Aizu Naoki

INTRODUCTION: Exercise has been recommended to suppress or prevent cognitive decline. Aerobic exercise (AE) may suppress cognitive decline via the fibronectin type III domain-containing protein 5 (FNDC5)/irisin/brain-derived neurotrophic factor (BDNF) pathway, and resistance training (RT) has a preventive effect on cognitive decline. However, the underlying mechanism remains unclear. This study verified the differences in the effects of AE and RT in suppressing and preventing cognitive decline based on the FNDC5/irisin/BDNF pathway. METHODS: We divided senescence-accelerated mouse-prone 8 into three groups: control (CON), AE, and RT and evaluated their memory during exercise intervention through a novel object recognition (NOR) task. We quantified FNDC5/irisin, mBDNF, and TrkB in the hippocampus using enzyme-linked immunosorbent assay and FNDC5 in skeletal muscle using Western blotting (WB). RESULTS: Behavioral analysis using NOR showed that values for both AE and RT were significantly greater than those for CON. WB analysis showed that the peripheral FNDC5 expression in the skeletal muscle was increased in AE. The expression levels of FNDC5/irisin and mBDNF in the hippocampus were significantly increased in both AE and RT compared with that in CON but that if TrkB was increased only in AE. CONCLUSION: No significant difference was observed between AE and RT in the inhibitory effect on age-related cognitive decline, and both groups were effective. The FNDC5/Irisin/BDNF pathway, which was the focus of this experiment, may be specific to AE. The mechanism that suppresses cognitive decline may differ depending on the type of exercise.

OBJECTIVES: This study investigates how online frame-of-reference (FOR) training of raters of the objective structured clinical examination (OSCE) for physical therapy students affects assessment accuracy. METHODS: The research was conducted in a 1-month-long randomized controlled trial. PARTICIPANTS: The participants were 36 physical therapists without experience assessing clinical skills using the OSCE. The training group completed the FOR training online, which was conducted once a week in two 90-minute sessions. The control group self-studied the rubric rating chart used in the assessment. As a measure of accuracy, weighted kappa coefficients were used to check the agreement between correct score and those assessment by the participant in the OSCE. RESULTS: The scores of the training group were higher than those of the control group in both post- and follow-up assessments, showing significant differences. No significant difference was found based on the assessment time and group for the high-agreement groups. Furthermore, scores of the low-accuracy training group were higher in the post- and follow-up assessments than those in the pre-assessment, showing significant differences. CONCLUSIONS: Online FOR training of the raters of the OSCE for physical therapists improved the assessment accuracy of the raters who had low accuracy in the pre-assessment; this improvement was maintained.

The sense of body ownership, the feeling that one's body belongs to oneself, is a crucial subjective conscious experience of one's body. Recent methodological advances regarding crossmodal illusions have provided novel insights into how multisensory interactions shape human perception and cognition, underpinning conscious experience, particularly alteration of body ownership. Moreover, in post-stroke rehabilitation, encouraging the use of the paretic limb in daily life is considered vital, as a settled sense of ownership and attentional engagement toward the paralyzed body part may promote increased frequency of its use and prevent learned nonuse. Therefore, in addition to traditional methods, novel interventions using neurorehabilitation techniques that induce self-body recognition are needed. This study investigated whether the illusory experience of a patient's ownership alterations of their paretic hand facilitates the enhancement in the range of motion of succeeding imitation movements. An experiment combining a modified version of the rubber hand illusion with imitation training was conducted with chronic hemiplegia. A larger imitation movement of the paretic hand was observed in the illusion-induced condition, indicating that the feeling of ownership toward the observed limb promotes the induction of intrinsic potential for motor performance. This training, using subjective experience, may help develop new post-stroke rehabilitation interventions.

