Chronotopic maps in human supplementary motor area.

Time is a fundamental dimension of everyday experiences. We can unmistakably sense its passage and adjust our behavior accordingly. Despite its ubiquity, the neuronal mechanisms underlying the capacity to perceive time remains unclear. Here, in two experiments using ultrahigh-field 7-Tesla (7T) functional magnetic resonance imaging (fMRI), we show that in the medial premotor cortex (supplementary motor area [SMA]) of the human brain, neural units tuned to different durations are orderly mapped in contiguous portions of the cortical surface so as to form chronomaps. The response of each portion in a chronomap is enhanced by neighboring durations and suppressed by nonpreferred durations represented in distant portions of the map. These findings suggest duration-sensitive tuning as a possible neural mechanism underlying the recognition of time and demonstrate, for the first time, that the representation of an abstract feature such as time can be instantiated by a topographical arrangement of duration-sensitive neural populations.

Duration Selectivity in Right Parietal Cortex Reflects the Subjective Experience of Time.

The perception of duration in the subsecond range has been hypothesized to be mediated by the population response of duration-sensitive units, each tuned to a preferred duration. One line of support for this hypothesis comes from neuroimaging studies showing that cortical regions, such as in parietal cortex exhibit duration tuning. It remains unclear whether this representation is based on the physical duration of the sensory input or the subjective duration, a question that is important given that our perception of the passage of time is often not veridical, but rather, biased by various contextual factors. Here we used fMRI to examine the neural correlates of subjective time perception in human participants. To manipulate perceived duration while holding physical duration constant, we used an adaptation method, in which, before judging the duration of a test stimulus, the participants were exposed to a train of adapting stimuli of a fixed duration. Behaviorally, this procedure produced a pronounced negative aftereffect: A short adaptor biased participants to judge stimuli as longer and a long adaptor-biased participants to judge stimuli as shorter. Duration tuning modulation, manifest as an attenuated BOLD response to stimuli similar in duration to the adaptor, was only observed in the right supramarginal gyrus (SMG) of the parietal lobe and middle occipital gyrus, bilaterally. Across individuals, the magnitude of the behavioral aftereffect was positively correlated with the magnitude of duration tuning modulation in SMG. These results indicate that duration-tuned neural populations in right SMG reflect the subjective experience of time.SIGNIFICANCE STATEMENT The subjective sense of time is a fundamental dimension of sensory experience. To investigate the neural basis of subjective time, we conducted an fMRI study, using an adaptation procedure that allowed us to manipulate perceived duration while holding physical duration constant. Regions within the occipital cortex and right parietal lobe showed duration tuning that was modulated when the test stimuli were similar in duration to the adaptor. Moreover, the magnitude of the distortion in perceived duration was correlated with the degree of duration tuning modulation in the parietal region. These results provide strong physiological evidence that the population coding of time in the right parietal cortex reflects our subjective experience of time.

Exaggerated groups: amplification in ensemble coding of temporal and spatial features.

The human visual system represents summary statistical information (e.g. average) along many visual dimensions efficiently. While studies have indicated that approximately the square root of the number of items in a set are effectively integrated through this ensemble coding, how those samples are determined is still unknown. Here, we report that salient items are preferentially weighted over the other less salient items, by demonstrating that the perceived means of spatial (i.e. size) and temporal (i.e. flickering temporal frequency (TF)) features of the group of items are positively biased as the number of items in the group increases. This illusory 'amplification effect' was not the product of decision bias but of perceptual bias. Moreover, our visual search experiments with similar stimuli suggested that this amplification effect was due to attraction of visual attention to the salient items (i.e. large or high TF items). These results support the idea that summary statistical information is extracted from sets with an implicit preferential weighting towards salient items. Our study suggests that this saliency-based weighting may reflect a more optimal and efficient integration strategy for the extraction of spatio-temporal statistical information from the environment, and may thus be a basic principle of ensemble coding.

Correction: Time Adaptation Shows Duration Selectivity in the Human Parietal Cortex.

[This corrects the article DOI: 10.1371/journal.pbio.1002262.].

Time Adaptation Shows Duration Selectivity in the Human Parietal Cortex.

Although psychological and computational models of time estimation have postulated the existence of neural representations tuned for specific durations, empirical evidence of this notion has been lacking. Here, using a functional magnetic resonance imaging (fMRI) adaptation paradigm, we show that the inferior parietal lobule (IPL) (corresponding to the supramarginal gyrus) exhibited reduction in neural activity due to adaptation when a visual stimulus of the same duration was repeatedly presented. Adaptation was strongest when stimuli of identical durations were repeated, and it gradually decreased as the difference between the reference and test durations increased. This tuning property generalized across a broad range of durations, indicating the presence of general time-representation mechanisms in the IPL. Furthermore, adaptation was observed irrespective of the subject's attention to time. Repetition of a nontemporal aspect of the stimulus (i.e., shape) did not produce neural adaptation in the IPL. These results provide neural evidence for duration-tuned representations in the human brain.

