Short-Term Effects of Vagus Nerve Stimulation on Learning and Evoked Activity in Auditory Cortex

Abstract

Chronic vagus nerve stimulation (VNS) has been shown to facilitate learning, but effects of acute VNS on neural coding and behavior remain less well understood. Ferrets implanted with cuff electrodes on the vagus nerve were trained by classical conditioning on an auditory tone frequency-reward association. One tone was associated with reward while another tone was not. Tone frequencies and reward associations were changed every 2 days, requiring learning of a new relationship. When tones were paired with VNS, animals consistently learned the new association within 2 days. When VNS occurred randomly between trials, learning within 2 days was unreliable. In passively listening animals, neural activity in primary auditory cortex and pupil size were recorded before and after acute VNS-tone pairing.After pairing with a neuron's best-frequency (BF) tone, responses by a subpopulation of neurons were reduced. VNS paired with an off-BF tone or during inter-trial intervals had no effect. The BF-specific reduction in neural responses after VNS remained, even after regressing out changes explained by pupil-indexed arousal. VNS induced brief dilation in the pupil, and the size of this change predicted the magnitude of persistent changes in the neural response. This interaction suggests that fluctuations in neuromodulation associated with arousal gate the long-term VNS effects on neural activity.

Vagus nerve stimulation drives selective circuit modulation through cholinergic reinforcement

“…This makes it difficult to disentangle direct VNS effects from changes in arousal. In contrast, another recent work demonstrated a VNSdriven suppression of neural response to an auditory tone that persisted even after arousal state was regressed from the neural response (Lai and David, 2021). Our trial design controls for movement state, and VNS did not produce any noticeable acute motor response.…”

Rapid Effects of Vagus Nerve Stimulation on Sensory Processing Through Activation of Neuromodulatory Systems

“…In general, these studies have delivered phasic VNS (e.g., 0.5 s, 30 Hz, 0.8 mA, 100 μs biphasic pulses) in pair with a specific sensory stimulus (e.g., a specific frequency auditory tone or tactile tap) repeatedly across multiple sessions (e.g., 300 times/day, 20 days). This alters sensory processing in a manner that facilitates detection of the specific paired stimulus ( Martinez-Vargas et al, 2009 ; Engineer et al, 2011 ; Meyers et al, 2019 ; Darrow et al, 2020 ; Lai and David, 2021 ) and accordingly disfavors detection of non-paired stimuli. This mechanism of action can be strengthened over multiple sessions of pairing to produce long-term permanent reorganization of sensory pathways that alters perception.…”

Cerebral cortex and hippocampus neural interaction during vagus nerve stimulation under in vivo large-scale imaging

“…So, there was no significant difference in neuronal activities between during VNS and pre-VNS baseline. Furthermore, the effects of VNS modulation varied among different parameters, and enhancement of performance of behavior tasks and cortical map plasticity was strongest in response to intermediate intensity of stimulation (Ghacibeh et al, 2006;Lai and David, 2021). Therefore, we concluded that there might be an individual difference in the effects of VNS modulation, and the optimal parameters were crucial to VNS application.…”