Temporal information is crucial for goal reaching, neuroeconomics, and the survival of humans and other animals, and requires multiple biological mechanisms to track time over multiple scales. In mammals, the circadian clock is located in the suprachiasmatic nucleus. Another timer, which is responsible for automatic motor control in the millisecond range, relies on the cerebellum. Finally, a general-purpose, flexible, cognitively-controlled timer that operates in the seconds-to-hours range involves the activation thalamo-cortico-striatal circuits.
The hallmark of interval timing is that the error in estimating a duration is proportional to the duration to be timed, a property known as scalar timing. Scalar timing resembles Weber's law, which applies to most sensory modalities.
The way that time is perceived, represented and estimated has traditionally been explained using a pacemaker–accumulator model, which is not only straightforward but also surprisingly powerful in explaining behavioural and biological data. Pharmacological studies support a dissociation of the clock stage, which is affected by dopaminergic manipulations, and the memory stage, which is affected by cholinergic manipulations.
Despite explaining many findings, the relevance of the pacemaker–accumulator model to the brain mechanisms that are involved in interval timing is unclear. New models will require investigation of recent neurobiological evidence.
An impaired ability to process time is found in patients with disorders of the dopamine system, such as Parkinson's disease, Huntington's disease and schizophrenia. By contrast, the failure of a neurological disorder — such as cerebellar injury — to affect interval timing is taken to indicate that the affected structures are not essential for temporal processing in the seconds-to-hours range.
Because interval timing depends on the intact striatum, but not on the intact cerebellum, the cerebellum is usually charged with millisecond timing and the basal ganglia with interval timing. Recent findings suggest that separate timing circuits can be dissociated when continuity, motor demands and attentional set are manipulated.
The basal ganglia, prefrontal cortex and posterior parietal cortex are activated in both interval-timing tasks, and tasks that require integration of somatosensory signals or quantity/number processing. Electrophysiological data are consistent with the involvement of these structures in number, sequence or magnitude representation as well as in interval timing, thereby supporting a mode-control model of counting and timing in which number and time are processed by the same neural circuits.
Functional MRI shows that two clusters of foci are activated during millisecond and interval timing tasks. The 'automatic timing' cluster is activated by tasks that require repetitive movements and involve short timing intervals, and includes the supplementary motor area and primary somatosensory cortex. The 'cognitively controlled timing' cluster is activated when the durations are longer and the amount of movement required is limited, and includes the dorsolateral prefrontal cortex, intraparietal sulcus and premotor cortex. The basal ganglia and the cerebellum are not specific to either cluster.
The striatal beat-frequency model describes interval timing as an emergent activity in the thalamo-cortico-striatal loops. In this model, timing is based on the coincidental activation of medium spiny neurons in the basal ganglia by cortical neural oscillators. The activity of the striatal neurons increases before the expected time of reward, and peaks at the criterion interval. The model demonstrates the scalar property, and incorporates features that would allow the integration of a number of lines of evidence into one vision of interval timing in the brain.
Time is a fundamental dimension of life. It is crucial for decisions about quantity, speed of movement and rate of return, as well as for motor control in walking, speech, playing or appreciating music, and participating in sports. Traditionally, the way in which time is perceived, represented and estimated has been explained using a pacemaker–accumulator model that is not only straightforward, but also surprisingly powerful in explaining behavioural and biological data. However, recent advances have challenged this traditional view. It is now proposed that the brain represents time in a distributed manner and tells the time by detecting the coincidental activation of different neural populations.
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Grothe, B. New roles for synaptic inhibition in sound localization. Nature Rev. Neurosci. 4, 540–550 (2003).
Richelle, M. & Lejeune, H. Time in Animal Behavior (Pergamon, New York, 1980).
Gallistel, C. R. The Organization of Behavior (MIT Press, Cambridge, Massachusetts, 1990).
Meck, W. H. (ed.) Functional and Neural Mechanisms of Interval Timing (CRC, Boca Raton, Florida, 2003).
Pastor, M. & Artieda, J. (eds) Time, Internal Clocks and Movement (Elsevier, Amsterdam, 1996).
Bradshaw, C. & Szabadi, E. (eds) Time and Behaviour: Psychological and Neurobehavioral Analyses (Elsevier, London, 1997).
