Long-Term Recording of Subthalamic Aperiodic Activities and Beta Bursts in Parkinson's Disease.

BACKGROUND: Local field potentials (LFPs) represent the summation of periodic (oscillations) and aperiodic (fractal) signals. Although previous studies showed changes in beta band oscillations and burst characteristics of the subthalamic nucleus (STN) in Parkinson's disease (PD), how aperiodic activity in the STN is related to PD pathophysiology is unknown. OBJECTIVES: The study aimed to characterize the long-term effects of STN-deep brain stimulation (DBS) and dopaminergic medications on aperiodic activities and beta bursts. METHODS: A total of 10 patients with PD participated in this longitudinal study. Simultaneous bilateral STN-LFP recordings were conducted in six separate visits during a period of 18 months using the Activa PC + S device in the off and on dopaminergic medication states. We used irregular-resampling auto-spectral analysis to separate oscillations and aperiodic components (exponent and offset) in the power spectrum of STN-LFP signals in beta band. RESULTS: Our results revealed a systematic increase in both the exponent and the offset of the aperiodic spectrum over 18 months following the DBS implantation, independent of the dopaminergic medication state of patients with PD. In contrast, beta burst durations and amplitudes were stable over time and were suppressed by dopaminergic medications. CONCLUSIONS: These findings indicate that oscillations and aperiodic activities reflect at least partially distinct yet complementary neural mechanisms, which should be considered in the design of robust biomarkers to optimize adaptive DBS. Given the link between increased gamma-aminobutyric acidergic (GABAergic) transmission and higher aperiodic activity, our findings suggest that long-term STN-DBS may relate to increased inhibition in the basal ganglia. © 2022 International Parkinson and Movement Disorder Society.

Individual slow wave events give rise to macroscopic fMRI signatures and drive the strength of the BOLD signal in human resting-state EEG-fMRI recordings.

The slow wave state is a general state of quiescence interrupted by sudden bursts of activity or so-called slow wave events (SWEs). Recently, the relationship between SWEs and blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals was assessed in rodent models which revealed cortex-wide BOLD activation. However, it remains unclear which macroscopic signature corresponds to these specific neurophysiological events in the human brain. Therefore, we analyzed simultaneous electroencephalographic (EEG)-fMRI data during human non-REM sleep. SWEs individually detected in the EEG data were used as predictors in event-related fMRI analyses to examine the relationship between SWEs and fMRI signals. For all 10 subjects we identified significant changes in BOLD activity associated with SWEs covering substantial parts of the gray matter. As demonstrated in rodents, we observed a direct relation of a neurophysiological event to specific BOLD activation patterns. We found a correlation between the number of SWEs and the spatial extent of these BOLD activation patterns and discovered that the amplitude of the BOLD response strongly depends on the SWE amplitude. As altered SWE propagation has recently been found in neuropsychiatric diseases, it is critical to reveal the brain's physiological slow wave state networks to potentially establish early imaging biomarkers for various diseases long before disease onset.

Automated real-time EEG sleep spindle detection for brain-state-dependent brain stimulation.

Sleep spindles are a hallmark electroencephalographic feature of non-rapid eye movement sleep, and are believed to be instrumental for sleep-dependent memory reactivation and consolidation. However, direct proof of their causal relevance is hard to obtain, and our understanding of their immediate neurophysiological consequences is limited. To investigate their causal role, spindles need to be targeted in real-time with sensory or non-invasive brain-stimulation techniques. While fully automated offline detection algorithms are well established, spindle detection in real-time is highly challenging due to their spontaneous and transient nature. Here, we present the real-time spindle detector, a robust multi-channel electroencephalographic signal-processing algorithm that enables the automated triggering of stimulation during sleep spindles in a phase-specific manner. We validated the real-time spindle detection method by streaming pre-recorded sleep electroencephalographic datasets to a real-time computer system running a Simulink® Real-Time™ implementation of the algorithm. Sleep spindles were detected with high levels of Sensitivity (~83%), Precision (~78%) and a convincing F1-Score (~81%) in reference to state-of-the-art offline algorithms (which reached similar or lower levels when compared with each other), for both naps and full nights, and largely independent of sleep scoring information. Detected spindles were comparable in frequency, duration, amplitude and symmetry, and showed the typical time-frequency characteristics as well as a centroparietal topography. Spindles were detected close to their centre and reliably at the predefined target phase. The real-time spindle detection algorithm therefore empowers researchers to target spindles during human sleep, and apply the stimulation method and experimental paradigm of their choice.

