Function Of Interstimulus Interval Research Articles

Subthalamic nucleus conditioning reduces premotor-motor interaction in Parkinson's disease

BackgroundDeep brain stimulation of the subthalamic nucleus is effective to alleviate motor symptoms in advanced Parkinson's disease. Using a novel conditioning paradigm, it has been shown that deep brain stimulation pulses from electrodes in the subthalamic nucleus modulate corticospinal excitability as determined with transcranial magnetic stimulation applied to the motor cortex. The mechanism of action is unclear. ObjectiveTo investigate the effects of subthalamic nucleus and dorsal premotor cortex conditioning on corticospinal excitability as a function of interstimulus intervals between target areas and deep brain stimulation frequencies. MethodsIn 19 patients with Parkinson's disease with subthalamic nucleus deep brain stimulation, the premotor-motor interaction was investigated in four different deep brain stimulation conditions (off, clinically used settings, 3 Hz, 20 Hz). Transcranial magnetic pulses were applied to the premotor and motor cortex and paired at certain intervals with deep brain stimulation pulses. The volume of tissue activated by deep brain stimulation was correlated with neurophysiological findings. ResultsThere was distinct motor cortex inhibition by premotor cortex conditioning at an interstimulus interval of 1 ms before the motor cortex stimulation. Subthalamic nucleus conditioning with deep brain stimulation frequencies of 3 and 20 Hz at an interstimulus interval of 10 ms between subthalamic nucleus and primary motor cortex reduced premotor-motor inhibition. The volume of tissue activated by deep brain stimulation correlated positively with this effect. Corticospinal excitability was not affected by subthalamic nucleus conditioning as used here. ConclusionsPremotor-motor inhibition is modulated by subthalamic nucleus conditioning, presumably through the monosynaptic hyperdirect pathway.

Subcortical short-term plasticity elicited by deep brain stimulation.

ObjectiveTo investigate local short‐term neuroplasticity elicited by subthalamic, thalamic, and pallidal deep brain stimulation (DBS) for movement disorders.MethodsDuring DBS surgery, we delivered pairs of stimulus pulses with both circular and directional leads across 90 interstimulus intervals in 17 participants and recorded local field potentials from unused contacts on the implanted electrode array. We removed the stimulus artifact, validated the neural origin of the underlying signals, and examined short‐term plasticity as a function of interstimulus interval and DBS target, using linear mixed effects models.ResultsDBS evokes short latency local field potentials that are readily detected with both circular and directional leads at all stimulation targets (0.31 ± 0.10 msec peak latency, mean ± SD). Peak amplitude, area, and latency are modified strongly by interstimulus interval (P < 0.001) and display absolute and relative refractory periods (0.56 ± 0.08 and 2.94 ± 1.05 msec, respectively). We also identified later oscillatory activity in the subthalamic‐pallidal circuit (4.50 ± 1.11 msec peak latency) that displays paired pulse facilitation (present in 5/8 subthalamic, 4/5 pallidal, and 0/6 thalamic trajectories, P = 0.018, Fisher’s exact test), and correlates with resting beta frequency power (P < 0.001), therapeutic DBS frequencies, and stimulation sites chosen later for therapy in the ambulatory setting (P = 0.031).InterpretationPaired DBS pulses synchronize local circuit electrophysiology and elicit short‐term neuroplasticity in the subthalamic‐pallidal circuit. Collectively, these responses likely represent the earliest detectable interaction between the DBS pulse and local neuronal tissue in humans. Evoked subcortical field potentials could serve as a predictive biomarker to guide the implementation of next‐generation directional and adaptive stimulation devices.