Fraisse, P. Psychologie du Temps (P. U. F., Paris, France, 1957).
Gibbon, J., Church, R. M. & Meck, W. H. in Timing and Time Perception Vol. 423 (eds Gibbon, J. & Allan, L. G.) 52–77 (The New York Academy of Sciences, New York, 1984).
Treisman, M. Temporal discrimination and the indifference interval. Implications for a model of the 'internal clock'. Psychol. Monogr. 77, 1–31 (1963).
Gibbon, J. & Allan, L. G. Timing and Time Perception (The New York Academy of Sciences, New York, 1984). A classic collection of papers relating to the scalar expectancy theory and other aspects of timing and time perception in humans and other animals.
Gibbon, J., Malapani, C., Dale, C. L. & Gallistel, C. R. Toward a neurobiology of temporal cognition: advances and challenges. Curr. Opin. Neurobiol. 7, 170–184 (1997).
Meck, W. H. Neuropharmacology of timing and time perception. Brain Res. Cogn. Brain Res. 3, 227–242 (1996).
Czeisler, C. A. et al. Stability, precision, and near-24-hour period of the human circadian pacemaker. Science 284, 2177–2181 (1999).
Kacelnik, A. Timing and foraging: Gibbon's scalar expectancy theory and optimal patch exploitation. Learn. Motiv. 33, 177–195 (2002).
Sohn, M. & Carlson, R. Implicit temporal tuning of working memory strategy during cognitive skill acquisition. Am. J. Psychol. 116, 239–256 (2003).
Bateson, M. & Kacelnik, A. Starling's preferences for predictable and unpredictable delays to food. Anim. Behav. 53, 1129–1142 (1997).
Ohyama, T., Gibbon, J., Deich, J. D. & Balsam, P. D. Temporal control during maintenance and extinction of conditioned keypecking in ring doves. Anim. Learn. Behav. 27, 89–98 (1999).
Buhusi, C. V., Sasaki, A. & Meck, W. H. Temporal integration as a function of signal and gap intensity in rats (Rattus norvegicus) and pigeons (Columba livia). J. Comp. Psychol. 116, 381–390 (2002).
Drew, M. R., Zupan, B., Cooke, A., Couvillon, P. A. & Balsam, P. D. Temporal control of conditioned responding in goldfish. J. Exp. Psychol. Anim. Behav. Process 31, 31–39 (2005)
Roberts, S. & Church, R. M. Control of an internal clock. J. Exp. Psych. Anim. Behav. Process. 4, 318–337 (1978).
Buhusi, C. V., Perera, D. & Meck, W. H. Memory for timing visual and auditory signals in albino and pigmented rats. J. Exp. Psychol. Anim. Behav. Process. 31, 18–30 (2005).
Gallistel, C. R., King, A. & McDonald, R. Sources of variability and systematic error in mouse timing behavior. J. Exp. Psychol. Anim. Behav. Process. 30, 3–16 (2004).
Gribova, A., Donchin, O., Bergman, H., Vaadia, E. & Cardoso de Oliveira, S. Timing of bimanual movements in human and non-human primates in relation to neuronal activity in primary motor cortex and supplementary motor area. Exp. Brain Res. 146, 322–335 (2002).
Brannon, E. M., Roussel, L. W., Meck, W. H. & Woldorff, M. Timing in the baby brain. Cogn. Brain Res. 21, 227–233 (2004).
Rakitin, B. C. et al. Scalar expectancy theory and peak-interval timing in humans. J. Exp. Psychol. Anim. Behav. Process. 24, 15–33 (1998).
Penney, T. B., Gibbon, J. & Meck, W. H. Differential effects of auditory and visual signals on clock speed and temporal memory. J. Exp. Psychol. Hum. Percept. Perform. 26, 1770–1787 (2000).
Edwards, C. J., Alder, T. B. & Rose, G. J. Auditory midbrain neurons that count. Nature Neurosci. 5, 934–936 (2002).
Schirmer, A. Timing speech: a review of lesion and neuroimaging findings. Cogn. Brain Res. 21, 269–287 (2004).
Mauk, M. D. & Buonomano, D. V. The neural basis of temporal processing. Annu. Rev. Neurosci. 27, 307–340 (2004).
