Search

Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique uniquely equipped to both examine and modulate neural systems and related cognitive and behavioral functions in humans. As an examination tool, TMS can be used in combination with EEG (TMS-EEG) to elucidate directly, objectively, and noninvasively the intrinsic properties of a specific cortical region, including excitation, inhibition, reactivity, and oscillatory activity, irrespective of the individual's conscious effort. Additionally, when applied in repetitive patterns, TMS has been shown to modulate brain networks in healthy individuals, as well as ameliorate symptoms in individuals with psychiatric disorders. The key role of TMS in assessing and modulating neural dysfunctions and associated clinical and cognitive deficits in psychiatric populations is therefore becoming increasingly evident. In this article, the authors review TMS-EEG studies in schizophrenia and mood disorders, as most TMS-EEG studies to date have focused on individuals with these disorders. The authors present the evidence on the efficacy of repetitive TMS (rTMS) and theta burst stimulation (TBS), when targeting specific cortical areas, in modulating neural circuits and ameliorating symptoms and abnormal behaviors in individuals with psychiatric disorders, especially when informed by resting-state and task-related neuroimaging measures. Examples of how the combination of TMS-EEG assessments and rTMS and TBS paradigms can be utilized to both characterize and modulate neural circuit alterations in individuals with psychiatric disorders are also provided. This approach, along with the evaluation of the behavioral effects of TMS-related neuromodulation, has the potential to lead to the development of more effective and personalized interventions for individuals with psychiatric disorders.

Concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) has emerged as a powerful tool to non-invasively probe brain circuits in humans, allowing for the assessment of several cortical properties such as excitability and connectivity. Over the past decade, this technique has been applied to various clinical populations, enabling the characterization and development of potential TMS-EEG predictors and markers of treatments and of the pathophysiology of brain disorders. The objective of this article is to present a comprehensive review of studies that have used TMS-EEG in clinical populations and to discuss potential clinical applications. To provide a technical and theoretical framework, we first give an overview of TMS-EEG methodology and discuss the current state of knowledge regarding the use of TMS-EEG to assess excitability, inhibition, plasticity and connectivity following neuromodulatory techniques in the healthy brain. We then review the insights afforded by TMS-EEG into the pathophysiology and predictors of treatment response in psychiatric and neurological conditions, before presenting recommendations for how to address some of the salient challenges faced in clinical TMS-EEG research. Finally, we conclude by presenting future directions in line with the tremendous potential of TMS-EEG as a clinical tool., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Our recent finding of a meditation-related increase in low-frequency NREM sleep EEG oscillatory activities peaking in the theta-alpha range (4-12 Hz) was not predicted. From a consolidated body of research on sleep homeostasis, we would expect a change peaking in slow wave activity (1-4 Hz) following an intense meditation session. Here we compared these changes in sleep with the post-meditation changes in waking rest scalp power to further characterize their functional significance. High-density EEG recordings were acquired from 27 long-term meditators (LTM) on three separate days at baseline and following two 8-hr sessions of either mindfulness or compassion-and-loving-kindness meditation. Thirty-one meditation-naïve participants (MNP) were recorded at the same time points. As a common effect of meditation practice, we found increases in low and fast waking EEG oscillations for LTM only, peaking at eight and 15 Hz respectively, over prefrontal, and left centro-parietal electrodes. Paralleling our previous findings in sleep, there was no significant difference between meditation styles in LTM as well as no difference between matched sessions in MNP. Meditation-related changes in wakefulness and NREM sleep were correlated across space and frequency. A significant correlation was found in the EEG low frequencies (<12 Hz). Since the peak of coupling was observed in the theta-alpha oscillatory range, sleep homeostatic response to meditation practice is not sufficient to explain our findings. Another likely phenomenon into play is a reverberation of meditation-related processes during subsequent sleep. Future studies should ascertain the interplay between these processes in promoting the beneficial effects of meditation practice., (© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Characterizing the neurobiology of schizophrenia and other major psychiatric disorders is one of the main challenges of the current research in psychiatry. The availability of Transcranial Magnetic Stimulation (TMS) allows to directly probe virtually any cortical areas, thus providing a unique way to assess the neurophysiological properties of cortical neurons. This article presents a review of studies employing TMS in combination with Motor Evoked Potentials (TMS/MEPs) and high density Electroencephalogram (TMS/hd-EEG) in schizophrenia and other major psychiatric disorders. Studies were identified by conducting a PubMed search using the following search item: "transcranial magnetic stimulation and (Schizophrenia or OCD or MDD or ADHD)". Studies that utilized TMS/MEP and/or TMS/hd-EEG measures to characterize cortical excitability, inhibition, oscillatory activity, and/or connectivity in psychiatric patients were selected. Across disorders, patients displayed a pattern of reduced cortical inhibition, and to a lesser extent increased excitability, in the motor cortex, which was most consistently established in Schizophrenia. Furthermore, psychiatric patients showed abnormalities in a number of TMS-evoked EEG oscillations, which was most prominent in the prefrontal cortex of Schizophrenia relative to healthy comparison subjects. Overall, results from this review point to significant impairments in cortical excitability, inhibition, and oscillatory activity, especially in frontal areas, in several major psychiatric disorders. Building on these findings, future studies employing TMS-based experimental paradigms may help elucidating the neurobiology of these psychiatric disorders, and may assess the contribution of TMS-related measures in monitoring and possibly maximizing the effectiveness of treatment interventions in psychiatric populations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Sleep spindles are wax and waning brain oscillations at a frequency range of 11-16 Hz, lasting 0.5-2 s, that define non-rapid eye movement sleep stage 2. Over the past few years, several independent studies pointed to a decrease of sleep spindles in schizophrenia. The aim of this review is to contextualize these findings within the growing literature on these oscillations across other neuro-psychiatric disorders. Indeed, spindles reflect the coordinated activity of thalamocortical networks, and their abnormality can be observed in a variety of conditions that disrupt local or global thalamocortical connectivity. Although the broad methodological variability across studies limits the possibility of drawing firm conclusions, impaired spindling activity has been observed in several neurodevelopmental and neurodegenerative disorders. Despite such lack of specificity, schizophrenia remains the only condition with a typical late adolescence to young adulthood onset in which impaired spindling has been consistently reported. Further research is necessary to clearly define the pathogenetic mechanisms that lead to this deficit and the validity of its widespread use as a clinical biomarker.

