Transcutaneous cervical vagus nerve stimulation improves sensory performance in humans: a randomized controlled crossover pilot study.

Accurate senses depend on high-fidelity encoding by sensory receptors and error-free processing in the brain. Progress has been made towards restoring damaged sensory receptors. However, methods for on-demand treatment of impaired central sensory processing are scarce. Prior invasive studies demonstrated that continuous vagus nerve stimulation (VNS) in rodents can activate the locus coeruleus-norepinephrine system to rapidly improve central sensory processing. Here, we investigated whether transcutaneous VNS improves sensory performance in humans. We conducted three sham-controlled experiments, each with 12 neurotypical adults, that measured the effects of transcutaneous VNS on metrics of auditory and visual performance, and heart rate variability (HRV). Continuous stimulation was delivered to cervical (tcVNS) or auricular (taVNS) branches of the vagus nerve while participants performed psychophysics tasks or passively viewed a display. Relative to sham stimulation, tcVNS improved auditory performance by 37% (p = 0.00052) and visual performance by 23% (p = 0.038). Participants with lower performance during sham conditions experienced larger tcVNS-evoked improvements (p = 0.0040). Lastly, tcVNS increased HRV during passive viewing, corroborating vagal engagement. No evidence for an effect of taVNS was observed. These findings validate the effectiveness of tcVNS in humans and position it as a method for on-demand interventions of impairments associated with central sensory processing dysfunction.

Rapid and transient enhancement of thalamic information transmission induced by vagus nerve stimulation.

OBJECTIVE: Vagus nerve stimulation (VNS) has been FDA-approved as a long-term, therapeutic treatment for multiple disorders, including pharmacoresistant epilepsy and depression. Here we elucidate the short-term effects of VNS on sensory processing. APPROACH: We employed an information theoretic approach to examine the effects of VNS on thalamocortical transmission of sensory-related information along the somatosensory pathway. MAIN RESULTS: We found that VNS enhanced the selectivity of the response of thalamic neurons to specific kinetic features in the stimuli, resulting in a significant increase in the efficiency and rate of stimulus-related information conveyed by thalamic spikes. VNS-induced improvements in thalamic sensory processing coincided with a decrease in thalamic burst firing. Importantly, we found VNS-induced enhancement of sensory processing had a rapid onset and offset, completely disappearing one minute after cessation of VNS. The timescales of these effects indicate against an underlying mechanism involving long-term neuroplasticity. We found several patterns of VNS (tonic, standard duty-cycle, and fast duty-cycle) all induced similar improvements in sensory processing. Under closer inspection we noticed that due to the fast timescale of VNS effects on sensory processing, standard duty-cycle VNS induced a fluctuating sensory processing state which may be sub-optimal for perceptual behavior. Fast duty-cycle VNS and continuous, tonic VNS induced quantitatively similar improvements in thalamic information transmission as standard duty-cycle VNS without inducing a fluctuating thalamic state. Further, we found the strength of VNS-induced improvements in sensory processing increased monotonically with amplitude and frequency of VNS. SIGNIFICANCE: These results demonstrate, for the first time, the feasibility of utilizing specific patterns of VNS to rapidly improve sensory processing and confirm fast duty-cycle and tonic patterns as optimal for this purpose, while showing standard duty-cycle VNS causes non-optimal fluctuations in thalamic state.

Locus coeruleus activation enhances thalamic feature selectivity via norepinephrine regulation of intrathalamic circuit dynamics.

We investigated locus coeruleus (LC) modulation of thalamic feature selectivity through reverse correlation analysis of single-unit recordings from different stages of the rat vibrissa pathway. LC activation increased feature selectivity, drastically improving thalamic information transmission. We found that this improvement was dependent on both local activation of α-adrenergic receptors and modulation of T-type calcium channels in the thalamus and was not due to LC modulation of trigeminothalamic feedforward or corticothalamic feedback inputs. Tonic spikes with LC stimulation carried three times the information as did tonic spikes without LC stimulation. Modeling confirmed norepinephrine regulation of intrathalamic circuit dynamics led to the improved information transmission. Behavioral data demonstrated that LC activation increased the perceptual performance of animals performing tactile discrimination tasks through LC-norepinephrine optimization of thalamic sensory processing. These results suggest a new subdimension within the tonic mode in which brain state can optimize thalamic sensory processing through modulation of intrathalamic circuit dynamics.