Mar Cortes

Physiological and modeling evidence for focal transcranial electrical brain stimulation in humans: A basis for high-definition tDCS

Transcranial Direct Current Stimulation (tDCS) is a non-invasive, low-cost, well-tolerated technique producing lasting modulation of cortical excitability. Behavioral and therapeutic outcomes of tDCS are linked to the targeted brain regions, but there is little evidence that current reaches the brain as intended. We aimed to: (1) validate a computational model for estimating cortical electric fields in human transcranial stimulation, and (2) assess the magnitude and spread of cortical electric field with a novel High-Definition tDCS (HD-tDCS) scalp montage using a 4 × 1-Ring electrode configuration. In three healthy adults, Transcranial Electrical Stimulation (TES) over primary motor cortex (M1) was delivered using the 4 × 1 montage (4 × cathode, surrounding a single central anode; montage radius ~3 cm) with sufficient intensity to elicit a discrete muscle twitch in the hand. The estimated current distribution in M1 was calculated using the individualized MRI-based model, and compared with the observed motor response across subjects. The response magnitude was quantified with stimulation over motor cortex as well as anterior and posterior to motor cortex. In each case the model data were consistent with the motor response across subjects. The estimated cortical electric fields with the 4 × 1 montage were compared (area, magnitude, direction) for TES and tDCS in each subject. We provide direct evidence in humans that TES with a 4 × 1-Ring configuration can activate motor cortex and that current does not substantially spread outside the stimulation area. Computational models predict that both TES and tDCS waveforms using the 4 × 1-Ring configuration generate electric fields in cortex with comparable gross current distribution, and preferentially directed normal (inward) currents. The agreement of modeling and experimental data for both current delivery and focality support the use of the HD-tDCS 4 × 1-Ring montage for cortically targeted neuromodulation.

Cerebellar Transcranial Direct Current Stimulation (ctDCS) A Novel Approach to Understanding Cerebellar Function in Health and Disease

The cerebellum is critical for both motor and cognitive control. Dysfunction of the cerebellum is a component of multiple neurological disorders. In recent years, interventions have been developed that aim to excite or inhibit the activity and function of the human cerebellum. Transcranial direct current stimulation of the cerebellum (ctDCS) promises to be a powerful tool for the modulation of cerebellar excitability. This technique has gained popularity in recent years as it can be used to investigate human cerebellar function, is easily delivered, is well tolerated, and has not shown serious adverse effects. Importantly, the ability of ctDCS to modify behavior makes it an interesting approach with a potential therapeutic role for neurological patients. Through both electrical and non-electrical effects (vascular, metabolic) ctDCS is thought to modify the activity of the cerebellum and alter the output from cerebellar nuclei. Physiological studies have shown a polarity-specific effect on the modulation of cerebellar–motor cortex connectivity, likely via cerebellar–thalamocortical pathways. Modeling studies that have assessed commonly used electrode montages have shown that the ctDCS-generated electric field reaches the human cerebellum with little diffusion to neighboring structures. The posterior and inferior parts of the cerebellum (i.e., lobules VI-VIII) seem particularly susceptible to modulation by ctDCS. Numerous studies have shown to date that ctDCS can modulate motor learning, and affect cognitive and emotional processes. Importantly, this intervention has a good safety profile; similar to when applied over cerebral areas. Thus, investigations have begun exploring ctDCS as a viable intervention for patients with neurological conditions.

Spinal associative stimulation: A non-invasive stimulation paradigm to modulate spinal excitability

OBJECTIVE Repetitive, paired peripheral and transcranial stimulation targeting the cerebral cortex can increase cortical excitability, outlasting the stimulation period. It is unknown whether paired stimulation specifically targeting the spinal cord can modulate spinal excitability. We tested whether the H-reflex facilitation from a sub-threshold conditioning TMS pulse could modulate spinal excitability if delivered repetitively. METHOD In 13 healthy subjects, we delivered single-pulse TMS (80% RMT) for the right soleus muscle, 20 ms prior to an electrical peripheral nerve stimulus delivered over the posterior tibial nerve on the same side at 0.1 Hz during 15 min. RESULTS PNS alone evoked an H-reflex of 0.25 mV ± 0.06 SEM, while pairing of TMS and PNS facilitated the H-reflex to 0.7 ± 0.11 mV. TMS-PNS pairs delivered at 0.1 Hz for 15 min progressively increased in the evoked response to ∼130% (r(2) = 0.97) of the starting amplitude (normalized to 1st min). Post-intervention, H-reflex threshold decreased (pre = 12.9 ± 1.7 mA; post =11.6 ± 1.6 mA; p = 0.04), as did the stimulus intensity at maximum H-reflex amplitude (pre = 23.5 ± 02.8 mA; post = 21.6 ± 2.6 mA; p = 0.03), and recruitment curve width (pre = 11.6 ± 1.5 mA; post = 10.93 ± 1.4 mA; p = 0.03). No such changes were observed with intervention of PNS or TMS alone. CONCLUSION Paired stimulation targeting spinal facilitatory interactions, when applied repetitively, can increase spinal excitability during and after the intervention. SIGNIFICANCE Spinal associative stimulation may have potential for neuromodulation in spinal cord injury patients.