Shaffer, H. in Timing and Time Perception Vol. 423 (eds Gibbon, J. & Allan, L.) 420–428 (The New York Academy of Sciences, New York, 1984).
Gibbon, J., Morrell, M. & Silver, R. Two kinds of timing in circadian incubation rhythm of ring doves. Am. J. Physiol. Regul. Integr. Comp. Physiol. 247, R1083–R1087 (1984).
Hinton, S. C. & Meck, W. H. The 'internal clocks' of circadian and interval timing. Endeavour 21, 82 (1997).
Reppert, S. M. & Weaver, D. R. Coordination of circadian timing in mammals. Nature 418, 935–941 (2002).
Levine, J. D., Funes, P., Dowse, H. B. & Hall, J. C. Resetting the circadian clock by social experience in Drosophila melanogaster. Science 298, 2010–2012 (2002).
Darlington, T. K. et al. Closing the circadian loop: clock-induced transcription of its own inhibitors per and tim. Science 280, 1599–1603 (1998).
Lewis, P. A., Miall, R. C., Daan, S. & Kacelnik, A. Interval timing in mice does not rely upon the circadian pacemaker. Neurosci. Lett. 348, 131–134 (2003).
Malapani, C., Dubois, B., Rancurel, G. & Gibbon, J. Cerebellar dysfunctions of temporal processing in the seconds range in humans. Neuroreport 9, 3907–3912 (1998).
Harrington, D. L., Lee, R. R., Boyd, L. A., Rapcsak, S. Z. & Knight, R. T. Does the representation of time depend on the cerebellum? Effect of cerebellar stroke. Brain 127, 561–574 (2004).
Spencer, R. M. C., Zelaznik, H. N., Diedrichsen, J. & Ivry, R. B. Disrupted timing of discontinuous but not continuous movements by cerebellar lesions. Science 300, 1437–1439 (2003).
Jueptner, M. & Weiller, C. A review of differences between basal ganglia and cerebellar control of movements as revealed by functional imaging studies. Brain 121, 1437–1449 (1998).
Shadmehr, R. & Holcomb, H. H. Neural correlates of motor memory consolidation. Science 277, 821–825 (1997).
Roberts, S. Isolation of an internal clock. J. Exp. Psychol. Anim. Behav. Process. 7, 242–268 (1981).
Gibbon, J. Scalar expectancy theory and Weber's law in animal timing. Psychol. Rev. 84, 279–325 (1977). This seminal paper introduced the influential scalar expectancy theory.
Weber, E. H. Annotationes Anatomicae et Physiologicae (Anatomical and Physiological Observations) (C. F. Kohler, Lipsiae (Leipzig), Germany, 1851).
Meck, W. H. & Malapani, C. Neuroimaging of interval timing. Brain Res. Cogn. Brain Res. 21, 133–137 (2004).
Hinton, S. C. in Functional and Neural Mechanisms of Interval Timing (ed. Meck, W. H.) 419–438 (CRC, Boca Raton, Florida, 2003).
Hinton, S. C. & Meck, W. H. Frontal-striatal circuitry activated by human peak-interval timing in the supra-seconds range. Cogn. Brain Res. 21, 171–182 (2004).
François, M. Contributions à l'étude du sens du temps: la température interne comme facteur de variation de l'appréciation subjective des durées. Année Psychol. 27, 186–204 (1927).
Woodrow, H. The reproduction of temporal intervals. J. Exp. Psychol. 13, 473–499 (1930).
Hoagland, H. The psychological control of judgements of duration: evidence for a chemical clock. J. Gen. Psychol. 9, 267–287 (1933).
Meck, W. H. Selective adjustment of the speed of internal clock and memory processes. J. Exp. Psychol. Anim. Behav. Process. 9, 171–201 (1983).
Maricq, A. V. & Church, R. M. The differential effects of haloperidol and methamphetamine on time estimation in the rat. Psychopharmacology (Berl.) 79, 10–15 (1983).
Meck, W. H. Affinity for the dopamine D2 receptor predicts neuroleptic potency in decreasing the speed of an internal clock. Pharmacol. Biochem. Behav. 25, 1185–1189 (1986).
