Duration judgements in patients with schizophrenia

BACKGROUND: The ability to encode time cues underlies many cognitive processes. In the light of schizophrenic patients' compromised cognitive abilities in a variety of domains, it is noteworthy that there are numerous reports of these patients displaying impaired timing abilities. However, the timing intervals that patients have been evaluated on in prior studies vary considerably in magnitude (e.g. 1 s, 1 min, 1 h etc.). METHOD: In order to obviate differences in abilities in chronometric counting and place minimal demands on cognitive processing, we chose tasks that involve making judgements about brief durations of time (< 1 s). RESULTS: On a temporal generalization task, patients were less accurate than controls at recognizing a standard duration. The performance of patients was also significantly different from controls on a temporal bisection task, in which participants categorized durations as short or long. Although time estimation may be closely intertwined with working memory, patients' working memory as measured by the digit span task did not correlate significantly with their performance on the duration judgement tasks. Moreover, lowered intelligence scores could not completely account for the findings. CONCLUSIONS: We take these results to suggest that patients with schizophrenia are less accurate at estimating brief time periods. These deficits may reflect dysfunction of biopsychological timing processes.     

Fos expression in the prefrontal cortex and nucleus accumbens following exposure to retrospective timing tasks

The dorsal striatum and prefrontal cortex have been implicated in interval timing. We examined whether performance of temporal discrimination tasks is associated with increased neuronal activation in these areas, as revealed by Fos expression, a marker for neuronal activation. In Experiment 1, rats were trained on a discrete-trials temporal discrimination task in which a light (22 cd/m2) was presented for a variable time, t (2.5-47.5 s), after which levers A and B were presented. A response on lever A was reinforced if t < 25 s, and a response on lever B was reinforced if t > 25 s. A second group was trained on a light-intensity discrimination procedure, in which a light of variable intensity, i (3.6-128.5 cd/m2) was presented for 25 s. A response on lever A was reinforced if i < 22 cd/m2, and a response on lever B was reinforced if i > 22 cd/m2. In Experiment 2, bisection procedures were used to assess temporal (200-800 ms, 22 cd/m2) and light-intensity (3.6-128.5 cd/m2, 400 ms) discrimination. The increase in proportional choice of lever B as a function of stimulus duration or intensity conformed to a two-parameter logistic equation. Fos expression in the prefrontal cortex and nucleus accumbens was higher in rats performing temporal discrimination tasks than in those performing light-intensity discrimination tasks, indicating greater neuronal activation in these areas during temporal discrimination tasks. Fos expression in the dorsal striatum did not differ between rats performing temporal and light-intensity discrimination tasks. These results suggest that the prefrontal cortex and nucleus accumbens are involved in temporal discrimination.     

Asymmetry of the discrimination function for temporal durations in human subjects

Ten human subjects were comparing durations of pairs of visual stimuli in a two-way forced-choice task. Mean durations of presented time intervals were -3 s ("short") or -6 s ("long"); the duration ratio was varied at nine levels. The Weber fractions for the short and long durations were approximately equal, -0.22. The ratio of subjective equality was almost exactly unity for the short durations, but it was significantly reduced (-0.76) for the long durations. This asymmetry of the discrimination function indicates time-dependent change of internal representations of past durations, and is well compatible with the "dual klepsydra model". Model-based estimates of the internal time representation loss rate, derived from the present data, are in a good agreement with values obtained from earlier studies on duration reproduction.     

The supplementary motor area in motor and sensory timing: evidence from slow brain potential changes

 The present study investigated the processing of durations on the order of seconds with slow cortical potential changes. The question is whether trial-to-trial fluctuations in temporal productions or judgments correspond to variations in the amplitude of surface Laplacians computed over particular scalp regions. Topographical analyses were done using the source derivation method. Subjects performed three successive tasks: (1) time production, in which they produced a 2.5-s interval separated by two brief trigger presses; (2) time discrimination, in which they detected small differences in intervals delimited by two brief clicks in comparison with a memorized standard interval; and (3) intensity discrimination (control task, devoid of time judgments), in which they detected small differences between the intensity of clicks, in comparison with standard clicks initially memorized. In order to focus on subjective differences, in the two discrimination tasks most comparison stimuli were identical to the standard, without the subjects being aware of it. At FCz, reflecting activity from the mesial frontocentral cortex that mainly includes the supplementary motor area (SMA), larger negativities were found during the longer target intervals, whether these were produced (task 1) or judged so (task 2). Those performance-dependent trends were restricted to the target intervals of the temporal tasks; they appeared neither during the 2 s preceding the target, nor during the control task. The data therefore suggest that the SMA subserves important functions in timing both sensory and motor tasks. We propose that the SMA either provides the ”pulse accumulation” process commonly postulated in models of time processing or that it receives output from this process through striatal efferent pathways. Received: 12 March 1998 / Accepted: 6 November 1998     