Short-interval intracortical inhibition as a function of inter-stimulus interval: Three methods compared

BackgroundShort-interval intracortical inhibition (SICI), as measured by threshold-tracking as a function of inter-stimulus interval (ISI), has been proposed as a useful biomarker for amyotrophic lateral sclerosis (ALS), but its relationship to conventional amplitude measurements has not been established. MethodsSerial tracking of SICI at increasing ISIs from 1 to 7 ms (T-SICIs) was compared in 50 healthy control subjects with the same ISIs tracked in parallel (T-SICIp), and with conventional amplitude measurements (A-SICI). For T-SICIp and A-SICI, pairs of conditioning and test stimuli with different ISIs were pseudo-randomised and interspersed with test-alone stimuli given at regular intervals. Thresholds were estimated by regression of log peak-to-peak amplitude on stimulus. ResultsT-SICIp and A-SICI were closely related: a ten-fold reduction in amplitude corresponding to an approximately 18% increase in threshold. Threshold increases were greater for T-SICIs than for T-SICIp at 3.5–5 ms (P < 0.001). This divergence depended on the initial settings and whether ISIs were progressively increased or decreased, and was attributed to the limitations of the serial tracking protocol. SICI variability between subjects was greatest for T-SICIs estimates and least for A-SICI, and only A-SICI estimates revealed a significant decline in inhibition with age. ConclusionsThe serial tracking protocol did not accurately show the dependence of inhibition on ISI. Randomising ISIs gives corresponding SICI measures, whether tracking thresholds or measuring amplitude measurements. SICI variability suggested that A-SICI measurements may be the most sensitive to loss of inhibition.

Age-related change in fast adaptation mechanisms measured with the scotopic full-field ERG

To quantify the response dynamics of fast adaptation mechanisms of the scotopic ERG in younger and older adults using full-field m-sequence flash stimulation. Scotopic ERGs were measured for a series of flashes separated by 65ms over a range of 260ms in 16 younger (20-26, 22.2±2.1; range mean ±1 SD) and 16 older (65-85, 71.2±7) observers without retinal pathology. A short-wavelength (λ peak=442nm) LED was used for scotopic stimulation, and the flashes ranged from 0.0001 to 0.01cdsm(-2). The complete binary kernel series was derived from the responses to the m-sequence flash stimulation, and the first- and second-order kernel responses were analyzed. The first-order kernel represented the response to a single, isolated flash, while the second-order kernels reflected the adapted flash responses that followed a single flash by one or more base intervals. B-wave amplitudes of the adapted flash responses were measured and plotted as a function of interstimulus interval to describe the recovery of the scotopic ERG. A linear function was fitted to the linear portion of the recovery curve, and the slope of the line was used to estimate the rate of fast adaptation recovery. The amplitudes of the isolated flash responses and rates of scotopic fast adaptation recovery were compared between the younger and older participants using a two-way ANOVA. The isolated flash responses and rates of recovery were found to be significantly lower in the older adults. However, there was no difference between the two age groups in response amplitude or recovery rate after correcting for age-related changes in the density of the ocular media. These results demonstrated that the rate of scotopic fast adaptation recovery of normal younger and older adults is similar when stimuli are equated for retinal illuminance.

Processing speaker variability in repetition and semantic/associative priming.

The effect of speaker variability on accessing the form and meaning of spoken words was evaluated in two short-term priming experiments. In the repetition priming experiment, participants listened to repeated or unrelated prime-target pairs, in which the prime and target were produced by the same speaker or different speakers. The results showed robust repetition priming, but only partial evidence of reduction of priming by speaker variability. In the semantic/associative priming experiment, participants listened to semantically/associatively related or unrelated prime-target pairs, in which the prime and target were produced by the same speaker or different speakers. The results showed robust semantic/associative priming, but the reduction of priming by speaker variability took place only for targets produced by the female speaker. There is no evidence that the speaker variability effect varied as a function of inter-stimulus interval. These findings suggest that speaker variability could affect access to word form and meaning, but the impact is relatively weak.

The Haas Effect—Lateral extent and perceptual weighting of localization cues

The Haas effect is a well-known manifestation of the precedence effect. Originally, Haas measured the echo threshold as a function of the primary auditory event and its single reflection being equally loud. What is not well known is the lateral position of the lead/lag pair as a function of inter-stimulus interval and level difference between lead and lag. How robust the Haas effect is in the localization dominance region was investigated, adjusting the level difference between lead and lag, and using 200 ms band-passed noise presented dichotically over headphones. In addition, the onset and offset cues were removed for half the trials and left intact for the other half to investigate the roles of onset and offset cues versus ongoing cues. Lateral displacement of the auditory event was recorded with an acoustic pointer. Analysis of these results help to reveal the perceptual weighting of localization cues in the Haas effect.

