Low-Intensity Pulsed Ultrasound Stimulation for Bone Fractures Healing: A Review.

Low-intensity pulsed ultrasound (LIPUS) is a developing technology, which has been proven to improve fracture healing process with minimal thermal effects. This noninvasive treatment accelerates bone formation through various molecular, biological, and biomechanical interactions with tissues and cells. Although LIPUS treatment has shown beneficial effects on different bone fracture locations, only very few studies have examined its effects on deeper bones. This study provides an overview on therapeutic ultrasound for fractured bones, possible mechanisms of action, clinical evidences, current limitations, and its future prospects.

EEG Monitoring Is Feasible and Reliable during Simultaneous Transcutaneous Electrical Spinal Cord Stimulation.

Transcutaneous electrical spinal cord stimulation (tSCS) is a non-invasive neuromodulatory technique that has in recent years been linked to improved volitional limb control in spinal-cord injured individuals. Although the technique is growing in popularity there is still uncertainty regarding the neural mechanisms underpinning sensory and motor recovery. Brain monitoring techniques such as electroencephalography (EEG) may provide further insights to the changes in coritcospinal excitability that have already been demonstrated using other techniques. It is unknown, however, whether intelligible EEG can be extracted while tSCS is being applied, owing to substantial high-amplitude artifacts associated with stimulation-based therapies. Here, for the first time, we characterise the artifacts that manifest in EEG when recorded simultaneously with tSCS. We recorded multi-channel EEG from 21 healthy volunteers as they took part in a resting state and movement task across two sessions: One with tSCS delivered to the cervical region of the neck, and one without tSCS. An offline analysis in the time and frequency domain showed that tSCS manifested as narrow, high-amplitude peaks with a spectral density contained at the stimulation frequency. We quantified the altered signals with descriptive statistics-kurtosis, root-mean-square, complexity, and zero crossings-and applied artifact-suppression techniques-superposition of moving averages, adaptive, median, and notch filtering-to explore whether the effects of tSCS could be suppressed. We found that the superposition of moving averages filter was the most successful technique at returning contaminated EEG to levels statistically similar to that of normal EEG. In the frequency domain, however, notch filtering was more effective at reducing the spectral power contribution of stimulation from frontal and central electrodes. An adaptive filter was more appropriate for channels closer to the stimulation site. Lastly, we found that tSCS posed no detriment the binary classification of upper-limb movements from sensorimotor rhythms, and that adaptive filtering resulted in poorer classification performance. Overall, we showed that, depending on the analysis, EEG monitoring during transcutaneous electrical spinal cord stimulation is feasible. This study supports future investigations using EEG to study the activity of the sensorimotor cortex during tSCS, and potentially paves the way to brain-computer interfaces operating in the presence of spinal stimulation.

A Compact and Lightweight Rehabilitative Exoskeleton to Restore Grasping Functions for People with Hand Paralysis.

Millions of individuals suffer from upper extremity paralysis caused by neurological disorders including stroke, traumatic brain injury, or spinal cord injury. Robotic hand exoskeletons can substitute the missing motor control and help restore the functions in daily operations. However, most of the hand exoskeletons are bulky, stationary, and cumbersome to use. We have modified a recent existing design (Tenoexo) to prototype a motorized, lightweight, fully wearable rehabilitative hand exoskeleton by combining rigid parts with a soft mechanism capable of producing various grasps needed for the execution of daily tasks. Mechanical evaluation of our exoskeleton showed that it can produce fingertip force up to 8 N and can cover 91.5° of range of motion in just 3 s. We further tested the performance of the developed robotic exoskeleton in two quadriplegics with chronic hand paralysis and observed immediate success on independent grasping of different daily objects. The results suggested that our exoskeleton is a viable option for hand function assistance, allowing patients to regain lost finger control for everyday activities.

Restoration of arm and hand functions via noninvasive cervical cord neuromodulation after traumatic brain injury: a case study.

