Neural Readout of a Latency Code in the Active Electrosensory System

The latency of spikes relative to a stimulus conveys sensory information across modalities. However, in most cases it remains unclear whether and how such latency codes are utilized by postsynaptic neurons. In the active electrosensory system of mormyrid fish, a latency code for stimulus amplitude in electroreceptor afferent nerve fibers (EAs) is hypothesized to be read out by a central reference provided by motor corollary discharge (CD). Here we demonstrate that CD enhances sensory responses in postsynaptic granular cells of the electrosensory lobe, but is not required for reading out EA input. Instead, diverse latency and spike count tuning across the EA population gives rise to graded information about stimulus amplitude that can be read out by standard integration of converging excitatory synaptic inputs. Inhibitory control over the temporal window of integration renders two granular cell subclasses differentially sensitive to information derived from relative spike latency versus spike count.

Block Phenomena During Electric Micro-Stimulation of Pyramidal Cells and Retinal Ganglion Cells

Electric micro-stimulation of the nervous system is a means to restore various body functions. The stimulus amplitude necessary to generate action potentials, the lower threshold (LT), is well characterized for many neuronal populations. However, electric overstimulation above an upper threshold (UT) prevents action potential generation and therefore hinders optimal neuro-rehabilitation. Previous studies demonstrated the impact of the UT in micro-stimulation of retinal ganglion cells (RGCs). The observed phenomenon is mostly explained by (i) reversed sodium ion flow in the soma membrane, and (ii) anodal surround block that hinders spike conduction in strongly hyperpolarized regions of the axon at high stimulus intensities. However, up to now, no detailed study of the nature of these phenomena has been presented, particularly for different cell types. Here, we present computational analyses of LT and UT for layer 5 pyramidal cells (PCs) as well as alpha RGCs. Model neurons were stimulated in close vicinity to the cell body and LTs and UTs as well as the ratio UT/LT were compared. Aside from a simple point source electrode and monophasic stimuli also realistic electrode and pulse configurations were examined. The analysis showed: (i) in RGCs, the soma contributed to action potential initiation and block for small electrode distances, whereas in PCs the soma played no role in LTs or UTs. (ii) In both cell types, action potential always initiated within the axon initial segment at LT. (iii) In contrast to a complete block of spike conductance at UT that occurred in RGCs, an incomplete block of spiking appeared in PC axon collaterals. (iv) PC axon collateral arrangement influenced UTs but had small impact on LTs. (v) Population responses of RGCs change from circular regions of activation to ring-shaped patterns for increasing stimulus amplitude. A better understanding of the stimulation window that can reliably activate target neurons will benefit the future development of neuroprostheses.

Predicting thickness perception of liquid food products from their non-Newtonian rheology

The “mouthfeel” of food products is a key factor in our perception of food quality and in our appreciation of food products. Extensive research has been performed on what determines mouthfeel, and how it can be linked to laboratory measurements and eventually predicted. This was mainly done on the basis of simple models that do not accurately take the rheology of the food products into account. Here, we show that the subjectively perceived “thickness” of liquid foods, or the force needed to make the sample flow or deform in the mouth, can be directly related to their non-Newtonian rheology. Measuring the shear-thinning rheology and modeling the squeeze flow between the tongue and the palate in the oral cavity allows to predict how a panel perceives soup “thickness”. This is done for various liquid bouillons with viscosities ranging from that of water to low-viscous soups and for high-viscous xanthan gum solutions. Our findings show that our tongues, just like our eyes and ears, are logarithmic measuring instruments in agreement with the Weber-Fechner law that predicts a logarithmic relation between stimulus amplitude and perceived strength. Our results pave the way for more accurate prediction of mouthfeel characteristics of liquid food products.

Treatment Tone Spacing and Acute Effects of Acoustic Coordinated Reset Stimulation in Tinnitus Patients

Acoustic coordinated reset (aCR) therapy for tinnitus aims to desynchronize neuronal populations in the auditory cortex that exhibit pathologically increased coincident firing. The original therapeutic paradigm involves fixed spacing of four low-intensity tones centered around the frequency of a tone matching the tinnitus pitch, fT, but it is unknown whether these tones are optimally spaced for induction of desynchronization. Computational and animal studies suggest that stimulus amplitude, and relatedly, spatial stimulation profiles, of coordinated reset pulses can have a major impact on the degree of desynchronization achievable. In this study, we transform the tone spacing of aCR into a scale that takes into account the frequency selectivity of the auditory system at each therapeutic tone’s center frequency via a measure called the gap index. Higher gap indices are indicative of more loosely spaced aCR tones. The gap index was found to be a significant predictor of symptomatic improvement, with larger gap indices, i.e., more loosely spaced aCR tones, resulting in reduction of tinnitus loudness and annoyance scores in the acute stimulation setting. A notable limitation of this study is the intimate relationship of hearing impairment with the gap index. Particularly, the shape of the audiogram in the vicinity of the tinnitus frequency can have a major impact on tone spacing. However, based on our findings we suggest hypotheses-based experimental protocols that may help to disentangle the impact of hearing loss and tone spacing on clinical outcome, to assess the electrophysiologic correlates of clinical improvement, and to elucidate the effects following chronic rather than acute stimulation.

