State-Dependent Gain Modulation of Spinal Motor Output.

Afferent somatosensory information plays a crucial role in modulating efferent motor output. A better understanding of this sensorimotor interplay may inform the design of neurorehabilitation interfaces. Current neurotechnological approaches that address motor restoration after trauma or stroke combine motor imagery (MI) and contingent somatosensory feedback, e.g., via peripheral stimulation, to induce corticospinal reorganization. These interventions may, however, change the motor output already at the spinal level dependent on alterations of the afferent input. Neuromuscular electrical stimulation (NMES) was combined with measurements of wrist deflection using a kinematic glove during either MI or rest. We investigated 360 NMES bursts to the right forearm of 12 healthy subjects at two frequencies (30 and 100 Hz) in random order. For each frequency, stimulation was assessed at nine intensities. Measuring the induced wrist deflection across different intensities allowed us to estimate the input-output curve (IOC) of the spinal motor output. MI decreased the slope of the IOC independent of the stimulation frequency. NMES with 100 Hz vs. 30 Hz decreased the threshold of the IOC. Human-machine interfaces for neurorehabilitation that combine MI and NMES need to consider bidirectional communication and may utilize the gain modulation of spinal circuitries by applying low-intensity, high-frequency stimulation.

Cumulative effects of single TMS pulses during beta-tACS are stimulation intensity-dependent.

BACKGROUND: Single transcranial magnetic stimulation (TMS) pulses activate different components of the motor cortex neural circuitry in a stimulation intensity-dependent way and may lead to a cumulative increase of corticospinal excitability (CSE) during the same stimulation session. Furthermore, transcranial alternating current stimulation (tACS) has been shown to increase in a frequency-specific way the level of CSE probed by single-pulse TMS. The interaction of these two phenomena, i.e. cumulative increases and baseline shifts of CSE, and the involved neural circuitry has not been studied yet. OBJECTIVE: The aim of this study was to investigate stimulation intensity-specific online effects of simultaneous TMS and tACS on CSE. METHODS: Single-pulse TMS was applied concurrent to 20 Hz tACS over the left primary motor cortex of thirteen healthy subjects to probe CSE indexed by motor evoked potentials (MEPs) recorded from the contralateral extensor carpi radialis muscle of the right hand during rest. Six different TMS intensities (90%, 100%, 110%, 120%, 130%, and 140% of resting motor threshold, RMT) were studied in a randomized blocked design. In each block, 40 pulses were applied with an inter-stimulus interval of 5 s and a jitter of ±0.5 s, i.e. at a stimulation frequency of 0.2-0.25 Hz. RESULTS: Beta-tACS has a general facilitatory effect on CSE across the tested TMS intensities. The results of the block wise regression of the MEP amplitudes show a more specific effect. Combining tACS and TMS leads to a cumulative increase in CSE for the stimulation intensity of 120% RMT only (p = 0.0004). CONCLUSION: CSE increases due to beta-tACS and cumulative TMS pulses may be mediated by different neuronal mechanisms.

Closed-loop adaptation of neurofeedback based on mental effort facilitates reinforcement learning of brain self-regulation.

OBJECTIVE: Considering self-rated mental effort during neurofeedback may improve training of brain self-regulation. METHODS: Twenty-one healthy, right-handed subjects performed kinesthetic motor imagery of opening their left hand, while threshold-based classification of beta-band desynchronization resulted in proprioceptive robotic feedback. The experiment consisted of two blocks in a cross-over design. The participants rated their perceived mental effort nine times per block. In the adaptive block, the threshold was adjusted on the basis of these ratings whereas adjustments were carried out at random in the other block. Electroencephalography was used to examine the cortical activation patterns during the training sessions. RESULTS: The perceived mental effort was correlated with the difficulty threshold of neurofeedback training. Adaptive threshold-setting reduced mental effort and increased the classification accuracy and positive predictive value. This was paralleled by an inter-hemispheric cortical activation pattern in low frequency bands connecting the right frontal and left parietal areas. Optimal balance of mental effort was achieved at thresholds significantly higher than maximum classification accuracy. CONCLUSION: Rating of mental effort is a feasible approach for effective threshold-adaptation during neurofeedback training. SIGNIFICANCE: Closed-loop adaptation of the neurofeedback difficulty level facilitates reinforcement learning of brain self-regulation.

Combining TMS and tACS for Closed-Loop Phase-Dependent Modulation of Corticospinal Excitability: A Feasibility Study.

