Electrical Stimulation publications

This study examined whether interaural amplitude modulation (AM) coherence influences binaural pitch fusion in cochlear implant (CI) users. Fourteen adults, including seven bimodal and seven bilateral CI users, completed fusion-range measurements using dichotic stimuli under unmodulated, coherent AM and two incoherent AM conditions involving interaural AM-phase and AM-rate mismatches. Coherent AM consistently broadened fusion ranges, often doubling those in the unmodulated condition, even with shallow modulation depth. In contrast, incoherent AM, including interaural phase or rate mismatches, narrowed fusion. These findings indicate that temporal-envelope coherence facilitates binaural integration in CI users, emphasizing its importance for auditory processing and CI sound-processing design.

Objectives. Spatial mapping of sound frequencies along the auditory pathway is refined through sound-evoked activity during early development. However, how neonatal auditory deprivation alters this organization remains unclear. This study examined frequency-specific spatial representations in the inferior colliculus (IC) using targeted low-frequency (apical) and high-frequency (basal) cochlear stimulation, enabling direct evaluation of low-frequency pathway integrity after neonatal deafness.Methods. Sixteen Sprague-Dawley rats (8 normal-hearing [NH] and 8 neonatally deafened [ND]) were studied. Neonatal deafness was induced by daily kanamycin injections from postnatal days 4 to 17. At 8–10 weeks of age, all animals underwent unilateral cochlear implantation with bipolar electrode pairs positioned in apical and basal cochlear regions to activate low- and high-frequency pathways. Multiunit responses were recorded from the contralateral IC using a multichannel linear electrode array. Spatial tuning curves (STCs) based on cumulative discriminability were used to assess thresholds, spread of excitation, and tonotopic precision. Spiral ganglion neuron (SGN) density was quantified histologically.Results. Despite 48%–67% SGN loss across cochlear turns, electrically evoked auditory brainstem response thresholds and IC thresholds were comparable between groups, indicating preserved peripheral excitability. However, ND rats exhibited significantly broader STCs (P=0.002) and reduced dorsoventral separation of apical and basal best sites (1.18± 0.67 mm vs. 1.80±0.40 mm, P=0.039), reflecting degraded central tonotopic precision. The effects were most pronounced for apical (low-frequency) stimulation, consistent with the selective vulnerability of low-frequency pathways to early auditory deprivation.Conclusion. These findings provide direct physiological evidence that early auditory experience is critical for refining frequency-organized connectivity in the auditory midbrain. The preferential degradation of apical (low-frequency) spatial tuning offers translational insights for optimizing stimulation strategies in early-onset deafness.

Neuromodulation is widely employed to enhance neural activity and restore impaired circuitry, yet current methods suffer from invasiveness, limited depth, or poor spatial resolution. Temporal interference stimulation (TIS) has emerged as a non-invasive approach to modulate deep brain regions via interference of high-frequency electric fields, achieving spatial selectivity. Despite its potential, the physiological effects remain unexplored. Here, we present a customized liquid metal-based neural interface to record electrophysiological responses to TIS across diverse neural tissues, from brain organoids to mouse brains. The softness of the interface minimizes invasiveness while ensuring stable access to deep neural regions. Electrophysiological analyses reveal TIS-induced dynamics in neurodevelopment and functional connectivity. Furthermore, we investigated latent neural dynamics, presenting population-level neural activity, to compare responses across models of differing complexity and maturity. By combining soft neural interfaces with multi-scale analyses, this study uncovers how neuromodulation shapes neural dynamics and supports the development of future therapeutic strategies.

