Neural Discharge Patterns Research Articles

Sex-specific impact of aging on muscle sympathetic neural discharge patterns during incremental rhythmic handgrip exercise

Sex-disparities exist in the risk of developing hypertension throughout the lifespan, with a greater prevalence of hypertension amongst postmenopausal females compared to similarly aged males. Though the underlying mechanisms are multifactorial, exaggerated sympathetic neuro-cardiovascular reactivity may be an important contributor. Indeed, postmenopausal females exhibit exaggerated exercise pressor responses compared to young adults, and older males. However, the interactive effects of age and sex on muscle sympathetic nerve activity (MSNA) and action potential (AP) coding patterns during exercise remains unclear. We hypothesized that older females would exhibit the greatest increase in MSNA and AP recruitment during exercise and post-exercise circulatory occlusion (PECO) relative to young males and females, as well as older males. MSNA and AP discharge patterns (microneurography and continuous wavelet transform) were assessed in 12 young males (YM (mean±SD); 26±4, years), 11 young females (YF; 25±4 years), 11 older males (OM; 71±11 years), and 12 older females (OF; 71±4 years) during incremental rhythmic handgrip exercise to fatigue followed by 2 minutes of PECO. At peak exercise, OM demonstrated a smaller change from baseline (Δ) in MSNA burst incidence (BI) compared to all other groups (YM: Δ8±9, YF: Δ9±8, OM: Δ-6±8, OF: Δ6±7 bursts/100heartbeats; all ANOVA post-hoc P<0.05), whereas ΔMSNA burst frequency (BF), Δburst amplitude (BA), and Δtotal activity were not different between groups (all P>0.05). Conversely, YM demonstrated greater ΔAPs/burst (YM: Δ5±3, OM: Δ0.4±3, OF: Δ2±2 APs/burst; post-hoc P<0.05) and ΔAP clusters/burst (YM: Δ2±1, OM: Δ0.1±1, OF: Δ0.7±0.7 Clusters/burst; post-hoc P<0.05) compared to OM and OF, but not compared to YF (Δ2±3 APs/burst and Δ0.9±0.8 clusters/burst; both P≥0.07). However, no group differences were observed in the recruitment of larger axons (YM: Δ6±2, YF: Δ4±2, OM: Δ2±5, OF: Δ4±3 clusters; P=0.33). Contrary to exercise, group-by-time interactions existed during PECO for ΔMSNA BF ( P<0.01), ΔBI ( P<0.01), and Δtotal activity ( P<0.01) where greater increases occurred during the first minute of PECO in young compared to older adults (all post-hoc P<0.05), whereas in the final minute of PECO, MSNA ΔBF and ΔBI were only greater in YM compared to OM and OF (all P<0.05), and total activity was greater in YM and YF compared to OF only (all P<0.05). No group-by-time interactions were observed for ΔMSNA BA ( P=0.37), ΔAPs/burst ( P=0.94), ΔAP clusters/burst ( P=0.95) or Δtotal AP clusters ( P=0.41) during PECO. Altogether, MSNA and AP reactivity during exercise was not exaggerated in OF, but age-related reductions in AP recruitment were observed in males. During PECO, MSNA responses were lower in older relative to young adults but, AP recruitment was unaltered by age. Thus, exaggerated MSNA or AP reactivity may not explain the greater prevalence of hypertension in OF. Supported by the Natural Sciences and Engineering Council of Canada, and IEEM Indirect Funds. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Differential regulation of sympathetic neural burst frequency and amplitude throughout normal pregnancy: a longitudinal study.

