Hugo Merchant

Neural Basis of the Perception and Estimation of Time

Understanding how sensory and motor processes are temporally integrated to control behavior in the hundredths of milliseconds-to-minutes range is a fascinating problem given that the basic electrophysiological properties of neurons operate on a millisecond timescale. Single-unit recording studies in monkeys have identified localized timing circuits, whereas neuropsychological studies of humans who have damage to the basal ganglia have indicated that core structures, such as the cortico-thalamic-basal ganglia circuit, play an important role in timing and time perception. Taken together, these data suggest that a core timing mechanism interacts with context-dependent areas. This idea of a temporal hub with a distributed network is used to investigate the abstract properties of interval tuning as well as temporal illusions and intersensory timing. We conclude by proposing that the interconnections built into this core timing mechanism are designed to provide a form of degeneracy as protection against injury, disease, or age-related decline.

Subsecond Timing in Primates: Comparison of Interval Production Between Human Subjects and Rhesus Monkeys

This study describes the psychometric similarities and differences in motor timing performance between 20 human subjects and three rhesus monkeys during two timing production tasks. These tasks involved tapping on a push-button to produce the same set of intervals (range of 450 to 1,000 ms), but they differed in the number of intervals produced (single vs. multiple) and the modality of the stimuli (auditory vs. visual) used to define the time intervals. The data showed that for both primate species, variability increased as a function of the length of the produced target interval across tasks, a result in accordance with the scalar property. Interestingly, the temporal performance of rhesus monkeys was equivalent to that of human subjects during both the production of single intervals and the tapping synchronization to a metronome. Overall, however, human subjects were more accurate than monkeys and showed less timing variability. This was especially true during the self-pacing phase of the multiple interval production task, a behavior that may be related to complex temporal cognition, such as speech and music execution. In addition, the well-known human bias toward auditory as opposed to visual cues for the accurate execution of time intervals was not evident in rhesus monkeys. These findings validate the rhesus monkey as an appropriate model for the study of the neural basis of time production, but also suggest that the exquisite temporal abilities of humans, which peak in speech and music performance, are not all shared with macaques.

Interval Tuning in the Primate Medial Premotor Cortex as a General Timing Mechanism

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 interval-tuned 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.

Information Processing in the Primate Basal Ganglia during Sensory-Guided and Internally Driven Rhythmic Tapping

Gamma (γ) and beta (β) 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 β- than the γ-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 β-band when aligned to movements, and a bias toward the synchronization phase for the γ-band when aligned to the stimuli. Our results suggest that γ-oscillations reflect local computations associated with stimulus processing, whereas β-activity involves the entrainment of large putaminal circuits, probably in conjunction with other elements of CBGT, during internally driven rhythmic tapping.

Measuring time with different neural chronometers during a synchronization-continuation task

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.

Finding the beat: a neural perspective across humans and non-human primates

Humans possess an ability to perceive and synchronize movements to the beat in music (‘beat perception and synchronization’), and recent neuroscientific data have offered new insights into this beat-finding capacity at multiple neural levels. Here, we review and compare behavioural and neural data on temporal and sequential processing during beat perception and entrainment tasks in macaques (including direct neural recording and local field potential (LFP)) and humans (including fMRI, EEG and MEG). These abilities rest upon a distributed set of circuits that include the motor cortico-basal-ganglia–thalamo-cortical (mCBGT) circuit, where the supplementary motor cortex (SMA) and the putamen are critical cortical and subcortical nodes, respectively. In addition, a cortical loop between motor and auditory areas, connected through delta and beta oscillatory activity, is deeply involved in these behaviours, with motor regions providing the predictive timing needed for the perception of, and entrainment to, musical rhythms. The neural discharge rate and the LFP oscillatory activity in the gamma- and beta-bands in the putamen and SMA of monkeys are tuned to the duration of intervals produced during a beat synchronization–continuation task (SCT). Hence, the tempo during beat synchronization is represented by different interval-tuned cells that are activated depending on the produced interval. In addition, cells in these areas are tuned to the serial-order elements of the SCT. Thus, the underpinnings of beat synchronization are intrinsically linked to the dynamics of cell populations tuned for duration and serial order throughout the mCBGT. We suggest that a cross-species comparison of behaviours and the neural circuits supporting them sets the stage for a new generation of neurally grounded computational models for beat perception and synchronization.