Background Direct current (DC) stimulation can modulate neuronal activity in ways that differ from pulsatile stimulation, but its intracranial use has been limited by concerns about tissue injury at the electrode/tissue interface. Quantitative safety limits for DC delivered through metal electrodes directly to the brain remain poorly defined. Objective To estimate histological safety boundaries for DC stimulation delivered through metal electrodes in a large-brain gyrencephalic animal model. Methods Cathodal DC stimulation was applied to the exposed cortical surface of ten anesthetized sheep using platinum–iridium disc electrodes typically used in clinical applications (surface area ≤ 4.15 mm 2 ). Currents of 5 to 1000 µA were delivered for 10 to 15 minutes at 36 cortical sites. Stimulation dose was quantified as charge density. Brains were removed shortly after stimulation and examined histologically for tissue damage, including necrosis, inflammation, gliosis, and demyelination. Lesion volumes were quantified and related to charge density. Results No lesions were observed at sites where no current or a low charge density (0.7 mC/mm 2 ) was delivered. With stimulation, lesion probability and volume increased with charge density, although variability was substantial. Lesions occurred in 3 of 18 sites at lower charge densities (1.4 to 10 mC/mm 2 ) and in 5 of 9 sites at higher charge densities (14.4 to 144.4 mC/mm 2 ). Linear regression of lesion volume against charge density yielded an estimated zero-lesion intercept of 2.3 mC/mm 2 , whereas alternative nonlinear models predicted thresholds up to 8.7 mC/mm 2 . Conclusion These findings suggest that it may be possible to apply cathodal DC stimulation directly to the cortical surface through metal electrodes without detectable histological damage when current intensity, duration, and electrode size are appropriately constrained. These findings provide quantitative guidance for the safe application of DC directly to neural tissue in experimental and translational neuromodulation studies.

Pain management strategies have progressed beyond traditional pharmacologic and physical interventions, integrating advanced neuromodulation techniques such as deep brain stimulation, peripheral nerve stimulation, and high‐frequency spinal cord stimulation (hSCS). Despite its clinical efficacy, the supraspinal mechanisms underlying hSCS remain poorly understood. Prior work in sheep demonstrated that hSCS modulates gamma (γ) band (70–150 Hz) activity in the primary somatosensory and association cortices, implicating cortical involvement in pain modulation. Given the interaction between low‐ and high‐oscillations, we hypothesized that hSCS modulates γ activity in a region‐ and time‐dependent manner through specific coupling with theta rhythms (θ, 4–8 Hz). To test this, we quantified θ–γ phase‐amplitude coupling (PAC) during tibial nerve stimulation (TNS) before (TNS 0 ) and after (TNS 1 ) hSCS to assess cortical processing of TNS‐evoked activity, while recording cortical (association and somatosensory cortices) neural activity using 96‐channel subdural electrocorticography (ECoG). We then computed the corresponding modulation index (MI) to quantify PAC strength. While the preferred θ phase of γ activity remained consistent across conditions in both cortical areas, θ‐γ coupling was more robust and stable in the association than the somatosensory cortex. However, MI increased significantly post‐hSCS in both cortices, indicating enhanced θ‐γ coupling during TNS 1 . Temporally, both cortices showed distinct response patterns: the somatosensory cortex exhibited strongest coupling increase early post‐hSCS, followed by a progressive decline, whereas the association cortex showed a more delayed and temporally distributed enhancement. These findings indicate that hSCS modulates cortical cross‐frequency interactions during TNS‐evoked sensory processing, wherein somatosensory and association cortices show distinct temporal coupling dynamics that may contribute to supraspinal mechanisms of pain modulation.

Current disease-sensing devices primarily focus on distinguishing between healthy and diseased states, effective for diagnosis but limited in guiding optimal intervention timing for prevention. We developed a tripartite framework identifying pre-disease state in depression, a reversible phase preceding irreversible onset. Using complex systems theory, we analyzed early-warning signals emerging as biological systems approach critical transitions. Continuous monitoring of nine multimodal biomarkers—spanning electrophysiological, behavioral, and biological—enabled classification into normal, pre-disease, and disease states by quantitatively defining critical points. An artificial intelligence agent classified disease states with 95.2% accuracy using multimodal data, enabled by ultrasoft neural probes for stable, low-damage recordings. Therapeutic validation with a skin-attachable wireless vagus nerve stimulator integrating soft three-dimensional electrodes demonstrated superior efficacy during pre-disease states. Subjects treated during pre-disease showed faster recovery and greater therapeutic responses, while those treated after disease onset failed to achieve full recovery. This framework provides evidence-based rationale for early intervention.

