Figure 3. Examples of stimulation-entrained finely-tuned gamma oscillations in both in-clinic and at-home recordings.

a, Example spectrogram of cortical activity in the on-medication state during systematic variations in stimulation amplitude (black dotted line), illustrating the phenomenon of stimulation-induced entrainment of gamma oscillations at half of the stimulation frequency (pat-1). Levodopa-induced finely-tuned gamma (FTG) oscillations occur at 80–90 Hz when stimulation amplitudes are low but become entrained to half the stimulation frequency (65 Hz) when stimulation exceeds a certain amplitude (1.5 mA in this example). b-c, Examples of biomarker identification using standardized in-clinic neural recordings (b, pat-2L, c, pat-1). Plots show power spectra during on- and off-levodopa states (mean±standard error of the mean), i.e., periods during which hyper- and hypokinetic symptoms would emerge, respectively. Recordings are collapsed across low and high stimulation amplitude conditions, which were both amplitudes at which FTG entrained to half the stimulation frequency. We found that medication yielded the largest effect on entrained finely-tuned gamma power at half the stimulation frequency in the STN (b, pat-2L) and motor cortex (c, pat-1) when controlling for effects of stimulation (Extended Data Fig. 2). Significant clusters are highlighted in gray. d-e, At-home recordings during constant stimulation amplitude and patients’ normal medication schedule in the STN (d, pat-2L) and motor cortex (e, pat-1). Patients marked their medication intake (red dashed line) and on- and off-set of their most bothersome symptom in their motor diary (completed in 30-minute intervals) and the streaming application⁹. Both patients had bothersome off-state symptoms, lower limb-dystonia (d, pat-2) and bradykinesia (e, pat-1). For both, FTG oscillations occur ~45 minutes after medication intake (red arrows), corresponding to a typical latency of onset for dopaminergic medication. When the patient marked their most bothersome symptom (indicated by the black dashed line) in their motor diary, FTG oscillations disappeared, indicating a transition to an off-medication state.