Increasing Stimulus Duration Research Articles

Sex and aging interact to modulate the rapid onset of arteriolar dilation in mouse skeletal muscle

Aging is associated with a reduction in blood flow to skeletal muscle and diminished exercise capacity. However, little is understood of how aging affects arteriolar dynamics in working skeletal muscle. We tested the hypothesis that aging impairs the rapid onset of vasodilation (ROV) in mouse gluteus maximus muscle. Responses of second-order arterioles [diameter: rest, 17 ± 1 μm; max (SNP), 29 ± 1 μm] to single tetanic contractions (100 Hz) were assessed in anesthetized C57Bl/6 mice using intravital microscopy in Young (3 mo) males (YM; n=7) and females (YF; n=5) and in Old (~20 mo) males (OM; n=7) and females (OF; n=6). With increasing stimulus duration (100–1000 ms), the magnitude of dilation increased (from 1 to 7 μm) in YM, YF, and OF (P<0.05) yet ROV was blunted consistently by >50% in OM (P<0.05). In contrast, 30-s rhythmic contractions at 2, 4, and 8 Hz resulted in steady-state dilations that increased with frequency (from 2 to 8 μm; P<0.05) and were not different between groups. Remarkably, the decrement in ROV in OM was reversed (P<0.05) with α-adrenoreceptor blockade (1 μM phentolamine). These data support the hypothesis that aging selectively impairs ROV in Old male mice through increased activation of α-adrenoreceptors. (NIH R21-AG19347 and HSFC)

Ischemia–Reperfusion Impairs Ascending Vasodilation in Feed Arteries of Hamster Skeletal Muscle

Vasodilation originating within the microcirculation ascends into proximal feed arteries during muscle contraction to attain peak levels of muscle blood flow. Ascending vasodilation (AVD) requires an intact endothelium, as does conducted vasodilation in response to acetylcholine (ACh). Whereas ischemia-reperfusion (I-R) can affect endothelial cell function, the effect of I-R on AVD is unknown. The authors tested the hypothesis that I-R (1h-1h) would impair AVD. Using the retractor muscle of anesthetized hamsters, contractions were evoked using field stimulation (200 ms at 40 Hz every 2 s for 1 min) and ACh was delivered using microiontophoresis (1 microm tip, 500-4000 ms pulse at 800 nA). Feed artery responses were monitored 500-1500 microm upstream. Neither resting (51 +/- 4 microm) nor maximal diameter (81 +/- 5 microm; 10 microm sodium nitroprusside) following I-R (n = 8) were different from time-matched controls (n = 10). With peak active tension of 23 +/- 4 mN x mm(-2), control AVD was 26 +/- 2 microm. Following I-R, active tension fell by 48% (p < .05) and AVD by 57% (p < .05). Stimulation at 70 Hz restored active tension but AVD remained depressed by nearly half (p < .05), as did local and conducted responses to ACh. Nevertheless, control responses to 500 ms ACh were restored by increasing stimulus duration to 4000 ms. Ischemia-reperfusion impairs the initiation of feed artery dilation with muscle contraction and with ACh while conduction along the vessel wall is preserved. Respective components of endothelial cell signaling events may differ in their susceptibility to I-R.

Adaptation in the rodent olfactory bulb measured by fMRI

Effective evaluation of the odor environment necessitates the ability to attenuate responses to potent background odors in favor of novel and less robust stimuli. Olfactory receptor neuron studies suggest that some of this adaptation takes place in the primary sensory neurons, but the more extensive adaptation seen in higher cortical areas implies the involvement of additional neural mechanisms. At 7.0 T, high-resolution fMRI was used to assess the response of the rodent olfactory bulb, the most peripheral cortical structure involved in olfactory processing, to a variety of odor stimuli. The results suggest that there are additional regulatory mechanisms in the olfactory bulb that result in greater adaptation in deeper areas than that seen in sensory receptors alone and that the resultant adaptation is positively affected by increasing stimulus duration and concentration and decreasing recovery time. The implications of these findings for the integration of peripheral input with perception are discussed.