BACKGROUND: The corticospinal excitability indexed by motor evoked potentials (MEPs) following transcranial magnetic stimulation (TMS) of the sensorimotor cortex is characterized by large variability. The instantaneous phase of cortical oscillations at the time of the stimulation has been suggested as a possible source of this variability. To explore this hypothesis, a specific phase needs to be targeted by TMS pulses with high temporal precision. OBJECTIVE: The aim of this feasibility study was to introduce a methodology capable of exploring the effects of phase-dependent stimulation by the concurrent application of alternating current stimulation (tACS) and TMS. METHOD: We applied online calibration and closed-loop TMS to target four specific phases (0°, 90°, 180° and 270°) of simultaneous 20 Hz tACS over the primary motor cortex (M1) of seven healthy subjects. RESULT: The integrated stimulation system was capable of hitting the target phase with high precision (SD ± 2.05 ms, i.e., ± 14.45°) inducing phase-dependent MEP modulation with a phase lag (CI95% = -40.37° to -99.61°) which was stable across subjects (p = 0.001). CONCLUSION: The combination of different neuromodulation techniques facilitates highly specific brain state-dependent stimulation, and may constitute a valuable tool for exploring the physiological and therapeutic effect of phase-dependent stimulation, e.g., in the context of neurorehabilitation.

Neurosensory effects of transcranial alternating current stimulation.

BACKGROUND: Electrical brain stimulation can elicit neurosensory side effects that are unrelated to the intended stimulation effects. This presents a challenge when designing studies with blinded control conditions. OBJECTIVE: The aim of this research was to investigate the role of different transcranial alternating current stimulation (tACS) parameters, i.e. intensity, frequency, and electrode montage, on the probability, duration and intensity of elicited neurosensory side effects. METHODS: In a first study, we examined the influence of tACS on sensations of phosphenes, dizziness, pressure, and skin sensation in fifteen healthy subjects, during 8 s of stimulation with different amplitudes (1500 µA, 1000 µA, 500 µA, 250 µA), frequencies (2 Hz, 4 Hz, 8 Hz, 16 Hz, 32 Hz, 64 Hz), and montages (F3/F4, F3/C4, F3/P4, P3/F4, P3/C4, P3/P4). In a second study, ten healthy subjects were exposed to 60 s of tACS (1000 µA, 2 Hz versus 16 Hz, F3/F4 versus P3/P4) and were asked to rate the intensity of sensations every 12 s. RESULTS: The first study showed that all stimulation parameters had an influence on the probability and intensity of sensations. Phosphenes were most likely and strongest for frontal montages and higher frequencies. Dizziness was most likely and strongest for parietal montages and at stimulation frequency of 4 Hz. Skin sensations and pressure was more likely when stimulation was performed across central regions and at posterior montages, respectively. The second study also revealed that the probability and the intensity of sensations were neither modified during more extended periods of stimulation nor affected by carry-over effects. CONCLUSION: We demonstrated that the strength and the likelihood of sensations elicited by tACS were specifically modulated by the stimulation parameters. The present work may therefore be instrumental in establishing effective blinding conditions for studies with tACS.

Brain Painting: First Evaluation of a New Brain-Computer Interface Application with ALS-Patients and Healthy Volunteers.

Brain-computer interfaces (BCIs) enable paralyzed patients to communicate; however, up to date, no creative expression was possible. The current study investigated the accuracy and user-friendliness of P300-Brain Painting, a new BCI application developed to paint pictures using brain activity only. Two different versions of the P300-Brain Painting application were tested: A colored matrix tested by a group of ALS-patients (n = 3) and healthy participants (n = 10), and a black and white matrix tested by healthy participants (n = 10). The three ALS-patients achieved high accuracies; two of them reaching above 89% accuracy. In healthy subjects, a comparison between the P300-Brain Painting application (colored matrix) and the P300-Spelling application revealed significantly lower accuracy and P300 amplitudes for the P300-Brain Painting application. This drop in accuracy and P300 amplitudes was not found when comparing the P300-Spelling application to an adapted, black and white matrix of the P300-Brain Painting application. By employing a black and white matrix, the accuracy of the P300-Brain Painting application was significantly enhanced and reached the accuracy of the P300-Spelling application. ALS-patients greatly enjoyed P300-Brain Painting and were able to use the application with the same accuracy as healthy subjects. P300-Brain Painting enables paralyzed patients to express themselves creatively and to participate in the prolific society through exhibitions.