noninvasive-temporal-interference-electrical-stimulation-for-spinal

Noninvasive Temporal Interference Electrical Stimulation for Spinal Cord Rehabilitation

Spinal cord injury (SCI) can lead to permanent loss of motor, sensory, and autonomic functions, presenting a significant clinical challenge for ...

Zhejiang University

Westlake University

 Traditional rehabilitation with uniformed intensity would ignore individual tolerance and introduce the second injury to stroke survivors due to overloaded training. However, effective control of the training intensity of different stroke survivors is still lacking. The purpose of the study was to investigate the rehabilitative effects of electromyography (EMG)-based fatigue-controlled treadmill training on rat stroke model.  Sprague-Dawley rats after intracerebral hemorrhage and EMG electrode implantation surgeries were randomly distributed into three groups: the control group (CTRL,  = 11), forced training group (FOR-T,  = 11), and fatigue-controlled training group (FAT-C,  = 11). The rehabilitation interventions were delivered every day from day 2 to day 14 post-stroke. No training was delivered to the CTRL group. The rats in the FOR-T group were forced to run on the treadmill without rest. The fatigue level was monitored in the FAT-C group through the drop rate of EMG mean power frequency, and rest was applied to the rats when the fatigue level exceeded the moderate fatigue threshold. The speed and accumulated running duration were comparable in the FAT-C and the FOR-T groups. Daily evaluation of the motor functions was performed using the modified Neurological Severity Score. Running symmetry was investigated by the symmetry index of EMG bursts collected from both hind limbs during training. The expression level of neurofilament-light in the striatum was measured to evaluate the neuroplasticity.  The FAT-C group showed significantly lower modified Neurological Severity Score compared with the FOR-T ( ≤ 0.003) and CTRL ( ≤ 0.003) groups. The FAT-C group showed a significant increase in the symmetry of hind limbs since day 7 ( = 0.000), whereas the FOR-T group did not ( = 0.349). The FAT-C group showed a higher concentration of neurofilament-light compared to the CTRL group ( = 0.005) in the unaffected striatum and the FOR-T group ( = 0.021) in the affected striatum.  The treadmill training with moderate fatigue level controlled was more effective in motor restoration than forced training. The fatigue-controlled physical training also demonstrated positive effects in the striatum neuroplasticity. This study indicated that protocol with individual fatigue-controlled training should be considered in both animal and clinical studies for better stroke rehabilitation.

Rehabilitation Effects of Fatigue-Controlled Treadmill Training After Stroke: A Rat Model Study.

Genetic variants in the GRIN genes that encode N-methyl-D-aspartate receptor (NMDAR) subunits have been identified in various neurodevelopmental disorders, including epilepsy. We identified a GRIN1 variant from an individual with early-onset epileptic encephalopathy, evaluated functional changes to NMDAR properties caused by the variant, and screened FDA-approved therapeutic compounds as potential treatments for the patient.

Recurrent seizure-related GRIN1 variant: Molecular mechanism and targeted therapy.

Spinal cord injury (SCI) results in devastating consequences for the motor and sensory function of patients due to neuronal loss and disrupted neural circuits, confronting poor prognosis and lack of effective therapies. A new therapeutic strategy is urgently required. Here, human amniotic epithelial cells (hAEC), featured with immunocompatibility, non-tumorgenicity and no ethical issues, were induced into neural-like cells by a compound cocktail, as evidenced with morphological change and the expression of neural cell markers. Interestingly, the hAEC-neural-like cells maintain the characteristic of low immunogenicity as hAEC. Aiming at SCI treatment in vivo, we constructed a 3D-printed GelMA hydrogel biomimetic spinal cord scaffold with micro-channels, in which hAEC-neural-like cells were well-induced and grown. In a rat full transection SCI model, hAEC-neural-like cell scaffolds that were implanted in the lesion demonstrated significant therapeutic effects; the neural circuit and hindlimb locomotion were partly recovered compared to little affection in the SCI rats receiving an empty scaffold or a sham implantation operation. Thus, the establishment of hAEC-neural-like cell biomimetic scaffolds may provide a safe and effective treatment strategy for SCI.

Therapeutic Effect of Biomimetic Scaffold Loaded with Human Amniotic Epithelial Cell-Derived Neural-like Cells for Spinal Cord Injury.

Accurate spike sorting to the appropriate neuron is crucial for neural activity analysis. To improve spike sorting performance, it is essential to fully leverage each processing step, including filtering, spike detection, feature extraction, and clustering. However, compared to the latter two steps that were widely studied and optimized, the filtering process was largely neglected. In this study, we proposed a fast and effective spike sorting method (MultiFq) based on multi-frequency composite waveform shapes acquired through an optimized filtering process. When combined with the classical PCA-Km spiking sorting algorithm, our proposed MultiFq significantly improved its sorting performance and achieved as high performance as the complex Wave-clus did in both the simulated and in vivo datasets. But, the combined method was about 10 times faster than Wave-clus (0.16 s vs. 2.06 s in simulated datasets; 0.46 s vs. 2.03 s in in vivo datasets). Furthermore, we demonstrated the compatibility of our MultiFq by combining it with other sorting algorithms, which consistently resulted in significant improvement in sorting accuracy with the maximum improvement at 35.04%. The above results demonstrated that our proposed method could significantly improve the sorting performance with low computation cost and good compatibility by leveraging the multi-frequency composite waveform shapes.

