An easy-to-implement, non-invasive head restraint method for monkey fMRI.

Functional magnetic resonance imaging (fMRI) in behaving monkeys has a strong potential to bridge the gap between human neuroimaging and primate neurophysiology. In monkey fMRI, to restrain head movements, researchers usually surgically implant a plastic head-post on the skull. Although time-proven to be effective, this technique could create burdens for animals, including a risk of infection and discomfort. Furthermore, the presence of extraneous objects on the skull, such as bone screws and dental cement, adversely affects signals near the cortical surface. These side effects are undesirable in terms of both the practical aspect of efficient data collection and the spirit of "refinement" from the 3R's. Here, we demonstrate that a completely non-invasive fMRI scan in awake monkeys is possible by using a plastic head mask made to fit the skull of individual animals. In all of the three monkeys tested, longitudinal, quantitative assessment of head movements showed that the plastic mask has effectively suppressed head movements, and we were able to obtain reliable retinotopic BOLD signals in a standard retinotopic mapping task. The present, easy-to-make plastic mask has a strong potential to simplify fMRI experiments in awake monkeys, while giving data that is as good as or even better quality than that obtained with the conventional head-post method.

Distinctive modes of cortical communications in tactile temporal order judgment.

Temporal order judgment of two successive tactile stimuli delivered to our hands is often inverted when we cross our hands. The present study aimed to identify time-frequency profiles of the interactions across the cortical network associated with the crossed-hand tactile temporal order judgment task using magnetoencephalography. We found that the interactions across the cortical network were channeled to a low-frequency band (5-10 Hz) when the hands were uncrossed. However, the interactions became activated in a higher band (12-18 Hz) when the hands were crossed. The participants with fewer inverted judgments relied mainly on the higher band, whereas those with more frequent inverted judgments (reversers) utilized both. Moreover, reversers showed greater cortical interactions in the higher band when their judgment was correct compared to when it was inverted. Overall, the results show that the cortical network communicates in two distinctive frequency modes during the crossed-hand tactile temporal order judgment task. A default mode of communications in the low-frequency band encourages inverted judgments, and correct judgment is robustly achieved by recruiting the high-frequency mode.

Neural Correlates of Temporal Presentness in the Precuneus: A Cross-linguistic fMRI Study based on Speech Stimuli.

The position of any event in time could be in the present, past, or future. This temporal discrimination is vitally important in our daily conversations, but it remains elusive how the human brain distinguishes among the past, present, and future. To address this issue, we searched for neural correlates of presentness, pastness, and futurity, each of which is automatically evoked when we hear sentences such as "it is raining now," "it rained yesterday," or "it will rain tomorrow." Here, we show that sentences that evoked "presentness" activated the bilateral precuneus more strongly than those that evoked "pastness" or "futurity." Interestingly, this contrast was shared across native speakers of Japanese, English, and Chinese languages, which vary considerably in their verb tense systems. The results suggest that the precuneus serves as a key region that provides the origin (that is, the Now) of our time perception irrespective of differences in tense systems across languages.

Automatic encoding of a target position relative to a natural scene.

We previously showed that the brain automatically represents a target position for reaching relative to a large square in the background. In the present study, we tested whether a natural scene with many complex details serves as an effective background for representing a target. In the first experiment, we used upright and inverted pictures of a natural scene. A shift of pictures significantly attenuated prism adaptation of reaching movements as long as they were upright. In one-third of participants, adaptation was almost completely cancelled whether the pictures were upright or inverted. It was remarkable that there were two distinct groups of participants, one who relies fully on the allocentric coordinate and the other who depended only when the scene was upright. In the second experiment, we examined how long it takes for a novel upright scene to serve as a background. A shift of the novel scene had no significant effects when it was presented for 500 ms before presenting a target, but significant effects were recovered when presented for 1,500 ms. These results show that a natural scene serves as a background against which a target is automatically represented once we spend 1,500 ms in the scene.NEW & NOTEWORTHY Prism adaptation of reaching was attenuated by a shift of natural scenes as long as they were upright. In one-third of participants, adaptation was fully canceled whether the scene was upright or inverted. When an upright scene was novel, it took 1,500 ms to prepare the scene for allocentric coding. These results show that a natural scene serves as a background against which a target is automatically represented once we spend 1,500 ms in the scene.

Modulation of Illusory Reversal in Tactile Temporal Order by the Phase of Posterior α Rhythm.