Electrophysiological localization of brain regions involved in perceptual memory

Event-related potentials (ERP) were recorded during perceptual discrimination and short-term memory, varying the interstimulus interval (1–10 s) in delayed spatial frequency discrimination. Accuracy of discrimination remained unimpaired across this time interval, but choice reaction times increased. A brain source localization (BESA) model showed that the activity of the parietal and right temporal sources increased with long retention intervals in a sequential activation pattern where a long-latency component of the parietal source specific to the memory condition was observed, the latency of which matched a memory-related increase in choice reaction times in the cognitive task. It is suggested that the temporal sources are involved in encoding and storage of visual information, and the parietal source is involved in memory retrieval. Received: 9 April 1998 / Accepted: 11 September 1998     

Slow brain potential and oscillatory EEG manifestations of impaired temporal preparation in Parkinson's disease

Performance in behavioral tasks is influenced by temporal expectations shaped by the temporal structure of the task. Such implicit temporal preparation is reflected in slow brain potentials and electroencephalographic oscillations and is attributed to interval timing mechanisms that probably depend on intact basal ganglia function. We investigated implicit timing in Parkinson's disease using a choice reaction task with two temporally regular stimulus presentation regimes, both including occasional deviant interstimulus intervals. Control subjects, but not patients, demonstrated temporal preparation in the form of an adjustment in time course of slow brain potentials to the duration of the interstimulus interval. However, in both groups, timing perturbations were accompanied by a slow brain potential amplitude drop at the time of expected stimulus occurrence, demonstrating intact representation of time in patients. In patients, oscillatory activity in beta and alpha bands showed attenuated preparatory desynchronization and reduced postmovement event-related synchronization, reflecting abnormal engagement and disengagement of sensorimotor and parietal areas. The results demonstrate profoundly deficient temporal preparation with preserved encoding of temporal information, a dissociation that may be explained by impaired dopamine-dependent motor learning. The results are discussed in the context of recent work on oscillatory activity in the basal ganglia.     

Contextual effects in interval-duration judgements in vision, audition and touch

We examined the effect of temporal context on discrimination of intervals marked by auditory, visual and tactile stimuli. Subjects were asked to compare the duration of the interval immediately preceded by an irrelevant “distractor” stimulus with an interval with no distractor. For short interval durations, the presence of the distractor affected greatly the apparent duration of the test stimulus: short distractors caused the test interval to appear shorter and vice versa. For very short reference durations (≤100 ms), the contextual effects were large, changing perceived duration by up to a factor of two. The effect of distractors reduced steadily for longer reference durations, to zero effect for durations greater than 500 ms. We found similar results for intervals defined by visual flashes, auditory tones and brief finger vibrations, all falling to zero effect at 500 ms. Under appropriate conditions, there were strong cross-modal interactions, particularly from audition to vision. We also measured the Weber fractions for duration discrimination and showed that under the conditions of this experiment, Weber fractions decreased steadily with duration, following a square-root law, similarly for all three modalities. The magnitude of the effect of the distractors on apparent duration correlated well with Weber fraction, showing that when duration discrimination was relatively more precise, the context dependency was less. The results were well fit by a simple Bayesian model combining noisy estimates of duration with the action of a resonance-like mechanism that tended to regularize the sound sequence intervals.     

How Is Temporal Processing Affected in Children with Attention-deficit/hyperactivity Disorder?

ABSTRACT

We compared the performance of children with ADHD and typically developing children on two temporal tasks, a bisection task and a reproduction task, in auditory and visual modalities. Children with ADHD presented a larger variability when performing auditory and visual temporal tasks. Moreover, they overestimated the durations in bisection tasks and underproduced duration intervals in the visual reproduction task. In the context of the pacemaker-accumulator model, these results suggest that temporal deficits might result from a dysfunction in the switch and/or memory impairment.     