Sympathetic activation is a hallmark of pregnancy. However, longitudinal assessments of muscle sympathetic nerve activity (MSNA) in pregnancy are scarce and have primarily focused on burst occurrence (frequency) at rest, despite burst strength (amplitude) representing distinct characteristics of sympathetic outflow. Thus, we assessed MSNA burst amplitude distributions in healthy women to determine the impact of normal pregnancy on neural discharge patterns in response to orthostatic stress. Twenty-six women were studied longitudinally during pre-, early- (4-8 wk of gestation), and late (32-36 wk) pregnancy, as well as postpartum (6-10 wk after delivery). MSNA, blood pressure (BP), and heart rate (HR) were measured in the supine posture and during graded head-up tilt (30° and 60° HUT). Mean and median MSNA burst amplitudes were used to characterize burst amplitude distribution. In late pregnancy, women demonstrated smaller increases in HR (P < 0.001) during 60° HUT and larger increases in systolic BP (P = 0.043) throughout orthostasis, compared with prepregnancy. The increase in MSNA burst frequency during late- relative to prepregnancy (Late: Δ14[10] vs. Pre: Δ21[9] bursts/min; P = 0.001) was smaller during 60° HUT, whereas increases in burst incidence were smaller in late- relative to prepregnancy throughout orthostasis (P = 0.009). Nonetheless, median burst amplitude was smaller throughout orthostasis in late compared with prepregnancy (P = 0.038). Thus, while supine MSNA burst frequency was greater in late pregnancy, increases in burst frequency and strength during orthostasis were attenuated. These smaller, orthostatically induced MSNA increases may reflect natural adaptions of pregnancy serving to prevent sympathetic hyper-reactivity that is common in pathological states.

A Measure of Concurrent Neural Firing Activity Based on Mutual Information.

Multiple methods have been developed in an attempt to quantify stimulus-induced neural coordination and to understand internal coordination of neuronal responses by examining the synchronization phenomena in neural discharge patterns. In this work we propose a novel approach to estimate the degree of concomitant firing between two neural units, based on a modified form of mutual information (MI) applied to a two-state representation of the firing activity. The binary profile of each single unit unfolds its discharge activity in time by decomposition into the state of neural quiescence/low activity and state of moderate firing/bursting. Then, the MI computed between the two binary streams is normalized by their minimum entropy and is taken as positive or negative depending on the prevalence of identical or opposite concomitant states. The resulting measure, denoted as Concurrent Firing Index based on MI (CFIMI), relies on a single input parameter and is otherwise assumption-free and symmetric. Exhaustive validation was carried out through controlled experiments in three simulation scenarios, showing that CFIMI is independent on firing rate and recording duration, and is sensitive to correlated and anti-correlated firing patterns. Its ability to detect non-correlated activity was assessed using ad-hoc surrogate data. Moreover, the evaluation of CFIMI on experimental recordings of spiking activity in retinal ganglion cells brought insights into the changes of neural synchrony over time. The proposed measure offers a novel perspective on the estimation of neural synchrony, providing information on the co-occurrence of firing states in the two analyzed trains over longer temporal scales compared to existing measures.

Case Studies in Physiology: Sympathetic neural discharge patterns in a healthy young male during end-expiratory breath hold-induced sinus pause.

This case study reports the efferent muscle sympathetic nerve activity (MSNA) discharge patterns during a sinus pause observed during a maximal end-expiratory apnea in a young healthy male (age = 26 yr). During a 15.3-s end-expiratory apnea following a bout of intermittent hypercapnic hypoxia, we observed a 5.2-s (R-R interval) sinus pause and integrated MSNA recording, demonstrating a square-wave discharge pattern atypical of sharp MSNA burst peaks entrained to cardiac cycles or during preventricular contractions. This abnormal MSNA discharge pattern was observed again during a follow-up experiment, where an end-expiratory apnea at baseline resulted in pronounced bradycardia (R-R intervals >2.5-s) but failed to reproduce the 5.2-s sinus pause. Action potential (AP) discharge patterns during MSNA bursts were detected using a continuous wavelet transform approach. AP discharge increased by 300% during the end-expiratory apnea with 5.2-s sinus pause compared with baseline and involved increased firing (i.e., rate-coding) of AP clusters (bins of AP with similar morphology) already present during baseline and pronounced recruitment of larger-amplitude AP clusters not present at baseline. Large-amplitude AP clusters continued to discharge during sinus pause. In summary, we show MSNA discharge during sinus pause and pronounced bradycardia during end-expiratory apnea, which demonstrates a square-wave discharge with recruitment of latent larger-amplitude AP clusters. The MSNA discharge was terminated before systole following sinus pause potentially through an inhibitory influence of inspiration, or cardiac mechanoreceptor feedback causing burst termination.NEW & NOTEWORTHY We characterize the occurrence of a square-wave discharge pattern of efferent muscle sympathetic nerve activity during a sinus pause in a young healthy male. This discharge pattern comprised large recruited action potential clusters undetected at baseline that continuously discharged during the sinus pause. Notably, this discharge pattern was still contained within a single cardiac cycle.

