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Objectives: Patients with borderline personality disorder (pw-BPD) have decreased levels of cognitive empathy, which may be subtended by mirror-like mechanisms in the somatosensory cortices, i.e., the Tactile Mirror System (TaMS). Here, we aimed to shed light on the TaMS and empathic deficits in pw-BPD focusing on connectivity, using transcranial magnetic stimulation and electroencephalography (TMS-EEG)., Methods: After study preregistration, we collected self-report measures of empathic abilities, behavioral performance in a visuo-tactile spatial congruency task investigating TaMS activity, and TMS-evoked potentials (TEPs) from 20 pw-BPD and 20 healthy controls. TMS was delivered over the right primary somatosensory cortex (S1) during touch observation and real touch delivery., Results: Pw-BPD reported significantly lower levels of cognitive empathy than controls and made significantly more errors in reporting the side of real touches during touch observation. Moreover, pw-BPD presented an altered connectivity pattern from S1-TEPs during touch perception and touch observation, in the last case without differences between human- and object-directed touches., Conclusions: The results do not support a specific impairment of TaMS in pw-BPD, but reveal significant behavioral and connectivity alterations within the somatosensory network during touch processing., Significance: The present findings temper the proposed role of the TaMS in BPD, while still highlighting the involvement of somatosensory network alterations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Federation of Clinical Neurophysiology. All rights reserved.)

Combining Non-Invasive Brain Stimulation (NIBS) techniques with the recording of brain electrophysiological activity is an increasingly widespread approach in neuroscience. Particularly successful has been the simultaneous combination of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG). Unfortunately, the strong magnetic pulse required to effectively interact with brain activity inevitably induces artifacts in the concurrent EEG acquisition. Therefore, a careful but aggressive pre-processing is required to efficiently remove artifacts. Unfortunately, as already reported in the literature, different preprocessing approaches can introduce variability in the results. Here we aim at characterizing the three main TMS-EEG preprocessing pipelines currently available, namely ARTIST (Wu et al., 2018), TESA (Rogasch et al., 2017) and SOUND/SSP-SIR (Mutanen et al., 2018, 2016), providing an insight to researchers who need to choose between different approaches. Differently from previous works, we tested the pipelines using a synthetic TMS-EEG signal with a known ground-truth (the artifacts-free to-be-reconstructed signal). In this way, it was possible to assess the reliability of each pipeline precisely and quantitatively, providing a more robust reference for future research. In summary, we found that all pipelines performed well, but with differences in terms of the spatio-temporal precision of the ground-truth reconstruction. Crucially, the three pipelines impacted differently on the inter-trial variability, with ARTIST introducing inter-trial variability not already intrinsic to the ground-truth signal., Competing Interests: Declaration of competing interest UZ received grants from the European Research Council (ERC), German Ministry of Education and Research (BMBF), German Research Foundation (DFG), and consulting fees from CorTec GmbH. All the other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Transcranial magnetic stimulation (TMS) evokes neuronal activity in the targeted cortex and connected brain regions. The evoked brain response can be measured with electroencephalography (EEG). TMS combined with simultaneous EEG (TMS-EEG) is widely used for studying cortical reactivity and connectivity at high spatiotemporal resolution. Methodologically, the combination of TMS with EEG is challenging, and there are many open questions in the field. Different TMS-EEG equipment and approaches for data collection and analysis are used. The lack of standardization may affect reproducibility and limit the comparability of results produced in different research laboratories. In addition, there is controversy about the extent to which auditory and somatosensory inputs contribute to transcranially evoked EEG. This review provides a guide for researchers who wish to use TMS-EEG to study the reactivity of the human cortex. A worldwide panel of experts working on TMS-EEG covered all aspects that should be considered in TMS-EEG experiments, providing methodological recommendations (when possible) for effective TMS-EEG recordings and analysis. The panel identified and discussed the challenges of the technique, particularly regarding recording procedures, artifact correction, analysis, and interpretation of the transcranial evoked potentials (TEPs). Therefore, this work offers an extensive overview of TMS-EEG methodology and thus may promote standardization of experimental and computational procedures across groups., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PJ has received consulting fees and shares a patent with Nexstim Oyj. PL has received consulting fees from Nexstim Oyj. HRS has received honoraria as speaker from Sanofi Genzyme, Denmark, Lundbeck