Interaction of numerosity and time in prefrontal and parietal cortex.

It has been proposed that numerical and temporal information are processed by partially overlapping magnitude systems. Interactions across different magnitude domains could occur both at the level of perception and decision-making. However, their neural correlates have been elusive. Here, using functional magnetic resonance imaging in humans, we show that the right intraparietal cortex (IPC) and inferior frontal gyrus (IFG) are jointly activated by duration and numerosity discrimination tasks, with a congruency effect in the right IFG. To determine whether the IPC and the IFG are involved in response conflict (or facilitation) or modulation of subjective passage of time by numerical information, we examined their functional roles using transcranial magnetic stimulation (TMS) and two different numerosity-time interaction tasks: duration discrimination and time reproduction tasks. Our results show that TMS of the right IFG impairs categorical duration discrimination, whereas that of the right IPC modulates the degree of influence of numerosity on time perception and impairs precise time estimation. These results indicate that the right IFG is specifically involved at the categorical decision stage, whereas bleeding of numerosity information on perception of time occurs within the IPC. Together, our findings suggest a two-stage model of numerosity-time interactions whereby the interaction at the perceptual level occurs within the parietal region and the interaction at categorical decisions takes place in the prefrontal cortex.

Dissociable neuroanatomical correlates of subsecond and suprasecond time perception.

The ability to estimate durations varies across individuals. Although previous studies have reported that individual differences in perceptual skills and cognitive capacities are reflected in brain structures, it remains unknown whether timing abilities are also reflected in the brain anatomy. Here, we show that individual differences in the ability to estimate subsecond and suprasecond durations correlate with gray matter (GM) volume in different parts of cortical and subcortical areas. Better ability to discriminate subsecond durations was associated with a larger GM volume in the bilateral anterior cerebellum, whereas better performance in estimating the suprasecond range was associated with a smaller GM volume in the inferior parietal lobule. These results indicate that regional GM volume is predictive of an individual's timing abilities. These morphological results support the notion that subsecond durations are processed in the motor system, whereas suprasecond durations are processed in the parietal cortex by utilizing the capacity of attention and working memory to keep track of time.

Effective connectivity in a duration selective cortico-cerebellar network.

How the human brain represents millisecond unit of time is far from clear. A recent neuroimaging study revealed the existence in the human premotor cortex of a topographic representation of time i.e., neuronal units selectively responsive to specific durations and topographically organized on the cortical surface. By using high resolution functional Magnetic Resonance Images here, we go beyond this previous work, showing duration preferences across a wide network of cortical and subcortical brain areas: from cerebellum to primary visual, parietal, premotor and prefrontal cortices. Most importantly, we identify the effective connectivity structure between these different brain areas and their duration selective neural units. The results highlight the role of the cerebellum as the network hub and that of medial premotor cortex as the final stage of duration recognition. Interestingly, when a specific duration is presented, only the communication strength between the units selective to that specific duration and to the neighboring durations is affected. These findings link for the first time, duration preferences within single brain region with connectivity dynamics between regions, suggesting a communication mode that is partially duration specific.

Longitudinal analysis of social isolation effects on finger tapping in the Blursday database.

The Blursday database is a collection of data obtained online from a longitudinal study where participants were asked to participate in several behavioral tasks and questionnaires during the COVID-19 pandemic from their homes. In this study, we analyzed the published data to explore (1) the longitudinal changes in temporal cognition observed from the data collected in the home-based setting (2), the effects of the voluntary quarantine measures implemented in Japan on temporal cognition, (3) whether the participant's temporal cognition is altered by the change in their psychological state or their cognitive abilities, and (4) whether the effects of the quarantine measures depend on the age of the individual. Results show that confinement measures were good predictors for the performance in both spontaneous finger-tapping task and paced finger-tapping task, though these were dependent on the age of the participant. In addition, cognitive scores were good predictors of the performance in the paced finger-tapping task but not the spontaneous finger-tapping task. Overall, this study provides evidence suggesting changes in both psychological, cognitive, and temporal cognition during the pandemic on the Japanese population despite its voluntary measures to deal with the new situation.

Temporal perceptual learning distinguishes between empty and filled intervals.

