Gad Alon

Functional MRI determination of a dose-response relationship to lower extremity neuromuscular electrical stimulation in healthy subjects

Abstract.Although empirical evidence supports the use of neuromuscular electrical stimulation (NMES) to treat physical impairments associated with stroke, the mechanisms underlying the efficacy of this modality are poorly understood. Recent studies have employed functional imaging to investigations of brain responses to median nerve stimulation. These studies suggest a dose-response relationship may exist between selected stimulation parameters and hemodynamic responses in sensorimotor regions. However, substantial gaps exist in this literature. The present study was designed to address these deficiencies. Ten healthy subjects participated. In phase one, four stimulus intensity levels were established: (1) sensory threshold [Th], (2) (MM−Th)×0.333+Th [low-intermediate level, LI], (3) (MM−Th)×0.666+Th [high-intermediate level, HI], and (4) maximal motor (MM). In phase two, subjects were scanned using a spiral-echoplanar imaging technique at each stimulus level. Image sets were analyzed to determine hemodynamic responses at the highest Pearson correlation level (r) ascertained for each of five areas of interest (AOI): (1) primary sensory, (2) primary motor, (3) cingulate gyrus, (4) thalamus, and (5) cerebellum. ANOVA demonstrated significant main effects for BOLD signal amplitude (p<0.05) changes in all AOI. Similarly, ANOVA showed significant differences in the volume of activation (p<0.05) with increasing stimulus intensity in four AOI. Secondary analyses of pooled data showed increasing probabilities of activation at higher stimulus intensities within each AOI. Collectively, these data indicate a dose-response relationship exists between lower extremity NMES and brain activation in specific neural regions. The current results, while limited in their generalizability, are foundational for future studies of interventions using NMES.

Functional electrical stimulation (FES) may modify the poor prognosis of stroke survivors with severe motor loss of the upper extremity: a preliminary study.

Alon G, Levitt AF, McCarthy PA: Functional electrical stimulation (FES) may modify the poor prognosis of stroke survivors with severe motor loss of the upper extremity: a preliminary study. Am J Phys Med Rehabil 2008;87:627–636. Objectives:This nonblinded, block-randomized clinical trial tested the hypothesis that task-oriented functional electrical stimulation (FES) can enhance the recovery of upper-extremity volitional motor control and functional ability in patients with poor prognosis. Design:Ischemic stroke survivors (FES + exercise group, n = 13, 17.4 ± 7.6 days after stroke, and exercise-only group n = 13, 23.8 ± 10.9 days after stroke) trained with task-specific exercises, 30 min, twice each day. The FES group practiced the exercises combined with FES that enabled opening and closing of the paretic hand and continued with FES without exercises for up to 90 mins of additional time twice a day. Both groups trained for 12 wks. Volitional motor control (modified Fugl–Meyer [mF-M]), hand function (Box & Blocks [B&B], and Jebsen–Taylor light object lift [J-T]) were video recorded for both upper extremities at baseline and at 4, 8, and 12 wks. Results:Mean mF-M score of the FES group (24 ± 13.7) was significantly better (P = 0.05) at 12 wks compared with the control group that scored 14.2 ± 10.6 points. The B&B mean score did not reach statistical significance (P = 0.058) in favor of the FES group (10.5 ± 2.4 blocks) over the control group (2.5 ± 4.9 blocks). The J-T task time did not differ between groups. Eight (FES) compared with three (control) patients regained the ability to transfer five or more blocks (P = 0.051), and six (FES) compared with two (control) completed the J-T task in 30 secs or less after 12 wks of training (P = 0.09). Conclusions:FES + exercise as used in this preliminary study is likely to minimize motor loss, but it may not significantly enhance the ability to use the upper extremity after ischemic stroke. Anecdotally, more patients may regain some functional ability after training with FES compared with training without FES. Patients with severe motor loss may require prolonged task-specific FES training.

