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.

Beat entrainment is the ability to entrain one's movements to a perceived periodic stimulus, such as a metronome or a pulse in music. Humans have a capacity to predictively respond to a periodic pulse and to dynamically adjust their movement timing to match the varying music tempos. Previous studies have shown that monkeys share some of the human capabilities for rhythmic entrainment, such as tapping regularly at the period of isochronous stimuli. However, it is still unknown whether monkeys can predictively entrain to dynamic tempo changes like humans. To address this question, we trained monkeys in three tapping tasks and compared their rhythmic entrainment abilities with those of humans. We found that, when immediate feedback about the timing of each movement is provided, monkeys can predictively entrain to an isochronous beat, generating tapping movements in anticipation of the metronome pulse. This ability also generalized to a novel untrained tempo. Notably, macaques can modify their tapping tempo by predicting the beat changes of accelerating and decelerating visual metronomes in a manner similar to humans. Our findings support the notion that nonhuman primates share with humans the ability of temporal anticipation during tapping to isochronous and smoothly changing sequences of stimuli.

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.

Our motor commands can be exquisitely timed according to the demands of the environment, and the ability to generate rhythms of different tempos is a hallmark of musical cognition. Yet, the neuronal underpinnings behind rhythmic tapping remain elusive. Here, we found that the activity of hundreds of primate medial premotor cortices (MPCs; pre-supplementary motor area [preSMA] and supplementary motor area [SMA]) neurons show a strong periodic pattern that becomes evident when their responses are projected into a state space using dimensionality reduction analysis. We show that different tapping tempos are encoded by circular trajectories that travelled at a constant speed but with different radii, and that this neuronal code is highly resilient to the number of participating neurons. Crucially, the changes in the amplitude of the oscillatory dynamics in neuronal state space are a signature of duration encoding during rhythmic timing, regardless of whether it is guided by an external metronome or is internally controlled and is not the result of repetitive motor commands. This dynamic state signal predicted the duration of the rhythmically produced intervals on a trial-by-trial basis. Furthermore, the increase in variability of the neural trajectories accounted for the scalar property, a hallmark feature of temporal processing across tasks and species. Finally, we found that the interval-dependent increments in the radius of periodic neural trajectories are the result of a larger number of neurons engaged in the production of longer intervals. Our results support the notion that rhythmic timing during tapping behaviors is encoded in the radial curvature of periodic MPC neural population trajectories.

Our motor commands can be exquisitely timed according to the demands of the environment, and the ability to generate rhythms of different tempos is a hallmark of musical cognition. Yet, the neuronal basis behind rhythmic tapping remains elusive. Here we found that the activity of hundreds of primate MPC neurons show a strong periodic pattern that becomes evident when their activity is projected into a lower dimensional state space. We show that different tempos are encoded by circular trajectories that travelled at a constant speed but with different radii, and that this neuronal code is highly resilient to the number of participating neurons. Crucially, the changes in the amplitude of the oscillatory dynamics in neuronal state space are a signature of beat-based timing, regardless of whether it is guided by an external metronome or is internally controlled and is not the result of repetitive motor commands. Furthermore, the increase in amplitude and variability of the neural trajectories accounted for the scalar property of interval timing. In addition, we found that the interval-dependent increments in the radius of periodic neural trajectories are the result of larger number of neurons engaged in the production of longer intervals. Our results support the notion that beat-based timing during rhythmic behaviors is encoded in the radial curvature of periodic MPC neural population trajectories.