Irregular Interstimulus Intervals Research Articles

Dynamics and Mechanisms of ERK Activation after Different Protocols that Induce Long-Term Synaptic Facilitation in Aplysia.

Phosphorylation of the MAPK family member extracellular signal-regulated kinase (ERK) is required to induce long-term synaptic plasticity, but little is known about its persistence. We examined ERK activation by three protocols that induce long-term synaptic facilitation (LTF) of the Aplysia sensorimotor synapse - the standard protocol (five 5-min pulses of 5-HT with interstimulus intervals (ISIs) of 20min), the enhanced protocol (five pulses with irregular ISIs, which induces greater and longer-lasting LTF) and the two-pulse protocol (two pulses with ISI 45min). Immunofluorescence revealed complex ERK activation. The standard and two-pulse protocols immediately increased active, phosphorylated ERK (pERK), which decayed within 5h. A second wave of increased pERK was detected 18h post-treatment for all protocols. This late phase was blocked by inhibitors of protein kinase A, TrkB and TGF-β. These results suggest that complex interactions among kinase pathways and growth factors contribute to the late increase of pERK. ERK activity returned to basal 24h after the standard or two-pulse protocols, but remained elevated 24h for the enhanced protocol. This 24-h elevation was also dependent on PKA and TGF-β, and partly on TrkB. These results begin to characterize long-lasting ERK activation, plausibly maintained by positive feedback involving growth factors and PKA, that appears essential to maintain LTF and LTM. Because many processes involved in LTF and late LTP are conserved among Aplysia and mammals, these findings highlight the importance of examining the dynamics of kinase cascades involved in vertebrate long-term memory.

Improved Transient Response Estimations in Predicting 40 Hz Auditory Steady-State Response Using Deconvolution Methods.

The auditory steady-state response (ASSR) is one of the main approaches in clinic for health screening and frequency-specific hearing assessment. However, its generation mechanism is still of much controversy. In the present study, the linear superposition hypothesis for the generation of ASSRs was investigated by comparing the relationships between the classical 40 Hz ASSR and three synthetic ASSRs obtained from three different templates for transient auditory evoked potential (AEP). These three AEPs are the traditional AEP at 5 Hz and two 40 Hz AEPs derived from two deconvolution algorithms using stimulus sequences, i.e., continuous loop averaging deconvolution (CLAD) and multi-rate steady-state average deconvolution (MSAD). CLAD requires irregular inter-stimulus intervals (ISIs) in the sequence while MSAD uses the same ISIs but evenly-spaced stimulus sequences which mimics the classical 40 Hz ASSR. It has been reported that these reconstructed templates show similar patterns but significant difference in morphology and distinct frequency characteristics in synthetic ASSRs. The prediction accuracies of ASSR using these templates show significant differences (p < 0.05) in 45.95, 36.28, and 10.84% of total time points within four cycles of ASSR for the traditional, CLAD, and MSAD templates, respectively, as compared with the classical 40 Hz ASSR, and the ASSR synthesized from the MSAD transient AEP suggests the best similarity. And such a similarity is also demonstrated at individuals only in MSAD showing no statistically significant difference (Hotelling's T2 test, T2 = 6.96, F = 0.80, p = 0.592) as compared with the classical 40 Hz ASSR. The present results indicate that both stimulation rate and sequencing factor (ISI variation) affect transient AEP reconstructions from steady-state stimulation protocols. Furthermore, both auditory brainstem response (ABR) and middle latency response (MLR) are observed in contributing to the composition of ASSR but with variable weights in three templates. The significantly improved prediction accuracy of ASSR achieved by MSAD strongly supports the linear superposition mechanism of ASSR if an accurate template of transient AEPs can be reconstructed. The capacity in obtaining both ASSR and its underlying transient components accurately and simultaneously has the potential to contribute significantly to diagnosis of patients with neuropsychiatric disorders.