INTRODUCTION: Although exercise can prevent cognitive decline due to aging, few elderly individuals are able to exercise for long. Therefore, an exercise method for older adults that is feasible for a long duration without overexertion is necessary. In this study, we focused on exercise by shaking. This study examined the possibility to prevent the decline in memory through regular and long-term shaking exercise using a senescence-accelerated mouse (SAM) model. Behavioral analysis was conducted, and histological changes in the mouse brain were examined to evaluate whether this stimulation method could become a novel exercise method. MATERIALS AND METHODS: The shaking exercise was applied to SAMP10 mice for 30 min 3 times per week for 25 continuous weeks. Behavioral analysis included a step-through passive avoidance test, whereas the histological analysis involved immunohistochemical staining using the anti-glutamate receptor (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors [AMPAR]) antibody in the hippocampus. The number and area of nerve cells in the hippocampal regions were measured and compared between groups. RESULTS: Behavioral analysis revealed that the shaking group retained memory longer than the control group, and memory capacity decline was suppressed. Additionally, histological examination showed that the shaking group had a higher number of AMPAR receptor-positive neurons per area in the hippocampal CA1 and CA3 regions than the control group, suggesting that degeneration and shedding of neurons due to aging was suppressed. DISCUSSION/CONCLUSION: We believe that shaking could become an exercise therapy that can reduce the decline in memory with aging and expect its human application in the future.

INTRODUCTION: The decline in spatial working memory is one of the earliest signs of normal brain aging. OBJECTIVE: We developed a novel physical exercise method, termed the "shaking exercise," to slow down this process. METHODS: The experimental protocol included administering the shaking exercise for 8-32 weeks in male senescence-accelerated mouse prone 10 (SAMP-10). They were subjected to the T-maze test, followed by immunohistochemical analysis, to assess the influence of the shaking exercise on the M1 muscarinic acetylcholine receptor (CHRM1) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) of the dorsal hippocampus and medial prefrontal cortex (dHC-mPFC). RESULTS: The T-maze test demonstrated that the shaking group had less hesitation in the face of selecting direction at week 24. In the immunohistochemical analysis, more CHRM1s were in the CA3 subregion and more AMPARs were in the subiculum. CHRM1s and AMPARs were maintained in the CA1 region and the mPFC. The CHRM1s seem to have a positive effect on the AMPAR in the dentate gyrus (DG) region and the CA3 region. In the CA1 region, CHRM1s were negatively correlated with AMPARs. In addition, high-density neurons were expressed in the shaking group in the upstream DG, the middle part and the distal part of CA3, the distal part of CA1, and the mPFC. CONCLUSIONS: Our results raise the possibility that maintenance of the spatial working memory effect observed with the shaking exercise is driven in part by the uneven affection of CHRM1s and AMPARs in the dHC-mPFC circuit system and significantly maintains the neuronal expression in the dHC-mPFC.

Patients with lower limb amputation experience "embodiment" while using a prosthesis, perceiving it as part of their body. Humans control their biological body parts and receive appropriate information by directing attention toward them, which is called body-specific attention. This study investigated whether patients with lower limb amputation similarly direct attention to prosthetic limbs. The participants were 11 patients with lower limb amputation who started training to walk with a prosthesis. Attention to the prosthetic foot was measured longitudinally by a visual detection task. In the initial stage of walking rehabilitation, the index of attention to the prosthetic foot was lower than that to the healthy foot. In the final stage, however, there was no significant difference between the two indexes of attention. Correlation analysis revealed that the longer the duration of prosthetic foot use, the greater the attention directed toward it. These findings indicate that using a prosthesis focuses attention akin to that of an individual's biological limb. Moreover, they expressed that the prosthesis felt like a part of their body when they could walk independently. These findings suggest that the use of prostheses causes integration of visual information and movement about the prosthesis, resulting in its subjective embodiment.