Objectives: To investigate the effects of transcutaneous electrical stimulation (tES) on upper limb functional rehabilitation in a patient with traumatic brain injury (TBI), and to identify the optimum stimulation parameters of tES. Design: A preliminary case study. Methods: Two successive interventions: Phase I-voluntary physical training (vPT) and Phase II - tES along with vPT (tES+vPT). tES was delivered at C3 and C6 cervical regions. Clinical assessments presented the variation of muscle tone and motor functions, before and after each training phase, and evaluated at 1-month follow up after the last intervention. Results: Our results indicate that vPT alone contributed to a release of muscle spasticity of both arms of the patient with no significant improvement of hand function, while tES+vPT further reduced the spasticity of the left arm, and improved the voluntary motor function of both arms. The grip forces were also increased after the tES+vPT treatment. We found that 1 ms biphasic tES at 30 Hz produced optimum motor outputs. Conclusion: The study demonstrates, for the first time, the potential benefits of cervical tES in regard to improving upper limb motor functions in a patient with chronic TBI.

Development of a battery-free ultrasonically powered functional electrical stimulator for movement restoration after paralyzing spinal cord injury.

BACKGROUND: Functional electrical stimulation (FES) is used to restore movements in paretic limbs after severe paralyses resulting from neurological injuries such as spinal cord injury (SCI). Most chronic FES systems utilize an implantable electrical stimulator to deliver a small electric current to the targeted muscle or nerve to stimulate muscle contractions. These implanted stimulators are generally bulky, mainly due to the size of the batteries. Furthermore, these battery-powered stimulators are required to be explanted every few years for battery replacement which may result in surgical failures or infections. Hence, a wireless power transfer technique is desirable to power these implantable stimulators. METHODS: Conventional wireless power transduction faces significant challenges for safe and efficient energy transfer through the skin and deep into the body. Inductive and electromagnetic power transduction is generally used for very short distances and may also interfere with other medical measurements such as X-ray and MRI. To address these issues, we have developed a wireless, ultrasonically powered, implantable piezoelectric stimulator. The stimulator is encapsulated with biocompatible materials. RESULTS: The stimulator is capable of harvesting a maximum of 5.95 mW electric power at an 8-mm depth under the skin from an ultrasound beam with about 380 mW/cm2 of acoustic intensity. The stimulator was implanted in several paraplegic rats with SCI. Our implanted stimulator successfully induced several hindlimb muscle contractions and restored leg movement. CONCLUSIONS: A battery-free miniature (10 mm diameter × 4 mm thickness) implantable stimulator, developed in the current study is capable of directly stimulating paretic muscles through external ultrasound signals. The required cost to develop the stimulator is relatively low as all the components are off the shelf.

Bangladesh Cerebral Palsy Register (BCPR): a pilot study to develop a national cerebral palsy (CP) register with surveillance of children for CP.

BACKGROUND: The causes and pathogenesis of cerebral palsy (CP) are all poorly understood, particularly in low- and middle-income countries (LMIC). There are gaps in knowledge about CP in Bangladesh, especially in the spheres of epidemiological research, intervention and service utilization. In high-income countries CP registers have made substantial contributions to our understanding of CP. In this paper, we describe a pilot study protocol to develop, implement, and evaluate a CP population register in Bangladesh (i.e., Bangladesh Cerebral Palsy Register - BCPR) to facilitate studies on prevalence, severity, aetiology, associated impairments and risk factors for CP. METHODS/DESIGN: The BCPR will utilise a modified version of the Australian Cerebral Palsy Register (ACPR) on a secured web-based platform hosted by the Cerebral Palsy Alliance Research Institute, Australia. A standard BCPR record form (i.e., data collection form) has been developed in consultation with local and international experts. Using this form, the BPCR will capture information about maternal health, birth history and the nature of disability in all children with CP aged <18 years. The pilot will be conducted in the Shahjadpur sub-district of Sirajgonj district in the northern part of Bangladesh. There are 296 villages in Shahjadpur, a total population of 561,076 (child population ~ 226,114), an estimated 70,998 households and 12,117 live births per annum. Children with CP will be identified by using the community based Key Informants Method (KIM). Data from the completed BPCR record together with details of assessment by a research physician will be entered into an online data repository. DISCUSSION: Once implemented, BCPR will be, to the best of our knowledge, the first formalised CP register from a LMIC. Establishment of the BCPR will enable estimates of prevalence; facilitate clinical surveillance and promote research to improve the care of individuals with CP in Bangladesh.

