The Strength of Alpha-Beta Oscillatory Coupling Predicts Motor Timing Precision.

Precise timing makes the difference between harmony and cacophony, but how the brain achieves precision during timing is unknown. In this study, human participants (7 females, 5 males) generated a time interval while being recorded with magnetoencephalography. Building on the proposal that the coupling of neural oscillations provides a temporal code for information processing in the brain, we tested whether the strength of oscillatory coupling was sensitive to self-generated temporal precision. On a per individual basis, we show the presence of alpha-beta phase-amplitude coupling whose strength was associated with the temporal precision of self-generated time intervals, not with their absolute duration. Our results provide evidence that active oscillatory coupling engages α oscillations in maintaining the precision of an endogenous temporal motor goal encoded in ß power; the when of self-timed actions. We propose that oscillatory coupling indexes the variance of neuronal computations, which translates into the precision of an individual's behavioral performance.SIGNIFICANCE STATEMENT Which neural mechanisms enable precise volitional timing in the brain is unknown, yet accurate and precise timing is essential in every realm of life. In this study, we build on the hypothesis that neural oscillations, and their coupling across time scales, are essential for the coding and for the transmission of information in the brain. We show the presence of alpha-beta phase-amplitude coupling (α-ß PAC) whose strength was associated with the temporal precision of self-generated time intervals, not with their absolute duration. α-ß PAC indexes the temporal precision with which information is represented in an individual's brain. Our results link large-scale neuronal variability on the one hand, and individuals' timing precision, on the other.

Precision Timing with α-ß Oscillatory Coupling: Stopwatch or Motor Control?

Precise timing is crucial for many behaviors ranging from conversational speech to athletic performance. The precision of motor timing has been suggested to result from the strength of phase-amplitude coupling (PAC) between the phase of alpha oscillations (α, 8-12 Hz) and the power of beta activity (ß, 14-30 Hz), herein referred to as α-ß PAC. The amplitude of ß oscillations has been proposed to code for temporally relevant information and the locking of ß power to the phase of α oscillations to maintain timing precision. Motor timing precision has at least two sources of variability: variability of timekeeping mechanism and variability of motor control. It is ambiguous to which of these two factors α-ß PAC should be ascribed: α-ß PAC could index precision of stopwatch-like internal timekeeping mechanisms, or α-ß PAC could index motor control precision. To disentangle these two hypotheses, we tested how oscillatory coupling at different stages of a time reproduction task related to temporal precision. Human participants encoded and subsequently reproduced a time interval while magnetoencephalography was recorded. The data show a robust α-ß PAC during both the encoding and reproduction of a temporal interval, a pattern that cannot be predicted by motor control accounts. Specifically, we found that timing precision resulted from the trade-off between the strength of α-ß PAC during the encoding and during the reproduction of intervals. These results support the hypothesis that α-ß PAC codes for the precision of temporal representations in the human brain.

Temporal Metacognition as the Decoding of Self-Generated Brain Dynamics.

Metacognition, the ability to know about one's thought process, is self-referential. Here, we combined psychophysics and time-resolved neuroimaging to explore metacognitive inference on the accuracy of a self-generated behavior. Human participants generated a time interval and evaluated the signed magnitude of their temporal production. We show that both self-generation and self-evaluation relied on the power of beta oscillations (ß; 15-40 Hz) with increases in early ß power predictive of increases in duration. We characterized the dynamics of ß power in a low-dimensional space (ß state-space trajectories) as a function of timing and found that the more distinct trajectories, the more accurate metacognitive inferences were. These results suggest that ß states instantiate an internal variable determining the fate of the timing network's trajectory, possibly as release from inhibition. Altogether, our study describes oscillatory mechanisms for timing, suggesting that temporal metacognition relies on inferential processes of self-generated dynamics.

Evaluation of Self-generated Behavior: Untangling Metacognitive Readout and Error Detection.