Matell, M. S., King, G. R. & Meck, W. H. Differential modulation of clock speed by the administration of intermittent versus continuous cocaine. Behav. Neurosci. 118, 150–156 (2004).
Rammsayer, T. H. On dopaminergic modulation of temporal information processing. Biol. Psychol. 36, 209–222 (1993).
Meck, W. H. Choline uptake in the frontal cortex is proportional to the absolute error of a temporal memory translation constant in mature and aged rats. Learn. Motiv. 33, 88–104 (2002).
Malapani, C. et al. Coupled temporal memories in Parkinson's disease: a dopamine-related dysfunction. J. Cogn. Neurosci. 10, 316–331 (1998).
Holson, R. R., Bowyer, J. F., Clausing, P. & Gough, B. Methamphetamine-stimulated striatal dopamine release declines rapidly over time following microdialysis probe insertion. Brain. Res. 739, 301–307 (1996).
Buhusi, C. V. & Meck, W. H. Differential effects of methamphetamine and haloperidol on the control of an internal clock. Behav. Neurosci. 116, 291–297 (2002).
Plenz, D. & Kital, S. T. A basal ganglia pacemaker formed by the subthalamic nucleus and external globus pallidus. Nature 400, 677–682 (1999).
Church, R. M. & Broadbent, H. A. Alternative representations of time, number, and rate. Cognition 37, 55–81 (1990).
Miall, R. C. The storage of time intervals using oscillating neurons. Neur. Comp. 1, 359–371 (1989).
Grossberg, S. & Schmajuk, N. A. Neural dynamics of adaptive timing and temporal discrimination during associative learning. Neural Netw. 2, 79–102 (1989).
Buhusi, C. V. & Schmajuk, N. A. Timing in simple conditioning and occasion setting: a neural network approach. Behav. Process. 45, 33–57 (1999).
Machens, C. K., Romo, R. & Brody, C. D. Flexible control of mutual inhibition: a neural model of two-interval discrimination. Science 307, 1121–1124 (2005).
Dragoi, V., Staddon, J. E., Palmer, R. G. & Buhusi, C. V. Interval timing as an emergent learning property. Psychol. Rev. 110, 126–144 (2003).
Killeen, P. R. & Fetterman, J. G. A behavioral theory of timing. Psychol. Rev. 95, 274–295 (1988).
Fraisse, P. Perception and estimation of time. Annu. Rev. Psychol. 35, 1–37 (1984).
Lewis, P. A. & Miall, R. C. in Functional and Neural Mechanisms of Interval Timing (ed. Meck, W. H.) 515–532 (CRC, Boca Raton, Florida, USA, 2003).
Malapani, C., Deweer, B. & Gibbon, J. Separating storage from retrieval dysfunction of temporal memory in Parkinson's disease. J. Cogn. Neurosci. 14, 311–322 (2002).
Paulsen, J. S. et al. fMRI biomarker of early neuronal dysfunction in presymptomatic Huntington's disease. Am. J. Neuroradiol. 25, 1715–1721 (2004). Proposes that the dysfunction of interval timing and the hyperactivation of SMA are early markers of Huntington's disease.
Rammsayer, T. Temporal discrimination in schizophrenic and affective disorders: evidence for a dopamine-dependent internal clock. Int. J. Neurosci. 53, 111–120 (1990).
Tracy, J. I. et al. Information-processing characteristics of explicit time estimation by patients with schizophrenia and normal controls. Percept. Mot. Skills 86, 515–526 (1998).
Volz, H. P. et al. Time estimation in schizophrenia: an fMRI study at adjusted levels of difficulty. Neuroreport 12, 313–316 (2001).
Elvevag, B., Brown, G. D. A., McCormack, T., Vousden, J. I. & Goldberg, T. E. Identification of tone duration, line length, and letter position: an experimental approach to timing and working memory deficits in schizophrenia. J. Abnorm. Psychol. 113, 509–521 (2004).
Penney, T. B., Meck, W. H., Roberts, S. A., Gibbon, J. & Erlenmeyer-Kimling, L. Interval-timing deficits in individuals at high risk for schizophrenia. Brain Cogn. 58, 109–118 (2005).
Wolpert, D. M., Miall, R. C. & Kawato, M. Internal models in the cerebellum. Trends Cogn. Sci. 2, 338–347 (1998).