The role of the paravertebral ganglia in human sympathetic neural discharge patterns.

The mechanisms affecting recruitment patterns of postganglionic sympathetic nerves remain unclear. The divergent and convergent preganglionic innervation patterns of postganglionic neurons and the presence of differently sized postganglionic nerves suggest that the ganglia may participate in modifying the discharge patterns of single sympathetic postganglionic neurons innervating the skeletal muscle circulation. Whether the ganglia affect the ordered behaviour of varying sized postganglionic sympathetic neurons in humans has not been studied. Trimethaphan infusion produced an ordered pattern of action potential (AP) de-recruitment whereby the firing of larger, low probability APs present at baseline was abolished first, followed by progressive decreased probability of smaller APs. Although integrated sympathetic bursts were no longer detected after several minutes of trimethaphan, firing of the smallest APs was detected. These data suggest the ganglia affect the distribution of firing probabilities exhibited by differently sized sympathetic neurons. The ganglia may contribute to sympathetic neural emission patterns involved in homeostatic regulation. Do the ganglia contribute to the ordered behaviour of postganglionic neuronal discharge within the sympathetic nervous system? To further understand the functional organization of the sympathetic nervous system we employed the microneurographic approach to record muscle sympathetic nerve activity (MSNA) and a continuous wavelet transform to study postganglionic action potential (AP) behaviour during nicotinic blockade at the ganglia (trimethaphan camsylate, 1-7mgmin-1 ) in seven females (37± 5 years). Trimethaphan elicited a progressive reduction in sympathetic outflow characterized by fewer integrated bursts with decaying amplitude. Underlying trimethaphan-mediated attenuations in integrated MSNA were reductions in AP incidence (186± 101 to 29± 31 AP(100 beats)-1 ) and AP content per integrated burst (7± 2 to 3± 1 APsburst-1 ) (both P< 0.01) in the final minute of detectable bursting activity in the trimethaphan condition, compared to baseline. We observed an ordered de-recruitment of larger to smaller AP clusters active at baseline (14± 3 to 8± 2 active AP clusters, P< 0.01). Following cessation of integrated bursts in the trimethaphan condition, the smallest 6± 2 sympathetic AP clusters persisted to fire in an asynchronous pattern (49± 41AP (100 beats)-1 ) in all participants. Valsalva's manoeuvre did not increase the incidence of these persistent APs (60± 42 AP(100 beats)-1 , P= 0.52), or recruit any larger APs in six of seven participants (6± 1 total AP clusters, P= 0.30). These data suggest that the ganglia participate in the ordered recruitment of differently sized postganglionic sympathetic nerves.

