Short Stimulus Durations Research Articles

Synaptic Remodeling through MAPK

Synaptic plasticity is a model for learning and memory. Dendrites, the sites of excitatory synaptic contacts, undergo morphological changes in response to stimuli. Wu et al. investigated the role of the mitogen-activated protein kinase (MAPK) pathway in changes in dendritic structure in response to multiple brief depolarizations over a period of minutes in cultured neurons or explants. Single stimuli (depolarizations induced by elevated extracellular K + ) of long or short duration produced a transient activation of the MAPKs, ERK1 and ERK2, measured as phosphorylation of these MAPKs. However, repeated spaced depolarizations produced a prolonged MAPK phosphorylation. Application of pharmacological inhibitors showed that the initial increase in MAPK activity depended on an increase in the concentration of free intracellular Ca 2+ , activation of calmodulin and calcium/calmodulin-dependent kinase, the small guanosine triphosphatase Ras, and MEK (the upstream kinase for ERK1 and 2). Persistent MAPK phosphorylation required continuous activity of MEK and was dependent on protein kinase A. In explants of dentate gyrus transfected to express green fluorescent protein, MAPK activity was found to be essential for changes in dendrite morphology (filopodial extensions and the formation of new spines) produced by multiple spaced stimulations. G.-Y. Wu, K. Deisseroth, R.W. Tsien, Spaced stimuli stabilize MAPK pathway activation and its effects on dendritic morphology. Nature Neurosci. 4 , 151-158 (2001). [Online Journal]

H reflex behavior in Parkinson's disease patients. Effect of stimulus duration

Electrical stimulus, with duration starting at 0.1ms and gradually increasing to 1.0ms, was used for eliciting the H reflex in 21 normal subjects and 48 patients with Parkinson's disease (PD). In 19 normal subjects (90.5%), the threshold for sensory fibers was lower than for motor fibers, and the H reflex was obtained before the M response for all duration stimuli. In 19 PD patients (39.6%), with mild or moderate rigidity (according to the motor part of UPDRS), the threshold for the H reflex and M response was the same or the M response threshold was lower in at least one of the legs for short stimulus duration (0.1-0.2ms). In 15 PD (31.2%) patients (most of them with severe rigidity), the threshold for M response was lower for all stimulus duration, and it was obtained before the H reflex. In 14 PD (29.2%) patients, the H reflex behavior was the same as in most normal subjects in one or both legs.These very significant differences in the behavior of the H reflex in PD patients (Fisher exact test, P<0.0001) could possibly be explained by changes in agonist-antagonist inhibition, and could be used as another parameter in the clinical assessment of extrapyramidal rigidity in PD patients.

Neural Representation of Sound Duration in the Inferior Colliculus of the Mouse

In this study we examined the neuronal responses of single units to different sound durations in the inferior colliculus (IC) of the mouse. One hundred and one recorded units were classified into onset (58%), sustained (9%), on-sustained (22%), pauser (9%) and chopper (2%) response patterns. Thirty-four percent of the recorded units showing stronger responses to long stimulus durations were defined as long-duration-selective neurons. Twenty-five percent of the units preferred a narrow range of sound durations and were classified as band-pass neurons. Ten percent of the units responded preferentially to short stimulus durations and thus displayed short-duration selectivity. Twelve percent of the units that responded with nearly constant spike counts to stimuli of varying duration were classified as all-pass neurons. In contrast to the result of no short-duration-selective neurons found in chinchilla IC, we observed that some of the onset units in the IC of the mouse displayed a short duration preference. The best duration range of the duration-selective neurons in the present study corresponds to the duration range of mouse calls. We suggest that an inhibitory mechanism contributes to the duration selectivity observed in the present study.

Improved auditory spatial acuity in visually deprived ferrets

We have examined the effects on auditory spatial acuity in the horizontal plane of depriving ferrets of patterned visual cues by binocular eyelid suture in infancy or for a comparable period in adulthood. Minimum audible angles (MAAs) were measured for 500-, 100- and 40-ms broadband noise bursts at the midline and at 45 degrees to one side. A logistic regression analysis revealed no consistent difference between the midline MAAs of normal and infant lid-sutured ferrets. However, the lateral field MAAs of the infant-deprived group were significantly smaller and showed less inter-subject variability than those of normal-sighted ferrets. The animals deprived in adulthood were tested in the lateral field only, firstly 6 months after binocular eyelid suture and again after a further 10 months. For the first test, the MAAs achieved by these animals with 500- and 100-ms noise bursts were significantly smaller than the normal values and no different from those of the infant-deprived group. A significant improvement in performance at the two shortest stimulus durations (100 and 40 ms) was observed when the adult-deprived animals were re-tested. Their second-test MAAs did not differ from those of the infant-deprived group at any of the three stimulus durations used, and both groups achieved significantly better scores than the normal-sighted control animals. These results show that prolonged visual deprivation in both juvenile and adult ferrets can lead to a significant improvement in auditory spatial acuity in the lateral sound field. This is consistent with reports that congenitally blind humans can localize peripheral sounds more accurately than normal controls.