Temporal perceptual learning (TPL) refers to improved temporal performance as a result of training with sub-second intervals. Most studies on TPL have focused on empty intervals (i.e. intervals marked by two brief stimuli); however, scholars have suggested that filled intervals (i.e. intervals presented as continuous sensory inputs) might have different underlying mechanisms. Therefore, the current study aimed to test whether empty and filled intervals yield similar TPL performance and whether such learning effects could transfer mutually. To this end, we trained two groups of participants with empty and filled intervals of 200 ms for four days, respectively. We found that the empty-interval group clearly improved their timing performances after training, and such an effect transferred to filled intervals of 200 ms. By contrast, the filled-interval group had neither learning nor transfer effect. Our results further shed light on the distinct mechanisms between empty and filled intervals in time perception while simultaneously replicating the classical findings on TPL involving empty intervals.

Microstructural Properties of Human Brain Revealed by Fractional Anisotropy Can Predict the After-Effect of Intermittent Theta Burst Stimulation.

Intermittent theta burst stimulation (iTBS) delivered by transcranial magnetic stimulation (TMS) produces a long-term potentiation-like after-effect useful for investigations of cortical function and of potential therapeutic value. However, the iTBS after-effect over the primary motor cortex (M1) as measured by changes in motor evoked potential (MEP) amplitude exhibits a largely unexplained variability across individuals. Here, we present evidence that individual differences in white matter (WM) and gray matter (GM) microstructural properties revealed by fractional anisotropy (FA) predict the magnitude of the iTBS-induced after-effect over M1. The MEP amplitude change in the early phase (5-10 min post-iTBS) was associated with FA values in WM tracts such as right superior longitudinal fasciculus and corpus callosum. By contrast, the MEP amplitude change in the late phase (15-30 min post-iTBS) was associated with FA in GM, primarily in right frontal cortex. These results suggest that the microstructural properties of regions connected directly or indirectly to the target region (M1) are crucial determinants of the iTBS after-effect. FA values indicative of these microstructural differences can predict the potential effectiveness of repetitive TMS for both investigational use and clinical application.

Hemispheric asymmetry of frequency-dependent suppression in the ipsilateral primary motor cortex during finger movement: a functional magnetic resonance imaging study.

Electrophysiological studies have suggested that the activity of the primary motor cortex (M1) during ipsilateral hand movement reflects both the ipsilateral innervation and the transcallosal inhibitory control from its counterpart in the opposite hemisphere, and that their asymmetry might cause hand dominancy. To examine the asymmetry of the involvement of the ipsilateral motor cortex during a unimanual motor task under frequency stress, we conducted block-design functional magnetic resonance imaging with 22 normal right-handed subjects. The task involved visually cued unimanual opponent finger movement at various rates. The contralateral M1 showed symmetric frequency-dependent activation. The ipsilateral M1 showed task-related deactivation at low frequencies without laterality. As the frequency of the left-hand movement increased, the left M1 showed a gradual decrease in the deactivation. This data suggests a frequency-dependent increased involvement of the left M1 in ipsilateral hand control. By contrast, the right M1 showed more prominent deactivation as the frequency of the right-hand movement increased. This suggests that there is an increased transcallosal inhibition from the left M1 to the right M1, which overwhelms the right M1 activation during ipsilateral hand movement. These results demonstrate the dominance of the left M1 in both ipsilateral innervation and transcallosal inhibition in right-handed individuals.

Representations of time in human frontoparietal cortex.

Precise time estimation is crucial in perception, action and social interaction. Previous neuroimaging studies in humans indicate that perceptual timing tasks involve multiple brain regions; however, whether the representation of time is localized or distributed in the brain remains elusive. Using ultra-high-field functional magnetic resonance imaging combined with multivariate pattern analyses, we show that duration information is decoded in multiple brain areas, including the bilateral parietal cortex, right inferior frontal gyrus and, albeit less clearly, the medial frontal cortex. Individual differences in the duration judgment accuracy were positively correlated with the decoding accuracy of duration in the right parietal cortex, suggesting that individuals with a better timing performance represent duration information in a more distinctive manner. Our study demonstrates that although time representation is widely distributed across frontoparietal regions, neural populations in the right parietal cortex play a crucial role in time estimation.

Age-dependent atypicalities in body- and face-sensitive activation of the EBA and FFA in individuals with ASD.