Advances in research on combining the opotogenetics with bionic olfaction sensor

There are plenty of amazing wonders existing in nature, and the crisis-crossing connections between them are performing their best duties. For example, biological olfactory system is an ingenious biosensor, since the olfactory sensory neurons in peripheral nervous respond to the external stimuli, then the signals are transmitted to the olfactory bulb to be integrated and processed, the axonal connection is precisely organized signals from about 1000 different types of odorant receptors, then sorted out in 1800 glomeruli in the mouse olfactory bulb, after delivered to the most advanced central nervous system, the information can be distinguished eventually. Cortical regions underlying vision, audition, and somatosens- ation receive sensory information from the thalamus and also make corticothalamic feedback projections that influence thalamic sensory processing. This process is responding with particularly high sentivity, specificity and rapidity. The ability to detect odorants is crucial for survival as it informs an organism with its environment: food, approaching predators, mates nearby, etc. During recently year, researchers have employed optogenetics technology to explore deeper in the mechanism of olfactory system. Microbial proteins that can be rapidly activated by light have been adapted for research in neuroscience, including ChR2 and NpHR, which permit millisecond-precision optical control of genetically defined cell types in intact neural tissue. This technology allows the use of light to alter neural processing at the level of single spikes and synaptic events, yielding a widely applicable tool for neuroscientists and biomedical engineers. An important question in the study of the olfactory system is the role of spatial factors in olfactory processing, but traditional methods have been relatively unsuccessful in elucidating their theories, odor stimulation evokes complex spatiotemporal activity in the olfactory bulb, suggesting that both the identity of activated neurons and the timing of their activity convey information about odors, the emergency of optogenetics technology can solve this problem efficiently. Biological olfactory systems can recognize and discriminate thousands of distinct odors with very high sensitivity and specificity, with the progress of research on olfactory mechanisms and the advancements of olfaction, many types of biomimetic olfactory-based biosensors have been developed by the combination of olfactory functional components with various secondary sensors. The bioinspired olfaction sensor is an innovative chemical sensing bionic system with far-reaching significance, it contains various biological components as the sensitive elements including olfactory receptors, olfactory cells and olfactory tissues, which has great applicable prospects in many fields for detecting specific odorants with high sensitivity, also by chronically coupling multiple microelectrodes to olfactory bulb of behaving rats, we extract an array of mitral/tufted cells which could generate odor-specific temporal patterns of neural discharge. They have great potential commercial prospects and promising applications in such fields as biomedicine, environmental monitoring, pharmaceutical screening and the quality control of food and water. This review interpreted the transferring mechanism of biological olfactory system and the applications of optogenetics in researches concerning the foundamental research of olfactory system. In addition, a combination of the work of our laboratory with other domestic and international researchers were presented here to predict the future scenario and the promising applications in disease diagnosis, environmental monitoring, military and food quality control.

Common therapeutic mechanisms of pallidal deep brain stimulation for hypo- and hyperkinetic movement disorders.

Abnormalities in cortico-basal ganglia (CBG) networks can cause a variety of movement disorders ranging from hypokinetic disorders, such as Parkinson's disease (PD), to hyperkinetic conditions, such as Tourette syndrome (TS). Each condition is characterized by distinct patterns of abnormal neural discharge (dysrhythmia) at both the local single-neuron level and the global network level. Despite divergent etiologies, behavioral phenotypes, and neurophysiological profiles, high-frequency deep brain stimulation (HF-DBS) in the basal ganglia has been shown to be effective for both hypo- and hyperkinetic disorders. The aim of this review is to compare and contrast the electrophysiological hallmarks of PD and TS phenotypes in nonhuman primates and discuss why the same treatment (HF-DBS targeted to the globus pallidus internus, GPi-DBS) is capable of ameliorating both symptom profiles. Recent studies have shown that therapeutic GPi-DBS entrains the spiking of neurons located in the vicinity of the stimulating electrode, resulting in strong stimulus-locked modulations in firing probability with minimal changes in the population-scale firing rate. This stimulus effect normalizes/suppresses the pathological firing patterns and dysrhythmia that underlie specific phenotypes in both the PD and TS models. We propose that the elimination of pathological states via stimulus-driven entrainment and suppression, while maintaining thalamocortical network excitability within a normal physiological range, provides a common therapeutic mechanism through which HF-DBS permits information transfer for purposive motor behavior through the CBG while ameliorating conditions with widely different symptom profiles.

Reciprocal functional interactions between the respiration/circulation center, the upper spinal cord, and the trigeminal system.