Imputation of direction of motion in one dimension

Under many conditions below the Nyquist limit, a drifting grating briefly displayed on a CRT is consistently perceived as moving in the opposite direction. Taking into account the sample-and-hold operation of CRT’s, we have derived the temporal-frequency spectra of the displayed gratings and found that they have a broad range of components moving in either direction. We have measured the perceived direction of motion of over 150 different short-duration stimuli, and we have studied the relation that performance bears to narrow-band power imbalance—the normalized difference between power in the positive- and negative-frequency half-lines within a specific band. Perceived direction of motion is highly related to power imbalance in 1-Hz-wide bands centered between 10 and 15 Hz, but none of these bands alone can account for more than 84–91% of the variance of the data, and each band ostensibly fails to explain data from a subset of the stimuli. When broadband power imbalance is determined by weighting the spectrum with an inverted-U-shaped function peaking at ∼12 Hz, the explained variance increases to 91–97%. Our results suggest that the imputation of direction of motion to stimuli with complex spectra is based on broadband power imbalance determined after weighting the temporal-frequency spectrum with an inverted-U-shaped function.

Sex and Hemispheric Differences for Rapid Auditory Processing in Normal Adults

Previous research suggests that left hemisphere specialisation for processing speech may specifically depend on rate-specific parameters, with rapidly successive or faster changing acoustic stimuli (e.g. stop consonant-vowel syllables) processed preferentially by the left hemisphere. The current study further investigates the involvement of the left hemisphere in processing rapidly changing auditory information, and examines the effects of sex on the organisation of this function. Twenty subjects participated in an auditory discrimination task involving the target identification of a two-tone sequence presented to one ear, paired with white noise to the contralateral ear. Analyses demonstrated a right ear advantage for males only at the shorter interstimulus interval durations (mean = 20msec) whereas no ear advantage was observed for women. These results suggest that the male brain is more lateralised for the processing of rapidly presented auditory tones, specifically at shorter stimulus durations.

Effect of signal duration on categorical loudness scaling in normal and in hearing-impaired listeners.

The present study sought to determine whether the duration of white-noise bursts affects their loudness category rating in the same way for hearing-impaired as for normally-hearing subjects. Twelve normally-hearing and 12 hearing-impaired subjects took part. Categorical loudness growth functions were obtained for 16.25 ms, 32.5 ms, 75 ms, 150 ms and 300 ms white noise bursts. Temporal integration of loudness was defined as the intensity difference needed for stimuli of different durations to result in identical category ratings. In normally-hearing subjects, temporal integration of loudness occurred mainly with the short-duration (16.25 ms and 32.5 ms) stimuli, whereas it was found with almost every stimulus duration in hearing-impaired subjects. In other words, temporal integration of loudness between 16.25 ms and 300 ms stimulus duration was greater in hearing-impaired listeners and there was a difference between normal and hearing-impaired subjects regarding change in loudness perception with stimulus duration. Consequently, the use of fixed-duration stimuli hinders loudness normalization.

Event-related fMRI of pain: entering a new era in imaging pain.

Previous imaging studies of pain used a block design of prolonged (up to 1 min) noxious stimulation that are not well tolerated and subject to temporal interactions. We describe an adaptation of event-related fMRI to study pain with short duration stimuli. Functional images were acquired with a spiral sequence on a 1.5T GE echospeed MRI system of the thalamus, anterior cingulate, insula and second somatosensory cortex during brief (1-3 s) noxious thermal stimulation of the hand of normal volunteers. An MRI-compatible computerized rating system continuously monitored subjects' pain. Brief pain-related activations were clearly identified in the cortex and thalamus with a hemodynamic delay of 3-6 s. These findings demonstrate that brief stimuli combined with on-line pain ratings can be used to study pain with fMRI.

