We express gratitude to the patients and medical staff of the Second Hospital of Jiaxing for their support and cooperation during the research process.

This study (Approval No. JXEY-2020SW038) was approved by the Medical Ethics Committee of the Second Hospital of Jiaxing, with all participants providing informed consent. It aimed to assess the feasibility and effectiveness of a protocol through a randomized, single-blind, controlled trial. Between January and December 2021, 60 stroke patients admitted to the Second Hospital of Jiaxing were enrolled.
NOTE: Inclusion criteria comprised: 1) confirmed diagnosis of cerebral infarction or hemorrhage via computed tomography (CT) or magnetic resonance imaging (MRI), 2) first-onset and unilateral lesion with a disease duration of 2 weeks to 3 months and a stable condition, 3) age 25-75 years, 4) absence of hemianopsia or unilateral spatial neglect, as well as no visual or auditory deficits, 5) conscious, compliant, and able to participate in rehabilitation treatment, 6) clear unilateral upper limb dysfunction with a modified Ashworth scale (MAS) grade &#8804; 216. Exclusion criteria included: 1) previous craniocerebral injury or other intracranial diseases, 2) severe myocardial infarction, angina pectoris, liver, kidney, lung, or other important organ diseases, malignant tumors, etc., 3) previous history of psychiatric disorders and epilepsy, 4) severe pain, numbness, or other sensory deficits on the hemiplegic side of the limbs, 5) significant limitation of movement in the bilateral upper limbs.
1. Study design
<ol>
	<li>Randomly divide patients (n = 60) who met the specified criteria into two groups: an experimental group (n = 30) and a control group (n = 30).</li>
	<li>Have a skilled occupational therapist complete the following functional assessments, who was unaware of the group assignments before and after a 6-week treatment period.
	<ol>
		<li>Motor evoked potential (MEP):
		<ol>
			<li>Elicit MEPs in patients using a magnetic stimulation therapy system following the guidelines established by Groppa et al.17.</li>
			<li>During the test, position the patient in front of the device in a stable and comfortable manner and place the recording electrode pads on the abductor pollicis brevis and wrist joint osseous process.</li>
			<li>Then, center the magnetic stimulation coil above the motor cortex on the injured side of the brain, with the coil handle positioned at a 45&#176; angle to the sagittal plane.</li>
			<li>Carry out stimulation of the motor cortex area 10 times at 100% intensity and record the presence or absence of motor-evoked potentials, along with their latency and amplitude. 
			NOTE: Due to the inability to detect motor evoked potentials in all patients, a thorough comparison and analysis of the latency and amplitude of the evoked potentials between the two patient groups was not feasible. Therefore, the study aimed to determine the presence or absence of MEPs and compare the percentage of detectable MEPs between two groups of patients. A higher percentage of detectable MEPs indicates a greater potential for enhancing corticospinal pathways in stroke patients.</li>
		</ol>
		</li>
		<li>Perform functional test for the hemiplegic upper extremity-Hong Kong (FTHUE-HK).
		<ol>
			<li>Utilize the scale to assess the patient&#39;s upper limb functionality, which includes 12 tasks, such as placing the hand on the knee and wringing a rag. 
			NOTE: Each task must be completed within 3 min and can only be attempted up to 3 times. The scale comprises 7 levels, with higher levels indicating better upper limb functionality18.</li>
		</ol>
		</li>
		<li>Use the Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE).
		<ol>
			<li>Utilize this scale to evaluate the motor function of the shoulder, elbow, forearm, wrist, and hand. 
			NOTE: A score of 0 indicates inability to perform the specified movement, a score of 1 indicates partial completion, and a score of 2 indicates full completion. The scale has a maximum score of 66 points, with higher scores indicating better upper limb motor function19.</li>
		</ol>
		</li>
		<li>Calculate the Modified Barthel index (MBI).
		<ol>
			<li>Utilize this scale to assess the patient&#39;s performance in activities of daily living. 
			NOTE: The scale consists of 10 items, including eating, dressing, bathing, etc., with a maximum score of 100 points. A higher score indicates greater independence in the patient&#39;s daily life20.</li>
		</ol>
		</li>
	</ol>
	</li>
	<li>Ensure that all patients are prescribed conventional medications, including anti-hypertensives, anti-diabetics, lipid regulators, etc., tailored to their individual conditions. 
	NOTE: The medication selection for stroke patients is based on their unique circumstances and may differ from one patient to another.</li>
	<li>Confirm that all patients received routine physical therapy, occupational therapy for the forearm and hand, and activities of daily living training for 6 weeks.</li>
	<li>Ensure that patients in the control group received routine occupational therapy targeting upper limb function for 1 h per day for 6 weeks. 