Ivry, R. B. & Spencer, R. M. The neural representation of time. Curr. Opin. Neurobiol. 14, 225–232 (2004).
Koekkoek, S. K. E. et al. Cerebellar LTD and learning-dependent timing of conditioned eyelid responses. Science 301, 1736–1739 (2003).
Rammsayer, T. H. & Brandler, S. Aspects of temporal information processing: a dimensional analysis. Psychol. Res. 69, 115–123 (2004).
Rammsayer, T. H. Neuropharmacological evidence for different timing mechanisms in humans. Q. J. Exp. Psychol. 52, 273–286 (1999).
Pfeuty, M., Ragot, R. & Pouthas, V. Processes involved in tempo perception: a CNV analysis. Psychophysiology 40, 69–76 (2003).
Meck, W. H. Neuropsychology of timing and time perception. Brain Cogn. 58, 1–8 (2005).
Matell, M. S. & Meck, W. H. Neuropsychological mechanisms of interval timing behavior. Bioessays 22, 94–103 (2000).
Matell, M. S. & Meck, W. H. Cortico-striatal circuits and interval timing: coincidence detection of oscillatory processes. Cogn. Brain Res. 21, 139–170 (2004). Develops the biological assumptions of the SBF model of interval timing, and shows simulations using this model.
Meck, W. H. & Benson, A. M. Dissecting the brain's internal clock: how frontal-striatal circuitry keeps time and shifts attention. Brain Cogn. 48, 195–211 (2002).
Ravizza, S. M. & Ivry, R. B. Comparison of the basal ganglia and cerebellum in shifting attention. J. Cogn. Neurosci. 13, 285–297 (2001).
Ivry, R. B., Spencer, R. M., Zelaznik, H. N. & Diedrichsen, J. The cerebellum and event timing. Ann. NY Acad. Sci. 978, 302–317 (2002).
Lewis, P. A. & Miall, R. C. Distinct systems for automatic and cognitively controlled time measurement: evidence from neuroimaging. Curr. Opin. Neurobiol. 13, 250–255 (2003). An original review of the brain areas that are activated in neuroimaging studies of interval timing as a function of the characteristics of the timing task.
Macar, F. et al. Activation of the supplementary motor area and of attentional networks during temporal processing. Exp. Brain Res. 142, 475–485 (2002). An excellent review of neuroimaging studies of interval timing that points out the importance of adequate control tasks.
Nieder, A. & Miller, E. K. Coding of cognitive magnitude: compressed scaling of numerical information in the primate prefrontal cortex. Neuron 37, 149–157 (2003).
Meck, W. H. & Church, R. M. A mode control model of counting and timing processes. J. Exp. Psychol. Anim. Behav. Process. 9, 320–334 (1983). Describes similarities between timing and counting in preverbal animals.
Feigenson, L., Dehaene, S. & Spelke, E. Core systems of number. Trends Cogn. Sci. 8, 307–314 (2004).
Walsh, V. A theory of magnitude: common cortical metrics of time, space and quantity. Trends Cogn. Sci. 7, 483–488 (2003).
Brannon, E. M. & Roitman, J. D. in Functional and Neural Mechanisms of Interval Timing (ed. Meck, W. H.) 143–182 (CRC, Boca Raton, Florida, USA, 2003).
Coull, J. T., Frith, C. D., Buchel, C. & Nobre, A. C. Orienting attention in time: behavioural and neuroanatomical distinction between exogenous and endogenous shifts. Neuropsychologia 38, 808–819 (2000).
Sawamura, H., Shima, K. & Tanji, J. Numerical representation for action in the parietal cortex of the monkey. Nature 415, 918–922 (2002). Shows changes in the firing of PPC neurons during a sequence of actions.
Nieder, A. & Miller, E. K. A parieto-frontal network for visual numerical information in the monkey. Proc. Natl Acad. Sci. USA 101, 7457–7462 (2004).
Nieder, A., Freedman, D. J. & Miller, E. K. Representation of the quantity of visual items in the primate prefrontal cortex. Science 297, 1708–1711 (2002).
Shuman, M. & Kanwisher, N. Numerical magnitude in the human parietal lobe: tests of representational generality and domain specificity. Neuron 44, 557–569 (2004).