Objective To evaluate the feasibility of using the acoustic change complex (ACC) as an objective cortical marker of continuous speech sound discrimination using connected Ling-six stimuli. Design Cortical auditory evoked potentials were recorded from 10 young adults with normal hearing using a continuous, pause-free sequence of the six Ling phonemes (/u-a-i-ʃ-s-m/). ACC responses were recorded in a passive listening paradigm with minimal electrodes. Reproducibility was assessed in a subset of participants retested 1 year later. Results Robust ACC responses were elicited for all six phonemic transitions in every participant, indicating reliable cortical discrimination within the continuous speech stream. Although response morphology varied across listeners, within-subject responses demonstrated strong reproducibility over a one-year interval (mean cross-correlation = 0.95). Conclusion Continuous Ling-six stimuli reliably evoke ACC responses reflecting cortical speech sound discrimination. This efficient and repeatable paradigm shows promise as an objective verification tool for auditory learning and sound discrimination, particularly in populations for whom behavioral assessment is unreliable.

Purpose: The UmboMic is a recently developed middle ear microphone that functions by detecting the sound-induced motion of the umbo [1]. To prepare for a live animal study of the in vivo performance of the UmboMic, we developed the surgical implantation and fixation system in cadaveric sheep ears. Methods: Temporal bones from seven female sheep were prepared for implantation of the UmboMic system. Fixation hardware for sheep was designed to secure the UmboMic sensor in position so that the sensing tip contacted the umbo in the middle-ear cavity and the non-sensing tail end was secured to the surrounding mastoid bone. First, pre-surgical micro-CT scans of the temporal bones and open-source software were used to simulate surgical drilling, and to virtually plan and fit the UmboMic fixation system. Then, in physical sheep temporal bones, sound-induced umbo motion was measured with a laser Doppler vibrometer as a preliminary step. After surgical implantation of the UmboMic system, the position of the UmboMic sensor was evaluated with microscopic visualization and post-surgical micro-CT. Implanted UmboMic sensor function in response to acoustic frequency sweeps to the external ear canal was measured in two specimens. Results: Measurements of sheep temporal bone anatomical dimensions with micro-CT showed that the facial recess featured a mean maximum height of 2.36 mm, length of 12.2 mm, and depth from outer opening surface of facial recess to the umbo of 11.1 mm. The amplitude of umbo motion prior to UmboMic implantation was consistent with that previously reported by [2], with a displacement of ~ 14 nm/Pa up to a frequency of 5.5 kHz, followed by a gradual drop-off. When bench tested and implanted in sheep temporal bones, the UmboMic sensitivity was as predicted from [1], ~ 1-2 fC/nm. Conclusion: When implanted in sheep cadaveric ears, UmboMic performance was similar to previous measurements in fresh human cadaveric temporal bones. The method of simulating surgical drilling using micro-CT and simple open-source software is economical and broadly applicable in understanding the 3D biological anatomy and implantable device design and customization. The UmboMic implantation in cadaveric sheep ears was possible, and this study represents a step towards planned live animal studies.

