Dose-response of tDCS effects on motor learning and cortical excitability: A preregistered study.

Multiple studies have demonstrated that transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) can influence corticospinal excitability and motor skill acquisition. However, the evidence for these effects is inconsistent, and a common neural substrate for these effects has not been directly demonstrated. To address this, we hypothesized that higher tDCS intensities would produce more robust effects, and uncover their relationship.

Safety and efficacy of transcranial direct current stimulation in addition to constraint-induced movement therapy for post-stroke motor recovery (TRANSPORT2): a phase 2, multicentre, randomised, sham-controlled triple-blind trial.

Background: Motor impairments contribute substantially to long-term disability following stroke. Studies of transcranial direct current stimulation (tDCS), combined with various rehabilitation therapies, have shown promising results in reducing motor impairment. We aimed to evaluate the safety and efficacy of three doses of tDCS in combination with modified constraint-induced movement therapy (mCIMT) in people who have had their first ischaemic stroke in the preceding 1-6 months.

TMS assessment of corticospinal tract integrity after stroke: broadening the concept to inform neurorehabilitation prescription.

Upper limb actions require intersegmental coordination of the scapula, shoulders, elbows, forearms, wrists, and hand muscles. Stroke hemiparesis, presenting as an impairment of an intersegmentally coordinated voluntary movement, is associated with altered integrity of corticospinal tract (CST) transmission from the motor cortex (M1) to muscles. Motor evoked potentials (MEPs) elicited by M1 transcranial magnetic stimulation (TMS) of "at rest" muscles, or as a backup, during muscle contraction have been used to identify CST integrity and predict the outcome after hemiparesis, under the implicit assumption that MEPs present in only one or two muscles are manifest surrogates of CST integrity for other muscles of the upper limbs.

Electric Field Navigated 1-Hz rTMS for Poststroke Motor Recovery: The E-FIT Randomized Controlled Trial.

Background: To determine if low-frequency repetitive transcranial magnetic stimulation targeting the primary motor cortex contralateral (M1) to the affected corticospinal tract in patients with hemiparetic stroke augments intensive training-related clinical improvement; an extension of the NICHE trial (Navigated Inhibitory rTMS to Contralesional Hemisphere Trial) using an alternative sham coil.

Methods: The present E-FIT trial (Electric Field Navigated 1Hz rTMS for Post-stroke Motor Recovery Trial) included 5 of 12 NICHE trial outpatient US rehabilitation centers. The stimulation protocol remained identical (1 Hz repetitive transcranial magnetic stimulation, M1, preceding 60-minute therapy, 18 sessions/6 wks; parallel arm randomized clinical trial).

Brk/PTK6 and Involucrin Expression May Predict Breast Cancer Cell Responses to Vitamin D3.

The process of human embryonic mammary development gives rise to the structures in which mammary cells share a developmental lineage with skin epithelial cells such as keratinocytes. As some breast carcinomas have previously been shown to express high levels of involucrin, a marker of keratinocyte differentiation, we hypothesised that some breast tumours may de-differentiate to a keratinocyte-derived 'evolutionary history'. To confirm our hypothesis, we investigated the frequency of involucrin expression along with that of Brk, a tyrosine kinase expressed in up to 86% of breast carcinomas whose normal expression patterns are restricted to differentiating epithelial cells, most notably those in the skin (keratinocytes) and the gastrointestinal tract.

Telerehabilitation Initiated Early in Post-Stroke Recovery: A Feasibility Study.

Background: Enhanced neural plasticity early after stroke suggests the potential to improve outcomes with intensive rehabilitation therapy. Most patients do not get such therapy, however, due to limited access, changing rehabilitation therapy settings, low therapy doses, and poor compliance.

Objective: To examine the feasibility, safety, and potential efficacy of an established telerehabilitation (TR) program after stroke initiated during admission to an inpatient rehabilitation facility (IRF) and completed in the patient's home.

Activation of MAP2K signaling by genetic engineering or HF-rTMS promotes corticospinal axon sprouting and functional regeneration.

Facilitating axon regeneration in the injured central nervous system remains a challenging task. RAF-MAP2K signaling plays a key role in axon elongation during nervous system development. Here, we show that conditional expression of a constitutively kinase-activated BRAF in mature corticospinal neurons elicited the expression of a set of transcription factors previously implicated in the regeneration of zebrafish retinal ganglion cell axons and promoted regeneration and sprouting of corticospinal tract (CST) axons after spinal cord injury in mice.

Corticospinal and intracortical responses from both motor cortices following unilateral concentric versus eccentric contractions.

Cross-education is the phenomenon where training of one limb can cause neuromuscular adaptations in the opposite untrained limb. This effect has been reported to be greater after eccentric (ECC) than concentric (CON) strength training; however, the underpinning neurophysiological mechanisms remain unclear. Thus, we compared responses to transcranial magnetic stimulation (TMS) in both motor cortices following single sessions of unilateral ECC and CON exercise of the elbow flexors.

Dataset of middle cerebral artery blood flow stability in response to high-definition transcranial electrical stimulation.

This supplementary dataset is supportive of the randomized sham-controlled, double-blind, crossover clinical trial investigating polarity- and intensity-dependent effects of high-definition transcranial electrical stimulation (HD-tDCS) applied over the right temporo-parietal junction on mean middle cerebral artery blood flow velocity (MCA-BFv) bilaterally. Data of eleven healthy right-handed adults (6 women, 5 men; mean age 31 ± 5.6 years old) were analyzed for MCA-BFv, assessed using transcranial doppler ultrasound on the stimulated and the contralateral hemisphere concomitantly, during and after 3 blocks of 2 min HD-tDCS at 1, 2, and 3 mA.

Intraclass Correlation in Paired Associative Stimulation and Metaplasticity.

