Effects of paired stimulation with specific waveforms on cortical and spinal plasticity in subjects with a chronic spinal cord injury.

BACKGROUND/PURPOSE: Paired stimulation can cause neuroplasticity in corticospinal and spinal pathways in subjects with a chronic spinal cord injury (SCI). We aimed to know the effects of different waveforms using paired stimulations with bicycling in subjects with a chronic SCI. METHODS: Recruited subjects with an SCI underwent three treatment interventions in random order for 4-20 min followed by 30 min of bicycling (control, repetitive transcranial magnetic stimulation (TMS; rTMS) at 20 Hz with transspinal direct current stimulation (tsDCS), and intermittent theta burst stimulation (iTBS) with tsDCS with a 1-week gap period. A TMS method was employed to record the resting motor threshold (RMT), the 90% values of which was used as the stimulation intensity, and the Hoffman (H)-reflex was measured by stimulating the tibial nerve in the popliteal fossa. The RMT, motor evoked potential (MEP) latency, MEP peak-to-peak amplitude, and H-reflex latency as primary variables and lower extremity motor scale (LEMS) and modified Ashworth spasticity scale (MAS) as secondary variables were analyzed before and after the interventions. RESULTS: The MEP latency, MEP amplitude, and LEMS significantly improved with the rTMS-iTBS/tsDCS or the rTMS-20 Hz/tsDCS (p < 0.050) protocols compared to the control intervention. All other outcome measures, including RMT, H-reflex latency, and MAS score showed some changes but did not fully attain a level of significance. CONCLUSION: The paired stimulation with rTMS-iTBS/tsDCS was equally effective to produce neuroplastic effect in subjects with chronic SCI compared to the conventional TMS-20 Hz/tsDCS intervention.

Motor Neuroplastic Effects of a Novel Paired Stimulation Technology in an Incomplete Spinal Cord Injury Animal Model.

Paired stimulation of the brain and spinal cord can remodel the central nervous tissue circuitry in an animal model to induce motor neuroplasticity. The effects of simultaneous stimulation vary according to the extent and severity of spinal cord injury. Therefore, our study aimed to determine the significant effects on an incomplete SCI rat brain and spinal cord through 3 min and 20 min stimulations after 4 weeks of intervention. Thirty-three Sprague Dawley rats were classified into six groups: (1) normal, (2) sham, (3) iTBS/tsDCS, (4) iTBS/ts-iTBS, (5) rTMS/tsDCS, and (6) rTMS/ts-iTBS. Paired stimulation of the brain cortex and spinal cord thoracic (T10) level was applied simultaneously for 3−20 min. The motor evoked potential (MEP) and Basso, Beattie, and Bresnahan (BBB) scores were recorded after every week of intervention for four weeks along with wheel training for 20 min. Three-minute stimulation with the iTBS/tsDCS intervention induced a significant (p < 0.050 *) increase in MEP after week 2 and week 4 treatments, while 3 min iTBS/ts-iTBS significantly improved MEP (p < 0.050 *) only after the week 3 intervention. The 20 min rTMS/ts-iTBS intervention showed a significant change only in post_5 min after week 4. The BBB score also changed significantly in all groups except for the 20 min rTMS/tsDCS intervention. iTBS/tsDCS and rTMS/ts-iTBS interventions induce neuroplasticity in an incomplete SCI animal model by significantly changing electrophysiological (MEP) and locomotion (BBB) outcomes.

Evaluation of Cognition and Cortical Excitability in Huntington's Disease.

BACKGROUND: Recent advances in neurophysiological techniques have contributed to our understanding of the pathophysiology of Huntington's disease (HD). Studies of the motor cortical excitability and central motor pathways have shown variable results. OBJECTIVES: Our aims were to evaluate the cortical excitability changes in HD using transcranial magnetic stimulation (TMS) and correlate the changes with cognitive impairment. METHODS: The study included 32 HD patients and 30 age- and gender-matched controls. The demographic and clinical profiles of the patients were recorded. All subjects were evaluated by TMS and resting motor threshold (RMT), central motor conduction time (CMCT), silent period (SP), short-interval intracortical inhibition (SICI), and intracortical facilitation were determined. A battery of neuropsychological tests was administered to all subjects. RESULTS: The mean age of the patients was 42.1±14.1 years, and that of controls 39.4±12.4 years (p=0.61). There was no significant difference in RMT and CMCT between the two groups. There was a mild prolongation of the contralateral SP in HD, but it was not significant. SICI was significantly reduced in HD (p<0.0001). A significant impairment in attention, verbal fluency, executive function, visuospatial function, learning, and memory was observed in HD patients. However, there was no correlation between cortical excitability changes and cognitive impairment. CONCLUSIONS: TMS is a valuable method of evaluating cortical excitability changes in HD. These patients have reduced SICI and significant impairment of cognition in multiple domains.

