Robot-assisted therapy in stratified intervention: a randomized controlled trial on poststroke motor recovery.

Objective: To compare the effects of robot-assisted therapy with conventional therapy for accelerating stratified intervention in poststroke patients with upper limb dysfunction. Background: For stroke survivors, recovery of upper extremity function remains a major challenge in rehabilitation. Literature has suggested that the rate of recovery may improve if treatments can be individualized to their clinical profiles. However, there still lack clinical evidence on how to create treatment tailored to individual patients. Robot-assisted Therapy (RT) provides a straightforward approach to adjustment of the assistance-resistance continuum for individual patients. In early Brunnstrom stages of recovery, patients benefit from assistance training, whereas in later stages the training is favored with resistance. Therefore, RT may enhance Conventional Therapy (CT) but the use of RT in stratified intervention has not been investigated. This study evaluated the possible benefit of adopting RT following a protocol of upper-limb training, which was stratified with the Brunnstrom stage of each individual. Methods: This study was a single-blinded randomized controlled trial. A total of 53 patients with stroke were recruited and randomized into 2 groups (CT, n = 27, 3 dropped out and RT, n = 26, 2 dropped out). Both groups were trained once per day, 5 days per week for 4 weeks. The CT group received 30 min of conventional therapy; the RT group received 30 min of upper limb robot-assisted training. Patients were assessed at the beginning, week-2, and week-4 of the treatment. The outcome measures included the Fugl-Meyer Assessment Upper-Extremity (FMA-UE) and the Modified Barthel Index (MBI). Results: Across the 4-week intervention, participants in the RT group recovered 1.979 points of FMA-UE per week, compared to 1.198 points per week in the CT group (t94 = 3.333, p < 0.01); the recovery rate was 0.781 points/week higher in the RT group than in the CT group. Moreover, the recovery of FMA-UE was faster in proximal joints (t94 = 3.199, p < 0.01), and for patients in Brunnstrom Stage III (t34 = 2.526, p < 0.05). The improvements in MBI were not significantly different between RT and CT. Conclusion: Robot-assisted therapy showed initial evidence for the acceleration of post-stroke recovery of motor function in the upper limb. Initial observations suggested that patients in Brunnstrom recovery stage III might benefit the most from the stratified intervention assisted by robotics. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=61834, Identifier [ChiCTR2000039010]. Registered 13 March 2020.

Efficacy and safety of hepatic arterial infusion chemotherapy combined with fruquintinib and tislelizumab for patients with microsatellite stable colorectal cancer liver metastasis following failure of multiple-line therapy.

Background and aim: The prognosis of microsatellite stable (MSS)-colorectal cancer liver metastasis (CRCLM) following failure of multi-line therapy remains dismal. The aim of this study is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) plus fruquintinib and tislelizumab (HAIC-F-T treatment) for MSS-CRCLM which failed from multiple-line therapy. Methods: From February 2021 to June 2023, 45 patients with MSS-CRCLM after failure of multiple-line therapy who received HAIC combined with fruquintinib and tislelizumab (HAIC-F-T triple treatment) were enrolled. The combination therapy included HAIC regimens with oxaliplatin and 5-fluorouracil or irinotecan, oxaliplatin, and 5-fluorouracil on days 1-2, intravenous tislelizumab (200 mg) before HAIC on day 1, and oral fruquintinb (3 mg/d) on day 3-21, every 4 weeks. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Results: The follow-up ended on June 22, 2024, with a median follow-up time of 17.5 months. The objective response rate was 42.2%, and the disease control rate was 82.2%. The median OS was 15.3 months (95% confidence interval [CI]:12.634-17.966), and the median PFS was 7.5 months (95% CI:5.318-9.682). The independent risk factors related to worse OS were previous PD-1 immunotherapy (P = 0.021) and the number of HAIC-F-T triple treatment cycles of ≤ 2 (P = 0.007). The incidence of grade 3 or higher adverse events (AEs) was 20%, with the most frequent grade 3 or higher AEs being abdominal pain (3/45, 6.7%). Conclusion: HAIC combined with fruquintinib and tislelizumab may be an alternative salvage treatment for patients with MSS-CRCLM following failure of multiple-line therapy.

Neurological activation during verbal fluency task and resting-state functional connectivity abnormalities in obsessive-compulsive disorder: a functional near-infrared spectroscopy study.