Electronic bypass of spinal lesions: activation of lower motor neurons directly driven by cortical neural signals.

BACKGROUND: Lower motor neurons in the spinal cord lose supraspinal inputs after complete spinal cord injury, leading to a loss of volitional control below the injury site. Extensive locomotor training with spinal cord stimulation can restore locomotion function after spinal cord injury in humans and animals. However, this locomotion is non-voluntary, meaning that subjects cannot control stimulation via their natural "intent". A recent study demonstrated an advanced system that triggers a stimulator using forelimb stepping electromyographic patterns to restore quadrupedal walking in rats with spinal cord transection. However, this indirect source of "intent" may mean that other non-stepping forelimb activities may false-trigger the spinal stimulator and thus produce unwanted hindlimb movements. METHODS: We hypothesized that there are distinguishable neural activities in the primary motor cortex during treadmill walking, even after low-thoracic spinal transection in adult guinea pigs. We developed an electronic spinal bridge, called "Motolink", which detects these neural patterns and triggers a "spinal" stimulator for hindlimb movement. This hardware can be head-mounted or carried in a backpack. Neural data were processed in real-time and transmitted to a computer for analysis by an embedded processor. Off-line neural spike analysis was conducted to calculate and preset the spike threshold for "Motolink" hardware. RESULTS: We identified correlated activities of primary motor cortex neurons during treadmill walking of guinea pigs with spinal cord transection. These neural activities were used to predict the kinematic states of the animals. The appropriate selection of spike threshold value enabled the "Motolink" system to detect the neural "intent" of walking, which triggered electrical stimulation of the spinal cord and induced stepping-like hindlimb movements. CONCLUSION: We present a direct cortical "intent"-driven electronic spinal bridge to restore hindlimb locomotion after complete spinal cord injury.

Effects of non-invasive cervical spinal cord neuromodulation by trans-spinal electrical stimulation on cortico-muscular descending patterns in upper extremity of chronic stroke.

Background: Trans-spinal electrical stimulation (tsES) to the intact spinal cord poststroke may modulate the cortico-muscular control in stroke survivors with diverse lesions in the brain. This work aimed to investigate the immediate effects of tsES on the cortico-muscular descending patterns during voluntary upper extremity (UE) muscle contractions by analyzing cortico-muscular coherence (CMCoh) and electromyography (EMG) in people with chronic stroke. Methods: Twelve chronic stroke participants were recruited to perform wrist-hand extension and flexion tasks at submaximal levels of voluntary contraction for the corresponding agonist flexors and extensors. During the tasks, the tsES was delivered to the cervical spinal cord with rectangular biphasic pulses. Electroencephalography (EEG) data were collected from the sensorimotor cortex, and the EMG data were recorded from both distal and proximal UE muscles. The CMCoh, laterality index (LI) of the peak CMCoh, and EMG activation level parameters under both non-tsES and tsES conditions were compared to evaluate the immediate effects of tsES on the cortico-muscular descending pathway. Results: The CMCoh and LI of peak CMCoh in the agonist distal muscles showed significant increases (p < 0.05) during the wrist-hand extension and flexion tasks with the application of tsES. The EMG activation levels of the antagonist distal muscle during wrist-hand extension were significantly decreased (p < 0.05) with tsES. Additionally, the proximal UE muscles exhibited significant decreases (p < 0.05) in peak CMCoh and EMG activation levels by applying tsES. There was a significant increase (p < 0.05) in LI of peak CMCoh of proximal UE muscles during tsES. Conclusion: The cervical spinal cord neuromodulation via tsES enhanced the residual descending excitatory control, activated the local inhibitory circuits within the spinal cord, and reduced the cortical and proximal muscular compensatory effects. These results suggested the potential of tsES as a supplementary input for improving UE motor functions in stroke rehabilitation.

Restoration of Over-Ground Walking via Non-Invasive Neuromodulation Therapy: A Single-Case Study.