Sustained firing in auditory cortex evoked by preferred stimuli

It has been well documented that neurons in the auditory cortex of anaesthetized animals generally display transient responses to acoustic stimulation, and typically respond to a brief stimulus with one or fewer action potentials. The number of action potentials evoked by each stimulus usually does not increase with increasing stimulus duration. Such observations have long puzzled researchers across disciplines and raised serious questions regarding the role of the auditory cortex in encoding ongoing acoustic signals. Contrary to these long-held views, here we show that single neurons in both primary (area A1) and lateral belt areas of the auditory cortex of awake marmoset monkeys (Callithrix jacchus) are capable of firing in a sustained manner over a prolonged period of time, especially when they are driven by their preferred stimuli. In contrast, responses become more transient or phasic when auditory cortex neurons respond to non-preferred stimuli. These findings suggest that when the auditory cortex is stimulated by a sound, a particular population of neurons fire maximally throughout the duration of the sound. Responses of other, less optimally driven neurons fade away quickly after stimulus onset. This results in a selective representation of the sound across both neuronal population and time.

A unifying basis of auditory thresholds based on temporal summation.

Thresholds of auditory-nerve (AN) fibers and auditory neurons are commonly specified in terms of sound pressure only, implying that they are independent of time. At the perceptual level, however, the sound pressure required for detection decreases with increasing stimulus duration, suggesting that the auditory system integrates sound over time. The quantity commonly believed to be integrated is sound intensity, implying that the auditory system would have an energy threshold. However, leaky integrators of intensity with time constants of hundreds of milliseconds are required to fit the data. Such time constants are unknown in physiology and are also incompatible with the high temporal resolution of the auditory system, creating the resolution-integration paradox. Here we demonstrate that cortical and perceptual responses are based on integration of the pressure envelope of the sound, as we have previously shown for AN fibers, rather than on intensity. The functions relating the pressure envelope integration thresholds and time for AN fibers, cortical neurons, and perception in the same species (cat), as well as for perception in many different vertebrate species, are remarkably similar. They are well described by a power law that resolves the resolution-integration paradox. The data argue for the integrator to be located in the first synapse in the auditory pathway and we discuss its mode of operation.

Effect of duration and inter-stimulus interval on auditory temporal order discrimination in young normal-hearing and elderly hearing-impaired listeners

Increasing the rate of presentation can have a deleterious effect on auditory processing, especially among the elderly. Rate can be manipulated by changing the duration of individual components of a sequence of sounds, by changing the inter-stimulus interval (ISI) between components, or both. Consequently, when age-related deficits in performance appear to be attributable to rate of stimulus presentation, it is often the case that alternative explanations in terms of the effects of stimulus duration or ISI are also possible. In this study, the independent effects of duration and ISI on the discrimination of temporal order for four-tone sequences were investigated in a group of young normal-hearing and elderly hearing-impaired listeners. It was found that discrimination performance was driven by the rate of presentation, rather than stimulus duration or ISI alone, for both groups of listeners. The performance of the two groups of listeners differed significantly for the fastest presentation rates, but was similar for the slower rates. Slowing the rate of presentation seemed to improve performance, regardless of whether this was done by increasing stimulus duration or increasing ISI, and this was observed for both groups of listeners. [Work supported, in part, by NIA.]

Differential modulation of light-evoked on- and off-EPSCs by paired-pulse stimulation in salamander retinal ganglion cells

Short-term plasticity of On- and Off-EPSPs, and its potential role in regulation of signal processing was studied in salamander retinal On–Off ganglion cells by whole-cell recording. Paired-pulse light stimulation resulted in a depression of On-, and an enhancement of Off-EPSCs. Recovery from depression and enhancement was exponential and complete by 20 s. Paired-pulse enhancement, but not depression, was abolished with increasing stimulus duration. Blockade of On-EPSC by l-2-amino-4-phosphonobutyrate (AP-4), an agonist at group III mGluRs, significantly increased Off-EPSCs evoked by short (<2 s) duration conditioning light stimuli, resulting in a reversal of the paired-pulse enhancement to depression. The acetylcholinesterase inhibitor eserine reduced Off-EPSC1 and increased the ratio of enhancement. An opposite effect was observed in the presence of the nACh receptor antagonist d-tubocurarine. AP-7, an antagonist of NMDA receptors attenuated the enhancement of Off-EPSCs. In current clamp mode paired-pulse stimulation resulted in a modulation of light evoked, as well as the depolarization-induced spike firing pattern of ganglion cells. The present study suggests that paired light stimulation differently modulates On and Off EPSPs, and the light-evoked spike firing pattern of On–Off ganglion cells.