When producing a duration, for instance, by pressing a key for 1 sec, the brain relies on self-generated neuronal dynamics to monitor the "flow of time." Evidence has suggested that the brain can also monitor itself monitoring time, the so-called self-evaluation. How are temporal errors inferred on the basis of purely internally driven brain dynamics with no external reference for time? Although studies have shown that participants can reliably detect temporal errors when generating a duration, the neural bases underlying the evaluation of this self-generated temporal behavior are unknown. Theories of psychological time have also remained silent about such self-evaluation abilities. We assessed the contributions of an error-detection mechanism, in which error detection results from the ability to estimate the latency of motor actions, and of a readout mechanism, in which errors would result from inferring the state of a duration representation. Error detection predicts a V-shape association between neural activity and self-evaluation at the offset of a produced interval, whereas the readout predicts a linear association. Here, human participants generated a time interval and evaluated the magnitude of their timing (first- and second-order behavioral judgments, respectively). Focusing on the MEG/EEG signatures after the termination of the self-generated duration, we found several cortical sources involved in performance monitoring displaying a linear association between the power of alpha (α = 8-14 Hz) oscillations and self-evaluation. Altogether, our results support the readout hypothesis and indicate that duration representation may be integrated for the evaluation of self-generated behavior.

Decoupling interval timing and climbing neural activity: a dissociation between CNV and N1P2 amplitudes.

It is often argued that climbing neural activity, as for example reflected by the contingent negative variation (CNV) in the electroencephalogram, is the signature of the subjective experience of time. According to this view, the resolution of the CNV coincides with termination of subjective timing processes. Paradoxically, behavioral data indicate that participants keep track of timing even after the standard interval (SI) has passed. This study addresses whether timing continues after CNV resolution. In Experiment 1, human participants were asked to discriminate time intervals while evoked potentials (EPs) elicited by the sound terminating a comparison interval (CI) were measured. As the amplitude of N1P2 components increases as a function of the temporal distance from the SI, and the latency of the P2 component followed the hazard rate of the CIs, timing processes continue after CNV resolution. Based on a novel experimental paradigm, statistical model comparisons and trial-by-trial analyses, Experiment 2 supports this finding as subjective time is more accurately indexed by the amplitude of early EPs than by CNV amplitude. These results provide the first direct evidence that subjective timing of multisecond intervals does not depend on climbing neural activity as indexed by the CNV and that the subjective experience of time is better reflected by distinct features of post-CI evoked potentials.

Distinct neural adaptations to time demand in the striatum and the hippocampus.

How do neural codes adjust to track time across a range of resolutions, from milliseconds to multi-seconds, as a function of the temporal frequency at which events occur? To address this question, we studied time-modulated cells in the striatum and the hippocampus, while macaques categorized three nested intervals within the sub-second or the supra-second range (up to 1, 2, 4, or 8 s), thereby modifying the temporal resolution needed to solve the task. Time-modulated cells carried more information for intervals with explicit timing demand, than for any other interval. The striatum, particularly the caudate, supported the most accurate temporal prediction throughout all time ranges. Strikingly, its temporal readout adjusted non-linearly to the time range, suggesting that the striatal resolution shifted from a precise millisecond to a coarse multi-second range as a function of demand. This is in line with monkey's behavioral latencies, which indicated that they tracked time until 2 s but employed a coarse categorization strategy for durations beyond. By contrast, the hippocampus discriminated only the beginning from the end of intervals, regardless of the range. We propose that the hippocampus may provide an overall poor signal marking an event's beginning, whereas the striatum optimizes neural resources to process time throughout an interval adapting to the ongoing timing necessity.

Single trial beta oscillations index time estimation.

Recent work shows that putamen-originating beta power oscillations serve as a carrier for temporal information during tapping tasks, with higher beta power associated with longer temporal reproductions. However, given the nature of tapping tasks, it is difficult to determine whether beta power dynamics observed in these tasks are linked to the generation or execution of motor programs or to the internal representation of time. To assess whether recent findings in animals generalize to human studies we reanalyzed existing EEG data of participants who estimated a 2.5s time interval with self-paced onset and offset keypresses. The results showed that the trial-to-trial beta power measured after the onset predicts the produced duration, such that higher beta power indexes longer produced durations. Moreover, although beta power measured before the first key-press also influenced the estimated interval, it did so independently from post-first-keypress beta power. These results suggest that initial motor inhibition plays an important role in interval production, and that this inhibition can be interpreted as a biased starting point of the decision processes involved in time estimation.