Individuals with autism spectrum disorder (ASD) have difficuly in recognizing bodies and faces, which are more pronounced in children than adults. If such difficulties originate from dysfunction of the extrastriate body area (EBA) and the fusiform face area (FFA), activation in these regions might be more atypical in children than in adults. We preformed functional magnetic resonance imaging while children and adults with ASD and age-matched typically developed (TD) individuals observed face, body, car, and scene. To examine various aspects, we performed individual region of interest (ROI) analysis, as well as conventional random effect group analysis. At individual ROI analysis, we examined the ratio of participants showing a category-sensitive response, the size of regions, location and activation patterns among the four object categories. Adults with ASD showed no atypicalities in activation of the EBA and FFA, whereas children with ASD showed atypical activation in these regions. Specifically, a smaller percentage of children with ASD showed face-sensitive activation of the FFA than TD children. Moreover, the size of the EBA was smaller in children with ASD than in TD children. Our results revealed atypicalities in both the FFA and EBA in children with ASD but not in adults with ASD.

[Brain Mechanisms for Measuring Time: Population Coding of Durations].

Temporal processing is crucial in many aspects of our perception and action. While there is mounting evidence for the encoding mechanisms of spatial ("where") and identity ("what") information, those of temporal information ("when") remain largely unknown. Recent studies suggested that, similarly to the basic visual stimulus features such as orientation, motion direction, and numerical quantity, event durations are also represented by a population of neurons that are tuned for specific, preferred durations. This paper first reviews recent psychophysical studies on duration aftereffect. Changes in the three parameters (response gain, shift, and width of tuning curves) are then discussed that may need to be taken into account in the putative duration-channel model. Next, the potential neural basis of the duration channels is examined by overviewing recent neuroimaging and electrophysiological studies on time perception. Finally, this paper proposes a general neural basis of timing that commonly represents time-differences independent of stimulus types (e.g., a single duration v.s. multiple brief events). This extends the idea of the "when pathway" from the perception of temporal order to the general timing mechanisms for the perception of duration, temporal frequency, and synchrony.

Attenuation of the contingency detection effect in the extrastriate body area in autism spectrum disorder.

Detection of the contingency between one's own behavior and consequent social events is important for normal social development, and impaired contingency detection may be a cause of autism spectrum disorder (ASD). To depict the neural underpinnings of this contingency effect, 19 adults with ASD and 22 control participants underwent functional MRI while imitating another's actions and their actions being imitated by the other. As the extrastriate body area (EBA) receives efference copies of one's own movements, we predicted that the EBA would show an atypical response during contingency detection in ASD. We manipulated two factors: the congruency of the executed and observed actions, and the order of action execution and observation. Both groups showed the congruency effect in the bilateral EBA during imitation. When action preceded observation, the left EBA of the control group showed the congruency effect, representing the response to being imitated, indicating contingency detection. The ASD group showed a reduced contingency effect in the left EBA. These results indicate that the function of the EBA in the contingency detection is altered in ASD.

Numerical quantity affects time estimation in the suprasecond range.

Of stimuli differing in the magnitude of their numerical information, the one with the larger numerosity is perceived to last longer than that with the smaller numerosity. This numerosity-time interaction is proposed to be due to a shared neural representation for numerical magnitude and time intervals in the parietal cortex. Neuroimaging studies of temporal processing suggest that subsecond and suprasecond intervals could be mediated by distinct neural substrates. However, whether the numerosity-time interaction occurs independently of the time intervals used in the tasks remains unknown. Here we show that numerical information interacts with time estimation in the suprasecond range in females, but not in males. Our results suggest that the numerical magnitude and suprasecond intervals have shared representations in the human brain, but the associative strength between these dimensions might be different between males and females.

The neural substrates of the warning effect: a functional magnetic resonance imaging study.

To test the hypothesis the warning effect is mediated by the top-down attentional modulation of the motor system, we conducted functional MRI using a Go/No-Go task with visual and auditory warning stimuli. For aurally-warned, visually-prompted trials, the auditory warning stimulus was presented for 1500ms, during which visual cues were presented that prompted either Go or No-Go responses. The same format was used for visually-warned, aurally-prompted trials. Both auditory and visual warning cues shortened the reaction time for the Go trials. The warning cues activated the right-lateralized parieto-frontal top-down attentional network, and motor cortical areas including the pre-supplementary motor area (pre-SMA), the bilateral dorsal premotor cortex, and the left primary motor cortex (M1). The warning-related activation of the pre-SMA matched the difference between its activation by Go-with-warning and by Go-without-warning. Thus, the pre-SMA was primed by the warning cue. The same pre-SMA priming effect was observed for the No-Go cue-related activation, consistent with its role in movement preparation and selection. Similar but less prominent Go cue-related priming was observed in the M1. Thus, the warning effect represents the pre-potentiation of the motor control pathway by the top-down attentional system, from the selection and preparation of the movement to its execution.