Independent Domains of Inhibitory Gating in Schizophrenia and the Effect of Stimulus Interval

Patients with schizophrenia are known to have inhibitory gating deficits in the suppression of evoked potential P50 response to repeated stimuli and the prepulse inhibition of the startle response. In the current study, the authors aimed to determine whether these two inhibitory gating measures are related in schizophrenia patients or whether abnormal P50 suppression and abnormal prepulse inhibition are independent neurophysiological characteristics of schizophrenia. The authors hypothesized that the relationship of the two measures may vary as a function of interstimulus intervals of stimulus presentations. Fifty-nine schizophrenia patients and 17 healthy comparison subjects were tested on both P50 suppression and prepulse inhibition. P50 suppression was measured using paired clicks with 500-msec interstimulus intervals. Prepulse inhibition was measured by using a series of prepulse-pulse pairs with interstimulus intervals ranging from 30 to 500 msec. Patients showed reduced P50 suppression and prepulse inhibition in relation to healthy comparison subjects. Concordance analysis showed that abnormal P50 suppression and abnormal prepulse inhibition do not necessarily occur together. Prepulse inhibition was most prominent at the 120-msec interstimulus interval, which was not correlated to P50 suppression. At the 500-msec interstimulus interval, prepulse inhibition was significantly but negatively correlated to P50 suppression. Prepulse inhibition at the other interstimulus intervals was not correlated with P50 suppression. These neurophysiological measures lack robust and direct relationships and likely mark independent aspects of abnormal brain inhibitory functions in schizophrenia.

Independent Domains of Inhibitory Gating in Schizophrenia and the Effect of Stimulus Interval

Objective: Patients with schizophrenia are known to have inhibitory gating deficits in the suppression of evoked potential P50 response to repeated stimuli and the prepulse inhibition of the startle response. In the current study, the authors aimed to determine whether these two inhibitory gating measures are related in schizophrenia patients or whether abnormal P50 suppression and abnormal prepulse inhibition are independent neurophysiological characteristics of schizophrenia. The authors hypothesized that the relationship of the two measures may vary as a function of interstimulus intervals of stimulus presentations. Method: Fifty-nine schizophrenia patients and 17 healthy comparison subjects were tested on both P50 suppression and prepulse inhibition. P50 suppression was measured using paired clicks with 500-msec interstimulus intervals. Prepulse inhibition was measured by using a series of prepulse-pulse pairs with interstimulus intervals ranging from 30 to 500 msec. Results: Patients showed reduced P50 suppression and prepulse inhibition in relation to healthy comparison subjects. Concordance analysis showed that abnormal P50 suppression and abnormal prepulse inhibition do not necessarily occur together. Prepulse inhibition was most prominent at the 120-msec interstimulus interval, which was not correlated to P50 suppression. At the 500-msec interstimulus interval, prepulse inhibition was significantly but negatively correlated to P50 suppression. Prepulse inhibition at the other interstimulus intervals was not correlated with P50 suppression. Conclusions: These neurophysiological measures lack robust and direct relationships and likely mark independent aspects of abnormal brain inhibitory functions in schizophrenia.

The slow formation of a pitch percept beyond the ending time of a short tone burst

The discriminability of short tone bursts differing in frequency was measured in terms of the sensitivity index d' as a function of interstimulus interval (ISI). The two stimuli presented on each trial consisted of either 6 or 30 sinusoidal cycles. When the frequency of the first stimulus varied randomly and widely from trial to trial (Experiment 1), discriminability was maximal for an ISI of about 400 msec in the 6-cycles condition and for a significantly longer ISI (of about 1 sec) in the 30-cycles condition. However, when the first stimulus had only two possible frequencies and the second stimulus was fixed (Experiment 2), the optimal ISI appeared to be about 400 msec in both conditions. A final experiment confirmed that, for tone bursts of 30 cycles, the optimal ISI was dependent on the perceptual uncertainty of the first stimulus. These results support the idea that the duration required to perceive the pitch of a sound as accurately as possible may far exceed the duration of the stimulus itself. More importantly, they indicate that the required duration is not a constant.

