Manipulation of stimulus waveform and frequency permits targeted fiber activation during vagus nerve stimulation in 2 rodent species

Cervical vagus nerve stimulation (VNS) provides relatively minimally-invasive access to vagal fiber populations innervating most visceral organs, making it an attractive therapy candidate for various diseases. To maximize desired and minimize off-target effects, VNS should be delivered in a fiber-selective manner. We sought to select and optimize parameters that preferentially activate large, intermediate or small-size vagal fibers in 2 animal species, rats and mice. We manipulated stimulus waveform and frequency of short-duration (10-s) stimulus trains (SSTs) at different intensities and measured fiber-specific stimulus-elicited compound action potentials, corresponding cardiorespiratory vagally-mediated responses and neuronal expression of c-FOS in sensory and motor brainstem nuclei. We compiled selectivity indices from those measurements to determine optimal parameters for each fiber type. Large- and intermediate-size fibers are activated by SSTs of 30 Hz frequency, using short-square and long-square or quasi-trapezoidal pulses, respectively, at different optimal intensities for different animals. Small-size fibers are activated by SSTs of frequencies >8KH at high stimulus intensities; using a computational model of vagal fibers we find that sodium channels may underlie this effect. All findings were consistent between rats and mice. Our study provides a robust design and optimization framework for targeting vagal fiber populations for improved safety and efficacy of VNS therapies.

Catalytic resonance theory: superVolcanoes, catalytic molecular pumps, and oscillatory steady state

Catalytic reactions on surfaces with forced oscillations in physical or electronic properties undergo controlled acceleration consistent with the selected parameters of frequency, amplitude, and external stimulus waveform.

Neural Transformation of Dissonant Intervals in the Auditory Brainstem

Acoustic periodicity is an important factor for discriminating consonant and dissonant intervals. While previous studies have found that the periodicity of musical intervals is temporally encoded by neural phase locking throughout the auditory system, how the nonlinearities of the auditory pathway influence the encoding of periodicity and how this effect is related to sensory consonance has been underexplored. By measuring human auditory brainstem responses (ABRs) to four diotically presented musical intervals with increasing degrees of dissonance, this study seeks to explicate how the subcortical auditory system transforms the neural representation of acoustic periodicity for consonant versus dissonant intervals. ABRs faithfully reflect neural activity in the brainstem synchronized to the stimulus while also capturing nonlinear aspects of auditory processing. Results show that for the most dissonant interval, which has a less periodic stimulus waveform than the most consonant interval, the aperiodicity of the stimulus is intensified in the subcortical response. The decreased periodicity of dissonant intervals is related to a larger number of nonlinearities (i.e., distortion products) in the response spectrum. Our findings suggest that the auditory system transforms the periodicity of dissonant intervals resulting in consonant and dissonant intervals becoming more distinct in the neural code than if they were to be processed by a linear auditory system.