Matell, M. S., Meck, W. H. & Nicolelis, M. A. Interval timing and the encoding of signal duration by ensembles of cortical and striatal neurons. Behav. Neurosci. 117, 760–773 (2003). Dissociates motor coding from time coding in striatal neurons.
Fiorillo, C. D., Tobler, P. N. & Schultz, W. Discrete coding of reward probability and uncertainty by dopamine neurons. Science 299, 1898–1902 (2003). Shows that in tasks that involve uncertainty, dopaminergic neurons burst at trial onset and at the expected time of reward, and show sustained activation throughout the trial.
Apicella, P., Scarnati, E., Ljungberg, T. & Schultz, W. Neuronal activity in monkey striatum related to the expectation of predictable environmental events. J. Neurophysiol. 68, 945–960 (1992).
Schultz, W., Apicella, P., Scarnati, E. & Ljungberg, T. Neuronal activity in monkey ventral striatum related to the expectation of reward. J. Neurosci. 12, 4595–4610 (1992).
Olton, D. S., Wenk, G. L., Church, R. M. & Meck, W. H. Attention and the frontal cortex as examined by simultaneous temporal processing. Neuropsychologia 26, 307–318 (1988).
Meck, W. H., Church, R. M., Wenk, G. L. & Olton, D. S. Nucleus basalis magnocellularis and medial septal area lesions differentially impair temporal memory. J. Neurosci. 7, 3505–3511 (1987).
Pang, K. C., Yoder, R. M. & Olton, D. S. Neurons in the lateral agranular frontal cortex have divided attention correlates in a simultaneous temporal processing task. Neuroscience 103, 615–628 (2001). A key study showing that cortical neurons are activated by simultaneous temporal processing.
Coull, J. T. & Nobre, A. C. Where and when to pay attention: the neural systems for directing attention to spatial locations and to time intervals as revealed by both PET and fMRI. J. Neurosci. 18, 7426–7435 (1998).
Rubia, K. et al. Prefrontal involvement in 'temporal bridging' and timing movement. Neuropsychologia 36, 1283–1293 (1998).
Ferrandez, A. M. et al. Basal ganglia and supplementary motor area subtend duration perception: an fMRI study. Neuroimage 19, 1532–1544 (2003).
Macar, F., Vidal, F. & Casini, L. The supplementary motor area in motor and sensory timing: evidence from slow brain potential changes. Exp. Brain Res. 125, 271–280 (1999).
Vidal, F., Bonnet, M. & Macar, F. Programming the duration of a motor sequence: role of the primary and supplementary motor areas in man. Exp. Brain Res. 106, 339–350 (1995).
Meck, W. H. & N'Diaye, K. Un modèle neurobiologique de la perception et de l'estimation du temps. Psychologie Francaise 50, 47–63 (2005).
Lustig, C., Matell, M. S. & Meck, W. H. Not 'just' a coincidence: frontal-striatal interactions in working memory and interval timing. Memory 13, 441–448 (2005).
Salinas, E. & Sejnowski, T. J. Correlated neuronal activity and the flow of neural information. Nature Rev. Neurosci. 2, 539–550 (2001).
Silva, L. R., Amitai, Y. & Connors, B. W. Intrinsic oscillations of neocortex generated by layer 5 pyramidal neurons. Science 251, 432–435 (1991).
Galarreta, M. & Hestrin, S. Spike transmission and synchrony detection in networks of GABAergic interneurons. Science 292, 2295–2299 (2001).
Riehle, A., Grun, S., Diesmann, M. & Aertsen, A. Spike synchronization and rate modulation differentially involved in motor cortical function. Science 278, 1950–1953 (1997).
Steinmetz, P. N. et al. Attention modulates synchronized neuronal firing in primate somatosensory cortex. Nature 404, 187–190 (2000).
Fries, P., Reynolds, J. H., Rorie, A. E. & Desimone, R. Modulation of oscillatory neuronal synchronization by selective visual attention. Science 291, 1560–1563 (2001).
Beiser, D. G. & Houk, J. C. Model of cortical-basal ganglionic processing: encoding the serial order of sensory events. Clin. Neurophysiol. 79, 3168–3188 (1998).
