Adenauer Girardi Casali

Background: Transcranial Magnetic Stimulation combined with electroencephalography (TMS-EEG) offers unique insights into cortical excitability and connectivity, yet current analyses are primarily limited to group-level inferences with little validation of individual reliability and feature redundancy. Objective: To construct a comprehensive, open-access, and reliable normative dataset of TMS-EEG features that enables individual-level comparison. Methods: We aggregated TMS-EEG data recorded over the primary motor cortex (M1) from 164 healthy adults (30.8 ± 9.8 years; 88 female) across nine studies using harmonized acquisition and preprocessing pipelines. Reliability analysis was conducted on a test-retest subset (N=57) for 968 extracted features, evaluating systematic bias, absolute error, and relative reliability (Intraclass Correlation Coefficient categorized by the lower bound of the 95% confidence interval). Additionally, feature clustering was performed to quantify redundancy and correlations across the high-dimensional feature space. We then established normative distributions and developed an online benchmarking platform. Results: Reliability analyses (N=57) of the high-dimensional feature set revealed that 525 out of 968 features (54.3%) met at least moderate reliability standards (ICC lower bound > 0.5). Cluster analysis indicated substantial redundancy among metrics, with three distinct clusters having a moderate-to-high internal correlation (|r|=0.64, 0.48, 0.39, respectively). Finally, normative data from the database identified abnormal results in a test patient, supporting the feasibility of individual-level classification in an open-science framework. Conclusions: Harmonization of data acquisition and analysis pipelines led to the development of a reliable normative M1 TMS-EEG reference. This publicly available resource provides a validated tool for future individual-level classifications and an open platform for ongoing community contributions.

Transcranial magnetic stimulation combined with electroencephalography (TMS–EEG) is a powerful technique for investigating human cortical circuits. However, characterizing TMS-evoked potentials (TEPs) at the group level typically relies on grand averaging across stimulus repetitions (trials) and subjects—an approach that assumes a level of spatial and temporal consistency that is often lacking in TEPs. Here, we introduce an adaptation of Group Task-Related Component Analysis (gTRCA), a novel multivariate signal decomposition method, to automatically extract TEP components that are maximally reproducible across both trials and subjects. Following the validation of a new permutation-based statistical test for gTRCA using simulated data, the method was applied to two independent TMS–EEG datasets, in which stimulation was targeted to the primary motor cortex (M1) in cohorts of 16 and 22 healthy participants. We found that gTRCA reliably identified TEP components that were reproducible at the group level. Notably, the main gTRCA component captured the key spatial, temporal, and spectral features of motor TEPs, remained robust despite reduced number of stimuli and participants, and was consistent across different recordings. These findings demonstrate that gTRCA affords a more reliable characterization of TEPs at the group level, thereby facilitating the translation of TMS–EEG research into clinical practice.

Objectives: Cortico-spinal excitability of the primary motor cortex (M1) is reduced in fibromyalgia, and repetitive transcranial magnetic stimulation (TMS) targeting M1 normalizes these changes and relieves symptoms. TMS combined with electroencephalography (TMS-EEG) allows the measurement of M1 excitability and its connectivity to other regions, which may help clarify neurophysiological effects in fibromyalgia. We assessed cortical excitability, oscillatory activity, and complexity in individuals with fibromyalgia compared to pain-free healthy controls. Methods: Global and local mean field power, peak-to-peak amplitude, event-related spectral perturbation, intertrial coherence (ITC), natural frequency, and perturbational complexity index (PCIst) of the EEG response after left-M1 TMS were compared between groups (n=18 fibromyalgia; n=15 controls). Pain intensity, interference, relief of current therapy, mood, and quality of life were assessed in individuals with fibromyalgia. Results: Compared with controls, individuals with fibromyalgia showed a reduction in the alpha-band ITC in middle and right parieto-occipital areas (P<0.05). Middle-parieto-occipital ITC negatively correlated with reported pain relief (rho=-0.552, p=0.019). The PCIst was lower in fibromyalgia compared with controls (P<0.01) and correlated with higher pain interference in general activity (rho=-0.486, p=0.042). Conclusion: Individuals with fibromyalgia showed abnormal cortical connectivity compared with asymptomatic controls. Significance: TMS-EEG measurements may provide insights on brain connectivity relevant for therapy.

