Distinct Roles of the Human Subthalamic Nucleus and Dorsal Pallidum in Parkinson's Disease Impulsivity.

BACKGROUND: Impulsivity and impulse control disorders are common in Parkinson's disease and lead to increased morbidity and reduced quality of life. Impulsivity is thought to arise from aberrant reward processing and inhibitory control, but it is unclear why deep brain stimulation of either the subthalamic nucleus (STN) or globus pallidus internus (GPi) affects levels of impulsivity. Our aim was to assess the role of the STN and GPi in impulsivity using invasive local field potential (LFP) recordings from deep brain stimulation electrodes. METHODS: We measured LFPs during a simple rewarding Go/NoGo paradigm in 39 female and male human patients with Parkinson's disease manifesting variable amounts of impulsivity who were undergoing unilateral deep brain stimulation of either the STN (18 nuclei) or GPi (28 nuclei). We identified reward-specific LFP event-related potentials and correlated them to impulsivity severity. RESULTS: LFPs in both structures modulated during reward-specific Go and NoGo stimulus evaluation, reward feedback, and loss feedback. Motor and limbic functions were anatomically separable in the GPi but not in the STN. Across participants, LFP reward processing responses in the STN and GPi uniquely depended on the severity of impulsivity. CONCLUSIONS: This study establishes LFP correlates of impulsivity within the STN and GPi regions. We propose a model for basal ganglia reward processing that includes the bottom-up role of the GPi in reward salience and the top-down role of the STN in cognitive control.

Wearable sensor-driven responsive deep brain stimulation for essential tremor.

BACKGROUND: Deep brain stimulation (DBS) is an effective surgical therapy for individuals with essential tremor (ET). However, DBS operates continuously, resulting in adverse effects such as postural instability or dysarthria. Continuous DBS (cDBS) also presents important practical issues including limited battery life of the implantable neurostimulator (INS). Collectively, these shortcomings impact optimal therapeutic benefit in ET. OBJECTIVE: The goal of the study was to establish a physiology-driven responsive DBS (rDBS) system to provide targeted and personalized therapy based on electromyography (EMG) signals. METHODS: Ten participants with ET underwent rDBS using Nexus-D, a Medtronic telemetry wand that acts as a direct conduit to the INS by modulating stimulation voltage. Two different rDBS paradigms were tested: one driven by one EMG (single-sensor) and another driven by two or more EMGs (multi-sensor). The feature(s) used in the rDBS algorithms was the pow2er in the participant's tremor frequency band derived from the sensors controlling stimulation. Both algorithms were trained on kinetic and postural data collected during DBS off and cDBS states. RESULTS: Using established clinical scales and objective measurements of tremor severity, we confirm that both rDBS paradigms deliver equivalent clinical benefit as cDBS. Moreover, both EMG-driven rDBS paradigms delivered less total electrical energy translating to an increase in the battery life of the INS. CONCLUSIONS: The results of this study verify that EMG-driven rDBS provides clinically equivalent tremor suppression compared to cDBS, while delivering less total electrical energy. Controlling stimulation using a dynamic rDBS paradigm can mitigate limitations of traditional cDBS systems.

Florida research open-source synchronization tool (FROST) for electrophysiology experiments.

BACKGROUND: Accurate interpretation of electrophysiological data in cognitive and behavioral experiments requires the acquisition of time labels, such as marking the exact start of a condition or moment a stimulus is presented to a research subject. NEW METHOD: Here we present an inexpensive (∼30 USD) device used as a central relay for multiple peripheral devices, such as a computer screen presenting an experiment, a pressure-sensor push button, a multi-button responder, a pulse oximeter sensor, a light-emitting diode trigger for camera synchronization, and more. We refer to this device as the Florida Research Open-source Synchronization Tool (FROST). FROST allows for easy hardware and Arduino-based firmware modifications that enable a standard platform for the integration of novel peripheral sensors. RESULTS: With two examples, we demonstrate the application of this device during human research experiments: intracranial-electroencephalography (EEG) recordings in a patient with epilepsy and surface-EEG recordings in a healthy participant. We provide an example setup for a rodent experiment as well. We also demonstrate the timing delays of our device. COMPARISON WITH EXISTING METHODS: There is currently very few existing open-source synchronization tools for electrophysiological research that enable customization with new device compatibility. We developed this tool to enable widespread replication for many applications through an open-source platform. CONCLUSIONS: FROST can be easily adapted for research experiments beyond the included example cases. All materials are open-source at github.com/Brain-Mapping-Lab/FROST.