The interplay of neural discharge patterns involved in “respiration”, “circulation”, “opening movements in the mandible”, and “locomotion” was investigated electrophysiologically in a decerebrate and arterially perfused in situ rat preparation. Sympathetic tone increased with increases in perfusion flow rate. All nerve discharges became clearly organized into discharge episodes of increasing frequency and duration punctuated by quiescent periods as the perfusion flow rate increased at 26°C. The modulated sympathetic tone at 10× total blood volume/ min activated the forelimb pattern generator and spontaneously generated fictive forelimb movement during discharge episodes. The coupling rhythm of respiration and locomotion during motion occurred at frequency ratios ranges of 1:2 and 1:3. Small increases in systemic pressure were always generated after the initiation of motion. Opening movements in the mandible, occurring during the inspiratory phase at all tested flow rates, were generated in both the inspiratory and expiratory phases during motion. Although the central mechanism for the entrainment of respiratory and locomotor rhythms has not been identified, a spinal-feedback mechanism generating fictive locomotion in the upper spinal cord contributed to generating the opening movement in the mandible in the expiratory phase during motion. The existence of this mechanism implies that there is a reciprocal functional interaction between the brainstem and the spinal cord, whereby the intake and output of air by the lungs is efficiently improved during movement by both nasal and mouth breathing. These results suggest that this reciprocal functional interaction plays an important role in increasing oxygenated blood flow during locomotion.

Detection and classification of natural odors with an in vivo bioelectronic nose.

The mammalian olfactory system is recognized as one of the most effective chemosensing systems. We thus investigated the potential of utilizing the rat's olfactory system to detect odors. By chronically coupling multiple microelectrodes to olfactory bulb of behaving rats, we extract an array of mitral/tufted cells (M/Ts) which could generate odor-specific temporal patterns of neural discharge. We performed multidimensional analysis of recorded M/Ts, finding that natural odors released from different fruit lead to distinct odor response patterns. Thus an array of M/Ts carried sufficient information to discriminate odors. This novel brain-machine interface using rat's olfaction presents a promising method for odor detection and discrimination, and it is the first step towards in vivo bioelectronic nose equipped with biological olfaction and artificial devices.

Optimal combination of neural temporal envelope and fine structure cues to explain speech identification in background noise.

The dichotomy between acoustic temporal envelope (ENV) and fine structure (TFS) cues has stimulated numerous studies over the past decade to understand the relative role of acoustic ENV and TFS in human speech perception. Such acoustic temporal speech cues produce distinct neural discharge patterns at the level of the auditory nerve, yet little is known about the central neural mechanisms underlying the dichotomy in speech perception between neural ENV and TFS cues. We explored the question of how the peripheral auditory system encodes neural ENV and TFS cues in steady or fluctuating background noise, and how the central auditory system combines these forms of neural information for speech identification. We sought to address this question by (1) measuring sentence identification in background noise for human subjects as a function of the degree of available acoustic TFS information and (2) examining the optimal combination of neural ENV and TFS cues to explain human speech perception performance using computational models of the peripheral auditory system and central neural observers. Speech-identification performance by human subjects decreased as the acoustic TFS information was degraded in the speech signals. The model predictions best matched human performance when a greater emphasis was placed on neural ENV coding rather than neural TFS. However, neural TFS cues were necessary to account for the full effect of background-noise modulations on human speech-identification performance.

Improved perception of speech in noise and Mandarin tones with acoustic simulations of harmonic coding for cochlear implants

Harmonic and temporal fine structure (TFS) information are important cues for speech perception in noise and music perception. However, due to the inherently coarse spectral and temporal resolution in electric hearing, the question of how to deliver harmonic and TFS information to cochlear implant (CI) users remains unresolved. A harmonic-single-sideband-encoder [(HSSE); Nie et al. (2008). Proceedings of IEEE International Conference on Acoustics, Speech, and Signal Processing; Lie et al., (2010). Proceedings of IEEE International Conference on Acoustics, Speech, and Signal Processing] strategy has been proposed that explicitly tracks the harmonics in speech and transforms them into modulators conveying both amplitude modulation and fundamental frequency information. For unvoiced speech, HSSE transforms the TFS into a slowly varying yet still noise-like signal. To investigate its potential, four- and eight-channel vocoder simulations of HSSE and the continuous-interleaved-sampling (CIS) strategy were implemented, respectively. Using these vocoders, five normal-hearing subjects' speech recognition performance was evaluated under different masking conditions; another five normal-hearing subjects' Mandarin tone identification performance was also evaluated. Additionally, the neural discharge patterns evoked by HSSE- and CIS-encoded Mandarin tone stimuli were simulated using an auditory nerve model. All subjects scored significantly higher with HSSE than with CIS vocoders. The modeling analysis demonstrated that HSSE can convey temporal pitch cues better than CIS. Overall, the results suggest that HSSE is a promising strategy to enhance speech perception with CIs.