Inducing attention not to blink: auditory entrainment improves conscious visual processing.

Our ability to allocate attention at different moments in time can sometimes fail to select stimuli occurring in close succession, preventing visual information from reaching awareness. This so-called attentional blink (AB) occurs when the second of two targets (T2) is presented closely after the first (T1) in a rapid serial visual presentation (RSVP). We hypothesized that entrainment to a rhythmic stream of stimuli-before visual targets appear-would reduce the AB. Experiment 1 tested the effect of auditory entrainment by presenting sounds with a regular or irregular interstimulus interval prior to a RSVP where T1 and T2 were separated by three possible lags (1, 3 and 8). Experiment 2 examined visual entrainment by presenting visual stimuli in place of auditory stimuli. Results revealed that irrespective of sensory modality, arrhythmic stimuli preceding the RSVP triggered an alerting effect that improved the T2 identification at lag 1, but impaired the recovery from the AB at lag 8. Importantly, only auditory rhythmic entrainment was effective in reducing the AB at lag 3. Our findings demonstrate that manipulating the pre-stimulus condition can reduce deficits in temporal attention characterizing the human cognitive architecture, suggesting innovative trainings for acquired and neurodevelopmental disorders.

Minimization of cochlear implant artifact in cortical auditory evoked potentials in children

ObjectivesIn congenitally deaf children fit with a cochlear implant, little is known about the maturation of the auditory cortex. Cortical auditory evoked potentials are a useful methodology to study the auditory cortical system of children with cochlear implants. Nevertheless, these recordings are contaminated by a cochlear implant artifact. The objective of this study was to use independent component analysis to minimize the artifact of the cochlear implant to study cortical auditory evoked potentials. Study designProspective study. MethodA total of 5 children ranging in age from 21 to 49 months who were fitted with a cochlear implant for at least 6 months were included in this study. The stimuli were pure tones (750Hz, 200ms duration, 70dB SPL) presented with an irregular interstimulus interval (1000–2000ms) via loud speakers. The cortical auditory evoked potentials were recorded from 17 Ag–AgCl electrodes referenced to the nose. The peak latency and amplitude of each deflection culminating at the fronto-central and temporal sites were analyzed. Main outcome measuresThe P100–N250 peak latencies and amplitudes of the cortical auditory evoked potentials recorded from children fitted with cochlear implants. Scalp map potentials distributions were done for each child for the N250 wave. ResultsThe use of independent component analysis permitted to minimize the cochlear implant artifact for the five children. Cortical auditory evoked potentials were recorded at fronto-central and temporal sites. Scalp map potentials distributions for the N2 wave showed activation of temporal generators contralateral at the CI for the five children. ConclusionThis preliminary electrophysiological study confirms the value and the limits of independent component analysis. It could allow longitudinal studies in cochlear implant users to examine the maturation of auditory cortex. It could also be used to identify objective cortical electrophysiological measures to help the fitting of CIs in children.

Next-Day Effects of Alcohol and an Additional Stressor on Memory and Psychomotor Performance

This study aimed to investigate the effects of a stressor, white noise, on cognitive performance of subjects in the compromised hangover state. The study followed a mixed factorial, counterbalanced, repeated-measures design with noise, order of testing, and time of testing as between-participants factors and state during testing as a within-participants factor. Seventy-eight participants performed memory and psychomotor tasks the morning after a regular night of drinking and the morning after a night of no alcohol consumption. Forty-eight participants were tested in the no-noise condition, and the other 30 participants had an additional factor of white noise during both testing sessions. Measures of memory and psychomotor performance are reported. The stressor (white noise) resulted in poorer memory performance only when participants had consumed alcohol the night before testing (F = 7.45, 1/66 df, p < .01). Stress also had a detrimental effect on simple reaction time the morning after alcohol consumption in both the task with regular interstimulus interval (F = 4.61, 1/65 df, p < .05) and irregular interstimulus interval (F = 4.45, 1/65 df, p < .05). The five-choice reaction time task revealed that initial move time and return time were slowed by stress and following a night of intoxication, but these factors did not interact. Stress interacted with time of testing and state in the measure of decision time, indicating that noise has a detrimental effect during the hangover state early in the morning and a detrimental effect during the no-hangover state early in the afternoon. The addition of a stressor results in a significant deterioration in memory and psychomotor performance when persons are in the compromised hangover condition.

