Adaptations during cognitive control involve theta oscillations within trials and beta oscillations across trials in both the human prefrontal cortex and subthalamic nucleus

The medial prefrontal cortex (mPFC) participates in conﬂict and feedback monitoring while the subthalamic nucleus (STN) adjusts actions, yet how these structures coordinate their activity during cognitive control remains poorly understood. We recorded from the human mPFC and STN during a novel response inhibition task involving cognitive control both within and across trials. Within-trial adaptations to conﬂict involved theta band activity. Yet despite conﬂict related increases in mPFC-STN theta phase synchrony, mPFC theta power reﬂected early response inhibition while STN theta power reﬂected later response execution. Across-trial adaptations to both conﬂict and errors involved beta band activity. Yet conﬂict and errors modulated mPFC beta power immediately following each response and modulated STN beta power only during the subsequent trial. Our data therefore demonstrate that the complementary roles of the mPFC and STN, rather than the speciﬁc frequencies themselves, govern the behavioral correlates of oscillatory activity during cognitive control. cognitive-theta and motoric-beta examining changes in neural activity in both the human STN and mPFC while participants perform a novel response inhibition task. speciﬁcally in how complementary activity within the STN and mPFC reﬂects cognitive control related to both the execution of a current action and the adjustments that are made for future actions. Using intra-operative microelectrode and subdural recordings captured during DBS surgery, we examine simultaneous oscillatory activity from the STN and the mPFC and ﬁnd a temporally sequenced, spatio-spectral segregation in the pattern of neural activity. Theta activity increases in both regions to adjust the current action during conﬂict, but theta increases in the mPFC and the STN seem to be involved during separate portions of the task. Beta activity, on the other hand, although also present at both sites, exhibits opposing behavior between the two regions. In the STN, beta activity primarily decreases and is involved in the direct control of gating a movement, whereas in the mPFC beta activity primarily increases and is involved in adaptations that occur as a result of error or conﬂict. Taken together, our results evidence the basic principle that the precise behavioral associations of oscillatory activity are determined not by frequency band per se, but by the circuits in which they are expressed. We made intraoperative recordings in 22 participants undergoing deep brain stimulation (DBS) surgery of the subthalamic nucleus (STN) for Parkinson’s disease. The study was conducted in accordance with an NIH IRB approved protocol, and all participants gave their written informed consent to take part in the study. Participants received no ﬁnancial compensation for their participation. Parkinson’s disease medications were stopped on the night before surgery (12 h preoperatively). We recorded while participants were alert, at rest and supine, and in an OFF state in the operating room. Sample-size estimation computations were not conducted prior to data collection. Instead, during a two year period (April 2014-April 2016) data were collected during all DBS cases in which the patient was willing and able to participate in the task. The goal was to collect between 10-20 recording sessions during this 24 month time period. Approximately one DBS case was done per month resulting in 22 total cases. The raw electrophysiology data and relevant code will be made available here: https://neuroscience.nih. gov/ninds/zaghloul/downloads.html As per routine DBS surgery, we used intraoperative microelectrode recordings to identify the STN based on ﬁring rate and pattern (increased spiking activity and background noise relative to the more dorsal zona incerta and thala-mus). We simultaneously advanced three targeting electrodes, separately spaced 2 mm apart, during each recording session (placed along a central, 2mm lateral, and 2mm anterior trajectory; Fig. 1c). Each targeting electrode consisted of a microelectrode contact and a macroelectrode contact positioned 3 mm dorsal to the microelectrode tip (Alpha Omega, Alpharetta, GA). Macroelectrode contacts were within the STN if the corresponding microelectrode contact was greater than 3 mm ventral to the dorsal border of the STN (identiﬁed by increased spiking activity and background noise relative to the more dorsal zona incerta and thalamus). We restricted all analyses only to signals captured from electrode contacts positioned within the STN. Raw signals were sampled at 1.5024