Objective: This study aims to investigate the activation of frontotemporal functional brain areas in patients with Obsessive-Compulsive Disorder (OCD) during a Verbal Fluency Task (VFT), and to compare their brain functional connectivity in a resting state with that of healthy controls. The goal is to deepen our understanding of the neuropathological mechanisms underlying OCD. Methods: 32 patients with OCD and 32 controls matched for age, gender, handedness, and years of education participated in this study, they were divided into OCD group and healthy comtrol group. We conducted VFT task tests and 10-minute resting state tests on both groups by using functional Near-Infrared Spectroscopy (fNIRS). The VFT was utilized to assess the activation (beta values) and the integral and centroid values of the frontal and bilateral temporal lobes, including brain areas BA9 and 46 (dorsolateral prefrontal cortex), BA10 (frontal pole), BA45 (inferior frontal gyrus), BA21 (middle temporal gyrus), and BA22 (superior temporal gyrus). We evaluated the functional connectivity levels of these areas during the resting state. Differences in these measures between OCD patients and healthy controls were analyzed using two-sample independent t-tests and non-parametric Mann-Whitney U tests. Results: During VFT, OCD had smaller integral values(z=5.371, p<0.001; t=4.720, p<0.001), and larger centroid values(t=-2.281, p=0.026; z=-2.182, p=0.029) compared to healthy controls, along with a reduced number of activated channels detected by fNIRS. Additionally, activation values (ß) in various functional brain areas, including BA9, BA46, BA10, BA45, BA21, and BA22, were significantly lower in the OCD group (all p< 0.01). In the resting state, notable disparities in functional connectivity were observed between the inferior frontal gyrus (IFG) and dorsolateral prefrontal cortex (DLPFC) in the OCD group, in comparison to the control group. Specifically, there was a significant increase in connectivity between the left IFG and right DLPFC, suggesting the presence of altered connectivity patterns in these areas. Conclusions: The study highlights significant disparities in neural activation and functional connectivity between OCD patients and healthy controls during VFT. Specifically, reduced activation was noted in the frontal and bilateral temporal lobes of OCD patients, alongside alterations in resting-state functional connectivity between the IFG and DLPFC. These findings contribute to our understanding of the neurobiological underpinnings of OCD and may guide future therapeutic strategies.

Hemodynamic activity is not parsimoniously tuned to index-of-difficulty in movement with dual requirements on speed-accuracy.

Background: Reaching movements are crucial for daily living and rehabilitation, for which Fitts' Law describes a speed-accuracy trade-off that movement time increases with task difficulty. This study aims to investigate whether cortical activation in motor-related areas is directly linked to task difficulty as defined by Fitts' Law. Understanding this relationship provides a physiological basis for parameter selection in therapeutic exercises. Methods: Sixteen healthy subjects performed 2D reaching movements using a rehabilitation robot, with their cortical responses detected using functional near-infrared spectroscopy (fNIRS). Task difficulty was manipulated by varying target size and distance, resulting in 3 levels of index-of-difficulty (ID). Kinematic signals were recorded alongside cortical activity to assess the relationship among movement time, task difficulty, and cortical activation. Results: Our results showed that movement time increased with ID by 0.2974s/bit across all subjects (conditional r2 = 0.6434, p < 0.0001), and all subjects showed individual trends conforming Fitts' Law (all p < 0.001). Neither activation in BA4 nor in BA6 showed a significant correlation with ID (p > 0.05), while both the target size and distance, as well as the interaction between them, showed a significant relationship with BA4 or BA6 activation (all p < 0.05). Conclusion: This study found that although kinematic measures supported Fitts' Law, cortical activity in motor-related areas during reaching movements did not correlate directly with task difficulty as defined by Fitts' Law. Additional factors such as muscle activation may call for different cortical control even when difficulty was identical.

Extrachromosomal circular DNA (eccDNA) characteristics in the bile and plasma of advanced perihilar cholangiocarcinoma patients and the construction of an eccDNA-related gene prognosis model.

