Premovement activity in the mesocortical system links peak force but not initiation of force generation under incentive motivation.

Motivation facilitates motor performance; however, the neural substrates of the psychological effects on motor performance remain unclear. We conducted a functional magnetic resonance imaging experiment while human subjects performed a ready-set-go task with monetary incentives. Although subjects were only motivated to respond quickly, increasing the incentives improved not only reaction time but also peak grip force. However, the trial-by-trial correlation between reaction time and peak grip force was weak. Extensive areas in the mesocortical system, including the ventral midbrain (VM) and cortical motor-related areas, exhibited motivation-dependent activity in the premovement "Ready" period when the anticipated monetary reward was displayed. This premovement activity in the mesocortical system correlated only with subsequent peak grip force, whereas the activity in motor-related areas alone was associated with subsequent reaction time and peak grip force. These findings suggest that the mesocortical system linking the VM and motor-related regions plays a role in controlling the peak of force generation indirectly associated with incentives but not the initiation of force generation.

The dorsal premotor cortex encodes the step-by-step planning processes for goal-directed motor behavior in humans.

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.

Cognitive control affects motor learning through local variations in GABA within the primary motor cortex.

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 integrative role of the M1 in motor sequence learning.

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.

Enhanced structural connectivity within the motor loop in professional boxers prior to a match.

Professional boxers train to reduce their body mass before a match to refine their body movements. To test the hypothesis that the well-defined movements of boxers are represented within the motor loop (cortico-striatal circuit), we first elucidated the brain structure and functional connectivity specific to boxers and then investigated plasticity in relation to boxing matches. We recruited 21 male boxers 1 month before a match (Time1) and compared them to 22 age-, sex-, and body mass index (BMI)-matched controls. Boxers were longitudinally followed up within 1 week prior to the match (Time2) and 1 month after the match (Time3). The BMIs of boxers significantly decreased at Time2 compared with those at Time1 and Time3. Compared to controls, boxers presented significantly higher gray matter volume in the left putamen, a critical region representing motor skill training. Boxers presented significantly higher functional connectivity than controls between the left primary motor cortex (M1) and left putamen, which is an essential region for establishing well-defined movements. Boxers also showed significantly higher structural connectivity in the same region within the motor loop from Time1 to Time2 than during other periods, which may represent the refined movements of their body induced by training for the match.

Frequency-specific task modulation of human brain functional networks: A fast fMRI study.

How coherent neural oscillations are involved in task execution is a fundamental question in neuroscience. Although several electrophysiological studies have tackled this issue, the brain-wide task modulation of neural coherence remains uncharacterized. Here, with a fast fMRI technique, we studied shifts of brain-wide neural coherence across different task states in the ultraslow frequency range (0.01-0.7 Hz). First, we examined whether the shifts of the brain-wide neural coherence occur in a frequency-dependent manner. We quantified the shift of a region's average neural coherence by the inter-state variance of the mean coherence between the region and the rest of the brain. A clustering analysis based on the variance's spatial correlation between frequency components revealed four frequency bands (0.01-0.15 Hz, 0.15-0.37 Hz, 0.37-0.53 Hz, and 0.53-0.7 Hz) showing band-specific shifts of the brain-wide neural coherence. Next, we investigated the similarity of the inter-state variance's spectra between all pairs of regions. We found that regions showing similar spectra correspond to those forming functional modules of the brain network. Then, we investigated the relationship between identified frequency bands and modules' inter-state variances. We found that modules showing the highest variance are those made up of parieto-occipital regions at 0.01-0.15 Hz, while it is replaced with another consisting of frontal regions above 0.15 Hz. Furthermore, these modules showed specific shifting patterns of the mean coherence across states at 0.01-0.15 Hz and above 0.15 Hz, suggesting that identified frequency bands differentially contribute to neural interactions during task execution. Our results highlight that usage of the fast fMRI enables brain-wide investigation of neural coherence up to 0.7 Hz, which opens a promising track for assessment of the large-scale neural interactions in the ultraslow frequency range.