Study Objectives: To examine nonrapid eye movement (NREM) sleep in insomnia using high-density electroencephalography (EEG)., Methods: All-night sleep recordings with 256 channel high-density EEG were analyzed for 8 insomnia subjects (5 females) and 8 sex and age-matched controls without sleep complaints. Spectral analyses were conducted using unpaired t-tests and topographical differences between groups were assessed using statistical non-parametric mapping. Five minute segments of deep NREM sleep were further analyzed using sLORETA cortical source imaging., Results: The initial topographic analysis of all-night NREM sleep EEG revealed that insomnia subjects had more high-frequency EEG activity (> 16 Hz) compared to good sleeping controls and that the difference between groups was widespread across the scalp. In addition, the analysis also showed that there was a more circumscribed difference in theta (4-8 Hz) and alpha (8-12 Hz) power bands between groups. When deep NREM sleep (N3) was examined separately, the high-frequency difference between groups diminished, whereas the higher regional alpha activity in insomnia subjects persisted. Source imaging analysis demonstrated that sensory and sensorimotor cortical areas consistently exhibited elevated levels of alpha activity during deep NREM sleep in insomnia subjects relative to good sleeping controls., Conclusions: These results suggest that even during the deepest stage of sleep, sensory and sensorimotor areas in insomnia subjects may still be relatively active compared to control subjects and to the rest of the sleeping brain., (© 2016 Associated Professional Sleep Societies, LLC.)

