Short Interstimulus Intervals Research Articles

Bilateral median nerve stimulation and High-Frequency Oscillations unveil interhemispheric inhibition of primary sensory cortex

ObjectiveThis study aimed at investigating the effect of median nerve stimulation on ipsilateral cortical potentials evoked by contralateral median nerve electrical stimulation. MethodsWe recorded somatosensory-evoked potentials (SEPs) from the left parietal cortex in 15 right-handed, healthy subjects. We administered bilateral median nerve stimulation, with the ipsilateral stimulation preceding the stimulation on the contralateral by intervals of 5, 10, 20, or 40 ms. We adjusted these intervals based on each individual’s N20 latency. As a measure of S1 excitability, the amplitude of the N20 and the area of the High Frequency Oscillation (HFO) burst were analyzed for each condition. ResultsThe results revealed significant inhibition of N20 amplitude by ipsilateral median nerve stimulation at interstimulus intervals (ISIs) between 5 and 40 ms. Late HFO burst was suppressed at short ISIs of 5 and 10 ms, pointing to a transcallosal inhibitory effect on S1 intracortical circuits. ConclusionsFindings suggest interhemispheric interaction between the primary somatosensory areas, supporting the existence of transcallosal transfer of tactile information. SignificanceThis study provides valuable insights into the interhemispheric connections between primary sensory areas and underscore the potential role of interhemispheric interactions in somatosensory processing.

Short-term changes in the physiology of the primary motor cortex following head impact exposure during a Canadian football game.

This study investigated the association between head impact exposure (HIE) during varsity Canadian football games and short-term changes in cortical excitability of the primary motor cortex (M1) using transcranial magnetic stimulation (TMS). Twenty-nine university-level male athletes wore instrumented mouth guards during a football game to measure HIE. TMS measurements were conducted 24 hours before and 1-2 hours after the game. Twenty control football athletes were submitted to a noncontact training session and underwent identical TMS assessments. Between-group changes in short-interval intracortical inhibition (SICI) ratios over time were conducted using two-way ANOVAs. The relationship between HIE (i.e., number, magnitude, and cumulative forces of impacts) and SICI (secondary outcome) was also investigated using Pearson correlations. Relative to controls, the group of athletes who had played a full-contact football game exhibited a significant intracortical disinhibition (p = 0.028) on the SICI 3-msec protocol (i.e., short interstimulus interval of 3 msec) within hours following the game. Moreover, exposure to ≥ 40g hits positively correlated with SICI disinhibition (p < 0.05). Athletes exposed to subconcussive hits associated with Canadian football exhibit abnormal M1 corticomotor inhibition function, particularly when the recorded impact magnitude was ≥ 40g. Given the deleterious effects of decreased inhibition on motor control and balance, systematically tracking head impact forces at each game and practice with contacts could prove useful for injury prevention in contact sports.

Synaptotagmin 7 Sculpts Short-Term Plasticity at a High Probability Synapse.

Synapses with high release probability (Pr ) tend to exhibit short-term synaptic depression. According to the prevailing model, this reflects the temporary depletion of release-ready vesicles after an initial action potential (AP). At the high-Pr layer 4 to layer 2/3 (L4-L2/3) synapse in rodent somatosensory cortex, short-term plasticity appears to contradict the depletion model: depression is absent at interstimulus intervals (ISIs) <50 ms and develops to a maximum at ∼200 ms. To understand the mechanism(s) underlying the biphasic time course of short-term plasticity at this synapse, we used whole-cell electrophysiology and two-photon calcium imaging in acute slices from male and female juvenile mice. We tested several candidate mechanisms including neuromodulation, postsynaptic receptor desensitization, and use-dependent changes in presynaptic AP-evoked calcium. We found that, at single L4-L2/3 synapses, Pr varies as a function of ISI, giving rise to the distinctive short-term plasticity time course. Furthermore, the higher-than-expected Pr at short ISIs depends on expression of synaptotagmin 7 (Syt7). Our results show that two distinct vesicle release processes summate to give rise to short-term plasticity at this synapse: (1) a basal, high-Pr release mechanism that undergoes rapid depression and recovers slowly (τ = ∼3 s) and (2) a Syt7-dependent mechanism that leads to a transient increase in Pr (τ = ∼100 ms) after the initial AP. We thus reveal how these synapses can maintain a very high probability of neurotransmission for multiple APs within a short time frame. Key words : depression; facilitation; short-term plasticity; synaptotagmin 7.

