Characterization and closed-loop control of infrared thalamocortical stimulation produces spatially constrained single-unit responses

Abstract

Deep brain stimulation (DBS) is a powerful tool for the treatment of circuitopathy-related neurological and psychiatric diseases and disorders such as Parkinson’s disease and obsessive-compulsive disorder, as well as a critical research tool for perturbing neural circuits and exploring neuroprostheses. Electrically-mediated DBS, however, is limited by the spread of stimulus currents into tissue unrelated to disease course and treatment, potentially causing undesirable patient side effects. In this work, we utilize infrared neural stimulation (INS), an optical neuromodulation technique that uses near to mid-infrared light to drive graded excitatory and inhibitory responses in nerves and neurons, to facilitate an optical and spatially constrained DBS paradigm. INS has been shown to provide spatially constrained responses in cortical neurons and, unlike other optical techniques, does not require genetic modification of the neural target. We show that INS produces graded, biophysically relevant single-unit responses with robust information transfer in rat thalamocortical circuits. Importantly, we show that cortical spread of activation from thalamic INS produces more spatially constrained response profiles than conventional electrical stimulation. Owing to observed spatial precision of INS, we used deep reinforcement learning for closed-loop control of thalamocortical circuits, creating real-time representations of stimulus-response dynamics while driving cortical neurons to precise firing patterns. Our data suggest that INS can serve as a targeted and dynamic stimulation paradigm for both open and closed-loop DBS.

Practical Bayesian Inference in Neuroscience: Or How I Learned to Stop Worrying and Embrace the Distribution

“…Bayesian hierarchical regressions can easily deal with complex models such as these. This data was part of a previous study ( Coventry et al, 2024 ).…”

“…Regression models, ANOVA models, and group comparisons are performed on single-unit activity recorded from IC neurons in response to auditory stimuli in young and aged rats ( Palombi et al, 2001 ; Simon et al, 2004 ; Rabang et al, 2012 ; Herrmann et al, 2017 ; Bartlett et al, 2024 ). Random-effects regression models are performed on single units recorded in the auditory cortex (A1) using high-density recording arrays in response to infrared neural stimulation (INS; Izzo et al, 2007 ; Cayce et al, 2011 , 2014 ; Coventry et al, 2024 ) of the medial geniculate body (MGB). All surgical procedures used in this study were approved by the Institutional Animal Care and Use Committee of Purdue University (West Lafayette, IN, #120400631) and in accordance with the guidelines of the American Association for Laboratory Animal Science and the National Institutes of Health guidelines for animal research.…”

“…INS is an optical technique that uses coherent infrared light to stimulate nerves and neurons without the need for genetic modification of the target or direct contact with tissue that offers spatially constrained activation above electrical stimulation ( Wells et al, 2005 ; Izzo et al, 2007 ; Cayce et al, 2011 , 2014 ; Coventry et al, 2020 , 2024 ). In this study, seven male Sprague Dawley rats were chronically implanted in A1 with 16 channel planar Utah-style arrays (TDT) and stimulating optrodes in the MGB of the auditory thalamus (Thorlabs).…”

“…The practice of the design of experiments and their resulting publications are rife with implicit priors that are often not acknowledged or realized when reporting results. As an example, consider the study of cortical extracellular single-unit recordings ( Paninski et al, 2004 ; Bartlett and Wang, 2007 ; De La Rocha et al, 2007 ; Coventry et al, 2024 ). The investigator could be leading a project with vast knowledge accumulated over years of study.…”