D. Desideri

Brain-State Dependent Stimulation in Human Motor Cortex for Plasticity Induction Using EEG-TMS

Non-invasive motor cortex stimulation may result in long-term potentiation (LTP)-like plasticity of corticospinal excitability, and this may be useful to support neurorehabilitation after lesion, such as in stroke. However, the reported plasticity effects show large interindividual variability, and even intraindividual reliability is moderate at best. One possible strategy to improve size effect and consistency is to couple pulsed transcranial magnetic stimulation (TMS) to the endogenous brain state. We show here that instantaneous brain states measured with EEG have significant impact on TMS-induced corticospinal excitability. Consistent stimulation on the negative peak of the ongoing µ-rhythm results in LTP-like plasticity in 21/23 subjects, while stimulation at the positive peak had no effect. Findings raise the intriguing possibility that real-time information of instantaneous brain state can be utilized to control efficacy of plasticity induction in humans, and this may be utilized in clinical settings to support therapeutic reorganization of brain networks.

Reduced Performance During a Sentence Repetition Task by Continuous Theta-Burst Magnetic Stimulation of the Pre-supplementary Motor Area

The pre-supplementary motor area (pre-SMA) is engaged in speech comprehension under difficult circumstances such as poor acoustic signal quality or time-critical conditions. Previous studies found that left pre-SMA is activated when subjects listen to accelerated speech. Here, the functional role of pre-SMA was tested for accelerated speech comprehension by inducing a transient “virtual lesion” using continuous theta-burst stimulation (cTBS). Participants were tested (1) prior to (pre-baseline), (2) 10 min after (test condition for the cTBS effect), and (3) 60 min after stimulation (post-baseline) using a sentence repetition task (formant-synthesized at rates of 8, 10, 12, 14, and 16 syllables/s). Speech comprehension was quantified by the percentage of correctly reproduced speech material. For high speech rates, subjects showed decreased performance after cTBS of pre-SMA. Regarding the error pattern, the number of incorrect words without any semantic or phonological similarity to the target context increased, while related words decreased. Thus, the transient impairment of pre-SMA seems to affect its inhibitory function that normally eliminates erroneous speech material prior to speaking or, in case of perception, prior to encoding into a semantically/pragmatically meaningful message.

Modulation of cortical responses by transcranial direct current stimulation of dorsolateral prefrontal cortex: A resting-state EEG and TMS-EEG study

BACKGROUND Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique with potential for cost-effective therapeutic neuromodulation. Although positive therapeutic effects were found by stimulating the dorsolateral prefrontal cortex (DLPFC), few studies have investigated physiological effects of DLPFC-tDCS. OBJECTIVES To investigate effects of tDCS with different parameter settings applied to the left DLPFC on cortical responses, measured by resting-state electroencephalography (rs-EEG) and transcranial magnetic stimulation (TMS)-evoked/induced EEG responses. METHODS 22 healthy subjects underwent 5 tDCS sessions with different tDCS parameter settings in a double-blinded randomized crossover design (1: 1.5 mA, anode left-DLPFC, cathode right-DLPFC; 2: 1.5 mA, cathode left-DLPFC, anode right-DLPFC; 3: 0.5 mA, anode left-DLPFC, cathode right-DLPFC; 4: 1.5 mA, anode left-DLPFC, cathode left deltoid muscle; 5: sham stimulation). Rs-EEG and TMS-EEG were recorded before and after tDCS. RESULTS Rs-EEG power spectrum analysis showed no difference comparing baseline with post stimulation in any of the tDCS conditions. TMS-EEG evoked potential amplitude decreased in parietal cortex after 1.5 mA left-DLPFC anodal tDCS, and TMS-induced gamma and theta oscillations decreased after all conditions using left-DLPFC anodal tDCS. Left-DLPFC cathodal tDCS did not lead to significant change. None of the post-intervention changes was different when comparing the effects across conditions, including sham. CONCLUSIONS Our study does not provide evidence that a single tDCS session results in significant changes in rs-EEG, using the current stimulation parameters. Significant changes in EEG responses to TMS pulses were observed following the anodal 1.5 mA tDCS interventions, although these changes were not statistically significant in a group comparison.