Sustained Negative BOLD, Blood Flow and Oxygen Consumption Response and Its Coupling to the Positive Response in the Human Brain

Most fMRI studies are based on the detection of a positive BOLD response (PBR). Here, we demonstrate and characterize a robust sustained negative BOLD response (NBR) in the human occipital cortex, triggered by stimulating part of the visual field. The NBR was spatially adjacent to but segregated from the PBR. It depended on the stimulus and thus on the pattern of neuronal activity. The time courses of the NBR and PBR were similar, and their amplitudes covaried both with increasing stimulus duration and increasing stimulus contrast. The NBR was associated with reductions in blood flow and with decreases in oxygen consumption. Our findings support the contribution to the NBR of (1) a significant component of reduction in neuronal activity and (2) possibly a component of hemodynamic changes independent of the local changes in neuronal activity.

Temporal Bisection in Children

Children aged 3, 5, and 8 years received training on a temporal bisection task, with standard short and long durations being presented as visual stimuli lasting 1 and 4 s or 2 and 8 s. Nonstandard comparison stimuli were spaced linearly between the standards. Psychophysical functions showed increasing proportions of “long” responses (responses appropriate to the long standard) with increasing stimulus duration, but were flatter in the younger children than in the 8-year-olds. Bisection points (the stimulus duration giving rise to 50% “long” responses) were close to the arithmetic mean of the short and long standards in most conditions. Statistical analyses and results from different theoretical models of the data all suggested that temporal sensitivity was higher in the 8-year-olds than in the younger groups, even when the possibility of random responding was controlled for.

Effect of duration of pitch-shifted feedback on vocal responses in patients with Parkinson's disease.

Study of the pitch-shift reflex is useful for the investigation of how auditory feedback is used in the control of voice fundamental frequency. The present study was an attempt to learn if the basal ganglia are involved in central mechanisms of the pitch-shift reflex by comparing measures of the reflex in a group of Parkinson's disease patients with those measures in a group of control participants. The effect of varying duration of the pitch-shift stimulus (PSS) on the voice fundamental frequency (F0) response in 10 Parkinson's disease (PD) patients and 10 age-matched unaffected participants was investigated. Participants were instructed to vocalize into a microphone while their voice was fed back to them over headphones. This feedback of the vocal signal was shifed in pitch either up or down, with the duration of this shift systematically manipulated at 100 ms, 500 ms, and 1000 ms. Although the participants were on medication, making interpretation of the results problematic with regard to basal ganglia function, it was reasoned that positive effects could nevertheless suggest basal ganglia involvement in this reflex and motivate further research. Results indicated that both groups responded to increased stimulus duration of the pitch-shift stimulus with increases in reflex peak time, magnitude, and end times. However, PD patients had significantly longer peak times and end times than control participants for stimulus durations of 100 ms. These results suggest that basal ganglia dysfunction may affect mechanisms relating to the execution and termination of the pitch-shift reflex for brief stimulus durations. The results also support hypotheses of impaired sensory integration of auditory feedback in PD patients.

Discrimination of spatial relations and features in faces: Effects of inversion and viewing duration

We studied discrimination of changes in eye position, mouth position, and eye colour at viewing durations ranging from 1 second to unlimited time. With upright faces, perception was rapid and did not improve above 2 seconds viewing time. Face inversion impaired discrimination of mouth position significantly, eye position slightly, but not eye colour. The 'inversion effect' for mouth position decreased with increasing stimulus duration, and disappeared when the subject knew that the only change in a trial was in mouth position. A subsequent experiment showed that the inversion impairment in the mouth region was not specific to spatial position but affected mouth colour to a lesser degree. When the mouth region was made more salient by increasing the frequency of mouth change trials, the inversion effect for mouth position decreased, and correlated with an increase in inversion effect for eye position but not eye colour. We conclude that the dominant effect of face inversion upon perception is decreased discrimination in less salient facial regions, that this impairment lessens with increasing viewing time, and that it affects both features and their spatial relations, though the effect on the latter is greater. These results are consistent with greater dependence on a serial component search strategy in inverted faces.