Learned nonuse is a major problem in upper limb (UL) rehabilitation after stroke. Among the various factors that contribute to learned nonuse, recent studies have focused on body representation of the paretic limb in the brain. We previously developed a method to measure body-specific attention, as a marker of body representation of the paretic limb and revealed a decline in body-specific attention to the paretic limb in chronic stroke patients by a cross-sectional study. However, longitudinal changes in body-specific attention and paretic arm use in daily life (real-world arm use) from the onset to the chronic phase, and their relationship, remain unknown. Here, in a longitudinal, prospective, observational study, we sought to elucidate the longitudinal changes in body-specific attention to the paretic limb and real-world arm use, and their relationship, by using accelerometers and psychophysical methods, respectively, in 25 patients with subacute stroke. Measurements were taken at baseline (TBL), 2 weeks (T2w), 1 month (T1M), 2 months (T2M), and 6 months (T6M) after enrollment. UL function was measured using the Fugl-Meyer Assessment (FMA) and Action Research Arm Test (ARAT). Real-world arm use was measured using accelerometers on both wrists. Body-specific attention was measured using a visual detection task. The UL function and real-world arm use improved up to T6M. Longitudinal changes in body-specific attention were most remarkable at T1M. Changes in body-specific attention up to T1M correlated positively with changes in real-world arm use up to T6M, and from T1M to T6M, and the latter more strongly correlated with changes in real-world arm use. Changes in real-world arm use up to T2M correlated positively with changes in FMA up to T2M and T6M. No correlation was found between body-specific attention and FMA scores. Thus, these results suggest that improved body-specific attention to the paretic limb during the early phase contributes to increasing long-term real-world arm use and that increased real-world use is associated with the recovery of UL function. Our results may contribute to the development of rehabilitation strategies to enhance adaptive changes in body representation in the brain and increase real-world arm use after stroke.

To execute the intended movement, the brain directs attention, called body-specific attention, to the body to obtain information useful for movement. Body-specific attention to the hands has been examined but not to the feet. We aimed to confirm the existence of body-specific attention to the hands and feet, and examine its relation to motor and sensory functions from a behavioral perspective. The study included two groups of 27 right-handed and right-footed healthy adults, respectively. Visual detection tasks were used to measure body-specific attention. We measured reaction times to visual stimuli on or off the self-body and calculated the index of body-specific attention score to subtract the reaction time on self-body from that off one. Participants were classified into low and high attention groups based on each left and right body-specific attention index. For motor functions, Experiment 1 comprised handgrip strength and ball-rotation tasks for the hands, and Experiment 2 comprised toe grip strength involved in postural control for the feet. For sensory functions, the tactile thresholds of the hands and feet were measured. The results showed that, in both hands, the reaction time to visual stimuli on the hand was significantly lesser than that offhand. In the foot, this facilitation effect was observed in the right foot but not the left, which showed the correlation between body-specific attention and the normalized toe gripping force, suggesting that body-specific attention affected postural control. In the hand, the number of rotations of the ball was higher in the high than in the low attention group, regardless of the elaboration exercise difficulty or the left or right hand. However, this relation was not observed in the handgripping task. Thus, body-specific attention to the hand is an important component of elaborate movements. The tactile threshold was higher in the high than in the low attention group, regardless of the side in hand and foot. The results suggested that more body-specific attention is directed to the limbs with lower tactile abilities, supporting the sensory information reaching the brain. Therefore, we suggested that body-specific attention regulates the sensory information to help motor control.

INTRODUCTION: The disabling effects of dementia, an incurable disease with little effect on mortality, affect society far more than many other conditions. OBJECTIVE: The aim of this study was to stop or delay the onset of dementia using low-cost methods such as physical exercise. METHODS: Senescence-accelerated model-prone (SAMP) 10 mice were made to perform a user-friendly shaking exercise for 25 weeks. The motor function and hippocampal functions (learning, spatial cognition) of the mice were evaluated using behavioral experiments. The degree of hippocampal aging was evaluated based on brain morphology. The association between behavioral performance of the mice and the degree of hippocampal aging was then evaluated. RESULTS: The behavioral test results showed that the shaking group had higher motor coordination (p < 0.01) and motor learning (p < 0.05). Significantly higher performances in the learning ability were observed in the shaking group at a middle-period experiment (p < 0.05); the spatial cognitive functions also improved (p < 0.05). The shaking group showed delayed ageing of cells in the dentate gyrus (DG; area: p < 0.01) and cornu Ammonis (CA; area: p < 0.01) regions of the hippocampus. CONCLUSIONS: The shaking exercise enhances the activity of mice and reduces age-associated decreases in learning and spatial cognitive functions. Regarding hippocampal morphology, shaking exercise can prevent non-functional protein accumulation, cell atrophy, and cell loss. Specifically, shaking exercise protects cell growth and regeneration in the DG area and enhances the learning function of the hippocampus. Furthermore, shaking exercise maintained the spatial cognitive function of cells in the CA3 and CA1 regions, and prevented the chronic loss of CA2 transmission that decreased the spatial memory decline in mice.