Temporal masking of multidimensional tactual stimuli.

Experiments were performed to examine the temporal masking properties of multidimensional tactual stimulation patterns delivered to the left index finger. The stimuli consisted of fixed-frequency sinusoidal motions in the kinesthetic (2 or 4 Hz), midfrequency (30 Hz), and cutaneous (300 Hz) frequency ranges. Seven stimuli composed of one, two, or three spectral components were constructed at each of two signal durations (125 or 250 ms). Subjects identified target signals under three different masking paradigms: forward masking, backward masking, and sandwiched masking (in which the target is presented between two maskers). Target identification was studied as a function of interstimulus interval (ISI) in the range 0 to 640 ms. For both signal durations, percent-correct scores increased with ISI for each of the three masking paradigms. Scores with forward and backward masking were similar and significantly higher than scores obtained with sandwiched masking. Analyses of error trials revealed that subjects showed a tendency to respond, more often than chance, with the masker, the composite of the masker and target, or the combination of the target and a component of the masker. The current results are compared to those obtained in previous studies of tactual recognition masking with brief cutaneous spatial patterns. The results are also discussed in terms of estimates of information transfer (IT) and IT rate, are compared to previous studies with multidimensional tactual signals, and are related to research on the development of tactual aids for the deaf.

Temporal discharge patterns evoked by rapid sequences of wide- and narrowband clicks in the primary auditory cortex of cat.

The present study investigated neural responses to rapid, repetitive stimuli in the primary auditory cortex (A1) of cats. We focused on two important issues regarding cortical coding of sequences of stimuli: temporal discharge patterns of A1 neurons as a function of inter-stimulus interval and cortical mechanisms for representing successive stimulus events separated by very short intervals. These issues were studied using wide- and narrowband click trains with inter-click intervals (ICIs) ranging from 3 to 100 ms as a class of representative sequential stimuli. The main findings of this study are 1) A1 units displayed, in response to click train stimuli, three distinct temporal discharge patterns that we classify as regions I, II, and III. At long ICIs nearly all A1 units exhibited typical stimulus-synchronized response patterns (region I) consistent with previously reported observations. At intermediate ICIs, no clear temporal structures were visible in the responses of most A1 units (region II). At short ICIs, temporal discharge patterns are characterized by the presence of either intrinsic oscillations (at approximately 10 Hz) or a change in discharge rate that was a monotonically decreasing function of ICI (region III). In some A1 units, temporal discharge patterns corresponding to region III were absent. 2) The boundary between regions I and II (synchronization boundary) had a median value of 39.8 ms ICI ([25%, 75%] = [20.4, 58. 8] ms ICI; n = 131). The median boundary between regions II and III was estimated at 6.3 ms ([25%, 75%] = [5.2, 9.7] ms ICI; n = 47) for units showing rate changes (rate-change boundary). 3) The boundary values between different regions appeared to be relatively independent of stimulus intensity (at modest sound levels) or the bandwidth of the clicks used. 4) There is a weak correlation between a unit's synchronization boundary and its response latency. Units with shorter latencies appeared to also have smaller boundary values. And 5) based on these findings, we proposed a two-stage model for A1 neurons to represent a wide range of ICIs. In this model, A1 uses a temporal code for explicitly representing long ICIs and a rate code for implicitly representing short ICIs.

Forward masking in normal-hearing, hearing-impaired, and noise-masked normal listeners

This study examined forward-masking functions in normal-hearing, hearing-impaired, and noise-masked normal listeners using a 300-ms, one-octave 80 dB SPL masker centered at 4000 Hz and a 20-ms, 4000-Hz pure-tone signal. Thresholds were measured as a function of interstimulus interval (0 to 150 ms), and a time constant (τ) was estimated from the best exponential fit to this function. No significant differences were found between τ values obtained from the normal-hearing (mean: 44 ms) and hearing-impaired (mean: 45 ms) subjects. Thus, temporal resolution in this task was not worse for the impaired listeners than for the normal listeners. Under the noise-masked condition, normal-hearing subjects completed the forward-masking task in the presence of a continuous 4000-Hz, one-octave noise, whose level was chosen to shift each subject’s threshold to match that of a hearing-impaired subject of equivalent age and gender. The mean τ value obtained in the noise-masked condition was 8 ms, which was significantly smaller than the τ values obtained from either group in the absence of a background masker. This curious finding suggests that use of a continuous noise masker to simulate hearing loss is not effective in this temporal resolution task. [Work supported by NIDCD.]

