Effects of stimulus pulse rate on somatosensory adaptation in the human cortex

BackgroundIntracortical microstimulation (ICMS) of the somatosensory cortex can restore sensation to people with neurological diseases. However, many aspects of ICMS are poorly understood, including the effect of continuous stimulation on percept intensity over time.ObjectiveHere, we evaluate how tactile percepts, evoked by ICMS in the somatosensory cortex of a human participant adapt over time.MethodsWe delivered continuous and intermittent ICMS to the somatosensory cortex and assessed the reported intensity of tactile percepts over time in a human participant. Experiments were conducted across approximately one year and linear mixed effects models were used to assess significance.ResultsContinuous stimulation at high frequencies led to rapid decreases in intensity, while low frequency stimulation maintained percept intensity for longer periods. Burst-modulated stimulation extended the time before the intensity began to decrease, but all protocols ultimately resulted in complete sensation loss within one minute. Intermittent stimulation paradigms with several seconds between stimulus trains also led to decreases in intensity on many electrodes, but never resulted in extinction of sensation after over three minutes of stimulation. Additionally, longer breaks between each pulse train resulted in some recovery of the stimulus-evoked percepts. For several electrodes, intermittent stimulation had almost no effect on the perceived intensity.ConclusionsIntermittent ICMS paradigms were more effective at maintaining percepts, and given that transient activity in the somatosensory cortex dominates the response to object contact, this stimulation method may mimic natural cortical activity and improve the perception of stimulation over time.

Effects of Mechanosensory Input on the Tracking of Pulsatile Odor Stimuli by Moth Antennal Lobe Neurons

Air turbulence ensures that in a natural environment insects tend to encounter odor stimuli in a pulsatile fashion. The frequency and duration of odor pulses varies with distance from the source, and hence successful mid-flight odor tracking requires resolution of spatiotemporal pulse dynamics. This requires both olfactory and mechanosensory input (from wind speed), a form of sensory integration observed within the antennal lobe (AL). In this work, we employ a model of the moth AL to study the effect of mechanosensory input on AL responses to pulsatile stimuli; in particular, we examine the ability of model neurons to: (1) encode the temporal length of a stimulus pulse; (2) resolve the temporal dynamics of a high frequency train of brief stimulus pulses. We find that AL glomeruli receiving olfactory input are adept at encoding the temporal length of a stimulus pulse but less effective at tracking the temporal dynamics of a pulse train, while glomeruli receiving mechanosensory input but little olfactory input can efficiently track the temporal dynamics of high frequency pulse delivery but poorly encode the duration of an individual pulse. Furthermore, we show that stronger intrinsic small-conductance calcium-dependent potassium (SK) currents tend to skew cells toward being better trackers of pulse frequency, while weaker SK currents tend to entail better encoding of the temporal length of individual pulses. We speculate a possible functional division of labor within the AL, wherein, for a particular odor, glomeruli receiving strong olfactory input exhibit prolonged spiking responses that facilitate detailed discrimination of odor features, while glomeruli receiving mechanosensory input (but little olfactory input) serve to resolve the temporal dynamics of brief, pulsatile odor encounters. Finally, we discuss how this hypothesis extends to explaining the functional significance of intraglomerular variability in observed phase II response patterns of AL neurons.

Design of an FPGA-Based Fuzzy Feedback Controller for Closed-Loop FES in Knee Joint Model

Functional electrical stimulation (FES) device has been widely used by spinal cord injury (SCI) patients in their rehab exercises to restore motor function to their paralysed muscles. The major challenge of muscle contraction induced by FES is early muscle fatigue due to the open-loop stimulation strategy. To reduce the early muscle fatigue phenomenon, a closed-loop FES system is proposed to track the angle of the limb’s movement and provide an accurate amount of charge according to the desired reference angle. Among the existing feedback controllers, fuzzy logic controller (FLC) has been found to exhibit good control performance in handling complex non-linear systems without developing any complex mathematical model. Recently, there has been considerable interest in the implementation of FLC in hardware embedded systems. Therefore, in this paper, a digital fuzzy feedback controller (FFC) embedded in a field-programmable gate array (FPGA) board was proposed. The digital FFC mainly consists of an analog-to-digital converter (ADC) Data Acquisition and FLC sub-modules. The FFC was designed to monitor and control the progress of knee extension movement by regulating the stimulus pulse width duration to meet the target angle. The knee is expected to extend to a maximum reference angle setting (70°, 40° or 30°) from its normal position of 0° once the stimulus charge is applied to the muscle by the FES device. Initially, the FLC was modelled using MATLAB Simulink. Then, the FLC was hardcoded into digital logic using hardware description language (HDL) Verilog codes. Thereafter, the performance of the digital FLC was tested with a knee extension model using the HDL co-simulation technique in MATLAB Simulink. Finally, for real-time verification, the designed digital FFC was downloaded to the Intel FPGA (DE2-115) board. The digital FFC utilized only 4% of the total FPGA (Cyclone IV E) logic elements (LEs) and required 238 µs to regulate stimulus pulse width data, including 3 µs for the FLC computation. The high processing speed of the digital FFC enables the stimulus pulse width duration to be updated every stimulation cycle. Furthermore, the implemented digital FFC has demonstrated good control performance in accurately controlling the stimulus pulse width duration to reach the desired reference angle with very small overshoot (1.4°) and steady-state error (0.4°). These promising results are very useful for a real-world closed-loop FES application.

