Exploring Methodological Issues in Mental Practice for Upper-Extremity Function Following Stroke-Related Paralysis: A Scoping Review.

In this scoping review, we aimed to comprehensively clarify the methodology of Mental practice (MP) by systematically mapping studies documenting the application of MP to post-stroke paralytic upper-extremity function. Specifically, when is an MP intervention most commonly applied after stroke onset? What is the corresponding MP load (intervention time, number of intervention days, and intervention period)? What are the most common methods of Motor Imagery (MI) recall and MI tasks used during the application of MP? Is MP often used in conjunction with individual rehabilitation? What are the paralyzed side's upper-limb and cognitive function levels at the start of an MP intervention? The research questions were identified according to PRISMA-ScR. The PubMed, Scopus, Medline, and Cochrane Library databases were used to screen articles published until 19 July 2022. In total, 694 English-language articles were identified, of which 61 were finally included. Most of the studies were conducted in the chronic phase after stroke onset, with limited interventions in the acute or subacute phase. The most common intervention time was ≤30 min and intervention frequency was 5 times/week in MP. An audio guide was most commonly used to recall MI during MP, and 50 studies examined the effects of MP in combination with individual rehabilitation. The Fugl-Meyer Assessment mean for the 38 studies, determined using the Fugl-Meyer Assessment, was 30.3 ± 11.5. Additional research with the aim of unifying the widely varying MP methodologies identified herein is warranted.

Long-range axonal projections of transplanted mouse embryonic stem cell-derived hypothalamic neurons into adult mouse brain.

The hypothalamus is comprised of heterogenous cell populations and includes highly complex neural circuits that regulate the autonomic nerve system. Its dysfunction therefore results in severe endocrine disorders. Although recent experiments have been conducted for in vitro organogenesis of hypothalamic neurons from embryonic stem (ES) or induced pluripotent stem (iPS) cells, whether these stem cell-derived hypothalamic neurons can be useful for regenerative medicine remains unclear. We therefore performed orthotopic transplantation of mouse ES cell (mESC)-derived hypothalamic neurons into adult mouse brains. We generated electrophysiologically functional hypothalamic neurons from mESCs and transplanted them into the supraoptic nucleus of mice. Grafts extended their axons along hypothalamic nerve bundles in host brain, and some of them even projected into the posterior pituitary (PPit), which consists of distal axons of the magnocellular neurons located in hypothalamic supraoptic and paraventricular nuclei. The axonal projections to the PPit were not observed when the mESC-derived hypothalamic neurons were ectopically transplanted into the substantia nigra reticular part. These findings suggest that our stem cell-based orthotopic transplantation approach might contribute to the establishment of regenerative medicine for hypothalamic and pituitary disorders.

Continuous Repetition Motor Imagery Training and Physical Practice Training Exert the Growth of Fatigue and Its Effect on Performance.

Continuous repetition of motor imagery leads to mental fatigue. This study aimed to examine whether fatigue caused by motor imagery training affects improvement in performance and the change in corticospinal excitability. The participants were divided into "physical practice training" and "motor imagery training" groups, and a visuomotor task (set at 50% of maximal voluntary contraction in participants) was performed to assess the training effect on fatigue. The measurements were recorded before and after training. Corticospinal excitability at rest was measured by transcranial magnetic stimulation according to the Neurophysiological Index. Subjective mental fatigue and muscle fatigue were assessed by using the visual analog scale and by measuring the pinch force, respectively. Additionally, the error area was evaluated and calculated at pre-, mid-, and post-terms after training, using a visuomotor task. After training, muscle fatigue, subjective mental fatigue, and decreased corticospinal excitability were noted in both of the groups. Moreover, the visuomotor task decreased the error area by training; however, there was no difference in the error area between the mid- and post-terms. In conclusion, motor imagery training resulted in central fatigue by continuous repetition, which influenced the improvement in performance in the same manner as physical practice training.

Characterization of Hypothalamic MCH Neuron Development in a 3D Differentiation System of Mouse Embryonic Stem Cells.

Hypothalamic melanin-concentrating hormone (MCH) neurons are important regulators of multiple physiological processes, such as sleep, feeding, and memory. Despite the increasing interest in their neuronal functions, the molecular mechanism underlying MCH neuron development remains poorly understood. We report that a three-dimensional culture of mouse embryonic stem cells (mESCs) can generate hypothalamic-like tissues containing MCH-positive neurons, which reproduce morphologic maturation, neuronal connectivity, and neuropeptide/neurotransmitter phenotype of native MCH neurons. Using this in vitro system, we demonstrate that Hedgehog (Hh) signaling serves to produce major neurochemical subtypes of MCH neurons characterized by the presence or absence of cocaine- and amphetamine-regulated transcript (CART). Without exogenous Hh signals, mESCs initially differentiated into dorsal hypothalamic/prethalamic progenitors and finally into MCH+CART+ neurons through a specific intermediate progenitor state. Conversely, activation of the Hh pathway specified ventral hypothalamic progenitors that generate both MCH+CART- and MCH+CART+ neurons. These results suggest that in vivo MCH neurons may originate from multiple cell lineages that arise through early dorsoventral patterning of the hypothalamus. Additionally, we found that Hh signaling supports the differentiation of mESCs into orexin/hypocretin neurons, a well-defined cell group intermingled with MCH neurons in the lateral hypothalamic area (LHA). The present study highlights and improves the utility of mESC culture in the analysis of the developmental programs of specific hypothalamic cell types.

