Search

The primary motor cortex (M1) is crucial for motor learning; however, its interaction with other brain areas during motor learning remains unclear. We hypothesized that the fronto-parietal execution network (FPN) provides learning-related information critical for the flexible cognitive control that is required for practice. We assessed network-level changes during sequential finger tapping learning under speed pressure by combining magnetic resonance spectroscopy and task and resting-state functional magnetic resonance imaging. There was a motor learning-related increase in preparatory activity in the fronto-parietal regions, including the right M1, overlapping the FPN and sensorimotor network (SMN). Learning-related increases in M1-seeded functional connectivity with the FPN, but not the SMN, were associated with decreased GABA/glutamate ratio in the M1, which were more prominent in the parietal than the frontal region. A decrease in the GABA/glutamate ratio in the right M1 was positively correlated with improvements in task performance (p = 0.042). Our findings indicate that motor learning driven by cognitive control is associated with local variations in the GABA/glutamate ratio in the M1 that reflects remote connectivity with the FPN, representing network-level motor sequence learning formations.

The dorsal premotor cortex (PMd) plays an essential role in visually guided goal-directed motor behavior. Although there are several planning processes for achieving goal-directed behavior, the separate neural processes are largely unknown. Here, we created a new visuo-goal task to investigate the step-by-step planning processes for visuomotor and visuo-goal behavior in humans. Using functional magnetic resonance imaging, we found activation in different portions of the bilateral PMd during each processing step. In particular, the activated area for rule-based visuomotor and visuo-goal mapping was located at the ventrorostral portion of the bilateral PMd, that for action plan specification was at the dorsocaudal portion of the left PMd, that for transformation was at the rostral portion of the left PMd, and that for action preparation was at the caudal portion of the bilateral PMd. Thus, the left PMd was involved throughout all of the processes, but the right PMd was involved only in rule-based visuomotor and visuo-goal mapping and action preparation. The locations related to each process were generally spatially separated from each other, but they overlapped partially. These findings revealed that there are functional subregions in the bilateral PMd in humans and these subregions form a functional gradient to achieve goal-directed behavior.

The primary motor cortex (M1) is crucial in motor learning. Whether the M1 encodes the motor engram for sequential finger tapping formed by an emphasis on speed is still inconclusive. The active states of engrams are hard to discriminate from the motor execution per se. As preparatory activity reflects the upcoming movement parameters, we hypothesized that the retrieval of motor engrams generated by different learning modes is reflected as a learning-related increase in the preparatory activity of the M1. To test this hypothesis, we evaluated the preparatory activity during the learning of sequential finger-tapping with the non-dominant left hand using a 7T functional MRI. Participants alternated between performing a tapping sequence as quickly as possible (maximum mode) or at a constant speed of 2 Hz paced by a sequence-specifying visual cue (constant mode). We found a training-related increase in preparatory activity in the network covering the bilateral anterior intraparietal sulcus and inferior parietal lobule extending to the right M1 during the maximum mode and the right M1 during the constant mode. These findings indicate that the M1, as the last effector of the motor output, integrates the motor engram distributed through the networks despite training mode differences.

The primary motor cortex (M1) is crucial for motor learning. However, the interaction of the M1 with other brain areas during motor learning remains unclear. We hypothesized that the fronto-parietal execution network (FPN) provides the learning-related information that is crucial for flexible cognitive control required for practice. We assessed the network-level changes during sequential finger-tapping learning “as fast and as accurately as possible”, by combining magnetic resonance spectroscopy, task functional magnetic resonance imaging (fMRI), and resting-state fMRI methods using a 7T MR machine. An increase in the glutamate/GABA ratio in the right M1 was positively correlated with task performance improvement. There was a motor learning-related increase in preparatory activity in the fronto-parietal region, with an overlap between the FPN and sensorimotor network (SMN). The learning-related increments in M1-seeded functional connectivity with the FPN, but not the SMN, were positively correlated with changes in the glutamate/GABA ratio in M1. These connectivity changes were more prominent in the parietal region than in the frontal region. Our findings indicate that motor learning driven by cognitive control is associated with local variation in the excitatory-inhibitory balance in the M1 that reflects remote connectivity with the FPN, thereby representing the formation of declarative procedural skills.