Neuroelectromagnetic signatures of the reproduction of supra-second durations.

When participants are asked to reproduce an earlier presented duration, EEG recordings typically show a slow potential that develops over the fronto-central regions of the brain and is assumed to be generated in the supplementary motor area (SMA). This contingent negative variation (CNV) has been linked to anticipation, preparation and formation of temporal judgment (Macar, Vidal, and Casini, 1999, Experimental Brain Research, 125(3), 271-80). Although the interpretation of the CNV amplitude is problematic (Kononowicz and Van Rijn, (2011), Frontiers in Integrative Neuroscience, 5(48); Ng, Tobin, and Penney, 2011, Frontiers in Integrative Neuroscience, 5(77)), the observation of this slow potential is extremely robust, and thus one could assume that magnetic recordings of brain activity should show similar activity patterns. However, interval timing studies using durations shorter than one second did not provide unequivocal evidence as to whether CNV has a magnetic counterpart (CMV). As interval timing has been typically associated with durations longer than one second, participants in this study were presented intervals of 2, 3 or 4s that had to be reproduced in setup similar to the seminal work of Elbert et al. (1991, Psychophysiology, 28(6), 648-55) while co-recording EEG and MEG. The EEG data showed a clear CNV during the standard and the reproduction interval. In the reproduction interval the CNV steadily builds up from the onset of interval for both stimulus and response locked data. The MEG data did not show a CNV-resembling ramping of activity, but only showed a pre-movement magnetic field (preMMF) that originated from the SMA, occurring approximately 0.6s before the termination of the timed interval. These findings support the notion that signatures of timing are more straightforwardly measured using EEG, and show that the measured MEG signal from the SMA is constrained to the end of reproduction interval, before the voluntary movement. Moreover, we investigated a link between timing behavior and the early iCNV and late CNV amplitudes to evaluate the hypothesis that these amplitudes reflect the accumulation of temporal pulses. Larger iCNV amplitudes predicted shorter reproduced durations. This effect was more pronounced for the 2s interval reproduction, suggesting that preparatory strategies depend on the length of reproduced interval. Similarly to Elbert et al. (1991, Psychophysiology, 28(6), 648-55), longer reproductions were associated with smaller CNV amplitudes, both between conditions and across participants within the same condition. As the temporal accumulation hypothesis predicts the inverse, these results support the proposal by Van Rijn et al. (2011, Frontiers in Integrative Neuroscience, 5) that the CNV reflects other temporally driven processes such as temporal expectation and preparation rather than temporal accumulation itself.

Slow potentials in time estimation: the role of temporal accumulation and habituation.

Numerous studies have shown that contingent negative variation (CNV) measured at fronto-central and parietal-central areas is closely related to interval timing. However, the exact nature of the relation between CNV and the underlying timing mechanisms is still a topic of discussion. On the one hand, it has been proposed that the CNV measured at supplementary motor area (SMA) is a direct reflection of the unfolding of time since a perceived onset, whereas other work has suggested that the increased amplitude reflects decision processes involved in interval timing. Strong evidence for the first view has been reported by Macar et al. (1999), who showed that variations in temporal performance were reflected in the measured CNV amplitude. If the CNV measured at SMA is a direct function of the passing of time, habituation effects are not expected. Here we report two replication studies, which both failed to replicate the expected performance-dependent variations. Even more powerful linear-mixed effect analyses failed to find any performance related effects on the CNV amplitude, whereas habituation effects were found. These studies therefore suggest that the CNV amplitude does not directly reflect the unfolding of time.

Contingent negative variation and its relation to time estimation: a theoretical evaluation.

The relation between the contingent negative variation (CNV) and time estimation is evaluated in terms of temporal accumulation and preparation processes. The conclusion is that the CNV as measured from the electroencephalogram (EEG) recorded at fronto-central and parietal-central areas is not a direct reflection of the underlying interval timing mechanism(s), but more likely represents a time-based response preparation/decision-making process.