Biology subjects

Yttri, E.

Publications and source records attributed to Yttri, E..

3 recordsLinked to original sources

bioRxiv2025

Differential modulation of movement speed with state-dependent deep brain stimulation in Parkinson's disease

Subthalamic deep brain stimulation (STN-DBS) provides unprecedented spatiotemporal precision for the treatment of Parkinsons disease (PD), allowing for direct real-time state-specific adjustments. Inspired by findings from optogenetic stimulation in mice, we hypothesized that STN-DBS effects on movement speed depend on ongoing movement kinematics that patients exhibit during stimulation. To investigate this hypothesis, we implemented a motor state-dependent closed-loop neurostimulation algorithm, adapting DBS burst delivery to ongoing movement speed in 24 PD patients. We found a stronger anti-bradykinetic effect, raising movement speed to the level of healthy controls, when STN-DBS was applied during fast but not slow movements, while only stimulating 5% of overall movement time. To study underlying brain circuits and neurophysiological mechanisms, we investigated the behavioral effects with MRI connectomics and motor cortex electrocorticography. Finally, we demonstrate that machine learning-based brain signal decoding can be used to predict continuous movement speed for fully embedded state-dependent closed-loop algorithms. Our findings provide novel insights into the state-dependency of invasive neuromodulation, which could inspire advanced state-dependent neurostimulation algorithms for brain disorders.

neuroscience↗

bioRxiv2024

Striatal modulation supports policy-specific reinforcement and not action selection

Two contrasting models dominate our understanding of basal ganglia function: action selection and reinforcement learning. Prolonged, indiscriminate stimulation of direct and indirect pathway striatal neurons produces effects consistent with the action selection; however this approach ignores the transient, movement-specific dynamics that characterize these cells. To determine how striatal subpopulations contribute to mouse behavior, we applied brief closed-loop optogenetic stimulation to modulate ongoing activity in a manner that directly dissociates the contrasting models: upon the detection of locomotor arrest or leftward turns. While action selection models predict that increased direct pathway stimulation should induce locomotion and turning contralaterally to the side of stimulation, selective stimulation biased behavioral policies towards more frequent locomotor arrest and leftward turns, regardless of the side of stimulation. Indirect pathway stimulation had the opposite effect. Behavior followed the policy associated with the change in striatal activity, providing a mechanism to enable the reinforcement a wide range of behavioral features to shape performance.

neuroscience↗

bioRxiv2024

An Investigation of Parameter-Dependent Cell-Type Specific Effects of Transcranial Focused Ultrasound Stimulation Using an Awake Head-Fixed Rodent Model

Transcranial focused ultrasound (tFUS) is a promising neuromodulation technique able to target shallow and deep brain structures with high precision. Previous studies have demonstrated that tFUS stimulation responses are both cell-type specific and controllable through altering stimulation parameters. Specifically, tFUS can elicit time-locked neural activity in regular spiking units (RSUs) that is sensitive to increases in pulse repetition frequency (PRF), while time-locked responses are not seen in fast spiking units (FSUs). These findings suggest a unique capability of tFUS to alter circuit network dynamics with cell-type specificity; however, these results could be biased by the use of anesthesia, which significantly modulates neural activities. In this study, we develop an awake head-fixed rat model specifically designed for tFUS study, and address a key question if tFUS still has cell-type specificity under awake conditions. Using this novel animal model, we examined a series of PRFs and burst duty cycles (DCs) to determine their effects on neuronal subpopulations without anesthesia. We conclude that cell-type specific time-locked and delayed responses to tFUS as well as PRF and DC sensitivity are present in the awake animal model and that despite some differences in response, isoflurane anesthesia is not a major confound in studying the cell-type specificity of ultrasound neuromodulation. We further determine that, in an awake, head-fixed setting, the preferred PRF and DC for inducing time-locked excitation with our pulsed tFUS paradigm are 1500 Hz and 60%, respectively.

neuroscience↗