Emotion perception from facial and vocal expressions is a multisensory process critical for human social interaction. When asked to judge emotions by attending to either face or voice, the accuracy was higher when facial expressions are congruent with vocal expressions than when they are incongruent. This congruency effect was shown to be affected by cultural background. Here we conducted functional MRI alongside a multisensory emotion perception task involving Japanese and Dutch participants. They were presented with movies in which congruent or incongruent emotions were expressed through faces and voices. The participants were asked to judge the emotion of either the face or the voice. Consistent with previous studies, behavioral results showed an interaction between group and task. fMRI results revealed that during voice-based judgement, congruency effects of the primary visual cortex, by means of the task related activity of congruent stimuli subtracted by that of incongruent stimuli, were more prominent in the Dutch group than in Japanese group. Finally, behavioral and neural congruency effects of the primary visual cortex were positively correlated only in the Dutch group. Taken together, our results show that culture affects the activities of early sensory areas in multisensory perception from facial and vocal expressions.

Daytime napping offers various benefits for healthy adults, including enhancement of motor skill learning. It remains controversial whether napping can provide the same enhancement as overnight sleep, and if so, whether the same neural underpinning is recruited. To investigate this issue, we conducted functional MRI during motor skill learning, before and after a short day-nap, in 13 participants, and compared them with a larger group (n=47) who were tested following regular overnight sleep. Training in a sequential finger-tapping task required participants to press a keyboard in the MRI scanner with their non-dominant left hand as quickly and accurately as possible. The nap group slept for 60min in the scanner after the training run, and the previously trained skill was subsequently re-tested. The whole-night sleep group went home after the training, and was tested the next day. Offline improvement of speed was observed in both groups, whereas accuracy was significantly improved only in the whole-night sleep group. Correspondingly, the offline increment in task-related activation was significant in the putamen of the whole-night group. This finding reveals a qualitative difference in the offline improvement effect between daytime napping and overnight sleep.

Neural substrates of motor engrams in the human brain are hard to identify because their dormant states are difficult to discriminate. We utilized eigenvector centrality (EC) to measure the network information that accumulates as an engram during learning. To discriminate engrams formed by emphasis on speed or accuracy, we conducted functional MRI on 58 normal volunteers as they performed a sequential finger-tapping task with the non-dominant left hand. Participants alternated between performing a tapping sequence as quickly as possible (maximum mode) or at a constant speed of 2 Hz, paced by a sequence-specifying visual cue (constant mode). We depicted the formation of the motor engram by characterizing the dormant state as the increase in EC of the resting epoch throughout the training course, and the ecphory, or activated state, as the increment in EC during the task epoch relative to the alternated resting epoch. We found that a network covering the left anterior intraparietal sulcus and inferior parietal lobule represented the engram for the speed of execution, whereas bilateral premotor cortex and right primary motor cortex represented the sequential order of movements. This constitutes the first demonstration of learning-mode specific motor engrams formed by only 30 min of training.

State self-esteem, the momentary feeling of self-worth, functions as a sociometer involved in maintenance of interpersonal relations. How others’ appraisal is subjectively interpreted to change state self-esteem is unknown, and the neural underpinnings of this process remain to be elucidated. We hypothesized that changes in state self-esteem are represented by the mentalizing network, which is modulated by interactions with regions involved in the subjective interpretation of others’ appraisal. To test this hypothesis, we conducted task-based and resting-state fMRI. Participants were repeatedly presented with their reputations, and then rated their pleasantness and reported their state self-esteem. To evaluate the individual sensitivity of the change in state self-esteem based on pleasantness (i.e., the subjective interpretation of reputation), we calculated evaluation sensitivity as the rate of change in state self-esteem per unit pleasantness. Evaluation sensitivity varied across participants, and was positively correlated with precuneus activity evoked by reputation rating. Resting-state fMRI revealed that evaluation sensitivity was positively correlated with functional connectivity of the precuneus with areas activated by negative reputation, but negatively correlated with areas activated by positive reputation. Thus, the precuneus, as the part of the mentalizing system, serves as a gateway for translating the subjective interpretation of reputation into state self-esteem.

