Lavrov, Igor

Abstract The inhibitory management effect is usually un- derestimated in artificial control systems, using biological anal- ogy. According to our hypothesis, the muscle hypertonus could be effectively compensated via stimulation by bio plausible patterns. We proposed the approach for the compensatory stimulation device in development of previously presented archi- tecture of neurointerface, where (1) neuroport is implemented as DAC and stimulator, (2) neuroterminal – as neurosimulation of a set of oscillator motifs on one-board computer. In the set of experiments with 5 volunteers we measured the efficacy of motor neuron inhibition via antagonist muscle or nerve stim- ulation registering muscle force with and without antagonist stimulation. For the agonist activation, we used both voluntary activity and electrical stimulation. In the case of stimulation of both agonist and antagonist muscles and nerves, we exper- imented with delays between muscles stimulation starts in the range 0...20 ms. We registered the subjective discomfort rate. We didn’t identify a significant difference between antagonist muscle and nerve stimulation in both voluntary and stimulation of agonist activity. We determined the most effective delay between stimulation of agonist and antagonist muscle/nerve as 10–20 ms.

Abstract In this study the effect of transcutaneous (tSCS) and epidural electrical spinal cord stimulation (EES) to facilitate volitional movements, balance, and non-motor functions was consecutively tested in two subjects with motor complete spinal cord injury (SCI). We hypothesized that tSCS and EES have different but complimentary effects on restoration after SCI. In both subjects tSCS demonstrated minimal improvement in volitional movements critical to initiate tSCS-enabled rehabilitation. Compared to tSCS, following EES demonstrated immediate restoration of volitional movements, while tSCS was more effective in improving balance. Continuous improvement in non-motor functions was found during tSCS-enabled and then EES-enabled rehabilitation. These results show significant difference in effect of tSCS and EES on recovery of neurologic functions and demonstrate advantages of consecutive tSCS and EES therapy of SCI. Proposed approach will help to select responsive to neuromodulation subjects and early initiate therapy, particularly for motor complete SCI with minimal effect from conventional rehabilitation.

The contemporary strategy for spinal cord injury (SCI) therapy aims to combine multiple approaches to control pathogenic mechanisms of neurodegeneration and stimulate neuroregeneration. In this study, a novel regenerative approach using an autologous leucoconcentrate enriched with transgenes encoding vascular endothelial growth factor (VEGF), glial cell line-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) combined with supra- and sub-lesional epidural electrical stimulation (EES) was tested on mini-pigs similar in morpho-physiological scale to humans. The complex analysis of the spinal cord recovery after a moderate contusion injury in treated mini-pigs compared to control animals revealed: better performance in behavioural and joint kinematics, restoration of electromyography characteristics, and improvement in selected immunohistology features related to cell survivability, synaptic protein expression, and glial reorganization above and below the injury. These results for the first time demonstrate the positive effect of intravenous infusion of autologous genetically-enriched leucoconcentrate producing recombinant molecules stimulating neuroregeneration combined with neuromodulation by translesional multisite EES on the restoration of the post-traumatic spinal cord in mini-pigs and suggest the high translational potential of this novel regenerative therapy for SCI patients.

Millions of people around the world suffer from disorders caused by injuries and diseases of the brain and spinal cord. The combination of brain-computer interfaces and neuromodulation technologies is a new approach that could revolutionize the treatment of these disorders. In this study, we tested the effectiveness of a technique in which a patient with a spinal cord injury first undergoes spinal cord stimulation and then participates in a rehabilitation session using a brain-computer interface based on the P300 principle, which decodes visual-motor transformation and uses an assistive robot that moves the patient’s arm, and virtual reality. All healthy participants of the study were able to combine these two techniques without any undesirable effects; studies on patients with spinal cord injury are ongoing. System integration of the two methods has been already performed, and in the future, upon completion of this work, the neural interface will be able to control the stimulation parameters. We propose such integrated systems as a new approach to neurorehabilitation. Key words: brain-computer interface, neuromodulation, spinal cord stimulation, spinal cord trauma, P300, visuomotor transformation.