Effects of the cardiac cycle on auditory processing: A preregistered study on mismatch negativity.

The systolic and diastolic phases of the cardiac cycle are known to affect perception and cognition differently. Higher order processing tends to be facilitated at systole, whereas sensory processing of external stimuli tends to be impaired at systole compared to diastole. The current study aims to examine whether the cardiac cycle affects auditory deviance detection, as reflected in the mismatch negativity (MMN) of the event-related brain potential (ERP). We recorded the intensity deviance response to deviant tones (70 dB) presented among standard tones (60 or 80 dB, depending on blocks) and calculated the MMN by subtracting standard ERP waveforms from deviant ERP waveforms. We also assessed intensity-dependent N1 and P2 amplitude changes by subtracting ERPs elicited by soft standard tones (60 dB) from ERPs elicited by loud standard tones (80 dB). These subtraction methods were used to eliminate phase-locked cardiac-related electric artifacts that overlap auditory ERPs. The endogenous MMN was expected to be larger at systole, reflecting the facilitation of memory-based auditory deviance detection, whereas the exogenous N1 and P2 would be smaller at systole, reflecting impaired exteroceptive sensory processing. However, after the elimination of cardiac-related artifacts, there were no significant differences between systole and diastole in any ERP components. The intensity-dependent N1 and P2 amplitude changes were not obvious in either cardiac phase, probably because of the short interstimulus intervals. The lack of a cardiac phase effect on MMN amplitude suggests that preattentive auditory processing may not be affected by bodily signals from the heart.

Contributed Session II: The relationship between temporal summation at detection threshold and fixational eye movements.

We studied the relationship between the threshold temporal summation of increment pulses and fixational eye-movements. Six participants completed a 2AFC increment detection task. Stimuli were 0.16 x 2.2 arcmin increments of 543 nm light presented via an AOSLO with a 60 Hz frame rate. Stimuli for temporal integration were two single frame presentations with a 16 ms (consecutive frames), 33 ms, 100 ms, or 300 ms inter-stimulus interval (ISI). Data were also collected for increments presented on a single frame. Stimuli were presented in either world-fixed coordinates (natural retinal image motion) or were stabilised on the retina. There were large differences in overall sensitivity across individuals, but the time-course of performance change with ISI was similar across participants. Thresholds for ISI=33 ms were close to performance with two consecutive frames, suggesting complete summation of light energy; whereas thresholds for ISI=300 ms were closer to the single-frame case, suggesting limited summation; and thresholds for ISI=100 ms were intermediate, suggesting residual summation. The effect of ISI on threshold was similar for stabilised stimuli and natural viewing, but there was a small trend towards lower thresholds for stabilised stimuli at short ISI and vice-versa at long ISI. We plan to present our results in the context of an ideal observer calculation that may clarify how the initial visual encoding, including temporal summation within cones, shapes performance.

Temporal speed prevails on interval duration in the SNARC-like effect for tempo.

The Spatial-Numerical Association of Response Codes (SNARC) effect is evidence of an association between number magnitude and response position, with faster left-key responses to small numbers and faster right-key responses to large numbers. Similarly, recent studies revealed a SNARC-like effect for tempo, defined as the speed of an auditory sequence, with faster left-key responses to slow tempo and faster right-key responses to fast tempo. In order to address some methodological issues of previous studies, in the present study we designed an experiment to investigate the occurrence of a SNARC-like effect for tempo, employing a novel procedure in which only two auditory beats in sequence with a very short interstimulus interval were used. In the "temporal speed" condition, participants were required to judge the temporal speed (slow or fast) of the sequence. In the "interval duration" condition, participants were required to judge the duration of the interval between the two beats (short or long). The results revealed a consistent SNARC-like effect in both conditions, with faster left-hand responses to slow tempo and faster right-hand responses to fast tempo. Interestingly, the consistency of the results across the two conditions indicates that the direction of the SNARC-like effect was influenced by temporal speed even when participants were explicitly required to focus on interval duration. Overall, the current study extends previous findings by employing a new paradigm that addresses potential confounding factors and strengthens evidence for the SNARC-like effect for tempo.

