Search

A robust adaptation to environmental changes is vital for survival. Almost all living organisms have a circadian timing system that allows adjusting their physiology to cyclic variations in the surrounding environment. Among vertebrates, many birds are also seasonal species, adapting their physiology to annual changes in photoperiod (amplitude, length and duration). Tawny Owls (Strix aluco) are nocturnal birds of prey that use vocalization as their principal mechanism of communication. Diurnal and seasonal changes in vocalization have been described for several vocal species, including songbirds. Comparable studies are lacking for owls. In the present work, we show that male Tawny Owls present a periodic vocalization pattern in the seconds-to-minutes range that is subject to both daily (early vs. late night) and seasonal (spring vs. summer) rhythmicity. These novel theory-generating findings appear to extend the role of the circadian system in regulating temporal events in the seconds-to-minutes range to other species.

The contributions of cortico-cerebellar and cortico-striatal circuits to timing and time perception have often been a point of contention. In this review we propose that the cerebellum principally functions to reduce variability, through the detection of stimulus onsets and the sub-division of longer durations, thus contributing to both sub-second and supra-second timing. This sensitivity of the cerebellum to stimulus dynamics and subsequent integration with motor control allows it to accurately measure intervals within a range of 100–2000 ms. For intervals in the supra-second range (e.g., >2000 ms), we propose that cerebellar output signals from the dentate nucleus pass through thalamic connections to the striatum, where cortico-thalamic-striatal circuits supporting higher-level cognitive functions take over. Moreover, the importance of intrinsic circuit dynamics as well as behavioral, neuroimaging, and lesion studies of the cerebellum and striatum are discussed in terms of a framework positing initiation, continuation, adjustment, and termination phases of temporal processing.

Male Sprague–Dawley rats were exposed to social defeat and subordination by aggressive male Long–Evans rats. The social defeat procedure involved the continuous exposure to an aggressive resident for 10 days, while living in a protective cage within the resident’s home cage with daily brief confrontations. These stress experiences resulted in 1) reduced body weight; 2) decreased social interaction; 3) increased ultrasonic vocalizations; 4) reduced sucrose preference (anhedonia); and 5) decreased clock speed while timing 15-s and 45-s target durations in a bi-peak procedure. Treatment with ketamine (15 mg/kg, i.p.) produced a rapid reversal of anhedonia and overproduction of duration. Taken together, these data provide the first evaluation of the effects of continuous social defeat and its associated depression-like symptoms on timing and time perception using a ‘state change’ design.

Basic mechanisms of interval timing and associative learning are shared by many animal species, and develop quickly in early life, particularly across infancy, and childhood. Indeed, John Wearden in his book “The Psychology of Time Perception”, which is based on decades of his own research with colleagues, and which our commentary serves to primarily review, has been instrumental in implementing animal models and methods in children and adults, and has revealed important similarities (and differences) between human timing (and that of animals) when considered within the context of scalar timing theory. These seminal studies provide a firm foundation upon which the contemporary multifaceted field of timing and time perception has since advanced. The contents of the book are arguably one piece of a larger puzzle, and as Wearden cautions, “The reader is warned that my own contribution to the field has been exaggerated here, but if you are not interested in your own work, why would anyone else be?” Surely there will be many interested readers, however the book is noticeably lacking in it neurobiological perspective. The mind (however it is conceived) needs a brain (even if behaviorists tend to say “the brain behaves”, and most neuroscientists currently have a tenuous grasp on the neural mechanisms of temporal cognition), and to truly understand the psychology of time, brain and behavior must go hand in hand regardless of the twists, turns, and detours along the way.

Time is a universal psychological dimension, but time perception has often been studied and discussed in relative isolation. Increasingly, researchers are searching for unifying principles and integrated models that link time perception to other domains. In this review, we survey the links between temporal cognition and other psychological processes. Specifically, we describe how subjective duration is affected by nontemporal stimulus properties (perception), the allocation of processing resources (attention), and past experience with the stimulus (memory). We show that many of these connections instantiate a "processing principle," according to which perceived time is positively related to perceptual vividity and the ease of extracting information from the stimulus. This empirical generalization generates testable predictions and provides a starting-point for integrated theoretical frameworks. By outlining some of the links between temporal cognition and other domains, and by providing a unifying principle for understanding these effects, we hope to encourage time-perception researchers to situate their work within broader theoretical frameworks, and that researchers from other fields will be inspired to apply their insights, techniques, and theorizing to improve our understanding of the representation and judgment of time. (PsycINFO Database Record

The ability to decipher where one needs to be and when it is most beneficial to be there are fundamental to the success of an organism. Humans along with other animals are able to extract duration and temporal order from external as well as internal stimuli, though lacking a dedicated sensory organ for time. A plethora of studies have focused on dorsal striatal and cerebellar networks as primary timing circuits with medium spiny neurons and Purkinje cells acting as the core temporal integrators within these circuits, respectively. However, recent findings have also made a strong case for the inclusion of the hippocampus with the discovery of hippocampal ‘time cells’. The denoted cells are pyramidal cells within the hippocampal CA1 area that exhibit increased firing rates in relation to elapsing durations, independent of the space and distance traveled. Previous behavioral work had implicated the role of the hippocampus in temporal processing, but only as of late has this work been substantiated with direct electrophysiological evidence. We describe the most recent evidence supporting the identification of ‘time cells’ in the subcortical structures of the striatum, hippocampus, and cerebellum and indicate how these different timing systems might be integrated into a common percept for time.

