed functional connectivity with lower network variability in treated PD. When we examine the system output, significant correlation is observed between variability in the cortico-basal ganglia network and muscle activity variability but only in the treated state. Rather than supporting a role of the basal ganglia in the transmission of noisy signals in patients with PD, these findings suggest that cortico-basal ganglia network interactions by fault or design, in the treated Parkinsonian state, are actually associated with improved cortical network output variability.