Gait and Hand Function Enhancement Following Training with a Multi-Segment Hybrid-Orthosis Stimulation System in Stroke Patients

The majority of stroke survivors continue to suffer residual functional deficits due to weakness and inadequate motor control of their paretic muscles. Non-invasive functional electrical stimulation has been limited to stimulation of only 1-2 muscle groups. The purpose of this study was to test if the use of a multi-segment hybrid orthosis-stimulation system combined with electrically augmented functional training would promote improvement in gait and hand functions of patients with chronic hemiparesis. A control group (n = 9) received individual instructions for specific functional training and self-exercised up to 60 minutes twice daily. The stimulated group (n = 10) received self-administered electrical stimulation training using the NESS system. Training time increased to 60 minutes twice daily and comprised of specific functional exercise. Each group trained for 3 months. Upper limb outcome measures included the Box & Block (B & B) and 3 sub-tests of the Jebsen-Taylor (J & T) battery. Gait outcomes included 10-meter walk time, speed, cadence, and number of steps. Post-test-pretest data were analyzed by unpaired t-tests (P = 0.05). The stimulated group improved significantly compared to the control group in B & B (7.9 +/- 4.5 vs 0.2 +/- 2.2 more blocks); J & T simulated feeding (12.6 +/- 14.8 vs 1.2 +/- 2.09 sec); J & T light object lift (8.2 +/- 9.7 vs. -0.3 +/- 2.8 sec); J & T heavy object lift (7.6 +/- 11.0 vs -0.8 +/- 1.6 sec); walk time (3.3 +/- 1.1 sec vs -0.3 +/- 1.8 sec); walking speed (0.33 +/- 0.12 vs. -0.01 +/- 0.1 m/sec); cadence (0.30 +/- 0.18 vs. -0.02 +/- 0.14 steps/sec). The number of steps over 10 m decreased 2.7 +/- 1.4 vs -0.2 +/- 1.98 steps. We concluded that electrically-dependent functional training with multi-segment hybrid orthosis-stimulation system can improve the studied functional outcomes of chronic stroke survivors.

Efficacy of a Hybrid Upper Limb Neuromuscular Electrical Stimulation System in Lessening Selected Impairments and Dysfunctions Consequent to Cerebral Damage

Objective: The purpose of this study was to test the efficacy of a new computerized neu romuscular electric stimulation system (Handmaster™) in improving selected im pairments and functional measures of patients who survived stroke and traumatic brain injury (TBI). Methods: Survivors of stroke (n = 13) and TBI (n = 7) with chronic paralysis lasting 6.8 ± 7.8 years (range 1 to 29 years) participated in a home program of elec trical stimulation. The device is a hybrid of a hand-forearm splint that incorporates five surface electrodes and a computerized electrical stimulator. The patterned stimu lation elicits finger flexion and extension, lateral pinch, and grasp of the paralyzed hand. Patients practiced daily for 3.4 ± 0.5 hours over a mean duration of 13.1 ± 6.6 weeks. Assessment included goniometric measurements of wrist and elbow rest ing posture, passive and active joints motion, linear distance of fingers to palm, Ash worth scale, and the ability to hold a 1 kg load in the affected hand. The Frenchay arm test represented hand function. Results : ANOVA tests and Wilcoxon signed rank test were employed. There were significant improvements (p = 0.01) in elbow, wrist, and fingers posture; Ash worth scale; volitional active elbow flexion (32.5 ± 12.7°); wrist extension (12.7 ± 11.1°) and flexion (9.03 ± 4.5°). Passive wrist extension improved 13.7 ± 3.6°. Thir teen patients (65 percent) had active wrist extension post stimulation compared with only three (15 percent) before study commencement. Partial completion of the Fren chay tasks were observed before stimulation in only three patients compared with partial completion of tasks by nine patients at study conclusion. Post stimulation, 16 of 20 patients were able to hold a 1 kg weight with the NESS system active, com pared with only three patients without it. Conclusions: Application of the NESS system for three to four hours daily im proves selected impairments and may help to restore partial hand functions of patients with chronic stroke or head injury. Key Words: Chronic—Stroke—Brain injury— Electrical stimulation—Motor recovery.