Bilateral intratympanic sodium arsenate injections (100 mg/ml in isotonic saline) in adult male Long Evans rats produced impairments in allocentric navigation using a 12-arm radial maze procedure as well as a motor test battery designed to evaluate vestibular function. In contrast, no impairments in the accuracy or precision of duration reproduction using 20-s and 80-s peak-interval procedures were observed when both target durations were associated with the same lever response, but distinguished by signal modality (e.g., light or sound). In contrast, an ordinal-reproduction procedure with 800, 3200, and 12,800 ms standards requiring the timing of self-initiated movements during the production phase revealed large impairments in the accuracy and precision of timing for vestibular lesioned rats. These impairments were greater on trials in which self-initiated body movements (e.g., holding down the response lever for a fixed duration) were required without the support of external stimuli signaling the onset and offset of the reproduced duration in contrast to trials in which such external support was provided. The conclusion is that space and time are separable entities and not simply the product of a generalized system, but they can be integrated into a common metric using gravity and self-initiated movement as a reference.

We present an integrated view of interval timing and reinforcement learning (RL) in the brain. The computational goal of RL is to maximize future rewards, and this depends crucially on a representation of time. Different RL systems in the brain process time in distinct ways. A model-based system learns 'what happens when', employing this internal model to generate action plans, while a model-free system learns to predict reward directly from a set of temporal basis functions. We describe how these systems are subserved by a computational division of labor between several brain regions, with a focus on the basal ganglia and the hippocampus, as well as how these regions are influenced by the neuromodulator dopamine.

Interval timing and working memory are critical components of cognition that are supported by neural oscillations in prefrontal-striatal-hippocampal circuits. In this review, the properties of interval timing and working memory are explored in terms of behavioral, anatomical, pharmacological, and neurophysiological findings. We then describe the various neurobiological theories that have been developed to explain these cognitive processes - largely independent of each other. Following this, a coupled excitatory - inhibitory oscillation (EIO) model of temporal processing is proposed to address the shared oscillatory properties of interval timing and working memory. Using this integrative approach, we describe a hybrid model explaining how interval timing and working memory can originate from the same oscillatory processes, but differ in terms of which dimension of the neural oscillation is utilized for the extraction of item, temporal order, and duration information. This extension of the striatal beat-frequency (SBF) model of interval timing (Matell and Meck, 2000, 2004) is based on prefrontal-striatal-hippocampal circuit dynamics and has direct relevance to the pathophysiological distortions observed in time perception and working memory in a variety of psychiatric and neurological conditions. (C) 2014 Elsevier Ltd. All rights reserved.

Time perception is fundamental and heavily researched, but the field faces a number of obstacles to theoretical progress. In this advanced review, we focus on three pieces of ‘bad news’ for time perception research: temporal perception is highly labile across changes in experimental context and task; there are pronounced individual differences not just in overall performance but in the use of different timing strategies and the effect of key variables; and laboratory studies typically bear little relation to timing in the ‘real world’. We describe recent examples of these issues and in each case offer some ‘good news’ by showing how new research is addressing these challenges to provide rich insights into the neural and information-processing bases of timing and time perception. © 2014 The Authors.

The overlap of neural circuits involved in episodic memory, relational learning, trace conditioning, and interval timing suggests the importance of hippocampal-dependent processes. Identifying the functional and neural mechanisms whereby the hippocampus plays a role in timing and decision-making, however, has been elusive. In this article we describe recent neurobiological findings, including the discovery of hippocampal ‘time cells’, dependency of duration discriminations in the minutes range on hippocampal function, and the correlation of hippocampal theta rhythm with specific features of temporal processing. These results provide novel insights into the ways in which the hippocampus might interact with the striatum in order to support both retrospective and prospective timing. Suggestions are also provided for future research on the role of the hippocampus in memory for elapsed time.

The journal Timing & Time Perception (Brill Publishers) was initiated with the realization that the study of ‘timing and time perception’ is growing exponentially with interest from fields as diverse as cognitive science, computer science, economics, philosophy, psychology, robotics, and neuroscience … to name just a few. As with any scientific endeavor, once a sufficient empirical base has been established it becomes both necessary and desirable to support such a rapidly growing enterprise with a platform for publishing integrative and multidisciplinary reviews. We are pleased to announce that Timing & Time Perception Reviews (a joint publication of the University of Groningen and Brill Publishers) is being launched as a diamond open-access journal with that goal firmly in mind. Some of the highlights of the inaugural issue are presented in our editorial along with examples of the types of ideas we would like to see developed in future submissions to the journal.

Animals, including fish, birds, rodents, non-human primates, and pre-verbal infants are able to discriminate the duration and number of events without the use of language. In this paper, we present the results of six experiments exploring the capability of adult rats to count 2–6 sequentially presented white-noise stimuli. The investigation focuses on the animal’s ability to exhibit spontaneous subtraction following the presentation of novel stimulus inversions in the auditory signals being counted. Results suggest that a subtraction operation between two opposite sensory representations may be a general processing strategy used for the comparison of stimulus magnitudes. These findings are discussed within the context of a mode-control model of timing and counting that relies on an analog temporal-integration process for the addition and subtraction of sequential events.