Visual behaviour of ADHD children during an attention test: an almost forgotten variable. Attention-Deficit Hyperactivity Disorder.

The goal of this study was to examine whether looking away behaviour of ADHD children interferes with their test performance. ADHD and normal children carried out two continuous performance tests (CPTs): one with a regular interstimulus interval (ISI), and the other with an irregular ISI. Children were instructed to push a response button when a target stimulus was presented on the monitor. The children's visual behaviour was recorded and scored offline. A micro-analysis of the visual behaviour indicated that ADHD children timed their looking away behaviour in the regular CPT: i.e. they looked away from the monitor and back in the interval between two succeeding stimuli. As a result they did not miss stimuli. Timing of looking away was less possible in the CPT with the irregular ISI. In this condition, looking away interfered with the ADHD children's task accuracy. In sum, looking away behaviour had a negative effect on the accuracy of test performance of ADHD children when stimuli were unpredictable. Looking away behaviour was not associated with the slower reaction times of the ADHD children. Hence, the often reported slowness of ADHD children is not to be explained by their visual behaviour.

Visual Behaviour of ADHD Children During an Attention Test: An Almost Forgotten Variable

The goal of this study was to examine whether looking away behaviour of ADHD children interferes with their test performance. ADHD and normal children carried out two continuous performance tests (CPTs): one with a regular interstimulus interval (ISI), and the other with an irregular ISI. Children were instructed to push a response button when a target stimulus was presented on the monitor. The children's visual behaviour was recorded and scored offline. A micro‐analysis of the visual behaviour indicated that ADHD children timed their looking away behaviour in the regular CPT: i.e. they looked away from the monitor and back in the interval between two succeeding stimuli. As a result they did not miss stimuli. Timing of looking away was less possible in the CPT with the irregular ISI. In this condition, looking away interfered with the ADHD children's task accuracy. In sum, looking away behaviour had a negative effect on the accuracy of test performance of ADHD children when stimuli were unpredictable. Looking away behaviour was not associated with the slower reaction times of the ADHD children. Hence, the often reported slowness of ADHD children is not to be explained by their visual behaviour.

Intermodal selective attention in monkeys. I: distribution and timing of effects across visual areas.

This study quantified the magnitude and timing of selective attention effects across areas of the macaque visual system, including the lateral geniculate nucleus (LGN), lower cortical areas V1 and V2, and multiple higher visual areas in the dorsal and ventral processing streams. We used one stimulus configuration and behavioral paradigm, with simultaneous recordings from different areas to allow direct comparison of the distribution and timing of attention effects across the system. Streams of interdigitated auditory and visual stimuli were presented at a high rate with an irregular interstimulus interval (mean of 4/s). Attention to visual stimuli was manipulated by requiring subjects to make discriminative behavioral responses to stimuli in one sensory modality, ignoring all stimuli in the other. The attended modality was alternated across trial blocks, and difficulty of discrimination was equated across modalities. Stimulus presentation was gated, so that no stimuli were presented unless the subject gazed at the center of the visual stimulus display. Visual stimuli were diffuse light flashes differing in intensity or color and subtending 12 degrees centered at the point of gaze. Laminar event-related potential (ERP) and current source density (CSD) response profiles were sampled during multiple paired penetrations in multiple visual areas with linear array multicontact electrodes. Attention effects were assessed by comparing responses to specific visual stimuli when attended versus when visual stimuli were looked at the same way, but ignored. Effects were quantified by computing a modulation index (MI), a ratio of the differential CSD response produced by attention to the sum responses to attended and ignored visual stimuli. The average MI increased up levels of the lower visual pathways from none in the LGN to 0.0278 in V1 to 0.101 in V2 to 0.170 in V4. Above the V2 level, attention effects were larger in ventral stream areas (MI = 0. 152) than in dorsal stream areas (MI = 0.052). Although onset latencies were shortest in dorsal stream areas, attentional modulation of the early response was small relative to the stimulus-evoked response. Higher ventral stream areas showed substantial attention effects at the earliest poststimulus time points, followed by the lower visual areas V2 and V1. In all areas, attentional modulation lagged the onset of the stimulus-evoked response, and attention effects grew over the time course of the neuronal response. The most powerful, consistent, and earliest attention effects were those found to occur in area V4, during the 100-300 ms poststimulus interval. Smaller effects occurred in V2 over the same interval, and the bulk of attention effects in V1 were later. In the accompanying paper, we describe the physiology of attention effects in V1, V2 and V4.

