Gamma Oscillations in the Hyperkinetic State Detected with Chronic Human Brain Recordings in Parkinson's Disease

Abstract

Hyperkinetic states are common in human movement disorders, but their neural basis remains uncertain. One such condition is dyskinesia, a serious adverse effect of medical and surgical treatment for Parkinson's disease (PD). To study this, we used a novel, totally implanted, bidirectional neural interface to obtain multisite long-term recordings. We focus our analysis on two patients with PD who experienced frequent dyskinesia and studied them both at rest and during voluntary movement. We show that dyskinesia is associated with a narrowband gamma oscillation in motor cortex between 60 and 90 Hz, a similar, though weaker, oscillation in subthalamic nucleus, and strong phase coherence between the two. Dyskinesia-related oscillations are minimally affected by voluntary movement. When dyskinesia persists during therapeutic deep brain stimulation (DBS), the peak frequency of this signal shifts to half the stimulation frequency. These findings suggest a circuit-level mechanism for the generation of dyskinesia as well as a promising control signal for closed-loop DBS.

Adaptive deep brain stimulation for Parkinson’s disease using motor cortex sensing

“…Indeed, for our particular control strategy (using a narrowband gamma feedback signal), the signal was more reliably detected in cortex compared to STN both on and off DBS (Figure 5). Furthermore, as we showed in our previous paper, the cortical signal was associated with an area under the curve value of 0.912 from a receiver operator curve analysis, compared to a value of 0.797 for STN 4 . In contrast, our approach utilizes an ECoG signal for feedback control, provides a higher amplitude signal that is much further from the source of stimulation artifact and does not limit the choice of DBS contacts available for stimulation (given the inability to record and stimulate from the same contact).…”

“…DBS parameters were selected to be as close to the patient’s clinical settings as possible, while minimizing artifacts related to stimulation and Activa PC+S recordings. (For instance, constant current was not used for algorithm prototyping due to artifacts associated with this mode 4 .) Details are provided in Table 2.…”

“…In this prototype, the signals to drive adaptive DBS were derived from electrocorticography (ECoG) power channels that record power directly from the Activa PC+S device (recordings were filtered using an analog filter prior to digitization). The narrowband gamma signal related to dyskinesia occurs at half the stimulation frequency, when dyskinesia is present (Figure 1A and 1C) 4 . Thus, for Patient 1 the power channel was centered at 80 Hz (+/− 2.5 Hz) (since his stimulation was delivered at 160 Hz) and for Patient 2 the power channel was centered at 65 Hz (+/− 2.5 Hz) (since his stimulation was delivered at 130 Hz).…”

Electrotherapy: Shock value

“…Meanwhile, Starr's team has identified signatures in the activity of motor-cortex neurons that predict the onset of parkinsonian symptoms, and devised an algorithm that initiates stimulation when these patterns are detected 8 . And Bronte-Stewart's team has developed an adaptive DBS platform that uses Bluetoothenabled smartwatches to detect the onset of tremor and then signal to the stimulator to respond accordingly 9 .…”

Neuromagnetic investigations of mechanisms and effects of STN-DBS and medication in Parkinson's disease

“…Wireless transmission of deep brain data along with mobile EEG setups can enable experiments where PD patients are mobile, compared to the relatively immobile setup in our studies with patients lying in supine position. The mobility of PD patients opens up for interesting possibilities of studying cortico-subcortical oscillatory dynamics during disease symptoms such as dyskinesia or freezing of gait and during dynamic experimentation settings like biking (Gratkowski et al, 2016;Swann et al, 2016).…”