The subjective temporal order of tactile stimuli, delivered sequentially to each hand with an interval of 100-300 ms, is often inverted when the arms are crossed. Based on data from behavioral and neuroimaging studies, it has been proposed that the reversal is due to a conflict between anatomical and spatial representations of the tactile signal or to the production of an inverted apparent motion signal. Because the α rhythms, which consist of a few distinct components, reportedly modulate tactile perception and apparent motion and serve as a 10 Hz timer, we hypothesized that the illusory reversal would be regulated by some of the α rhythms. To test this hypothesis, we conducted magnetoencephalographic recordings in both male and female participants during the tactile temporal order judgment task. We decomposed the α rhythms into five independent components and discovered that the illusory reversal was modulated by the phase of one independent component with strong current sources near the parieto-occipital (PO) sulcus (peri-PO component). As expected, the estimated current sources distributed over the human MST implicated to represent tactile apparent motion, in addition to the intraparietal region implicated in mapping tactile signals in space. However, the strongest source was located in the precuneus that occupies a central hub region in the cortical networks and receives tactile inputs through a tecto-thalamic pathway. These results suggest that the peri-PO component plays an essential role in regulating tactile temporal perception by modulating the thalamic nuclei that interconnect the superior colliculus with the cortical networks.SIGNIFICANCE STATEMENT Despite a long-held hypothesis that the posterior α rhythm serves as a 10 Hz timer that regulates human temporal perception, the contribution of the α rhythms in temporal perception is still unclear. We examined how the α rhythms influence tactile temporal order judgment. Judgment reversal depended on the phase of one particular α rhythm with its source near the parieto-occipital sulcus. The peri-parieto-occipital α rhythm may play a crucial role in organizing tactile temporal perception.

Short-latency allocentric control of saccadic eye movements.

It is generally accepted that the neural circuits that are implicated in saccade control use retinotopically coded target locations. However, several studies have revealed that nonretinotopic representation is also used. This idea raises a question about whether nonretinotopic coding is egocentric (head or body centered) or allocentric (environment centered). In the current study, we hypothesized that allocentric coding may play a crucial role in immediate saccade control. To test this hypothesis, we used an immediate double-step saccade task toward two sequentially flashed targets with a frame in the background, and we examined whether the end point of the second saccade was affected by a transient shift of the background that participants were told to ignore. When the background was shifted transiently upward (or downward) during the flash of the second target, the second saccade generally erred the target downward (or upward), which was in the direction opposite to the shift of the background. The effect on the second saccade became significant within 150 ms after the frame was presented for decoding and was built up for 200 ms thereafter. When the second saccade was not adjusted, a small, corrective saccade followed within 300 ms. The effect scaled linearly with the shift size up to 3° for a noncorrective second saccade and up to 6° for a corrective saccade. The present results show that an allocentric location of a target is rapidly represented by the brain and used for controlling saccades. NEW & NOTEWORTHY: We found that the saccade end point was shifted from the actual target position toward the direction expected from allocentric coding when a large frame in the background was transiently shifted during the period of target presentation. The effect occurred within 150 ms. The present study provides direct evidence that the brain rapidly uses allocentric coding of a target to control immediate saccades.

Blink-related momentary activation of the default mode network while viewing videos.

It remains unknown why we generate spontaneous eyeblinks every few seconds, more often than necessary for ocular lubrication. Because eyeblinks tend to occur at implicit breakpoints while viewing videos, we hypothesized that eyeblinks are actively involved in the release of attention. We show that while viewing videos, cortical activity momentarily decreases in the dorsal attention network after blink onset but increases in the default-mode network implicated in internal processing. In contrast, physical blackouts of the video do not elicit such reciprocal changes in brain networks. The results suggest that eyeblinks are actively involved in the process of attentional disengagement during a cognitive behavior by momentarily activating the default-mode network while deactivating the dorsal attention network.

Three timescales in prism adaptation.

It has been proposed that motor adaptation depends on at least two learning systems, one that learns fast but with poor retention and another that learns slowly but with better retention (Smith MA, Ghazizadeh A, Shadmehr R. PLoS Biol 4: e179, 2006). This two-state model has been shown to account for a range of behavior in the force field adaptation task. In the present study, we examined whether such a two-state model could also account for behavior arising from adaptation to a prismatic displacement of the visual field. We first confirmed that an "adaptation rebound," a critical prediction of the two-state model, occurred when visual feedback was deprived after an adaptation-extinction episode. We then examined the speed of decay of the prism aftereffect (without any visual feedback) after repetitions of 30, 150, and 500 trials of prism exposure. The speed of decay decreased with the number of exposure trials, a phenomenon that was best explained by assuming an "ultraslow" system, in addition to the fast and slow systems. Finally, we compared retention of aftereffects 24 h after 150 or 500 trials of exposure: retention was significantly greater after 500 than 150 trials. This difference in retention could not be explained by the two-state model but was well explained by the three-state model as arising from the difference in the amount of adaptation of the "ultraslow process." These results suggest that there are not only fast and slow systems but also an ultraslow learning system in prism adaptation that is activated by prolonged prism exposure of 150-500 trials.