Anxiety disorders are highly prevalent and often refractory to existing treatments, motivating the development of alternative neuromodulatory strategies. Peripheral bioelectronic approaches targeting the gut–brain axis such as vagus nerve stimulation (VNS) demonstrate that modulation of visceral afferent pathways can influence central emotional circuits. Gastric electrical stimulation (GES) is a clinically established therapy for gastrointestinal motility disorders. While the stomach is densely innervated by vagal afferents, the effect of GES on anxiety-related behavior has not been systematically examined. We sought to identify neural pathways engaged by GES and effects of continuous chronic GES on behavior. To do this, we developed a gastric stimulation platform for rodents, a fully implantable, untethered system enabling chronic neuromodulation in freely moving rats. We combined this with cross-species whole-brain activity mapping in mice to interrogate circuit-level mechanisms. Using open field and elevated plus mazes, together with machine-learning-based behavioral tracking and multivariate modeling, we show that acute GES induces a robust, context-dependent anxiogenic phenotype characterized by reduced exploration and increased freezing, particularly in novel open-field environments. In contrast, chronic GES produces a divergent post-stimulation behavioral profile marked by enhanced exploratory behavior relative to acutely stimulated animals, indicating temporally dynamic reorganization of anxiety-related behavior. Principal component analysis and hierarchical clustering further revealed that stimulation reshapes the multivariate structure of behavioral features rather than shifting animals along a single anxiety continuum. Whole-brain c-Fos mapping revealed anatomically distributed modulation of limbic–cortical networks following gastric stimulation, including suppression of ventral medial entorhinal cortex, excitation of nucleus tractus solitarii and heterogeneous recruitment of amygdalar and hippocampal subregions. These circuit-level patterns align with the behavioral dissociation between contextual exploration and explicit threat avoidance, providing convergent cross-species evidence that gastric stimulation engages distributed anxiety-related networks. Together, these findings establish the first freely moving behavioral model of chronic gastric neuromodulation, demonstrate temporally dynamic and context-sensitive effects on anxiety-like behavior, and provide systems-level validation that the stomach can serve as a viable peripheral access point for modulating central emotional circuits.

A hallmark of intelligence is proficiency in solving new problems, including those that substantially differ from previously seen problems. Problem solving in turn depends on the goal-directed generation of novel ideas and behaviours 1 , which has been proposed to involve internal representations of discrete units (or symbols) that can be recombined into numerous possible composite representations 1–7 . Although this view has been influential in cognitive-level explanations of behaviour, definitive evidence for a neuronal substrate of symbols has remained elusive. Here we identify a neural population that encodes action symbols—recombinable representations of discrete units of motor behaviour—in a specific area of the frontal cortex. In macaque monkeys performing a drawing-like task, we found behavioural evidence that action elements (strokes) exhibit three crucial features that indicate an underlying symbolic representation: (1) invariance over low-level motor parameters; (2) categorical structure, which reflects discrete action types; and (3) recombination into novel sequences. Based on simultaneous neural recordings across eight regions of the motor, premotor and prefrontal cortex, we identified population activity specifically in the ventral premotor cortex that encodes planned actions in a manner that also reflects invariance, categorical structure and recombination. These findings reveal a neural representation of action symbols localized to the ventral premotor cortex and a putative neural substrate for symbolic operations.

Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for brain disorders, but its therapeutic mechanism is poorly understood. We developed a mouse model of rTMS with superior clinical face validity and investigated the neural mechanism by which accelerated intermittent theta burst stimulation (aiTBS), the first rapid-acting rTMS antidepressant protocol, reversed chronic stress-induced behavioral deficits. Using fiber photometry, we showed that aiTBS drives distinct patterns of neural activity in intratelencephalic (IT) and pyramidal tract (PT) projection neurons in dorsomedial prefrontal cortex (dmPFC). However, only IT neurons exhibited persistently increased activity during both aiTBS and subsequent depression-related behaviors. aiTBS reversed stress-related loss of dendritic spines on IT, but not PT neurons, further demonstrating cell type-specific effects of stimulation. Chemogenetically inhibiting dmPFC IT, but not PT neurons, during rTMS blocked the antidepressant-like behavioral effects of aiTBS. Thus, we demonstrate a prefrontal mechanism linking rapid aiTBS-driven therapeutic effects to cell type-specific circuit plasticity.