	NOTE: The routine occupational therapy targeting upper limb function includes motor control training for the shoulder and elbow joints, roller training, hoop training, and reaching for objects training.</li>
	<li>Confirm that patients in the experimental group received routine occupational therapy targeting upper limb function for 30 min per day, in addition to dual upper limb task-oriented robotic system training for 30 min per day for 6 weeks.</li>
</ol>
2. Dual upper limb task-oriented robotic system training session
NOTE: Only the stroke patients in the experimental group received these training sessions.
<ol>
	<li>Start the robotic system equipment, turn on the system&#39;s computer screen, open the ULCOT Rehab application, and enter the main interface of the system.</li>
	<li>During the initial training session, click Register to establish a personal file for each patient, mainly including name, gender, age, case number, diagnosis, affected side, and other relevant medical contents.</li>
	<li>Click Login on the main interface of the system, select the patient who needs training from the list, and enter the interface of the training system for that patient.</li>
	<li>Assist the patient in positioning themselves in front of the robotic device, ensuring a safe and comfortable distance.</li>
	<li>Click Adjustment on the interface of the patient training system to enter the interface of equipment parameter adjustment and set the appropriate parameters for the patient. 
	NOTE: It is not necessary to set parameters for each training session. Upon logging into the patient&#39;s training system interface, the system automatically adjusts to the parameters established during the patient&#39;s previous training session. The therapist can then modify the corresponding parameters in accordance with the therapeutic goals. If no changes to the parameters are needed, the user can click Training in the training system interface to access the training program setting interface.
	<ol>
		<li>Click on + or - to increase or decrease the height of the platform in the Platform Height Adjustment module. Adjust the height of the equipment platform based on the patient&#39;s height.</li>
		<li>Click + or - to increase or decrease the tilt angle of the system&#39;s robot arm in the Arm Tilt Angle Adjustment module. Adjust the tilt angle of the robotic arm according to the patient&#39;s shoulder flexion and extension training goals (the higher the target, the greater the angle).</li>
		<li>Click + or - to increase or decrease the angle between the two robot arms in the Arm Angle Adjustment module. Adjust the angle between the robotic arms according to the patient&#39;s upper limb adduction and abduction training goals (the higher the goal, the greater the angle).</li>
	</ol>
	</li>
	<li>Click Training in the patient training system interface to enter the training program setting interface.
	<ol>
		<li>Select an appropriate training program based on the patient&#39;s upper limb functional status. When the upper limb on the hemiplegic side is unable to actively manipulate the mechanical handle through the full range of motion, opt for the assisted training program.</li>
		<li>Conversely, if the upper limb on the hemiplegic side is capable of actively manipulating the mechanical handle to complete the full range of motion, choose the resistance training program.</li>
	</ol>
	</li>
	<li>Explain and demonstrate the training methods of the selected items and inform relevant precautions to ensure that patients know how to perform the training session safely and accurately.</li>
	<li>Help the patient to fix their hands on the handles at the end of the two robotic arms (Figure 1).</li>
	<li>Conduct dual upper limb task-oriented robot system training.
	<ol>
		<li>For patients who are unable to actively manipulate the mechanical handle to achieve a full range of motion on the hemiplegic side of the upper limb, click Assistance in the training program setting interface to enter the assisted training mode interface. 
		NOTE: The therapist may select Air Flying game or Ping-Pong game for the patient in assisted training mode. It should be noted that patients may only select one game per training session.
		<ol>
			<li>Set the time to 30 min in the Training Time module, and select the level set for the patient in the Assisted Level module. 
			NOTE: This mode offers 6 levels of assistance, with level 6 involving the affected upper limb being driven by both the robot and the healthy upper limb during bilateral upper limb training. On the other hand, level 1 entails the affected upper limb participating in bilateral upper limb training directly without external force. The training session commences at level 6, and the patient can progress to the next level after achieving a full score at each level. Once the patient attains a full training score at assistance level 1, they are deemed ready for resistance mode training.</li>
			<li>Click Air Flying or Ping-Pong, then click Start to enter the game interface.</li>