Gait Training in Human Spinal Cord Injury Using Electromechanical Systems: Effect of Device Type and Patient Characteristics

OBJECTIVE To report the clinical improvements in spinal cord injury (SCI) patients associated with intensive gait training using electromechanical systems according to patient characteristics. DESIGN Prospective longitudinal study. SETTING Inpatient SCI rehabilitation center. PARTICIPANTS Adults with SCI (n=130). INTERVENTION Patients received locomotor training with 2 different electromechanical devices, 5 days per week for 8 weeks. MAIN OUTCOME MEASURES Lower-extremity motor score, Walking Index for Spinal Cord Injury, and 10-meter walking test data were collected at the baseline, midpoint, and end of the program. Patients were stratified according to the American Spinal Injury Association (ASIA) category, time since injury, and injury etiology. A subgroup of traumatic ASIA grade C and D patients were compared with data obtained from the European Multicenter Study about Human Spinal Cord Injury (EM-SCI). RESULTS One hundred and five patients completed the program. Significant gains in lower-limb motor function and gait were observed for both types of electromechanical device systems, to a similar degree. The greatest rate of improvement was shown in the motor incomplete SCI patients, and for patients <6 months postinjury. The positive response associated with training was not affected by injury etiology, age, sex, or lesion level. The trajectory of improvement was significantly enhanced relative to patients receiving the conventional standard of care without electromechanical systems (EM-SCI). CONCLUSIONS The use of electromechanical systems for intensive gait training in SCI is associated with a marked improvement in lower-limb motor function and gait across a diverse range of patients and is most evident in motor incomplete patients, and for patients who begin the regimen early in the recovery process.

An observational report of intensive robotic and manual gait training in sub-acute stroke

BackgroundThe use of automated electromechanical devices for gait training in neurological patients is increasing, yet the functional outcomes of well-defined training programs using these devices and the characteristics of patients that would most benefit are seldom reported in the literature. In an observational study of functional outcomes, we aimed to provide a benchmark for expected change in gait function in early stroke patients, from an intensive inpatient rehabilitation program including both robotic and manual gait training.MethodsWe followed 103 sub-acute stroke patients who met the clinical inclusion criteria for Body Weight Supported Robotic Gait Training (BWSRGT). Patients completed an intensive 8-week gait-training program comprising robotic gait training (weeks 0-4) followed by manual gait training (weeks 4-8). A change in clinical function was determined by the following assessments taken at 0, 4 and 8 weeks (baseline, mid-point and end-point respectively): Functional Ambulatory Categories (FAC), 10 m Walking Test (10 MWT), and Tinetti Gait and Balance Scales.ResultsOver half of the patients made a clinically meaningful improvement on the Tinetti Gait Scale (> 3 points) and Tinetti Balance Scale (> 5 points), while over 80% of the patients increased at least 1 point on the FAC scale (0-5) and improved walking speed by more than 0.2 m/s. Patients responded positively in gait function regardless of variables gender, age, aetiology (hemorrhagic/ischemic), and affected hemisphere. The most robust and significant change was observed for patients in the FAC categories two and three. The therapy was well tolerated and no patients withdrew for factors related to the type or intensity of training.ConclusionsEight-weeks of intensive rehabilitation including robotic and manual gait training was well tolerated by early stroke patients, and was associated with significant gains in function. Patients with mid-level gait dysfunction showed the most robust improvement following robotic training.

Intensity Dependent Effects of Transcranial Direct Current Stimulation on Corticospinal Excitability in Chronic Spinal Cord Injury

OBJECTIVE To investigate the effects of anodal transcranial direct current stimulation (a-tDCS) intensity on corticospinal excitability and affected muscle activation in individuals with chronic spinal cord injury (SCI). DESIGN Single-blind, randomized, sham-controlled, crossover study. SETTING Medical research institute and rehabilitation hospital. PARTICIPANTS Volunteers (N = 9) with chronic SCI and motor dysfunction in wrist extensor muscles. INTERVENTIONS Three single session exposures to 20 minutes of a-tDCS (anode over the extensor carpi radialis [ECR] muscle representation on the left primary motor cortex, cathode over the right supraorbital area) using 1 mA, 2 mA, or sham stimulation, delivered at rest, with at least 1 week between sessions. MAIN OUTCOME MEASURES Corticospinal excitability was assessed with motor-evoked potentials (MEPs) from the ECR muscle using surface electromyography after transcranial magnetic stimulation. Changes in spinal excitability, sensory threshold, and muscle strength were also investigated. RESULTS Mean MEP amplitude significantly increased by approximately 40% immediately after 2mA a-tDCS (pre: 0.36 ± 0.1 mV; post: 0.47 ± 0.11 mV; P = .001), but not with 1 mA or sham. Maximal voluntary contraction measures remained unaltered across all conditions. Sensory threshold significantly decreased over time after 1mA (P = .002) and 2mA (P = .039) a-tDCS and did not change with sham. F-wave persistence showed a nonsignificant trend for increase (pre: 32% ± 12%; post: 41% ± 10%; follow-up: 46% ± 12%) after 2 mA stimulation. No adverse effects were reported with any of the experimental conditions. CONCLUSIONS The a-tDCS can transiently raise corticospinal excitability to affected muscles in patients with chronic SCI after 2 mA stimulation. Sensory perception can improve with both 1 and 2 mA stimulation. This study gives support to the safe and effective use of a-tDCS using small electrodes in patients with SCI and highlights the importance of stimulation intensity.