Houk, J. C. in Models of Information Processing in the Basal Ganglia (eds Houk, J. C., Davis, J. L. & Beiser, D. G.) 3–10 (MIT Press, Cambridge, Massachusetts, USA, 1995).
Charpier, S. & Deniau, J. M. In vivo activity-dependent plasticity at cortico-striatal connections: evidence for physiological long-term potentiation. Proc. Natl Acad. Sci. USA 94, 7036–7040 (1997).
Gubellini, P., Pisani, A., Centonze, D., Bernardi, G. & Calabresi, P. Metabotropic glutamate receptors and striatal synaptic plasticity: implications for neurological diseases. Prog. Neurobiol. 74, 271–300 (2004).
Schultz, W. Neural coding of basic reward terms of animal learning theory, game theory, microeconomics and behavioural ecology. Curr. Opin. Neurobiol. 14, 139–147 (2004).
Schultz, W. Multiple reward signals in the brain. Nature Rev. Neurosci. 1, 199–207 (2000).
van Rossum, M. C. W. A novel spike distance. Neural Comput. 13, 751–763 (2001).
Glimcher, P. W. Decisions, Uncertainty, and the Brain: The Science of Neuroeconomics (MIT Press, Cambridge, Massachusetts, USA, 2004).
Meck, W. H. Interval timing and genomics: what makes mutant mice tick? Int. J. Comp. Psychol. 14, 211–231 (2001).
Aschoff, J. in Timing and Time Perception Vol. 423 (eds Gibbon, J. & Allan, L. G.) 442–468 (The New York Academy of Sciences, New York, 1984).
Rousseau, R., Poirier, J. & Lemyre, L. Duration discrimination of empty time intervals marked by intermodal pulses. Percept. Psychophys. 34, 541–548 (1983).
Rammsayer, T. H. & Vogel, W. H. Pharmacologic properties of the internal clock underlying time perception in humans. Neuropsychobiology 26, 71–80 (1992).
Harrington, D. L., Haaland, K. Y. & Hermanowicz, N. Temporal processing in the basal ganglia. Neuropsychology 12, 3–12 (1998).
Nagarajan, S. S., Blake, D. T., Wright, B. A., Byl, N. & Merzenich, M. M. Practice-related improvements in somatosensory interval discrimination are temporally specific but generalize across skin location, hemisphere, and modality. J. Neurosci. 18, 1559–1570 (1998).
Karmarkar, U. R. & Buonomano, D. V. Temporal specificity of perceptual learning in an auditory discrimination task. Learn. Mem. 10, 141–147 (2003).
Lejeune, H. & Wearden, J. H. The comparative psychology of fixed-interval responding: some quantitative analyses. Learn. Motiv. 22, 84–111 (1991).
Church, R. M. & Gibbon, J. Temporal generalization. J. Exp. Psychol. Anim. Behav. Process. 8, 165–186 (1982).
Gibbon, J. in The Psychology of Learning and Motivation (ed. Bower, G.) 105–135 (Academic, New York, 1986).
Gibbon, J., Fairhurst, S. & Goldberg, B. in Time and Behaviour: Psychological and Neurobehavioral Analyses Vol. 120 (eds Bradshaw, C. & Szabadi, E.) 329–374 (Elsevier, London, 1997).
Wearden, J. H., Denovan, L., Fakhri, M. & Haworth, R. Scalar timing in temporal generalization in humans with longer stimulus durations. J. Exp. Psychol. Anim. Behav. Process. 23, 502–511 (1997).
Crystal, J. Circadian time perception. J. Exp. Psychol. Anim. Behav. Process. 27, 68–78 (2001).
Malapani, C. & Rakitin, B. in Functional and Neural Mechanisms of Interval Timing (ed. Meck, W. H.) 485–513 (CRC, Boca Raton, Florida, 2003).
Coull, J. T., Vidal, F., Nazarian, B. & Macar, F. Functional anatomy of the attentional modulation of time estimation. Science 303, 1506–1508 (2004). A state-of-the-art neuroimaging study using a dynamic control task and parametric variation of the interval-timing procedure.
We would like to thank M. Matell for providing data for figures 5 and 7. This work was supported, in part, by a grant from the National Institute of Mental Health to C.V.B. and a James McKeen Cattell award to W.H.M.
