The neural representation of time

Neuroscience & Biobehavioral Reviews, 2016

Interactive Roles of Cerebellum and Striatum in Timing 2 HIGHLIGHTS  Examine cortico-thalamo-striatal and cerebellar contributions to sub-and super-second timing  Identify aspects of cerebellar and striatal architecture relevant to timing  Discuss role of degeneracy for timing within distributed neural networks  Propose an integrative model of cerebellar/striatal timing with distinct phases of temporal  processing

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.

Brain, 2004

The neural systems that regulate temporal aspects of behaviours within the range of several hundred milliseconds, several seconds and even longer periods remain debated. Parametric studies of timing across these interval ranges, which seem to have psychological significance, have not yet been carried out by any single study using neuroscience methods. Most research has studied patients with neurological damage on a single timing task, typically testing only one interval. This body of work led to the influential neuropsychological model of Ivry and colleagues, in which the cerebellum is viewed as a central timekeeping mechanism that computes time for intervals in the range of several hundred milliseconds . The strongest support for this proposal comes from studies demonstrating that patients with cerebellar damage are impaired on tests in which they must explicitly estimate or reproduce the duration of an interval lasting several hundred milliseconds. As we pointed out in our paper, evidence for the cerebellar timing model has been limited in primarily two ways. First, most studies have included patients with cerebellar atrophy. The use of these patients to draw direct inferences about the role of the cerebellum in any behaviour is limited because degenerative cerebellar atrophy is rarely restricted to the cerebellum and may damage other brain regions. Indeed, cerebellar atrophy patients show marked deficits in temporal processing relative to patients with cerebellar damage due to stroke . This problem cannot be overstated, given that damage to various areas of the cerebral cortex also produces deficits in timing intervals in the range of hundreds of milliseconds and seconds . These data suggest at least two possibilities. First, timing may be centralized, but the role of various brain regions is difficult to distinguish because experimental methods do not adequately differentiate deficits in timekeeping mechanisms from other processes that support timing (e.g. memory, attention). Alternatively, timing may be a distributed process supported by more than one brain region. A second limitation is that most studies have not provided evidence that cerebellar damage produces timing deficits across more than one interval and/or more than one test of timing. This is important because prevailing theories maintain that a common timekeeping mechanism supports timing in different tasks and different intervals within a similar psychological range. For these reasons, we set out to provide a stronger test of the cerebellar timing hypothesis by studying a large sample of patients with chronic cerebellar damage due to stroke and examining performance on two different timing tasks, each of which contained two different standard interval conditions. We hypothesized that patients should show deficits on all four conditions if the cerebellum regulates a timekeeping mechanism.

The Cerebellum, 2018

Time perception is an essential element of conscious and subconscious experience, coordinating our perception and interaction with the surrounding environment. In recent years, major technological advances in the field of neuroscience have helped foster new insights into the processing of temporal information, including extending our knowledge of the role of the cerebellum as one of the key nodes in the brain for this function. This consensus paper provides a state-of-the-art picture from the experts in the field of the cerebellar research on a variety of crucial issues related to temporal processing, drawing on recent anatomical, neurophysiological, behavioral, and clinical research. The cerebellar granular layer appears especially well-suited for timing operations required to confer millisecond precision for cerebellar computations. This may be most evident in the manner the cerebellum controls the duration of the timing of agonist-antagonist EMG bursts associated with fast goal-directed voluntary movements. In concert with adaptive processes, interactions within the cerebellar cortex are sufficient to support sub-second timing. However, supra-second timing seems to require cortical and basal ganglia networks, perhaps operating in concert with Cerebellum. Additionally, sensory information such as an unexpected stimulus can be forwarded to the cerebellum via the climbing fiber system, providing a temporally constrained mechanism to adjust ongoing behavior and modify future processing. Patients with cerebellar disorders exhibit impairments on a range of tasks that require precise timing, and recent evidence suggest that timing problems observed in other neurological conditions such as Parkinson's disease, essential tremor, and dystonia, may reflect disrupted interactions between the basal ganglia and cerebellum. The complex concepts emerging from this consensus paper should provide a foundation for further discussion, helping identify basic research questions required to understand how the brain represents and utilizes time, as well as delineating ways in which this knowledge can help improve the lives of those with neurological conditions that disrupt this most elemental sense. The panel of experts agrees that timing control in the brain is a complex concept in whom cerebellar circuitry is deeply involved. The concept of a timing machine has now expanded to clinical disorders.

Brain, 2004

The Journal of Neuroscience, 2006

Timing has been proposed as a basic function of the cerebellar cortex (particularly the climbing fiber afferents and their sole source, the inferior olive) that explains the contribution of the cerebellum to both motor control and nonmotor cognitive functions. However, whether the olivo-cerebellar system mediates time perception without motor behavior remains controversial. We used event-related functional magnetic resonance imaging to dissociate the neural correlates of the perceptual from the motor aspects of timing. The results show activation of multiple areas within the cerebellar cortex during both perception and motor performance of temporal sequences. The results further show that the inferior olive was activated only when subjects perceived the temporal sequences without motor activity. This finding is most consistent with electrophysiological studies showing decreased responsiveness of the inferior olivary neurons to sensory input during expected, self-produced movement. O...

1998

Precise timing of sensory information from multiple sensory streams is essential for many aspects of human perception and action. Animal and human research implicates the basal ganglia and cerebellar systems in timekeeping operations, but investi- gations into the role of the cerebral cortex have been limited. Individuals with focal left (LHD) or right hemisphere (RHD) lesions and control subjects performed

European Journal of Neuroscience, 2002

Recent evidence that the cerebellum and the basal ganglia are activated during the performance of cognitive and attention tasks challenges the prevailing view of their primary function in motor control. The speci®c roles of the basal ganglia and the cerebellum in cognition, however, have been dif®cult to identify. At least three functional hypotheses regarding their roles have been proposed. The ®rst hypothesis suggests that their main function is to switch attentional set. The second hypothesis states that they provide error signals regarding stimuli or rewards. The third hypothesis is that they operate as an internal timing system, providing a precise representation of temporal information. Using functional magnetic resonance imaging, we tested these three hypotheses using a task-switching experiment with a 2 Q 2 factorial design varying timing (random relative to ®xed) and task order (unpredictable relative to predictable). This design allowed us to test whether switching between tasks, timing irregularity and/or task order unpredictability activate the basal ganglia and/or the cerebellum. We show that the cerebellum is primarily activated with timing irregularity while the anterior striatum is activated with task order unpredictability, supporting their distinctive roles in two forms of readjustment. Task order unpredictability alone, independent of reward delivery, is suf®cient to induce striatal activation. In addition, activation of the cerebellum and basal ganglia were not speci®c to switching attention because these regions were both activated during switching between tasks and during the simultaneous maintenance of two tasks without switching between them.

2007

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

Brain, 2003