Shin-Ichi Izumi

Motor Control and Neural Plasticity through Interhemispheric Interactions

The corpus callosum, which is the largest white matter structure in the human brain, connects the 2 cerebral hemispheres. It plays a crucial role in maintaining the independent processing of the hemispheres and in integrating information between both hemispheres. The functional integrity of interhemispheric interactions can be tested electrophysiologically in humans by using transcranial magnetic stimulation, electroencephalography, and functional magnetic resonance imaging. As a brain structural imaging, diffusion tensor imaging has revealed the microstructural connectivity underlying interhemispheric interactions. Sex, age, and motor training in addition to the size of the corpus callosum influence interhemispheric interactions. Several neurological disorders change hemispheric asymmetry directly by impairing the corpus callosum. Moreover, stroke lesions and unilateral peripheral impairments such as amputation alter interhemispheric interactions indirectly. Noninvasive brain stimulation changes the interhemispheric interactions between both motor cortices. Recently, these brain stimulation techniques were applied in the clinical rehabilitation of patients with stroke by ameliorating the deteriorated modulation of interhemispheric interactions. Here, we review the interhemispheric interactions and mechanisms underlying the pathogenesis of these interactions and propose rehabilitative approaches for appropriate cortical reorganization.

Prevalence and Length of Recovery of Pusher Syndrome Based on Cerebral Hemispheric Lesion Side in Patients With Acute Stroke

Background and Purpose— The aim of this study was to determine if side of cerebral hemisphere lesion affects the prevalence and time course of pushing behavior (PB) after stroke. Methods— A total of 1660 patients with acute stroke were investigated. PB was assessed using the standardized Scale for Contraversive Pushing. Risk ratios were used to evaluate the differences in the prevalence of PB between right cerebral hemisphere-damaged (RCD) and left cerebral hemisphere-damaged (LCD) patients. The differences in the time course among 35 (27 RCD and 8 LCD) patients were evaluated by analyzing Scale for Contraversive Pushing scores with the Kaplan–Meier method using a log-rank test. Results— PB was observed in 156 (9.4%) patients. The prevalence of PB was significantly higher in RCD (97 of 556 [17.4%]) than in LCD (57 of 599 [9.5%]) patients; risk ratio was 1.83 (95% CI, 1.35–2.49). The log-rank test indicated that RCD patients exhibited a significantly slower recovery than LCD patients (P=0.027). Conclusions— The number of RCD patients who exhibited PB was higher than that of LCD patients. The duration of recovery from PB was longer in RCD patients than in LCD patients.

Combinations of stroke neurorehabilitation to facilitate motor recovery: perspectives on Hebbian plasticity and homeostatic metaplasticity

Motor recovery after stroke involves developing new neural connections, acquiring new functions, and compensating for impairments. These processes are related to neural plasticity. Various novel stroke rehabilitation techniques based on basic science and clinical studies of neural plasticity have been developed to aid motor recovery. Current research aims to determine whether using combinations of these techniques can synergistically improve motor recovery. When different stroke neurorehabilitation therapies are combined, the timing of each therapeutic program must be considered to enable optimal neural plasticity. Synchronizing stroke rehabilitation with voluntary neural and/or muscle activity can lead to motor recovery by targeting Hebbian plasticity. This reinforces the neural connections between paretic muscles and the residual motor area. Homeostatic metaplasticity, which stabilizes the activity of neurons and neural circuits, can either augment or reduce the synergic effect depending on the timing of combination therapy and types of neurorehabilitation that are used. Moreover, the possibility that the threshold and degree of induced plasticity can be altered after stroke should be noted. This review focuses on the mechanisms underlying combinations of neurorehabilitation approaches and their future clinical applications. We suggest therapeutic approaches for cortical reorganization and maximal functional gain in patients with stroke, based on the processes of Hebbian plasticity and homeostatic metaplasticity. Few of the possible combinations of stroke neurorehabilitation have been tested experimentally; therefore, further studies are required to determine the appropriate combination for motor recovery.

Maladaptive change of body representation in the brain after damage to central or peripheral nervous system

Our brain has great flexibility to cope with various changes in the environment. Use-dependent plasticity, a kind of functional plasticity, plays the most important role in this ability to cope. For example, the functional recovery of paretic limb motor movement during post-stroke rehabilitation depends mainly on how much it is used. Patients with hemiparesis, however, tend to gradually disuse the paretic limb because of its motor impairment. Decreased use of the paretic hand then leads to further functional decline brought by use-dependent plasticity. To break this negative loop, body representation, which is the conscious and unconscious information regarding body state stored in the brain, is key for using the paretic limb because it plays an important role in selecting an effector while a motor program is generated. In an attempt to understand body representation in the brain, we reviewed animal and human literature mainly on the alterations of the sensory maps in the primary somatosensory cortex corresponding to the changes in limb usage caused by peripheral or central nervous system damage.