Extrachromosomal DNAs (eccDNAs) frequently carry amplified oncogenes. This investigation aimed to examine the occurrence and role of eccDNAs in individuals diagnosed with advanced perihilar cholangiocarcinoma (pCCA) who exhibited distinct prognostic outcomes. Five patients with poor survival outcomes and five with better outcomes were selected among patients who received first-line hepatic arterial infusion chemotherapy from June 2021 to June 2022. The extracted eccDNAs were amplified for high-throughput sequencing. Genes associated with the differentially expressed eccDNAs were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The differentially expressed bile eccDNA-related genes were used to construct a prognostic model. Across all 10 patients, a total of 19,024 and 3,048 eccDNAs were identified in bile and plasma, respectively. The concentration of eccDNA detected in the bile was 9-fold higher than that in plasma. The chromosome distribution of the eccDNAs were similar between bile and matched plasma. GO and KEGG pathway analyses showed enrichment in the mitogen-activated protein kinase (MAPK) and Wnt/ß-catenin pathways in patients with poor survival outcomes. According to the prognostic model constructed by eccDNA-related genes, the high-risk group of cholangiocarcinoma patients displayed significantly shorter overall survival (p < 0.001). Moreover, the degree of infiltration of immunosuppressive cells was higher in patients in the high-risk group. In conclusion, EccDNA could be detected in bile and plasma of pCCA patients, with a higher concentration. A prognostic model based on eccDNA-related genes showed the potential to predict the survival and immune microenvironment of patients with cholangiocarcinoma.

NLCECA score: a serum inflammatory-tumor biomarker score to predict survival of advanced perihilar cholangiocarcinoma after hepatic arterial infusion chemotherapy.

Prognostic features in advanced perihilar cholangiocarcinoma (pCCA) patients who received first-line hepatic arterial infusion chemotherapy (HAIC) are unknown. The purpose of our study was to develop an applicable score based on serum inflammatory-tumor biomarkers to predict the survival of advanced pCCA patients who received first-line HAIC. In total, 106 advanced pCCA patients were enrolled as the training cohort. The optimal cutoff values of baseline variables were defined by the receiver operating characteristic method or according to previous publications. According to the results of Cox regression analysis, baseline neutrophil-to-lymphocyte ratio (NLR) > 3.19, carcinoembryonic antigen (CEA) > 10 ng/mL, and carbohydrate antigen 19-9 (CA19-9) > 200 U/mL were identified as independent survival predictors, which were used to develop the NLCECA score (NLR, CEA, and CA19-9). When including the NLCECA score in the multivariate analysis, the NLCECA score was the only independent predictor of survival. The risk of survival decreased by 111.9% for each 1-point increase in the NLCECA score. Additionally, the NLCECA score could also predict survival in another 33 patients in the validation cohort (P < 0.001). In summary, the NLCECA score is a potential biomarker system for predicting the survival of advanced pCCA patients who received first-line HAIC.

Using sEMG Signal Frequency to Evaluate Post-Stroke Elbow Spasticity.

Spasticity is a motor disorder with high prevalence and critical consequences following a stroke. Reliable and sensitive measurements are important to guide the selection and evaluation of treatment strategies. Technology-assisted methods, such as the surface electromyography (sEMG) technique, have been developed to measure spasticity as sensitive and accurate alternatives to commonly used clinical scales. However, sEMG amplitude based measures may confound spasticity-induced muscle activities with other types of muscle contractions. This study thus introduces the idea of using sEMG frequency information to detect spasticity as a potential solution to overcome the limitations of existing sEMG based measures. The preliminary results of three patients demonstrate the possibility and future research directions for this approach.

Differentiation in additive and multiplicative inputs to motoneuron pool as origins of spasticity - a neuromorphic modeling study.

Spasticity is characterized by a velocity-dependent increase in the tonic stretch reflex. Evidence suggests that spasticity originates from hyperactivity in the descending tract or reflex loop. To pinpoint the source of hyperactivity, however, is difficult due to lack of human data in-vivo. Thus, we implemented a neuromorphic model to revive the neurodynamics with spiking neuronal activity. Two types of input were modeled: (1) the additive condition (ADD) to apply tonic synaptic inputs directly into the reflex loop; (2) the multiplicative (MUL) condition to adjust the loop gains within the reflex loop. Results show that both conditions produced antagonist EMG responses resembling patient data. The timing of spasticity is more sensitive to the ADD condition, whereas the amplitude of spastic EMG is more sensitive to the MUL condition. In conclusion, our model shows that both additive and multiplicative hyperactivities suffice to elicit velocity-dependent spastic electromyographic signals (EMG), but with different sensitivities. This simulation study suggests that spasticity caused by different origins may be discernable by the progression of severity, which may help individualized goalsetting and parameter-selection in rehabilitation.Clinical Relevance-Potential application of neuromorphic modeling on spasticity includes selection of parameters for therapeutic plans, such as movement range, repetition, and load.