Variability in 5- and 8-year-olds’ memory for duration: an interfering task in temporal bisection

The purpose of this experiment was to investigate 5- and 8-year-olds’ long-term memory for stimulus duration in a bisection task. Children were trained to discriminate between a short and a long standard duration presented as visual stimulus for 2 and 8 s, respectively. They had then to decide whether an intermediate stimulus duration was more similar to the short or to the long standard in two identical testing phases separated by an interfering task lasting for 15 min (immediate test vs. deferred test). The results showed that the 5- and the 8-year-olds produced orderly psychophysical functions. However, the 8-year-olds produced psychophysical functions, which increased more abruptly with the increasing stimulus duration. Nevertheless, whatever the age of children tested, the psychophysical function curves were flatter in the deferred test than in the immediate test, and more particularly in the 5-year-olds. Furthermore, the 5-year-olds produced fewer ‘long’ responses in the deferred than in the immediate test. Modeling of the data suggests that the variability of the representation of the standard in long-term memory was higher in the 5- than in the 8-year-olds and that the interfering task increased this memory variability.

Localization of brief sounds: effects of level and background noise.

Listeners show systematic errors in vertical-plane localization of wide-band sounds when tested with brief-duration stimuli at high intensities, but long-duration sounds at any comfortable level do not produce such errors. Improvements in high-level sound localization associated with increased stimulus duration might result from temporal integration or from adaptation that might allow reliable processing of later portions of the stimulus. Free-field localization judgments were obtained for clicks and for 3- and 100-ms noise bursts presented at sensation levels from 30 to 55 dB. For the brief (clicks and 3-ms) stimuli, listeners showed compression of elevation judgments and increased rates and unusual patterns of front/back confusion at sensation levels higher than 40-45 dB. At lower sensation levels, brief sounds were localized accurately. The localization task was repeated using 3-ms noise burst targets in a background of spatially diffuse, wide-band noise intended to pre-adapt the system prior to the target onset. For high-level targets, the addition of background noise afforded mild release from the elevation compression effect. Finally, a train of identical, high-level, 3-ms bursts was found to be localized more accurately than a single burst. These results support the adaptation hypothesis.

Visual motion sensitivity in dyslexia: evidence for temporal and energy integration deficits

In addition to poor literacy skills, developmental dyslexia has been associated with multisensory deficits for dynamic stimulus detection. In vision these deficits have been suggested to result from impaired sensitivity of cells within the retino-cortical magnocellular pathway and extrastriate areas in the dorsal stream to which they project. One consequence of such selectively reduced sensitivity is a difficulty in extracting motion coherence from dynamic noise, a deficit associated with both developmental dyslexia and persons with extrastriate, dorsal stream lesions. However the precise nature of the mechanism(s) underlying these perceptual deficits in dyslexia remain unknown. In this study, we obtained motion detection thresholds for 10 dyslexic and 10 control adults while varying the spatial and temporal parameters of the random dot kinematogram (RDK) stimuli. In Experiment 1 stimulus duration was manipulated to test whether dyslexics are specifically impaired for detecting short duration, rather than longer stimuli. Dot density was varied in Experiment 2 to examine whether dyslexics’ reduced motion sensitivity was affected by the amount of motion energy present in the RDKs. Dyslexics were consistently less sensitive to coherent motion than controls in both experiments. Increasing stimulus duration did not improve dyslexics’ performance, whereas increasing dot density did. Thus increasing motion energy assisted the dyslexics, suggesting that their motion detectors have a lower signal to noise ratio, perhaps due to spatial undersampling.

Activity-dependent extracellular K+ accumulation in rat optic nerve: the role of glial and axonal Na+ pumps.

