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

Abstract

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.

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

“…(E) Enhanced feature selectivity of VPm neurons during VNS results in a significant increase in amount of the sensory-related information transmitted per spike. Adopted from Rodenkirch and Wang (2020) .…”

“…Therefore, our team next investigated whether tonic VNS would drive similar rapid beneficial effects on sensory processing. Through testing the effects of multiple patterns of VNS on sensory processing, the beneficial effect was found to be highly transient (i.e., benefit begins to dissipate within seconds of ceasing VNS) ( Rodenkirch and Wang, 2020 ). For example, duty-cycled VNS (30 s on/60 s off duty cycle, 30 Hz, 500 μs biphasic pulses) enhanced tactile sensory processing during the on cycle, but this enhancement rapidly dissipated during the off cycle, suggesting that cycling VNS on and off creates fluctuations in sensory processing that would likely be sub-optimal for discrimination.…”

The Neuromodulatory Role of the Noradrenergic and Cholinergic Systems and Their Interplay in Cognitive Functions: A Focused Review

“…More recent work, however, has also highlighted the role of ACh in attentional effort, orienting, and the detection of behaviorally significant stimuli [ 17 , 18 ]. Norepinephrine (NE) has classically been viewed as a major mediator of arousal that plays an important role in regulating the efficiency of external sensory processing [ 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. Recent work expanding on this has revealed a varied and complex role for the noradrenergic system in everything from memory formation [ 26 ] to executive function and attention [ 27 , 28 ], to cognitive flexibility [ 29 , 30 ], and to decision-making [ 31 , 32 , 33 ].…”

The clinical effect of vagus nerve stimulation in the treatment of patients with a minimally conscious state

“…VNS can influence important components of the limbic system via the anatomical projection pathways, such as the amygdala, hippocampus, thalamus, hypothalamus, and neocortex via recruiting monoaminergic signalings, which include glutamate (Glu), serotonin (5-HT), dopamine (DA), and norepinephrine (NE) [34]. VNS can also directly lead to the rapid and transient enhancement of the thalamic information transmission [35] and the activation of brain regions which covers more than 76% of the brain volume [36]. Thus, VNS-activated brain regions were involved in the dominant corticothalamic circuits in which the disconnections in the cortico-cortical and thalamo-cortical pathways mediated the neural mechanisms of the impaired consciousness [4,21].…”