Five experiments were conducted to determine the effects of hippocampal damage on timing and the memory for temporal events. In Experiments 1-3, rats were trained to discriminate between auditory signals that differed in both duration (2 or 8 s) and rate (2 or 16 cycles/s). Half of the rats were trained to discriminate duration, and half were trained to discriminate rate. After rats acquired the relevant discrimination, signals with intermediate durations and rates were presented to obtain psychophysical functions that related signal duration and/or rate to response choice. Rats then received either lesions of the fimbria-fornix or control operations. Postoperatively, the accuracy of duration and rate discriminations as measured by the difference limen (DL) was unaffected by the lesion, but the point of subjective equality (PSE) was shifted to a shorter duration and a slower rate by the lesion in Experiment 1. Both rats with lesions and rats with control operations showed cross-modal transfer of duration and rate from the auditory signals used in training to visual signals used in testing in Experiment 2. A 5-s delay was imposed between the end of a signal and the opportunity to respond in Experiment 3. The delay served as a retention interval for the rats trained in the rate discrimination, and the rats with fimbria-fornix lesions were selectively impaired by the addition of the delay as measured by an increase in the DL. The delay did not serve as a retention interval for rats trained in the duration discrimination because they were able to continue timing through the delay. A peak procedure was employed in Experiment 4. The maximum response rate of control rats was approximately at the time of scheduled reinforcement (20 s), but the maximum response rate of rats with fimbria-fornix lesions was reliably earlier than the time of scheduled reinforcement. When a 5-s gap was imposed in the signal, control rats summed the signal durations before and after the gap, whereas rats with fimbria-fornix lesions showed no retention of the signal duration prior to the gap. Experiment 5 continued the testing of the rats used in Experiments 1-4 and showed that rats with lesions had an impairment in a test of spatial working memory in an eight-arm radial maze. Taken together, these results demonstrate that a fimbria-fornix lesion interferes with temporal and spatial working memory, reduces the remembered time of reinforcement stored in reference memory, and has no effect on the animal's sensitivity to stimulus duration.

Temporal and social processing are intricately linked. The temporal extent and organization of interactional behaviors both within and between individuals critically determine interaction success. Conversely, social signals and social context influence time perception by, for example, altering subjective duration and making an event seem ‘out of sync'. An ‘internal clock' involving subcortically orchestrated cortical oscillations that represent temporal information, such as duration and rhythm, as well as insular projections linking temporal information with internal and external experiences is proposed as the core of these reciprocal interactions. The timing of social relative to non-social stimuli augments right insular activity and recruits right superior temporal cortex. Together, these reciprocal pathways may enable the exchange and respective modulation of temporal and social computations.

This review outlines the basic psychological and neurobiological processes associated with age-related distortions in timing and time perception in the hundredths of milliseconds-to-minutes range. The difficulty in separating indirect effects of impairments in attention and memory from direct effects on timing mechanisms is addressed. The main premise is that normal aging is commonly associated with increased noise and temporal uncertainty as a result of impairments in attention and memory as well as the possible reduction in the accuracy and precision of a central timing mechanism supported by dopamine-glutamate interactions in cortico-striatal circuits. Pertinent to these findings, potential interventions that may reduce the likelihood of observing age-related declines in timing are discussed. Bayesian optimization models are able to account for the adaptive changes observed in time perception by assuming that older adults are more likely to base their temporal judgments on statistical inferences derived from multiple trials than on a single trial's clock reading, which is more susceptible to distortion. We propose that the timing functions assigned to the age-sensitive fronto-striatal network can be subserved by other neural networks typically associated with finely-tuned perceptuo-motor adjustments, through degeneracy principles (different structures serving a common function).

The claustrum has been proposed as a possible neural candidate for the coordination of conscious experience due to its extensive ‘connectome’. Herein we propose that the claustrum contributes to consciousness by supporting the temporal integration of cortical oscillations in response to multisensory input. A close link between conscious awareness and interval timing is suggested by models of consciousness and conjunctive changes in meta-awareness and timing in multiple contexts and conditions. Using the striatal beat-frequency model of interval timing as a framework, we propose that the claustrum integrates varying frequencies of neural oscillations in different sensory cortices into a coherent pattern that binds different and overlapping temporal percepts into a unitary conscious representation. The proposed coordination of the striatum and claustrum allows for time-based dimensions of multisensory integration and decision-making to be incorporated into consciousness.

Although fear-producing treatments (e.g., electric shock) and pleasure-inducing treatments (e.g., methamphetamine) have different emotional valences, they both produce physiological arousal and lead to effects on timing and time perception that have been interpreted as reflecting an increase in speed of an internal clock. In this commentary, we review the results reported by Fayolle et al. (2015):Behav. Process., 120, 135–140) and Meck (1983: J. Exp. Psychol. Anim. Behav. Process., 9, 171–201) using electric shock and by Maricq et al. (1981: J. Exp. Psychol. Anim. Behav. Process., 7, 18–30) using methamphetamine in a duration-bisection procedure across multiple duration ranges. The psychometric functions obtained from this procedure relate the proportion ‘long’ responses to signal durations spaced between a pair of ‘short’ and ‘long’ anchor durations. Horizontal shifts in these functions can be described in terms of attention or arousal processes depending upon whether they are a fixed number of seconds independent of the timed durations (additive) or proportional to the durations being timed (multiplicative). Multiplicative effects are thought to result from a change in clock speed that is regulated by dopamine activity in the medial prefrontal cortex. These dopaminergic effects are discussed within the context of the striatal beat frequency model of interval timing (Matell & Meck, 2004:Cogn. Brain Res.,21, 139–170) and clinical implications for the effects of emotional reactivity on temporal cognition (Parker et al., 2013:Front. Integr. Neurosci., 7, 75).