Spinal cord injuries (SCI) can result in sensory and motor dysfunctions, which were long considered permanent. Recent advancement in electrical neuromodulation has been proven to restore sensorimotor function in people with SCI. These stimulation protocols, however, were mostly invasive, expensive, and difficult to implement. In this study, transcutaneous electrical stimulation (tES) was used to restore over-ground walking of an individual with 21 years of chronic paralysis from a cervical SCI. After a total of 66 weeks of rehabilitation training with tES, which included standing, functional reaching, reclined sit-up, treadmill walking, and active biking, significant improvement in lower-limb volitional movements and overall light touch sensation were shown as measured by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) score. By the end of the study, the participant could walk in a 4-m walking test with the aid of a walking frame and ankle-foot orthoses. The successful sensorimotor recovery of our study participant sheds light on the future of non-invasive neuromodulation treatment for SCI paralysis.

Effect of Cervical Transcutaneous Spinal Cord Stimulation on Sensorimotor Cortical Activity during Upper-Limb Movements in Healthy Individuals.

Transcutaneous spinal cord stimulation (tSCS) can improve upper-limb motor function after spinal cord injury. A number of studies have attempted to deduce the corticospinal mechanisms which are modulated following tSCS, with many relying on transcranial magnetic stimulation to provide measures of corticospinal excitability. Other metrics, such as cortical oscillations, may provide an alternative and complementary perspective on the physiological effect of tSCS. Hence, the present study recorded EEG from 30 healthy volunteers to investigate if and how cortical oscillatory dynamics are altered by 10 min of continuous cervical tSCS. Participants performed repetitive upper-limb movements and resting-state tasks while tSCS was delivered to the posterior side of the neck as EEG was recorded simultaneously. The intensity of tSCS was tailored to each participant based on their maximum tolerance (mean: 50 ± 20 mA). A control session was conducted without tSCS. Changes to sensorimotor cortical activity during movement were quantified in terms of event-related (de)synchronisation (ERD/ERS). Our analysis revealed that, on a group level, there was no consistency in terms of the direction of ERD modulation during tSCS, nor was there a dose-effect between tSCS and ERD/ERS. Resting-state oscillatory power was compared before and after tSCS but no statistically significant difference was found in terms of alpha peak frequency or alpha power. However, participants who received the highest stimulation intensities had significantly weakened ERD/ERS (10% ERS) compared to when tSCS was not applied (25% ERD; p = 0.016), suggestive of cortical inhibition. Overall, our results demonstrated that a single 10 min session of tSCS delivered to the cervical region of the spine was not sufficient to induce consistent changes in sensorimotor cortical activity among the entire cohort. However, under high intensities there may be an inhibitory effect at the cortical level. Future work should investigate, with a larger sample size, the effect of session duration and tSCS intensity on cortical oscillations.

Caregivers' Knowledge, Attitude, and Practice towards Pressure Injuries in Spinal Cord Injury at Rehabilitation Center in Bangladesh.

The purpose of this study was to determine caregivers' knowledge, attitude, and practice (KAP) on the prevention and care of pressure injuries (PIs) in individuals with spinal cord injury. A quantitative cross-sectional study with descriptive correlation design was used to implement a modified semistructured questionnaire using a convenient sampling method. McDonald's standard of learning outcome measurement criteria was used to categorize caregivers' KAP. A Pearson product-moment correlation coefficient (r) was utilized to assess the relationships between caregivers' KAP, with a p value of 0.05 or less considered statistically significant. The study findings indicate that caregivers had a moderate level of knowledge (M = 73.68%, SD = 6.43), a neutral attitude (M = 70.32%, SD = 6.89), and a moderate level of practice (M = 74.77%, SD = 9.08). A positive correlation existed between caregivers' knowledge and attitude (r = 0.30, p < 0.01), as well as between knowledge and practice (r = 0.37, p < 0.01). Nevertheless, there was no correlation between attitude and practice (r = 0.12, p > 0.05). The study findings suggest that caregivers need to develop a positive attitude and expand their knowledge in order to improve their practice. The KAP factors that require higher priority were positioning and turning the patient, preventing skin breakdown, assessing weight changes over time, interest in patient care, additional care for PIs, frequently changing the individual's position, priority to PI care, interest in other types of care other than PIs, using special cushions, consulting doctors on a regular basis, being aware of clothing and fabrics, proper transfer technique, pressure relief, and skin inspection, among others.

Trans-Spinal Electrical Stimulation Therapy for Functional Rehabilitation after Spinal Cord Injury: Review.

