Research on interval timing strongly implicates the cerebellum and the basal ganglia as part of the timing network of the brain. Here we tested the hypothesis that the brain uses differential timing mechanisms and networks-specifically, that the cerebellum subserves the perception of the absolute duration of time intervals, whereas the basal ganglia mediate perception of time intervals relative to a regular beat. In a functional magnetic resonance imaging experiment, we asked human subjects to judge the difference in duration of two successive time intervals as a function of the preceding context of an irregular sequence of clicks (where the task relies on encoding the absolute duration of time intervals) or a regular sequence of clicks (where the regular beat provides an extra cue for relative timing). We found significant activations in an olivocerebellar network comprising the inferior olive, vermis, and deep cerebellar nuclei including the dentate nucleus during absolute, duration-based timing and a striato-thalamo-cortical network comprising the putamen, caudate nucleus, thalamus, supplementary motor area, premotor cortex, and dorsolateral prefrontal cortex during relative, beat-based timing. Our results support two distinct timing mechanisms and underlying subsystems: first, a network comprising the inferior olive and the cerebellum that acts as a precision clock to mediate absolute, duration-based timing, and second, a distinct network for relative, beatbased timing incorporating a striato-thalamo-cortical network.

Accurate timing is an integral aspect of sensory and motor processes such as the perception of speech and music and the execution of skilled movement. Neuropsychological studies of time perception in patient groups and functional neuroimaging studies of timing in normal participants suggest common neural substrates for perceptual and motor timing. A timing system is implicated in core regions of the motor network such as the cerebellum, inferior olive, basal ganglia, pre-supplementary, and supplementary motor area, pre-motor cortex as well as higher-level areas such as the prefrontal cortex. In this article, we assess how distinct parts of the timing system subserve different aspects of perceptual timing. We previously established brain bases for absolute, duration-based timing and relative, beat-based timing in the olivocerebellar and striato-thalamo-cortical circuits respectively (Teki et al., 2011). However, neurophysiological and neuroanatomical studies provide a basis to suggest that timing functions of these circuits may not be independent. Here, we propose a unified model of time perception based on coordinated activity in the core striatal and olivocerebellar networks that are interconnected with each other and the cerebral cortex through multiple synaptic pathways. Timing in this unified model is proposed to involve serial beat-based striatal activation followed by absolute olivocerebellar timing mechanisms.

This work tests the hypothesis that the cerebellum is critical to the perception of the timing of sensory events. Auditory tasks were used to assess two types of timing in a group of patients with a stereotyped specific degeneration of the cerebellum: the analysis of single time intervals requiring absolute measurements of time, and the holistic analysis of rhythmic patterns based on relative measures of time using an underlying regular beat. The data support a specific role for the cerebellum only in the absolute timing of single subsecond intervals but not in the relative timing of rhythmic sequences with a regular beat. The findings support the existence of a stopwatch-like cerebellar timing mechanism for absolute intervals that is distinct from mechanisms for entrainment with a regular beat.T he relevance of the human cerebellum to the perception of time intervals and rhythmic sequences is controversial. Involvement of the cerebellum in perceptual timing (the perception of the timing of sensory events), in addition to its role in motor timing (the timed execution of movements), has been suggested by a number of studies (1-6). One distinction that we wish to address here, which has not been made clear in previous work, is between the absolute, duration-based timing of single subsecond intervals and the relative timing of subsecond intervals based on a regular beat. Functional imaging studies suggest neural activity in the human cerebellum during the perception of the absolute duration of single time intervals (7,8) as well as rhythmic patterns with a regular beat (9-13). However, previous lesion work to assess an obligatory cerebellar role in the perception of single time intervals has not yielded consistent results (4,(14)(15)(16)(17). Previous lesion work to assess any obligatory role of the cerebellum in the analysis of rhythmic sequences has assessed only deficits in related motor activity, such as tapping out a beat (4,14,18), that do not allow clear inference about perception.In this study, we test whether the cerebellum is a critical substrate for perceptual tasks that require the absolute, durationbased analysis of single time intervals as well as those that require the relative analysis of time intervals within rhythmic patterns based on a regular beat. Perceptual tests were conducted in the auditory domain, where accurate temporal encoding of sensory events is essential and entrainment with a beat is induced naturally. Tasks were administered to a group of 34 patients with a stereotyped cerebellar degeneration and a matched control group of 40 healthy individuals. Two absolute timing tasks tested the perception of single intervals for a variable and a fixed reference duration, respectively ( Fig. 1 A and B). Three relative timing tasks tested the beat-based analysis of rhythmic sequences, including the detection of the presence of a roughly regular beat (19), a deviation from an isochronous beat (20) and a distortion of a rhythmic pattern with a metrical beat (21) (Fig. 1 C-E). The data support a ce...

Perception relies on the integration of sensory information and prior expectations. Here we show that selective neurodegeneration of human frontal speech regions results in delayed reconciliation of predictions in temporal cortex. These temporal regions were not atrophic, displayed normal evoked magnetic and electrical power, and preserved neural sensitivity to manipulations of sensory detail. Frontal neurodegeneration does not prevent the perceptual effects of contextual information; instead, prior expectations are applied inflexibly. The precision of predictions correlates with beta power, in line with theoretical models of the neural instantiation of predictive coding. Fronto-temporal interactions are enhanced while participants reconcile prior predictions with degraded sensory signals. Excessively precise predictions can explain several challenging phenomena in frontal aphasias, including agrammatism and subjective difficulties with speech perception. This work demonstrates that higher-level frontal mechanisms for cognitive and behavioural flexibility make a causal functional contribution to the hierarchical generative models underlying speech perception.

Cerebellar functions in two types of perceptual timing were assessed: the absolute (duration-based) timing of single intervals and the relative (beat-based) timing of rhythmic sequences. Continuous transcranial magnetic theta-burst stimulation (cTBS) was applied over the medial cerebellum and performance was measured adaptively before and after stimulation. A large and significant effect was found in the TBS (n = 12) compared to the SHAM (n = 12) group for single-interval timing but not for the detection of a regular beat or a deviation from it. The data support the existence of distinct perceptual timing mechanisms and an obligatory role of the cerebellum in absolute interval timing with a functional dissociation from relative timing of interval within rhythmic sequences based on a regular beat.