Perspectives on yoga inputs in the management of chronic pain.

Chronic pain is multi-dimensional. At the physical level itself, beyond the nociceptive pathway, there is hyper arousal state of the components of the nervous system, which negatively influences tension component of the muscles, patterns of breathing, energy levels and mindset, all of which exacerbate the distress and affect the quality of life of the individual and family. Beginning with the physical body, Yoga eventually influences all aspects of the person: vital, mental, emotional, intellectual and spiritual. It offers various levels and approaches to relax, energize, remodel and strengthen body and psyche. The asanas and pranayama harmonize the physiological system and initiate a “relaxation response” in the neuro endocrinal system. This consists of decreased metabolism, quieter breathing, stable blood pressure, reduced muscle tension, lower heart rate and slow brain wave pattern. As the neural discharge pattern gets modulated, hyper arousal of the nervous system and the static load on postural muscle come down. The function of viscera improves with the sense of relaxation and sleep gets deeper and sustained; fatigue diminishes. Several subtle level notional corrections can happen in case the subject meditates and that changes the context of the disease, pain and the meaning of life. Meditation and pranayama, along with relaxing asanas, can help individuals deal with the emotional aspects of chronic pain, reduce anxiety and depression effectively and improve the quality of life perceived.

Challenges and opportunities in processing muscle sympathetic nerve activity with wavelet denoising techniques: Detecting single action potentials in multiunit sympathetic nerve recordings in humans

An important issue in analysis of muscle sympathetic nerve activity (MSNA), particularly those measures made in humans, is the problem that background noise of varying levels from recording to recording may interfere with accurate assessment of neural discharge patterns and overall activity. In this study, the utility of wavelet denoising approaches for processing MSNA signals was examined with emphasis on 1) determining whether this approach could improve the signal-to-noise (SNR) in the integrated neurogram, and 2) detecting intra-burst single action potential spikes. The utility of wavelet denoising was examined in simulated data and in original human data with three recordings of varying SNR (low, moderate and high) obtained from two healthy individuals. Only in the high SNR signal was the noise removed without concurrent loss of signal. Using a threshold-detecting algorithm individual depolarization spikes were detected in denoised recordings of high original SNR (> 3:1) from four individuals and the interspike interval characteristics of these were quantified on a burst-by-burst basis. Compared with baseline (15 ± 1 spikes/burst) a reflexive increase in spike count (29 ± 4 spikes/burst) was observed during a held maximal inspiration ( P < 0.01) with concurrent reductions in inter-spike interval ( P < 0.01). The findings indicate that within multiunit bursts of sympathetic neural activity in the band-pass filtered neural signal, there are particular frequency components that appear to be shared between the signal and noise. This may limit the utility of wavelet denoising to enhance detection of neural bursts in the integrated neurogram of MSNA. However, opportunities exist with this approach to detect variations in action potential contributions within each burst of MSNA. This latter observation suggests that this denoising approach provides a new probe to explore MSNA discharge patterns.

Selection and parameterization of cortical neurons for neuroprosthetic control

When designing neuroprosthetic interfaces for motor function, it is crucial to have a system that can extract reliable information from available neural signals and produce an output suitable for real life applications. Systems designed to date have relied on establishing a relationship between neural discharge patterns in motor cortical areas and limb movement, an approach not suitable for patients who require such implants but who are unable to provide proper motor behavior to initially tune the system. We describe here a method that allows rapid tuning of a population vector-based system for neural control without arm movements. We trained highly motivated primates to observe a 3D center-out task as the computer played it very slowly. Based on only 10–12 s of neuronal activity observed in M1 and PMd, we generated an initial mapping between neural activity and device motion that the animal could successfully use for neuroprosthetic control. Subsequent tunings of the parameters led to improvements in control, but the initial selection of neurons and estimated preferred direction for those cells remained stable throughout the remainder of the day. Using this system, we have observed that the contribution of individual neurons to the overall control of the system is very heterogeneous. We thus derived a novel measure of unit quality and an indexing scheme that allowed us to rate each neuron's contribution to the overall control. In offline tests, we found that fewer than half of the units made positive contributions to the performance. We tested this experimentally by having the animals control the neuroprosthetic system using only the 20 best neurons. We found that performance in this case was better than when the entire set of available neurons was used. Based on these results, we believe that, with careful task design, it is feasible to parameterize control systems without any overt behaviors and that subsequent control system design will be enhanced with cautious unit selection. These improvements can lead to systems demanding lower bandwidth and computational power, and will pave the way for more feasible clinical systems.

