Optimizing auditory brainstem response acquisition using interleaved frequencies

Auditory brainstem responses (ABRs) require averaging responses to hundreds or thousands of repetitions of a stimulus (e.g., tone pip) to obtain a measurable evoked response at the scalp. Fast repetition rates lead to changes in ABR amplitude and latency due to adaptation. To minimize the effect of adaptation, stimulus rates are sometimes as low as 10 to 13.3 stimuli per second, requiring long acquisition times. The trade-off between reducing acquisition time and minimizing the effect of adaptation on ABR responses is an especially important consideration for studies of cochlear synaptopathy, which use the amplitude of short latency responses (wave 1) to assess auditory nerve survival. It has been proposed that adaptation during ABR acquisition can be reduced by interleaving tones at different frequencies, rather than testing each frequency serially. With careful ordering of frequencies and levels in the stimulus train, adaptation in the auditory nerve can be minimized, thereby permitting an increase in the rate at which tone bursts are presented. However, widespread adoption of this stimulus design has been hindered by lack of available software. Here, we develop and validate an interleaved stimulus design to optimize the rate of ABR measurement while minimizing adaptation. We implement this method in an open-source data acquisition software tool that permits either serial or interleaved ABR measurements. The open-source software library, psiexperiment, is compatible with widely-used ABR hardware. Consistent with previous studies, careful design of an interleaved stimulus train can reduce ABR acquisition time by more than half, with minimal effect on ABR thresholds and wave 1 latency, while improving measures of wave 1 amplitude.

Intraoperative identification of the corticospinal tract and dorsal column of the spinal cord by electrical stimulation

ObjectivesAnatomical identification of the corticospinal tract (CT) and the dorsal column (DC) of the exposed spinal cord is difficult when anatomical landmarks are distorted by tumour growth. Neurophysiological identification is complicated by the fact that direct stimulation of the DC may result in muscle motor responses due to the centrally activated H-reflex. This study aims to provide a technique for intraoperative neurophysiological differentiation between CT and DC in the exposed spinal cord.MethodsRecordings were obtained from 32 consecutive patients undergoing spinal cord tumour surgery from July 2015 to March 2017. A double train stimulation paradigm with an intertrain interval of 60 ms was devised with recording of responses from limb muscles.ResultsIn non-spastic patients (55% of cohort) an identical second response was noted following the first CT response, but the second response was absent after DC stimulation. In patients with pre-existing spasticity (45%), CT stimulation again resulted in two identical responses, whereas DC stimulation generated a second response that differed substantially from the first one. The recovery times of interneurons in the spinal cord grey matter were much shorter for the CT than those for the DC. Therefore, when a second stimulus train was applied 60 ms after the first, the CT-fibre interneurons had already recovered ready to generate a second response, whereas the DC interneurons were still in the refractory period.ConclusionsMapping of the spinal cord using double train stimulation allows neurophysiological distinction of CT from DC pathways during spinal cord surgery in patients with and without pre-existing spasticity.

Intracellular calcium movements during relaxation and recovery of superfast muscle fibers of the toadfish swimbladder