			<li>Air Flying game: Instruct the patient to control a virtual airplane displayed on the computer screen by maneuvering the affected upper limb through the healthy side with the assistance of a robotic device, enabling the patient to optimize their efforts in guiding the virtual airplane along the designated flight trajectory while simultaneously capturing virtual gold coins (Figure 2).</li>
			<li>Ping-Pong game: With the assistance of the robot, instruct the patient to use the unaffected side to drive the affected side upper limb to control the virtual table tennis racket and move the racket to catch the flying ping-pong (Figure 3).</li>
		</ol>
		</li>
		<li>For patients who are able to actively manipulate the mechanical handle to achieve a full range of motion on the hemiplegic side of the upper limb, click Resistance in the training program settings interface to access the resistance training mode interface. 
		NOTE: In the resistance training mode, participants can choose from five available games: Air Flying, Ping-Pong, Bridge &#38; Road, Weight-Lifting, and Pop Matching. Only one game may be selected for each training session.
		<ol>
			<li>Set the time to 30 min in the Training Time module, and select the resistance levels of the healthy side and the affected side, respectively, in the Healthy Level and Affected Level modules. 
			NOTE: In the resistance training mode, resistance levels can be individually set for the patient&#39;s healthy and affected sides based on upper limb muscle strength. Levels range from 1 (lowest resistance) to 10 (highest resistance). The initial treatment involved the selection of Level 1 resistance, with patients permitted to progress to the subsequent level upon achieving a perfect score on each level of training.</li>
			<li>In the Healthy Side Resistance Direction and Affected Side Resistance Direction modules, select the resistance direction indicated by the system for the patient&#39;s healthy side and the affected side of the upper limb during resistance training, respectively. 
			NOTE: The direction of resistance is selected for the patient according to the purpose of the exercise, including push and pull.</li>
			<li>Select the amount of time the target needs to be held in the Holding Time module. 
			NOTE: The time is determined based on the patient&#39;s upper limb function, ranging from 1 to 10 s. The longer the time, the more challenging it becomes. If the set holding time is 10 s and the training score is perfect, the resistance level will be increased for the next session. The Air Flying and Ping-Pong games do not include this step.</li>
			<li>Click to select one of the following games: Air Flying, Ping-Pong, Bridge &#38; Road, Weight-Lifting, and Pop Matching. Click Start to enter the game interface.</li>
			<li>Air Flying game: Instruct the patient to control the virtual airplane by resisting the resistance given by the robotic arm on both the healthy and affected upper limbs, enabling the patient to optimize their efforts in guiding the virtual airplane along the designated flight trajectory while simultaneously capturing virtual gold coins.</li>
			<li>Ping-Pong game: Instruct the patient to control the virtual table tennis racket by resisting the resistance given by the robotic arm on both the healthy and affected upper limbs and move the racket to catch the flying ping-pong.</li>
			<li>Bridge &#38; Road game: Have&#160;the patient control both ends of a wooden&#160;bridge on the screen by resisting the resistance&#160;given by the robotic arm on both the healthy&#160;and affected upper limbs, move two ladder platforms of different heights, and hold them&#160;for a certain time to allow the virtual character&#160;to pass (Figure 4).</li>
			<li>Weight-Lifting game: Have&#160;the patient control the ends of a weight-lifting&#160;barbell displayed on a screen by resisting the&#160;resistance given by the robotic arm on both the healthy 
			and affected upper limbs,&#160;adjusting its position to reach a target location&#160;by varying the distance and maintaining that&#160;position for a specified duration&#160;(Figure 5).</li>
			<li>Pop Matching game:&#160;Have the patient control two virtual 
			fingers located at the left and right ends&#160;of the screen by resisting the resistance given&#160;by the robotic arm on both the healthy and&#160;affected upper limbs, select identical items from the left and right columns of pictures&#160;through the virtual fingers and maintain this position for a 
			designated duration (Figure 6). 
			NOTE: The system verifies whether the selected pictures on both sides are the same; if they are, the selected pictures are eliminated. If they do not match, the patient is prompted to re-select.</li>
		</ol>
		</li>
	</ol>
	</li>
</ol>
3. Follow-up procedure
<ol>
	<li>Utilize statistical software to analyze the assessment data collected, determining appropriate analysis methods based on the data type.</li>
	<li>Elucidate the significance of the data results and evaluate the impact of dual upper limb task-oriented robot system training on upper limb function in stroke patients.</li>
</ol>