Preserved corticospinal conduction without voluntary movement after spinal cord injury

Study design:Case report.Objectives:To identify preserved corticomotor connection in chronic spinal cord injury (SCI) in the absence of clinically observable movement.Setting:Rehabilitation Hospital and Medical Research Institute, NY, USA.Methods:The motor-evoked potential (MEP) response to transcranial magnetic stimulation (TMS) was recorded using surface electromyography from the right biceps brachii, extersor carpi radialis (ECR), flexor carpi radialis (FCR) and abductor pollicis brevis (APB) muscles in a 31-year-old male traumatic SCI chronic patient—ASIA B, injury level C5. Motor power scores were additionally obtained from a clinician blinded to the results of TMS.Results:TMS could consistently elicit MEPs of normal latency, phase and amplitude, in the severely affected ECR muscle but not the similarly affected FCR muscle. The response in proximal and unaffected biceps muscle was larger than the healthy subject, whereas no response was obtained in the distal APB muscle as expected.Conclusion:TMS can identify residual pathways not apparent from clinical assessment alone, which may have prescriptive value for rehabilitation.

Improved motor performance in chronic spinal cord injury following upper-limb robotic training

BACKGROUND Recovering upper-limb motor function has important implications for improving independence of patients with tetraplegia after traumatic spinal cord injury (SCI). OBJECTIVE To evaluate the feasibility, safety and effectiveness of robotic-assisted training of upper limb in a chronic SCI population. METHODS A total of 10 chronic tetraplegic SCI patients (C4 to C6 level of injury, American Spinal Injury Association Impairment Scale, A to D) participated in a 6-week wrist-robot training protocol (1 hour/day 3 times/week). The following outcome measures were recorded at baseline and after the robotic training: a) motor performance, assessed by robot-measured kinematics, b) corticospinal excitability measured by transcranial magnetic stimulation (TMS), and c) changes in clinical scales: motor strength (Upper extremity motor score), pain level (Visual Analog Scale) and spasticity (Modified Ashworth scale). RESULTS No adverse effects were observed during or after the robotic training. Statistically significant improvements were found in motor performance kinematics: aim (pre 1.17 ± 0.11 raduans, post 1.03 ± 0.08 raduans, p = 0.03) and smoothness of movement (pre 0.26 ± 0.03, post 0.31 ± 0.02, p = 0.03). These changes were not accompanied by changes in upper-extremity muscle strength or corticospinal excitability. No changes in pain or spasticity were found. CONCLUSIONS Robotic-assisted training of the upper limb over six weeks is a feasible and safe intervention that can enhance movement kinematics without negatively affecting pain or spasticity in chronic SCI. In addition, robot-assisted devices are an excellent tool to quantify motor performance (kinematics) and can be used to sensitively measure changes after a given rehabilitative intervention.

Transcranial Magnetic Stimulation as an Investigative Tool for Motor Dysfunction and Recovery in Stroke: An Overview for Neurorehabilitation Clinicians

Rationale:  An improved understanding of motor dysfunction and recovery after stroke has important clinical implications that may lead to the design of more effective rehabilitation strategies for patients with hemiparesis.

Stroke subtype and motor impairment influence contralesional excitability

Objective: The nonlesioned motor cortex (M1NL) is thought to be hyperexcitable in patients with subacute or chronic stroke and offers a promising therapeutic target. However, whether M1NL excitability behaves the same for subcortical and cortical strokes is unknown. The aim of the present study was to determine whether cortical, or purely subcortical, strokes have a different effect on M1NL excitability. Methods: We looked for correlations between the Fugl-Meyer (FM) score and M1NL resting motor threshold (RMTNL) in 34 stroke survivors classified according to lesion location (cortico-subcortical or purely subcortical). In addition to the FM, the Wolf Motor Score and motor power were measured. Results: FM correlated with RMTNL for subcortical (r = 0.82; p = 0.001) but not for cortical strokes (r = 0.11; p = 0.62). Likewise, Wolf Motor Score (r = −0.62; p = 0.03) and motor power (r = 0.64; p = 0.023) were correlated with RMTNL for the subcortical group, but not for the cortical group. Conclusion: We show that the impact on M1NL depends on lesion location and conclude that protocols aimed at reducing M1NL cortical excitability may be worth exploring for subcortical but not for cortical stroke.