Modulation of error-sensitivity during a prism adaptation task in people with cerebellar degeneration.

Cerebellar damage can profoundly impair human motor adaptation. For example, if reaching movements are perturbed abruptly, cerebellar damage impairs the ability to learn from the perturbation-induced errors. Interestingly, if the perturbation is imposed gradually over many trials, people with cerebellar damage may exhibit improved adaptation. However, this result is controversial, since the differential effects of gradual vs. abrupt protocols have not been observed in all studies. To examine this question, we recruited patients with pure cerebellar ataxia due to cerebellar cortical atrophy (n = 13) and asked them to reach to a target while viewing the scene through wedge prisms. The prisms were computer controlled, making it possible to impose the full perturbation abruptly in one trial, or build up the perturbation gradually over many trials. To control visual feedback, we employed shutter glasses that removed visual feedback during the reach, allowing us to measure trial-by-trial learning from error (termed error-sensitivity), and trial-by-trial decay of motor memory (termed forgetting). We found that the patients benefited significantly from the gradual protocol, improving their performance with respect to the abrupt protocol by exhibiting smaller errors during the exposure block, and producing larger aftereffects during the postexposure block. Trial-by-trial analysis suggested that this improvement was due to increased error-sensitivity in the gradual protocol. Therefore, cerebellar patients exhibited an improved ability to learn from error if they experienced those errors gradually. This improvement coincided with increased error-sensitivity and was present in both groups of subjects, suggesting that control of error-sensitivity may be spared despite cerebellar damage.

Automatic representation of a visual stimulus relative to a background in the right precuneus.

Our brains represent the position of a visual stimulus egocentrically, in either retinal or craniotopic coordinates. In addition, recent behavioral studies have shown that the stimulus position is automatically represented allocentrically relative to a large frame in the background. Here, we investigated neural correlates of the 'background coordinate' using an fMRI adaptation technique. A red dot was presented at different locations on a screen, in combination with a rectangular frame that was also presented at different locations, while the participants looked at a fixation cross. When the red dot was presented repeatedly at the same location relative to the rectangular frame, the fMRI signals significantly decreased in the right precuneus. No adaptation was observed after repeated presentations relative to a small, but salient, landmark. These results suggest that the background coordinate is implemented in the right precuneus.

Cancelling prism adaptation by a shift of background: a novel utility of allocentric coordinates for extracting motor errors.

Many previous studies have reported that our brains are able to encode a target position not only in body-centered coordinates but also in terms of landmarks in the background. The importance of such allocentric memory increases when we are forced to complete a delayed reaching task after the target has disappeared. However, the merit of allocentric memory in natural situations in which we are free to make an immediate reach toward a target has remained elusive. We hypothesized that allocentric memory is essential even in an immediate reach for dissociating between error attributable to the motor system and error attributable to target motion. We show here in humans that prism adaptation, that is, adaptation of reaching movements in response to errors attributable to displacement of the visual field, can be cancelled or enhanced simply by moving the background in mid-flight of the reaching movement. The results provide direct evidence for the novel contribution of allocentric memory in providing information on "where I intended to go," thereby discriminating the effect of target motion from the error resulting from the issued motor control signals.

Neural correlates of tactile temporal-order judgment in humans: an fMRI study.

Little is known about the neuronal mechanisms underlying the temporal ordering of tactile signals. We examined the brain regions involved in judgments of the temporal order of successive taps delivered to both hands. Participants received identical stimuli while engaging in 2 different tasks: Judging the temporal order and judging the numerosity of points of tactile stimulation. Comparisons of the functional magnetic resonance imaging data obtained during the 2 tasks revealed regions that were more strongly activated with the judgments of the temporal order than with the judgments of numerosity under both arms-uncrossed and -crossed conditions: The bilateral premotor cortices, the bilateral middle frontal gyri, the bilateral inferior parietal cortices and supramarginal gyri, and the bilateral posterior part of the superior and middle temporal gyri. Stronger activation was found in some of these areas that implicated for remapping tactile stimuli to spatial coordinates after the participants crossed their arms. The activation in the perisylvian areas overlapped with the human visual-motion-sensitive areas in the posterior part. Based on these results, we propose that the temporal order of tactile signals is determined by combining spatial representations of stimuli in the parietal and prefrontal cortices with representations of "motion" or "changes" in the multisensory perisylvian cortex.