O031 The Inter-stimulus Interval Effect in the Psychomotor Vigilance Task

Abstract Introduction The Psychomotor Vigilance Task (PVT) is a widely used measure of the effects of sleep deprivation on vigilant attention. The test requires a rapid response to a stimulus occurring at random inter-stimulus intervals (ISIs) between 2 and 10 seconds following a previous response. A few studies have found an ISI effect where shorter ISIs (2-4s) have slower reaction times (RTs) than longer ISIs (8-10s). How this ISI effect is impacted by circadian timing has yet to be investigated. Method This study compared the ISI effect at 3 time points coinciding with 5, 23 (circadian trough), and 29 hours of wakefulness. Data were taken from 16 healthy participants during a 30 hour period of sleep deprivation. Results A repeated-measures (3 x 3) ANOVA (3 time points, 3 ISIs) found that RTs were slower and lapses (RT&amp;gt;500msec) more frequent in short ISIs compared with medium and long ISIs. RTs were also slower and lapses more frequent at the circadian trough compared to both the early testing session and after 29h of total sleep deprivation. Discussion Increased lapses in shorter ISIs could be explained by an involuntary mental “rest period” after responding, that gets longer and more frequent under sleep pressure from both circadian and homeostatic sleep pressure. These findings have implications for interpreting PVT results and their application to everyday tasks, such as driving. Further research could involve neuroimaging the brain’s responses during different ISIs to confirm the mental ‘rest period’ following a response in the PVT task.

Monaural and dichotic forward masking in the dolphin's auditory system.

Short-latency auditory-evoked potentials (AEPs) were recorded non-invasively in the bottlenose dolphin Tursiops truncatus. The stimuli were two sound clicks that were played either monaurally (both clicks to one and the same acoustic window) or dichotically (the leading stimulus (masker) to one acoustic window and the delayed stimulus (test) to the other window). The ratio of the levels of the two stimuli was 0, 10, or 20dB (at 10 and 20dB, the leading stimulus was of a higher level). The inter-stimulus intervals (ISIs) varied from 0.15 to 10ms. The test response magnitude was assessed by correlation analysis as a percentage of the control (non-masked) response. At monaural stimulation, the test response was of a constant magnitude (5-6% of the control) at ISIs of 0.15-0.3ms and recovered at longer ISIs. At dichotic stimulation, the deepest suppression of the test response occurred at ISIs of 0.5-0.7ms. The response was slightly suppressed at short ISIs (0.15-0.3ms) and recovered at ISIs longer than 0.5-0.7ms. The relation of parameters of the forward masking to echolocation in dolphins is discussed.

Amyloid-β Effects on Peripheral Nerve: A New Model System.

Although there are many biochemical methods to measure amyloid-β (Aβ)42 concentration, one of the critical issues in the study of the effects of Aβ42 on the nervous system is a simple physiological measurement. The in vitro rat sciatic nerve model is employed and the nerve action potential (NAP) is quantified with different stimuli while exposed to different concentrations of Aβ42. Aβ42 predominantly reduces the NAP amplitude with minimal effects on other parameters except at low stimulus currents and short inter-stimulus intervals. The effects of Aβ42 are significantly concentration-dependent, with a maximum reduction in NAP amplitude at a concentration of 70 nM and smaller effects on the NAP amplitude at higher and lower concentrations. However, even physiologic concentrations in the range of 70 pM did reduce the NAP amplitude. The effects of Aβ42 became maximal 5-8 h after exposure and did not reverse during a 30 min washout period. The in vitro rat sciatic nerve model is sensitive to the effects of physiologic concentrations of Aβ42. These experiments suggest that the effect of Aβ42 is a very complex function of concentration that may be the result of amyloid-related changes in membrane properties or sodium channels.

