Hypersynchrony despite pathologically reduced beta oscillations in patients with Parkinson's disease: a pharmaco-magnetoencephalography study

Abstract

Parkinson's disease (PD) is a progressive debilitating neurodegenerative disorder clinically manifest by motor, posture and gait abnormalities. Human neurophysiological studies recording local field potentials within the subthalamic nucleus and scalp-based electroencephalography have shown pathological beta synchrony throughout the basal ganglia-thalamic-cortical motor network in PD. Notably, suppression of this pathological beta synchrony by dopamine replacement therapy or deep-brain stimulation has been associated with improved motor function. However, due to the invasive nature of these studies, it remains unknown whether this "pathological beta" is actually stronger than that observed in healthy demographically matched controls. We used magnetoencephalography to investigate neuronal synchrony and oscillatory amplitude in the beta range and lower frequencies during the resting state in patients with PD and a matched group of patients without neurological disease. Patients with PD were studied both in the practically defined drug "OFF" state, and after administration of dopamine replacements. We found that beta oscillatory amplitude was reduced bilaterally in the primary motor regions of unmedicated patients with PD compared with controls. Administration of dopaminergic medications significantly increased beta oscillatory activity, thus having a normalizing effect. Interestingly, we also found significantly stronger beta synchrony (i.e., hypersynchrony) between the primary motor regions in unmedicated patients with PD compared with controls, and that medication reduced this coupling which is in agreement with the intraoperative studies. These results are consistent with the known functionality of the basal ganglia-thalamic-cortical motor circuit and the likely consequences of beta hypersynchrony in the subthalamic nucleus of patients with PD.

Neuroimaging with magnetoencephalography: A dynamic view of brain pathophysiology

“…107 Recent work from our laboratory confirmed that un-medicated patients with PD have pathologically high synchrony between the primary motor cortices, and further showed that these patients have significantly diminished beta amplitude relative to demographically-matched controls during the resting-state. 112 Interestingly, administration of dopaminergic medication selectively ameliorated these differences in beta amplitude. 112 …”

“…112 Interestingly, administration of dopaminergic medication selectively ameliorated these differences in beta amplitude. 112 …”

Is an absolute level of cortical beta suppression required for proper movement? Magnetoencephalographic evidence from healthy aging

“…Further, a multitude of studies examining the neurophysiology of movement disorders, such as Parkinson’s disease (Brown, 2007; Cassidy et al, 2002; Heinrichs-Graham et al, 2014a; Heinrichs-Graham et al, 2014b; Little and Brown, 2014; Pollok et al, 2012; Weinberger et al, 2006), cerebral palsy (Kurz et al, 2014), Tourette syndrome (Franzkowiak et al, 2010; Niccolai et al, 2015; Tinaz et al, 2014), dystonia (Hinkley et al, 2012), and stroke (Rossiter et al, 2014a; Shiner et al, 2015; Wilson et al, 2011a) have shown aberrant sensorimotor beta power at rest and/or during movement. These beta aberrations are often correlated with symptom severity, which suggests that the degree of motor impairment is closely tied to beta activity in the motor cortices.…”

Neural mechanisms of transient neocortical beta rhythms: Converging evidence from humans, computational modeling, monkeys, and mice

“…Local beta oscillations and their coordination between regions are implicated in numerous functions, including sensory perception, selective attention, and motor planning and initiation (2,3,6,7,9,(11)(12)(13)(14)(15). Neocortical beta oscillations are disrupted in various neuropathologies, most notably Parkinson's disease (PD), in which treatments that alleviate motor symptoms also reverse the neocortical beta disruption (16,17). Although associations between beta and performance suggest a crucial role in brain function, beta rhythmicity might not be important per se but instead may be an epiphenomenal consequence of other important processes.…”

“…These findings make several predictions about optimal states for perceptual and motor performance and guide causal interventions to modulate beta for optimal function. beta rhythm | magnetoencephalography | computational modeling | sensorimotor processing | Parkinson's disease B eta band rhythms (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) are a commonly observed activity pattern in the brain. They are found with magnetoencephalography (MEG) (1)(2)(3)(4), EEG (5,6), and local field potential (LFP) recordings from neocortex (7)(8)(9) and are preserved across species (10).…”