Spike timing in CA3 pyramidal cells during behavior: implications for synaptic transmission

Spike timing is thought to be an important mechanism for transmitting information in the CNS. Recent studies have emphasized millisecond precision in spike timing to allow temporal summation of rapid synaptic signals. However, spike timing over slower time scales could also be important, through mechanisms including activity-dependent synaptic plasticity or temporal summation of slow postsynaptic potentials (PSPs) such as those mediated by kainate receptors. To determine the extent to which these slower mechanisms contribute to information processing, it is first necessary to understand the properties of behaviorally relevant spike timing over this slow time scale. In this study, we examine the activity of CA3 pyramidal cells during the performance of a complex behavioral task in rats. Sustained firing rates vary over a wide range, and the firing rate of a cell is poorly correlated with the behavioral cues to which the cell responds. Nonrandom interactions between successive spikes can last for several seconds, but the nonrandom distribution of interspike intervals (ISIs) can account for the majority of nonrandom multi-spike patterns. During a stimulus, cellular responses are temporally complex, causing a shift in spike timing that favors intermediate ISIs over short and long ISIs. Response discrimination between related stimuli occurs through changes in both response time-course and response intensity. Precise synchrony between cells is limited, but loosely correlated firing between cells is common. This study indicates that spike timing is regulated over long time scales and suggests that slow synaptic mechanisms could play a substantial role in information processing in the CNS.     

Repetitive TMS of cerebellum interferes with millisecond time processing

Time processing is important in several cognitive and motor functions, but it is still unclear how the human brain perceives time intervals of different durations. Processing of time in millisecond and second intervals may depend on different neural networks and there is now considerable evidence to suggest that these intervals are possibly measured by independent brain mechanisms. Using repetitive transcranial magnetic stimulation (rTMS), we determined that the cerebellum is essential in explicit temporal processing of millisecond time intervals. In the first experiment, subjects’ performance in a time reproduction task of short (400–600 ms) and long (1,600–2,400 ms) intervals, were evaluated immediately after application of inhibitory rTMS trains over the left and right lateral cerebellum (Cb) and the right dorsolateral prefrontal cortex (DLPFC). We found that rTMS over the lateral cerebellum impaired time perception in the short interval (millisecond range) only; for the second range intervals, impaired timing was found selectively for stimulation of the right DLPFC. In the second experiment, we observed that cerebellar involvement in millisecond time processing was evident when the time intervals were encoded but not when they were retrieved from memory. Our results are consistent with the hypothesis that the cerebellum can be considered as an internal timing system, deputed to assess millisecond time intervals.     

Activation of the supplementary motor area and of attentional networks during temporal processing

This paper first provides a survey of the expanding brain imaging literature in the field of time processing, showing that particular task features (discrete vs rhythmic, perceptual vs motor) do not significantly affect the basic pattern of activation observed. Next, positron emission tomography (PET) data obtained in a timing task (temporal reproduction) with two distinct duration ranges (2.2--3.2 and 9--13 s) are reported. The stimuli consisted of vibrations applied to the subject's right middle finger. When the vibration ended, the subject estimated an interval identical to its length before pressing a response button. The control task used cued responses with comparable intervals and stimuli. The pattern of activation obtained in the timing task as compared to control mainly included areas having attentional functions (the right dorsolateral prefrontal, inferior parietal, and anterior cingulate cortices), and the supplementary motor area (SMA). No significant difference was seen as a function of the duration range. It is argued, firstly, that involvement of the attentional areas derives from specific relations between attention and the temporal accumulator, as described by dominant timing models; and, secondly, that the SMA, or more probably one of its subregions, subserves time processing.     

Two-point tactile discrimination ability is influenced by temporal features of stimulation

Two-point discrimination threshold is commonly used for assessing tactile spatial resolution. Since the effect of temporal features of cutaneous test stimulation on spatial discrimination ability is not yet well known, we determined whether the ability to discriminate between two stimulus locations varies with the interstimulus interval (ISI) of sequentially presented tactile stimuli or the length of the stimulus train. Electrotactile stimuli were applied to one or two locations on the skin of the thenar eminence of the hand in healthy human subjects. Tactile discrimination ability was determined using methods based on the signal detection theory allowing the assessment of sensory performance, independent of the subject’s response criterion. With stimulus pairs, the ability to discriminate spatial features of stimulation (one location vs. two stimulus locations 4 cm apart) was improved when the ISI was equal to or longer than that required for tactile temporal discrimination. With stimulus trains, the ability to discriminate spatial features of stimulation was significantly improved with an increase in the stimulus train (from 3 to 11 pulses corresponding to train lengths from 40 to 200 ms). These results indicate that temporal features of tactile stimulation significantly influence sensory performance in a tactile spatial discrimination task. Precise control of temporal stimulus parameters should help to reduce variations in results on the two-point discrimination threshold.     