Spinal cord injury (SCI) is one of the most debilitating injuries in the world. Complications after SCI, such as respiratory issues, bowel/bladder incontinency, pressure ulcers, autonomic dysreflexia, spasticity, pain, etc., lead to immense suffering, a remarkable reduction in life expectancy, and even premature death. Traditional rehabilitations for people with SCI are often insignificant or ineffective due to the severity and complexity of the injury. However, the recent development of noninvasive electrical neuromodulation treatments to the spinal cord have shed a ray of hope for these individuals to regain some of their lost functions, a reduction in secondary complications, and an improvement in their life quality. For this review, 250 articles were screened and about 150 were included to summarize the two most promising noninvasive spinal cord electrical stimulation methods of SCI rehabilitation treatment, namely, trans-spinal direct current stimulation (tsDCS) and trans-spinal pulsed current stimulation (tsPCS). Both treatments have demonstrated good success in not only improving the sensorimotor function, but also autonomic functions. Due to the noninvasive nature and lower costs of these treatments, in the coming years, we expect these treatments to be integrated into regular rehabilitation therapies worldwide.

Combined Transcutaneous Electrical Spinal Cord Stimulation and Task-Specific Rehabilitation Improves Trunk and Sitting Functions in People with Chronic Tetraplegia.

The aim of this study was to examine the effects of transcutaneous electrical spinal cord stimulation (TSCS) and conventional task-specific rehabilitation (TSR) on trunk control and sitting stability in people with chronic tetraplegia secondary to a spinal cord injury (SCI). Five individuals with complete cervical (C4-C7) cord injury participated in 24-week therapy that combined TSCS and TSR in the first 12 weeks, followed by TSR alone for another 12 weeks. The TSCS was delivered simultaneously at T11 and L1 spinal levels, at a frequency ranging from 20-30 Hz with 0.1-1.0 ms. pulse width biphasically. Although the neurological prognosis did not manifest after either treatment, the results show that there were significant increases in forward reach distance (10.3 ± 4.5 cm), right lateral reach distance (3.7 ± 1.8 cm), and left lateral reach distance (3.0 ± 0.9 cm) after the combinational treatment (TSCS+TSR). The stimulation also significantly improved the participants' trunk control and function in sitting. Additionally, the trunk range of motion and the electromyographic response of the trunk muscles were significantly elevated after TSCS+TSR. The TSCS+TSR intervention improved independent trunk control with significantly increased static and dynamic sitting balance, which were maintained throughout the TSR period and the follow-up period, indicating long-term sustainable recovery.

Brain-Computer Interface Priming for Cervical Transcutaneous Spinal Cord Stimulation Therapy: An Exploratory Case Study.

Loss of arm and hand function is one of the most devastating consequences of cervical spinal cord injury (SCI). Although some residual functional neurons often pass the site of injury, recovery after SCI is extremely limited. Recent efforts have aimed to augment traditional rehabilitation by combining exercise-based training with techniques such as transcutaneous spinal cord stimulation (tSCS), and movement priming. Such methods have been linked with elevated corticospinal excitability, and enhanced neuroplastic effects following activity-based therapy. In the present study, we investigated the potential for facilitating tSCS-based exercise-training with brain-computer interface (BCI) motor priming. An individual with chronic AIS A cervical SCI with both sensory and motor complete tetraplegia participated in a two-phase cross-over intervention whereby they engaged in 15 sessions of intensive tSCS-mediated hand training for 1 h, 3 times/week, followed by a two week washout period, and a further 15 sessions of tSCS training with bimanual BCI motor priming preceding each session. We found using the Graded Redefined Assessment for Strength, Sensibility, and Prehension that the participant's arm and hand function improved considerably across each phase of the study: from 96/232 points at baseline, to 117/232 after tSCS training alone, and to 131/232 points after BCI priming with tSCS training, reflecting improved strength, sensation, and gross and fine motor skills. Improved motor scores and heightened perception to sharp sensations improved the neurological level of injury from C4 to C5 following training and improvements were generally maintained four weeks after the final training session. Although functional improvements were similar regardless of the presence of BCI priming, there was a moderate improvement of bilateral strength only when priming preceded tSCS training, perhaps suggesting a benefit of motor priming for tSCS training.