Automatic Versus Strategic Effects of Phonology and Orthography on Auditory Lexical Access in Brain-Damaged Patients as a Function of Inter-Stimulus Interval

The influence of both phonological and orthographic information on auditory lexical access was examined in left- and right-hemisphere-damaged individuals using a lexical decision paradigm. Subjects were presented with prime-target pairs that were either phonologically related ( tooth-youth), orthographically related ( touch-couch), both phonologically and orthographically related ( blood-flood), or unrelated ( bill-tent), at two inter-stimulus intervals (ISI) – 100 ms and 750 ms – to tap more automatic versus more strategic processing. All groups demonstrated effects of orthography at both ISIs (facilitory at 100 ms ISI and inhibitory at 750 ms ISI), supporting the findings by Leonard and Baum (1997) that effects of orthography emerge independent of site of brain damage and suggesting that orthographic effects in auditory word recognition tend to be largely strategic. A facilitory effect of phonology was also found for all groups at both ISIs. The findings are discussed in relation to theories of lexical activation in brain-damaged individuals.

Visual Memory for Multiple Gabor Targets

Visual memory for spatial frequency in stationary Gabor targets was measured as a function of interstimulus interval (ISI 2 or 8 s), number of targets (2, 3, or 4), and pre-cueing versus post-cueing of the critical target. The width of the Gabor and the initial and final spatial frequency were varied to eliminate confounding variables such as number of cycles, apparent contrast, and initial or final spatial frequency. A signal-detection analysis was employed, in which the subject was required to determine whether the spatial frequency of a selected Gabor target was the same or different over the ISI. The data were analysed by plotting d' as a function of spatial- frequency difference. The results show only small and inconsistent decreases in d' as a function of the ISI. There was little change in d' in any condition except certain 3 and 4 target post-cueing conditions, where its magnitude was halved. It was expected that pre-cueing should be superior to post-cueing because, although the Gabor displays are the same, effectively only one pre-cued target needs to be retained over the ISI. However, the expected effect did not always occur. In some spatial-frequency conditions, discrimination performance was maintained even for the most difficult condition (4 targets, 8 s ISI, post-cueing). It is concluded that there is a durable representation of stimulus spatial frequency in visual memory. Under optimum conditions, 2 – 4 targets can be remembered for 8 s with minimal change in d'.

Activation trace lifetime of human cortical responses evoked by apparent visual motion

Visually evoked magnetoencephalographic responses were recorded from 11 healthy humans to 1.1×1.1° oblique gratings moving quickly 0.2° rightwards and back once every 0.2–6.4 s. The aim was to study the duration of sensory memory in the motion-specific visual cortex called V5. Responses from the V5 region peaked at 140–180 ms after stimulus onset. Signal-to-noise ratio allowed source identification in eight subjects: bilaterally in four and unilaterally in four. The response strength as a function of interstimulus interval determined an activation trace lifetime, reflecting how long the preceding stimuli affect the response to the following stimulus, i.e. how long the V5 cortex `remembers' each stimulus. The lifetimes varied interindividually from 0.4 to 1.4 s, but were within 0.1 s in the hemispheres of the four subjects with bilaterally identified sources.

A comparison of varieties of “second-order” motion

Bistable apparent-movement displays were created using four different kinds of “second-order” stimuli in which figures were defined by binocular disparity, spatial phase shifts of periodic luminance distributions, relative motion, and texture-element orientation differences. For each display, characteristics of the local structure of the figures, backgrounds, or both were varied. For each experimental condition, the type of apparent movement seen as a function of interstimulus interval was measured, and it was found that the relationship between perceived apparent movement and interstimulus interval differed across the types of displays viewed. The results suggest that the transformations between first-order stimulus properties and second-order motion may be too complex to imply a single uniform class of second-order motion detectors. Alternative physiological accounts of the results are discussed.

Preferred rates of repetitive tapping and categorical time production.