AS, Denmark, and Novartis, Denmark, as consultant from Sanofi Genzyme, Denmark, Lophora, Denmark, and Lundbeck AS, Denmark, and as editor-in-chief (Neuroimage Clinical) and senior editor (NeuroImage) from Elsevier Publishers, Amsterdam, The Netherlands. He has received royalties as book editor from Springer Publishers, Stuttgart, Germany and from Gyldendal Publishers, Copenhagen, Denmark. TPM has successfully applied for funding for a collaborative research project (project not started at the time of the submission) with Bittium Biosignals Oy (Kuopio, Finland). SC is advisor and share-holder of Intrinsic Power, a spinf-off of the University of Milan., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The concurrent combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) can unveil functional neural mechanisms with applications in basic and clinical research. In particular, TMS-evoked potentials (TEPs) potentially allow studying excitability and connectivity of the cortex in a causal manner that is not easily or non-invasively attainable with other neuroimaging techniques. The TEP waveform is obtained by isolating the EEG responses phase-locked to the time of TMS application. The intended component in a TEP waveform is the cortical activation by the TMS-induced electric current, free of instrumental and physiological artifact sources. This artifact-free cortical activation can be referred to as 'true' TEP. However, due to many unwanted auxiliary effects of TMS, the interpretation of 'true' TEPs has not been free of controversy. This paper reviews the most recent understandings of 'true' TEPs and their application. In the first part of the paper, TEP components are defined according to recommended methodologies. In the second part, the verification of 'true' TEP is discussed along with its sensitivity to brain-state, age, and disease. The various proposed origins of TEP components are then presented in the context of existing literature. Throughout the paper, lessons learned from the past TMS-EEG studies are highlighted to guide the identification and interpretation of 'true' TEPs in future studies., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Transcranial magnetic stimulation (TMS)-evoked potentials (TEPs) allow one to assess cortical excitability and effective connectivity in clinical and basic research. However, obtaining clean TEPs is challenging due to the various TMS-related artifacts that contaminate the electroencephalographic (EEG) signal when the TMS pulse is delivered. Different preprocessing approaches have been employed to remove the artifacts, but the degree of artifact reduction or signal distortion introduced in this phase of analysis is still unknown. Knowing and controlling this potential source of uncertainty will increase the inter-rater reliability of TEPs and improve the comparability between TMS-EEG studies. The goal of this study was to assess the variability in TEP waveforms due to of the use of different preprocessing pipelines. To accomplish this aim, we preprocessed the same TMS-EEG data with four different pipelines and compared the results. The dataset was obtained from 16 subjects in two identical recording sessions, each session consisting of both left dorsolateral prefrontal cortex and left inferior parietal lobule stimulation at 100% of the resting motor threshold. Considerable differences in TEP amplitudes and global mean field power (GMFP) were found between the preprocessing pipelines. Topographies of TEPs from the different pipelines were all highly correlated (ρ>0.8) at latencies over 100 ms. By contrast, waveforms at latencies under 100 ms showed a variable level of correlation, with ρ ranging between 0.2 and 0.9. Moreover, the test-retest reliability of TEPs depended on the preprocessing pipeline. Taken together, these results take us to suggest that the choice of the preprocessing approach has a marked impact on the final TEP, and that further studies are needed to understand advantages and disadvantages of the different approaches., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2021. Published by Elsevier Inc.)

The human brain is a complex network in which hundreds of brain regions are interconnected via thousands of axonal pathways. The capability of such a complex system emerges from specific interactions among smaller entities, a set of events that can be described by the activation of interconnections between brain areas. Studies that focus on brain connectivity have the aim of understanding and modeling brain function, taking into account the spatiotemporal dynamics of neural communication between brain regions. Much of the current knowledge regarding brain connectivity has been obtained from stand-alone neuroimaging methods. Nevertheless, the use of a multimodal approach seems to be a powerful way to investigate effective brain connectivity, overcoming the limitations of unimodal approaches. In this review, we will present the advantages of an integrative approach in which transcranial magnetic stimulation-electroencephalography coregistration is combined with magnetic resonance imaging methods to explore effective neural interactions. Moreover, we will describe possible implementations of the integrative approach in open- and closed-loop frameworks where real-time brain activity becomes a contributor to the study of cognitive brain networks.

