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...

Gamma (␥) and beta (␤) oscillations seem to play complementary functions in the cortico-basal ganglia-thalamo-cortical circuit (CBGT) during motor behavior. We investigated the time-varying changes of the putaminal spiking activity and the spectral power of local field potentials (LFPs) during a task where the rhythmic tapping of monkeys was guided by isochronous stimuli separated by a fixed duration (synchronization phase), followed by a period of internally timed movements (continuation phase). We found that the power of both bands and the discharge rate of cells showed an orderly change in magnitude as a function of the duration and/or the serial order of the intervals executed rhythmically. More LFPs were tuned to duration and/or serial order in the ␤-than the ␥-band, although different values of preferred features were represented by single cells and by both bands. Importantly, in the LFPs tuned to serial order, there was a strong bias toward the continuation phase for the ␤-band when aligned to movements, and a bias toward the synchronization phase for the ␥-band when aligned to the stimuli. Our results suggest that ␥-oscillations reflect local computations associated with stimulus processing, whereas ␤-activity involves the entrainment of large putaminal circuits, probably in conjunction with other elements of CBGT, during internally driven rhythmic tapping.

We determined the encoding properties of single cells and the decoding accuracy of cell populations in the medial premotor cortex (MPC) of Rhesus monkeys to represent in a time-varying fashion the duration and serial order of six intervals produced rhythmically during a synchronization-continuation tapping task. We found that MPC represented the temporal and sequential structure of rhythmic movements by activating small ensembles of neurons that encoded the duration or the serial order in rapid succession, so that the pattern of active neurons changed dramatically within each interval. Interestingly, the width of the encoding or decoding function for serial order increased as a function of duration. Finally, we found that the strength of correlation in spontaneous activity of the individual cells varied as a function of the timing of their recruitment. These results demonstrate the existence of dynamic representations in MPC for the duration and serial order of intervals produced rhythmically and suggest that this dynamic code depends on ensembles of interconnected neurons that provide a strong synaptic drive to the next ensemble in a consecutive chain of neural events.

It was recently shown that rhythmic entrainment, long considered a human-specific mechanism, can be demonstrated in a selected group of bird species, and, somewhat surprisingly, not in more closely related species such as nonhuman primates. This observation supports the vocal learning hypothesis that suggests rhythmic entrainment to be a by-product of the vocal learning mechanisms that are shared by several bird and mammal species, including humans, but that are only weakly developed, or missing entirely, in nonhuman primates. To test this hypothesis we measured auditory event-related potentials (ERPs) in two rhesus monkeys (Macaca mulatta), probing a well-documented component in humans, the mismatch negativity (MMN) to study rhythmic expectation. We demonstrate for the first time in rhesus monkeys that, in response to infrequent deviants in pitch that were presented in a continuous sound stream using an oddball paradigm, a comparable ERP component can be detected with negative deflections in early latencies (Experiment 1). Subsequently we tested whether rhesus monkeys can detect gaps (omissions at random positions in the sound stream; Experiment 2) and, using more complex stimuli, also the beat (omissions at the first position of a musical unit, i.e. the ‘downbeat’; Experiment 3). In contrast to what has been shown in human adults and newborns (using identical stimuli and experimental paradigm), the results suggest that rhesus monkeys are not able to detect the beat in music. These findings are in support of the hypothesis that beat induction (the cognitive mechanism that supports the perception of a regular pulse from a varying rhythm) is species-specific and absent in nonhuman primates. In addition, the findings support the auditory timing dissociation hypothesis, with rhesus monkeys being sensitive to rhythmic grouping (detecting the start of a rhythmic group), but not to the induced beat (detecting a regularity from a varying rhythm).

␤ oscillations in the basal ganglia have been associated with interval timing. We recorded the putaminal local field potentials (LFPs) from monkeys performing a synchronization-continuation task (SCT) and a serial reaction-time task (RTT), where the animals produced regularly and irregularly paced tapping sequences, respectively. We compared the activation profile of ␤ oscillations between tasks and found transient bursts of ␤ activity in both the RTT and SCT. During the RTT, ␤ power was higher at the beginning of the task, especially when LFPs were aligned to the stimuli. During the SCT, ␤ was higher during the internally driven continuation phase, especially for tap-aligned LFPs. Interestingly, a set of LFPs showed an initial burst of ␤ at the beginning of the SCT, similar to the RTT, followed by a decrease in ␤ oscillations during the synchronization phase, to finally rebound during the continuation phase. The rebound during the continuation phase of the SCT suggests that the corticostriatal circuit is involved in the control of internally driven motor sequences. In turn, the transient bursts of ␤ activity at the beginning of both tasks suggest that the basal ganglia produce a general initiation signal that engages the motor system in different sequential behaviors.