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Levy, T. J.

Publications and source records attributed to Levy, T. J..

3 recordsLinked to original sources

A standardized, surgically relevant map of organ-spesific branch emergence in the human vagus nerve

IntroductionVagus nerve stimulation modulates airway, cardiac, pulmonary, and gastrointestinal functions through respective organ-specific branches. Knowledge of where along the nerve vagal branches emerge may support alternative surgical placement of stimulation devices to activate targeted functions while avoiding off-target effects. However, no quantified map of the emergence of vagal branches and their relationship to surgically relevant anatomical landmarks exists in humans. MethodsFifty-eight vagus nerves (29 left, 29 right) from 29 embalmed donor bodies (15 females) were dissected from the jugular foramen through the thoracic cavity. Branches were traced to end organs and allocated to one of seven groups (sympathetic, muscular, vascular, cardiac, pulmonary, esophageal, or multiple targets) and several sub-groups. Distances between branch emergence and jugular foramen (JF) were normalized to three anatomical landmarks: carotid bifurcation, laryngeal prominence, and superior border of clavicle. ResultsEmergence of branches follows a proximal-to-distal order (median [IQR] distance from JF): sympathetic (3.9 cm [3.0-6.6]), muscular (6.2 [3.4-17.0]), vascular (9.6 [5.5-15.1]), cardiac (20.1 [16.9-22.5]), pulmonary (25.0 [22.8-27.6]), and esophageal (26.5 [24.3-29.1]). Branches emerge into two embryological domains separated at the clavicle: pharyngeal arch branches cluster proximally (7.3 cm [3.9-14.0]) and primitive mediastinum branches cluster distally (24.2 cm [20.9-27.1]), with sympathetic, muscular, and vascular sub-groups occupying distinct zones within the proximal domain. The longest branch-free intervals are all left-sided, occurring around the laryngeal prominence (3.0 cm [1.8-5.7]), the superior border of the clavicle (2.7 cm [1.3- 5.2]), and the carotid bifurcation (2.2 cm [0.9-5.7]). Several "target" branches are maximally separated from "off-target" branches at specific distances: sympathetic vs. cervical/ muscular/ vascular at 6/8 cm (L/R), cardiac vs. carotid sinus at 14/10 cm, and recurrent laryngeal vs. other muscular at 18/13 cm. Minimal differences are found between male and female donors. ConclusionThis study describes a quantified, landmark-registered map of cervical and thoracic vagal branch emergence and provides an anatomical reference that may help guide more selective device design and placement.

neuroscience↗

Longitudinal Characterization of Compound Action Potentials in Chronic Vagus Nerve Recordings in Mice

The vagus nerve (VN) mediates bidirectional communication between the body and brain to maintain physiological homeostasis; likewise, alterations in ongoing vagal signaling may be indicators of disease and/or contribute to disease pathogenesis. Even though extensively documented in acute experiments, ongoing vagal activity has not been characterized longitudinally, over days or weeks, in mice, a preferred preclinical model. In addition, even though many VN recordings in mice occur during anesthesia, the effects of anesthesia on vagal signaling are unknown. This study uses a chronic implant mouse model to record vagal activity in anesthetized and awake, behaving animals for an average of 10 weeks and up to 6 months. Individual compound action potentials (CAPs) are tracked across multiple days by quantifying comparisons in features, including firing rates, waveform shape, inter-CAP interval histograms, and phase-locking to cardiac and respiratory signals while demonstrating long-term electrode-nerve interface viability and stable signal-to-noise ratios. Additionally, cytokine challenge experiments produced detectable CAP responses up to 3 months after electrode implantation. Lastly, awake recordings incorporated video analysis to identify and remove motion artifacts to preserve and extract neural and cardiac recordings during behavior. Results reveal diverse CAP populations with diverse physiological coupling and firing rates modulated by anesthesia. This work highlights the potential of chronic VN recordings to assess long-term changes in vagal activity in health and disease, with implications in discovery of autonomic markers of disease and closed-loop VNS stimulation strategies.

neuroscience↗

A method to quantify autonomic nervous system function in healthy, able-bodied individuals

The autonomic nervous system (ANS), which maintains physiological homeostasis in various organ systems via parasympathetic and sympathetic branches, is altered in common diffuse and focal conditions. Sensitive, quantitative biomarkers could detect changes in ANS function, first here in healthy participants and eventually in patients displaying dysautonomia. This framework combines controlled autonomic testing with feature extraction from physiological responses. Twenty-one individuals were assessed in two morning and two afternoon sessions over two weeks. Each session included five standard clinical tests probing autonomic function: squat test, cold pressor test, diving reflex test, deep breathing, and Valsalva maneuver. Noninvasive sensors captured continuous electrocardiography, blood pressure, breathing, electrodermal activity, and pupil diameter. Heart rate, heart rate variability, mean arterial pressure, electrodermal activity, and pupil diameter responses to the perturbations were extracted, and averages across participants were computed. A template matching algorithm calculated scaling and stretching features that optimally fit the average to an individual response. These features were grouped based on test and modality to derive sympathetic and parasympathetic indices for this healthy population. A significant positive correlation (p = 0.000377) was found between sympathetic amplitude response and body mass index. Additionally, longer duration and larger amplitude sympathetic and longer duration parasympathetic responses occurred in afternoon testing sessions; larger amplitude parasympathetic responses occurred in morning sessions. These results demonstrate the robustness and sensitivity of an algorithmic approach to extract multimodal responses from standard tests. This novel method of quantifying ANS function can be used for early diagnosis, measurement of disease progression, or treatment evaluation.

bioengineering↗