Dual Upper Limb Robotic Training in Stroke Rehabilitation

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The authors declare no conflicts of interest or financial disclosures in this study.

Bilateral training has been shown to normalize intercortical inhibition in stroke patients, facilitate brain functional network reorganization, and ultimately enhance upper limb function21. This study presents a program for upper limb functional training in stroke patients utilizing a dual upper limb task-oriented robotic system. The program integrates bilateral upper limb movement, task-oriented activities, and robot-assisted training to enhance the rehabilitation of upper limb function in stroke...

Stroke is one of the major causes of disability and the second leading cause of death globally1,2. Stroke patients often face various challenges, such as motor, sensory, and cognitive deficits3. Upper limb dysfunction is a common problem after stroke, characterized by muscle weakness, spasticity, and reduced motor ability of the upper limb on the hemiplegic side4. It is reported to be present in more than 70% of stroke patients, and only around 5% recover to normal, while 20% regain some upper limb capabilities5. More than half of human life requires the participation of the upper limbs6, and upper limb dysfunction after a stroke severely affects patients' activities of daily living7, significantly decreasing their quality of life8 and increasing their financial burden9. Therefore, it is particularly important to explore effective methods of upper limb functional rehabilitation.
Various clinical upper limb rehabilitation treatments, such as mirror therapy, constraint-induced movement therapy, functional electrical stimulation, and other active or passive training, are commonly utilized for stroke patients3,10. In recent years, bilateral arm training has garnered increased attention6,11,12. It has been demonstrated to enhance neural connectivity between the sensorimotor areas of both ipsilateral and contralateral hemispheres12. This type of training helps correct abnormalities in interhemispheric inhibition, facilitates reorganization of brain functional networks, and ultimately leads to improvements in upper limb function12,13. Furthermore, robot-assisted training has also been shown to assist patients in consistently executing accurate limb movements and engaging in task-specific training14. This process provides the brain with substantial feedback stimulation, ultimately boosting neuroplasticity and aiding in the restoration of upper limb function in individuals with hemiplegia14,15. There is currently limited research on strategies utilizing robot-assisted dual upper limb training for stroke patients. This study employed a dual upper limb task-oriented robotic system to combine robot-assisted training with bilateral upper limb training. The robotic device was utilized to aid stroke patients in conducting dual upper limb task-oriented training with high repetitions in a proper movement pattern. The objective of the research was to evaluate the effects of this method on the corticospinal pathway, upper-limb function, and activities of daily living in stroke survivors, with the aim of discovering innovative strategies for upper limb functional rehabilitation.

<table><tbody><tr><td>Dual upper limb task-oriented robotic system</td><td>Auckland Tongji Rehabilitation Medical Equipment Research Center, Tongji Zhejiang College</td><td>N/A</td><td>The dual upper limb task-oriented robotic system can aid stroke patients in bilateral upper limb virtual game training by regulating force transmission between the healthy and affected upper limbs.</td></tr><tr><td>Magnetic stimulation therapy system</td><td>Sichuan Junjian Wanfeng Medical Equipment Co.,Ltd.</td><td>http://www.jjwf-med.com</td><td>&lt;br/&gt; This system can be used to measure the Motor evoked potential (MEP)</td></tr><tr><td>SPSS 25.0</td><td>IBM</td><td>Version 25.0</td><td>https://www.ibm.com/support/pages/downloading-ibm-spss-statistics-25</td></tr></tbody></table>

application of a dual upper limb task-oriented robotic system for the functional recovery of the upper limb in stroke patients

Highly repetitive and task-oriented training has been shown to promote the recovery of limb function in stroke patients. Additionally, bilateral arm training can help stroke survivors regain their upper limb function and improve their daily activities. The dual upper limb task-oriented robotic system is designed to assist the healthy side of the stroke patient in driving the affected side to perform bilateral arm training through the use of a robotic device. It can also guide the patient in carrying out dual upper limb coordinated movements and engage them in a task-oriented virtual game using force feedback and human-computer interaction technology. This study aimed to assess the efficacy of the system in enhancing upper limb function and activities of daily living in stroke patients. The assessment methods used included motor evoked potential (MEP), functional test for the hemiplegic upper extremity-Hong Kong (FTHUE-HK), Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE), and modified Barthel index (MBI). The results of the study indicate that the dual upper limb task-oriented robotic system can significantly improve the corticospinal pathway, upper limb function, and activities of daily living in stroke patients after 6 weeks of treatment. This system can serve as an effective adjunct to upper limb functional rehabilitation in stroke survivors, reducing the dependence on rehabilitation therapists. In conclusion, the dual upper limb task-oriented robotic system provides a new strategy for post-stroke limb functional rehabilitation and holds great potential for application, as it offers certain social and financial benefits.

A total of 60 stroke patients were divided into a control group (n = 30) and an experimental group (n = 30) for this study. Upon comparing age, gender, stroke type, disease duration, side of hemiplegia, and other general information between the two groups, no statistically significant differences were found (P &#62; 0.05), indicating their comparability (Table 1). Patients in the experimental group, who underwent training with a dual upper limb task-oriented robotic system, showed greater improvements in...

Author Spotlight: Enhancing Upper Limb Rehabilitation in Stroke Patients Through Advanced Robotic and Neuromodulation Technologies

This experimental protocol outlines the use of a dual upper limb task-oriented robotic system for stroke patients with upper limb dysfunction. The findings indicate that this system can significantly improve stroke patients' upper limb function and daily living activities.

Application of a Dual Upper Limb Task-Oriented Robotic System for the Functional Recovery of the Upper Limb in Stroke Patients

Highly repetitive and task-oriented training has been shown to promote the recovery of limb function in stroke patients. Additionally, bilateral arm ...

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Research

JoVE Journal

Medicine

479 Views.  Graduate School of Zhejiang Chinese Medical University. Ons onderzoek is gericht op de revalidatie van patiënten die een beroerte of traumatisch hersenletsel hebben gehad, en we proberen de impact te onderzoeken van onze robot-geassisteerde trainingsstrategie voor de bovenste ledematen op het herstel van de functie van de bovenste ledematen bij patiënten met een beroerte. Ons protocol integreert bilaterale training van de bovenste ledematen, taakgerichte activiteiten en robotondersteunde training om de revalidat...