Noninvasive assessment of the activity of the shoulder girdle muscles using ultrasound real-time tissue elastography.

The purpose of this study was to clarify whether the activity of the shoulder girdle muscles could be estimated by measuring the elasticity of these muscles under several levels of muscle contraction through ultrasound real-time tissue elastography (RTE). Ten healthy men performed submaximal voluntary contractions (MVC) in each manual muscle testing position for the middle deltoid, upper trapezius, supraspinatus, levator scapulae, and rhomboid major. The elasticity of these muscles was measured using ultrasound RTE during the task. The strain ratio of the muscle to an acoustic coupler was calculated as an assessment index of the muscle elasticity. Higher strain ratio values imply lower elasticity. In addition, the electromyographic activity was recorded from surface electrodes attached only to the middle deltoid and upper trapezius. The strain ratios were negatively correlated with the normalized root mean square values for the middle deltoid (r=-0.659, p<0.001) and upper trapezius (r=-0.554, p<0.001). The strain ratios of all the muscles decreased with an increase from 10% MVC force to 30% MVC force. Ultrasound RTE may be useful for noninvasively assessing the activity of the shoulder girdle muscles at certain shoulder positions with low levels of muscle contraction.

Relationship between activation of ankle muscles and quasi-joint stiffness in early and middle stances during gait in patients with hemiparesis

It is unclear whether muscle contraction is necessary to increase quasi-joint stiffness (QJS) of the ankle joint during gait in patients with hemiparesis. The purpose of the present study was to investigate the relationship between QJS and muscle activation at the ankle joint in the stance phase during gait in patients with hemiparesis. Spatiotemporal and kinetic gait parameters and activation of the medial head of the gastrocnemius (MG), soleus (SOL), and tibialis anterior (TA) muscles were measured using a 3-dimensional motion analysis system and surface electromyography, in 21 patients with hemiparesis due to stroke and 10 healthy individuals. In the early stance, the QJS on the paretic side (PS) of patients was greater than that on the non-PS (p<0.05) and not significantly correlated with activation of the three muscles. In the middle stance, the QJS on the PS was lower than that on the non-PS (p<0.05) and that on the right side of controls (p<0.001), which was positively correlated with activation of the MG (r=0.51, p<0.05) and SOL (r=0.49, p<0.05). In the patients with hemiparesis, plantarflexor activation may not contribute to QJS in the early stance. On the other hand, QJS in the middle stance may be attributed to activation of the MG and SOL. Our findings suggest that activation of the MG and SOL in the middle stance on the PS may require to be enhanced to increase QJS during gait in patients with hemiparesis.

Integration of Teaching Processes and Learning Assessment in the Prefrontal Cortex during a Video Game Teaching-learning Task.

Human teaching is a social interaction that supports reciprocal and dynamical feedback between the teacher and the student. The prefrontal cortex (PFC) is a region of particular interest due to its demonstrated role in social interaction. In the present study, we evaluated the PFC activity simultaneously in two individuals playing the role of a teacher and student in a video game teaching–learning task. For that, we used two wearable near-infrared spectroscopy (NIRS) devices in order to elucidate the neural mechanisms underlying cognitive interactions between teachers and students. Fifteen teacher–student pairs in total (N = 30) participated in this study. Each teacher was instructed to teach the video game to their student partner, without speaking. The PFC activity was simultaneously evaluated in both participants using a wearable 16-channel NIRS system during the video game teaching–learning task. Two sessions, each including a triplet of a 30-s teaching–learning task, were performed in order to evaluate changes in PFC activity after advancement of teaching–learning state. Changes in the teachers’ left PFC activity between the first and second session positively correlated with those observed in students (r = 0.694, p = 0.004). Moreover, among teachers, multiple regression analysis revealed a correlation between the left PFC activity and the assessment gap between one’s own teaching and the student’s understanding (β = 0.649, p = 0.009). Activity in the left PFC changed synchronously in both teachers and students after advancement of the teaching–learning state. The left PFC of teachers may be involved in integrating information regarding one’s own teaching process and the student’s learning state. The present observations indicate that simultaneous recording and analysis of brain activity data during teacher–student interactions may be useful in the field of educational neuroscience.