Human Auditory Fast and Slow Omitted Stimulus Potentials and Steady-State Responses

Two kinds of omitted stimulus potentials (OSP) are called “fast” and “slow.” Fast OSPs, recently found with visual stimuli, are here extended to auditory; they occur after omissions or after the end of trains of 1 to > 20 Hz clicks. Slow OSPs, long known, follow trains of 0.3 to 4 Hz. Each has its constant peak latency after the due-time of the first missing stimulus, as though the system is expecting something quite accurately on schedule. They differ in dynamics and slow OSPs require the subject to attend; fast OSPs do not. Steady-state responses (SSR) at a critical click rate of 6–7 Hz sometimes appear to alternate between two forms and OSPs may depend on which they follow. Fast OSPs can occur to the first, second and even the third omissions after the end of a train. Short conditioning periods suffice. Irregular interstimulus intervals do not reduce fast OSPs but attenuate slow OSPs.

Sympathetic skin response in diabetic neuropathy: a prospective clinical and neurophysiological trial on 100 patients

Sympathetic skin response (SSR) can be employed to assess axonal damage of sympathetic sudomotor neurons in neuropathy. We examined a population of 100 patients with diabetic neuropathy, and 100 age- and sex-matched healthy volunteers. SSR was recorded from the skin of the hand and foot by means of surface electrodes. Stimulation was applied with 30 mA over the median nerve at the wrist contralateral to the derivation site. Irregular interstimulus intervals of more than one minute were applied. Peak-to-peak amplitude measurement showed values of 2.91 ± 1.10 mV on the hand and 1.37 ± 0.54 mV on the foot. Latencies lasted 1.44 ± 0.10 s on the hand and 2.12 ± 0.15 s on the foot. A total of 37% of the diabetics showed loss of SSR, a further 39% showed amplitude reductions or latency prolongations: Altogether, 76% of all diabetics did not show normal test results. The clinical stage of diabetic neuropathy exerted a significant influence: the further developed the clinical picture of the disease was, the more pathologic were the results of SSR testing. However, even at early stages of neuropathy abnormal values of amplitude reduction or latency prolongation could be observed in over 50% of the patients. SSR examinations performed in diabetics with no or only slight clinical signs of neuropathy may be able to detect those subjects with autonomic disturbances at an initial stage.