Video: Auteur in de schijnwerpers: verbetering van de revalidatie van de bovenste ledematen bij patiënten met een beroerte door middel van geavanceerde robot- en neuromod

Driving Simulation in the Clinic: Testing Visual Exploratory Behavior in Daily Life Activities in Patients with Visual Field Defects

Patients suffering from homonymous hemianopia after infarction of the posterior cerebral artery (PCA) report different degrees of constraint in daily life, despite similar visual deficits. We assume this could be due to variable development of compensatory strategies such as altered visual scanning behavior. Scanning compensatory therapy (SCT) is studied as part of the visual training after infarction next to vision restoration therapy. SCT consists of learning to make larger eye movements into the blind field enlarging the visual field of search, which has been proven to be the most useful strategy1, not only in natural search tasks but also in mastering daily life activities2. Nevertheless, in clinical routine it is difficult to identify individual levels and training effects of compensatory behavior, since it requires measurement of eye movements in a head unrestrained condition. Studies demonstrated that unrestrained head movements alter the visual exploratory behavior compared to a head-restrained laboratory condition3. Martin et al.4 and Hayhoe et al.5 showed that behavior demonstrated in a laboratory setting cannot be assigned easily to a natural condition. Hence, our goal was to develop a study set-up which uncovers different compensatory oculomotor strategies quickly in a realistic testing situation: Patients are tested in the clinical environment in a driving simulator. SILAB software (Wuerzburg Institute for Traffic Sciences GmbH (WIVW)) was used to program driving scenarios of varying complexity and recording the driver's performance. The software was combined with a head mounted infrared video pupil tracker, recording head- and eye-movements (EyeSeeCam, University of Munich Hospital, Clinical Neurosciences).
The positioning of the patient in the driving simulator and the positioning, adjustment and calibration of the camera is demonstrated. Typical performances of a patient with and without compensatory strategy and a healthy control are illustrated in this pilot study. Different oculomotor behaviors (frequency and amplitude of eye- and head-movements) are evaluated very quickly during the drive itself by dynamic overlay pictures indicating where the subjects gaze is located on the screen, and by analyzing the data. Compensatory gaze behavior in a patient leads to a driving performance comparable to a healthy control, while the performance of a patient without compensatory behavior is significantly worse. The data of eye- and head-movement-behavior as well as driving performance are discussed with respect to different oculomotor strategies and in a broader context with respect to possible training effects throughout the testing session and implications on rehabilitation potential.

Patients with visual deficits after stroke report about different constraints in daily life most likely due to variable compensatory strategies, which are difficult to differentiate in clinical routine. We present a clinical set-up which allows measurement of different compensatory head- and eye-movement-strategies and evaluating their effects on driving performance.

Patients suffering from homonymous hemianopia after infarction of the posterior cerebral artery (PCA) report different degrees of constraint in daily ...

Utilizing Repetitive Transcranial Magnetic Stimulation to Improve Language Function in Stroke Patients with Chronic Non-fluent Aphasia

Transcranial magnetic stimulation (TMS) has been shown to significantly improve language function in patients with non-fluent aphasia1. In this experiment, we demonstrate the administration of low-frequency repetitive TMS (rTMS) to an optimal stimulation site in the right hemisphere in patients with chronic non-fluent aphasia. A battery of standardized language measures is administered in order to assess baseline performance. Patients are subsequently randomized to either receive real rTMS or initial sham stimulation. Patients in the real stimulation undergo a site-finding phase, comprised of a series of six rTMS sessions administered over five days; stimulation is delivered to a different site in the right frontal lobe during each of these sessions. Each site-finding session consists of 600 pulses of 1 Hz rTMS, preceded and followed by a picture-naming task. By comparing the degree of transient change in naming ability elicited by stimulation of candidate sites, we are able to locate the area of optimal response for each individual patient. We then administer rTMS to this site during the treatment phase. During treatment, patients undergo a total of ten days of stimulation over the span of two weeks; each session is comprised of 20 min of 1 Hz rTMS delivered at 90% resting motor threshold. Stimulation is paired with an fMRI-naming task on the first and last days of treatment. After the treatment phase is complete, the language battery obtained at baseline is repeated two and six months following stimulation in order to identify rTMS-induced changes in performance. The fMRI-naming task is also repeated two and six months following treatment. Patients who are randomized to the sham arm of the study undergo sham site-finding, sham treatment, fMRI-naming studies, and repeat language testing two months after completing sham treatment. Sham patients then cross over into the real stimulation arm, completing real site-finding, real treatment, fMRI, and two- and six-month post-stimulation language testing.

