Adaptation of the Corticomuscular and Biomechanical Systems of Pianists.

Independent control of movements between the fingers plays a role in hand dexterity characterizing skilled individuals. However, it remains unknown whether and in what manner neuromuscular and biomechanical constraints on the movement independence of the fingers depend on motor expertise. Here, we compared motor dexterity, corticospinal excitability of multiple muscles, muscular activation, and anatomical features of the fingers between the pianists and nonpianists. When the ring finger was passively moved by a robot, passive motions produced at the adjacent fingers were smaller for the pianists than the nonpianists, indicating reduced biomechanical constraint of fingers in the pianists. In contrast, when the ring finger moved actively, we found no group difference in passive motions produced at the adjacent fingers; however, reduced inhibition of corticospinal excitability of the adjacent fingers in the pianists compared with the nonpianists. This suggests strengthened neuromuscular coupling between the fingers of the pianists, enhancing the production of coordinated finger movements. These group differences were not evident during the index and little finger movements. Together, pianists show expertise-dependent biomechanical and neurophysiological adaptations, specifically at the finger with innately low movement independence. Such contrasting adaptations of pianists may subserve dexterous control of both the individuated and coordinated finger movements.

Modulation of cerebellar brain inhibition during temporal adaptive learning in a coincident timing task.

In the present study, we examined the role of the cerebellum in temporal adaptive learning during a coincident timing task, i.e., a baseball-like hitting task involving a moving ball presented on a computer monitor. The subjects were required to change the timing of their responses based on imposed temporal perturbations. Using paired-pulse transcranial magnetic stimulation, we measured cerebellar brain inhibition (CBI) before, during, and after the temporal adaptive learning. Reductions in CBI only occurred during and after the temporal adaptive learning, regardless of the direction of the temporal perturbations. In addition, the changes in CBI were correlated with the magnitude of the adaptation. Here, we showed that the cerebellum is essential for learning about and controlling the timing of movements during temporal adaptation. Furthermore, changes in cerebellar-primary motor cortex connectivity occurred during temporal adaptation, as has been previously reported for spatial adaptation.

Specialized Somatosensory-Motor Integration Functions in Musicians.

Somatosensory signals play roles in the fine control of dexterous movements through a somatosensory-motor integration mechanism. While skilled individuals are typically characterized by fine-tuned somatosensory functions and dexterous motor skills, it remains unknown whether and in what manner their bridging mechanism, the tactile-motor and proprioceptive-motor integration functions, plastically changes through extensive sensorimotor experiences. Here, we addressed this issue by comparing physiological indices of these functions between pianists and nonmusicians. Both tactile and proprioceptive stimuli to the right index finger inhibited corticospinal excitability measured by a transcranial magnetic stimulation method. However, the tactile and proprioceptive stimuli exerted weaker and stronger inhibitory effects, respectively, on corticospinal excitability in pianists than in nonmusicians. The results of the electroencephalogram measurements revealed no significant group difference in the amplitude of cortical responses to the somatosensory stimuli around the motor and somatosensory cortices, suggesting that the group difference in the inhibitory effects reflects neuroplastic adaptation of the somatosensory-motor integration functions in pianists. Penalized regression analyses further revealed an association between these integration functions and motor performance in the pianists, suggesting that extensive piano practice reorganizes somatosensory-motor integration functions so as to enable fine control of dexterous finger movements during piano performances.

Reorganization of finger covariation patterns represented in the corticospinal system by learning of a novel movement irrelevant to common daily movements.