Event-related potentials in the retina and optic tectum of fish

1. Compound field potentials were recorded with up to 18 microelectrodes in comb, brush, or spear arrays on and in the optic tectum and with suction electrodes from the distal stump of the cut optic nerve and from the optic nerve head in the opened eye in elasmobranchs and teleosts. Diffuse light flashes of different durations and submaximal intensities were delivered in trains with regular or irregular interstimulus intervals (ISI). 2. Event-related potentials (ERPs) are visible in single trials and begin at 50-200 ms after an "oddball" flash, especially one that is slightly weaker, briefer, or delayed by as little as 6% of ISI, compared with the more frequent stimulus. ERPs to the opposite condition are not of the same form or size. 3. One or more stimuli were omitted from a train or the train terminated after various conditioning times. Deflections occur beyond the expected visual-evoked potentials (VEPs) to the last flash and are called omitted-stimulus potentials (OSPs). They occur on schedule--approximately 100 ms after the next flash would be due--almost independent of intensity, duration, or conditioning time. They are considered to be ERPs without any necessary implication or denial of a temporally specific expectation. 4. Three components of OSP occur alone or in combination: an initial fast peak, a slow wave, and an oscillatory spindle up to ls or more in duration. This resembles the OFF response to steady light. 5. All these components are already present in the retina with optic nerve cut. 6. The same mean ISI with a high proportion of jitter gives OSPs with only slightly longer latencies and smaller amplitudes; the OSP acts as though the retina makes an integrated prediction of ISI, intensity, and duration. 7. During a conditioning train the equilibrium between excitation and inhibition after each flash changes according to frequency, intensity, duration, and conditioning time; the VEP reflects this in a shape unique to the ISI; inhibition increases rapidly after each flash and then decays slowly according to the recent mean ISI. This allows rebound disinhibition after missing, weak, or delayed flashes (OSP or ERP) or causes an altered VEP after a longer or stronger oddball. 8. It seems unlikely that the OSP or oddball ERP in fish tectum is equivalent to mammalian ERPs under the same regime or signals higher cognitive events, because they are already present in the retina, require flash frequencies greater than 1 Hz, and grow with frequency up to and beyond flicker fusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Conduction of trains of impulses in uniform myelinated fibers: Computed dependence on stimulus frequency

The conduction of trains of action potentials in myelinated fibers was studied using computer simulations based on a modification of the Hodgkin-Huxley equations. Stimulation at short but regular interstimulus intervals caused some stimuli to fail to elicit propagated action potentials. Propagated impulse trains observed close to the stimulation site, elicited by high frequency stimulus trains, took the form of ‘clusters’ of impulses, e.g. doublets or triplets. When these impulse trains were observed at distances farther from the stimulation site, interspike intervals were more uniform. For interstimulus intervals of less than 10 ms, distant intervals between impulses were relatively insensitive to the temporal patterning of impulses at the initiation zone and tended toward regular intervals corresponding to the average interstimulus intervals for propagated stimuli. This tendency toward uniform intervals between impulses was also observed for lower average frequency stimulus trains with irregular interstimulus intervals. Moreover, for the first two stimuli in a train, there was a very strong tendency toward impulse entrainment. These results indicate that intervals between impulses along unbranched myelinated axons are not fixed, but vary according to the site along the conduction pathway where they are observed. The tendency toward entrainment, and regularization of intervals, may represent a factor limiting the frequency with which interval-coded impulses are initiated.

Habituation during sleep.

ABSTRACTIn some recent reports, authors have found no evidence for habituation during sleep, and have concluded that habituation and sleep are incompatible. This finding was tested using skin potential, heart rate, and EEG responses to a 70 dB, 1 sec, 1000 Hz tone, in sleep stages 2, 4, and REM, with daytime controls. Interstimulus intervals used ranged from 10 to 30 sec.Autonomic responses analyzed separately for each series of stimuli showed significant habituation, except for heart rate responses in REM and in the daytime (drowsy) controls. EEG responses also demonstrated habituation. An interstimulus interval effect was found with EEG K‐complexes, habituation occurring more slowly or not at all with the longer, irregular interstimulus intervals.It is suggested that previous failure to detect habituation has been due to a technique of averaging responses over hourly periods and/or the use of long irregular interstimulus intervals. It is concluded that habituation is indeed possible in human sleep if stimulus intervals are not long.