A model of the perceptual asymmetry between peaks and troughs of frequency modulation.

Pitch discrimination at peaks of frequency modulation is better than at troughs [L. Demany and K. I. McAnally, J. Acoust. Soc. Am. 96, 706-715 (1989)]. A similar asymmetry emerges within a time-domain pitch perception model based on autocorrelation. The model requires the following assumptions: (a) The neural discharge patterns must be temporally sharpened to a single narrow pulse per period (possibly by neural convergence within the cochlear nucleus). (b) Autocorrelation must be implemented as a cross correlation between the neural pulse train and a delayed pulse train convolved with a short kernel function. This kernel function must be asymmetric in time. (c) Pitch discrimination must rely on higher-order modes of the autocorrelation function. This particular implementation of the autocorrelation model produces modes that are sharper for peaks than for troughs, and thus accounts for the pitch discrimination asymmetry observed experimentally. As a by-product it can account for "hyperacute" discrimination observed at peaks of triangular modulation.

Concurrent vowel identification. III. A neural model of harmonic interference cancellation

This paper presents a “neural cancellation filter” capable of segregating weak targets from competing harmonic backgrounds, and a model of concurrent vowel segregation based upon it. The elementary cancellation filter comprises a delay line and an inhibitory synapse. Filters within each peripheral channel are tuned to the period of the competing sound to suppress its correlates within the neural discharge pattern. In combination with a pattern matching model based on autocorrelation functions summed over channels, the cancellation filter forms a model of concurrent vowel identification. The model predicts the number of vowels reported for each stimulus (when subjects are allowed to report one or two) and identification rates. It belongs to the class of “harmonic cancellation” models that are supported by experimental evidence that vowel identification is better when competing sounds are harmonic than inharmonic. Two alternative schemes using the same filter are also considered. One derives a “place” representation from the magnitude of the filter output. The other uses the ratio of filter input/output to select channels.

A biologically motivated neural network architecture for visuomotor control

In this paper, a new version of an earlier computational model of the primate saccadic system is described which has been investigated for its effectiveness in robot visuomotor control. The model consists of a recurrent neural network representing the superior colliculus, which supplies control signals to a lumped model of the burst generator. A genetic algorithm is proposed to train the lateral connective weights of the recurrent neural network, and the network is trained so that it produces dynamic activity that is very close to the observed collicular neural discharge patterns in primates. By means of a supervised training algorithm, the feedforward and feedback weights of this new model are trained, so that the model produces a wide range of saccades that are very similar to real eye movements. It has been shown mathematically that this algorithm is a close approximation of the gradient descent method of optimization. An earlier set of simulations with single and double target locations, as well as some new simulations pertaining to the robustness of the model, are then carried out. The reliability of the biological visuomotor system is demonstrated through these simulations, and theoretical issues pertaining to the reliability of this system are addressed. Finally, a novel strategy for robot visuomotor control, based on the model, is suggested.

Point process models of single-neuron discharges.

In most neural systems, neurons communicate via sequences of action potentials. Contemporary models assume that the action potentials' times of occurrence rather than their waveforms convey information. The mathematical tool for describing sequences of events occurring in time and/or space is the theory of point processes. Using this theory, we show that neural discharge patterns convey time-varying information intermingled with the neuron's response characteristics. We review the basic techniques for analyzing single-neuron discharge patterns and describe what they reveal about the underlying point process model. By applying information theory and estimation theory to point processes, we describe the fundamental limits on how well information can be represented by and extracted from neural discharges. We illustrate applying these results by considering recordings from the lower auditory pathway.