Discriminative fear conditioning requires learning to dissociate between safety cues and cues that predict negative outcomes yet little is known about what processes contribute to discriminative fear learning. According to attentional models of time perception, processes that distract from timing result in temporal underestimation. If discriminative fear learning only requires learning what cues predict what outcomes, and threatening stimuli distract attention from timing, then better discriminative fear learning should predict greater temporal distortion on threat trials. Alternatively, if discriminative fear learning also reflects a more accurate perceptual experience of time in threatening contexts, discriminative fear learning scores would predict less temporal distortion on threat trials, as time is perceived more veridically. Healthy young adults completed discriminative fear conditioning in which they learned to associate one stimulus (CS+) with aversive electrical stimulation and another stimulus (CS−) with non-aversive tactile stimulation and then an ordinal-comparison timing task during which CSs were presented as task-irrelevant distractors. Consistent with predictions, we found an overall temporal underestimation bias on CS+ relative to CS− trials. Differential skin conductance responses to the CS+ versus the CS− during conditioning served as a physiological index of discriminative fear conditioning and this measure predicted the magnitude of the underestimation bias, such that individuals exhibiting greater discriminative fear conditioning showed less underestimation on CS+ versus CS− trials. These results are discussed with respect to the nature of discriminative fear learning and the relationship between temporal distortions and maladaptive threat processing in anxiety.

Like other senses, our perception of time is not veridical, but rather, is modulated by changes in environmental context. Anecdotal experiences suggest that emotions can be powerful modulators of time perception; nevertheless, the functional and neural mechanisms underlying emotion-induced temporal distortions remain unclear. Widely accepted pacemaker-accumulator models of time perception suggest that changes in arousal and attention have unique influences on temporal judgments and contribute to emotional distortions of time perception. However, such models conflict with current views of arousal and attention suggesting that current models of time perception do not adequately explain the variability in emotion-induced temporal distortions. Instead, findings provide support for a new perspective of emotion-induced temporal distortions that emphasizes both the unique and interactive influences of arousal and attention on time perception over time. Using this framework, we discuss plausible functional and neural mechanisms of emotion-induced temporal distortions and how these temporal distortions may have important implications for our understanding of how emotions modulate our perceptual experiences in service of adaptive responding to biologically relevant stimuli.

Aged male rats at 10, 20, and 30 mo of age were trained on a 2.0 vs. 8.0-s duration bisection procedure using both auditory and visual signals and were then tested with visual signal durations in which the spacing of the intermediate signal durations was held constant as the short (S) and long (L) anchor durations were moved progressively closer to each other across blocks of sessions. Auditory clicks also preceded some trials in order to determine the potential effects of arousal and/or distraction on the timing of visual signals. The consequences of aging, reducing the S:L ratio, and auditory clicks were to increase the likelihood of observing reversals in response classifications around the geometric mean of the anchor durations. Taken together, these results suggest that the bisection "reversal effect" is dependent upon the calculation of the subjective mid-point between the two anchor durations and the differential setting of response thresholds around this category boundary as a function of temporal context.

We all have a sense of time. Yet, there are no sensory receptors specifically dedicated for perceiving time. It is an almost uniquely intangible sensation: we cannot see time in the way that we see color, shape, or even location. So how is time represented in the brain? We explore the neural substrates of metrical representations of time such as duration estimation (explicit timing) or temporal expectation (implicit timing). Basal ganglia (BG), supplementary motor area, cerebellum, and prefrontal cortex have all been linked to the explicit estimation of duration. However, each region may have a functionally discrete role and will be differentially implicated depending upon task context. Among these, the dorsal striatum of the BG and, more specifically, its ascending nigrostriatal dopaminergic pathway seems to be the most crucial of these regions, as shown by converging functional neuroimaging, neuropsychological, and psychopharmacological investigations in humans, as well as lesion and pharmacological studies in animals. Moreover, neuronal firing rates in both striatal and interconnected frontal areas vary as a function of duration, suggesting a neurophysiological mechanism for the representation of time in the brain, with the excitatory-inhibitory balance of interactions among distinct subtypes of striatal neuron serving to fine-tune temporal accuracy and precision.

Choline supplementation of the maternal diet has long-term facilitative effects on spatial and temporal memory processes in the offspring. To further delineate the impact of early nutritional status on brain and behavior, we examined effects of prenatal-choline availability on hippocampal oscillatory frequency bands in 12 month-old male and female rats. Adult offspring of time-pregnant dams that were given a deficient level of choline (DEF=0.0 g/kg), sufficient choline (CON=1.1 g/kg) or supplemental choline (SUP=3.5 g/kg) in their chow during embryonic days (ED) 12-17 were implanted with an electroencephalograph (EEG) electrode in the hippocampal dentate gyrus in combination with an electromyograph (EMG) electrode patch implanted in the nuchal muscle. Five consecutive 8-h recording sessions revealed differential patterns of EEG activity as a function of awake, slow-wave sleep (SWS) and rapid-eye movement (REM) sleep states and prenatal choline status. The main finding was that SUP rats displayed increased power levels of gamma (30-100 Hz) band oscillations during all phases of the sleep/wake cycle. These findings are discussed within the context of a general review of neuronal oscillations (e.g., delta, theta, and gamma bands) and synchronization across multiple brain regions in relation to sleep-dependent memory consolidation in the hippocampus.

