Biology subjects

Hickman, J.

Publications and source records attributed to Hickman, J..

4 recordsLinked to original sources

bioRxiv2025

A Bioelectric Router for Adaptive Isochronous Neurostimulation

ObjectiveMultipolar intracranial electrical brain stimulation (iEBS) is a method that has potential to improve clinical applications of mono- and bipolar iEBS. Current tools for researching multipolar iEBS are proprietary, can have high entry costs, lack flexibility in managing different stimulation parameters and electrodes, and can include clinical features unnecessary for the requisite exploratory research. This is a factor limiting the progress in understanding and applying multipolar iEBS effectively. To address these challenges, we developed the Bioelectric Router for Adaptive Isochronous Neuro stimulation (BRAINS) board. ApproachThe BRAINS board is a cost-effective and customizable device designed to facilitate multipolar stimulation experiments across a 16-channel electrode array using common research electrode setups. The BRAINS board interfaces with a microcontroller, allowing users to configure each channel for cathodal or anodal input, establish a grounded connection, or maintain a floating state. The design prioritizes ease of integration by leveraging standard tools like a microcontroller and an analog signal isolators while providing options to customize setups according to experimental conditions. It also ensures output isolation, reduces noise, and supports remote configuration changes for rapid switching of electrode states. To test the efficacy of the board, we performed bench-top validation of monopolar, bipolar, and multipolar stimulation regimes. The same regimes were tested in vivo in mouse primary visual cortex and measured using Neuropixel recordings. Main ResultsThe BRAINS board demonstrates no meaningful differences in Root Mean Square Error (RMSE) noise or signal-to-noise ratio compared to the baseline performance of the isolated stimulator alone. The board supports configuration changes at a rate of up to 600 Hz without introducing residual noise, enabling high-frequency switching necessary for temporally multiplexed multipolar stimulation. SignificanceThe BRAINS board represents a significant advancement in exploratory brain stimulation research by providing a user-friendly, customizable, open source, and cost-effective tool capable of conducting sophisticated, reproducible, and finely controlled stimulation experiments. With a capacity for effectively real-time information processing and efficient parameter exploration the BRAINS board can enhance both exploratory research on iEBS and enable improved clinical use of multipolar and closed-loop iEBS.

neuroscience↗

bioRxiv2021

Vagus nerve stimulation accelerates motor learning through cholinergic modulation

Vagus nerve stimulation (VNS) is a neuromodulation therapy for a broad and rapidly expanding set of neurologic conditions. Classically used to treat epilepsy and depression, VNS has recently received FDA approval for stroke rehabilitation and is under preclinical and clinical investigation for other neurologic indications. Despite benefits across a diverse range of neurological disorders, the mechanism through which VNS influences central nervous system circuitry is not well described, limiting therapeutic optimization. A deeper understanding of the influence of VNS on neural circuits and activity is needed to maximize the use of VNS therapy across a broad range of neurologic conditions. To investigate how VNS can influence the neurons and circuits that underlie behavior, we paired VNS with upper limb movement in mice learning a skilled motor task. We leveraged genetic tools to perform optogenetic circuit dissection, as well as longitudinal in vivo imaging of calcium activity in cortical neurons to understand the effect of VNS on neural function. We found that VNS robustly enhanced motor learning when temporally paired with successful movement outcome, while randomly applied VNS impaired learning. This suggests that temporally-precise VNS may act through augmenting outcome cues, such as reinforcement signals. Within motor cortex, VNS paired with movement outcome selectively modulates the neural population that represents outcome, but not other movement-related neurons, across both acute and behaviorally-relevant timescales. Phasic cholinergic signaling from basal forebrain is required both for VNS-driven improvements in motor learning and the effects on neural activity in M1. These results indicate that VNS enhances motor learning through precisely-timed phasic cholinergic signaling to reinforce outcome, resulting in the recruitment of specific, behaviorally-relevant cortical circuits. A deeper understanding of the mechanisms of VNS on neurons, circuits and behavior provides new opportunities to optimize VNS to treat neurologic conditions.

neuroscience↗

bioRxiv2021

Closed-loop automated reaching apparatus (CLARA) for interrogating motor systems

Objective: Personalized neurostimulation is a rapidly expanding category of therapeutics for a broad range of indications. Development of these innovative neurological devices requires high-throughput systems for closed-loop stimulation of model organisms, while monitoring physiological signals and complex, naturalistic behaviors. To address this need, we developed CLARA, a closed-loop automated reaching apparatus. Approach: Using breakthroughs in computer vision, CLARA integrates fully-automated, markerless kinematic tracking of multiple features we use to classify animal behavior and precisely deliver neural stimulation based on behavioral outcomes. CLARA is compatible with advanced neurophysiological tools, enabling the testing of neurostimulation devices and identification of novel neurological biomarkers. Results: The CLARA system tracks unconstrained skilled reach behavior in 3D at 150hz without physical markers. The system fully automates trial initiation and pellet delivery and is capable of accurately delivering stimulation in response to trial outcome with sub-quarter second latency. Mice perform the skilled reach task in the CLARA system at a proficiency similar to manually trained animals. Kinematic data from the CLARA system provided novel insights into the dynamics of reach consistency over the course of learning, suggesting that changes are driven entirely by unsuccessful reach accuracy. Additionally, using the closed-loop capabilities of CLARA, we demonstrate that vagus nerve stimulation (VNS) delivered on reach success improves skilled reach performance and increases reach trajectory consistency in healthy animals. Significance: The CLARA system is the first mouse behavior apparatus that uses markerless pose tracking to provide real-time closed-loop stimulation in response to the outcome of an unconstrained motor task. Additionally, we demonstrate that the CLARA system was essential for our finding that VNS given after successful completion of a motor task improves performance in healthy animals. This approach has high translational relevance for developing neurostimulation technology based on complex human behavior.

neuroscience↗

bioRxiv2020

An implant for long-term cervical vagus nerve stimulation in mice

Vagus nerve stimulation (VNS) is a neuromodulation therapy with the potential to treat a wide range of chronic conditions in which inflammation is implicated, including type 2 diabetes, obesity and atherosclerosis. Many of these diseases have well-established mouse models, but due to the significant surgical and engineering challenges that accompany a reliable interface for long-term VNS in mice, the therapeutic implications of this bioelectronic therapy remain unexplored. Here, we describe a long-term VNS implant in mice, developed at 3 research laboratories and validated for across-lab reproducibility. Implant functionality was evaluated over 3-8 weeks in 81 anesthetized or behaving mice by determining the stimulus intensity required to elicit a change in heart rate (heart rate threshold, HRT). HRT was also used as a method to standardize stimulation dosing. Overall, 60-90% of implants produced stimulus-evoked physiological responses for at least 4 weeks, with HRT values stabilizing after the second week of implantation. Furthermore, stimulation delivered through 6-week-old implants decreased TNF levels in a subset of mice with acute inflammation caused by endotoxemia. Histological examination of 4- to 6-week-old implants revealed fibrotic encapsulation and no gross fiber loss. This implantation and dosing approach provides a tool to systematically investigate the therapeutic potential of long-term VNS in chronic diseases modeled in the mouse, the most widely used vertebrate species in biomedical research.Competing Interest StatementThe authors have declared no competing interest.View Full Text

bioengineering↗