How dexterous finger movements are acquired by the nervous system is a fundamental question in the neuroscience field. Previous studies have demonstrated that finger movements can be decomposed into finger covariation patterns, and these patterns are represented in the corticospinal system. However, it remains unclear how such covariation patterns represented in the corticospinal system develop during the acquisition of novel finger movements. In this study, each subject learned to perform a novel finger movement, which was mapped to a region outside the movement subspace spanned by common finger movements seen in daily life, through a custom task. After subjects practiced the task, we detected changes in the finger covariation patterns derived from artificially (transcranial magnetic stimulation) evoked finger joint movements. The artificially evoked movement-derived patterns seen after the training period were associated with both the novel and common finger movements. Regarding the patterns extracted from the artificially evoked movements, the number required to explain most of the variance in the data was unchanged after the training period. Our results indicate that novel finger movements are acquired through the reorganization of preexisting finger covariation patterns represented in the corticospinal system rather than the development of new patterns. These findings might have implications for the basic mechanism responsible for the development of movement repertories in the nervous system.NEW & NOTEWORTHY Various types of finger movements involve common finger covariation patterns, and these patterns are represented in the corticospinal system. Here we examined how a novel finger covariation pattern is acquired in that system through training of a novel finger movement that is irrelevant to common finger movements. Using transcranial magnetic stimulation, we found that the preexisting patterns that contribute to finer control of finger movements are rapidly reorganized to encode the novel pattern through the training.

Acquisition of skilled finger movements is accompanied by reorganization of the corticospinal system.

Dexterous finger movements are often characterized by highly coordinated movements. Such coordination might be derived from reorganization of the corticospinal system. In this study, we investigated 1) the manner in which finger movement covariation patterns are acquired, by examining the effects of the implicit and explicit learning of a serial reaction time task (SRTT), and 2) how such changes in finger coordination are represented in the corticospinal system. The subjects learned a button press sequence in both implicit and explicit learning conditions. In the implicit conditions, they were naive about what they were learning, whereas in the explicit conditions the subjects consciously learned the order of the sequence elements. Principal component analysis decomposed both the voluntary movements produced during the SRTT and the passive movements evoked by transcranial magnetic stimulation (TMS) over the primary motor cortex into a set of five finger joint covariation patterns. The structures of the voluntary and passive TMS-evoked movement patterns were reorganized by implicit learning but not explicit learning. Furthermore, in the implicit learning conditions the finger covariation patterns derived from the TMS-evoked and voluntary movements spanned similar movement subspaces. These results provide the first evidence that skilled sequential finger movements are acquired differently through implicit and explicit learning, i.e., the changes in finger coordination patterns induced by implicit learning are accompanied by functional reorganization of the corticospinal system, whereas explicit learning results in faster recruitment of individual finger movements without causing any changes in finger coordination. NEW & NOTEWORTHY Skilled sequential multifinger movements are characterized as highly coordinated movement patterns. These finger coordination patterns are represented in the corticospinal system, yet it still remains unclear how these patterns are acquired through implicit and explicit motor sequence learning. A direct comparison of learning-related changes between actively generated finger movements and passively evoked finger movements by TMS provided evidence that finger coordination patterns represented in the corticospinal system are reorganized through implicit, but not explicit, sequence learning.

Functional difference in short- and long-latency interhemispheric inhibitions from active to resting hemisphere during a unilateral muscle contraction.

The aim of the present study was to investigate whether there is a functional difference in short-latency (SIHI) and long-latency (LIHI) interhemispheric inhibition from the active to the resting primary motor cortex (M1) with paired-pulse transcranial magnetic stimulation during a unilateral muscle contraction. In nine healthy right-handed participants, IHI was tested from the dominant to the nondominant M1 and vice versa under resting conditions or during performance of a sustained unilateral muscle contraction with the right or left first dorsal interosseous muscle at 10% and 30% maximum voluntary contraction. To obtain measurements of SIHI and LIHI, a conditioning stimulus (CS) was applied over the M1 contralateral to the muscle contraction, followed by a test stimulus over the M1 ipsilateral to the muscle contraction at short (10 ms) and long (40 ms) interstimulus intervals. We used four CS intensities to investigate SIHI and LIHI from the active to the resting M1 systematically. The amount of IHI during the unilateral muscle contractions showed a significant difference between SIHI and LIHI, but the amount of IHI during the resting condition did not. In particular, SIHI during the muscle contractions, but not LIHI, significantly increased with increase in CS intensity compared with the resting condition. Laterality of IHI was not detected in any of the experimental conditions. The present study provides novel evidence that a functional difference between SIHI and LIHI from the active to the resting M1 exists during unilateral muscle contractions.

Active perceptual learning involves motor exploration and adaptation of predictive sensory integration.