Cross-modal transfer of the conditioned eyeblink response during interstimulus interval discrimination training in young rats

Eyeblink classical conditioning (EBC) was observed across a broad developmental period with tasks utilizing two interstimulus intervals (ISIs). In ISI discrimination, two distinct conditioned stimuli (CSs; light and tone) are reinforced with a periocular shock unconditioned stimulus (US) at two different CS-US intervals. Temporal uncertainty is identical in design with the exception that the same CS is presented at both intervals. Developmental changes in conditioning have been reported in each task beyond ages when single-ISI learning is well developed. The present study sought to replicate and extend these previous findings by testing each task at four separate ages. Consistent with previous findings, younger rats (postnatal day--PD23 and 30) trained in ISI discrimination showed evidence of enhanced cross-modal influence of the short CS-US pairing upon long CS conditioning relative to older subjects. ISI discrimination training at PD43-47 yielded outcomes similar to those in adults (PD65-71). Cross-modal transfer effects in this task therefore appear to diminish between PD30 and PD43-47. Comparisons of ISI discrimination with temporal uncertainty indicated that cross-modal transfer in ISI discrimination at the youngest ages did not represent complete generalization across CSs. ISI discrimination undergoes a more protracted developmental emergence than single-cue EBC and may be a more sensitive indicator of developmental disorders involving cerebellar dysfunction.     

Auditory dominance over vision in the perception of interval duration

The “ventriloquist effect” refers to the fact that vision usually dominates hearing in spatial localization, and this has been shown to be consistent with optimal integration of visual and auditory signals (Alais and Burr in Curr Biol 14(3):257–262, 2004). For temporal localization, however, auditory stimuli often “capture” visual stimuli, in what has become known as “temporal ventriloquism”. We examined this quantitatively using a bisection task, confirming that sound does tend to dominate the perceived timing of audio-visual stimuli. The dominance was predicted qualitatively by considering the better temporal localization of audition, but the quantitative fit was less than perfect, with more weight being given to audition than predicted from thresholds. As predicted by optimal cue combination, the temporal localization of audio-visual stimuli was better than for either sense alone.     

Effects of lesions to the cerebellar vermis and hemispheres on timing and counting in rats

The effects of lesions to the cerebellum on numerical and temporal discrimination were examined in rats using a psychophysical choice procedure. Lesions to the cerebellar hemispheres but not the cerebellar vermis produced performance deficits in a numerical discrimination task (2-8 events) and a milliseconds temporal discrimination task (0.2-0.8 s). However, temporal discriminations in the seconds range (2-8 s) were unaffected by either type of lesion. Using W. H. Meck and R. M. Church's (1983) mode-control model of timing and counting, these findings suggest that damage to the cerebellar hemispheres influences a source of constant variability (e.g., switch processes) because constant variability is a prominent source of error during both milliseconds timing and counting but is masked by other sources of variability when timing longer durations (>2 s).     

Taste response variability and temporal coding in the nucleus of the solitary tract of the rat

Theories of taste coding in the brain stem have been based on the idea that taste responses are integrated over time without regard to the temporal structure of the taste-evoked spike train. In the present experiment, the reliability of response rate across stimulus repetitions and the potential contribution of temporal coding to the discrimination of taste stimuli was examined. Taste stimuli representing the four basic taste qualities were presented repeatedly, and electrophysiological responses were recorded from single cells in the nucleus of the solitary tract (NTS) of anesthetized rats. Blocks of the four tastants were repeated for as long as the cell remained isolated. Nineteen cells were recorded with between 8 and 27 repetitions of each stimulus. Response magnitude to a given tastant varied widely within some NTS cells. This impacted the determination of both the breadth of tuning and best stimulus for a given cell. The contribution of spike timing and the pattern of interspike intervals to discrimination of taste stimuli was evaluated by an information-theoretic approach based on two families of metrics. Spike timing significantly contributed to the discrimination of taste qualities in 10 of 19 (53%) cells. This contribution was especially notable during the initial 2 s of the response. Those cells that showed the most variable firing rates in response to repetition of taste stimuli tended to show the largest contribution of temporal coding. These results suggest that, in addition to response rate, the temporal parameters of responses may convey information about taste stimuli in the NTS.     