Perception of microstimulation frequency in human somatosensory cortex

Microstimulation in the somatosensory cortex can evoke artificial tactile percepts and can be incorporated into bidirectional brain-computer interfaces (BCIs) to restore function after injury or disease. However, little is known about how stimulation parameters themselves affect perception. Here, we stimulated through microelectrode arrays implanted in the somatosensory cortex of two human participants with cervical spinal cord injury and varied the stimulus amplitude, frequency and train duration. Increasing the amplitude and train duration increased the perceived intensity on all tested electrodes. Surprisingly, we found that increasing the frequency evoked more intense percepts on some electrodes but evoked less intense percepts on other electrodes. These different frequency-intensity relationships were divided into three groups which also evoked distinct percept qualities at different stimulus frequencies. Neighboring electrode sites were more likely to belong to the same group. These results support the idea that stimulation frequency directly controls tactile perception and that these different percepts may be related to the organization of somatosensory cortex, which will facilitate principled development of stimulation strategies for bidirectional BCIs.

A Computational Model of Phosphene Appearance for Epiretinal Prostheses

Retinal neuroprostheses are the only FDA-approved treatment option for blinding degenerative diseases. A major outstanding challenge is to develop a computational model that can accurately predict the elicited visual percepts (phosphenes) across a wide range of electrical stimuli. Here we present a phenomenological model that predicts phosphene appearance as a function of stimulus amplitude, frequency, and pulse duration. The model uses a simulated map of nerve fiber bundles in the retina to produce phosphenes with accurate brightness, size, orientation, and elongation. We validate the model on psychophysical data from two independent studies, showing that it generalizes well to new data, even with different stimuli and on different electrodes. Whereas previous models focused on either spatial or temporal aspects of the elicited phosphenes in isolation, we describe a more comprehensive approach that is able to account for many reported visual effects. The model is designed to be flexible and extensible, and can be fit to data from a specific user. Overall this work is an important first step towards predicting visual outcomes in retinal prosthesis users across a wide range of stimuli.

Sensory restoration by epidural stimulation of the lateral spinal cord in upper-limb amputees

Restoring somatosensory feedback to people with limb amputations is crucial to improve prosthetic control. Multiple studies have demonstrated that peripheral nerve stimulation and targeted reinnervation can provide somatotopically relevant sensory feedback. While effective, the surgical procedures required for these techniques remain a major barrier to translatability. Here, we demonstrate in four people with upper-limb amputation that epidural spinal cord stimulation (SCS), a common clinical technique to treat pain, evoked somatosensory percepts that were perceived as emanating from the missing arm and hand. Over up to 29 days, stimulation evoked sensory percepts in consistent locations in the missing hand regardless of time since amputation or level of amputation. Evoked sensations were occasionally described as naturalistic (e.g. touch or pressure), but were often paresthesias. Increasing stimulus amplitude increased the perceived intensity linearly, without increasing area of the sensations. These results demonstrate the potential of SCS as a tool to restore somatosensation after amputations.

Perceptual responses to microstimulation frequency are spatially organized in human somatosensory cortex

SummaryMicrostimulation in the somatosensory cortex can evoke artificial tactile percepts and can be incorporated into bidirectional brain-computer interfaces (BCIs) to restore function after injury or disease. However, little is known about how stimulation parameters themselves affect perception. Here, we stimulated through microelectrode arrays implanted in the somatosensory cortex of a human participant with a cervical spinal cord injury and varied the stimulus amplitude, duration, and frequency. Increasing the amplitude and duration increased the perceived intensity on all tested electrodes. Surprisingly, we found that increasing the frequency evoked more intense percepts on some electrodes but evoked less intense percepts on most electrodes. Electrodes divided into three groups which evoked distinct perceptual qualities that depended on the stimulus frequency and were spatially organized in cortex. These results contribute to our growing understanding of the structure and function of the somatosensory cortex and will facilitate principled development of stimulation strategies for bidirectional BCIs.