Are non-human primates capable of rhythmic entrainment? Evidence for the gradual audiomotor evolution hypothesis

We propose a decomposition of the neurocognitive mechanisms that might underlie interval-based timing and rhythmic entrainment. Next to reviewing the concepts central to the definition of rhythmic entrainment, we discuss recent studies that suggest rhythmic entrainment to be specific to humans and a selected group of bird species, but, surprisingly, is not obvious in non-human primates. On the basis of these studies we propose the gradual audiomotor evolution hypothesis that suggests that humans fully share interval-based timing with other primates, but only partially share the ability of rhythmic entrainment (or beat-based timing). This hypothesis accommodates the fact that non-human primates (i.e., macaques) performance is comparable to humans in single interval tasks (such as interval reproduction, categorization, and interception), but show differences in multiple interval tasks (such as rhythmic entrainment, synchronization, and continuation). Furthermore, it is in line with the observation that macaques can, apparently, synchronize in the visual domain, but show less sensitivity in the auditory domain. And finally, while macaques are sensitive to interval-based timing and rhythmic grouping, the absence of a strong coupling between the auditory and motor system of non-human primates might be the reason why macaques cannot rhythmically entrain in the way humans do.

Interval timing and Parkinson's disease: heterogeneity in temporal performance.

Interval timing deficiencies in Parkinson’s disease (PD) patients have been a matter of debate. Here we test the possibility of PD heterogeneity as a source for this discrepancy. Temporal performance of PD patients and control subjects was assessed during two interval tapping tasks and during a categorization task of time intervals. These tasks involved temporal processing of intervals in the hundreds of milliseconds range; however, they also covered a wide range of behavioral contexts, differing in their perceptual, decision-making, memory, and execution requirements. The results showed the following significant findings. First, there were two clearly segregated subgroups of PD patients: one with high temporal variability in the three timing tasks, and another with a temporal variability that did not differ substantially from control subjects. In contrast, PD patients with high and low temporal variability showed similar perceptual, decision-making, memory, and execution performance in a set of control tasks. Second, a slope analysis, designed to dissociate time-dependent from time-independent sources of variation, revealed that the increase in variability in this group of PD patients was mainly due to an increment in the variability associated with the timing mechanism. Third, while the control subjects showed significant correlations in performance variability across tasks, PD patients, and particularly those with high temporal variability, did not show such task correlations. Finally, the results showed that dopaminergic treatment restored the correlation effect in PD patients, producing a highly significant correlation between the inter-task variability. Altogether, these results indicate that a subpopulation of PD patients shows a strong disruption in temporal processing in the hundreds of milliseconds range. These findings are discussed in terms of the role of dopamine as a tuning element for the synchronization of temporal processing across different behavioral contexts in PD patients.

Rhesus Monkeys (Macaca mulatta) Detect Rhythmic Groups in Music, but Not the Beat

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).

The Context of Temporal Processing Is Represented in the Multidimensional Relationships between Timing Tasks

In the present study we determined the performance interrelations of ten different tasks that involved the processing of temporal intervals in the subsecond range, using multidimensional analyses. Twenty human subjects executed the following explicit timing tasks: interval categorization and discrimination (perceptual tasks), and single and multiple interval tapping (production tasks). In addition, the subjects performed a continuous circle-drawing task that has been considered an implicit timing paradigm, since time is an emergent property of the produced spatial trajectory. All tasks could be also classified as single or multiple interval paradigms. Auditory or visual markers were used to define the intervals. Performance variability, a measure that reflects the temporal and non-temporal processes for each task, was used to construct a dissimilarity matrix that quantifies the distances between pairs of tasks. Hierarchical clustering and multidimensional scaling were carried out on the dissimilarity matrix, and the results showed a prominent segregation of explicit and implicit timing tasks, and a clear grouping between single and multiple interval paradigms. In contrast, other variables such as the marker modality were not as crucial to explain the performance between tasks. Thus, using this methodology we revealed a probable functional arrangement of neural systems engaged during different timing behaviors.