The neural basis of the imitation drive

Spontaneous imitation is assumed to underlie the acquisition of important skills by infants, including language and social interaction. In this study, functional magnetic resonance imaging (fMRI) was used to examine the neural basis of ‘spontaneously’ driven imitation, which has not yet been fully investigated. Healthy participants were presented with movie clips of meaningless bimanual actions and instructed to observe and imitate them during an fMRI scan. The participants were subsequently shown the movie clips again and asked to evaluate the strength of their ‘urge to imitate’ (Urge) for each action. We searched for cortical areas where the degree of activation positively correlated with Urge scores; significant positive correlations were observed in the right supplementary motor area (SMA) and bilateral midcingulate cortex (MCC) under the imitation condition. These areas were not explained by explicit reasons for imitation or the kinematic characteristics of the actions. Previous studies performed in monkeys and humans have implicated the SMA and MCC/caudal cingulate zone in voluntary actions. This study also confirmed the functional connectivity between Urge and imitation performance using a psychophysiological interaction analysis. Thus, our findings reveal the critical neural components that underlie spontaneous imitation and provide possible reasons why infants imitate spontaneously.

Induction of Neurite Outgrowth in PC12 Cells Treated with Temperature-Controlled Repeated Thermal Stimulation

To promote the functional restoration of the nervous system following injury, it is necessary to provide optimal extracellular signals that can induce neuronal regenerative activities, particularly neurite formation. This study aimed to examine the regulation of neuritogenesis by temperature-controlled repeated thermal stimulation (TRTS) in rat PC12 pheochromocytoma cells, which can be induced by neurotrophic factors to differentiate into neuron-like cells with elongated neurites. A heating plate was used to apply thermal stimulation, and the correlation of culture medium temperature with varying surface temperature of the heating plate was monitored. Plated PC12 cells were exposed to TRTS at two different temperatures via heating plate (preset surface temperature of the heating plate, 39.5°C or 42°C) in growth or differentiating medium for up to 18 h per day. We then measured the extent of growth, neuritogenesis, or acetylcholine esterase (AChE) activity (a neuronal marker). To analyze the mechanisms underlying the effects of TRTS on these cells, we examined changes in intracellular signaling using the following: tropomyosin-related kinase A inhibitor GW441756; p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580; and MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor U0126 with its inactive analog, U0124, as a control. While a TRTS of 39.5°C did not decrease the growth rate of cells in the cell growth assay, it did increase the number of neurite-bearing PC12 cells and AChE activity without the addition of other neuritogenesis inducers. Furthermore, U0126, and SB203580, but not U0124 and GW441756, considerably inhibited TRTS-induced neuritogenesis. These results suggest that TRTS can induce neuritogenesis and that participation of both the ERK1/2 and p38 MAPK signaling pathways is required for TRTS-dependent neuritogenesis in PC12 cells. Thus, TRTS may be an effective technique for regenerative neuromedicine.

Development of Clinicians' Communication Skills Influences the Satisfaction, Motivation, and Quality of Life of Patients with Stroke

Objective: To evaluate the influence of structuring the clinician’s communication according to coaching theory on stroke patients’ quality of life and satisfaction. Methods: Prospective observational study was carried out at outpatient clinics for patients in the chronic poststroke phase. Thirty-four clinicians involved in the management of patients with stroke and their105 patients in the chronic post-stroke phase. The clinicians enrolled in this study received training in communication skills based on coaching theory and utilized these skills when interviewing their patients with stroke. We assessed the main outcome measures and the clinicians’ self-assessments of their communication skills before and after the training. The main outcomes were the patients’ (1) satisfaction, (2) health-related quality of life, and (3) goal setting and action scores. Results: The training significantly increased the patients’ satisfaction with the clinicians’ communication (46.8 before training vs. 48.6 after training, p<0.001), overall satisfaction (16.8 vs. 17.4, p<0.001), and goal setting/action (14.6 vs. 15.2, p<0.05) scores. Additionally, the training significantly increased the SF-36 subscale scores for bodily pain (56.6 vs. 65.0, p<0.01), general health (49.8 vs. 54.1, p<0.05), and social function (61.1 vs. 69.9, p<0.05).The patients whose satisfaction with the clinician’s communication improved exhibited significantly greater improvements in their physical function scores and tended to exhibit greater improvements in their bodily pain and vitality scores than the no-improvement group. Furthermore, the patients whose goal setting and action improved tended to have greater improvements in their physical function, role limitation by physical problems, and mental health scores than the noimprovement group. Conclusion: Training in coaching theory-based communication skills influenced stroke patients’ satisfaction, goal setting and action, and HQOL. Clinicians should intentionally use structured communication to facilitate patients’ active involvement in their rehabilitation.