Evaluation of the early response in fMRI in individual subjects using short stimulus duration

Optical imaging studies have provided evidence of an initial increase in deoxyhemoglobin following the onset of neuronal stimulation/activation and demonstrated that this initial increase could be spatially more specific to the site of neuronal activity. These studies also raised the possibility of improving the specificity of fMRI by selective mapping of this early response. Previous MR studies reported the observation of this early response but were limited in scope and not in full agreement. This paper presents a more extensive study that (a) demonstrates the initial signal decrease in individual subjects and (b) examines its dependence on stimulus duration and subject. Binocular visual stimulation experiments were performed on 14 subjects using echo-planar imaging (EPI) with high temporal resolution. An initial signal decrease was consistently observed in regions that were more localized than those displaying the delayed positive response. In agreement with previous fMRI and optical imaging findings, the maximum signal decrease was 1-2% and occurred at approximately 2 s after the onset of the stimulus, depending on the subject. For stimulus longer then 3.0 s, the temporal dynamics and the amount of signal change of the early response was essentially independent of the stimulus duration, while the delayed response and the post-stimulus undershoot increased both in terms of magnitude and rise time as the duration of the stimulus increased; this observation is concordant with the recent optical imaging study.

Neural activity in the medial geniculate nucleus during auditory trace conditioning.

In classical trace conditioning the acquisition of a conditioned response (CR) is possible even though an interval (the trace interval) elapses between the conditioned stimulus (CS) and unconditioned stimulus (US). This implies that some neural representation of the CS (the stimulus trace) is able to support association between the two stimuli. The medial geniculate nucleus (MGN), particularly the medial division (mMGN), has been identified as one site in the auditory pathway where associative related changes in neural activity occur. If neurons in the MGN are involved in such a sensory trace and in acquisition of a CR, then it is expected that activity following an acoustic CS should be related to both stimulus and response. This study examined the extracellular activity of single units in the MGN during differential auditory trace conditioning of the rabbit nictitating membrane response (NMR). Two 150-ms tones (600 Hz and 1200 Hz) served as CS+ and CS-, and the US was periorbital electrostimulation. Changes in activity during the stimulus and trace interval were largest in the medial and dorsal MGN divisions on CS+ trials and on trials in which a CR was made. Examination of probe stimuli of short (50 ms) and long (600 ms) duration suggested that both CR latency and activity changes in the trace interval were related to stimulus duration and time-locked to stimulus offset. Comparisons of neural activity on the basis of fast or slow CR responses revealed different patterns of response--activity on fast CR trials was generally greater and tended to occur earlier. These results suggest that MGN neurons are involved in the maintenance of a sensory memory trace and possibly play a part in CR generation and timing.

Encoding of sound duration by neurons in the auditory cortex of the little brown bat, Myotis lucifugus.

Responses of 117 single- or multi-units in the auditory cortex (AC) of bats (Myotis lucifugus) to tone bursts of different stimulus durations (1-400 ms) were studied over a wide range of stimulus intensities to determine how stimulus duration is represented in the AC. 36% of AC neurons responded more strongly to short stimulus durations showing short-pass duration response functions, 31% responded equally to all pulse durations (i.e., all-pass), 18% responded preferentially to stimuli having longer durations (i.e., long-pass), and 15% responded to a narrow range of stimulus durations (i.e., band-pass). Neurons showing long-pass and short-pass duration response functions were narrowly distributed within two horizontal slabs of the cortex, over the rostrocaudal extent of the AC. The effects of stimulus level on duration selectivity were evaluated for 17 AC neurons. For 65% of these units, an increase in stimulus intensity resulted in a progressive decrease in the best duration. In light of the unusual intensity-dependent duration responses of AC neurons, we hypothesized that the response selectivities of AC neurons is different from that in the brainstem. This hypothesis was validated by results of study of the duration response characteristics of single neurons in the inferior colliculus.

Atomic Scale Imaging and Analysis of T' Precipitates in Al-Mg-Zn Alloys

The inability to sustain attention has been proposed as a core deficit in schizophrenia. The Continuous Performance Task (AX-CPT) and the Rapid Visual Information Processing Task (RVP) are widely used neuropsychological tasks to measure sustained attention. The RVP displays numbers as stimuli, whereas the AX-CPT uses letters. Ten patients with chronic schizophrenia and 18 healthy control subjects were studied using four different versions of the RVP. The versions differed with regard to stimulus presentation time (600 vs. 1,200 ms) and the number of target sequences to be memorized: either one sequence (low cognitive load) or two sequences (high cognitive load). Schizophrenic patients showed a reduced number of hits only on the task version with 600 ms stimulus duration coupled with high cognitive load. The combination of high cognitive load and short stimulus duration created a critical performance breaking point for schizophrenic patients. This finding supports the hypothesis that patients have an impaired ability to coactivate different cognitive performances; thus the results favor the theory of impaired functional connectivity in schizophrenia.