The authors declare no competing financial interests.
- GLOBAL POSITIONING SYSTEM
(GPS). A network of artificial satellite transmitters that provide highly accurate position fixes for Earth-based, portable receivers.
- COINCIDENCE DETECTION
The activation of neurons not by single inputs, but by the simultaneous activity of several inputs. For example, coincidental activation or inactivation of specific dendritic inputs might trigger a neuron to fire, thereby transforming a time code into a rate code. Similarly, in the binaural auditory system, coincidental activation that results from hearing a sound with a specific interaural time difference is used to transform a time code into a spatial code.
- INTERAURAL TIME DIFFERENCE
The difference in the time of arrival of a sound wave at an animal's two ears. It ranges from 100 μs in gerbils to about 650 μs in humans and is one of the sources of information used by various species to make a topographic representation of space.
- INTERVAL TIMING
Perception, estimation and discrimination of durations in the range of seconds-to-minutes-to-hours.
- CIRCADIAN RHYTHMS
Repetition of certain phenomena in living organisms at about the same time each day. The most thought of circadian rhythm is sleep, but other examples include body temperature, blood pressure, and the production of hormones and digestive secretions.
- MILLISECOND TIMING
Perception, estimation and discrimination of durations in the sub-second range.
- WEBER'S LAW
Formulated by Ernst Weber in 1831 to explain the relationship between the physical intensity of a stimulus and the sensory experience that it causes. Weber's Law states that the increase in a stimulus needed to produce a just-noticeable difference is constant. Later, Gustav Fechner (1801–1887) generalized Weber's law by proposing that sensation increases as the logarithm of stimulus intensity: S = k logI, where S = subjective experience, I = physical intensity, and k = constant.
To signal the end of the to-be-timed duration to the participant, a feedback signal is presented. In experiments involving animals, the feedback is usually an appetitive stimulus (for example, food) or aversive stimulus (for example, footshock). In experiments that involve human participants, the feedback may take various forms, including verbal reward, gaining 'points', and so on.
- TEMPORAL MEMORY TRANSLATION CONSTANT
A parameter in the scalar expectancy theory that is responsible for producing scalar transforms of sensory input taken from an internal clock and stored in temporal memory. It is used to explain systematic discrepancies in the accuracy of temporal memory.
- NEURAL OSCILLATOR
Repetitive, periodical activation of a neuron. The intrinsic mechanisms that control the period of the oscillator (the interval between two neuronal spikes) range from fast ion currents (for example, 40 Hz oscillations in sparsely spiny neurons in the frontal cortex) to slow transcriptional feedback loops (for example, 24-h oscillation in the SCN).
- ATTENTIONAL SET
Set of to-be-attended features that are primed for use in a specific task, such that participants would be more likely to attend to the features in the attentional set than to other features of the task.
- MOTOR SET
Sets of to-be-activated motor programs that are primed for use in a specific task, such that participants would be more likely to respond using one of the motor programs in the motor set than using other responses.
- DELAYED MATCHING-TO-SAMPLE TASKS
Presentation of a stimulus is followed by a delay, after which a choice is offered and the originally presented stimulus must be chosen. With small stimulus sets, the stimuli are frequently repeated, and therefore become highly familiar. So, typically, such tasks are most readily solved by short-term or working memory rather than by long-term memory mechanisms.
- LONG-TERM POTENTIATION
(LTP). An enduring increase in the amplitude of excitatory postsynaptic potentials as a result of high-frequency (tetanic) stimulation of afferent pathways. It is measured both as the amplitude of excitatory postsynaptic potentials and as the magnitude of the postsynaptic-cell population spike. LTP is most frequently studied in the hippocampus and is often considered to be the cellular basis of learning and memory in vertebrates.
- LONG-TERM DEPRESSION
(LTD). An enduring weakening of synaptic strength that is thought to interact with LTP in the cellular mechanisms of learning and memory in structures such as the hippocampus and cerebellum. Unlike LTP, which is produced by brief high-frequency stimulation, LTD can be produced by long-term, low-frequency stimulation.
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Buhusi, C., Meck, W. What makes us tick? Functional and neural mechanisms of interval timing. Nat Rev Neurosci 6, 755–765 (2005). https://doi.org/10.1038/nrn1764
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