The effects of prenatal choline availability on contextual processing in a 30-s peak-interval (PI) procedure with gaps (1, 5, 10, and 15 s) were assessed in adult male rats. Neither supplementation nor deprivation of prenatal choline affected baseline timing performance in the PI procedure. However, prenatal choline availability significantly altered the contextual processing of gaps inserted into the to-be-timed signal (light on). Choline-supplemented rats displayed a high degree of context sensitivity as indicated by clock resetting when presented with a gap in the signal (light off). In contrast, choline-deficient rats showed no such effect and stopped their clocks during the gap. Control rats exhibited an intermediate level of contextual processing in between stop and full reset. When switched to a reversed gap condition in which rats timed the absence of the light and the presence of the light served as a gap, all groups reset their clocks following a gap. Furthermore, when filling the intertrial interval (ITI) with a distinctive stimulus (e.g., sound), both choline-supplemented and control rats rightward shifted their PI functions less on trials with gaps than choline-deficient rats, indicating greater contextual sensitivity and reduced clock resetting under these conditions. Overall, these data support the view that prenatal choline availability affects the sensitivity to the context in which gaps are inserted in the to-be-timed signal, thereby influencing whether rats run, stop, or reset their clocks.

The indirect dopamine (DA) agonist methamphetamine (MAP) is evaluated in terms of its impact on the speed of temporal processing across multiple time scales involving both interval and circadian timing. Behavioral and neuropharmacological aspects of drug abuse, habit formation, neurotoxicity, and the potential links between interval and circadian timing are reviewed. The view that emerges is one in which the full spectrum of MAP-induced effects on timing and time perception is both complex and dynamic in as much as it involves DA-glutamate interactions and gene expression within cortico-striatal circuitry spanning oscillation periods ranging from milliseconds to multiple hours. The conclusion is that the psychostimulant properties of MAP are very much embedded within the context of temporal prediction and the anticipation of reward.

Choline supplementation of the maternal diet has a long-term facilitative effect on timing and temporal memory of the offspring. To further delineate the impact of early nutritional status on interval timing, we examined effects of prenatal choline supplementation on the temporal sensitivity of adult (6 months) male rats. Rats that were given sufficient choline in their chow (CON: 1.1 g/kg) or supplemental choline added to their drinking water (SUP: 3.5 g/kg) during embryonic days (ED) 12-17 were trained with a peak-interval procedure that was shifted among 75%, 50%, and 25% probabilities of reinforcement with transitions from 18 s-->36 s-->72 s temporal criteria. Prenatal choline supplementation systematically sharpened interval timing functions by reducing the associative/non-temporal response enhancing effects of reinforcement probability on the Start response threshold, thereby reducing non-scalar sources of variance in the left-hand portion of the Gaussian-shaped response functions. No effect was observed for the Stop response threshold as a function of any of these manipulations. In addition, independence of peak time and peak rate was demonstrated as a function of reinforcement probability for both prenatal choline-supplemented and control rats. Overall, these results suggest that prenatal choline supplementation facilitates timing by reducing impulsive responding early in the interval, thereby improving the superimposition of peak functions for different temporal criteria.

Our sense of time is altered by our emotions to such an extent that time seems to fly when we are having fun and drags when we are bored. Recent studies using standardized emotional material provide a unique opportunity for understanding the neurocognitive mechanisms that underlie the effects of emotion on timing and time perception in the milliseconds-to-hours range. We outline how these new findings can be explained within the framework of internal-clock models and describe how emotional arousal and valence interact to produce both increases and decreases in attentional time sharing and clock speed. The study of time and emotion is at a crossroads, and we outline possible examples for future directions.

Methamphetamine intoxication has long-term consequences on dopaminergic function and corticostriatal-mediated behaviors in humans and other animals. In order to determine the potential impact on timing and temporal memory, we examined methamphetamine dose regimens that have been linked to neurotoxicity in adult (8 months) male rats. Rats that were given repetitive, high-dose methamphetamine (3.0 mg/kg ip × 4 injections/2 h) or saline injections were trained on a 2-s vs 8-s bisection procedure using auditory and visual signal durations. Following the high-dose regimen, baseline timing performance was reestablished prior to the rats' receiving reversal training in which the spatial/temporal mapping of the anchor durations (2 s and 8 s) to response options (left or right lever) was reversed. Low-dose methamphetamine (0.5 mg/kg ip) or saline injections were subsequently used to evaluate the effectiveness of the neurotoxic doses in terms of modifying the horizontal leftward shifts associated with increases in clock speed. Overall, the results indicate that MAP intoxication leads to reduced auditory/visual differences in clock speed, deficits in reversal learning, distortions in temporal memory, and lowered dopaminergic regulation of clock speed consistent with damage to prefrontal cortex and corticostriatal circuitry.