The mating call of the Atlantic toadfish is generated by bursts of high-frequency twitches of the superfast twitch fibers that surround the swimbladder. At 16°C, a calling period can last several hours, with individual 80–100-Hz calls lasting ∼500 ms interleaved with silent periods (intercall intervals) lasting ∼10 s. To understand the intracellular movements of Ca2+ during the intercall intervals, superfast fibers were microinjected with fluo-4, a high-affinity fluorescent Ca2+ indicator, and stimulated by trains of 40 action potentials at 83 Hz, which mimics fiber activity during calling. The fluo-4 fluorescence signal was measured during and after the stimulus trains; the signal was also simulated with a kinetic model of the underlying myoplasmic Ca2+ movements, including the binding and transport of Ca2+ by the sarcoplasmic reticulum (SR) Ca2+ pumps. The estimated total amount of Ca2+ released from the SR during a first stimulus train is ∼6.5 mM (concentration referred to the myoplasmic water volume). At 40 ms after cessation of stimulation, the myoplasmic free Ca2+ concentration ([Ca2+]) is below the threshold for force generation (∼3 µM), yet the estimated concentration of released Ca2+ remaining in the myoplasm (Δ[CaM]) is large, ∼5 mM, with ∼80% bound to parvalbumin. At 10 s after stimulation, [Ca2+] is ∼90 nM (three times the assumed resting level) and Δ[CaM] is ∼1.3 mM, with 97% bound to parvalbumin. Ca2+ movements during the intercall interval thus appear to be strongly influenced by (a) the accumulation of Ca2+ on parvalbumin and (b) the slow rate of Ca2+ pumping that ensues when parvalbumin lowers [Ca2+] near the resting level. With repetitive stimulus trains initiated at 10-s intervals, Ca2+ release and pumping come quickly into balance as a result of the stability (negative feedback) supplied by the increased rate of Ca2+ pumping at higher [Ca2+].

The Time Course of the Amplitude and Latency in the Auditory Late Response Evoked by Repeated Tone Bursts

Background: This study provides a detailed description of the time course of amplitude and latency in the auditory late response (ALR) elicited by repeated tone bursts. Research Design: Tone bursts (50 and 80 dB SPL) were presented via insert earphones in trains of ten with interstimulus intervals (ISIs) of 0.7 and 2 msec and an intertrain interval of 15 sec. Averages were derived independently for each tone burst within the train across the total number of train presentations. Study Sample: Participants were 14 normal-hearing young adults. Data Collection and Analysis: Data were analyzed in terms of the amplitudes and latencies of the N1 and P2 waves of the ALR as well as the N1-P2 amplitude. Results: The N1-P2 amplitude was a more stable measure than the amplitude of individual N1 and P2 peaks. The N1-P2 amplitude was maximal for the first tone burst and decreased in a nonmonotonic pattern for the remainder of the tone bursts within a stimulus train. The amplitude decrement was dependent on stimulus intensity and ISI. The latencies of N1 and P2 were maximal for the first tone burst and reduced approximately 20% for the rest of the stimuli in a train. The time course of N1 and P2 latencies was not dependent on stimulus intensity and ISI. Conclusions: The reduction of latency in the time course of the ALR might be related to the fact that neurons with shorter latencies had faster recovery speed from adaptation and/or refractoriness than those with longer latencies. This finding is meaningful in the context of future research to restore normal adaptation in abnormal hearing populations such as cochlear implant patients.

Refractoriness of sural nerve in humans

High-frequency stimulation of peripheral nerve bundles is frequently used in clinical tests and physiologic experiments to study presynaptic and postsynaptic effects. To understand the postsynaptic effects, it is important to ensure that each pulse in the train is equally effective in stimulating the presynaptic nerve bundle; however, the optimal interpulse interval (IPI) and the stimulus intensity at which each pulse is equally effective in stimulating the same number of axons are not known. The magnitude of the compound action potential produced by each pulse in a train was tested on the sural nerve of 4 healthy human subjects. The stimulus train (2–4 pulses) was applied to the sural nerve at the lateral malleolus, and neural responses were recorded from just below the knee. With 2-pulse trains, families of curves between IPIs (1–6 ms) and normalized amplitudes of the second response were plotted for different stimulus intensities. Visual inspection of the data showed that the curves fell into 2 groups: with stimulus intensities <2.5× perception threshold (Th), the test response appeared partially at longer IPIs, whereas with stimulus intensities ≥3× Th, partial recovery of the test response was earlier. The interval for complete recovery was statistically the same for low- and high-intensity stimulation. With more than 2 pulses in a stimulus train (IPI = 5 ms), the amplitude of the compound action potential (CAP) was not affected significantly. These results are important in understanding both the presynaptic and postsynaptic responses when presynaptic axon bundles are stimulated at high frequencies.