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

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 magnitud