We explore the use of repetitive transcranial magnetic stimulation (rTMS) to improve language abilities in patients with chronic stroke and non-fluent aphasia. After identifying a site in the right frontal gyrus for each patient that responds optimally to stimulation, we target this site during ten days of rTMS treatment.

Transcranial magnetic stimulation (TMS) has been shown to significantly improve language function in patients with non-fluent aphasia1. In this ...

Lesion Explorer: A Video-guided, Standardized Protocol for Accurate and Reliable MRI-derived Volumetrics in Alzheimer's Disease and Normal Elderly

Obtaining in vivo human brain tissue volumetrics from MRI is often complicated by various technical and biological issues. These challenges are exacerbated when significant brain atrophy and age-related white matter changes (e.g. Leukoaraiosis) are present. Lesion Explorer (LE) is an accurate and reliable neuroimaging pipeline specifically developed to address such issues commonly observed on MRI of Alzheimer's disease and normal elderly. The pipeline is a complex set of semi-automatic procedures which has been previously validated in a series of internal and external reliability tests1,2. However, LE's accuracy and reliability is highly dependent on properly trained manual operators to execute commands, identify distinct anatomical landmarks, and manually edit/verify various computer-generated segmentation outputs.
LE can be divided into 3 main components, each requiring a set of commands and manual operations: 1) Brain-Sizer, 2) SABRE, and 3) Lesion-Seg. Brain-Sizer's manual operations involve editing of the automatic skull-stripped total intracranial vault (TIV) extraction mask, designation of ventricular cerebrospinal fluid (vCSF), and removal of subtentorial structures. The SABRE component requires checking of image alignment along the anterior and posterior commissure (ACPC) plane, and identification of several anatomical landmarks required for regional parcellation. Finally, the Lesion-Seg component involves manual checking of the automatic lesion segmentation of subcortical hyperintensities (SH) for false positive errors.
While on-site training of the LE pipeline is preferable, readily available visual teaching tools with interactive training images are a viable alternative. Developed to ensure a high degree of accuracy and reliability, the following is a step-by-step, video-guided, standardized protocol for LE's manual procedures.

Lesion Explorer (LE) is a semi-automatic, image-processing pipeline developed to obtain regional brain tissue and subcortical hyperintensity lesion volumetrics from structural MRI of Alzheimer's disease and normal elderly. To ensure a high level of accuracy and reliability, the following is a video-guided, standardized protocol for LE's manual procedures.

Obtaining in vivo human brain tissue volumetrics from MRI is often complicated by various technical and biological issues. These challenges are ...

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke

Examining molecular mechanisms involved in neuropathological conditions, such as ischemic stroke, can be difficult when using whole animal systems. As such, primary or &#39;neuronal-like&#39; cell culture systems are commonly utilized. While&#160;these systems are relatively easy to work with, and are useful model systems in which various functional outcomes (such as cell death) can be readily quantified, the examined outcomes and pathways in cultured immature neurons (such as excitotoxicity-mediated cell death pathways) are not necessarily the same as those observed in mature brain, or in intact tissue. Therefore, there is the need to develop models in which cellular mechanisms in mature neural tissue can be examined. We have developed an in vitro technique that can be used to investigate a variety of molecular pathways in intact nervous tissue. The technique described herein utilizes rat cortical tissue, but this technique can be adapted to use tissue from a variety of species (such as mouse, rabbit, guinea pig, and chicken) or brain regions (for example, hippocampus, striatum, etc.). Additionally, a variety of stimulations/treatments can be used (for example, excitotoxic, administration of inhibitors, etc.). In conclusion, the brain slice model described herein can be used to examine a variety of molecular mechanisms involved in excitotoxicity-mediated brain injury.

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke

We have developed a brain slice model which can be used to examine molecular mechanisms involved in excitotoxicity-mediated brain injury.&#160;This technique generates viable mature brain tissue and reduces animal numbers required for experimentation, whilst keeping the neuronal circuitry, cellular interactions, and postsynaptic compartments partly intact.

Examining molecular mechanisms involved in neuropathological conditions, such as ischemic stroke, can be difficult when using whole animal systems. As ...

Robotic Mirror Therapy System for Functional Recovery of Hemiplegic Arms

Mirror therapy has been performed as effective occupational therapy in a clinical setting for functional recovery of a hemiplegic arm after stroke. It is conducted by eliciting an illusion through use of a mirror as if the hemiplegic arm is moving in real-time while moving the healthy arm. It can facilitate brain neuroplasticity through activation of the sensorimotor cortex. However, conventional mirror therapy has a critical limitation in that the hemiplegic arm is not actually moving. Thus, we developed a real-time 2-axis mirror robot system as a simple add-on module for conventional mirror therapy using a closed feedback mechanism, which enables real-time movement of the hemiplegic arm. We used 3 Attitude and Heading Reference System sensors, 2 brushless DC motors for elbow and wrist joints, and exoskeletal frames. In a feasibility study on 6 healthy subjects, robotic mirror therapy was safe and feasible. We further selected tasks useful for activities of daily living training through feedback from rehabilitation doctors. A chronic stroke patient showed improvement in the Fugl-Meyer assessment scale and elbow flexor spasticity after a 2-week application of the mirror robot system. Robotic mirror therapy may enhance proprioceptive input to the sensory cortex, which is considered to be important in neuroplasticity and functional recovery of hemiplegic arms. The mirror robot system presented herein can be easily developed and utilized effectively to advance occupational therapy.

