Restoration of coherent reach-grasp-pull movement via sequential intraneural peripheral nerve stimulation in rats.

Objective.Peripheral nerve stimulation (PNS) has been demonstrated as an effective way to selectively activate muscles and to produce fine hand movements. However, sequential multi-joint upper limb movements, which are critical for paralysis rehabilitation, has not been tested with PNS. Here, we aimed to restore multiple upper limb joint movements through an intraneural interface with a single electrode, achieving coherent reach-grasp-pull movement tasks through sequential stimulation.Approach.A transverse intrafascicular multichannel electrode was implanted under the axilla of the rat's upper limb, traversing the musculocutaneous, radial, median, and ulnar nerves. Intramuscular electrodes were implanted into the biceps brachii (BB), triceps brachii (TB), flexor carpi radialis (FCR), and extensor carpi radialis (ECR) muscles to record electromyographic (EMG) activity and video recordings were used to capture the kinematics of elbow, wrist, and digit joints. Charge-balanced biphasic pulses were applied to different channels to recruit distinct upper limb muscles, with concurrent recording of EMG signals and joint kinematics to assess the efficacy of the stimulation. Finally, a sequential stimulation protocol was employed by generating coordinated pulses in different channels.Main results.BB, TB, FCR and ECR muscles were selectively activated and various upper limb movements, including elbow flexion, elbow extension, wrist flexion, wrist extension, digit flexion, and digit extension, were reliably generated. The modulation effects of stimulation parameters, including pulse width, amplitude, and frequency, on induced joint movements were investigated and reach-grasp-pull movement was elicited by sequential stimulation.Significance.Our results demonstrated the feasibility of sequential intraneural stimulation for functional multi-joint movement restoration, providing a new approach for clinical rehabilitation in paralyzed patients.

Combination of Matching Responsive Stimulations of Hippocampus and Subiculum for Effective Seizure Suppression in Temporal Lobe Epilepsy.

Responsive neural stimulation (RNS) is considered a promising neural modulation therapy for refractory epilepsy. Combined stimulation on different targets may hold great promise for improving the efficacy of seizure control since neural activity changed dynamically within associated brain targets in the epileptic network. Three major issues need to be further explored to achieve better efficacy of combined stimulation: (1) which nodes within the epileptogenic network should be chosen as stimulation targets? (2) What stimulus frequency should be delivered to different targets? and (3) Could the efficacy of RNS for seizure control be optimized by combined different stimulation targets together? In our current study, Granger causality (GC) method was applied to analyze epileptogenic networks for finding key targets of RNS. Single target stimulation (100 µA amplitude, 300 µs pulse width, 5s duration, biphasic, charge-balanced) with high frequency (130 Hz, HFS) or low frequency (5 Hz, LFS) was firstly delivered by our lab designed RNS systems to CA3, CA1, subiculum (SUB) of hippocampi, and anterior nucleus of thalamus (ANT). The efficacy of combined stimulation with different groups of frequencies was finally assessed to find out better combined key targets with optimal stimulus frequency. Our results showed that stimulation individually delivered to SUB and CA1 could shorten the average duration of seizures. Different stimulation frequencies impacted the efficacy of seizure control, as HFS delivered to CA1 and LFS delivered to SUB, respectively, were more effective for shortening the average duration of electrographic seizure in Sprague-Dawley rats (n = 3). Moreover, the synchronous stimulation of HFS in CA1 combined with LFS in SUB reduced the duration of discharge significantly in rats (n = 6). The combination of responsive stimulation at different targets may be an inspiration to optimize stimulation therapy for epilepsy.

An Energy Efficient AdaBoost Cascade Method for Long-Term Seizure Detection in Portable Neurostimulators.

Responsive neurostimulation (RNS) is becoming a promising therapy in refractory epilepsy control. In a RNS system, a critical challenge is how to detect seizure onsets accurately with low computational costs. In this study, an energy efficient AdaBoost cascade method for robust long-term seizure detection from local field potential (LFP) signals was proposed and evaluated in a portable neurostimulator. The AdaBoost cascade method included two stages: a seizure candidate detection stage (stage1) and a false alarm rejection stage (stage2). Since seizure activities occurred occasionally in most cases, most normal signal segments can be efficiently classified in stage1. A small percent of suspicious segments were fed into stage2 for more strict examination, where more sophisticated features were extracted to precisely identify seizure activities and reduce false alarms. To further optimize energy efficiency for hardware implementation, we proposed a soft-cascade algorithm for stage2 to reduce the computational costs. Our method was implemented in a generalized neurostimulator and evaluated online with four rats with chronic temporal lobe epilepsy (TLE). A total of 2280.1 hours of LFP signals were recorded and analyzed. Our approach achieves a detection rate of 91.6%, 3.85/h false alarm rate, and 2.31 second detection delay. With the two-stage cascade approach, 98.13% of computational costs could be reduced, with respect to the time of calculation of all features. Our method can detect seizure onsets precisely with high energy efficiency, which is suitable for hardware implementation in portable neuro-stimulators. Therefore, this proposed approach is promising to provide effective and robust performances in long-term seizure detection in neurostimulators for responsive seizure control.

Acute Seizure Control Efficacy of Multi-Site Closed-Loop Stimulation in a Temporal Lobe Seizure Model.

The closed-loop electrical stimulation is emerging as a promising neural modulation therapy for refractory epilepsy. However, the efficacy of electrical stimulation is less than optimal and the mechanism of seizure control is still unclear. In this paper, we evaluated the acute seizure control efficacy of the multi-site closed-loop stimulation (MSCLS) in a rodent model with a custom designed closed-loop neurostimulator. A total of 18 rats were injected with kainic-acid in CA3 of the left hippocampus to induce acute temporal lobe seizures. Instead of single target stimulation, four target sites in left hemisphere including CA1 and CA3 of the hippocampus, sub-thalamic nucleus, and M1 region of the motor cortex were selected for both recording and stimulation. A low-cost efficient multi-site seizure detection algorithm was implemented in the neurostimulator for MSCLS. With MSCLS treatment, the rats without status-epilepsy (SE) significantly reduced the seizure duration and the number of generalized seizures in each site. When considering the rats developed SE, the MSCLS could also alleviate the seizure severity, but had little effect on the seizure duration and seizure number. In conclusion, although the efficacy of MSCLS was still limited by the stimulation sites, stimulation parameters, and seizure model chosen in this paper, the MSCLS itself would be a promising direction for the refractory seizure treatment.