Quantitative Evaluations of Geometrical Distortion Corrections in Cortical Surface-Based Analysis of High-Resolution Functional MRI Data at 7T.

BACKGROUND: Although 7T functional MRI (fMRI) provides better signal-to-noise ratio and higher spatial resolution than 3T fMRI, geometric distortions become more challenging because fMRI is more susceptible to distortions than structural MRI. Accurate alignment of 7T fMRI to structural MRI data is critical for precise cortical surface-based analysis. PURPOSE: To quantify the effectiveness of distortion corrections of 7T fMRI data. STUDY TYPE: Prospective. SUBJECTS: Fifteen healthy individuals aged 19-26 years (mean: 21.9 years). FIELD STRENGTH/SEQUENCE: Multiband gradient-echo echo-planar imaging sequence at 7T; 3D T1 /T2 -weighted sequences (magnetization prepared rapid acquisition with gradient echo [MPRAGE] and sampling perfection with application optimized contrast using different flip angle evolution [SPACE]) at 3T. ASSESSMENT: fMRI data at 7T were registered to cortical surfaces reconstructed from 3T structural data acquired in the same subjects. Distortions induced by B0 inhomogeneity and gradient nonlinearity (B0 and gradient distortions) were evaluated as cortical fallout (misregistration of noncortical areas) and displacement (misregistration along gray matter). STATISTICAL TESTS: Repeated measures analyses of variance with post-hoc t-tests with Bonferroni correction. RESULTS: The accuracy of fully corrected fMRI images based on the intensity distribution was 89.2%. Without any corrections, 9.7% of vertices in the whole surfaces were fallout and the average displacement was 0.96 mm for the rest of the vertices. B0 and gradient distortion corrections significantly reduced the fallout (to 2.1% and 8.7%) and displacement (to 0.29 mm and 0.86 mm). These corrections were effective even around regions with moderate distortions (the somatosensory and visual cortices for B0 distortion, and the anterior frontal, inferior temporal, and posterior occipital cortices for gradient distortion). DATA CONCLUSION: B0 distortion correction is crucial for surface-based analysis of fine-resolution fMRI at 7T. Gradient distortion correction should be considered when regions of interest include regions distant from the isocenter of scanners. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY STAGE: 1.

Intensive granulocyte and monocyte adsorption apheresis for generalized pustular psoriasis.

Granulocyte and monocyte adsorption apheresis (GMA) is usually performed weekly (consisting of five sessions) for refractory skin diseases, such as generalized pustular psoriasis (GPP). The time to remission of inflammatory bowel diseases has been reported to be significantly shorter in intensive GMA (twice a week) than in regular GMA (once a week). Despite several reports of GPP cases treated with intensive GMA, the efficacy of intensive GMA has not been verified in GPP. Herein, we present two GPP patients with a mutation in the IL36RN gene, who initially received regular GMA, and intensive GMA upon recurrence. There were no adverse effects during regular and intensive GMA for both patients. Because concomitant medication was only prednisolone (20 mg/day) during regular and intensive GMA, intensive GMA showed superiority to regular GMA in patient 1. Although concomitant medications were different between regular and intensive GMA in patient 2, these drugs had been used before the start of each GMA therapy. We cannot neglect the effects of concomitant drugs, but we observed a shorter time to remission in intensive GMA than that in regular GMA in both patients. More case studies will be necessary for evaluating the clinical efficacy of intensive GMA.

The motor engram as a dynamic change of the cortical network during early sequence learning: An fMRI study.

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.

Prosocial behavior toward estranged persons modulates the interaction between midline cortical structures and the reward system.