A Fast and Effective Spike Sorting Method Based on Multi-Frequency Composite Waveform Shapes.

Stem cells play critical roles in cell therapies and tissue engineering for nerve repair. However, achieving effective delivery of high cell density remains a challenge. Here, a novel cell delivery platform termed the hyper expansion scaffold (HES) is developed to enable high cell loading. HES facilitated self-promoted and efficient cell absorption via a dual driving force model. In vitro tests revealed that the HES rapidly expanded 80-fold in size upon absorbing 2.6 million human amniotic epithelial stem cells (hAESCs) within 2 min, representing over a 400% increase in loading capacity versus controls. This enhanced uptake benefited from macroscopic swelling forces as well as microscale capillary action. In spinal cord injury (SCI) rats, HES-hAESCs promoted functional recovery and axonal projection by reducing neuroinflammation and improving the neurotrophic microenvironment surrounding the lesions. In summary, the dual driving forces model provides a new rationale for engineering hydrogel scaffolds to facilitate self-promoted cell absorption. The HES platform demonstrates great potential as a powerful and efficient vehicle for delivering high densities of hAESCs to promote clinical treatment and repair of SCI.

A 3D-Printed Dual Driving Forces Scaffold with Self-Promoted Cell Absorption for Spinal Cord Injury Repair.

N-methyl-D-aspartate receptors (NMDARs) are members of the glutamate receptor family and participate in excitatory postsynaptic transmission throughout the central nervous system. Genetic variants in GRIN genes encoding NMDAR subunits are associated with a spectrum of neurological disorders. The M3 transmembrane helices of the NMDAR couple directly to the agonist-binding domains and form a helical bundle crossing in the closed receptors that occludes the pore. The M3 functions as a transduction element whose conformational change couples ligand binding to opening of an ion conducting pore. In this study, we report the functional consequences of 48 de novo missense variants in GRIN1, GRIN2A, and GRIN2B that alter residues in the M3 transmembrane helix. These de novo variants were identified in children with neurological and neuropsychiatric disorders including epilepsy, developmental delay, intellectual disability, hypotonia and attention deficit hyperactivity disorder. All 48 variants in M3 for which comprehensive testing was completed produce a gain-of-function (28/48) compared to loss-of-function (9/48); 11 variants had an indeterminant phenotype. This supports the idea that a key structural feature of the M3 gate exists to stabilize the closed state so that agonist binding can drive channel opening. Given that most M3 variants enhance channel gating, we assessed the potency of FDA-approved NMDAR channel blockers on these variant receptors. These data provide new insight into the structure-function relationship of the NMDAR gate, and suggest that variants within the M3 transmembrane helix produce a gain-of-function.

De novo GRIN variants in M3 helix associated with neurological disorders control channel gating of NMDA receptor.

This study aimed to compare and evaluate different transverse width indices for diagnosing maxillary transverse deficiency (MTD), a common malocclusion characterized by uncoordinated dental arches, crossbites, and tooth crowding.

Comparative evaluation of transverse width indices for diagnosing maxillary transverse deficiency.

Rehabilitation devices assist individuals with movement disorders by supporting daily activities and facilitating effective rehabilitation training. Accurate and early motor intention detection is vital for real-time device applications. However, traditional methods of motor intention detection often rely on single-mode signals, such as EEG or EMG alone, which can be limited by low signal quality and reduced stability. This study proposes a multimodal fusion method based on EEG-EMG functional connectivity to detect sitting and standing intentions before movement execution, enabling timely intervention and reducing latency in rehabilitation devices.

Fusion of EEG and EMG signals for detecting pre-movement intention of sitting and standing in healthy individuals and patients with spinal cord injury.

Article	Year
Rehabilitation Effects of Fatigue-Controlled Treadmill Training After Stroke: A Rat Model Study. Frontiers in bioengineering and biotechnology\| PubMed ID: 33330421	2020
Recurrent seizure-related GRIN1 variant: Molecular mechanism and targeted therapy. Annals of clinical and translational neurology\| PubMed ID: 34227748	2021
Therapeutic Effect of Biomimetic Scaffold Loaded with Human Amniotic Epithelial Cell-Derived Neural-like Cells for Spinal Cord Injury. Bioengineering (Basel, Switzerland)\| PubMed ID: 36290504	2022
A Fast and Effective Spike Sorting Method Based on Multi-Frequency Composite Waveform Shapes. Brain sciences\| PubMed ID: 37626512	2023
A 3D-Printed Dual Driving Forces Scaffold with Self-Promoted Cell Absorption for Spinal Cord Injury Repair. Advanced science (Weinheim, Baden-Wurttemberg, Germany)\| PubMed ID: 37870182	2023
De novo GRIN variants in M3 helix associated with neurological disorders control channel gating of NMDA receptor. Cellular and molecular life sciences : CMLS\| PubMed ID: 38538865	2024
Comparative evaluation of transverse width indices for diagnosing maxillary transverse deficiency. BMC oral health\| PubMed ID: 39020356	2024
Fusion of EEG and EMG signals for detecting pre-movement intention of sitting and standing in healthy individuals and patients with spinal cord injury. Frontiers in neuroscience\| PubMed ID: 39926014	2025

Yuchen Xu

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