Our ability to perceive both externally generated and self-generated sensory stimuli can be enhanced through training, known as passive and active perceptual learning (APL). Here, we sought to explore the mechanisms underlying APL by using active haptic training (AHT), which has been demonstrated to enhance the somatosensory perception of a finger in a trained motor skill. In total 120 pianists participated in this study. First, AHT reorganized the muscular coordination during the piano keystroke. Second, AHT increased the relative reliance on afferent sensory information relative to predicted one, in contrast to no increment of overall perceptual sensitivity. Finally, AHT improved feedback movement control of keystrokes. These results suggest that APL involves active exploration and adaptation of predictive sensory integration, which underlies the co-enhancement of active perception and feedback control of movements of well-trained individuals.

Passive somatosensory training enhances piano skill in adolescent and adult pianists: A preliminary study.

Sensory afferent information, such as auditory and somatosensory feedback while moving, plays a crucial role in both control and learning of motor performance across the lifespan. Music performance requires skillful integration of multimodal sensory information for the production of dexterous movements. However, it has not been understood what roles somatosensory afferent information plays in the acquisition and sophistication of specialized motor skills of musicians across different stages of development. In the present preliminary study, we addressed this issue by using a novel technique with a hand exoskeleton robot that can externally move the fingers of pianists. Short-term exposure to fast and complex finger movements generated by the exoskeleton (i.e., passive movements) increased the maximum rate of repetitive piano keystrokes by the pianists. This indicates that somatosensory inputs derived from the externally generated motions enhanced the quickness of the sequential finger movements in piano performance, even though the pianists did not voluntarily move the fingers. The enhancement of motor skill through passive somatosensory training using the exoskeleton was more pronounced in adolescent pianists than adult pianists. These preliminary results implicate a sensitive period of neuroplasticity of the somatosensory-motor system of trained pianists, which emphasizes the importance of somatosensory-motor training in professional music education during adolescence.

Multisensory interactions on auditory and somatosensory information in expert pianists.

Fine-tuned sensory functions typically characterize skilled individuals. Although numerous studies demonstrated enhanced unimodal sensory functions at both neural and behavioral levels in skilled individuals, little is known about their multisensory interaction function, especially multisensory integration and selective attention that involve volitional control of information derived from multiple sensory organs. In the current study, expert pianists and musically untrained individuals performed five sets of intensity discrimination tasks at the auditory and somatosensory modalities with different conditions: (1) auditory stimulus, (2) somatosensory stimulus, (3) congruent auditory and somatosensory stimuli (i.e., multisensory integration), (4) auditory and task-irrelevant somatosensory stimuli, and (5) somatosensory and task-irrelevant auditory stimuli. In the fourth and fifth conditions, participants were instructed to ignore a task-irrelevant stimulus and to pay attention to a task-relevant stimulus (i.e., selective attention), respectively. While the discrimination perception was superior in the condition (3) compared to the better one of the individual unimodal conditions only in the pianists, the task-irrelevant somatosensory stimulus worsened the auditory discrimination more in the pianists than the nonmusicians. These findings indicate unique multisensory interactions in expert pianists, which enables pianists to efficiently integrate the auditory and somatosensory information, but exacerbates top-down selective inhibition of somatosensory information during auditory processing.

Effects of ozonized glycerin on inflammation of mammary glands induced by intramammary lipopolysaccharide infusion in goats.

Although ozone shows antimicrobial activity against mastitis-causing pathogens in ruminants, its anti-inflammatory effect on mammary glands remains unclear. The aim of this study was to examine the anti-inflammatory effects of ozonized glycerin (OG) on experimentally induced inflammation in the mammary glands of six Shiba and two Tokara lactating goats. We infused 1 µg lipopolysaccharide (LPS) into all udders on day -1. On day 0, post LPS infusion, OG (ozone group), and glycerin (control group) were infused into the right and left sides of the udders, respectively. Milk samples were collected once daily from days -1 to 7. The somatic cell count and lactoperoxidase (LPO) activity, along with the interleukin-1ß (IL-1ß), tumor necrosis factor-α, IL-8, IL-10, lactoferrin, and sodium ion concentrations in milk were measured. IL-8, IL-10, and lactoferrin levels after LPS infusion in the ozone group were significantly lower than those in the control group, and the LPO activity tended to be lower than that observed in the control group. This study showed that OG has anti-inflammatory potential against LPS-induced inflammation in the mammary glands.