Non-invasive electrical stimulation of the brain (ESB) modifies the resting-state network connectivity of the primary motor cortex: A proof of concept fMRI study

An innovative method to obtain fMRI resting-state network maps during non-invasive electrical stimulation of the brain (ESB) was developed and tested. Five healthy volunteers participated in 2 fMRI sessions. In session one, a transcranial direct current stimulator (tDCS) was applied placing the positive electrode (31.5 cm(2)) over the right M1 of the cortex and the negative electrode (31.5 cm(2)) over the left supra-orbital area of the head. In session two, a monophasic pulsed current stimulator (tPCS) was applied using the identical electrode placement. Imaging was performed on a Siemens 3T Tim Trio scanner with a 12-channel head coil. At each session, five consecutive functional scans were obtained: 1) resting-state without stimulation (Rest-1), 2) a motor scan consisting of self-paced, bilateral finger-thumb opposition task, 3) resting-state with ESB (Stim-1), 4) resting-state without stimulation (Rest-2), and 5) resting-state with ESB, replicating Stim-1 (Stim-2). Data were analyzed using AFNI and MATLAB. For motor task fMRI analysis, a general linear model (GLM) determined the voxels in the right and left M1 that were significantly correlated with the motor task paradigm. The resting-state time series from the voxels in the R-M1 were averaged and the resulting time series used as a regressor in a GLM analysis to identify M1 connectivity maps. Connectivity maps were quantified as R(2) values, and then combined to give overlap maps for each of the experimental conditions. Fourier analysis determined the energy in the normalized signal average time courses extracted from L-M1 and R-M1 for each of the resting-state scans. Both tDCS and tPCS lowered the R(2) values and energy of the averaged time course in the right and left M1 ROI. The effect of the tPCS appeared more pronounced and less variable among subjects. Applying non-invasive ESB during fMRI scanning may down regulate the motor cortexs resting-state network connectivity.

Defining and Measuring Residual Deficits of the Upper Extremity Following Stroke: A New Perspective

Abstract Purpose: To propose and test a new measure to quantify residual deficits (Rd) following stroke and provide preliminary evidence supporting its usefulness. Methods: Patients (N = 46) were stratified based on projected rate of upper extremity recovery and were randomly assigned to task-oriented (control) or task-oriented plus functional electrical stimulation (FES) training groups. All performed the Box & Blocks and the Jebsen-Taylor light object lift tests with the nonparetic and paretic upper extremities. A modified Fugl-Meyer test was performed on the paretic upper extremity. The calculation Rd = 100 − (paretic/nonparetic × 100) was made for each subgroup: task-specific training alone (control subgroup) or task-specific training plus functional electrical stimulation (FES subgroup). Data from each of these two groups were analyzed separately. Results: Intrasession and between-sessions tests of the nonparetic or paretic extremity yielded interclass correlation (ICC) values between 0.77 and 0.99. After training for 12 weeks, the Rd of the paretic upper extremity of patients who used the FES was significantly less compared to the control group (p < .05). The deficits of patients with slow recovery profile were as expected much greater. Conclusions: Rd is a valid, highly reproducible, and dimensionless outcome measure. It should permit objective comparison of effectiveness between and within various rehabilitative intervention options regardless of the outcome measure(s) used.

Intensive Training of Subjects with Chronic Hemiparesis on a Motorized Cycle Combined with Functional Electrical Stimulation (FES): A Feasibility and Safety Study

BACKGROUND AND PURPOSE This study tested the safety and ability of subjects with chronic hemiplegia to tolerate intensive training using a motorized cycle combined with functional electrical stimulation (FES) system. METHODS A case series of 10 subjects with chronic stroke participated in 30-minute three times per week cycling on a stationary motorized cycling system combined with FES (RT300(TM) ). The stimulation activated the dorsal and plantar flexors, the quadriceps and the hamstrings using four channels and a stimulation pattern that assisted cycling motion of the paretic lower limb. Patients were instructed to cycle as close as possible to 60 rpm and the resistance to cycling was gradually increased using a computer-based algorithm. The training lasted eight weeks. RESULTS All 10 participants completed the training without adverse reactions to the training or the FES. The kcal utilized during the training increased significantly (p = 0.0003) between session 1 (2.2 ± 0.47), session 12 (4.3 ± 1.2) and session 24 (7.5 ± 1.8). Peak pedaling power increased from 6.5 ± 0.5 W pre-training to 18.0 ± 5.4 W post-training. Locomotion variables that improved significantly were time to complete the get up and go test (45.4 ± 54.9 seconds vs. 34.0 ± 31.8 seconds) a 24.6% improvement (p = 0.03) and gait velocity, which increased 25.0% from 0.4 ± 0.3 m/sec to 0.5 ± 0.4 m/sec (p = 0.01). CONCLUSION Using a motorized cycle combined with FES intensive training appears safe and can be tolerated by patients with chronic stroke of wide age range, diverse severity of cardio-pulmonary deconditioning, motor loss and locomotor deficits.

