The precise quantification of time during motor performance is critical for many complex behaviors, including musical execution, speech articulation, and sports; however, its neural mechanisms are primarily unknown. We found that neurons in the medial premotor cortex (MPC) of behaving monkeys are tuned to the duration of produced intervals during rhythmic tapping tasks. Interval-tuned neurons showed similar preferred intervals across tapping behaviors that varied in the number of produced intervals and the modality used to drive temporal processing. In addition, we found that the same population of neurons is able to multiplex the ordinal structure of a sequence of rhythmic movements and a wide range of durations in the range of hundreds of milliseconds. Our results also revealed a possible gain mechanism for encoding the total number of intervals in a sequence of temporalized movements, where intervaltuned cells show a multiplicative effect of their activity for longer sequences of intervals. These data suggest that MPC is part of a core timing network that uses interval tuning as a signal to represent temporal processing in a variety of behavioral contexts where time is explicitly quantified.

Temporal information processing is critical for many complex behaviors including speech and music cognition, yet its neural substrate remains elusive. We examined the neurophysiological properties of medial premotor cortex (MPC) of two Rhesus monkeys during the execution of a synchronization-continuation tapping task that includes the basic sensorimotor components of a variety of rhythmic behaviors. We show that time-keeping in the MPC is governed by separate cell populations. One group encoded the time remaining for an action, showing activity whose duration changed as a function of interval duration, reaching a peak at similar magnitudes and times with respect to the movement. The other cell group showed a response that increased in duration or magnitude as a function of the elapsed time from the last movement. Hence, the sensorimotor loops engaged during the task may depend on the cyclic interplay between different neuronal chronometers that quantify the time passed and the remaining time for an action.medial premotor area | timing neurophysiology | supplementary motor area I nterval timing in the milliseconds is a prerequisite for many complex behaviors, such as the perception and production of speech (1), the execution and appreciation of music and dance (2, 3), and the performance of a large variety of sports (4). Time in music comes in a variety of patterns, which include isochronous sequences where temporal intervals are of a single constant duration or, more commonly, sequences containing intervals of many durations. In addition, the ability to capture and interpret the beats in a rhythmic pattern allows people to move and dance in time to music (3). Music and dance, then, are behaviors that depend on intricate loops of perception and action, where temporal processing can be involved during the synchronization of movements with sensory information or during the internal generation of movement sequences (2). In a simplified version of these activities, numerous studies have examined how subjects synchronize taps with pacing isochronous auditory stimuli and then continue tapping at the instructed rate without the advantage of the sensory metronome (5). Thus, the cyclic nature of the synchronizationcontinuation task (SCT) implies that subjects must keep track of the time elapsed since the previous sensorimotor events as well as the time remaining until the next events.Functional imaging studies have shown that the basal ganglia, the medial premotor cortex (MPC, pre-and supplementary motor areas), the prefrontal and posterior parietal cortex, and the cerebellum are the main nodes of a timing network that is engaged during different time production and perception tasks, including the SCT (6, 7). These studies suggest the existence of a partially overlapping distributed system for the temporal information processing in a variety of sensorimotor contexts that reach a complexity peak during musical cognition and speech, but that also include the production and estimation of single intervals (2,8).Neurophysiolog...

We determined the response properties of neurons in the primate medial premotor cortex that were classified as sensory or motor during isochronous tapping to a visual or auditory metronome, using different target intervals and three sequential elements in the task. The cell classification was based on a warping transformation, which determined whether the cell activity was statistically aligned to sensory or motor events, finding a large proportion of cells classified as sensory or motor. Two distinctive clusters of sensory cells were observed, i.e. one cell population with short response-onset latencies to the previous stimulus, and another that was probably predicting the occurrence of the next stimuli. These cells were called sensory-driven and stimulus-predicting neurons, respectively. Sensory-driven neurons showed a clear bias towards the visual modality and were more responsive to the first stimulus, with a decrease in activity for the following sequential elements of the metronome. In contrast, stimulus-predicting neurons were bimodal and showed similar response profiles across serial-order elements. Motor cells showed a consecutive activity onset across discrete neural ensembles, generating a rapid succession of activation patterns between the two taps defining a produced interval. The cyclical configuration in activation profiles engaged more motor cells as the serial-order elements progressed across the task, and the rate of cell recruitment over time decreased as a function of the target interval. Our findings support the idea that motor cells were responsible for the rhythmic progression of taps in the task, gaining more importance as the trial advanced, while, simultaneously, the sensory-driven cells lost their functional impact.

Perceptual categorization depends on the assignment of different stimuli to specific groups based, in principle, on the notion of flexible categorical boundaries. To determine the neural basis of categorical boundaries, we record the activity of pre-SMA neurons of monkeys executing an interval categorization task in which the limit between short and long categories changes between blocks of trials within a session. A large population of cells encodes this boundary by reaching a constant peak of activity close to the corresponding subjective limit. Notably, the time at which this peak is reached changes according to the categorical boundary of the current block, predicting the monkeys’ categorical decision on a trial-by-trial basis. In addition, pre-SMA cells also represent the category selected by the monkeys and the outcome of the decision. These results suggest that the pre-SMA adaptively encodes subjective duration boundaries between short and long durations and contains crucial neural information to categorize intervals and evaluate the outcome of such perceptual decisions.

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