Differential gene expression associated with inflammation and blood pressure regulation induced by concentrated ambient particle exposure.

Epidemiological studies have indicated that exposure to particle matter (PM) increased the risk of respiratory and cardiovascular morbidity and mortality. It is suggested that PM smaller than 2.5 µm in aerodynamic diameter (PM(2.5)) may contribute to these responses. However, the molecular mechanism is still unknown. To elucidate the changes in molecular level, we investigated the gene expression profile of concentrated ambient particles (CAPs)-exposed rats. Aged F344 rats were exposed with CAPs (594 µg/m(3)) or clean air 4 h per day for 3 days, and lung and heart tissues were then excised for DNA microarray analysis. Expression profiles related to inflammation and blood pressure regulation revealed differential expression of 7 genes in the lung and that of 3 genes in the heart ventricle. According to the complement activation-associated genes, complement factor B (Bf), complement component 2 and 4a (C4a), and C1 inhibitor genes were up-regulated in CAPs-exposed rat lung. Bf and C4a genes were also up-regulated in the heart. These suggest the treated animal ready for production of these proteins when activation of complement cascade is required. Pro-inflammatory cytokine, interleukin-1ß, was also up-regulated in CAPs-exposed rat lung. Gene related with blood pressure regulation (angiotensin I converting enzyme) was also up-regulated in CAPs-exposed rat lung. Negative regulator of blood pressure (neuropeptide Y) was down-regulated in CAPs-exposed rat heart. These results indicate that CAPs may affect respiratory and cardiovascular organs by activation of inflammatory responses and disintegration of blood pressure regulation in early stage of CAPs exposure.

[Central venous catheterization complication by a guide wire].

Central venous catheterization using the Seldinger technique is a well known and often used method. On the other hand, there are also well known complications by needle puncture or by indwelling catheter, there are few reports about a guide wire which got hung up around the tricuspid valve. We report a case in which a guide wire got hung up to the chordae tendineae of the tricuspid valve. To insert the AVA 3Xi (Edwards life science Co. Iervine) from the right internal jugular vein, we inserted a guide wire without ease. Resistance appeared when we tried to remove the wire for 20 cm from the inserted state. The X-ray and the transesophageal echocardiography, showed the guide wire in the right ventricle. As actions to be taken, we advanced the central vein catheter of the EXCV catheter kit (Nippon Sherwood Medical Industries Co., Ltd.) to the tip, and a the guide wire was easily removed. There are many reports of the complication by the central venepuncture, but there are few reports about the guide wire which was entrapped in the vicinity of a tricuspid valve. The tip of the guide wire in this case was bent excessively, but the cause of the damage did not become clear by investigation. When a guide wire became hard to withdraw, we should never withdraw a guide wire blindly, but should search a cause and we should use the material which was matched with the cause.

Acquisition of motor memory determines the interindividual variability of learning-induced plasticity in the primary motor cortex.

Acquisition of new motor skills induces plastic reorganization in the primary motor cortex (M1). Previous studies have demonstrated the increases in the M1 excitability through motor skill learning. However, this M1 reorganization is highly variable between individuals even though they improve their skill performance through the same training protocol. To reveal the source of this interindividual variability, we examined the relationship between an acquisition of memory-guided feedforward movements and the learning-induced increases in the M1 excitability. Twenty-eight subjects participated in experiment 1. We asked subjects to learn a visuomotor tracking task. The subjects controlled a cursor on a PC monitor to pursue a target line by performing ankle dorsiflexion and plantar flexion. In experiment 1, we removed the online visual feedback provided by the cursor movement once every six trials, which enabled us to assess whether the subjects could perform accurate memory-guided movements. Motor-evoked potentials (MEP) were elicited in the tibialis anterior muscle by transcranial magnetic stimulation of the relevant M1 before and after the learning of the visuomotor tracking task and after half the trials. We found that the MEP amplitude was increased along with the improvement in memory-guided movements. In experiment 2 ( n = 10), we confirmed this relationship by examining whether the improvement in memory-guided movements induces increases in MEP amplitude. The results of this study indicate that the plastic reorganization of the M1 induced by the learning of a visuomotor skill is associated with the acquisition of memory-guided movements. NEW & NOTEWORTHY Acquisition of novel motor skills increases excitability of the primary motor cortex (M1). We recently reported that the amount of increases in the M1 excitability is highly variable between individuals even though they learned the same skill to the similar extent, yet the sources of this interindividual variability still remain unclear. The present study revealed that this interindividual variability is associated with whether individuals acquire a motor memory, which enables them to produce accurate memory-guided movements.

