Phase–amplitude coupling changes may underlie DBS success in parkinsonism

By Eleanor McDermid, Senior medwireNews Reporter

Deep-brain stimulation (DBS) of the subthalamic nucleus (STN) may improve motor symptoms in patients with Parkinson’s disease (PD) by reducing excessive cortical phase–amplitude coupling (PAC), researchers report in Nature Neuroscience.

STN DBS reduced coupling between the phase of beta oscillations (13–30 Hz) and the amplitude of broadband activity (50–200 Hz), say Coralie de Hemptinne (University of California, San Francisco, USA) and study co-authors. It did not consistently alter either parameter, instead reducing the interaction between the two.

The team previously identified exaggerated PAC in the primary motor cortex of PD patients. As reduction of PAC is necessary for movement execution, they believe the increased PAC in PD patients causes akinesia and rigidity during the resting state and movement preparation, and bradykinesia during movement execution.

They say their new findings “underscore the importance of exaggerated PAC in PD, point to a new mechanism for the therapeutic effect of DBS and suggest the incorporation of cortical PAC measures into the design of closed-loop DBS protocols.”

The 23 patients in the study, who were scheduled to undergo DBS implantation, had excessive PAC, which was “strongly reduced” during STN stimulation and increased again when stimulation was turned off. Changes in PAC occurred only in the primary motor cortex, and within 2–4 seconds of stimulation being switched on or off.

Furthermore, patients’ rigidity scores (item 22 of the Unified Parkinson’s disease Rating Scale) significantly decreased during STN stimulation and returned to baseline after it was switched off. Rigidity scores correlated with average PAC, although the changes in these parameters caused by STN stimulation did not significantly correlate, which the researchers attribute to the small changes in rigidity scores (between 0 and 2). Tremor scores did not correlate with PAC.

The researchers measured PAC in 12 of the patients while they performed a movement task. They found that the patients were able to reduce PAC in order to execute the task, with PAC decreasing between the hold phase (patients waiting for their cue), the preparation phase (the cue appears) and the movement phase. However, STN stimulation significantly enhanced the reduction in all phases, and was accompanied by a significant reduction in the time needed to complete the task.

The team had speculated that PAC reduction by STN stimulation would be attributable to decreases in beta oscillations, but found that 13 patients had decreases in beta power during stimulation, while 10 had increases. Instead, PAC reduction was due to decreased interaction between beta oscillations and broadband activity.

This suggests that increased PAC could be a biomarker of parkinsonism, and could be used as a control signal for a closed-loop DBS system that could overcome some of the main limitations of current therapy, they say.

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