Unlabelled: BACKGROUND OBJECTIVE: measurement of plastic brain changes induced by a novel rehabilitative approach is a key requirement for validating its biological rationale linking the potential therapeutic gains to the changes in brain physiology., Objective: Based on an emerging notion linking cortical plastic changes to EEG sleep slow-wave activity (SWA) regulation, we aimed to assess the acute plastic changes induced by an imitation-based speech therapy in individuals with aphasia by comparing sleep SWA changes before and after therapy., Methods: A total of 13 left-hemispheric stroke patients underwent language assessment with the Western Aphasia Battery (WAB) before and after 2 consecutive high-density (hd) EEG sleep recordings interleaved by a daytime session of imitation-based speech therapy (Intensive Mouth Imitation and Talking for Aphasia Therapeutic Effects [IMITATE]). This protocol is thought to stimulate bilateral connections between the inferior parietal lobule and the ventral premotor areas., Results: A single exposure to IMITATE resulted in increases in local EEG SWA during subsequent sleep over the same regions predicted by the therapeutic rationale, particularly over the right hemisphere (unaffected by the lesion). Furthermore, changes in SWA over the left-precentral areas predicted changes in WAB repetition scores in our group, supporting the role of perilesional areas in predicting positive functional responses., Conclusions: Our results suggest that SWA changes occurring in brain areas activated during imitation-based aphasia therapy may reflect the acute plastic changes induced by this intervention. Further testing will be needed to evaluate SWA as a non-invasive assessment of changes induced by the therapy and as a predictor of positive long-term clinical outcome.

Study Objectives: Obstructive sleep apnea (OSA) is associated with significant alterations in neuronal integrity resulting from either hypoxemia and/or sleep loss. A large body of imaging research supports reductions in gray matter volume, alterations in white matter integrity and resting state activity, and functional abnormalities in response to cognitive challenge in various brain regions in patients with OSA. In this study, we used high-density electroencephalography (hdEEG), a functional imaging tool that could potentially be used during routine clinical care, to examine the regional distribution of neural activity in a non-clinical sample of untreated men and women with moderate/severe OSA., Design: Sleep was recorded with 256-channel EEG in relatively healthy subjects with apnea-hypopnea index (AHI) > 10, as well as age-, sex-, and body mass index-matched controls selected from a research population initially recruited for a study on sleep and meditation., Setting: Sleep laboratory., Patients or Participants: Nine subjects with AHI > 10 and nine matched controls., Interventions: N/A., Measurements and Results: Topographic analysis of hdEEG data revealed a broadband reduction in EEG power in a circumscribed region overlying the parietal cortex in OSA subjects. This parietal reduction in neural activity was present, to some extent, across all frequency bands in all stages and episodes of nonrapid eye movement sleep., Conclusion: This investigation suggests that regional deficits in electroencephalography (EEG) power generation may be a useful clinical marker for neural disruption in obstructive sleep apnea, and that high-density EEG may have the sensitivity to detect pathological cortical changes early in the disease process.

Study Objectives: Prolonged wakefulness leads to a progressive increase in sleep pressure, reflected in a global increase in slow wave activity (SWA, 0.5-4.5 Hz) in the sleep electroencephalogram (EEG). A global increase in wake theta activity (5-9 Hz) also occurs. Recently, it was shown that prolonged wakefulness in rodents leads to signs of "local sleep" in an otherwise awake brain, accompanied by a slow/theta wave (2-6 Hz) in the local EEG that occurs at different times in different cortical areas. Compelling evidence in animals and humans also indicates that sleep is locally regulated by the amount of experience-dependent plasticity. Here, we asked whether the extended practice of tasks that involve specific brain circuits results in increased occurrence of local intermittent theta waves in the human EEG, above and beyond the global EEG changes previously described., Design: Participants recorded with high-density EEG completed 2 experiments during which they stayed awake ≥ 24 h practicing a language task (audiobook listening [AB]) or a visuomotor task (driving simulator [DS])., Setting: Sleep laboratory., Patients or Participants: 16 healthy participants (7 females)., Interventions: Two extended wake periods., Measurements and Results: Both conditions resulted in global increases in resting wake EEG theta power at the end of 24 h of wake, accompanied by increased sleepiness. Moreover, wake theta power as well as the occurrence and amplitude of theta waves showed regional, task-dependent changes, increasing more over left frontal derivations in AB, and over posterior parietal regions in DS. These local changes in wake theta power correlated with similar local changes in sleep low frequencies including SWA., Conclusions: Extended experience-dependent plasticity of specific circuits results in a local increase of the wake theta EEG power in those regions, followed by more intense sleep, as reflected by SWA, over the same areas.