Cochlear implants (CIs) have successfully restored hearing in more than one million patients with severe to profound hearing loss worldwide. Although CIs effectively restore speech perception in quiet environments, sound localization remains challenging for bilateral CI users, particularly their ability to utilize interaural time differences (ITDs). The majority of clinical CI processors use a coding strategy that encodes ITD information only in the envelope of electrical pulse trains rather than their pulse timing, which may contribute to the poorer spatial hearing perception of CI users. We recently demonstrated in a behavioural study on early deafened, bilaterally CI‐implanted rats that pulse timing ITDs completely dominate ITD perception, whereas sensitivity to envelope ITDs is almost negligible in comparison. Building on this, we here investigated the neurophysiological sensitivity of the inferior colliculus (IC) to envelope and pulse timing ITDs at two different pulse rates (900 and 4500 pulses/s) and three different stimulation modulations (5, 20 and 100 Hz) in CI rats with different hearing experiences. Our results indicate that IC neurons exhibit far greater sensitivity to pulse timing ITD than envelope ITD independent of pulse rate, modulation rate or hearing experience. These findings suggest that to improve binaural hearing outcomes in bilateral CI users, clinical stimulation strategies should provide informative pulse timing ITDs. image Key points Current bilateral cochlear implants mostly provide time cues of arriving sound in the envelope of stimulation rather than in the timing of pulses. A behavioural study on cochlear implanted rats has shown that pulse timing dominates binaural hearing. Here we examined the neural sensitivity to independent changes in time cues presented on the envelope or pulse timing, respectively, in rats with bilateral cochlear implants and different hearing experiences. Auditory midbrain neurons were consistently more sensitive to changes in pulse timing rather than envelope, irrespective of stimulus pulse rate, modulation rate or an animal's hearing experience.

Background Transcranial electrical stimulation (TES) has limited spatial focus and depth penetration, constraining its therapeutic efficacy. Intersectional Short-Pulse (ISP) stimulation was developed to overcome these limitations by delivering rapidly switching pulses that can be temporally integrated by neuronal membranes. Here, we aimed to establish the biophysical basis of ISP-induced temporal summation and to test whether this mechanism enables effective brain modulation in vivo. Methods We combined finite-element modeling, cadaver measurements ( n = 2 human cadavers), and biophysically realistic NEURON simulations to characterize the spatial and temporal properties of ISP-induced electric fields. In vivo whole-cell patch-clamp recordings were performed in the rat somatosensory cortex (female Wistar rat) to test the membrane-level integration of sequential electric field pulses. Functional efficacy was evaluated using closed-loop ISP stimulation in a hippocampal kindling model of temporal lobe epilepsy in male Long–Evans rats ( n = 11 animals, >500 induced seizures analyzed across conditions). Results Here we show that neurons integrate sequential ISP pulses in a non-vectorial, temporally accumulative manner, consistent with membrane-level charge integration rather than extracellular field superposition. ISP and conventional TES simulations produced similar instantaneous field magnitudes, but ISP stimulation resulted in more uniform neuronal excitability across brain depths. Closed-loop ISP stimulation significantly outperformed conventional TES in reducing seizure duration and severity. ISP reduced hippocampal seizure duration by 45% and 35% compared to SHAM stimulation and conventional TES, and significantly reduced motor seizure severity. Conclusions ISP stimulation provides a non-invasive neuromodulation approach that enhances deep brain engagement through rapid, temporally structured pulse sequences. These findings demonstrate effective seizure suppression in a rodent model and support the translational potential of ISP for disorders involving pathological neural dynamics.