Heavier Load Alters Upper Limb Muscle Synergy with Correlated fNIRS Responses in BA4 and BA6.

In neurorehabilitation, motor performances may improve if patients could accomplish the training by overcoming mechanical loads. When the load inertia is increased, it has been found to trigger linear responses in motor-related cortices. The cortical responses, however, are unclear whether they also correlate to changes in muscular patterns. Therefore, it remains difficult to justify the magnitude of load during rehabilitation because of the gap between cortical and muscular activation. Here, we test the hypothesis that increases in load inertia may alter the muscle synergies, and the change in synergy may correlate with cortical activation. Twelve healthy subjects participated in the study. Each subject lifted dumbbells (either 0, 3, or 15 pounds) from the resting position to the armpit repetitively at 1 Hz. Surface electromyographic signals were collected from 8 muscles around the shoulder and the elbow, and hemodynamic signals were collected using functional near-infrared spectroscopy from motor-related regions Brodmann Area 4 (BA4) and BA6. Results showed that, given higher inertia, the synergy vectors differed farther from the baseline. Moreover, synergy similarity on the vector decreased linearly with cortical responses in BA4 and BA6, which associated with increases in inertia. Despite studies in literature that movements with similar kinematics tend not to differ in synergy vectors, we show a different possibility that the synergy vectors may deviate from a baseline. At least 2 consequences of adding inertia have been identified: to decrease synergy similarity and to increase motor cortical activity. The dual effects potentially provide a new benchmark for therapeutic goal setting.

Substitutive proprioception feedback of a prosthetic wrist by electrotactile stimulation.

Objective: Sensory feedback of upper-limb prostheses is widely desired and studied. As important components of proprioception, position, and movement feedback help users to control prostheses better. Among various feedback methods, electrotactile stimulation is a potential method for coding proprioceptive information of a prosthesis. This study was motivated by the need for proprioception information for a prosthetic wrist. The flexion-extension (FE) position and movement information of the prosthetic wrist are transmitted back to the human body through multichannel electrotactile stimulation. Approach: We developed an electrotactile scheme to encode the FE position and movement of the prosthetic wrist and designed an integrated experimental platform. A preliminary experiment on the sensory threshold and discomfort threshold was performed. Then, two proprioceptive feedback experiments were performed: a position sense experiment (Exp 1) and a movement sense experiment (Exp 2). Each experiment included a learning session and a test session. The success rate (SR) and discrimination reaction time (DRT) were analyzed to evaluate the recognition effect. The acceptance of the electrotactile scheme was evaluated by a questionnaire. Main results: Our results showed that the average position SRs of five able-bodied subjects, amputee 1, and amputee 2 were 83.78, 97.78, and 84.44%, respectively. The average movement SR, and the direction and range SR of wrist movement in five able-bodied subjects were 76.25, 96.67%, respectively. Amputee 1 and amputee 2 had movement SRs of 87.78 and 90.00% and direction and range SRs of 64.58 and 77.08%, respectively. The average DRT of five able-bodied subjects was less than 1.5 s and that of amputees was less than 3.5 s. Conclusion: The results indicate that after a short period of learning, the subjects can sense the position and movement of wrist FE. The proposed substitutive scheme has the potential for amputees to sense a prosthetic wrist, thus enhancing the human-machine interaction.

Increased Inertia Triggers Linear Responses in Motor Cortices during Large-Extent Movements-A fNIRS Study.