Error Patterns on the Continuous Performance Test in Non‐Medicated and Medicated Samples of Children With and Without ADHD: A Meta‐Analytic Review

We systematically reviewed the patterns of Continuous Performance Test (CPT) errors of omission and commission exhibited by normal children and children with Attention Deficit and Hyperactivity Disorder (ADHD) under no drug, placebo and methylphenidate drug conditions. Findings from 26 studies were submitted to a meta-analytic procedure. In contrast to the contradictory findings of individual reports, our results revealed that children with ADHD made significantly more errors of omission and commission than normal children. As well, in children with ADHD and treated with methylphenidate, statistically significant reductions in the rate of both error types were noted. The effects of methylphenidate on the percentage of hits (i.e. 1 - omissions) were greater in experiments using shorter stimulus duration, smaller number of trials and higher probability of a target. Using Signal Detection Theory (SDT) parameters, we found that children with ADHD were less sensitive to the difference between targets and non-targets than their normal counterparts, while showing a comparable response bias. Similarly, the effects of methylphenidate were restricted to improving the sensitivity, while not affecting response bias, in both normal children and those with ADHD.

A Computational Model of the Perceived Velocity of Moving Plaids

Local motion detection mechanisms generally lead to one component of the optic flow becoming indeterminate. One way to solve this ‘aperture problem’ is to compute the optic flow which minimises some smoothing constraint. With iterative schemes the computed velocity array is suboptimal relative to the constraint until the process has converged. Under the original assumption that the iteration rate is sufficiently low to allow the perception of suboptimal flows at short stimulus durations, iterative gradient models give an accurate description of biases in the perception of tilted line velocity. We examine whether this approach can be applied to moving sinusoidal plaids. Our simulations are in agreement with a number of psychophysical results on both speed and direction perception. In particular we show that the effect of stimulus duration on the perceived direction of type II plaids [Yo and Wilson, 1992 Vision Research32(1)] can be accounted for without recourse to second-order mechanisms. The effects of contrast and component directions on the evolution rate of this bias are well reproduced. The model also successfully describes the effect of spatial frequency, and data obtained with gratings. These results suggest that iterative gradient schemes can model the dynamics of interactions between local velocity detectors, as revealed by psychophysical experiments with lines and plaids.

Fourier and Non-Fourier Pattern Discrimination Compared

Various studies indicate the existence of non-Fourier visual mechanisms that can extract non-luminance cues (e.g., contrast modulation) as well as a Fourier mechanism that deals with luminance variation only. We compared the pattern discrimination performance of the non-Fourier mechanism with that of the Fourier mechanism by using orientation discrimination and spatial-frequency discrimination tasks. The Fourier patterns used were D6s, the sixth spatial derivative of a Gaussian function multiplied by another Gaussian function in the orthogonal dimension. The corresponding non-Fourier patterns were D6 contrast-modulated cosine gratings. Our results showed a similar trend for the non-Fourier and the Fourier performance at various peak spatial-frequencies or orientations of D6. However, the discrimination threshold of the non-Fourier mechanism was about two-fold higher than that of the Fourier mechanism. The oblique effect was also stronger for non-Fourier patterns. In addition, worse performance for non-Fourier patterns at short stimulus durations (around 33.3 msec) was consistent with the prediction of the two-stage non-Fourier model, which requires more time for the additional rectification and filtering operations. Copyright © 1996 Elsevier Science Ltd.

Evaluation of the early response in fMRI using short stimulus duration

Evaluation of the early response in fMRI using short stimulus duration

The peripheral auditory characteristics of noctuid moths: information encoding and endogenous noise

The ability of the noctuid A1 cell acoustic receptor to encode biologically relevant information from bat echolocation calls is examined. Short-duration stimuli (less than approximately 6 ms) reduce the dynamic resolution of the receptor, making intensity, and hence range, estimates of foraging bats unreliable. This low dynamic range is further reduced by inaccurate encoding of stimulus intensity, reducing the real dynamic range of the A1 cell to 1 bit at stimulus durations below 3.1 ms. Interspike interval is also an unreliable measure of stimulus intensity at low stimulus levels and/or for short-duration stimuli. The quantity of information encoded per stimulus is reduced as the presentation rate of stimuli is increased. The spontaneous generation of A1 cell action potentials may reduce the ability of the moth to discriminate bat from non-bat signals. Even with a recognition criterion of three A1 cell spikes per call, the moth would regularly make wrong decisions about a bat being present in the immediate environment. Removing this noise would necessitate a considerable loss of information through filtering at the interneurone level. It is proposed that, for bats using short-duration calls, the moth would only be able to recognise an approaching bat from the repetitious nature of the incoming signal.