Helping behavior is motivated by empathic concern for others in distress. Although empathic concern is pervasive in daily life, its neural mechanisms remain unclear. Empathic concern involves the suppression of the emotional response to others' distress, which occurs when individuals distance themselves emotionally from the distressed individual. We hypothesized that helping behavior induced by empathic concern, accompanied by perspective-taking, would attenuate the neural activation representing aversive feelings. We also predicted reward system activation due to the positive feeling resulting from helping behavior. Participant underwent functional magnetic resonance imaging while playing a virtual ball-toss game. In some blocks ("concern condition"), one player ("isolated player") did not receive ball-tosses from other players. In this condition, participants increased ball-tosses to the isolated player (helping behavior). Participants then evaluated the improved enjoyment of the isolated player resulting from their helping behavior. Anterior cingulate activation during the concern condition was attenuated by the evaluation of the effect of helping behavior. The right temporoparietal junction, which is involved in perspective-taking and the dorsal striatum, part of the reward system, were also activated during the concern condition. These results suggest that humans can attenuate affective arousal by anticipating the positive outcome of empathic concern through perspective-taking.

Romantic relationship, a widespread feature of human society, is one of the most influential factors in daily life. Although stimuli related to romantic love or being in a romantic relationship commonly result in enhancement of activation or functional connectivity of the reward system, including the striatum, the structure underlying romantic relationship-related regions remain unclear. Because individual experiences can alter gray matter within the adult human brain, we hypothesized that romantic relationship is associated with structural differences in the striatum related to the positive subjective experience of being in a romantic relationship. Because intimate romantic relationships contribute to perceived subjective happiness, this subjective enhancement of happiness might be accompanied by the experience of positive events related to being in a romantic relationship. To test this hypothesis and elucidate the structure involved, we compared subjective happiness, an indirect measure of the existence of positive experiences caused by being in a romantic relationship, of participants with or without romantic partners (N = 68). Furthermore, we also conducted a voxel-based morphometry (VBM) study of the effects of being in a romantic relationship (N = 113). Being in a romantic relationship was associated with greater subjective happiness and reduced gray matter density within the right dorsal striatum. These results suggest that being in a romantic relationship enhances perceived subjective happiness via positive experiences. Furthermore, the observed reduction in gray matter density in the right dorsal striatum may reflect an increase in saliency of social reward within a romantic relationship. Thus, being in a romantic relationship is associated with positive experiences and a reduction of gray matter density in the right dorsal striatum, representing a modulation of social reward.

Positive social interactions contribute to the sense that one’s life has meaning. Enjoyment of feelings associated through social interaction motivates humans to build social connections according to their personal preferences. Therefore, we hypothesized that social interaction itself activates the reward system in a manner that depends upon individual interaction preferences. To test this hypothesis, we conducted a functional magnetic resonance imaging (fMRI) study in which 38 participants played a virtual ball-toss game in which the number of ball tosses to the participant was either similar to (normal-frequency condition) or higher than (high-frequency condition) the number of tosses to the other players. Participants reported greater-than-anticipated enjoyment during the high-frequency condition, suggesting that receiving a social reward led to unexpected positive feelings. Consistent with this, the high-frequency condition produced stronger activation in the ventral striatum, which is part of the reward system, and the precuneus, representing positive self-image, which might be translated to social reward. Furthermore, ventral striatal activation covaried with individual participants’ preference for interactions with others. These findings suggest that an elevated frequency of social interaction is represented as a social reward, which might motivate individuals to promote social interaction in a manner that is modulated by personal preference.