Activities of daily living consist of accurate, coordinated movements, which require the upper limbs to constantly interact with environmental loads. The magnitude of the load was shown to affect kinematic outcomes in healthy subjects. Moreover, the increase in load facilitates the recovery of motor function in patients with neurological disorders. Although Brodmann Areas 4 and 6 were found to be active during loaded movements, it remains unclear whether stronger activation can be triggered simply by increasing the load magnitude. If such a linear relationship exists, it may provide a basis for the closed-loop adjustment of treatment plans in neurorehabilitation. Fourteen healthy participants were instructed to lift their hands to their armpits. The movements were grouped in blocks of 25 s. Each block was assigned a magnitude of inertial loads, either 0 pounds (bare hand), 3 pounds, or 15 pounds. Hemodynamic fNIRS signals were recorded throughout the experiment. Both channel-wise and ROI-wise analyses found significant activations against all three magnitudes of inertia. The generalized linear model revealed significant increases in the beta coefficient of 0.001673/pound in BA4 and 0.001338/pound in BA6. The linear trend was stronger in BA6 (conditional r2 = 0.9218) than in BA4 (conditional r2 = 0.8323).

A Practical Post-Stroke Elbow Spasticity Assessment Using an Upper Limb Rehabilitation Robot: A Validation Study.

Spasticity is a motor disorder characterised by a velocity-dependent increase in muscle tone, which is critical in neurorehabilitation given its high prevalence and potential negative influence among the post-stroke population. Accurate measurement of spasticity is important as it guides the strategy of spasticity treatment and evaluates the effectiveness of spasticity management. However, spasticity is commonly measured using clinical scales which may lack objectivity and reliability. Although many technology-assisted measures have been developed, showing their potential as accurate and reliable alternatives to standard clinical scales, they have not been widely adopted in clinical practice due to their low usability and feasibility. This paper thus introduces an easy-to-use robotic based measure of elbow spasticity and its evaluation protocol. Preliminary results collected with one post-stroke patient and one healthy control subject are presented and demonstrate the feasibility of the approach.

A pilot study of synergy-based FES for upper-extremity poststroke rehabilitation.

A previous study indicated that synergy-based functional electrical stimulation (FES) may improve instantaneous upper-limb motor performance for stroke survivors. However, it remains unclear whether the improvements will sustain over time to achieve functional gains associated with a task-oriented training (TOT). This pilot study was designed to investigate whether there is any promising sign of functional benefits. A TOT protocol with repeated forward and lateral reaching movements assisted by synergy-based FES was conducted in 16 patients (9 FES, 7 Sham) with post-stroke hemiparesis. FES stimuli were applied to 7 upper-extremity muscles of elbow and shoulder during patient movements. Envelopes of stimuli were individualized by re-composing the muscle synergies extracted from a healthy subject. After a five-day training for one hour each day, synergy-based FES induced higher increases in Fugl-Meyer scores (6.67 ± 5.20) than did the Sham (2.00 ± 2.38, p < 0.05). Peak velocity of forward reaching movements increased with a slope 73% steeper in FES group than Sham. In lateral reaching movements, the change in synergy similarity correlated with the change in elbow flexion for the FES group, but not the Sham group. Our results indicate that synergy-based FES therapy induced clinically traceable signs of improvements in poststroke motor performance. The muscle activation in patients also showed promising sign of alteration by FES. Results suggest that a larger scale clinical trial of synergy-based FES may be feasible towards an individualized therapeutic regimen.

A Biorealistic Computational Model Unfolds Human-Like Compliant Properties for Control of Hand Prosthesis.

Objective: Human neuromuscular reflex control provides a biological model for a compliant hand prosthesis. Here we present a computational approach to understanding the emerging human-like compliance, force and position control, and stiffness adaptation in a prosthetic hand with a replica of human neuromuscular reflex. Methods: A virtual twin of prosthetic hand was constructed in the MuJoCo environment with a tendon-driven anthropomorphic hand structure. Biorealistic mathematic models of muscle, spindle, spiking-neurons and monosynaptic reflex were implemented in neuromorphic chips to drive the virtual hand for real-time control. Results: Simulation showed that the virtual hand acquired human-like ability to control fingertip position, force and stiffness for grasp, as well as the capacity to interact with soft objects by adaptively adjusting hand stiffness. Conclusion: The biorealistic neuromorphic reflex model restores human-like neuromuscular properties for hand prosthesis to interact with soft objects.

Biorealistic Control of Hand Prosthesis Augments Functional Performance of Individuals With Amputation.