Initial experiences with Direct Imaging of Neuronal Activity (DIANA) in humans

Abstract Functional MRI (fMRI) has been widely used to study activity patterns in the human brain. It infers neuronal activity from the associated hemodynamic response, which fundamentally limits its spatiotemporal specificity. In mice, the Direct Imaging of Neuronal Activity (DIANA) method revealed MRI signals that correlated with extracellular electric activity, showing high spatiotemporal specificity. In this work, we attempted DIANA in humans. Five experimental paradigms were tested, exploring different stimulus types (flickering noise patterns, and naturalistic images), stimulus durations (50–200 ms), and imaging resolution (2 × 2 × 5 mm3 and 1 × 1 × 5 mm3). Regions of interest (ROI) were derived from Blood Oxygen Level Dependent (BOLD) fMRI acquisitions (both EPI and FLASH based) and T1-weighted anatomical scans. In Paradigm I (n = 1), using flickering noise patterns, signals were detected that resembled possible functional activity from a small ROI. However, changes in stimulus duration did not lead to corresponding signal changes (Paradigm II; n = 1). Therefore, care should be taken not to mistake artifacts for neuronal activity. In Paradigm III (n = 3), when averaged across multiple subjects, a ~200 ms long 0.02% signal increase was observed ~100 ms after the stimulus onset (10x smaller than the expected signal). However, white matter control ROIs showed similarly large signal fluctuations. In Paradigm IV (n = 3), naturalistic image stimuli were used, but did not reveal signs of a potential functional signal. To reduce partial voluming effects and improve ROI definition, in Paradigm V (n = 3), we acquired data with higher resolution (1 × 1 × 5 mm3) using naturalistic images. However, no sign of activation was found. It is important to note that repetitive experiments with short interstimulus intervals were found to be strenuous for the subjects, which likely impacted data quality. To obtain better data, improvements in sequence and stimulus designs are needed to maximize the DIANA signal and minimize confounds. However, without a clear understanding of DIANA’s biophysical underpinnings it is difficult to do so. Therefore, it may be more effective to first investigate DIANA signals with simultaneously recorded electrophysiological signals in more controlled settings, e.g., in anesthetized mice.

Cortical excitability in human somatosensory and visual cortex: implications for plasticity and learning - a minireview.

The balance of excitation and inhibition plays a key role in plasticity and learning. A frequently used, reliable approach to assess intracortical inhibition relies on measuring paired-pulse behavior. Moreover, recent developments of magnetic resonance spectroscopy allows measuring GABA and glutamate concentrations. We give an overview about approaches employed to obtain information about excitatory states in human participants and discuss their putative relation. We summarize paired-pulse techniques and basic findings characterizing paired-pulse suppression in somatosensory (SI) and (VI) visual areas. Paired-pulse suppression describes the effect of paired sensory stimulation at short interstimulus intervals where the cortical response to the second stimulus is significantly suppressed. Simultaneous assessments of paired-pulse suppression in SI and VI indicated that cortical excitability is not a global phenomenon, but instead reflects the properties of local sensory processing. We review studies using non-invasive brain stimulation and perceptual learning experiments that assessed both perceptual changes and accompanying changes of cortical excitability in parallel. Independent of the nature of the excitation/inhibition marker used these data imply a close relationship between altered excitability and altered performance. These results suggest a framework where increased or decreased excitability is linked with improved or impaired perceptual performance. Recent findings have expanded the potential role of cortical excitability by demonstrating that inhibition markers such as GABA concentrations, paired-pulse suppression or alpha power predict to a substantial degree subsequent perceptual learning outcome. This opens the door for a targeted intervention where subsequent plasticity and learning processes are enhanced by altering prior baseline states of excitability.

Brain Functional Connectivity Networks do not Return to Resting-state During Control Trials in Block Design Experiments.

Many studies on morphology analysis show that if short inter-stimulus intervals separate tasks, the hemodynamic response amplitude will return to the resting-state baseline before the subsequent stimulation onset; hence, responses to successive tasks do not overlap. Accordingly, popular brain imaging analysis techniques assume changes in hemodynamic response amplitude subside after a short time (around 15 seconds). However, whether this assumption holds when studying brain functional connectivity has yet to be investigated. This paper assesses whether or not the functional connectivity network in control trials returns to the resting-state functional connectivity network. Traditionally, control trials in block-design experiments are used to evaluate response morphology to no stimulus. We analyzed data from an event-related experiment with audio and visual stimuli and resting state. Our results showed that functional connectivity networks during control trials were more similar to that of tasks than resting-state networks. In other words, contrary to task-related changes in the hemodynamic amplitude, where responses settle after a short time, the brain's functional connectivity networks do not return to their intrinsic resting-state network in such short intervals.