Electrically evoked auditory brainstem response in peripherally myelin-deficient mice

The integrity of the myelin sheath is important for normal electrophysiological function and survival of neurons that make up the auditory nerve. It is hypothesized that myelin deficiency of the auditory nerve may change the electrophysiologic characteristics of the auditory system, especially the temporal properties. In this study, the electrically evoked auditory brainstem response (EABR) was systematically evaluated in Tr J and P o-DT-A mice. Both of these mice have a deficit of their peripheral myelin. Correlation between the EABR and degree of myelin deficiency was also evaluated. The EABR in both strains of poorly myelinated mice exhibited prolonged latency, decreased amplitude, elevated threshold of wave I evoked by short-duration stimuli (20 μs/phase). A 2-pulse stimulation paradigm was used to evaluate refractory properties. Myelin-deficient mice exhibited slower recovery from the refractory state than controls. Long-duration stimuli (4 ms/phase) were used to assess integration properties. Myelin-deficient mice demonstrated prolonged wave I latency and more gradual latency changes with current level. Myelin thickness showed a strong correlation with EABR threshold for short-duration stimulation ( r = −0.784), maximum wave I latency ( r = −0.778) and the time constant of the wave I latency-current level function ( r = −0.736) for long-duration stimulation and normalized wave I recovery functions ( r = −0.718). These findings suggest that EABR measurement may be a promising tool to assess the electrically stimulated properties of auditory neurons, particularly related to the status of myelin sheath.

A statistically based method to generate response maps objectively

One scheme to classify the physiological response properties of single units in the cochlear nucleus is based on the average discharge rate of the unit and is reflected in the distribution of excitatory and inhibitory regions in a frequency-level map (response map) that spans the unit's receptive area (e.g., Evans and Nelson, 1973; Young and Brownell, 1976; Young and Voigt, 1982; Shofner and Young, 1985, Spirou and Young, 1991). Typically, discharge rate versus level curves are acquired at many frequencies and the investigator determines that a unit is excited or inhibited at a given level if the driven rate is above or below a spontaneous rate estimate by a specified criterion (for example, 20%). The investigator then encloses regions of excitation and inhibition where responses over adjacent frequencies and levels are consistent. In the present report, we describe an objective 3-step computer-based method to generate response maps: raw driven and spontaneous rate estimates are smoothed with a low-pass spatial filter; a unit is said to be excited or inhibited at a given level if the filtered driven rate is above or below the mean filtered spontaneous rate for that frequency by a specified criterion (percentage or statistical); and resultant response maps are median spatial filtered to eliminate spurious regions. The results shown here demonstrate that use of a statistical criterion provides a more reliable detection of excitation and inhibition than a 20% criterion, particularly when the variance of the rate estimates is high. Further, the statistically based method permits unit classification based on response map data that are more rapidly acquired with shorter duration stimuli (32 vs. 200 ms). Although this method is applied to units recorded in the dorsal cochlear nucleus, the technique may be applicable to studies of receptive fields and their plasticity in other systems.

Contrast sensitivity in dyslexia.

Contrast sensitivity was determined for dyslexic and normal readers. When testing with temporally ramped (i.e. stimuli with gradual temporal onsets and offsets) gratings of 0.6, 4.0, and 12.0 cycles/deg, we found no difference in contrast sensitivity between dyslexic readers and controls. Using 12.0 cycles/deg gratings with transient (i.e. abrupt) onsets and offsets, we found that dyslexic individuals had, compared to controls, markedly inferior contrast sensitivity at the shortest stimulus durations (i.e. 17, 34, and 102 ms). This deficit may reflect more sluggish temporal summation. There was no difference in sensitivity to 0.6 cycles/deg gratings with transient onsets and offsets. Under these conditions, the two groups showed a consistent and equal increase in sensitivity relative to the ramped baseline condition at 0.6 cycles/deg at the longer stimulus durations. This demonstrates that dyslexic readers have no deficit in their ability to detect stimulus transients, a finding which appears to be inconsistent with a transient system deficit. That detection of the low-frequency stimuli was mediated by the transient system is further indicated by the fact that these stimuli were more susceptible to forward masking than were the high-frequency stimuli. The effects of masking of both high and low spatial-frequency stimuli were about equal for dyslexic readers and controls. This is not in agreement with the transient system deficit theory, according to which one would expect there to be less masking of high spatial-frequency stimuli in the case of dyslexic readers.