A method for using video presentation to increase the vividness and activity of cortical regions during motor imagery tasks.

In recent years, mental practice (MP) using laterally inverted video of a subject's non-paralyzed upper limb to improve the vividness of presented motor imagery (MI) has been shown to be effective for improving the function of a paralyzed upper limb. However, no studies have yet assessed the activity of cortical regions engaged during MI task performance using inverse video presentations and neurophysiological indicators. This study sought to investigate changes in MI vividness and hemodynamic changes in the cerebral cortex during MI performance under the following three conditions in near-infrared spectroscopy: MI-only without inverse video presentation (MI-only), MI with action observation (AO) of an inverse video presentation of another person's hand (AO + MI (other hand)), and MI with AO of an inverse video presentation of a participant's own hand (AO + MI (own hand)). Participants included 66 healthy right-handed adults (41 men and 25 women; mean age: 26.3 ± 4.3 years). There were 23 patients in the MI-only group (mean age: 26.4 ± 4.1 years), 20 in the AO + MI (other hand) group (mean age: 25.9 ± 5.0 years), and 23 in the AO + MI (own hand) group (mean age: 26.9 ± 4.1 years). The MI task involved transferring 1 cm × 1 cm blocks from one plate to another, once per second, using chopsticks held in the non-dominant hand. Based on a visual analog scale (VAS), MI vividness was significantly higher in the AO + MI (own hand) group than in the MI-only group and the AO + MI (other hand) group. A main effect of condition was revealed in terms of MI vividness, as well as regions of interest (ROIs) in certain brain areas associated with motor processing. The data suggest that inverse video presentation of a person's own hand enhances the MI vividness and increases the activity of motor-related cortical areas during MI. This study was approved by the Institutional Ethics Committee of Nagasaki University Graduate School of Biomedical and Health Sciences (approval No. 18121303) on January 18, 2019.

Comparison of cerebral activation between motor execution and motor imagery of self-feeding activity.

Motor imagery is defined as an act wherein an individual contemplates a mental action of motor execution without apparent action. Mental practice executed by repetitive motor imagery can improve motor performance without simultaneous sensory input or overt output. We aimed to investigate cerebral hemodynamics during motor imagery and motor execution of a self-feeding activity using chopsticks. This study included 21 healthy right-handed volunteers. The self-feeding activity task comprised either motor imagery or motor execution of eating sliced cucumber pickles with chopsticks to examine eight regions of interest: pre-supplementary motor area, supplementary motor area, bilateral prefrontal cortex, premotor area, and sensorimotor cortex. The mean oxyhemoglobin levels were detected using near-infrared spectroscopy to reflect cerebral activation. The mean oxyhemoglobin levels during motor execution were significantly higher in the left sensorimotor cortex than in the supplementary motor area and the left premotor area. Moreover, significantly higher oxyhemoglobin levels were detected in the supplementary motor area and the left premotor area during motor imagery, compared to motor execution. Supplementary motor area and premotor area had important roles in the motor imagery of self-feeding activity. Moreover, the activation levels of the supplementary motor area and the premotor area during motor execution and motor imagery are likely affected by intentional cognitive processes. Levels of cerebral activation differed in some areas during motor execution and motor imagery of a self-feeding activity. This study was approved by the Ethical Review Committee of Nagasaki University (approval No. 18110801) on December 10, 2018.

Corticospinal excitability during motor imagery is diminished by continuous repetition-induced fatigue.

Application of continuous repetition of motor imagery can improve the performance of exercise tasks. However, there is a lack of more detailed neurophysiological evidence to support the formulation of clear standards for interventions using motor imagery. Moreover, identification of motor imagery intervention time is necessary because it exhibits possible central fatigue. Therefore, the purpose of this study was to elucidate the development of fatigue during continuous repetition of motor imagery through objective and subjective evaluation. The study involved two experiments. In experiment 1, 14 healthy young volunteers were required to imagine grasping and lifting a 1.5-L plastic bottle using the whole hand. Each participant performed the motor imagery task 100 times under each condition with 48 hours interval between two conditions: 500 mL or 1500 mL of water in the bottle during the demonstration phase. Mental fatigue and a decrease in pinch power appeared under the 1500-mL condition. There were changes in concentration ability or corticospinal excitability, as assessed by motor evoked potentials, between each set with continuous repetition of motor imagery also under the 1500-mL condition. Therefore, in experiment 2, 12 healthy volunteers were required to perform the motor imagery task 200 times under the 1500-mL condition. Both concentration ability and corticospinal excitability decreased. This is the first study to show that continuous repetition of motor imagery can decrease corticospinal excitability in addition to producing mental fatigue. This study was approved by the Institutional Ethics Committee at the Nagasaki University Graduate School of Biomedical and Health Sciences (approval No. 18121302) on January 30, 2019.