Patients with olfactory loss exhibit pronounced adaptation to chemosensory stimuli: an electrophysiological study.

Pronounced chemosensory adaptation affects many patients with olfactory loss. The study aimed to investigate adaptation to olfactory and trigeminal nasal stimuli in patients with olfactory loss in comparison to controls using electrophysiological measures. Thirty-four patients with olfactory loss (mean age ± SD = 59 ± 16 years) and 17 healthy volunteers (mean age ± SD = 50 ± 14 years) were recruited. Sniffin’ sticks test was used for evaluation of olfactory function and EEG-derived chemosensory event-related potentials were recorded. Intranasal stimuli were presented using high-precision, computer-controlled stimulators based on the principles of air-dilution olfactometry. Data were analyzed in two different approaches according to the relatively short or long inter-stimulus interval. A decreased peak amplitude or a prolonged latency was considered as an expression of adaptation. The majority of participants (88%) responded reliably to chemosensory stimulation. Patients with olfactory loss exhibited pronounced olfactory and trigeminal adaptation within the long-term design, without such effects in healthy controls. Odor sensitivity correlated with both olfactory and trigeminal amplitude changes: the worse the olfactory sensitivity, the more pronounced chemosensory adaptation. The results help to explain the patients’ complaints in terms of the fast adaptation towards chemosensory stimuli, for example during eating and drinking. The differences in adaptation in patients with olfactory loss and healthy controls could serve as a clinical criterion to gauge olfactory dysfunction.

Effects of working memory load and CS-US intervals on delay eyeblink conditioning

Eyeblink conditioning is used in many species to study motor learning and make inferences about cerebellar function. However, the discrepancies in performance between humans and other species combined with evidence that volition and awareness can modulate learning suggest that eyeblink conditioning is not merely a passive form of learning that relies on only the cerebellum. Here we explored two ways to reduce the influence of volition and awareness on eyeblink conditioning: (1) using a short interstimulus interval, and (2) having participants do working memory tasks during the conditioning. Our results show that participants trained with short interstimulus intervals (150 ms and 250 ms) produce very few conditioned responses after 100 trials. Participants trained with a longer interstimulus interval (500 ms) who simultaneously did working memory tasks produced fewer conditioned responses than participants who watched a movie during the training. Our results suggest that having participants perform working memory tasks during eyeblink conditioning can be a viable strategy for studying cerebellar learning that is absent of influences from awareness and volition. This could enhance the comparability of the results obtained in human studies with those in animal models.

Feasibility and optimal choice of stimulation parameters for supramaximal stimulation of motor evoked potentials

Purpose: The aim was to investigate the feasibility and optimal stimulation parameters for supramaximal stimulation of muscle recorded transcranial electrical stimulation motor evoked potentials (mTc-MEP). Methods: Forty-seven consecutive patients that underwent scoliosis surgery were included. First, the feasibility of supramaximal stimulation was assessed for two settings (setting 1: pulse duration 0.075ms, interstimulus interval (ISI) 1.5ms; setting 2: pulse duration 0.300ms, ISI 3ms). Thereafter, three mTc-MEP parameters were considered for both settings; (1) elicitability, (2) amplitude, and (3) if supramaximal stimulation was achieved with ≥ 20 V below maximum output. Finally, ISIs (1ms–4ms) were optimized for setting 1. Results: Nine patients (19.15%) were excluded. Of the remaining patients, supramaximal stimulation was achieved in all patients for setting 1, and in 26 (68.42%) for setting 2. In one patient, mTc-MEPs were elicitable in more muscles for setting (1) Amplitudes were not significantly different. Stimulation voltage could be increased ≥ 20 V in all 38 patients for setting 1 and in 10 (38.46%) for setting (2) Optimal ISI’s differed widely. Conclusion: We recommend using setting 1 when monitoring mTc-MEPs with supramaximal stimulation, after which an individualized ISI optimization can be performed. Moreover, when using supramaximal stimulation, short ISI’s (i.e. 1ms or 1.5ms) can be the optimal ISI for obtaining the highest mTc-MEP amplitude.