Matching supplementary motor area-primary motor cortex paired transcranial magnetic stimulation improves motor dysfunction in Parkinson's disease: a single-center, double-blind randomized controlled clinical trial protocol.

Background: Non-invasive neuroregulation techniques have been demonstrated to improve certain motor symptoms in Parkinson's disease (PD). However, the currently employed regulatory techniques primarily concentrate on stimulating single target points, neglecting the functional regulation of networks and circuits. The supplementary motor area (SMA) has a significant value in motor control, and its functionality is often impaired in patients with PD. The matching SMA-primary motor cortex (M1) paired transcranial magnetic stimulation (TMS) treatment protocol, which benefits patients by modulating the sequential and functional connections between the SMA and M1, was elucidated in this study. Methods: This was a single-center, double-blind, randomized controlled clinical trial. We recruited 78 subjects and allocated them in a 1:1 ratio by stratified randomization into the paired stimulation (n = 39) and conventional stimulation groups (n = 39). Each patient underwent 3 weeks of matching SMA-M1 paired TMS or sham-paired stimulation. The subjects were evaluated before treatment initiation, 3 weeks into the intervention, and 3 months after the cessation of therapy. The primary outcome measure in this study was the Unified Parkinson's Disease Rating Scale III, and the secondary outcome measures included non-motor functional assessment, quality of life (Parkinson's Disease Questionnaire-39), and objective assessments (electromyography and functional near-infrared spectroscopy). Discussion: Clinical protocols aimed at single targets using non-invasive neuroregulation techniques often improve only one function. Emphasizing the circuit and network regulation in PD is important for enhancing the effectiveness of TMS rehabilitation. Pairing the regulation of cortical circuits may be a potential treatment method for PD. As a crucial node in motor control, the SMA has direct fiber connections with basal ganglia circuits and complex fiber connections with M1, which are responsible for motor execution. SMA regulation may indirectly regulate the function of basal ganglia circuits. Therefore, the developed cortical pairing stimulation pattern can reshape the control of information flow from the SMA to M1. The novel neuroregulation model designed for this study is based on the circuit mechanisms of PD and previous research results, with a scientific foundation and the potential to be a means of neuroregulation for PD.Clinical trial registration: ClinicalTrials.gov, identifier [ChiCTR2400083325].

Acute intermittent hypoxia boosts spinal plasticity in humans with tetraplegia.

Paired corticospinal-motoneuronal stimulation (PCMS) elicits spinal synaptic plasticity in humans with chronic incomplete cervical spinal cord injury (SCI). Here, we examined whether PCMS-induced plasticity could be potentiated by acute intermittent hypoxia (AIH), a treatment also known to induce spinal synaptic plasticity in humans with chronic incomplete cervical SCI. During PCMS, we used 180 pairs of stimuli where corticospinal volleys evoked by transcranial magnetic stimulation over the hand representation of the primary motor cortex were timed to arrive at corticospinal-motoneuronal synapses of the first dorsal interosseous (FDI) muscle ~1-2 ms before the arrival of antidromic potentials elicited in motoneurons by electrical stimulation of the ulnar nerve. During AIH, participants were exposed to brief alternating episodes of hypoxic inspired gas (1 min episodes of 9% O2) and room air (1 min episodes of 20.9% O2). We examined corticospinal function by measuring motor evoked potentials (MEPs) elicited by cortical and subcortical stimulation of corticospinal axons and voluntary motor output in the FDI muscle before and after 30 min of PCMS combined with AIH (PCMS+AIH) or sham AIH (PCMS+sham-AIH). The amplitude of MEPs evoked by magnetic and electrical stimulation increased after both protocols, but most after PCMS+AIH, consistent with the hypothesis that their combined effects arise from spinal plasticity. Both protocols increased electromyographic activity in the FDI muscle to a similar extent. Thus, PCMS effects on spinal synapses of hand motoneurons can be potentiated by AIH. The possibility of different thresholds for physiological vs behavioral gains needs to be considered during combinatorial treatments.

