Elevated synchrony in Parkinson disease detected with electroencephalography

Abstract

Objective Parkinson's disease (PD) can be difficult to diagnose and treat. Development of a biomarker for PD would reduce these challenges by providing an objective measure of disease. Emerging theories suggest PD is characterized by excessive synchronization in the beta frequency band (~20 Hz) throughout basal ganglia-thalamo-cortical loops. Recently we showed with invasive electrocorticography (ECoG) that one robust measure of this synchronization is the coupling of beta phase to broadband gamma amplitude (i.e. phase amplitude coupling, PAC). Other recent work suggests that high frequency activity is detectable at the scalp using electroencephalography (EEG). Motivated by these findings, we tested whether beta-gamma PAC over sensorimotor cortex, recorded non-invasively with EEG, differs between PD patients Off and On medications, and healthy Control subjects. Methods Resting EEG was compared from 15 PD patients and 16 healthy control subjects. PD patients were tested On and Off medications on different days, in a counterbalanced order. For each dataset we calculated PAC and compared results across groups. Results PAC was elevated in the patients Off medications compared to On medications (p=0.008) and for patients Off medications compared to Controls (p=0.009). Interpretation Elevated PAC is detectable using scalp EEG in PD patients Off medications compared to On, and compared to healthy Controls. This suggests that EEG PAC may provide a non-invasive biomarker of the Parkinsonian state. This biomarker could be used as a control signal for closed-loop control of deep brain stimulation devices, for adjustment of dopaminergic treatment, and also has the potential to aid in diagnosis.

Pallidal low β-low γ phase-amplitude coupling inversely correlates with Parkinson disease symptoms

“…Recent reports in the literature suggest that coupling and not merely the power of β oscillations may be an important underpinning of PD pathophysiology (de Hemptinne et al, 2015; Swann et al, 2015; Wang et al, 2016). So far, the literature has been largely focused on analysis of STN and motor cortical LFPs.…”

“…While β oscillations have dominated the discussion of the pathophysiology of PD, recent studies suggest that the power of these oscillations may not be as important as their coupling with other neural activity both within or across nodes of the motor BGTC circuit, whether in the form of phase amplitude coupling (PAC), coherence, or phase synchronization (de Hemptinne et al, 2013, 2015; Oswal et al, 2016; Ozkurt et al, 2011; Swann et al, 2015; Weiss et al, 2015; van Wijk et al, 2016; Yang et al, 2014). β-broadband γ PAC in the motor cortex (M1) is exaggerated in patients with PD compared to patients with epilepsy or healthy controls and these coupling patterns change with pathological state (de Hemptinne et al, 2013; Swann et al, 2015).…”

“…β-broadband γ PAC in the motor cortex (M1) is exaggerated in patients with PD compared to patients with epilepsy or healthy controls and these coupling patterns change with pathological state (de Hemptinne et al, 2013; Swann et al, 2015). Amplified PAC between β band and high frequency oscillations (HFO: 200–500 Hz) is also observed at the dorsal border of STN, closest to the contact used for deep brain stimulation (DBS) (Yang et al, 2014) and is significantly reduced with dopaminergic medication (Lopez-Azcarate et al, 2010; van Wijk et al, 2016).…”

“…Amplified PAC between β band and high frequency oscillations (HFO: 200–500 Hz) is also observed at the dorsal border of STN, closest to the contact used for deep brain stimulation (DBS) (Yang et al, 2014) and is significantly reduced with dopaminergic medication (Lopez-Azcarate et al, 2010; van Wijk et al, 2016). Therapeutic DBS reduces and nearly eliminates the coupling within M1 motor cortex (de Hemptinne et al, 2015) as does dopaminergic therapy (Swann et al, 2015). Moreover, a recent report shows that STN DBS not only modulates local STN β oscillations, but also suppresses coherence between motor cortices and STN (Oswal et al, 2016).…”

Therapeutic applications of BCI technologies

“…Researchers in the Starr lab at UCSF have promising preliminary results demonstrating acquired volitional control of beta power from the DBS electrode in the STN in a few participants with DBS stimulators that allow for chronic signal acquisition and feedback (Activa PC+S, Medtronic, USA). It might also be possible to use PD-related brain signal features recorded non-invasively from the scalp [66]. …”