Sustained Long-Term Outcomes With Closed-Loop Spinal Cord Stimulation: 12-Month Results of the Prospective, Multicenter, Open-Label Avalon Study

BACKGROUND Spinal cord stimulation (SCS) activates the dorsal column fibers using electrical stimuli. Current SCS systems function in fixed-output mode, delivering the same stimulus regardless of spinal cord (SC) activation. OBJECTIVE To present long-term outcomes of a novel closed-loop SCS system that aims to maintain the SC activation near a set target level and within a therapeutic window for each patient. SC activation is measured through the evoked compound action potential (ECAP) generated by each stimulus pulse. METHODS Fifty patients with lower back and/or leg pain who were successfully trialed received a permanent system (Evoke; Saluda Medical, Sydney, Australia). Ratings of pain (visual analog scale), quality of life, function, sleep, and medication use were collected at baseline and at each visit. SC activation levels were reported in summary statistics. The therapeutic window for each individual patient was defined as the range of ECAP amplitudes between sensation threshold and uncomfortably strong stimulation. RESULTS At 12 mo, the proportion of patients with ≥50% relief was 76.9% (back), 79.3% (leg), and 81.4% (overall), and the proportion with ≥80% pain relief was 56.4% (back), 58.6% (leg), and 53.5% (overall). Patients spent a median of 84.9% of their time with stimulation in their therapeutic window, and 68.8% (22/32) eliminated or reduced their opioid intake. Statistically significant improvements in secondary outcomes were observed. CONCLUSION The majority of patients experienced more than 80% pain relief with stable SC activation, as measured by ECAP amplitude at 12 mo, providing evidence for the long-term effectiveness of the Evoke closed-loop SCS system.

Synthetic cassettes for pH-mediated sensing, counting and containment

As pH is fundamental to all biological processes, pH-responsive bacterial genetic circuits enable precise sensing in any environment. Where unintentional release of engineered bacteria poses a concern, coupling pH sensing to expression of a toxin creates an effective bacterial containment system. Here, we present a pH-sensitive kill switch (acidic Termination of Replicating Population; acidTRP), based on the E. coli asr promoter, with a survival ratio of less than 1 in 106. We integrate acidTRP with cryodeath to produce a two-factor containment system with a combined survival ratio of less than 1 in 1011 whilst maintaining evolutionary stability. We further develop a pulse-counting circuit with single cell readout for each administered stimulus pulse. We use this pulse-counter to record multiple pH changes and combine it with acidTRP to make a two-count acid-sensitive kill switch. These results demonstrate the ability to build complex genetic systems for biological containment.

Optogenetic assessment of VIP, PV, SOM and NOS inhibitory neuron activity and cerebral blood flow regulation in mouse somato-sensory cortex

The impact of different neuronal populations on local cerebral blood flow (CBF) regulation is not well known and insight into these relationships could enhance the interpretation of brain function and dysfunction from brain imaging data. We investigated the role of sub-types of inhibitory neuron activity on the regulation of CBF using optogenetics, laser Doppler flowmetry and different transgenic mouse models (parvalbumin (PV), vasoactive intestinal peptide (VIP), somatostatin (SOM) and nitric oxide synthase (NOS)). Whisker stimulation was used to verify that typical CBF responses were obtained in all mice. Photo-stimulation of SOM-cre and NOS-cre mice produced significant increases in CBF that were similar to whisker responses. In NOS-cre mice, CBF responses scaled with the photo-stimulus pulse duration and frequency. In SOM-cre mice, CBF increases were followed by decreases. In VIP-cre mice, photo-stimulation did not consistently produce significant changes in CBF, while slower increases in CBF that peaked 14–18 s after stimulation onset were observed in PV-cre mice. Control experiments performed in non-expressing regions showed no changes in CBF. These findings suggest that dysfunction in NOS or SOM neurons can have a significant impact on vascular responses that are detected by brain imaging methods like functional magnetic resonance imaging (fMRI).