Good reputation enhances positive self-image, which motivates prosocial behavior, a phenomenon known as indirect reciprocity. Thus, good reputation should promote prosocial behavior toward estranged people to whom affective responses leading to direct reciprocity are suppressed. We predicted that such behaviors involve an interrelationship between self-image, processed in the medial prefrontal cortex (mPFC) and precuneus, and social reward, processed in the reward system. To test our hypothesis, we performed fMRI on 21 participants during a virtual ball-toss game after subjects formed negative impressions (estrangement) or neutral impressions of other players. During some blocks of the game, the other players did not receive tosses, and participants could increase tosses to them (i.e. engage in prosocial behavior). Participants significantly increased tosses to all isolated players; therefore, prosocial behavior occurred irrespective of estrangement. Prosocial behavior toward estranged players enhanced positive self-image and increased activation of the anterior mPFC and precuneus. The precuneus exhibited enhanced functional connectivity with the striatum. Thus, a positive self-image, represented by an interaction between the midline cortical structures and striatum, plays key roles in prosocial behavior toward estranged people.

Neural correlates underlying change in state self-esteem.

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.

Qualitative differences in offline improvement of procedural memory by daytime napping and overnight sleep: An fMRI study.

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.

Being in a Romantic Relationship Is Associated with Reduced Gray Matter Density in Striatum and Increased Subjective Happiness.

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 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.

Increased frequency of social interaction is associated with enjoyment enhancement and reward system activation.

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.

Helping behavior induced by empathic concern attenuates anterior cingulate activation in response to others' distress.

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.

Activation cross-sections of deuteron induced reaction of natural Ni up to 40 MeV.

Production cross-sections of (nat)Ni(d,x)(56,57)Ni, (55,56,57,58)Co, (52,54)Mn, and (51)Cr nuclear reactions were measured up to 40 MeV by using the stacked foil technique. The results were compared with the literature values, TALYS 1.4 and TENDL-2012. Spline fits were made on the selected data, from which physical yields were calculated and compared with the literature and our directly measured thick target yield values. (nat)Ni(d,x)(56,57,58)Co reactions were analyzed for beam monitoring and thin layer activation (TLA). Rate of production of (55)Co was compared between proton and deuteron induced reactions.

PDK1 inhibition is a novel therapeutic target in multiple myeloma.

BACKGROUND: Cancer cells utilise the glycolytic pathway even when adequate oxygen is present, a phenomenon known as the Warburg effect. We examined whether this system is operative in multiple myeloma (MM) cells and whether glycolysis inhibition is a potential therapeutic modality. METHODS: The MM cells were purified from 59 patients using CD138-immunomagnetic beads. The expression levels of genes associated with glycolysis, c-MYC, GLUT1, LDHA, HIF1A and pyruvate dehydrogenase kinase-1 (PDK1) were determined by real-time PCR. Glucose consumption and lactate production by MM cell lines were analysed. Oxamate, an LDH inhibitor, and dichloroacetate (DCA), a PDK1 inhibitor, were employed. Inhibition of PDK1 expression was achieved using a siRNA. RESULTS: High LDHA expression was found to be an indicator of poor prognosis. It was also positively correlated with the expression of PDK1, c-MYC and GLUT1. Greater glucose consumption and lactate production in MM cells was associated with higher LDHA expression. All the glycolysis inhibitors (oxamate, DCA and PDK1 siRNA) induced apoptosis in MM cells. DCA combined with bortezomib showed additive cytotoxic effects. CONCLUSION: The present data suggest that the Warburg effect is operative in MM cells. As PDK1 is not overexpressed in normal tissues, PDK1 inhibition could serve as a novel therapeutic approach.

Development of a rapid source preparation method for high-resolution alpha-particle spectrometry.

In order to prepare sources of short-lived actinides for alpha-particle spectrometry, a coprecipitation method with Sm hydroxide was developed. The preparation procedure can be completed within 5 min with a high chemical yield of over 90%. It was found that the uniformity of the produced sources was sufficient to provide a high resolution of better than 20 keV. Under this method, we successfully measured the alpha-particle spectrum of short-lived Cf isotopes produced in the (238)U((12)C, xn) reaction.