The present study examined the clock-speed modulating effects of acute cocaine administration in groups of male rats that received different amounts of baseline training on a 36-s peak-interval procedure prior to initial drug injection. After injection of cocaine (10, 15, or 20mg/kg, ip), rats that had received a minimal amount of training (e.g.,or=30 sessions) prior to drug administration displayed a horizontal leftward shift in their timing functions indicating that the speed of the internal clock was increased. In contrast, rats that had received an extended amount of training (e.g.,or=180 sessions) prior to cocaine (15 mg/kg, ip) administration did not produce this "classic" curve-shift effect, but instead displayed a general disruption of temporal control following drug administration. Importantly, when co-administered with a behaviorally ineffective dose of ketamine (10mg/kg, ip) the ability of cocaine to modulate clock speed in rats receiving extended training was restored. A glutamate "lock/unlock" hypothesis is used to explain the observed dopamine-glutamate interactions as a function of timing behaviors becoming learned habits.

Representations of abstract quantities such as time and number are essential for survival. A number of studies have revealed that both humans and nonhuman animals are able to nonverbally estimate time and number; striking similarities in the behavioral data suggest a common magnitude-representation system shared across species. It is unclear, however, whether these representations provide animals with a true concept of time and number, as posited by Gallistel and Gelman (2000) . In this article, we review the prominent cognitive and neurobiological models of timing and counting and explore the current evidence suggesting that nonhuman animals represent these quantities in a modality-independent (i.e., abstract) and ordered manner. Avenues for future research in the area of temporal and mathematical cognition are also discussed.

Drugs that modulate the effective level of dopamine (DA) in cortico-striatal circuits have been shown to alter the perception of time in the seconds-to-minutes range. How this relationship changes as a function of repeated experience with the reinforcement contingencies and the gradual adaptation of the underlying neural circuits remains unclear.The present study examined the clock-speed enhancing effects of methamphetamine (MAP 0.5 or 1.0 mg/kg, ip) in groups of rats that received different levels of baseline training (20, 60, or 120 sessions) on a 50-s peak-interval (PI) procedure before initial drug administration.A curvilinear relationship was observed such that rats that received either minimal or intermediate levels of training (or=60 sessions) displayed dose- x training-related horizontal leftward shifts in their timing functions, suggesting that the speed of the internal clock was increased. In contrast, rats that had received an extended level of training (or=120 sessions) did not show this "classic" DA agonist curve-shift effect, but instead displayed a dose-dependent disruption of temporal control after MAP administration. A transition from DA-sensitive to DA-insensitive mechanisms is proposed to account for the loss of control of clock speed, as timing behaviors associated with the PI procedure gradually become learned habits through the strengthening of DA-glutamate connections.

This experiment investigated the effect of signal modality on time perception in 5- and 8-year-old children as well as young adults using a duration bisection task in which auditory and visual signals were presented in the same test session and shared common anchor durations. Durations were judged shorter for visual than for auditory signals by all age groups. However, the magnitude of this modality difference was larger in the children than in the adults. Sensitivity to time was also observed to increase with age for both modalities. Taken together, these two observations suggest that the greater modality effect on duration judgments for the children, for whom attentional abilities are considered limited, is the result of visual signals requiring more attentional resources than are needed for the processing of auditory signals. Within the framework of the information-processing model of Scalar Timing Theory, these effects are consistent with a developmental difference in the operation of the "attentional switch" used to transfer pulses from the pacemaker into the accumulator. Specifically, although timing is more automatic for auditory than visual signals in both children and young adults, children have greater difficulty in keeping the switch in the closed state during the timing of visual signals.

The present study examined the effects of photoperiod on spatial and temporal memory in adult Sprague-Dawley rats that were conceived and reared in different day lengths, i.e., short day (SD-8:16 light/dark) and long day (LD-16:8 light/dark). Both male and female LD rats demonstrated increased spatial memory capacity as evidenced by a lower number of choices to criterion in a 12-arm radial maze task relative to the performance of SD rats. SD rats also demonstrated a distortion in the content of temporal memory as evidenced by a proportional rightward shift in the 20 and 60 s temporal criteria trained using the peak-interval procedure that is consistent with reduced cholinergic function. The conclusion is that both spatial and temporal memory are sensitive to photoperiod variation in laboratory rats in a manner similar to that previously observed for reproductive behaviour.

Previous research indicates that dopamine controls both the speed of an internal clock [Maricq, A.V., Church, R.M., 1983. The differential effects of haloperidol and methamphetamine on time estimation in the rat. Psychopharmacology 79, 10-15] and sharing of resources between the timer and other cognitive processes [Buhusi, C.V., 2003. Dopaminergic mechanisms of interval timing and attention. In: Meck, W.H. (Ed.), Functional and Neural Mechanisms of Interval Timing. CRC Press, Boca Raton, FL, pp. 317-338]. For example, dopamine agonist methamphetamine increases the speed of an internal clock and resets timing after a gap, while dopamine antagonist haloperidol decreases the speed of an internal clock and stops timing during a gap [Buhusi, C.V., Meck, W.H., 2002. Differential effects of methamphetamine and haloperidol on the control of an internal clock. Behav. Neurosci. 116, 291-297]. Using a 20-s peak-interval procedure with gaps we examined the acute effects of clozapine (2.0mg/kg i.p.), which exerts differential effects on dopamine and serotonin in the cortex and striatum, two brain areas involved in interval timing and working memory. Relative to saline, clozapine injections shifted the response functions leftward both in trials with and without gaps, suggesting that clozapine increased the speed of an internal clock and facilitated the maintenance of the pre-gap interval in working memory. These results suggest that clozapine exerts effects in different brain areas in a manner that allows for the pharmacological separation of clock speed and working memory as a function of peak trials without and with gaps.