Relationship between the changes in M1 excitability after motor learning and arousal state as assessed by short-latency afferent inhibition.

To examine the factors that influence the inter-individual differences in the changes in primary motor cortex (M1) excitability seen after motor learning, we investigated the relationship between the amplitude of transcranial magnetic stimulation-induced motor evoked potentials (MEP) and short-latency afferent inhibition (SAI) after motor learning, based on the working hypothesis that SAI can be used to evaluate cortical acetylcholine (ACh) activity. To confirm this working hypothesis, we manipulated the arousal state of the subjects using a vigilance task, the outcomes of which might be correlated with cortical ACh activity, and investigated the effects of arousal state on SAI. As a result, we showed that SAI was significantly affected by arousal state. Consequently, we concluded that the subjects' arousal state during motor learning tasks is one of factors to influence on inter-individual differences in the changes in M1 excitability seen after motor learning tasks.

A speed congenic rat strain bearing the tongue cancer susceptibility locus Tscc1 from Dark-Agouti rats.

We previously reported that Dark-Agouti (DA) rats are highly susceptible to 4-nitroquinoline 1-oxide (4NQO)-induced tongue cancer (TC), whereas Wistar/Furth (WF) rats are barely susceptible. Linkage analysis of reciprocal (DAxWF)F2 rats demonstrated five quantitative trait loci, Tongue squamous cell carcinoma 1-5 (Tscc1-5) determining the size and number of the TCs. The major susceptibility locus Tscc1 is mapped on rat chromosome 19. In the present study, we used a marker-assisted speed congenic procedure to construct WF.DA-Tscc1 (WF-T1D) rats, i.e. WF rats carrying a DA-derived Tscc1 chromosomal segment, and evaluated the effect of a single Tscc1 on 4NQO-induced tongue carcinogenesis. In WF-T1D rats, the incidence, number and size of 4NQO-induced TCs were significantly higher than those in WF rats, indicating that the introgressed segment contains one of the susceptibility loci for 4NQO-induced TCs from DA rats. Detection of a single nucleotide polymorphism in NQO1, one of the Tscc1 candidate genes, enabled us to map NQO1 in the Tscc1 segment between D19Wox8 and D19Wox7 on chromosome 19. Possible relevance of NQO1 polymorphism to TC susceptibility is discussed.

Selective loss of resistant alleles at p15INK4B and p16INK4A genes in chemically-induced rat tongue cancers.

We previously reported that susceptibility to 4-nitroquinoline 1-oxide (4NQO)-induced tongue cancer in Dark-Agouti (DA) and Wistar/Furth (WF) rats was determined by a number of quantitative trait loci. In this article, we further scrutinized one of the quantitative trait loci at a suggestive level on rat chromosome 5. Analyzing a DNA panel of 130 (DAxWF) F2 rats treated with 4NQO showed a quantitative trait loci, containing p15INK4B and p16INK4A. To study the possible relevance of these genes in the development of tongue cancer, we examined 45 4NQO-induced tongue cancers in 100 (DAxWF) F1 rats for loss of heterozygosity. The incidence of loss of heterozygosity at p15INK4B and p16INK4A genes in large advanced tongue cancers was 37.8% and 40.0%, respectively, and the WF allele was selectively lost. Accumulation of loss of heterozygosity and methylation of the promoter regions in the tumour suppressor genes in advanced tumours suggests that they may play a role in tongue cancer progression.

Different Effects of Implicit and Explicit Motor Sequence Learning on Latency of Motor Evoked Potential Evoked by Transcranial Magnetic Stimulation on the Primary Motor Cortex.