Temporal processing deficit in children and adolescents with autism spectrum disorder: An online assessment.

The sensory deficit has been considered as one of the core features in children and adolescents with autism spectrum disorder (ASD). The present study aimed to examine the temporal processing of simple and more complex auditory inputs in ASD children and adolescents with an online assessment that can be conducted remotely. One hundred fifty-eight children and adolescents aged 5-17 years participated in this study, including 79 ASD participants and 79 typically developing (TD) participants. The online assessment consisted of two temporal-order judgment tasks that required repeating the sequence of two pure tones or consonant-vowel (CV) syllabic pairs at varying interstimulus intervals (ISIs). Significantly lower accuracy rates were found in ASD than TD participants in the pure tone and the CV conditions with both short and long ISI. In addition, ASD participants (M = 245.97 ms) showed a significantly higher passing threshold than TD participants (M = 178.84 ms) in the CV task. Receiver operating characteristic analysis found that the age × ISI passing threshold composite yielded a sensitivity of 74.7% and a specificity of 50.6% at the cutoff point of -0.307 in differentiating ASD participants from TD participants. In sum, children and adolescents with ASD showed impaired temporal processing of both simple and more complex auditory stimuli, and the online assessment seems to be sensitive in differentiating individuals with ASD from those with TD.

Short-and long-latency afferent inhibition of the human leg motor cortex by H-reflex subthreshold electrical stimulation at the popliteal fossa

In humans, peripheral sensory stimulation inhibits subsequent motor evoked potentials (MEPs) induced by transcranial magnetic stimulation; this process is referred to as short- or long-latency afferent inhibition (SAI or LAI, respectively), depending on the inter-stimulus interval (ISI) length. Although upper limb SAI and LAI have been well studied, lower limb SAI and LAI remain under-investigated. Here, we examined the time course of the soleus (SOL) muscle MEP following electrical tibial nerve (TN) stimulation at the popliteal fossa at ISIs of 20–220 ms. When the conditioning stimulus intensity was three-fold the perceptual threshold, MEP amplitudes were inhibited at an ISI of 220 ms, but not at shorter ISIs. TN stimulation just below the Hoffman (H)-reflex threshold intensity inhibited MEP amplitudes at ISIs of 30, 35, 100, 180 and 200 ms. However, the relationship between MEP inhibition and the P30 latency of somatosensory evoked potentials (SEPs) did not show corresponding ISIs at the SEP P30 latency that maximizes MEP inhibition. To clarify whether the site of afferent-induced MEP inhibition occurs at the cortical or spinal level, we examined the time course of SOL H-reflex following TN stimulation. H-reflex amplitudes were not significantly inhibited at ISIs where MEP inhibition occurred but at an ISI of 120 ms. Our findings indicate that stronger peripheral sensory stimulation is required for lower limb than for upper limb SAI and LAI and that lower limb SAI and LAI are of cortical origin. Moreover, the direct pathway from the periphery to the primary motor cortex may contribute to lower limb SAI.

Effects of exogenous and endogenous cues on attentional orienting in deaf adults.

Adults who are deaf have been shown to have better visual attentional orienting than those with typical hearing, especially when the target is located in the periphery of the visual field. However, most studies in this population have assessed exogenous visual attention orienting (bottom-up processing of external cues) rather than endogenous visual attention orienting (top-down processing of internal cues). We used a target detection task to assess both types of visual attention orienting. A modified cue-target paradigm was adopted to assess the facilitation effects of exogenous and endogenous cues during short and long inter-stimulus intervals (ISI), using a 2 (Group: deaf/typically hearing) * 2 (Location: central/peripheral) * 2 (Cue Type: exogenous/endogenous) mixed factorial design. ANOVAs showed that both exogenous cues and endogenous cues can facilitate deaf adults’ visual attentional orienting, and the facilitation effect of exogenous cues on attention orienting was significantly stronger for deaf participants than hearing participants. When the ISI was long, the effect was significantly stronger when the exogenous cue appeared in the periphery of the visual field. In the periphery, deaf adults benefited most from exogenous cues, whereas hearing adults benefited most from endogenous cues. The results suggest that not only exogenous cues but also endogenous cues can facilitate deaf adults’ visual attentional orienting. However, the effect of exogenous cues appears to be greater, especially when the stimulus appears in the peripheral visual field.

