Pre-supplementary Motor Cortex Mediates Learning Transfer from Perceptual to Motor Timing.

When we intensively train a timing skill, such as learning to play the piano, we not only produce brain changes associated with task-specific learning but also improve our performance in other temporal behaviors that depend on these tuned neural resources. Since the neural basis of time learning and generalization is still unknown, we measured the changes in neural activity associated with the transfer of learning from perceptual to motor timing in a large sample of subjects (n = 65; 39 women). We found that intense training in an interval discrimination task increased the acuity of time perception in a group of subjects that also exhibited learning transfer, expressed as a reduction in inter-tap interval variability during an internally driven periodic motor task. In addition, we found subjects with no learning and/or generalization effects. Notably, functional imaging showed an increase in pre-supplementary motor area and caudate-putamen activity between the post- and pre-training sessions of the tapping task. This increase was specific to the subjects that generalized their timing acuity from the perceptual to the motor context. These results emphasize the central role of the cortico-basal ganglia circuit in the generalization of timing abilities between tasks.

A Second Introduction to the Neurobiology of Interval Timing.

Time is a critical variable that organisms must be able to measure in order to survive in a constantly changing environment. Initially, this paper describes the myriad of contexts where time is estimated or predicted and suggests that timing is not a single process and probably depends on a set of different neural mechanisms. Consistent with this hypothesis, the explosion of neurophysiological and imaging studies in the last 10 years suggests that different brain circuits and neural mechanisms are involved in the ability to tell and use time to control behavior across contexts. Then, we develop a conceptual framework that defines time as a family of different phenomena and propose a taxonomy with sensory, perceptual, motor, and sensorimotor timing as the pillars of temporal processing in the range of hundreds of milliseconds.

Diverse Time Encoding Strategies Within the Medial Premotor Areas of the Primate.

The measurement of time in the subsecond scale is critical for many sophisticated behaviors, yet its neural underpinnings are largely unknown. Recent neurophysiological experiments from our laboratory have shown that the neural activity in the medial premotor areas (MPC) of macaques can represent different aspects of temporal processing. During single interval categorization, we found that preSMA encodes a subjective category limit by reaching a peak of activity at a time that divides the set of test intervals into short and long. We also observed neural signals associated with the category selected by the subjects and the reward outcomes of the perceptual decision. On the other hand, we have studied the behavioral and neurophysiological basis of rhythmic timing. First, we have shown in different tapping tasks that macaques are able to produce predictively and accurately intervals that are cued by auditory or visual metronomes or when intervals are produced internally without sensory guidance. In addition, we found that the rhythmic timing mechanism in MPC is governed by different layers of neural clocks. Next, the instantaneous activity of single cells shows ramping activity that encodes the elapsed or remaining time for a tapping movement. In addition, we found MPC neurons that build neural sequences, forming dynamic patterns of activation that flexibly cover all the produced interval depending on the tapping tempo. This rhythmic neural clock resets on every interval providing an internal representation of pulse. Furthermore, the MPC cells show mixed selectivity, encoding not only elapsed time, but also the tempo of the tapping and the serial order element in the rhythmic sequence. Hence, MPC can map different task parameters, including the passage of time, using different cell populations. Finally, the projection of the time varying activity of MPC hundreds of cells into a low dimensional state space showed circular neural trajectories whose geometry represented the internal pulse and the tapping tempo. Overall, these findings support the notion that MPC is part of the core timing mechanism for both single interval and rhythmic timing, using neural clocks with different encoding principles, probably to flexibly encode and mix the timing representation with other task parameters.

Common neural mechanisms supporting time judgements in humans and monkeys.

There has been an increasing interest in identifying the biological underpinnings of human time perception, for which purpose research in non-human primates (NHP) is common. Although previous work, based on behaviour, suggests that similar mechanisms support time perception across species, the neural correlates of time estimation in humans and NHP have not been directly compared. In this study, we assess whether brain evoked responses during a time categorization task are similar across species. Specifically, we assess putative differences in post-interval evoked potentials as a function of perceived duration in human EEG (N = 24) and local field potential (LFP) and spike recordings in pre-supplementary motor area (pre-SMA) of one monkey. Event-related potentials (ERPs) differed significantly after the presentation of the temporal interval between "short" and "long" perceived durations in both species, even when the objective duration of the stimuli was the same. Interestingly, the polarity of the reported ERPs was reversed for incorrect trials (i.e., the ERP of a "long" stimulus looked like the ERP of a "short" stimulus when a time categorization error was made). Hence, our results show that post-interval potentials reflect the perceived (rather than the objective) duration of the presented time interval in both NHP and humans. In addition, firing rates in monkey's pre-SMA also differed significantly between short and long perceived durations and were reversed in incorrect trials. Together, our results show that common neural mechanisms support time categorization in NHP and humans, thereby suggesting that NHP are a good model for investigating human time perception.

Keeping time and rhythm by internal simulation of sensory stimuli and behavioral actions.

Effective behavior often requires synchronizing our actions with changes in the environment. Rhythmic changes in the environment are easy to predict, and we can readily time our actions to them. Yet, how the brain encodes and maintains rhythms is not known. Here, we trained primates to internally maintain rhythms of different tempos and performed large-scale recordings of neuronal activity across the sensory-motor hierarchy. Results show that maintaining rhythms engages multiple brain areas, including visual, parietal, premotor, prefrontal, and hippocampal regions. Each recorded area displayed oscillations in firing rates and oscillations in broadband local field potential power that reflected the temporal and spatial characteristics of an internal metronome, which flexibly encoded fast, medium, and slow tempos. The presence of widespread metronome-related activity, in the absence of stimuli and motor activity, suggests that internal simulation of stimuli and actions underlies timekeeping and rhythm maintenance.