Regular interstimulus interval as a critical determinant of short-term “habituation” of the auditory averaged evoked response

In order to delineate the critical condition for the short-term “habituation” of the cortical auditory averaged evoked response, two levels of activation were combined with regular vs irregular interstimulus intervals in a 2 by 2 factorial design. Averages were computed across 24 trains of 10 click stimuli each. It was found that a regular interstimulus interval produced a rapid exponential decreasing function within trains for the N1-P2 component regardless of activation level. High activation, however, resulted in smaller P2-N2 components.

The effect of frequency variation upon RT to the second of two shortly spaced auditory stimuli

A prepulse of a duration of 25 msec (S 1) was followed by an auditory reaction stimulus (S 2) requiring a binary choice. The stimuli were separated by an irregular interstimulus interval (ISI), ranging from 10 to 500 msec. The effect of S 1 upon the reaction time (RT) to S 2 was examined under the condition that S 1 was a choice from three alternatives instead of having a fixed value. In part 1 of the main experiment, S 1 was assigned the values of 1250, 2000 and 2750 Hz and S 2 was 1000 and 3000 Hz. In part 2, the values were 750, 1500 and 3000 Hz (S 1) and 500 and 4000 Hz (S 2). Under the single-valued S 1 conditions S 1 was assigned the middle values of the three-valued S 1 conditions. No difference was found in general performance between the single-valued and three-valued S 1 conditions in both parts. Moreover, the relationship of RT with ISI was similar. A second question concerned the effect of the magnitude of the frequency differences between S 1 and S 2 upon RT. The data demonstrated that RT varies monotonously with the frequency separation of S 1 and S 2. This relationship was most pronounced for the shortest ISIs (10, 50, 75 msec). This finding is not in accordance with the inhibition hypothesis based on the neurophysiological research of Nelson and Erulkar (1963). The results give support to the suggestion that the frequency of S 1 has an effect upon the processing of the frequency of S 2 operating independently from its function as a trigger for response preparation. An additional experiment proved that the frequency separation of the two S 2 values, as used in part 1 and part 2 of the main experiment, did not influence RT significantly.

Selective attention and “habituation” of the auditory averaged evoked response in humans

The study examined the effects of direction of attention and interstimulus interval on the rate of amplitude decrement over time of the vertex auditory evoked response in humans. Short-term or stimulus-by-stimulus changes were studied by averaging across 24 discretely presented trains each of 10 click stimuli. Long-term or train-by-train changes were studied by averaging over successive pairs of trains. When attending to the clicks, the subject performed a reaction-time (RT) task with the click as stimulus; when ignoring the clicks he performed RTs to a visual stimulus. Both RT tasks were performed with irregular interstimulus intervals of 2.4 – 3.6 and 8 – 12 s, each of the 8 subjects being thus studied on four occasions. Attending to the stimuli and long interstimulus intervals enhanced the P 1-N 1-P 2 components. Amplitude decreased over time both for stimulus-by-stimulus and train-by-train averages. Somewhat unexpectedly, there was a slight but significant tendency towards a steeper slope for the attending and long interstimulus interval conditions, probably following on the larger initial responses for these conditions.

The effect of time intervals between two shortly spaced acoustic signals on response times to the second

An experiment on the psychological refractory period was carried out, in which two successively presented acoustic signals were given to four Ss. S 1 was a single-valued click not requiring an overt reaction, and S 2 was a double-valued tone asking for a binary choice response. Interspacing of S 1 and S 2 was regular and irregular. The interstimulus intervals (ISI) ranged from 50 to 500 msec. The presence of S 1 yielded an inverse relationship between RT and ISI from 50 to 250 msec for all Ss, but at longer ISI RT tended to increase. Time uncertainty exerted a lengthening effect on RT. Further, the curvilinearity between RT and ISI was more marked. Omission of S 1 effectuated nearly no discrepancy between regular and irregular ISI presentation, but RT in the without S 1 conditions were generally longer than RT in the with S 1 conditions.