Reliability estimation of grouped functional imaging data using penalized maximum likelihood

We analyzed grouped fMRI data and developed a reliability analysis for such data using the method of penalized maximum likelihood (ML). Specifically, this technique was applied to a somatosensory paradigm that used a mechanical probe to provide noxious stimuli to the foot, and a paradigm consisting of four levels of graded peripheral neuromuscular electrical stimulation (NMES). In each case, reliability maps of activation were generated. Receiver operating characteristic (ROC) curves were constructed in the case of the graded NMES paradigm for each level of stimulation, which revealed an increase in the specificity of activation with increasing stimulation levels. In addition, penalized ML was used to determine whether the grouped reliability maps obtained from one stimulus level were significantly different from those obtained at other levels. The results show a significant difference (P < 0.01) in the reliability of activation from one stimulation level to the next. These results are in agreement with those obtained using generalized linear modeling (GLM). While the reliability maps generated are not directly comparable, they are qualitatively similar to those obtained by controlling the expected false discovery rate (FDR). The proposed methodology can be used to objectively compare activation maps between groups, as well as to perform reliability assessments. Furthermore, this method potentially can be used to assess the longitudinal effect of treatment therapies within a group. Magn Reson Med 53:1126–1134, 2005.

Is Transcranial Electrical Stimulation (TCES) a Safe Intervention for Children with Cerebral Palsy

We tested the safety of transcranial electrical stimulation (TCES) applied to seven children (age range 2.5 to 7.5 years) with a confirmed diagnosis of cerebral palsy (CP). Adverse responses were assessed by negative changes in the gross motor function mea sure test (GMFM), the popliteal angle, and the occurrence of any undesired systemic responses such as seizure, nausea, vomiting, or sleep disruption. The tests first were given before the commencement of a physical therapy exercise (PTE) program com bined with a home program of TCES. The tests were repeated after 8 weeks of PTE + TCES and once again after an additional 8 weeks of PT + TCES. One of the 8- week periods involved placebo stimulation in a double-blind design. Stimulator am plitude was 0.5 mA of peak current, phase charge was 0.0166 μC, and the averaged RMS current was 249 microamperes. This level was below threshold of sensory nerve excitation, and the child did not perceive the stimulation. Electrodes were placed over the right and left temporal areas of the skull. The stimulation was applied by the par ents for 10 minutes, twice a day, 7 days each week. The total goal GMFM scores were greater after both active and placebo stimulation. The popliteal angle improved irre spective of the stimulation intervention. No adverse systemic responses were reported. These results support the hypothesis that TCES as used in this study is a safe proce dure.

Transcutaneous electrical stimulation devices tests

At the present time, there is only one standard test that evaluates the performance of transcutaneous electrical nerve stimulator (TENS) devices. The rationale for this test is not well documented and its scope and limitations are unclear. The thrust of this paper is to discuss the selected factors that are likely to affect the performance standard. These include stimulus waveform, constant current versus constant current voltage output and electrode size. Each of these parameters have been shown to influence the stimulation output and the conductive characteristics of human tissue. Stimulating with different waveforms significantly affects peak current, peak voltage and total pulse charge, but insignificantly affects the phase charge. Using a different electrode size alter all stimulus output values during excitation of peripheral nerves, indicating tile need to specify electrode size for simulated tissue loads. Data show that a single load is not adequate to simulate the conductive medium of human tissue. Instead a family of loads is considered and their validation for testing conditions is discussed.