In a constrained finger-tapping task, in which a subject attempts to match the rate of tapping responses to the rate of a pacer stimulus, interresponse interval (IRI) was a nonlinear function of interstimulus interval (ISI), in agreement with the results of Collyer, Broadbent, and Church (1992). In an unconstrained task, the subjects were not given an ISI to match, but were instructed to tap at their preferred rate, one that seemed not too fast or too slow for comfortable production. The distribution of preferred IRIs was bimodal rather than unimodal, with modes at 272 and 450 msec. Preferred IRIs also tended to become shorter over successive sessions. Time intervals that were preferred in the unconstrained task tended to be intervals that were overproduced (IRI > ISI) when they were used as ISIs in the constrained task. A multiple-oscillator model of timing developed by Church and Broadbent (1990) was used to simulate the two tasks. The nonlinearity in constrained tapping, termed the oscillator signature, and the bimodal distribution in unconstrained tapping were both exhibited by the model. The nature of the experimental results and the success of the simulation in capturing them both provide further support for a multiple-oscillator view of timing.

Concomitant heart rate and eyeblink Pavlovian conditioning in human subjects as a function of interstimulus interval.

Pavlovian heart rate and eyeblink conditioning were simultaneously assessed in human subjects. Tone durations of 0.6, 1.1, and 2.1 s were employed in separate groups of subjects as the conditioned stimulus. A 100-ms corneal airpuff, which served as the unconditioned stimulus, overlapped the last 100 ms of the tone in each group, thus producing interstimulus intervals of 0.5, 1.0, and 2.0 s. Other groups of pseudoconditioning subjects received explicitly unpaired tone and airpuff presentations of identical durations but in a pseudorandom sequence so that they never occurred together. The best eyeblink conditioning was observed in the group with the .5-s interstimulus interval, although the 1.0-s group also demonstrated some evidence of eyeblink conditioning. The group with the 2.0-s interstimulus interval showed a lower overall rate of conditioned response occurrence and the highest rate of pseudoconditioned responding. The conditioned heart rate response in all three conditioning groups consisted of cardiac decelerations, but tone-evoked cardiac accelerations were observed in the pseudoconditioning groups. The magnitude of the cardiac deceleration was comparable in all three conditioning groups.

Age differences in the temporal continuity of gratings as a function of their spatial frequency

This study compared young and elderly observers on the continuity of sinusoidal grating-pairs as a function of interstimulus interval (ISI) and spatial frequency (.5, 1.0, 2.0, 4.0, 8.0, and 12.0 c/deg). Consistent with prior research, the maximum ISI over which pattern continuity was maintained increased with spatial frequency. In addition, among older observers, grating continuity occurred at significantly longer ISI's at the two lowest spatial frequencies; no age difference was observed at the higher spatial frequencies. These results could not be attributed to an age difference in retinal illumination associated with pupillary miosis. However, they do indicate an age-related decline in detecting visual offset and are consistent with the hypothesis of a decline in the effectiveness of the transient visual channels.

Reflex facilitation of the rabbit nictitating membrane response by an auditory stimulus as a function of interstimulus interval.

The ability of an auditory stimulus to facilitate the amplitude and latency of the unconditioned nictitating membrane (NM) response in rabbits was investigated over a wide range of interstimulus intervals (ISIs) for both delay (Experiments 1-4) and trace (Experiments 3 and 4) procedures. The auditory stimulus was a 1000-Hz tone (T) at either 85 or 95 dB, and the reflex-eliciting stimulus was a 2.0 psi (pounds per square inch) corneal air puff (AP). The results indicate that (a) robust facilitation of the NM response, as measured by an increased amplitude and a reduced latency, can be obtained at long ISIs (2,000-32,000 ms); (b) increasing the tone intensity can increase reflex facilitation of the peak amplitude; (c) at comparable ISIs, delay procedures produce more facilitation of both amplitude and latency than do trace procedures; and (d) when trace procedures are used, amplitude and latency facilitation by a 125-ms tone follows an inverted U-shaped ISI function in which facilitation peaks between 125 and 500 ms, rapidly decreases between 1,000 and 2,000 ms, and disappears by 4,000 ms.