Comparison of cortical EEG responses to realistic sham versus real TMS of human motor cortex

BACKGROUND The analysis of cortical responses to transcranial magnetic stimulation (TMS) recorded by electroencephalography (EEG) has been successfully applied to study human cortical physiology. However, in addition to the (desired) activation of cortical neurons and fibers, TMS also causes (undesired) indirect brain responses through auditory and somatosensory stimulation, which may contribute significantly to the overall EEG signal and mask the effects of intervention on direct cortical responses. OBJECTIVES To test differences in EEG responses to real TMS at intensities above and below resting motor threshold (RMT) and a realistic sham stimulation. METHODS 12 healthy subjects participated in one session in which single-pulse TMS was applied to the left motor cortex in 3 different blocks, 150 pulses per block: 110%RMT, 90%RMT and realistic sham stimulation. Cortical responses were collected by a 64 electrode EEG system. TMS evoked potentials (TEPs) and TMS induced oscillations were analyzed. METHODS 12 healthy subjects participated in one session in which single-pulse TMS was applied to the left motor cortex in 3 different blocks, 150 pulses per block: 110%RMT, 90%RMT and realistic sham stimulation. Cortical responses were collected by a 64-channel EEG system. TMS evoked potentials (TEPs) and TMS induced oscillations were analyzed. RESULTS TEPs from all conditions differed significantly, with TEPs from 110%RMT showing overall highest amplitudes and realistic sham lowest amplitudes. Sham stimulation had only minor effects on induced cortical oscillations compared to pre-stimulus baseline, TMS at 90%RMT resulted in a significant increase (50-200 m s) followed by a decrease (200-500 m s) in power of alpha and beta oscillations; TMS at 110% RMT led to an additional increase in beta power at late latencies (650-800 m s). CONCLUSIONS Real TMS of motor cortex results in cortical responses significantly different from realistic sham. These differences very likely reflect to a significant extent direct activation of neurons, rather than sensory evoked activity.

P124 Real-time source-level EEG network activity state triggered TMS with millisecond resolution

Question Closed-loop methods that trigger the TMS pulse based on the EEG signal are increasingly available, however, current systems rely on the data of a small number of channels and the signal at sensor level cannot be localized to a specific brain area. The challenge is to analyze a sufficient number of EEG channels in real-time to enable spatially localized estimation of individual brain network activity. Methods EEG data is acquired using a high-density TMS compatible recording system and streamed online to a real-time digital processing system based on Simulink. A sliding window of data is used to estimate the sources that give rise to the EEG signal using a spatial filter computation executed on the processor as the signal is acquired. The forward model is computed based on the MRI data using a FEM model to solve the forward problem. The leadfields are calculated employing the neuronavigated electrode positions and then employed to compute the real-time LCMV beamforming. Instantaneous phase is estimated at multiple source-level location simultaneously using parallel sliding windows of band-pass filtered data preceding the current time, each extended into the future in real-time using autoregressive model, with instantaneous phase estimated using a Hilbert transform. Results A latency of Conclusions A novel technique enabling TMS triggered by the instantaneous phase-state of the individual network is presented. This is a significant extension of the current state-of-the-art and could enable the development of more effective personalized closed-loop neuromodulatory stimulation protocols.

Motor cortex excitability in seizure-free STX1B mutation carriers with a history of epilepsy and febrile seizures

OBJECTIVE Mutations in STX1B encoding the presynaptic protein syntaxin-1B are associated with febrile seizures with or without epilepsy. It is unclear to what extent these mutations are linked to abnormalities of cortical glutamatergic or GABAergic neurotransmission. We explored this question using single- and paired-pulse transcranial magnetic stimulation (TMS) excitability markers. METHODS We studied nine currently asymptomatic adult STX1B mutation carriers with history of epilepsy and febrile seizures, who had been seizure-free for at least eight years without antiepileptic drug treatment, and ten healthy age-matched controls. Resting motor threshold (RMT), and input-output curves of motor evoked potential (MEP) amplitude, short-interval intracortical inhibition (SICI, marker of GABAAergic excitability) and intracortical facilitation (ICF, marker of glutamatergic excitability) were tested. RESULTS RMT, and input-output curves of MEP amplitude, SICI and ICF revealed no significant differences between STX1B mutation carriers and healthy controls. CONCLUSIONS Findings suggest normal motor cortical GABAAergic and glutamatergic excitability in currently asymptomatic STX1B mutation carriers. SIGNIFICANCE TMS measures of motor cortical excitability show utility in demonstrating normal excitability in adult STX1B mutation carriers with history of seizures.