The impact of closed-loop intracortical stimulation on neural activity in brain-injured, anesthetized animals

Bioelectronic Medicine

David J. Guggenmos¹  Randolph J. Nudo¹  Lorenzo De Michieli²  Marianna Semprini²  Alberto Averna³  Michela Chiappalone⁴  Marta Carè⁴  Federico Barban⁴ 

[1] Department of Rehabilitation Medicine, University of Kansas Medical Center, 66160, Kansas City, USA;Landon Center on Aging, University of Kansas Medical Center, 66160, Kansas, USA;Rehab Technologies, Istituto Italiano di Tecnologia, 16163, Genoa, Italy;Rehab Technologies, Istituto Italiano di Tecnologia, 16163, Genoa, Italy;Aldo Ravelli Research Center for Neurotechnology and Experimental Neurotherapeutics, Department of Health Sciences, University of Milan, 20142, Milan, Italy;Rehab Technologies, Istituto Italiano di Tecnologia, 16163, Genoa, Italy;Department of Informatics, Bioengineering, Robotics System Engineering (DIBRIS), University of Genova, 16145, Genoa, Italy;

关键词: Activity-dependent stimulation;    Firing;    In vivo;    Micro-electrode arrays;    Spike;    Stroke;    Synchronization;   

DOI  :  10.1186/s42234-022-00086-y

来源: Springer

【 摘 要 】

BackgroundAcquired brain injuries, such as stroke, are a major cause of long-term disability worldwide. Intracortical microstimulation (ICMS) can be used successfully to assist in guiding appropriate connections to restore lost sensorimotor integration. Activity-Dependent Stimulation (ADS) is a specific type of closed-loop ICMS that aims at coupling the activity of two different brain regions by stimulating one in response to activity in the other. Recently, ADS was used to effectively promote behavioral recovery in rodent models following a unilateral traumatic brain injury in the primary motor cortex. While behavioral benefits have been described, the neurophysiological changes in spared areas in response to this type of stimulation have not been fully characterized. Here we explored how single-unit spiking activity is impacted by a focal ischemic lesion and, subsequently, by an ADS treatment.MethodsIntracortical microelectrode arrays were implanted in the ipsilesional rostral forelimb area (RFA) to record spike activity and to trigger intracortical microstimulation in the primary somatosensory area (S1) of anaesthetized Long Evans rats. An ischemic injury was induced in the caudal forelimb area through microinjections of Endothelin-1. Activity from both RFA and S1 was recorded and analyzed off-line by evaluating possible changes, either induced by the lesion in the Control group or by stimulation in the ADS group.ResultsWe found that the ischemic lesion in the motor area led to an overall increase in spike activity within RFA and a decrease in S1 with respect to the baseline condition. Subsequent treatment with ADS increased the firing rate in both RFA and S1. Post-stimulation spiking activity was significantly higher compared to pre-stimulation activity in the ADS animals versus non-stimulated controls. Moreover, stimulation promoted the generation of highly synchronized bursting patterns in both RFA and S1 only in the ADS group.ConclusionsThis study describes the impact on single-unit activity in ipsilesional areas immediately following a cortical infarct and demonstrates that application of ADS is effective in altering this activity.

【 授权许可】

CC BY