1. We measured activity-dependent changes in [K+]o with K(+)-selective microelectrodes in adult rat optic nerve, a CNS white matter tract, to investigate the factors responsible for post-stimulus recovery of [K+]o. 2. Post-stimulus recovery of [K+]o followed a double-exponential time course with an initial, fast time constant, tau fast, of 0.9 +/- 0.2 s (mean +/- S.D.) and a later, slow time constant, tau slow, of 4.2 +/- 1 s following a 1 s, 100 Hz stimulus. tau fast, but not tau slow, decreased with increasing activity-dependent rises in [K+]o. tau slow, but not tau fast, increased with increasing stimulus duration. 3. Post-stimulus recovery of [K+]o was temperature sensitive. The apparent temperature coefficients (Q10, 27-37 degrees C) for the fast and slow components following a 1 s, 100 Hz stimulus were 1.7 and 2.6, respectively. 4. Post-stimulus recovery of [K+]o was sensitive to Na+ pump inhibition with 50 microM strophanthidin. Following a 1 s, 100 Hz stimulus, 50 microM strophanthidin increased tau fast and tau slow by 81 and 464%, respectively. Strophanthidin reduced the temperature sensitivity of post-stimulus recovery of [K+]o. 5. Post-stimulus recovery of [K+]o was minimally affected by the K+ channel blocker Ba2+ (0.2 mM). Following a 10 s, 100 Hz stimulus, 0.2 mM Ba2+ increased tau fast and tau slow by 24 and 18%, respectively. 6. Stimulated increases in [K+]o were followed by undershoots of [K+]o. Post-stimulus undershoot amplitude increased with stimulus duration but was independent of the peak preceding [K+]o increase. 7. These observations imply that two distinct processes contribute to post-stimulus recovery of [K+]o in central white matter. The results are compatible with a model of K+ removal that attributes the fast, initial phase of K+ removal to K+ uptake by glial Na+ pumps and the slower, sustained decline to K+ uptake via axonal Na+ pumps.

Speed tuning of motion segmentation and discrimination

Motion transparency requires that the visual system distinguish different motion vectors and selectively integrate similar motion vectors over space into the perception of multiple surfaces moving through or over each other. Using large-field (7×7°) displays containing two populations of random-dots moving in the same (horizontal) direction but at different speeds, we examined speed-based segmentation by measuring the speed difference above which observers can perceive two moving surfaces. We systematically investigated this ‘speed-segmentation’ threshold as a function of speed and stimulus duration, and found that it increases sharply for speeds above ≈8 °/s. In addition, speed-segmentation thresholds decrease with stimulus duration out to ≈200 ms. In contrast, under matched conditions, speed-discrimination thresholds stay low at least out to 16 °/s and decrease with increasing stimulus duration at a faster rate than for speed segmentation. Thus, motion segmentation and motion discrimination exhibit different speed selectivity and different temporal integration characteristics. Results are discussed in terms of the speed preferences of different neuronal populations within the primate visual cortex.

Pre-Attentive Discriminability of Sound Order as a Function of Tone Duration and Interstimulus Interval: A Mismatch Negativity Study

The present study addressed the pre-attentive processing of sound order. Event-related potentials were recorded from reading subjects while they were presented with pairs of two tones differing from each other in frequency (1000 vs. 1500 Hz). The within-pair (silent) interstimulus interval (ISI) was, in separate blocks, varied between 0 and 245 ms to determine the minimum separation in time needed for detecting the reversed order of the two frequencies. In standard tone pairs (p = 0.9), the frequencies were in an ascending order, whereas in the deviant pairs (p = 0.1), their order was reversed. Tone durations of 5 and 20 ms were employed in separate experiments. With the 20-ms stimulus duration, the change-specific mismatch negativity (MMN) component was elicited with all within-pair ISIs employed (0, 10, 30, 90 ms). With the 5-ms stimulus duration, however, MMN was elicited only with the 245-ms ISI but not with 95-ms or shorter ISIs. These results show that increased stimulus duration considerably improves perceiving the order of two tones at the pre-attentive level. They also indicate that the accuracy of the processing of temporal information can be probed with MMN. This finding, together with the fact that MMN elicitation does not require the subject’s voluntary attention, suggests that MMN might be used in the assessment of temporal processing deficits in clinical disorders in which patients are not motivated or able to give their verbal or motor response.

Action potential-dependent calcium transients in myenteric S neurons of the guinea-pig ileum

