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What makes us tick? Functional and neural mechanisms of interval timing

Nature Reviews Neuroscience volume 6, pages 755–765 (2005)Cite this article

Key Points

  • 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.

Abstract

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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Figure 1: Timing across different timescales.
Figure 2: The scalar property is a hallmark of interval timing at both the behavioural and neural levels.
Figure 3: The pacemaker–accumulator model and dopaminergic and cholinergic synapses.
Figure 4: Interval timing in patients with Parkinson's disease, Huntington's disease and cerebellar lesions.
Figure 5: Electrophysiological evidence for the involvement of thalamo-cortico-striatal circuits in the representation of time and numerosity.
Figure 6: Differential activation of the circuits involved in the processing of time and colour.
Figure 7: The striatal beat-frequency model.

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Acknowledgements

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.

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  1. Department of Psychological and Brain Sciences, Duke University, 103 Research Drive, GSRB-2 Building, Room 3010, Durham, 27708, North Carolina, USA

    Catalin V. Buhusi & Warren H. Meck

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Correspondence to Warren H. Meck.

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DATABASES

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FURTHER INFORMATION

The Internet Encyclopedia of Philosophy Time

Glossary

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.

FEEDBACK

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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