Background: Transcranial Magnetic Stimulation (TMS) with simultaneous Electroencephalogram (TMS-EEG) allows assessing the neurophysiological properties of cortical neurons. However, TMS-evoked EEG potentials (TEPs) can be affected by components unrelated to TMS direct neuronal activation. Accurate, automatic tools are therefore needed to establish the quality of TEPs. Objective: To assess the discriminability of EEG responses to TMS vs. EEG responses to sham stimulations using sequence-to-sequence machine learning (ML). Methods: Two indipendent TMS-EEG datasets including TMS and several sham stimulation conditions were obtained from the left motor area of healthy volunteers (N=33 across datasets). A Bi-directional Long Short-Term Memory (BiLSTM) ML network was used to label each time point of the EEG signals as pertaining to TMS or sham conditions. Main outcome measures included accuracy at single-trial level and after averaging five to twenty trials. Results: For TMS conditions, post-stimulus vs. baseline/pre-stimulus EEG comparisons yielded moderate (60%-75%) single-trial accuracy and high-accuracy (>75%) for 20 trials across datasets, while for sham conditions post- vs. baseline/pre-stimulus EEG comparisons yielded lower accuracy rates than for TMS conditions, except for unmasked auditory stimulation. Furthermore, baseline/pre-stimulus TMS vs. baseline/pre-stimulus sham EEG comparisons showed chance-level accuracy, whereas post-stimulus TMS vs. post-stimulus sham EEG comparisons had moderate (single trial) to high (20 trial) accuracy, except for TMS with and without the click noise masking. Single-subject findings were comparable to group-level results across datasets. Conclusions: TEPs after active TMS are discernible from various sham stimulations even after a handful of trials and at the single-subject level using a BiLSTM ML approach.

Transcranial Magnetic Stimulation (TMS) evokes electroencephalographic (EEG) responses that can persist for hundreds of milliseconds. While the first 80 ms after the pulse are widely accepted to reflect genuine cortical responses to TMS, later components have mainly been attributed to the effects of sensory co-stimulations. Here we reappraise this view by investigating the target-specificity of the spatiotemporal evolution of TMS-evoked potentials (TEPs). To this end, we compared TEPs elicited by targeting the premotor and primary motor cortices in 16 healthy subjects, under conditions designed to optimize TMS effectiveness on the cortex while minimizing peripheral confounds. As a counterfactual, we conducted the same comparison on the EEG responses evoked by realistic sham TMS and high-intensity somatosensory scalp stimulation. We found that EEG responses to motor and premotor TMS can exhibit distinct spatiotemporal evolutions, lasting up to 300 ms, both at the group and single-subject levels. These differences were absent or marginally detectable in both realistic sham TMS and high-intensity somatosensory scalp stimulation. Our findings suggest that, when effectiveness is optimized and peripheral confounds are controlled, TMS elicits specific long-lasting genuine EEG responses that reflect the initial engagement of specific cortical targets. These results challenge previous assumptions and highlight how TMS-EEG can be reliably used to assess large-scale properties within corticothalamic networks.

Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) is a powerful technique for investigating human cortical circuits. However, characterizing TMS-evoked potentials (TEPs) at the group level typically relies on grand averaging across stimulus repetitions (trials) and subjects – an approach that assumes a level of spatial and temporal consistency that is often lacking in TEPs. Here, we introduce an adaptation of Group Task-Related Component Analysis (gTRCA), a novel multivariate signal decomposition method, to automatically extract TEP components that are maximally reproducible across both trials and subjects. Following the validation of a new permutation-based statistical test for gTRCA using simulated data, the method was applied to two independent TMS-EEG datasets, in which stimulation was targeted to the primary motor cortex (M1) in cohorts of 16 and 22 healthy participants. We found that gTRCA reliably identified TEP components that were reproducible at the group level. Notably, the main gTRCA component captured the key spatial, temporal, and spectral features of motor TEPs, remained robust despite reduced number of stimuli and participants, and was consistent across different recordings. These findings demonstrate that gTRCA affords a more reliable characterization of TEPs at the group level, thereby facilitating the translation of TMS-EEG research into clinical practice.

INTRODUCTION: Despite being considered least important for clinical practice in the pyramid of evidence for recommendations, sometimes scientists' expert opinions could help to better understand the summarization of updated publications. OBJECTIVE: To provide a major summarized update about brain imaging and stimulation of the nervous system in health and disease. METHODS: Comprehensive review developed by experts in each subarea of knowledge in neuroimaging and non-invasive stimulation of the nervous system. A team of researchers and clinic experts was invited to present an update on their area of expertise. RESULTS: In basics on brain imaging techniques, we approach general and quantitative electroencephalography, functional magnetic resonance imaging, functional near-infrared spectroscopy, and experimental paradigms in brain imaging studies. Were included associations between transcranial magnetic stimulation and electromyography, electroencephalography, and functional near-infrared stimulation to evaluate brain activity. Furthermore, we showed several actualized central and peripheral neuromodulation techniques. And finally, we presented different clinical and performance uses of non-invasive neuromodulation. CONCLUSION: To our knowledge, this is a major summarized and concentrated update about brain imaging and stimulation that can benefit neuroscience researchers and clinicians from different levels of experience.