The human hand has compliant properties arising from muscle biomechanics and neural reflexes, which are absent in conventional prosthetic hands. We recently proved the feasibility to restore neuromuscular reflex control (NRC) to prosthetic hands using real-time computing neuromorphic chips. Here we show that restored NRC augments the ability of individuals with forearm amputation to complete grasping tasks, including standard Box and Blocks Test (BBT), Golf Balls Test (GBT), and Potato Chips Test (PCT). The latter two were more challenging, but novel to prosthesis tests. Performance of a biorealistic controller (BC) with restored NRC was compared to that of a proportional linear feedback (PLF) controller. Eleven individuals with forearm amputation were divided into two groups: one with experience of myocontrol of a prosthetic hand and another without any. Controller performances were evaluated by success rate, failure (drop/break) rate in each grasping task. In controller property tests, biorealistic control achieved a better compliant property with a 23.2% wider range of stiffness adjustment than that of PLF control. In functional grasping tests, participants could control prosthetic hands more rapidly and steadily with neuromuscular reflex. For participants with myocontrol experience, biorealistic control yielded 20.4, 39.4, and 195.2% improvements in BBT, GBT, and PCT, respectively, compared to PLF control. Interestingly, greater improvements were achieved by participants without any myocontrol experience for BBT, GBT, and PCT at 27.4, 48.9, and 344.3%, respectively. The functional gain of biorealistic control over conventional control was more dramatic in more difficult grasp tasks of GBT and PCT, demonstrating the advantage of NRC. Results support the hypothesis that restoring neuromuscular reflex in hand prosthesis can improve neural motor compatibility to human sensorimotor system, hence enabling individuals with amputation to perform delicate grasps that are not tested with conventional prosthetic hands.

Effect of Fascicle Length Range on Force Generation of Model-Based Biomimetic Controller for Tendon-Driven Prosthetic Hand.

Model-based biomimetic control with neuro-muscular reflex requires accurate representation of muscle fascicle length, which affects both force generation capability of muscle and dynamics of muscle spindle. However, physiological data are insufficient to guide the selection of range of fascicle length for task control. Here a reverse engineering approach was used to investigate the effects of different fascicle length range on controller's force control ability, so as to justify the selection of operating range of muscle length for a grasp force task. We compared 3 different ranges of fascicle length for their effects on force generation, i.e. R1: 0.5 - 1.0 Lo, R2: 0.5 - 1.3 Lo and R3: 0.5 - 1.6 Lo. The rationale to test these range selections was based on both physiological realism and engineering considerations. The steady state force output and transient force responses were evaluated with a range of step inputs as controller input. Results show that the prosthetic finger can produce a linear steady state force response with all 3 ranges of fascicle length. Peak force was the largest with R3. Fascicle length range had no significant effect on the rise time in force generation tasks. Results suggest that a wider range of fascicle length may be more favorable for force capacity, since the contact point of force control may well fall near the optimal length (Lo) region.

Evaluation of Model-Based Biomimetic Control of Prosthetic Finger Force for Grasp.

Restoring neuromuscular reflex properties in the control of a prosthetic hand may potentially approach human-level grasp functions in the prosthetic hand. Previous studies have confirmed the feasibility of real-time emulation of a monosynaptic spinal reflex loop for prosthetic control. This study continues to explore how well the biomimetic controller could enable the amputee to perform force-control tasks that required both strength and error-tolerance. The biomimetic controller was programmed on a neuromorphic chip for real-time emulation of reflex. The model-calculated force of finger flexor was used to drive a torque motor, which pulled a tendon that flexed prosthetic fingers. Force control ability was evaluated in a "press-without-break" task, which required participants to press a force transducer toward a target level, but never exceeding a breakage threshold. The same task was tested either with the index finger or the full hand; the performance of the biomimetic controller was compared to a proportional linear feedback (PLF) controller, and the contralateral normal hand. Data from finger pressing task in 5 amputees showed that the biomimetic controller and the PLF controller achieved 95.8% and 66.9% the performance of contralateral finger in success rate; 50.0% and 25.1% in stability of force control; 59.9% and 42.8% in information throughput; and 51.5% and 38.4% in completion time. The biomimetic controller outperformed the PLF controller in all performance indices. Similar trends were observed with full-hand grasp task. The biomimetic controller exhibited capacity and behavior closer to contralateral normal hand. Results suggest that incorporating neuromuscular reflex properties in the biomimetic controller may provide human-like capacity of force regulation, which may enhance motor performance of amputees operating a tendon-driven prosthetic hand.