Clinical manifestations of Alzheimer's disease (AD) are associated with a breakdown in large-scale communication, such that AD may be considered as a "disconnection syndrome." An established method to test effective connectivity is the combination of transcranial magnetic stimulation with electroencephalography (TMS-EEG) because the TMS-induced cortical response propagates to distant anatomically connected regions. To investigate whether prefrontal connectivity alterations may predict disease severity, we explored the relationship of dorsolateral prefrontal cortex connectivity (derived from TMS-EEG) with cognitive decline (measured with Mini Mental State Examination and a face-name association memory task) in 26 patients with AD. The amplitude of TMS-EEG evoked component P30, which was found to be generated in the right superior parietal cortex, predicted Mini Mental State Examination and face-name memory scores: higher P30 amplitudes predicted poorer cognitive and memory performances. The present results indicate that advancing disease severity might be associated with effective connectivity increase involving long-distance frontoparietal connections, which might represent a maladaptive pathogenic mechanism reflecting a damaged excitatory-inhibitory balance between anterior and posterior regions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Recent developments in neuroscience have emphasised the importance of integrated distributed networks of brain areas for successful cognitive functioning. Our current understanding is that the brain has a modular organisation in which segregated networks supporting specialised processing are linked through a few long-range connections, ensuring processing integration. Although such architecture is structurally stable, it appears to be flexible in its functioning, enabling long-range connections to regulate the information flow and facilitate communication among the relevant modules, depending on the contingent cognitive demands. Here we show how insights brought by the coregistration of transcranial magnetic stimulation and electroencephalography (TMS-EEG) integrate and support recent models of functional brain architecture. Moreover, we will highlight the types of data that can be obtained through TMS-EEG, such as the timing of signal propagation, the excitatory/inhibitory nature of connections and causality. Last, we will discuss recent emerging applications of TMS-EEG in the study of brain disorders., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The memory-guided saccade paradigm is an ideal experimental model for studying spatial working memory. Both the posterior parietal cortex and frontal cortex are known to play a role in working memory; however, there is much debate about the degree of their involvement in the retention of information. We used event-related potentials and electromagnetic tomography to clarify the precise time course and location of the neural correlates of spatial working memory during a memory-guided saccade task in humans. We observed sustained activity in the inferior parietal lobe and extrastriate areas that persisted for the entire duration of the sensory- and memory-phases. This time course reveals that these regions participate in both initial sensory processing of visual cues and in the short-term maintenance of spatial location memory. Similar sustained activation was also observed in the anterior cingulate cortex, probably reflecting attentive control during the task. Differential activity between conditions was also recorded in the dorsolateral prefrontal cortex and in the frontal eye fields, but only during the initial part of the memory-phase. This finding suggests that these areas are not involved in the storage of spatial information, but rather in response selection and in transformation of spatial information into a motor coordinate framework, respectively. By exploiting techniques that provide exquisite temporal resolution and reasonably precise anatomical localization, this study provides evidence supporting the key role of inferior parietal lobe in the storage of spatial information during a working memory guided saccade., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: The combination of brain stimulation by transcranial magnetic stimulation (TMS) and simultaneous electroencephalographic (EEG) recording has the potential to be of great value for understanding human brain functions. Recording EEG during TMS can be technically challenging because TMS induces a very strong electrical field that can saturate recording amplifiers for a long duration. Advances in amplifier technology, however, have led to the development of TMS-compatible EEG equipment that can work in very high, time-varying magnetic fields without saturation. The aim of the present study was to identify stimulus-related artifacts, and to provide experimental data containing the length of the artifact induced by the magnetic field and its variations with respect to the experimental setting., Methods: A phantom head was stimulated to record the artifact while excluding cortical responses. We tested different types of electrodes, coils, models of stimulator, and frequencies and intensities of stimulation to see how these parameters influence the duration of the artifact., Results: The electrical artifact produced by the magnetic pulse lasted approximately 5 ms following TMS onset. Its length was invariant irrespective of different experimental conditions., Conclusions: These data suggest that it is possible to analyze the cortical evoked response induced by TMS 5 ms after TMS onset., Significance: The possibility to study the early physiological responses to TMS stimulation may have valuable implications for both clinical and experimental purposes, providing information about the early direct cortical response of the stimulated areas.