Ready to detect a reversal of time's arrow: a psychophysical study using short video clips in daily scenes.

It is generally believed that time flows in one direction and that a reversal of time's arrow would render the external world non-sensical. We evaluated our ability to tell the direction of time's arrow in a wide range of dynamic scenes in our daily life by presenting 360 video clips in the correct or incorrect direction. Participants, who judged the direction in a speeded manner, erred in 39% of trials when a video was played in reverse, but in only 9% when it was played normally. Due to the bias favouring the 'forward' judgement, the reaction was generally faster for the forward response. However, the reaction became paradoxically faster and more synchronous for the detection of reversal in some critical occasions such as forward motion, free fall, diffusion, division and addition of materials by hand. Another experiment with a fraction of the video clips revealed that reversal replay of these videos provided instantaneous evidence strong enough to overtake the forward judgement bias. We suggest that our brain is equipped with a system that predicts how the external organisms behave or move in these critical occasions and that the prediction error of the system contributes to the fast 'reversal' detection.

Influence of skin blood flow on near-infrared spectroscopy signals measured on the forehead during a verbal fluency task.

Brain activity during a verbal fluency task (VFT) has been the target of many functional imaging studies. Most studies using near-infrared spectroscopy (NIRS) have reported major activation in the frontal pole, but those using PET or fMRI have not. This led us to hypothesize that changes in the NIRS signals measured in the forehead during VFT were due to changes in skin blood flow. To test this hypothesis, we measured NIRS signals and the Doppler tissue blood flow signals in the foreheads of 50 participants. The measurements were performed while each participant produced words during two 60-s periods with an interval of 100 s. In addition to a conventional optode separation distance of 30 mm (FAR channels), we used a short distance--5mm (NEAR channels)--to measure NIRS signals that originated exclusively from surface tissues. The oxygenated hemoglobin (oxyHb) concentration in the FAR and NEAR channels, as well as the Doppler blood flow signal, increased in a similar manner during the two periods of word production; the signal increase in the first period was twice as high as that in the second period. Accordingly, the mean changes in oxyHb concentration in the FAR channels were correlated closely with the changes in the NEAR channels (R(2) = 0.91) and with the integrated Doppler skin blood flow signal (R(2) = 0.94). Furthermore, task-related NIRS responses disappeared when we blocked skin blood flows by pressing a small area that covered a pair of optodes. Additionally, changes in the FAR channel signals were correlated closely with the magnitude of pulsatile waves in the Doppler signal (R(2) = 0.92), but these signals were not highly correlated with the pulse rate (R(2) = 0.43). These results suggest that a major part of the task-related changes in the oxyHb concentration in the forehead is due to task-related changes in the skin blood flow, which is under different autonomic control than heart rate.

Applying independent component analysis to detect silent speech in magnetic resonance imaging signals.

Independent component analysis (ICA) can be usefully applied to functional imaging studies to evaluate the spatial extent and temporal profile of task-related brain activity. It requires no a priori assumptions about the anatomical areas that are activated or the temporal profile of the activity. We applied spatial ICA to detect a voluntary but hidden response of silent speech. To validate the method against a standard model-based approach, we used the silent speech of a tongue twister as a 'Yes' response to single questions that were delivered at given times. In the first task, we attempted to estimate one number that was chosen by a participant from 10 possibilities. In the second task, we increased the possibilities to 1000. In both tasks, spatial ICA was as effective as the model-based method for determining the number in the subject's mind (80-90% correct per digit), but spatial ICA outperformed the model-based method in terms of time, especially in the 1000-possibility task. In the model-based method, calculation time increased by 30-fold, to 15 h, because of the necessity of testing 1000 possibilities. In contrast, the calculation time for spatial ICA remained as short as 30 min. In addition, spatial ICA detected an unexpected response that occurred by mistake. This advantage was validated in a third task, with 13 500 possibilities, in which participants had the freedom to choose when to make one of four responses. We conclude that spatial ICA is effective for detecting the onset of silent speech, especially when it occurs unexpectedly.