What is the contribution of voluntary and reflex processes to sensorimotor control of balance?

The contribution to balance of spinal and transcortical processes including the long-latency reflex is well known. The control of balance has been modelled previously as a continuous, state feedback controller representing, long-latency reflexes. However, the contribution of slower, variable delay processes has not been quantified. Compared with fixed delay processes (spinal, transcortical), we hypothesize that variable delay processes provide the largest contribution to balance and are sensitive to historical context as well as current states. Twenty-two healthy participants used a myoelectric control signal from their leg muscles to maintain balance of their own body while strapped to an actuated, inverted pendulum. We study the myoelectric control signal (u) in relation to the independent disturbance (d) comprising paired, discrete perturbations of varying inter-stimulus-interval (ISI). We fit the closed loop response, u from d, using one linear and two non-linear non-parametric (many parameter) models. Model M1 (ARX) is a generalized, high-order linear-time-invariant (LTI) process with fixed delay. Model M1 is equivalent to any parametric, closed-loop, continuous, linear-time-invariant (LTI), state feedback model. Model M2, a single non-linear process (fixed delay, time-varying amplitude), adds an optimized response amplitude to each stimulus. Model M3, two non-linear processes (one fixed delay, one variable delay, each of time-varying amplitude), add a second process of optimized delay and optimized response amplitude to each stimulus. At short ISI, the myoelectric control signals deviated systematically both from the fixed delay LTI process (M1), and also from the fixed delay, time-varying amplitude process (M2) and not from the two-process model (M3). Analysis of M3 (all fixed delay and variable delay response amplitudes) showed the variable (compared with fixed) delay process 1) made the largest contribution to the response, 2) exhibited refractoriness (increased delay related to short ISI) and 3) was sensitive to stimulus history (stimulus direction 2 relative to stimulus 1). For this whole-body balance task and for these impulsive stimuli, non-linear processes at variable delay are central to control of balance. Compared with fixed delay processes (spinal, transcortical), variable delay processes provided the largest contribution to balance and were sensitive to historical context as well as current states.

Temporal Dynamics of Neural Responses in Human Visual Cortex.

Neural responses to visual stimuli exhibit complex temporal dynamics, including subadditive temporal summation, response reduction with repeated or sustained stimuli (adaptation), and slower dynamics at low contrast. These phenomena are often studied independently. Here, we demonstrate these phenomena within the same experiment and model the underlying neural computations with a single computational model. We extracted time-varying responses from electrocorticographic recordings from patients presented with stimuli that varied in duration, interstimulus interval (ISI) and contrast. Aggregating data across patients from both sexes yielded 98 electrodes with robust visual responses, covering both earlier (V1-V3) and higher-order (V3a/b, LO, TO, IPS) retinotopic maps. In all regions, the temporal dynamics of neural responses exhibit several nonlinear features. Peak response amplitude saturates with high contrast and longer stimulus durations, the response to a second stimulus is suppressed for short ISIs and recovers for longer ISIs, and response latency decreases with increasing contrast. These features are accurately captured by a computational model composed of a small set of canonical neuronal operations, that is, linear filtering, rectification, exponentiation, and a delayed divisive normalization. We find that an increased normalization term captures both contrast- and adaptation-related response reductions, suggesting potentially shared underlying mechanisms. We additionally demonstrate both changes and invariance in temporal response dynamics between earlier and higher-order visual areas. Together, our results reveal the presence of a wide range of temporal and contrast-dependent neuronal dynamics in the human visual cortex and demonstrate that a simple model captures these dynamics at millisecond resolution.SIGNIFICANCE STATEMENT Sensory inputs and neural responses change continuously over time. It is especially challenging to understand a system that has both dynamic inputs and outputs. Here, we use a computational modeling approach that specifies computations to convert a time-varying input stimulus to a neural response time course, and we use this to predict neural activity measured in the human visual cortex. We show that this computational model predicts a wide variety of complex neural response shapes, which we induced experimentally by manipulating the duration, repetition, and contrast of visual stimuli. By comparing data and model predictions, we uncover systematic properties of temporal dynamics of neural signals, allowing us to better understand how the brain processes dynamic sensory information.