Temporal prediction modulates the evaluative processing of “good” action feedback: An electrophysiological study

The present study aimed to investigate whether or not the evaluative processing of action feedback can be modulated by temporal prediction. For this purpose, we examined the effects of the predictability of the timing of action feedback on an ERP effect that indexed the evaluative processing of action feedback, that is, an ERP effect that has been interpreted as a feedback‐related negativity (FRN) elicited by “bad” action feedback or a reward positivity (RewP) elicited by “good” action feedback. In two types of experimental blocks, the participants performed a gambling task in which they chose one of two cards and received an action feedback that indicated monetary gain or loss. In fixed blocks, the time interval between the participant's choice and the onset of the action feedback was fixed at 0, 500, or 1,000 ms in separate blocks; thus, the timing of action feedback was predictable. In mixed blocks, the time interval was randomly chosen from the same three intervals with equal probability; thus, the timing was less predictable. The results showed that the FRN/RewP was smaller in mixed than fixed blocks for the 0‐ms interval trial, whereas there was no difference between the two block types for the 500‐ms and 1,000‐ms interval trials. Interestingly, the smaller FRN/RewP was due to the modulation of gain ERPs rather than loss ERPs. These results suggest that temporal prediction can modulate the evaluative processing of action feedback, and particularly good feedback, such as that which indicates monetary gain.     

Effects of fimbria-fornix lesion on the temporal discrimination revealed by peak interval procedure in rats

When temporal discrimination is examined by a peak interval (PI) procedure in rats, a shortening of peak time is induced by the fimbria-fornix (FF) lesion. The aim of this research is to investigate the extent of peak time shortening induced by FF lesion and the acquisition process of temporal discrimination. In FF lesioned rats, the peak time was very short (about 13 sec) in earlier phase, then became longer as the training progressed and reached a steady level, which was approximately 20% shorter than control rats. These results suggest that the "non-timing process" is involved in addition to the "timing process" in FF lesioned rats.     

Altered time judgements highlight common mechanisms of time and space perception

ABSTRACT

Space, numbers and time share similar processing mechanisms mediated by parietal cortex. In parallel to the spatial representation of numbers along a horizontal line, temporal information is mapped on a horizontal axis with short intervals (and the past) represented to the left of long intervals (and the future). Little is known about the representation of time in the presence of visuo-spatial deficits. We here report two experiments on the comparative judgment of time. Experiment 1 required patients with left-sided neglect to indicate which of two consecutively presented silent intervals was longer. Their judgments were better if the first interval was longer and they judged the first interval longer on trials in which the two intervals were equally long. These results were not present in right-hemispheric damaged patients without neglect and healthy controls. They are in line with a previously reported finding in a single patient with neglect, but not readily compatible with findings of neglect patients’ comparative length judgments. In Experiment 2, healthy participants’ performance on an identical task improved for trials with a first-longer interval after caloric vestibular stimulation (CVS) of the right ear with warm water.     

Phasic heart rate responses to performance feedback in a time production task: effects of information versus valence

This study examined the cardiac concomitants of feedback processing in a time production task derived from [Mittner et al., J. Cogn. Neurosci. 9 (1997) 788]. Participants performed the time production task (i.e. 1-s intervals) under two conditions. In the experimental condition, feedback informed them that the produced interval was within or outside the acceptable range (too long or too short). In the other, yoked-control, condition feedback was unrelated to the actual estimate. The performance findings indicated that in the experimental condition, participants tended to adjust the new interval in the direction indicated by the feedback. In the control condition, however, the adjustments were largely unrelated to the information provided by the feedback. Heart rate slowed to feedback stimuli indicating that the estimate was outside the acceptable range. Surprisingly, cardiac slowing did not discriminate between experimental and control conditions. This finding seems to suggest that heart rate is sensitive to the valence rather than the information provided by the feedback. This finding is discussed vis-à-vis current neuroimaging and psychophysiological studies of performance monitoring.