The present experiment examined the effects of cocaine (0.0 and 15 mg/kg, i.p.) and ketamine (0.0, 10.0 and 15 mg/kg, i.p.) on timing behavior using a 12-s differential reinforcement of low rates (DRL) procedure and a 2- vs. 8-s bisection procedure in rats. DRL (time production) and bisection (time perception) procedures are sensitive to effects of dopaminergic drugs and provide an assessment of the accuracy and precision of interval timing as well as the subject's level of impulsivity. When administered to rats trained on either the DRL or the bisection procedure, cocaine shifted the psychophysical functions leftward relative to control conditions. In contrast, ketamine produced no change in the temporal control of behavior on either procedure. These differential effects of cocaine and ketamine are consistent with previous reports suggesting that dopamine levels in the dorsal striatum, but not in prefrontal cortex, ventral striatum or hippocampal regions, are crucial for the regulation of the speed of an internal clock.

Drugs that increase dopamine (DA) transmission have been shown to produce an overestimation of time in duration production procedures as exhibited by horizontal leftward shifts of the psychophysical functions. However, the generality of these results has been inconsistent in the literature.The present report evaluates the effects of five doses of methamphetamine (MAP) (0.5-1.5 mg/kg, i.p.) on two duration production procedures, the single duration peak-interval (PI) procedure and the multiduration tri-peak procedure in rats.We replicated and extended prior results by showing a dose-dependent proportional overestimation of time that was equivalent on both procedures (i.e., subjects behaved as though they expected reinforcement to be available earlier in real time). Single-trials analyses demonstrated that the reduction in peak rate that is often observed after MAP administration is due to an increase in the proportion of trials in which responding occurred at very low rates and without temporal control. However, these low-rate trials were not the source of the leftward shift in the temporal estimates. Rather, we found that the leftward shift of the PI functions was due to proportional changes in the placement of temporally controlled high-rate responding, which is consistent with a DA-mediated alteration in clock speed.

Gaps and distracters were presented during the timed signal to examine whether the stop/reset mechanism is activated by (a) changes in the timed signal (switch hypothesis), (b) ITI-like events (ambiguity hypothesis), or (c) processes concurrent with the timing process (time-sharing hypothesis). While the switch and ambiguity hypotheses predict that rats should time through (ignore) distracters, the time-sharing hypothesis predicts that extraneous events (e.g., gaps and distracters) delay timing by causing working memory to decay in proportion to the events' salience. The authors found that response functions were displaced by both gaps and distracters, in accord with the time-sharing hypothesis. Computer simulations show that the time-sharing and memory-decay hypotheses can mechanistically address present data, and reflect different levels of the same model.

Patients with unilateral (left or right) medial temporal lobe lesions and normal control (NC) volunteers participated in two experiments, both using a duration bisection procedure. Experiment 1 assessed discrimination of auditory and visual signal durations ranging from 2 to 8 s, in the same test session. Patients and NC participants judged auditory signals as longer than equivalent duration visual signals. The difference between auditory and visual time discrimination was equivalent for the three groups, suggesting that a unilateral temporal lobe resection does not modulate the modality effect. To document interval-timing abilities after temporal lobe resection for different duration ranges, Experiment 2 investigated the discrimination of brief, 50-200 ms, auditory durations in the same patients. Overall, patients with right temporal lobe resection were found to have more variable duration judgments across both signal modality and duration range. These findings suggest the involvement of the right temporal lobe at the level of the decision process in temporal discriminations.

The authors hypothesized that during a gap in a timed signal, the time accumulated during the pregap interval decays at a rate proportional to the perceived salience of the gap, influenced by sensory acuity and signal intensity. When timing visual signals, albino (Sprague-Dawley) rats, which have poor visual acuity, stopped timing irrespective of gap duration, whereas pigmented (Long-Evans) rats, which have good visual acuity, stopped timing for short gaps but reset timing for long gaps. Pigmented rats stopped timing during a gap in a low-intensity visual signal and reset after a gap in a high-intensity visual signal, suggesting that memory for time in the gap procedure varies with the perceived salience of the gap, possibly through an attentional mechanism.

The relationship between the magnitude of the error in the content of temporal memory and sodium-dependent high-affinity choline uptake (SDHACU) in the frontal cortex and hippocampus was examined in mature (10- to 16-month-old) and aged (24- to 30-month-old) male rats. The peak time of the response rate distribution that relates the probability of a response to signal duration in a 20-s peak-interval timing procedure was used to index the remembered time of reinforcement. Regression analyses indicated that SDHACU in the frontal cortex of both mature and aged rats and in the hippocampus of aged rats is proportional to the absolute error in the content of temporal memory. These biochemical effects of peak-interval training were also compared with biochemical measures taken from control rats that received random-interval training. This comparison indicated that the observed changes in SDHACU were dependent upon the predictability of the programmed time of reinforcement and age-related changes in memory encoding and retrieval.

Immediate repetition of a stimulus reduces its apparent duration relative to a novel item. Recent work indicates that this may reflect suppressed cortical responses to repeated stimuli, arising from neural adaptation and/or the predictive coding of expected stimuli. This article summarizes recent behavioral and neurobiological studies linking perceived time to the magnitude of cortical responses, including work suggesting that variations in GABA-mediated cortical inhibition may underlie some of the individual differences in time perception. We suggest that the firing of cortical neurons can be modified using simple recurrent networks with time-dependent processes that are modulated by GABA levels. These local networks feed into a core-timing network used to integrate across stimulus inputs/modalities, thereby allowing for the coordination of multiple duration ranges and effector systems.