OBJECTIVE: To examine whether reduced body-specific attention to a paretic limb is found in chronic stroke patients in a time-dependent manner. METHODS: Twenty-one patients with chronic hemiparesis (10 left and 11 right hemiparesis) after subcortical stroke and 18 age-matched healthy controls were recruited in this study. Standard neuropsychological examinations showed no clear evidence of spatial neglect in any patient. In order to quantitatively measure spatial attention to the paretic hand, a visual detection task for detecting a target appearing on the surface of either a paretic or dummy hand was used. This task can measure the body facilitation effect, which makes faster detection of a target on the body compared with one far from the body. RESULTS: In stroke patients, there was no difference in the reaction time for a visual target between the paretic and the dummy hands, while the healthy participants showed faster detection for the visual target on the real hand than on the dummy one. The index of the body facilitation effect, subtracting the reaction time for the target-on-paretic hand from that for the target-on-dummy one, was correlated with the duration since onset and with finger function test on the Stroke Impairment Assessment Set. CONCLUSIONS: The reduction of the body facilitation effect in the paretic limb suggests the decline of body-specific attention to the paretic one in patients with chronic hemiparesis. This decline of body-specific attention, leading to neglect for the paretic limb, will be one of the most serious problems for rehabilitation based on use-dependent plasticity.

<p>&ensp;&ensp;It is well known that patients with chronic hemiplegia following brain damage often face difficulties in improving motor function, owing to maladaptive changes to cortical representation of the affected limbs. However, frequent training of paretic limbs enlarges their cortical representation by use-dependent plastic ity. Nevertheless, these processes interact to produce a downward learning, providing negative feedback from paretic limbs, which results in further 'learned nonuse'. This sensory disturbance leads to a gradual alteration of the representation of the body in the brain;consequently, there is a failure to generate efficient motor output.<br>&ensp;&ensp;This review describes several kinds of treatment to break this negative loop and to overcome this learned nonuse phenomenon underlying a number of disorders of body representation related to sensory and motor impairment using non-invasive techniques, boosting their multisensory capabilities, weakened by brain damage. We also introduce the effects of illusory ownership, the conscious experience of altered internal body representation induced by patterns of multisensory stimulation, on imitative movement performed by participants from a first-person perspective just after experiencing the crossmodal illusion as an example of therapeutic applications. These clinical applications illustrate the potential of neurorehabilitation for restor ing the maladaptive alterations of body representation corresponding to decreased frequency of usage caused by damage of peripheral or central nervous system.</p>

ヒトは長時間立った状態を維持する際に、無意識に体の重心を左右に移動させて疲労を抑制する。これは穏やかな全身運動を行っている状態であるといえる。振動板の上で静止立位を維持することは、静止した場所に立つよりより効果的な全身運動を誘導すると考えられる。振動刺激が骨密度減少に与える効果について調べた。骨ミネラル密度(BMD)減少モデルマウスに振動刺激を与えると、大腿骨強度の減少が抑制された。骨の部位により抑制の程度に差がみられた。BMD減少抑制効果は骨の形態、組成、物理的分析により確認された。この方法はヒトにおいても有用であることが示唆された。振動刺激による全身運動は高齢者のみでなく若年者に対しても、骨折予防および健康促進における理学療法として有用であると考えられた。