What Underlies a Greater Reversal in Tactile Temporal Order Judgment When the Hands Are Crossed? A Structural MRI Study.

Our subjective temporal order of two successive tactile stimuli, delivered one to each hand, is often inverted when our hands are crossed. However, there is great variability among different individuals. We addressed the question of why some show almost complete reversal, but others show little reversal. To this end, we obtained structural magnetic resonance imaging data from 42 participants who also participated in the tactile temporal order judgment (TOJ) task. We extracted the cortical thickness and the convoluted surface area as cortical characteristics in 68 regions. We found that the participants with a thinner, larger, and more convoluted cerebral cortex in 10 regions, including the right pars-orbitalis, right and left postcentral gyri, left precuneus, left superior parietal lobule, right middle temporal gyrus, left superior temporal gyrus, right cuneus, left supramarginal gyrus, and right rostral middle frontal gyrus, showed a smaller degree of judgment reversal. In light of major theoretical accounts, we suggest that cortical elaboration in the aforementioned regions improve the crossed-hand TOJ performance through better integration of the tactile stimuli with the correct spatial representations in the left parietal regions, better representation of spatial information in the postcentral gyrus, or improvement of top-down inhibitory control by the right pars-orbitalis.

Deficit in visual temporal integration in autism spectrum disorders.

Individuals with autism spectrum disorders (ASD) are superior in processing local features. Frith and Happe conceptualize this cognitive bias as 'weak central coherence', implying that a local enhancement derives from a weakness in integrating local elements into a coherent whole. The suggested deficit has been challenged, however, because individuals with ASD were not found to be inferior to normal controls in holistic perception. In these opposing studies, however, subjects were encouraged to ignore local features and attend to the whole. Therefore, no one has directly tested whether individuals with ASD are able to integrate local elements over time into a whole image. Here, we report a weakness of individuals with ASD in naming familiar objects moved behind a narrow slit, which was worsened by the absence of local salient features. The results indicate that individuals with ASD have a clear deficit in integrating local visual information over time into a global whole, providing direct evidence for the weak central coherence hypothesis.

Atypical gaze patterns in children and adults with autism spectrum disorders dissociated from developmental changes in gaze behaviour.

Eye tracking has been used to investigate gaze behaviours in individuals with autism spectrum disorder (ASD). However, traditional analysis has yet to find behavioural characteristics shared by both children and adults with ASD. To distinguish core ASD gaze behaviours from those that change with development, we examined temporo-spatial gaze patterns in children and adults with and without ASD while they viewed video clips. We summarized the gaze patterns of 104 participants using multidimensional scaling so that participants with similar gaze patterns would cluster together in a two-dimensional plane. Control participants clustered in the centre, reflecting a standard gaze behaviour, whereas participants with ASD were distributed around the periphery. Moreover, children and adults were separated on the plane, thereby showing a clear effect of development on gaze behaviours. Post hoc frame-by-frame analyses revealed the following findings: (i) both ASD groups shifted their gaze away from a speaker earlier than the control groups; (ii) both ASD groups showed a particular preference for letters; and (iii) typical infants preferred to watch the mouth rather than the eyes during speech, a preference that reversed with development. These results highlight the importance of taking the effect of development into account when addressing gaze behaviours characteristic of ASD.

Eyeblink entrainment at breakpoints of speech.

The eyes play an essential role in social communication. Eyeblinks, however, have thus far received minor attention. We previously showed that subjects blink in synchrony while viewing the same video stories (Nakano et al. in Proc R Soc B 276:3635-3644, 2009). We therefore hypothesized that eyeblinks are synchronized between listener and speaker in face-to-face conversation. Here, we show that listeners blinked with a delay of 0.25-0.5 s after the speaker blinked when the listeners viewed close-up video clips (with sound) of the speaker's face. Furthermore, this entrainment was selectively triggered by speaker's eyeblinks occurring at the end and during pauses in speech. Eyeblink entrainment was not observed when viewing identical video clips without sound, indicating that blink entrainment was not an automatic imitation. We therefore suggest that eyeblink entrainment reflects smooth communication between interactants.

Bayesian calibration of simultaneity in tactile temporal order judgment.

Human judgment of the temporal order of two sensory signals is liable to change depending on our prior experiences. Previous studies have reported that signals presented at short intervals but in the same order as the most frequently repeated signal are perceived as occurring simultaneously. Here we report opposite perceptual changes that conform to a Bayesian integration theory in judging the order of two stimuli delivered one to each hand.