Understanding how cells use complex transcriptional programs to alter their fate in response to specific stimuli is an important question in biology. For the MCF-7 human breast cancer cell line, we applied gene expression trajectory models to identify the genes involved in driving cell fate transitions. We modified trajectory models to account for the scenario where cells were exposed to different stimuli, in this case epidermal growth factor and heregulin, to arrive at different cell fates, i.e. proliferation and differentiation respectively. Using genome-wide CAGE time series data collected from the FANTOM5 consortium, we identified the sets of promoters that were involved in the transition of MCF-7 cells to their specific fates versus those with expression changes that were generic to both stimuli. Of the 1,552 promoters identified, 1,091 had stimulus-specific expression while 461 promoters had generic expression profiles over the time course surveyed. Many of these stimulus-specific promoters mapped to key regulators of the ERK (extracellular signal-regulated kinases) signaling pathway such as FHL2 (four and a half LIM domains 2). We observed that in general, generic promoters peaked in their expression early on in the time course, while stimulus-specific promoters tended to show activation of their expression at a later stage. The genes that mapped to stimulus-specific promoters were enriched for pathways that control focal adhesion, p53 signaling and MAPK signaling while generic promoters were enriched for cell death, transcription and the cell cycle. We identified 162 genes that were controlled by an alternative promoter during the time course where a subset of 37 genes had separate promoters that were classified as stimulus-specific and generic. The results of our study highlighted the degree of complexity involved in regulating a cell fate transition where multiple promoters mapping to the same gene can demonstrate quite divergent expression profiles.

OBJECTIVES. This preliminary study examined sensory processing and its relationship to occupational performance in children with fragile X syndrome (FXS) to guide research and evidence-based practice. METHOD. Fifteen school-aged boys with full-mutation FXS were assessed with three occupational performance measures (School Function Assessment, Vineland Adaptive Behavior Scales, play duration) and three sensory processing measures (Sensory Profile, Tactile Defensiveness and Discrimination Test–Revised, Sensory Approach–Avoidance Rating). Data were analyzed using partial correlation procedures. RESULTS. Several significant correlations were found, independent of effects of age and IQ. Avoidance of sensory experiences (internally controlled) was associated with lower levels of school participation, self-care, and play. Aversion to touch from externally controlled sources was associated with a trend toward greater independence in self-care—opposite of expectations. CONCLUSION. This study links sensory processing vulnerabilities with individual differences in occupational performance and supports a dynamic view of self-organizing systems. Children’s uses of avoidant versus independent behaviors may reflect different self-regulatory or coping strategies that potentially mediate the relationship between sensory processing deficits and occupational behaviors and warrant further investigation.

We evaluated the effect of YM022 [(R)-1-[2,3-dihydro-1-(2'- methylphenacyl)-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl]-3- (3-methylphenyl)urea], a potent and selective gastrin/cholecystokinin-B receptor antagonist, on gastric acid secretion and gastric and duodenal lesions in rats. Oral YM022 (0.1-10 mumol/kg), famotidine (0.3-30 mumol/kg) and omeprazole (3-100 mumol/kg) dose-dependently suppressed acid secretion in pylorusligated rats with ED50 values of 0.83, 1.63 and 10.9 mumol/kg, respectively. YM022 (1-10 mumol/kg p.o.), famotidine (1-10 mumol/kg p.o.) and omeprazole (10-100 mumol/kg p.o.) prevented indomethacin-induced gastric lesions in a dose-related manner. The potency of YM022 was comparable to that of famotidine and was 8 times greater than that of omeprazole. YM022 and famotidine partially inhibited gastric damage induced by water-immersion and restraint stress, whereas omeprazole abolished these lesions. In an acidified ethanol-induced gastric injury model, all three drugs inhibited the formation of erosions. The YM022 dosage required in this model was much greater than that required in the inhibition of gastric acid. The inhibitory effect of YM022 was partially reversed by indomethacin, indicating the involvement of a prostaglandin-mediated pathway. YM022 (3-100 mumol/kg p.o.), famotidine (1-30 mumol/kg p.o.) and omeprazole (3-100 mumol/kg p.o.) inhibited mepirizole-induced duodenal ulcers. On the basis of ED50 values, YM022 was 5 times less potent than famotidine and as potent as omeprazole against mepirizole-induced duodenal ulcers. These results suggest that YM022 possesses antisecretory and antiulcer activities that are as potent as those of famotidine in rats and that YM022 represents a useful therapeutic agent in the treatment of peptic ulcer disease.