Resolving equivocal gain modulation of corticospinal excitability.

The ratio between the input and output of neuronal populations, usually referred to as gain modulation, is rhythmically modulated along the oscillatory cycle. Previous research on spinal neurons, however, revealed contradictory findings: both uni- and bimodal patterns of increased responsiveness for synaptic input have been proposed for the oscillatory beta rhythm. In this study, we compared previous approaches of phase estimation directly on simulated data and empirically tested the corresponding predictions in healthy males and females. We applied single-pulse transcranial magnetic stimulation over the primary motor cortex at rest, and assessed the spinal output generated by this input. Specifically, the peak-to-peak amplitude of the motor evoked potential in the contralateral forearm was estimated as a function of the EMG phase at which the stimulus was applied. The findings indicated that human spinal neurons adhere to a unimodal pattern of increased responsiveness, and suggest that the rising phase of the upper beta band maximizes gain modulation. Importantly, a bimodal pattern of increased responsiveness was shown to result in an artifact during data analysis and filtering. This observation of invalid preprocessing could be generalized to other frequency bands (i.e., delta, theta, alpha, and gamma), different task conditions (i.e., voluntary muscle contraction), and EEG-based phase estimations. Appropriate analysis algorithms, such as broad-band filtering, enable us to accurately determine gain modulation of neuronal populations and to avoid erroneous phase estimations. This may facilitate novel phase-specific interventions for targeted neuromodulation.

Different oscillatory entrainment of cortical networks during motor imagery and neurofeedback in right and left handers.

Volitional modulation and neurofeedback of sensorimotor oscillatory activity is currently being evaluated as a strategy to facilitate motor restoration following stroke. Knowledge on the interplay between this regional brain self-regulation, distributed network entrainment and handedness is, however, limited. In a randomized cross-over design, twenty-one healthy subjects (twelve right-handers [RH], nine left-handers [LH]) performed kinesthetic motor imagery of left (48 trials) and right finger extension (48 trials). A brain-machine interface turned event-related desynchronization in the beta frequency-band (16-22 Hz) during motor imagery into passive hand opening by a robotic orthosis. Thereby, every participant subsequently activated either the dominant (DH) or non-dominant hemisphere (NDH) to control contralateral hand opening. The task-related cortical networks were studied with electroencephalography. The magnitude of the induced oscillatory modulation range in the sensorimotor cortex was independent of both handedness (RH, LH) and hemispheric specialization (DH, NDH). However, the regional beta-band modulation was associated with different alpha-band networks in RH and LH: RH presented a stronger inter-hemispheric connectivity, while LH revealed a stronger intra-hemispheric interaction. Notably, these distinct network entrainments were independent of hemispheric specialization. In healthy subjects, sensorimotor beta-band activity can be robustly modulated by motor imagery and proprioceptive feedback in both hemispheres independent of handedness. However, right and left handers show different oscillatory entrainment of cortical alpha-band networks during neurofeedback. This finding may inform neurofeedback interventions in future to align them more precisely with the underlying physiology.

State-dependent brain stimulation: Power or phase?

BACKGROUND: Intrinsic motor cortex activity modifies corticospinal excitability (CSE) in accordance with both oscillatory power fluctuations and phase-specific modulation along the oscillatory beta cycle, particularly in the 16-17 Hz frequency bin. OBJECTIVE: To determine the magnitude of CSE and the relevance of stimulation timing for input gain mediated by either oscillatory power or phase. METHODS: We applied single-pulse transcranial magnetic stimulation (TMS) over the primary motor cortex of healthy subjects at rest during electroencephalography recordings. The corticospinal gain modulation was indexed by the amplitude variability of the induced motor-evoked potentials recorded from the forearm muscle. RESULTS: Low compared to high beta power led to a robust 40-70% CSE increase over a wide range of power values. By contrast, the phase modulation was critically dependent on the precise timing of the stimuli to the rising phase of the oscillatory beta cycle, but could then achieve CSE increases of 180%. CONCLUSION: These findings can influence closed-loop, state-dependent stimulation in the context of neurorehabilitation.

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.

Brain State-Dependent Closed-Loop Modulation of Paired Associative Stimulation Controlled by Sensorimotor Desynchronization.

BACKGROUND: Pairing peripheral electrical stimulation (ES) and transcranial magnetic stimulation (TMS) increases corticospinal excitability when applied with a specific temporal pattern. When the two stimulation techniques are applied separately, motor imagery (MI)-related oscillatory modulation amplifies both ES-related cortical effects-sensorimotor event-related desynchronization (ERD), and TMS-induced peripheral responses-motor-evoked potentials (MEP). However, the influence of brain self-regulation on the associative pairing of these stimulation techniques is still unclear. OBJECTIVE: The aim of this pilot study was to investigate the effects of MI-related ERD during associative ES and TMS on subsequent corticospinal excitability. METHOD: The paired application of functional electrical stimulation (FES) of the extensor digitorum communis (EDC) muscle and subsequent single-pulse TMS (110% resting motor threshold (RMT)) of the contralateral primary motor cortex (M1) was controlled by beta-band (16-22 Hz) ERD during MI of finger extension and applied within a brain-machine interface environment in six healthy subjects. Neural correlates were probed by acquiring the stimulus-response curve (SRC) of both MEP peak-to-peak amplitude and area under the curve (AUC) before and after the intervention. RESULT: The application of approximately 150 pairs of associative FES and TMS resulted in a significant increase of MEP amplitudes and AUC, indicating that the induced increase of corticospinal excitability was mediated by the recruitment of additional neuronal pools. MEP increases were brain state-dependent and correlated with beta-band ERD, but not with the background EDC muscle activity; this finding was independent of the FES intensity applied. CONCLUSION: These results could be relevant for developing closed-loop therapeutic approaches such as the application of brain state-dependent, paired associative stimulation (PAS) in the context of neurorehabilitation.

Habituation analysis of chirp vs. tone evoked auditory late responses.

We have recently shown that tone evoked auditory late responses are able to proof that habituation is occurring [1], [2]. The sweep to sweep analysis using time scale coherence method from [1] is used. Where clear results using tone evoked ALRs were obtained. Now it is of interest how does the results behave using chirp evoked ALRs compared to tone evoked ALRs so that basilar membrane dispersion is compensated. We presented three different tone bursts and three different band limited chirps to 10 subjects using two different loudness levels which the subjects determined themselves before as medium and uncomfortably loud. The 3 chirps are band limited within 3 different ranges, the chirp with the lowest center frequency has the smallest range (according to octave-band). Chirps and tone bursts are using the same center frequencies.