Buspirone Dose-Response on Facilitating Forelimb Functional Recovery in Cervical Spinal Cord Injured Rats.

Buspirone, widely used as a neuropsychiatric drug, has also shown potentials for motor function recovery of injured spinal cord. However, the optimum dosages of such treatment remain unclear. In this study, we investigated the dose-response of Buspirone treatment on reaching and grasping function in cervical cord injured rats. Seventeen adult Sprague-Dawley rats were trained to reach and grasp sugar pellets before a C4 bilateral dorsal column crush injury. After 1 week post-injury, the rats were divided into 3 groups to receive 1 of 3 different dosages of Buspirone (i.p., 1 dose/day: 1.5, n = 5; 2.5, n = 6 and 3.5 mg/kg b.w., n = 6). Forelimb reaching and grip strength test were recorded once per week, within 1 hour of Buspirone administration for 11 weeks post-injury. Different dose groups began to exhibit differences in reaching scores from 4 weeks post-injury. From 4-11 weeks post-injury, the reaching scores were highest in the lowest-dose group rats compared to the other 2 dose groups rats. Average grip strength was also found higher in the lowest-dose rats. Our results demonstrate a significant dose-dependence of Buspirone on the recovery of forelimb motor functions after cervical cord injury with the best performance occurring at the lowest dose tested.

Serotonergic Facilitation of Forelimb Functional Recovery in Rats with Cervical Spinal Cord Injury.

Serotonergic agents can improve the recovery of motor ability after a spinal cord injury. Herein, we compare the effects of buspirone, a 5-HT1A receptor partial agonist, to fluoxetine, a selective serotonin reuptake inhibitor, on forelimb motor function recovery after a C4 bilateral dorsal funiculi crush in adult female rats. After injury, single pellet reaching performance and forelimb muscle activity decreased in all rats. From 1 to 6 weeks after injury, rats were tested on these tasks with and without buspirone (1-2 mg/kg) or fluoxetine (1-5 mg/kg). Reaching and grasping success rates of buspirone-treated rats improved rapidly within 2 weeks after injury and plateaued over the next 4 weeks of testing. Electromyography (EMG) from selected muscles in the dominant forelimb showed that buspirone-treated animals used new reaching strategies to achieve success after the injury. However, forelimb performance dramatically decreased within 2 weeks of buspirone withdrawal. In contrast, fluoxetine treatment resulted in a more progressive rate of improvement in forelimb performance over 8 weeks after injury. Neither buspirone nor fluoxetine significantly improved quadrupedal locomotion on the horizontal ladder test. The improved accuracy of reaching and grasping, patterns of muscle activity, and increased excitability of spinal motor-evoked potentials after buspirone administration reflect extensive reorganization of connectivity within and between supraspinal and spinal sensory-motor netxcopy works. Thus, both serotonergic drugs, buspirone and fluoxetine, neuromodulated these networks to physiological states that enabled markedly improved forelimb function after cervical spinal cord injury.

Disruption to normal excitatory and inhibitory function within the medial prefrontal cortex in people with chronic pain.

BACKGROUND: Growing evidence indicates a link between changes in the medial prefrontal cortex and the pathophysiology of chronic pain. In particular, chronic pain is associated with altered medial prefrontal anatomy and biochemistry. Due to the comorbid affective disorders seen across all pain conditions, the medial prefrontal cortex is a region of significance as it is involved in emotional processing. We have recently reported that a decrease in medial prefrontal N-acetylaspartate and glutamate is associated with increased emotional dysregulation, indicating there are neurotransmitter imbalances in chronic pain. Therefore, we compared medial prefrontal neurochemistry in 24 people with chronic pain conditions to 24 age and sex-matched healthy controls with no history of chronic pain. METHOD: GABA-edited MEGA-PRESS was used to measure GABA+ levels, and short TE PRESS was used to measure glutamate levels in the medial prefrontal cortex. Psychometric measures regarding pain intensity a week before scanning, during the scan and the total duration of chronic pain, were also recorded and compared to measured GABA+ and glutamate levels. RESULTS: This study reveals that the presence of chronic pain is associated with significant decreases in medial prefrontal GABA+ and glutamate. These findings support the hypothesis that chronic pain is associated with altered medial prefrontal biochemistry. CONCLUSION: The dysregulation of glutamatergic and GABAergic neurotransmitter systems supports a model of disinhibition of chronic pain, which may play a key role in both the experience of persistent pain and its associated affective disturbances. SIGNIFICANCE: This study reveals a significant reduction in γ-aminobutyric acid (GABA+ ) and glutamate within the medial prefrontal cortex in chronic pain sufferers. While the current findings should be considered with reference to a small sample size, the disruption to normal excitatory and inhibitory medial prefrontal cortex function may be key in the development and maintenance of chronic pain and comorbid mental health disorders.