We developed a real-time mirror robot system for functional recovery of hemiplegic arms using automatic control technology, conducted a clinical study on healthy subjects, and determined tasks through feedback from rehabilitation doctors. This simple mirror robot can be applied effectively to occupational therapy in stroke patients with a hemiplegic arm.

Mirror therapy has been performed as effective occupational therapy in a clinical setting for functional recovery of a hemiplegic arm after stroke. It is ...

Bioengineering

Remote Limb Ischemic Preconditioning:  A Neuroprotective Technique in Rodents

Sublethal ischemia protects tissues against subsequent, more severe ischemia through the upregulation of endogenous mechanisms in the affected tissue. Sublethal ischemia has also been shown to upregulate protective mechanisms in remote tissues. A brief period of ischemia (5-10 min) in the hind limb of mammals induces self-protective responses in the brain, lung, heart and retina. The effect is known as remote ischemic preconditioning (RIP). It is a therapeutically promising way of protecting vital organs, and is already under clinical trials for heart and brain injuries. This publication demonstrates a controlled, minimally invasive method of making a limb &#8211; specifically the hind limb of a rat &#8211; ischemic. A blood pressure cuff developed for use in human neonates is connected to a manual sphygmomanometer and used to apply 160 mmHg pressure around the upper part of the hind limb. A probe designed to detect skin temperature is used to verify the ischemia, by recording the drop in skin temperature caused by pressure-induced occlusion of the leg arteries, and the rise in temperature which follows release of the cuff. This method of RIP affords protection to the rat retina against bright light-induced damage and degeneration.

Remote ischemic preconditioning (RIP) is a method of conditioning tissues against damaging stress. We have established a method of remote ischemia at the hind limb, by inflating a sphygmomanometer cuff for 5-10 min. The neuroprotective capabilities of RIP have been demonstrated in a model of retinal degeneration in rodents.

Sublethal ischemia protects tissues against subsequent, more severe ischemia through the upregulation of endogenous mechanisms in the affected tissue. ...

Orthotopic Hind Limb Transplantation in the Mouse

In vivo animal model systems, and in particular mouse models, have evolved into powerful and versatile scientific tools indispensable to basic and translational research in the field of transplantation medicine. A vast array of reagents is available exclusively in this setting, including mono- and polyclonal antibodies for both diagnostic and interventional applications. In addition, a vast number of genotyped, inbred, transgenic, and knock out strains allow detailed investigation of the individual contributions of humoral and cellular components to the complex interplay of an immune response and make the mouse the gold standard for immunological research. 
Vascularized Composite Allotransplantation (VCA) delineates a novel field of transplantation using allografts to replace "like with like" in patients suffering traumatic or congenital tissue loss. This surgical methodological protocol shows the use of a non-suture cuff technique for super-microvascular anastomosis in an orthotopic mouse hind limb transplantation model. The model specifically allows for comparison between established paradigms in solid organ transplantation with a novel form of transplants consisting of various different tissue components. Uniquely, this model allows for the transplantation of a viable vascularized bone marrow compartment and niche that have the potential to exert a beneficial effect on the balance of immune acceptance and rejection. This technique provides a tool to investigate alloantigen recognition and allograft rejection and acceptance, as well as enables the pursuit of functional nerve regeneration studies to further advance this novel field of transplantation.

This novel model for orthotopic hind limb transplantation in the mouse, applying a non-suture cuff technique for super-microvascular anastomosis, provides a powerful tool for in&#160;vivo mechanistic immunological research related to vascularized composite allotransplantation (VCA).

In vivo animal model systems, and in particular mouse models, have evolved into powerful and versatile scientific tools indispensable to basic and ...

