Deep brain stimulation (DBS) is a neurosurgical technique that regulates neuron activity by using internal pulse generators to electrodes in specific target areas of the brain. As a blind treatment, DBS is widely used in the field of mental and neurological diseases, although its mechanism of action is still unclear. In the past 10 years, DBS has shown a certain positive effect in animal models and patients with Alzheimer's disease (AD), but there are also different results that may be related to the stimulation parameters of DBS. Based on this, determining the optimal stimulation parameters for DBS in AD and understanding its mechanism of action are essential to promote the clinical application of DBS in AD. This review aims to explore the therapeutic effect of DBS in AD, and to analyze its stimulation parameters and potential mechanism of action. The keywords “Deep brain stimulation” and “Alzheimer's Disease” were used for systematic searches in the literature databases of Web of Science and PubMed (from 1900 to September 29, 2020). All human clinical studies and animal studies were reported in English, including individual case studies and long-term follow-up studies, were included. These studies described the therapeutic effects of DBS in AD. The results included 16 human clinical studies and 14 animal studies, of which 28 studies clearly demonstrated the positive effect of DBS in AD. We analyzed the current stimulation parameters of DBS in AD from stimulation target, stimulation frequency, stimulation start time, stimulation duration, unilateral/bilateral treatment and current intensity, etc., and we also discussed its potential mechanism of action from multiple aspects, including regulating related neural networks, promoting nerve oscillation, reducing β-amyloid and tau levels, reducing neuroinflammation, regulating the cholinergic system, inducing the synthesis of nerve growth factor.

The electrophoretic motion of a spherical nanoparticle, subject to an axial electric field in a nanotube filled with an electrolyte solution, has been investigated using a continuum theory, which consists of the Nernst-Planck equations for the ionic concentrations, the Poisson equation for the electric potential in the solution, and the Stokes equation for the hydrodynamic field. In particular, the effects of nonuniform surface charge distributions around the nanoparticle on its axial electrophoretic motion are examined with changes in the bulk electrolyte concentration and the surface charge of the tube's wall. A particle with a nonuniform charge distribution is shown to induce a corresponding complex ionic concentration field, which in turn influences the electric field and the fluid motion surrounding the particle and thus its electrophoretic velocity. As a result, contrary to the relatively simple dynamics of a particle with a uniform surface charge, dominated by the irradiating electrostatic force, that with a nonuniform surface charge distribution shows various intriguing behaviors due to the additional interplay of the nonuniform electro-osmotic effects.

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Purpose: Amyotrophic lateral sclerosis (ALS) is a motor neuro-degenerative disorder that also damages extra-motor neural pathways. A significant proportion of existing evidence describe alterations in the strengths of functional connectivity, whereas the changes in the density of these functional connections have not been explored. Therefore, our study seeks to identify ALS-induced alternations in the resting-state functional connectivity density (FCD).Methods: Two groups comprising of 38 ALS patients and 35 healthy participants (age and gender matched) were subjected to the resting-state functional magnetic resonance imaging (MRI) scanning. An ultra-fast graph theory method known as FCD mapping was utilized to calculate the voxel-wise short- and long-range FCD values of the brain for each participant. FCD values of patients and controls were compared based on voxels in order to discern cerebral regions that possessed significant FCD alterations. For areas demonstrating a group effect of atypical FCD in ALS, seed-based functional connectivity analysis was then investigated. Partial correlation analyses were carried out between aberrant FCDs and several clinical variables, controlling for age, gender, and total intracranial volume.Results: Patients with ALS were found to have decreased short-range FCD in the primary motor cortex and increased long-range FCD in the premotor cortex. Extra-motor areas that also displayed extensive FCD alterations encompassed the temporal cortex, insula, cingulate gyrus, occipital cortex, and inferior parietal lobule. Seed-based correlation analysis further demonstrated that these regions also possessed disrupted functional connectivity. However, no significant correlations were identified between aberrant FCDs and clinical variables.Conclusion: FCD changes in the regions identified represent communication deficits and impaired functional brain dynamics, which might underlie the motor, motor control, language, visuoperceptual and high-order cognitive deficits in ALS. These findings support the fact that ALS is a disorder affecting multiple systems. We gain a deeper insight of the neural mechanisms underlying ALS.

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A high-throughput cell electrofusion microfluidic chip has been designed, fabricated on a silicon-on-insulator wafer and tested for in vitro cell fusion under a low applied voltage. The developed chip consists of six individual straight microchannels with a 40-μm thickness conductive highly doped Si layer as the microchannel wall. In each microchannel, there are 75 pairs of counter protruding microelectrodes, between which the cell electrofusion is performed. The entire highly doped Si layer is covered by a 2-μm thickness aluminum film to maintain a consistent electric field between different protruding microelectrode pairs. A 150-nm thickness SiO₂ film is subsequently deposited on the top face of each protruding microelectrode for better biocompatibility. Owing to the short distance between two counter protruding microelectrodes, a high electric field can be generated for cell electrofusion with a low voltage imposed across the electrodes. Both mammalian cells and plant protoplasts were used to test the cell electrofusion. About 42-68% cells were aligned to form cell-cell pairs by the dielectrophoretic force. After cell alignment, cell pairs were fused to form hybrid cells under the control of cell electroporation and electrofusion signals. The averaged fusion efficiency in the paired cells is above 40% (the highest was about 60%), which is much higher than the traditional polyethylene glycol method (<5%) and traditional electrofusion methods (∼12%). An individual cell electrofusion process could be completed within 10 min, indicating a capability of high throughput.

It is important for rehabilitation exoskeletons to move with a spatiotemporal motion patterns that well match the upper-limb joint kinematic characteristics. However, few efforts have been made to manipulate the motion control based on human kinematic synergies. This work analyzed the spatiotemporal kinematic synergies of right arm reaching movement and investigated their potential usage in upper limb assistive exoskeleton motion planning. Ten right-handed subjects were asked to reach 10 target button locations placed on a cardboard in front. The kinematic data of right arm were tracked by a motion capture system. Angular velocities over time for shoulder flexion/extension, shoulder abduction/adduction, shoulder internal/external rotation, and elbow flexion/extension were computed. Principal component analysis (PCA) was used to derive kinematic synergies from the reaching task for each subject. We found that the first four synergies can explain more than 94% of the variance. Moreover, the joint coordination patterns were dynamically regulated over time as the number of kinematic synergy (PC) increased. The synergies with different order played different roles in reaching movement. Our results indicated that the low-order synergies represented the overall trend of motion patterns, while the high-order synergies described the fine motions at specific moving phases. A 4-DoF upper limb assistive exoskeleton was modeled in SolidWorks to simulate assistive exoskeleton movement pattern based on kinematic synergy. An exoskeleton Denavit-Hartenberg (D-H) model was established to estimate the exoskeleton moving pattern in reaching tasks. The results further confirmed that kinematic synergies could be used for exoskeleton motion planning, and different principal components contributed to the motion trajectory and end-point accuracy to some extent. The findings of this study may provide novel but simplified strategies for the development of rehabilitation and assistive robotic systems approximating the motion pattern of natural upper-limb motor function.

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