Tuning, spontaneous activity and tonotopic map in chicken cochlear ganglion neurons following sound-induced hair cell loss and regeneration

Adult chickens were exposed for 48 h to a 525 Hz, 120 dB SPL tone that destroyed the hair cells and tectorial membrane in a crescent-shaped patch along the abneural edge of the basilar papilla. Single-unit recordings were obtained from cochlear ganglion neurons 0–1, 5, 14 and 28 days post-exposure to determine what effect the cochlear lesion had on neural discharge patterns and if the discharge patterns fully recovered. Immediately after exposure, the tuning curves were extremely broad and CF thresholds were elevated by 30–40 dB. In addition, the average spontaneous rate and percentage of neurons with interspike interval histograms with preferred intervals were greatly reduced, Tuning curves and spontaneous activity started to recover by 5 days post-exposure; however, some W-shaped tuning curves with two distinct tips and a hypersensitive tail were observed at this time. W-shaped tuning curves disappeared and spontaneous activity recovered to normal levels 14–28 days post-exposure. However, the CF thresholds of the most sensitive neurons were still slightly elevated, tuning curve slopes below CF were shallower than normal, and thresholds in the low-frequency tail of the tuning curves were often hypersensitive. These functional deficits were most closely associated with residual damage to the upper fibrous layer of the tectorial membrane. To determine if the cochlear frequency-place map was altered by the cochlear lesion, four physiologically characterized neurons were labeled with biocytin at 5 days post-exposure. The CFs of the labeled neurons were consistent with the normal frequency-place map (Chen et al. (1994) Hearing Research 81, 130–136) indicating that the tonotopic map was not altered.

Intrinsic discharge patterns and somatosensory inputs for neurons in raccoon primary somatosensory cortex

1. Discharge patterns of neurons are regulated by synaptic inputs and by intrinsic membrane properties such as their complement of ionic conductances. Discharge patterns evoked by synaptic inputs are often used to identify the source and modality of sensory input. However, the interpretation of these discharge patterns may be complicated if different neurons respond to the same synaptic input with a variety of discharge patterns due to differences in intrinsic membrane properties. The purposes of this study were 1) to investigate intrinsic discharge patterns of neurons in primary somatosensory cortex of raccoon in vivo and 2) to use somatosensory postsynaptic potentials evoked by stimulation of forepaw digits to determine thalamocortical connectivity for the same neurons. 2. Conventional intracellular recordings with sharp electrodes were made from 121 neurons in the cortical representation of glabrous skin of digit four (d4). Intracellular injection of identical current pulses (100-120 ms in duration) elicited various patterns of discharge in different neurons. Neurons were classified on the basis of these intrinsic patterns of discharge, rates of spike adaptation, and characteristics of spike waveforms. Three main groups were identified: regular spiking (RS) neurons, intrinsic bursting (IB) neurons, and fast spiking (FS) neurons. Subclasses were identified for the RS and IB groups. 3. Neurons were tested for somatosensory inputs by stimulating electrically d3, d4, and d5. Excitatory postsynaptic potentials (EPSPs) were elicited in 100% of the neurons by electrical stimulation of d4, the "on-focus" digit. EPSPs were usually followed by inhibitory postsynaptic potentials (IPSPs). Many neurons (41%) responded with EPSP-IPSP sequences after stimulation of d3 or d5, the "off-focus" digits. 4. Latencies of somatosensory EPSPs and IPSPs were used to determine the synaptic order in the cortical circuitry of RS, IB, and FS neurons. EPSPs with monosynaptic thalamocortical latencies were recorded in RS, IB, and FS neurons. 5. We conclude that precise patterns of neural discharge in primary somatosensory cortex cannot be reliable estimates of sensory inputs reaching these neurons because patterns of discharge are so strongly influenced by intrinsic membrane properties. Ionic conductances governing patterns of neuronal discharge seem almost identical in intact cortex of raccoon, rat, and cat, and in slices of rodent cortex, because similar patterns of discharge are found. The consistency of patterns of discharge across species and types of preparation suggests that these intrinsic membrane properties are a general property of cerebral cortical neurons and should be considered when evaluation sensory coding by these neurons.