Motor training induces plastic changes in the primary motor cortex (M1). However, it is unclear whether and how the latency of motor-evoked potentials (MEP) and MEP amplitude are affected by implicit and/or explicit motor learning. Here, we investigated the changes in M1 excitability and MEP latency induced by implicit and explicit motor learning. The subjects performed a serial reaction time task (SRTT) with their five fingers. In this task, visual cues were lit up sequentially along with a predetermined order. Through training, the subjects learned the order of sequence implicitly and explicitly. Before and after the SRTT, we recorded MEP at 25 stimulation points around the hot spot for the flexor pollicis brevis (FPB) muscle. Although no changes in MEP amplitude were observed in either session, we found increases in MEP latency and changes in histogram of MEP latency after implicit learning. Our results suggest that reorganization across the motor cortices occurs during the acquisition of implicit knowledge. In contrast, acquisition of explicit knowledge does not appear to induce the reorganization based on the measures we recorded. The fact that the above mentioned increases in MEP latency occurred without any alterations in MEP amplitude suggests that learning has different effects on different physiological signals. In conclusion, our results propose that analyzing a combination of some indices of M1 excitability, such as MEP amplitude and MEP latency, is encouraged in order to understand plasticity across motor cortices.

Effects of Sesaminol Feeding on Brain Aß Accumulation in a Senescence-Accelerated Mouse-Prone 8.

Alzheimer's disease (AD) is characterized by the progressive accumulation of extracellular ß-amyloid (Aß) aggregates. Recently, the senescence-accelerated mouse-prone 8 (SAMP8) model was highlighted as a useful model of age-related AD. Therefore, we used the SAMP8 mouse to investigate the preventive effects of sesame lignans on the onset of AD-like pathology. In preliminary in vitro studies, sesaminol showed the greatest inhibitory effect on Aß oligomerization and fibril formation relative to sesamin, sesamolin, and sesaminol triglucoside. Hence, sesaminol was selected for further evaluation in vivo. In SAMP8 mice, feed-through sesaminol (0.05%, w/w, in standard chow) administered over a 16 week period reduced brain Aß accumulation and decreased serum 8-hydroxydeoxyguanosine, an indicator of oxidative stress. Furthermore, sesaminol administration increased the gene and protein expression of ADAM10, which is a protease centrally involved in the non-amyloidogenic processing of amyloid precursor protein. Taken together, these data suggest that long-term consumption of sesaminol may inhibit the accumulation of pathogenic Aß in the brain.

Changes in the Spinal Neural Circuits are Dependent on the Movement Speed of the Visuomotor Task.

Previous studies have shown that spinal neural circuits are modulated by motor skill training. However, the effects of task movement speed on changes in spinal neural circuits have not been clarified. The aim of this research was to investigate whether spinal neural circuits were affected by task movement speed. Thirty-eight healthy subjects participated in this study. In experiment 1, the effects of task movement speed on the spinal neural circuits were examined. Eighteen subjects performed a visuomotor task involving ankle muscle slow (nine subjects) or fast (nine subjects) movement speed. Another nine subjects performed a non-visuomotor task (controls) in fast movement speed. The motor task training lasted for 20 min. The amounts of D1 inhibition and reciprocal Ia inhibition were measured using H-relfex condition-test paradigm and recorded before, and at 5, 15, and 30 min after the training session. In experiment 2, using transcranial magnetic stimulation (TMS), the effects of corticospinal descending inputs on the presynaptic inhibitory pathway were examined before and after performing either a visuomotor (eight subjects) or a control task (eight subjects). All measurements were taken under resting conditions. The amount of D1 inhibition increased after the visuomotor task irrespective of movement speed (P < 0.01). The amount of reciprocal Ia inhibition increased with fast movement speed conditioning (P < 0.01), but was unchanged by slow movement speed conditioning. These changes lasted up to 15 min in D1 inhibition and 5 min in reciprocal Ia inhibition after the training session. The control task did not induce changes in D1 inhibition and reciprocal Ia inhibition. The TMS conditioned inhibitory effects of presynaptic inhibitory pathways decreased following visuomotor tasks (P < 0.01). The size of test H-reflex was almost the same size throughout experiments. The results suggest that supraspinal descending inputs for controlling joint movement are responsible for changes in the spinal neural circuits, and that task movement speed is one of the critical factors for inducing plastic changes in reciprocal Ia inhibition.