Transcutaneous (TSS) and epidural spinal stimulation (ESS) are electrophysiological techniques that have been used to investigate the interactions between exogenous electrical stimuli and spinal sensorimotor networks that integrate descending motor signals with afferent inputs from the periphery during motor tasks such as standing and stepping. Recently, pilot-phase clinical trials using ESS and TSS have demonstrated restoration of motor functions that were previously lost due to spinal cord injury (SCI). However, the spinal network interactions that occur in response to TSS or ESS pulses with spared descending connections across the site of SCI have yet to be characterized. Therefore, we examined the effects of delivering TSS or ESS pulses to the lumbosacral spinal cord in nine individuals with chronic SCI. During low-frequency stimulation, participants were instructed to relax or attempt maximum voluntary contraction to perform full leg flexion while supine. We observed similar lower-extremity neuromusculature activation during TSS and ESS when performed in the same participants while instructed to relax. Interestingly, when participants were instructed to attempt lower-extremity muscle contractions, both TSS- and ESS-evoked motor responses were significantly inhibited across all muscles. Participants with clinically complete SCI tested with ESS and participants with clinically incomplete SCI tested with TSS demonstrated greater ability to modulate evoked responses than participants with motor complete SCI tested with TSS, although this was not statistically significant due to a low number of subjects in each subgroup. These results suggest that descending commands combined with spinal stimulation may increase activity of inhibitory interneuronal circuitry within spinal sensorimotor networks in individuals with SCI, which may be relevant in the context of regaining functional motor outcomes.

PurposeElectrical epidural spinal cord stimulation (SCS) is used as a treatment for chronic pain as well as to partially restore motor function after a spinal cord injury. Monitoring the spinal cord activity during SCS with fMRI could provide important and objective measures of integrative responses to treatment. Unfortunately, spinal cord fMRI is severely challenged by motion and susceptibility artifacts induced by the implanted electrode and bones. This pilot study introduces multi‐band sweep imaging with Fourier transformation (MB‐SWIFT) technique for spinal cord fMRI during SCS in rats. Given the close to zero acquisition delay and high bandwidth in 3 dimensions, MB‐SWIFT is demonstrated to be highly tolerant to motion and susceptibility‐induced artifacts and thus holds promise for fMRI during SCS.MethodsMB‐SWIFT with 0.78 × 0.78 × 1.50 mm3 spatial resolution and 3‐s temporal resolution was used at 9.4 Tesla in rats undergoing epidural SCS at different frequencies. Its performance was compared with spin echo EPI. The origin of the functional contrast was also explored using suppression bands.ResultsMB‐SWIFT was tolerant to electrode‐induced artifacts and respiratory motion, leading to substantially higher fMRI sensitivity than spin echo fMRI. Clear stimulation frequency‐dependent responses to SCS were detected in the rat spinal cord close to the stimulation site. The origin of MB‐SWIFT fMRI signals was consistent with dominant inflow effects.ConclusionfMRI of the rat spinal cord during SCS can be consistently achieved with MB‐SWIFT, thus providing a valuable experimental framework for assessing the effects of SCS on the central nervous system.

Abstract Electrical stimulation of the cerebral cortex (ESCC) has been used to treat intractable neuropathic pain for nearly two decades, however, no standardized approach for this technique has been developed. In order to optimize targeting and validate the effect of ESCC before placing the permanent grid, we introduced initial assessment with trial stimulation, using a temporary grid of subdural electrodes. In this retrospective study we evaluate the role of electrode location on cerebral cortex in control of neuropathic pain and the role of trial stimulation in target-optimization for ESCC. Location of the temporary grid electrodes and location of permanent electrodes were evaluated in correlation with the long-term efficacy of ESCC. The results of this study demonstrate that the long-term effect of subdural pre-motor cortex stimulation is at least the same or higher compare to effect of subdural motor or combined pre-motor and motor cortex stimulation. These results also demonstrate that the initial trial stimulation helps to optimize permanent electrode positions in relation to the optimal functional target that is critical in cases when brain shift is expected. Proposed methodology and novel results open a new direction for development of neuromodulation techniques to control chronic neuropathic pain.

The translation of new therapies for spinal cord injury to clinical trials can be facilitated with large animal models close in morpho-physiological scale to humans. Here, we report functional restoration and morphological reorganization after spinal contusion in pigs, following a combined treatment of locomotor training facilitated with epidural electrical stimulation (EES) and cell-mediated triple gene therapy with umbilical cord blood mononuclear cells overexpressing recombinant vascular endothelial growth factor, glial-derived neurotrophic factor, and neural cell adhesion molecule. Preliminary results obtained on a small sample of pigs 2 months after spinal contusion revealed the difference in post-traumatic spinal cord outcomes in control and treated animals. In treated pigs, motor performance was enabled by EES and the corresponding morpho-functional changes in hind limb skeletal muscles were accompanied by the reorganization of the glial cell, the reaction of stress cell, and synaptic proteins. Our data demonstrate effects of combined EES-facilitated motor training and cell-mediated triple gene therapy after spinal contusion in large animals, informing a background for further animal studies and clinical translation.