Paired associative stimulation (PAS) is a widely used noninvasive brain stimulation protocol to assess neural plasticity. Its reproducibility, however, has been rarely tested and with mixed results. With two consecutive studies, we aimed to provide further tests and a more systematic assessment of PAS reproducibility.

Middle cerebral artery blood flow stability in response to high-definition transcranial electrical stimulation: A randomized sham-controlled clinical trial.

Since neuronal activity is coupled with neurovascular activity, we aimed to analyze the cerebral blood flow hemodynamics during and following high-definition transcranial direct current stimulation (HD-tDCS). We assessed the mean middle cerebral artery blood flow velocity (MCA-BFv) bilaterally using transcranial doppler ultrasound, during and after HD-tDCS, in eleven right-handed healthy adult participants (6 women, 5 men; mean age 31 ± 5.6 years old), with no evidence of brain or cardiovascular dysfunction.

Using noise for the better: The effects of transcranial random noise stimulation on the brain and behavior.

Van der Groen, O., Potok, W., Wenderoth, N.

Walking improvement in chronic incomplete spinal cord injury with exoskeleton robotic training (WISE): a randomized controlled trial.

Study Design: Clinical trial.

Objective: To demonstrate that a 12-week exoskeleton-based robotic gait training regimen can lead to a clinically meaningful improvement in independent gait speed, in community-dwelling participants with chronic incomplete spinal cord injury (iSCI).

Setting: Outpatient rehabilitation or research institute.

Post-stroke outcomes predicted from multivariate lesion-behaviour and lesion network mapping.

Clinicians and scientists alike have long sought to predict the course and severity of chronic post-stroke cognitive and motor outcomes, as the ability to do so would inform treatment and rehabilitation strategies. However, it remains difficult to make accurate predictions about chronic post-stroke outcomes due, in large part, to high inter-individual variability in recovery and a reliance on clinical heuristics rather than empirical methods. The neuroanatomical location of a stroke is a key variable associated with long-term outcomes, and because lesion location can be derived from routinely collected clinical neuroimaging data there is an opportunity to use this information to make empirically based predictions about post-stroke deficits.

Robotic Kinematic measures of the arm in chronic Stroke: part 2 - strong correlation with clinical outcome measures.

Background: A detailed sensorimotor evaluation is essential in planning effective, individualized therapy post-stroke. Robotic kinematic assay may offer better accuracy and resolution to understand stroke recovery. Here we investigate the added value of distal wrist measurement to a proximal robotic kinematic assay to improve its correlation with clinical upper extremity measures in chronic stroke.

Robotic Kinematic measures of the arm in chronic Stroke: part 1 - Motor Recovery patterns from tDCS preceding intensive training.

Background: Effectiveness of robotic therapy and transcranial direct current stimulation is conventionally assessed with clinical measures. Robotic metrics may be more objective and sensitive for measuring the efficacy of interventions on stroke survivor's motor recovery. This study investigated if robotic metrics detect a difference in outcomes, not seen in clinical measures, in a study of transcranial direct current stimulation (tDCS) preceding robotic therapy.

Transcranial Random Noise Stimulation Modulates Neural Processing of Sensory and Motor Circuits, from Potential Cellular Mechanisms to Behavior: A Scoping Review.

Noise introduced in the human nervous system from cellular to systems levels can have a major impact on signal processing. Using transcranial stimulation, electrical noise can be added to cortical circuits to modulate neuronal activity and enhance function in the healthy brain and in neurologic patients. Transcranial random noise stimulation (tRNS) is a promising technique that is less well understood than other non-invasive neuromodulatory methods.

Abnormal synergistic gait mitigation in acute stroke using an innovative ankle-knee-hip interlimb humanoid robot: a preliminary randomized controlled trial.

Abnormal spasticity and associated synergistic patterns are the most common neuromuscular impairments affecting ankle-knee-hip interlimb coordinated gait kinematics and kinetics in patients with hemiparetic stroke. Although patients with hemiparetic stroke undergo various treatments to improve gait and movement, it remains unknown how spasticity and associated synergistic patterns change after robot-assisted and conventional treatment. We developed an innovative ankle-knee-hip interlimb coordinated humanoid robot (ICT) to mitigate abnormal spasticity and synergistic patterns.

Conformation-Specific Inhibitory Anti-MMP-7 Monoclonal Antibody Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Chemotherapeutic Cell Kill.

Matrix metalloproteases (MMPs) undergo post-translational modifications including pro-domain shedding. The activated forms of these enzymes are effective drug targets, but generating potent biological inhibitors against them remains challenging. We report the generation of anti-MMP-7 inhibitory monoclonal antibody (GSM-192), using an alternating immunization strategy with an active site mimicry antigen and the activated enzyme.

Intense Arm Rehabilitation Therapy Improves the Modified Rankin Scale Score: Association Between Gains in Impairment and Function.

Objective: To evaluate the effect of intensive rehabilitation on the modified Rankin Scale (mRS), a measure of activities limitation commonly used in acute stroke studies, and to define the specific changes in body structure/function (motor impairment) most related to mRS gains.

Methods: Patients were enrolled >90 days poststroke. Each was evaluated before and 30 days after a 6-week course of daily rehabilitation targeting the arm.

Training in the practice of noninvasive brain stimulation: Recommendations from an IFCN committee.

As the field of noninvasive brain stimulation (NIBS) expands, there is a growing need for comprehensive guidelines on training practitioners in the safe and effective administration of NIBS techniques in their various research and clinical applications. This article provides recommendations on the structure and content of this training. Three different types of practitioners are considered (Technicians, Clinicians, and Scientists), to attempt to cover the range of education and responsibilities of practitioners in NIBS from the laboratory to the clinic.