Movement-Related Changes in Local and Long-Range Synchronization in Parkinson's Disease Revealed by Simultaneous Magnetoencephalography and Intracranial Recordings

Abstract

Functional neurosurgery has afforded the opportunity to assess interactions between populations of neurons in the human cerebral cortex and basal ganglia in patients with Parkinson's disease (PD). Interactions occur over a wide range of frequencies, and the functional significance of those Ͼ30 Hz is particularly unclear. Do they improve movement, and, if so, in what way? We acquired simultaneously magnetoencephalography and direct recordings from the subthalamic nucleus (STN) in 17 PD patients. We examined the effect of synchronous and sequential finger movements and of the dopamine prodrug levodopa on induced power in the contralateral primary motor cortex (M1) and STN and on the coherence between the two structures. We observed discrete peaks in M1 and STN power at 60 -90 Hz and at 300 -400 Hz. All these power peaks increased with movement and levodopa treatment. Only STN activity at 60 -90 Hz was coherent with activity in M1. Directionality analysis showed that STN gamma activity at 60 -90 Hz tended to drive gamma activity in M1. The effects of levodopa on both local and distant synchronization at 60 -90 Hz correlated with the degree of improvement in bradykinesiarigidity as did local STN activity at 300 -400 Hz. Despite this, there were no effects of movement type, nor interactions between movement type and levodopa in the STN, nor in the coherence between STN and M1. We conclude that synchronization at 60 -90 Hz in the basal ganglia cortical network is prokinetic but likely through a modulatory effect rather than any involvement in explicit motor processing.

Cognitive Factors Modulate Activity within the Human Subthalamic Nucleus during Voluntary Movement in Parkinson's Disease

“…Recent models of motor control recognize the need for a general mechanism to regulate the effort expended during a task according to task demands and cost-benefit contingencies (Todorov and Jordan, 2002;Guigon et al, 2007). This function has been associated with the basal ganglia, where the function is considered to rely on dopaminergic input (Mazzoni et al, 2007;Niv and Rivlin-Etzion, 2007), in line with the interaction between dopaminergic therapy and task complexity in the current study. Although the LFP changes we describe by no means prove a role for the STN in the coding of effort, they serve to demonstrate that changes in oscillatory dynamics in the STN cannot simply be accounted for in terms of the selection and parameterization of motor variables, such as force; in our paradigm the movements made did not differ, but the resources needed to achieve them did.…”

“…Previous work has demonstrated that gamma activity in the basal ganglia correlates with force or velocity, but has failed to dissociate these from effort (Anzak et al, 2012;Brücke et al, 2012;Tan et al, 2013a). One study explicitly contrasted simple, synchronous, and complex sequential finger movements and found no change in perimovement gamma activity in the STN (Litvak et al, 2012), although it could be argued that the demands of the complex task were less challenging than in the current paradigm.…”

“…This was performed for each subject across the different conditions (Յ8 in total, as documented in Table 2, and drawn from Յ4 blocks of trials on and Յ4 blocks off medication). The benefits of robust averaging for increasing the signal-to-noise ratio in data with low trial numbers have been previously demonstrated (Litvak et al, 2012;Oswal et al, 2013). In essence, robust averaging is a special case of the robust general linear model (Wager et al, 2005).…”

“…Crucially, the effects of task complexity in increasing perimovement beta band desynchronization and gamma synchronization are potentiated by levodopa, evidenced by the bidirectional interaction between medication and task complexity. Thus, the ability to perform effortful actions may be impaired in hypodopaminergic states, such as untreated Parkinson's disease (Mazzoni et al, 2007).…”

“…This would place perimovement spectral changes in the STN at the executive end of processing and disassociate them from any link to the representation of action values thought to be important elsewhere in the basal ganglia (Samejima et al, 2005). Alternatively, they may relate to higher-order phenomena, such as the cognitive or motor effort to be exerted in an action that is then organized elsewhere (Mazzoni et al, 2007;Niv and Rivlin-Etzion, 2007;Salamone et al, 2009;Turner and Desmurget, 2010). Again, the extent to which perimovement spectral changes in the STN are modulated by contextual factors, such as potential reward, and by task complexity would seem to be critical information in characterizing the functional associations of these oscillations.…”