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Ganzer, P. D.

Publications and source records attributed to Ganzer, P. D..

4 recordsLinked to original sources

Characterizing The Multimodal Sympathetic Nervous System Startle Response

The human startle reflex has primarily been characterized by its repeatable, coordinated, and temporally patterned somatomotor responses. In this study, we assessed whether startle-evoked sympathetic nervous system (SNS) responses might also constitute a repeatable, coordinated, and temporally structured output. Using a noninvasive tactile startle stimulus, we simultaneously recorded startle-evoked electrodermal activity, photoplethysmography-derived blood volume indices, heart rate, blood pressure, stroke volume, and cardiac output in healthy participants. Our results demonstrate that startle elicits a reproducible and patterned constellation of SNS responses - a multimodal SNS startle signature - with conserved temporal relationships across effector systems. The SNS startle signature was composed of robust bilateral peripheral responses, including palmar sweating, cutaneous vasoconstriction, and biphasic cutaneous venous-capillary blood volume changes, in addition to more mild central hemodynamic changes. In contrast to previous startle reflex studies, there was no influence of biological sex or cardiac-cycle gating on responses. Lastly, the SNS startle signature exhibited features of a potentially attractive diagnostic, associated with robust responder discrimination and high response reliability across repeated trials. Overall, these findings fill a critical knowledge gap and also suggest the potential utility of this multimodal signature for assessing autonomic dysfunction.

physiology↗

Chronic Cervical Midline Contusion in Rats Disrupts Aerobic, Muscular, and Cardiovascular Function

Cardiovascular dysfunction significantly contributes to morbidity and mortality following cervical spinal cord injury (SCI). Unfortunately, only a limited number of preclinical models have been developed for investigating cardiovascular dysfunction following cervical SCI. Furthermore, the broader consequences of cervical SCI on aerobic capacity and muscle endurance during physiological stress testing also remains understudied preclinically. Therefore, in this study we assessed potential deficits across multiple physiological systems in a rat model of cervical SCI using a battery of stress tests. Female Sprague-Dawley rats (n = 20) received either a C8 midline contusion (cSCI) or laminectomy alone as a control (LAM). Exercise stress testing was conducted to evaluate cardiorespiratory fitness and recovery using a metabolic treadmill, or forelimb fitness using the isometric pull task. Orthostatic stress testing and pharmacological stress testing were also performed to more directly challenge the cardiovascular system. Our findings demonstrate a decline in aerobic fitness in cSCI rats, as evidenced by dysregulated excess post-exercise oxygen consumption. cSCI rats also exhibited impaired muscle endurance compared to LAM. During orthostatic stress testing, 70% of cSCI rats experienced an approximately 25 mmHg decrease in systolic blood pressure and 20 mmHg decrease in diastolic blood pressure, in addition to modest but significant decreases in heart rate, myocardial contractility index, stroke volume index, and cardiac output index. During dobutamine infusion, cardiac output index and stroke volume index were significantly reduced following cSCI compared to LAM. Overall, these stress testing results suggest that preclinical cervical SCI in rats can lead to, and therefore model, clinically relevant impairments in cardiopulmonary exercise performance, muscle endurance, and cardiovascular function.

physiology↗

Dynamic Detection and Reversal of Myocardial Ischemia Using an Artificially Intelligent Bioelectronic Medicine

SummaryMyocardial ischemia is spontaneous, usually asymptomatic, and contributes to fatal cardiovascular consequences. Importantly, biological neural networks cannot reliably detect and correct myocardial ischemia on their own. In this study, we demonstrate an artificially intelligent and responsive bioelectronic medicine, where an artificial neural network (ANN) supplements biological neural networks enabling reliable detection and correction of myocardial ischemia. ANNs were first trained to decode spontaneous cardiovascular stress and myocardial ischemia with an overall accuracy of [~]92%. ANN-controlled vagus nerve stimulation (VNS) reversed the major biomarkers of myocardial ischemia with no side effects. In contrast, open-loop VNS or ANN-controlled VNS following a caudal vagotomy essentially failed to reverse correlates of myocardial ischemia. Lastly, variants of ANNs were used to meet clinically relevant needs, including interpretable visualizations and unsupervised detection of emerging cardiovascular stress states. Overall, these results demonstrate that ANNs can supplement deficient biological neural networks via an artificially intelligent bioelectronic medicine system.

bioengineering↗

Augmenting Quadriplegic Hand Function Using a Sensorimotor Demultiplexing Neural Interface

BackgroundThe sense of touch is a key component of motor function. Severe spinal cord injury (SCI) should essentially eliminate sensory information transmission to the brain, that originates from skin innervated from below the lesion. We assessed the hypothesis that, following SCI, residual hand sensory information is transmitted to the brain, can be decoded amongst competing sensorimotor signals, and used to enhance the sense of touch via an intracortically controlled closed-loop brain-computer interface (BCI) system.\n\nMethodsExperiments were performed with a participant who has an AIS-A C5 SCI and an intracortical recording array implanted in left primary motor cortex (M1). Sensory stimulation and standard clinical sensorimotor functional assessments were used throughout a series of several mechanistic experiments.\n\nFindingsOur results demonstrate that residual afferent hand sensory signals surprisingly reach human primary motor cortex and can be simultaneously demultiplexed from ongoing efferent motor intention, enabling closed-loop sensory feedback during brain-computer interface (BCI) operation. The closed-loop sensory feedback system was able to detect residual sensory signals from up to the C8 spinal level. Using the closed-loop sensory feedback system enabled significantly enhanced object touch detection, sense of agency, movement speed, and other sensorimotor functions.\n\nInterpretationTo our knowledge, this is the first demonstration of simultaneously decoding multiplexed afferent and efferent activity from human cortex to control multiple assistive devices, constituting a sensorimotor demultiplexing BCI. Overall, our results support the hypothesis that sub-perceptual neural signals can be decoded reliably and transformed to conscious perception, significantly augmenting function.\n\nFundingInternal funding was provided for this study from Battelle Memorial Institute and The Ohio State University Center for Neuromodulation.

neuroscience↗