Targeting Sensory and Motor Integration for Recovery of Movement After CNS Injury.

The central nervous system (CNS) integrates sensory and motor information to acquire skilled movements, known as sensory-motor integration (SMI). The reciprocal interaction of the sensory and motor systems is a prerequisite for learning and performing skilled movement. Injury to various nodes of the sensorimotor network causes impairment in movement execution and learning. Stimulation methods have been developed to directly recruit the sensorimotor system and modulate neural networks to restore movement after CNS injury. Part 1 reviews the main processes and anatomical interactions responsible for SMI in health. Part 2 details the effects of injury on sites critical for SMI, including the spinal cord, cerebellum, and cerebral cortex. Finally, Part 3 reviews the application of activity-dependent plasticity in ways that specifically target integration of sensory and motor systems. Understanding of each of these components is needed to advance strategies targeting SMI to improve rehabilitation in humans after injury.

Transcranial Direct Current Stimulation Effects on Single and Paired Flash Visual Evoked Potentials.

Transcranial direct current stimulation (tDCS) applied over the occipital cortex has a controversial effect on the visual cortex excitability. Paired flash visual evoked potentials (paired F-VEPs) offer a unique method to express neural inhibition within the visual system. However, no studies have explored the effects of tDCS on F-VEPs in humans. The aim of this study was to evaluate the changes of single- and paired-F-VEPs during and after tDCS in healthy humans. Twenty-six healthy volunteers participated. F-VEPs were recorded from occipital electrodes with closed eyes. Stimuli were single flashes, intermingled to flash pairs at the interstimulus interval of 125, 62.5, 50, 33.3, 16.6, and 11.1 ms (internal frequency of 8, 16, 20, 30, 60, and 90 Hz). The single F-VEP was split into a "main complex" and a "late response." As to paired stimuli, the "test" F-VEP emerged from electronic subtraction of the single-F-VEP to the paired-F-VEP. In experiment 1, the return electrode was located on the scalp and we studied changes in F-VEPs after anodal, cathodal (1 mA, 15 min) and sham stimulation. A second experiment was performed in which F-VEPs were recorded before, during and after tDCS stimulation (anodal and cathodal) with the return electrode on the neck. F-VEPs recorded in experiment 1 did not detect any significant change after tDCS. In experiment 2 anodal polarization significantly increased the P2 latency (P = .031) and reduced the amplitude of the "late response" of the single F-VEP (P = .008). As for the paired F-VEPs, no significant changes were detected. In conclusion, low-intensity anodal tDCS has weak inhibitory aftereffects on the single F-VEP and no effects on the paired F-VEPs. Further methodological studies are needed to improve polarization efficacy.

Impaired visual inhibition in migraine with aura.

OBJECTIVE: The pathophysiology of migraine with or without aura (MA, MO) is still a matter of debate. We thus studied patients with MA and MO by means of paired-pulse flash-visual evoked potentials (paired F-VEPs). This technique, recently revived, analyses the overall excitability of visual system as detected from the cortical occipital signal. METHODS: We enrolled 13 adult patients with MO and 13 with MA. Twenty-two normal subjects of similar age and sex acted as controls. Stimuli were single flashes, intermingled at random to flash pairs at critical interstimulus intervals (ISIs, 16.5-125ms) with closed and open eyes. The "single"(unconditioned) F-VEP was split into a "main complex" (50-200ms after the flash) and a "late response" (200-400ms). As for paired stimulation, the "test" F-VEP emerged from electronic subtraction of the "single" F-VEP to the "paired" F-VEP. Its size was expressed as "test"/"single"F-VEP∗100. RESULTS: As for paired F-VEPs, the "main complex" of the "test" F-VEP in the MA group did not show the size reduction (at ISIs 50-62.5ms) which was typical among the control and MO groups (p⩽0.016) in the "eyes-closed" state. CONCLUSIONS: Paired F-VEPs document a defective neural inhibition in the visual system of patients with MA. SIGNIFICANCE: Paired F-VEPs may warrant inclusion in future preclinical/clinical studies, to evaluate its potential role in the pathophysiology and management of MA.