Sleep spindles are an electroencephalographic (EEG) hallmark of non-rapid eye movement (NREM) sleep and are believed to mediate many sleep-related functions, from memory consolidation to cortical development. Spindles differ in location, frequency, and association with slow waves, but whether this heterogeneity may reflect different physiological processes and potentially serve different functional roles remains unclear. Here we used a unique opportunity to record intracranial depth EEG and single-unit activity in multiple brain regions of neurosurgical patients to better characterize spindle activity in human sleep. We find that spindles occur across multiple neocortical regions, and less frequently also in the parahippocampal gyrus and hippocampus. Most spindles are spatially restricted to specific brain regions. In addition, spindle frequency is topographically organized with a sharp transition around the supplementary motor area between fast (13-15 Hz) centroparietal spindles often occurring with slow-wave up-states, and slow (9-12 Hz) frontal spindles occurring 200 ms later on average. Spindle variability across regions may reflect the underlying thalamocortical projections. We also find that during individual spindles, frequency decreases within and between regions. In addition, deeper NREM sleep is associated with a reduction in spindle occurrence and spindle frequency. Frequency changes between regions, during individual spindles, and across sleep may reflect the same phenomenon, the underlying level of thalamocortical hyperpolarization. Finally, during spindles neuronal firing rates are not consistently modulated, although some neurons exhibit phase-locked discharges. Overall, anatomical considerations can account well for regional spindle characteristics, while variable hyperpolarization levels can explain differences in spindle frequency.

A single pulse of Transcranial Magnetic Stimulation (TMS) generates electroencephalogram (EEG) oscillations that are thought to reflect intrinsic properties of the stimulated cortical area and its fast interactions with other cortical areas. Thus, a tool to decompose TMS-evoked oscillations in the time-frequency domain on a millisecond timescale and on a broadband frequency range may help to understand information transfer across cortical oscillators. Some recent studies have employed algorithms based on the Wavelet Transform (WT) to study TMS-evoked EEG oscillations in healthy and pathological conditions. However, these methods do not allow to describe TMS-evoked EEG oscillations with high resolution in time and frequency domains simultaneously. Here, we first develop an algorithm based on Hilbert-Huang Transform (HHT) to compute statistically significant time-frequency spectra of TMS-evoked EEG oscillations on a single trial basis. Then, we compared the performances of the HHT-based algorithm with the WT-based one by applying both of them to a set of simulated signals. Finally, we applied both algorithms to real TMS-evoked potentials recorded in healthy or schizophrenic subjects. We found that the HHT-based algorithm outperforms the WT-based one in detecting the time onset of TMS-evoked oscillations in the classical EEG bands. These results suggest that the HHT-based algorithm may be used to study the communication between different cortical oscillators on a fine time scale., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: Intracortical inhibition (SICI) and facilitation (ICF) in the human motor cortex can be measured using a paired pulse transcranial magnetic stimulation (ppTMS) protocol. Recently, a technical device has been introduced, which allows recording electroencephalographic (EEG) responses to TMS of a given scalp site. The latency, amplitude and scalp topography of such responses are considered a reflection of cortico-cortical connectivity and functional state. The aim of the present study is to better characterize the neuronal circuits underlying motor cortex connectivity as well as the mechanisms regulating its balance between inhibition and facilitation by means of EEG navigated-ppTMS coregistration., Methods: Sub-threshold and supra-threshold single and ppTMS of the left primary motor cortex were carried out during a multi-channel EEG recording on 8 healthy volunteers; the between-pulse intervals used in the paired pulse trials were 3 (for SICI) and 11 ms (for ICF). Motor evoked potentials (MEPs) from the opposite hand were simultaneously recorded., Results: Single and ppTMS induced EEG responses characterized by a sequence of negative deflections peaking at approximately 7, 18, 44, 100 and 280 ms alternated with positive peaks at approximately 13, 30, 60 and 190 ms post-TMS. Moreover, ppTMS modulated both EEG evoked activity and MEPs. Amplitude variability of EEG responses was correlated with - and therefore might partially explain - amplitude variability of MEPs., Interpretation: EEG-ppTMS is a promising tool to better characterize the neuronal circuits underlying cortical effective connectivity as well as the mechanisms regulating the balance between inhibition and facilitation within the human cortices and the corticospinal pathway., (Copyright © 2010 Elsevier Inc. All rights reserved.)