Spinal Cord Injury: Lessons about Neuroplasticity from Paired Associative Stimulation.

Paired associative stimulation (PAS) is a noninvasive neuromodulation method with rare cases of adverse effects for the patients with neurological injuries such as spinal cord injury (SCI). PAS is based on the principles of associative long-term potentiation and depression where the activation of presynaptic and postsynaptic neurons correlated in time is artificially induced. Statistically significant improvement in motor functions after applying PAS has been reported by several research groups. With further standardization of the technique, PAS could be an effective treatment for functional rehabilitation of SCI patients. In this review, we have summarized the methods and findings of PAS on SCI rehabilitation to facilitate the readers to understand the potentials and limitations of PAS for its future clinical use.

Reversing 21 years of chronic paralysis via non-invasive spinal cord neuromodulation: a case study.

OBJECTIVE: The objective of the current study was to investigate if a non-invasive spinal cord neuromodulation modality could restore sensorimotor functions in a patient with chronic spinal cord injury (SCI). METHODS: In this study, transcutaneous electrical stimulation (tES) to the spinal cord was utilized to restore sensorimotor functions in a chronic SCI patient who sustained a traumatic C7 cervical cord injury 21 years ago. At baseline, the patient had very limited volitional movement in her right leg, and her left leg was completely paralyzed. tES parameters were optimized in eight stimulation sessions before the treatment. The therapeutic stimulation involved biphasic tES, applied to T11 and L1 spinal levels during a 1-hour standing and walking training, 2-4 times per week for 16 weeks. RESULTS: Our pre-treatment tests indicated that a shorter burst duration (100 µsec) was more effective than a longer burst duration of tES in improving functional movements. After 32 training sessions with tES, the patient regained significant left-leg volitional movements (grade 0 to grade 10 according to the ISNCSCI scale). Right-leg motor scores also increased from 17 to 21. The tES treatment also improved her pinprick sensation (from 73 to 79). Upon completion of the treatment (52 sessions), the patient's standing ability noticeably improved. She could stabilize her knee to stand without any assistance. She could also squat while holding onto a walker. INTERPRETATION: These promising results demonstrate beneficial effects of non-invasive tES in regaining volitional control of plegic lower limbs in patients with chronic paralysis.

Ultrasound-driven piezoelectric current activates spinal cord neurocircuits and restores locomotion in rats with spinal cord injury.

BACKGROUND: Neuromodulation via electrical stimulation (ES) is a common technique to treat numerous brain and spinal cord related neurological conditions. In the present study, we examined the efficacy of piezoelectric stimulation (pES) by a custom miniature piezostimulator to activate the spinal cord neurocircuit in comparison with conventional epidural ES in rats. METHODS: Stimulation electrodes were implanted on L2 and S1 spinal cord and were connected to a head-plug for ES, and a piezostimulator for pES. EMG electrodes were implanted into hindlimb muscles. To generate piezoelectric current, an ultrasound beam was delivered by an external ultrasound probe. Motor evoked potentials (MEPs) were recorded during the piezoelectric stimulation and compared with the signals generated by the ES. RESULTS: Our results suggest that ultrasound intensity as low as 0.1 mW/cm2 could induce MEPs in the hindlimbs. No significant difference was found either in MEPs or in muscle recruitments for ES and pES. Similar to ES, pES induced by 22.5 mW/cm2 ultrasound restored locomotion in paralyzed rats with complete thoracic cord injury. Locomotion EMG signals indicated that pES works same as ES. CONCLUSION: We propose piezoelectric stimulation as a new avenue of neuromodulation with features overtaking conventional electrical stimulation to serve future bioelectronic medicine. Video abstract.