Many neurological and psychiatric disorders stem from maladaptive conditioning and resist treatment. Tinnitus, as one example, is the distressing perception of sound in the absence of an external source. One of the network systems implicated in multiple disorders is the 'salience network', associated with positive/negative reward, habit formation, motivation, valuation and mood. However, it is not known whether directly modulating the 'salience network' at its anatomical and physiological core, in the ventral striatum, more specifically the nucleus accumbens, could be beneficial. Here we show that a novel treatment approach, targeting the salience network, can reduce tinnitus perception in a rat model. We found that bilateral rewarding stimulation of the nucleus accumbens, when paired with non-tinnitus tones, was most effective. A combined approach using rewarding accumbens stimulation and dysrewarding lateral habenula stimulation - paired with non-tinnitus and tinnitus tones, respectively - also suppressed tinnitus but caused negative effects. Our results demonstrate how the rewarding stimulation can recondition brain networks to effectively remove the salience of tinnitus frequencies. We anticipate that our unique reconditioning strategy has broader therapeutic applications for other brain disorders rooted in maladaptive learning.

Magnetogenetic deep brain stimulation (MG‐DBS) represents a wireless neuromodulation that has demonstrated long‐lasting behavioral benefits in Parkinson's disease models. However, the circuit‐level mechanisms underlying these therapeutic effects have remained uncharacterized due to limitations of conventional neural interfaces. We present a bio‐integrable soft neural interface featuring ultrasoft liquid‐metal probes with bioresorbable stiffeners and customizable interconnects directly printed onto cranial surfaces to match individual skull anatomy and nanoparticle injection sites. This platform enables stable multi‐regional recordings from deep brain structures without chronic tissue damage. We systematically investigate MG‐DBS therapeutic mechanisms in a Parkinson's disease mouse model. Circuit‐level analysis reveals that MG‐DBS modulates pathological beta‐band oscillations and inter‐regional synchrony across the cortico‐basal ganglia‐thalamic circuit. Direct comparison with conventional electrical DBS demonstrates that MG‐DBS effects persisted approximately fifteen‐fold longer after stimulation cessation. Our electrophysiological recordings elucidate the mechanistic basis for this sustained therapeutic effect, providing unprecedented insights into magnetogenetic neuromodulation dynamics.

Human vision relies on photoreceptor cells in the outer retina that are sensitive to visible light. However, many people suffer from blindness due to retinal diseases that cause photoreceptor degeneration. Electrical stimulation of retinal neurons can recreate the action potentials associated with seeing that are generated by these cells. Here we report a thin artificial retina that can be adhered to the epiretinal surface and can convert near-infrared (NIR) light into electrical stimuli that selectively stimulate ganglion cells. The artificial retina consists of a NIR-sensitive phototransistor array and three-dimensional liquid metal micropillar electrodes. The liquid metal electrodes enhance proximity to retinal ganglion cells, providing effective charge injection while minimizing tissue damage, owing to their low Young’s modulus. Ex vivo studies demonstrate its biocompatibility, and in vivo studies using healthy and blind mice demonstrate perception of both visible and NIR light, as indicated by cortical recordings and behavioural tests. The retina could, in the future, be used to create a NIR visual channel in patients with photoreceptor degenerative blindness without interfering with their remaining natural vision.

Implantable biohybrid systems with computer-controlled actuation offer the capacity to modulate biological forces, but require biocompatible, self-sustaining, and scalable actuators. Engineering biological muscles can fulfill this need. However, muscle fatigue limits the fundamental capabilities of muscle-actuated systems. Here we present a fatigue-resistant myoneural actuator (MNA) with engineered recruitment biophysics in a rodent model. The MNA is based on manipulating native axonal composition through sensory reinnervation. This regenerative approach establishes functional neuromuscular junctions and redirects volitional control to computer control via nerve stimulation while maintaining self-sustainability. Compared to native muscles without the myoneural manipulation, fatigue resistance is augmented by 260%. Furthermore, we demonstrate closed-loop control with reversible neural isolation of the actuator, preventing unintended neural signaling to the central nervous system during operation. To illustrate the potential of the MNA technology, we present a biohybrid neuroprosthetic interface and a biohybrid organ system capable of modulating neural afferents and organ mechanics, respectively. Our framework demonstrates augmented biological muscle actuation while maintaining inherent tissue properties, bridging the technological gap for implantable biohybrid systems.