Development of a Novel Task-oriented Rehabilitation Program using a Bimanual Exoskeleton Robotic Hand

A robot-assisted hand is used for the rehabilitation of patients with impaired upper limb function, particularly for stroke patients with a loss of motor control. However, it is unclear how conventional occupational training strategies can be applied to the use of rehabilitation robots. Novel robotic technologies and occupational therapy concepts are used to develop a protocol that allows patients with impaired upper limb function to grasp objects using their affected hand through a variety of pinching and grasping functions. To conduct this appropriately, we used five types of objects: a peg, a rectangular cube, a cube, a ball, and a cylindrical bar. We also equipped the patients with a robotic hand, the Mirror Hand, an exoskeleton&#160;hand that is fitted to the subject&#8217;s affected hand and follows the movement of the sensor glove fitted to their unaffected hand (bimanual movement training (BMT)). This study had two stages. Three healthy subjects were first recruited to test the feasibility and acceptability of the training program. Three patients with hand dysfunction caused by stroke were then recruited to confirm the feasibility and acceptability of the training program, which was conducted on 3 consecutive days. On each day, the patient was monitored during 5 min of movement in a passive range of motion, 5 min of robot-assisted bimanual movement, and task-oriented training using the five objects. The results showed that both healthy subjects and subjects who had suffered a stroke in conjunction with the robotic hand could successfully grasp the objects. Both healthy subjects and those who had suffered a stroke performed well with the robot-assisted task-oriented training program in terms of feasibility and acceptability.

This study reports the development of a novel robot-assisted task-oriented program for hand rehabilitation. The developmental process consists of experiments using both healthy subjects and subjects who have had a stroke and suffered from subsequent motor control dysfunction.

A robot-assisted hand is used for the rehabilitation of patients with impaired upper limb function, particularly for stroke patients with a loss of motor ...

Enhancing Stroke Rehabilitation with Virtual Reality-Based Occupational Training

Cognitive Function and Upper Limb Rehabilitation Training Post-Stroke Using a Digital Occupational Training System

Stroke rehabilitation often requires frequent and intensive therapy to improve functional recovery. Virtual reality (VR) technology has shown the potential to meet these demands by providing engaging and motivating therapy options. The digital occupational training system is a VR application that utilizes cutting-edge technologies, including multi-touch screens, virtual reality, and human-computer interaction, to offer diverse training techniques for advanced cognitive capacity and hand-eye coordination abilities. The objective of this study was to assess the effectiveness of this program in enhancing cognitive function and upper extremity rehabilitation in stroke patients. The training and assessment consist of five cognitive modules covering perception, attention, memory, logical reasoning, and calculation, along with hand-eye coordination training. This research indicates that after eight weeks of training, the digital occupational training system can significantly improve cognitive function, daily living skills, attention, and self-care abilities in stroke patients. This software can be employed as a time-saving and clinically effective rehabilitation aid to complement traditional one-on-one occupational therapy sessions. In summary, the digital occupational training system shows promise and offers potential financial benefits as a tool to support the functional recovery of stroke patients.

Author Spotlight: Rehabilitation of Stroke Patients With a Digital Occupational Training System

The current protocol outlines how the VR-based digital occupational training system enhances the rehabilitation of patients with cognitive impairment and upper limb dysfunction following a stroke.

Stroke rehabilitation often requires frequent and intensive therapy to improve functional recovery. Virtual reality (VR) technology has shown the ...

Integrated Robotic and Conventional Therapy for Post-Stroke Upper Limb Recovery

Enhancing Upper Limb Function and Motor Skills Post-Stroke Through an Upper Limb Rehabilitation Robot

Cerebrovascular accidents, commonly known as strokes, represent a prevalent neurological event leading to significant upper limb disabilities, thereby profoundly affecting individuals' activities of daily living and diminishing their quality of life. Traditional rehabilitation methods for upper limb recovery post-stroke are often hindered by limitations, including therapist and patient fatigue, reliance on singular training methodologies, and lack of sustained motivation. Addressing these challenges, this study introduces an upper limb rehabilitation robot, which uses intelligent feedback motion control to improve therapeutic outcomes. The system is distinguished by its capability to adjust the direction and magnitude of force feedback dynamically, based on the detection of spastic movements during exercises, thereby offering a tailored therapeutic experience. This system is equipped with four distinct training modes, intelligent assessment of joint range of motion, and the ability to personalize training programs. Moreover, it provides an immersive interactive gaming experience coupled with comprehensive safety measures. This multifaceted approach not only elevates the engagement and interest of participants beyond traditional rehabilitation protocols but also demonstrates significant improvements in upper limb functionality and the activities of daily living among hemiplegic patients. The system exemplifies an advanced tool in upper limb rehabilitation, offering a synergistic blend of precision, personalization, and interactive engagement, thereby broadening the therapeutic options available to stroke survivors.

Author Spotlight: Enhancing Post-Stroke Upper Limb Rehabilitation with Robotic Technologies for Improved Motor Recovery and Functional Outcomes

This protocol describes an upper limb rehabilitation robot that provides intelligent feedback through four modes. These modes enhance upper limb function and flexibility, thereby improving patients' quality of life.

Cerebrovascular accidents, commonly known as strokes, represent a prevalent neurological event leading to significant upper limb disabilities, thereby ...

Application of a Dual Upper Limb Task-Oriented Robotic System for the Functional Recovery of the Upper Limb in Stroke Patients

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