Francisco Aboitiz*, F. Xavier Castellanos and Ximena Carrasco Departamento de Psiquiatria, Facultad de Medicina, and Centro Interdisciplinario de Neurociencia, Pontificia Universidad Catolica de Chile, Santiago, Chile New York University Child Study Center, Nathan Kline Institute for Psychiatric Research, New York, NY, USA Servicio de Neurologia y Psiquiatria infantil, Hospital Luis Calvo Mackenna Facultad de Medicina, Universidad de Chile, Santiago, Chile

Age-related changes in attention and interval timing as a function of time of day were examined using a temporal bisection task with single and compound auditory and visual stimuli. Half of the participants in each age group were tested in the morning, and half were tested in the afternoon. Duration judgments were found to be shorter for visual signals than for auditory signals. This discrepancy was greater in the morning than in the afternoon and larger for the older than for the younger adults. Young adults showed equal sensitivity to signal duration for single and compound trials and higher sensitivity in the afternoon than in the morning for both signal modalities. In contrast, older adults showed impaired sensitivity on compound trials and the greatest sensitivity overall to single visual trials in the morning. These results suggest that age-related reductions in attentional resources may cause older adults to focus on signals that require controlled attention during specific phases of the circadian cycle.

The effects of signal modality on duration classification in college students were studied with the duration bisection task. When auditory and visual signals were presented in the same test session and shared common anchor durations, visual signals were classified as shorter than equivalent duration auditory signals. This occurred when auditory and visual signals were presented sequentially in the same test session and when presented simultaneously but asynchronously. Presentation of a single modality signal within a test session, or both modalities but with different anchor durations did not result in classification differences. The authors posit a model in which auditory and visual signals drive an internal clock at different rates. The clock rate difference is due to an attentional effect on the mode switch and is revealed only when the memories for the short and long anchor durations consist of a mix of contributions from accumulations generated by both the fast auditory and slower visual clock rates. When this occurs auditory signals seem longer than visual signals relative to the composite memory representation.

Contrary to data showing sensitivity to nontemporal properties of timed signals, current theories of interval timing assume that animals can use the presence or absence of a signal as equally valid cues as long as duration is the most predictive feature. Consequently, the authors examined rats' behavior when timing the absence of a visual or auditory stimulus in trace conditioning and in a "reversed" gap procedure. Memory for timing was tested by presenting the stimulus as a reversed gap into its timed absence. Results suggest that in trace conditioning (Experiment 1), rats time for the absence of a stimulus by using its offset as a time marker. As in the standard gap procedure, the insertion of a reversed gap was expected to "stop" rats' internal clock. In contrast, a reversed gap of 1-, 5-, or 15-s duration "reset" the timing process in both trace conditioning (Experiment 2) and the reversed gap procedure (Experiment 3). A direct comparison of the standard and reversed gap procedures (Experiment 4) supported these findings. Results suggest that attentional mechanisms involving the salience or content of the gap might contribute to the response rule adopted in a gap procedure. When an ongoing timed interval is interrupted by a break or gap, animals seem to suspend their temporal processing and choose a response rule that falls between two extremes: They may restart the entire timing process, a phenomenon usually called "reset" (Church, 1978; W. A. Roberts, Cheng, & Cohen, 1989) or they may "stop" timing for the duration of the gap and resume it after the gap (Church, 1978; Meek, Church, & Olton, 1984; S. Roberts

Behavioral paradigms applicable for use in both human and nonhuman subjects for investigating aspects of timing behavior are presented with a view towards exploring their strengths, weaknesses, and utility in a variety of experimental situations. Tri-peak, peak interval, differential reinforcement of low rate responding, and temporal response differentiation procedures are highlighted. In addition, the application of timing tasks in preclinical and clinical settings is discussed: pharmacological manipulations are providing information on the neurotransmitters involved and species differences; normative data for children are being developed; and noninvasive imaging procedures are being employed in adult human subjects to explore the involvement of specific brain areas.

Dysfunction of the basal ganglia and the brain nuclei interconnected with them leads to disturbances of movement and cognition, including disordered timing of movement and perceptual timing deflcits. Patients with Parkinson's disease (PD) were studied in temporal reproduction tasks. We examined PD patients when brain dopamine (DA) transmission was impaired (OFF state) and when DA transmission was reestablished, at the time of maximal clinical beneflt following administration of levodopa + apomorphine (ON state). Patients reproduced target times of 8 and 21 sec trained in blocked trials with the peak interval procedure, which were veridical in the ON state, comparable to normative performance by healthy young and aged controls (Experiment 1). In the OFF state, temporal reproduction was impaired in both accuracy and precision (variance). The 8-sec signal was reproduced as longer and the 21-sec signal was reproduced as shorter than they actually were (Experiment 1). This fimigrationfl effect was dependent upon training of two different durations. When PD patients were trained on 21 sec only (Experiment 2), they showed a reproduction error in the long direction, opposite to the error produced under the dual training condition of Experiment 1. The results are discussed as a mutual attraction between temporal processing systems, in memory and clock stages, when dopaminergic regulation in the striatum is dysfunctional.