Neural interfaces for monitoring and modulating spinal nerve activity are increasingly being designed to be flexible and stretchable to enhance their biomechanical compatibility and integration. However, excessive flexibility introduces practical limitations such as difficulty in insertion into narrow spinal spaces and long-term electrical instability, hindering real-world applications. In this study, we developed a spinal nerve interface by incorporating a liquid-metal conductor and dynamic stiffness-based variable-compliance structure, which can address the challenges of current flexible neural interface technologies. During insertion, the dynamic stiffness enhancer minimizes unintended buckling and ensures minimally invasive implantation into the intended target. The proximity of the proposed device to the spinal cord increases as it flexes automatically and rapidly in a humid environment. The liquid-metal conductor maintained stable electrical properties in freely moving rats, ensuring reliable and sustained functionality. This study lays the foundation for practical, fully implantable spinal bioelectronics designed with a focus on ease of implantation and long-term functionality.

Background: In Parkinson's disease, motor network electrophysiology frequently exhibits excessive beta oscillations. The cornerstone of therapeutic efficacy lies in the ability to modulate these pathological oscillations. Transcranial alternating current stimulation (tACS), a non-invasive method that applies oscillating electric fields to modulate ongoing brain activity, offers a promising approach. Objective: The objective of the manuscript is to investigate the dose-dependent effects of tACS on motor network cortical neurons in a Parkinson's disease model. Methods: We recorded neuronal spike activity in the motor cortex in parkinsonian non-human primates during tACS to determine how stimulation-induced electric fields affect spike timing. Results: Strong electric fields entrained neural activity at the stimulation frequency but altered the preferred spiking phase. Conversely, weak fields disrupted beta-band synchronization by modulating spike timing and phase preference. Frequency-matched stimulation significantly enhanced entrainment when aligned with endogenous oscillatory activity. Conclusion: Thus, with appropriately chosen stimulation parameters, tACS exhibits significant potential for controlling and modulating pathological oscillatory patterns that are characteristic of many neurological disorders.

Stimulation of sensory vagal pathways is typically delivered via invasive, cervical vagus nerve stimulation (cVNS) or noninvasive, trans-auricular nerve stimulation (taNS). While both methods are investigated therapeutically, their effects on brain physiology remain poorly understood, hindering mechanistic insights and stimulus optimization. In 6 awake nonhuman primates, we recorded cortical vagal-evoked potentials (VEPs) from subdural electrodes placed in prefrontal, sensorimotor and parietal cortical areas, in response to cVNS or taNS. Across 478 different taNS and cVNS protocols, we varied stimulation side, intensity, frequency, pulse count, and pulse width and assessed independent effects on amplitude and latency of early (EC; 30-100 ms), intermediate (IC; 101-200 ms) and late components (LC; 201-500 ms) of VEPs. Fixed and random effects of stimulation parameters and subjects, respectively, on VEPs were assessed using a linear mixed-effects model. Overall, cVNS elicits more robust VEPs than taNS, with larger EC, IC and LC amplitudes, in both hemispheres. cVNS-elicited ECs and LCs are largest in PFC and PC areas, whereas ICs are largest in SM areas. On the other hand, taNS generally does not elicit area-specific responses. cVNS-elicited ECs have slower latency than ta-NS elicited ECs. Higher stimulation frequencies and intensities and a longer pulse width elicit larger ECs and ICs for cVNS, and to some extent for taNS. Both short and long cVNS trains elicit stronger ECs, and long trains elicit slower ICs. Earlobe stimulation elicits VEPs that partially overlap with those from taNS. In conclusion, cVNS and taNS elicit cortical VEPs in a manner consistent with distinct engagement of ascending vagal pathways, with both similarities and differences in the effects of stimulation parameters on evoked responses.