Simultaneous intracellular microelectrode recording and Fura-2 imaging was used to investigate the relationship between intracellular calcium ion concentration ([Ca 2+] i) and excitability of tonic S neurons in intact myenteric plexus of the guinea-pig ileum. S neurons were impaled in myenteric ganglia, at locations near connections with internodal strands. The calcium indicator Fura-2 was loaded via the recording microelectrode. The estimated [Ca 2+] i of these neurons was approximately 95 nM ( n=25). Intracellular current injection (200 ms pulses, 0.2 nA, delivered at 0.05 Hz) resulted in action potential firing throughout the stimulus pulse, accompanied by transient increases in [Ca 2+] i (to approximately 240 nM, n=12). Increasing the number of evoked action potentials by increasing stimulus duration (100–500 ms) or intensity (0.05–0.3 nA) produced correspondingly larger [Ca 2+] i transients. Single action potentials rarely produced resolvable [Ca 2+] i events, while short bursts of action potentials (three to five events) invariably produced resolvable [Ca 2+] i increases. Some neurons demonstrated spontaneous action potential firing, which was accompanied by sustained [Ca 2+] i increases. Action potential firing and [Ca 2+] i increases were also observed by activation of slow synaptic input to these neurons, in cases where the slow depolarization initiated action potential firing. Action potentials (evoked or spontaneous) and associated [Ca 2+] i transients were abolished by tetrodotoxin (1 μM). ω-conotoxin GVIA (100 nM) reduced [Ca 2+] i transients by approximately 67%, suggesting that calcium influx through N-type calcium channels contributes to evoked [Ca 2+] i increases. The S neurons in this study showed prominent afterhyperpolarizations following bursts of action potential firing. The time-course of afterhyperpolarizations was correlated with the time-course of evoked [Ca 2+] i transients. Afterhyperpolarizations were blocked by tetrodotoxin and reduced by ω-conotoxin GVIA, suggesting that calcium influx through N-type channels contributes to these events. The electrical properties of Fura-2-loaded neurons were not significantly different from properties of neurons recorded without Fura-2 injection, suggesting that Fura-2 injection alone does not significantly influence the electrical properties of these cells. These data indicate that myenteric S neurons in situ show prominent, activity-dependent increases in [Ca 2+] i. These events can be generated spontaneously, or be evoked by intracellular current injection or synaptic activation. [Ca 2+] i transients in these neurons appear to involve action potential-dependent opening of N-type calcium channels, and the elevation in [Ca 2+] i increase may underlie afterhyperpolarizations and regulate excitability of these enteric neurons.

Detection of short pure-tone stimuli in the noctuid ear: what are temporal integration and integration time all about?

Temporal integration in the A1 acoustic receptor cell of noctuid moths (Lepidoptera: Noctuidae) was studied. This was done by recording from the auditory nerve of Spodoptera littoralis and Noctua pronuba while stimulating with short-duration tone pulses. Consistent with previous experiments of the same kind, a decrease in threshold was observed with increasing stimulus duration. These threshold improvements, however, were larger than expected from an energy detector model of the receptor based on previous experiments with double clicks. This difference was analysed and could be attributed to a bias introduced by the choice of threshold criterion. If a fixed number of spikes elicited per stimulation is used as criterion, this will tend to lower the measured thresholds for long durations because for long stimuli, more time is available for accumulation of the spikes needed to exceed the criterion. It appears that temporal integration in the noctuid ear can be characterised by different time constants. One, termed the intrinsic time constant, is measured in the double-click experiments and provides information about the temporal integration and resolution within the receptor cell. Behavioural time constants, on the other hand, characterise the temporal integration reflected in the behaviour of the animals.

Spectro-temporal influence on auditory cortical evoked potential thresholds

Previous studies from our laboratory have shown that auditory cortical evoked potential thresholds (N1-P2) decrease with increasing stimulus duration. Similar to behavioral studies of auditory temporal integration, N1-P2 threshold improvement was greater for 1000-Hz than 4000-Hz stimuli. It is unclear whether spectral splatter at short durations contributed to the threshold differences across frequency. The present study investigated spectro-temporal influence on N1-P2 thresholds by manipulating the stimulus rise–fall time, total duration, and stimulus type. Thresholds were estimated in three temporal conditions to compare stimuli with equal rise–fall (2 ms) but different total durations (8, 36 ms), and stimuli with different rise–fall (2, 16 ms) but equal total durations (36 ms). Broadband noise bursts and 1000-Hz tones were used to test each temporal condition. Preliminary results show that thresholds for both noise and tonal stimuli decrease with increasing total duration. No significant differences in threshold were observed as a function of rise–fall time nor were significant differences observed as a function of the stimulus type. The results suggest that N1-P2 thresholds are determined primarily by changes in total duration and that thresholds for short durations at 1000 Hz are not adversely affected by spectral splatter. [Work supported by NSF.]