Repetitive Transcranial Magnetic Stimulation on the Affected Hemisphere Enhances Hand Functional Recovery in Subacute Adult Stroke Patients: A Randomized Trial.

Objectives: Either motor training or repetitive transcranial magnetic stimulation (rTMS) could modulate the neural plasticity after stroke. Therefore, synchronizing the two interventions may optimize the efficiency of recovery. In the present study, we aim to investigate the effect of rTMS along with hand grip training on the neurobehavioral and hand functional recovery in one cohort of subacute stroke patients. Methods: Thirty-nine stroke patients were enrolled in a single-center, single-blinded, randomized clinical trial. We tested different intervention effects of rTMS and hand grip training (group A), rTMS alone (group B), and hand grip training alone (group C). For the rTMS-treated groups, patients received 10 consecutive sessions of 5-Hz stimulation over the affected hemisphere with 750 pulses. Jebsen-Taylor Hand Function Test (JTHFT), Fugl-Meyer assessment of upper extremity (FMA-UE), grip strength, modified Barthel index (mBI), and ipsilesional motor evoked potential (iMEP) latency were assessed and compared across the groups. Results: We found that only rTMS along with hand grip training group all improved in JTHFT, FMA-UE, grip strength, and mBI (p ≤ 0.01) compared with the baseline among the three groups. Furthermore, this study demonstrated that rTMS plus hand grip training had much better results in improvement of neurobehavioral outcomes compared to the rTMS alone- and hand grip training alone-treated patients (p < 0.05). However, no significant differences were detected in neurophysiologic outcome between intra-groups and inter-groups (p > 0.05). Conclusion: These proof-of-concept results suggested that rTMS alone with hand grip training was a unique approach to promote hand functional recovery in stroke patients. It provided important information to design a large-scale multi-center clinical trial to further demonstrate the efficiency of the combination of central and peripheral stimulation. Clinical Trial Registration: http://www.chictr.org.cn (#ChiCTR1900023443).

Next-Generation Prosthetic Hand: from Biomimetic to Biorealistic.

Integrating a prosthetic hand to amputees with seamless neural compatibility presents a grand challenge to neuroscientists and neural engineers for more than half century. Mimicking anatomical structure or appearance of human hand does not lead to improved neural connectivity to the sensorimotor system of amputees. The functions of modern prosthetic hands do not match the dexterity of human hand due primarily to lack of sensory awareness and compliant actuation. Lately, progress in restoring sensory feedback has marked a significant step forward in improving neural continuity of sensory information from prosthetic hands to amputees. However, little effort has been made to replicate the compliant property of biological muscle when actuating prosthetic hands. Furthermore, a full-fledged biorealistic approach to designing prosthetic hands has not been contemplated in neuroprosthetic research. In this perspective article, we advance a novel view that a prosthetic hand can be integrated harmoniously with amputees only if neural compatibility to the sensorimotor system is achieved. Our ongoing research supports that the next-generation prosthetic hand must incorporate biologically realistic actuation, sensing, and reflex functions in order to fully attain neural compatibility.

Neuromorphic Model of Reflex for Realtime Human-Like Compliant Control of Prosthetic Hand.

Current control of prosthetic hands is ineffective when grasping deformable, irregular, or heavy objects. In humans, grasping is achieved under spinal reflexive control of the musculotendon skeletal structure, which produces a hand stiffness commensurate with the task. We hypothesize that mimicking reflex on a prosthetic hand may improve grasping performance and safety when interacting with human. Here, we present a design of compliant controller for prosthetic hand with a neuromorphic model of human reflex. The model includes 6 motoneuron pools containing 768 spiking neurons, 1 muscle spindle with 128 spiking afferents, and 1 modified Hill-type muscle. Models are implemented using neuromorphic hardware with 1 kHz real-time computing. Experimental tests showed that the prosthetic hand could sustain a 40 N load compared to 95 N for an adult. Stiffness range was adjustable from 60 to 640 N/m, about 46.6% of that of human hand. The grasping velocity could be ramped up to 14.4 cm/s, or 24% of the human peak velocity. The complaint control could switch between free movement and contact force when pressing a deformable beam. The amputee can achieve a 47% information throughput of healthy humans. Overall, the reflex-enabled prosthetic hand demonstrated the attributes of human compliant grasping with the neuromorphic model of spinal neuromuscular reflex.