Real-time, closed-loop, or open-loop stimulation? Navigating a terminological jungle.

Recent advancements in real-time brain stimulation in the sleep field have led to many exciting findings. However, they have also opened up terminological ambiguities about what constitutes "open-loop", "closed-loop", and "real-time" designs. Here, we address core theoretical aspects of these terms in the hopes of strengthening future research on this topic.

Inferring Causality from Noninvasive Brain Stimulation in Cognitive Neuroscience.

Noninvasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation or transcranial direct and alternating current stimulation, are advocated as measures to enable causal inference in cognitive neuroscience experiments. Transcending the limitations of purely correlative neuroimaging measures and experimental sensory stimulation, they allow to experimentally manipulate brain activity and study its consequences for perception, cognition, and eventually, behavior. Although this is true in principle, particular caution is advised when interpreting brain stimulation experiments in a causal manner. Research hypotheses are often oversimplified, disregarding the underlying (implicitly assumed) complex chain of causation, namely, that the stimulation technique has to generate an electric field in the brain tissue, which then evokes or modulates neuronal activity both locally in the target region and in connected remote sites of the network, which in consequence affects the cognitive function of interest and eventually results in a change of the behavioral measure. Importantly, every link in this causal chain of effects can be confounded by several factors that have to be experimentally eliminated or controlled to attribute the observed results to their assumed cause. This is complicated by the fact that many of the mediating and confounding variables are not directly observable and dose-response relationships are often nonlinear. We will walk the reader through the chain of causation for a generic cognitive neuroscience NIBS study, discuss possible confounds, and advise appropriate control conditions. If crucial assumptions are explicitly tested (where possible) and confounds are experimentally well controlled, NIBS can indeed reveal cause-effect relationships in cognitive neuroscience studies.

Concurrent TMS-fMRI for causal network perturbation and proof of target engagement.

The experimental manipulation of neural activity by neurostimulation techniques overcomes the inherent limitations of correlative recordings, enabling the researcher to investigate causal brain-behavior relationships. But only when stimulation and recordings are combined, the direct impact of the stimulation on neural activity can be evaluated. In humans, this can be achieved non-invasively through the concurrent combination of transcranial magnetic stimulation (TMS) with functional magnetic resonance imaging (fMRI). Concurrent TMS-fMRI allows the assessment of the neurovascular responses evoked by TMS with excellent spatial resolution and full-brain coverage. This enables the functional mapping of both local and remote network effects of TMS in cortical as well as deep subcortical structures, offering unique opportunities for basic research and clinical applications. The purpose of this review is to introduce the reader to this powerful tool. We will introduce the technical challenges and state-of-the art solutions and provide a comprehensive overview of the existing literature and the available experimental approaches. We will highlight the unique insights that can be gained from concurrent TMS-fMRI, including the state-dependent assessment of neural responsiveness and inter-regional effective connectivity, the demonstration of functional target engagement, and the systematic evaluation of stimulation parameters. We will also discuss how concurrent TMS-fMRI during a behavioral task can help to link behavioral TMS effects to changes in neural network activity and to identify peripheral co-stimulation confounds. Finally, we will review the use of concurrent TMS-fMRI for developing TMS treatments of psychiatric and neurological disorders and suggest future improvements for further advancing the application of concurrent TMS-fMRI.

Oscillatory brain activity associated with skin conductance responses in the context of risk.

Understanding the neural correlates of risk-sensitive skin conductance responses can provide insights into their connection to emotional and cognitive processes. To provide insights into this connection, we studied the cortical correlates of risk-sensitive skin conductance peaks using electroencephalography. Fluctuations in skin conductance responses were elicited while participants played a threat-of-shock card game. Precise temporal information about skin conductance peaks was obtained by applying continuous decomposition analysis on raw electrodermal signals. Shortly preceding skin conductance peaks, we observed a decrease in oscillatory power in the frequency range between 3 and 17 Hz in occipitotemporal cortical areas. Atlas-based analysis indicated the left lingual gyrus as the source of the power decrease. The oscillatory power averaged across 3-17 Hz showed a significant negative relationship with the skin conductance peak amplitude. Our findings indicate a possible interaction between attention and threat perception.NEW & NOTEWORTHY We studied neural oscillations associated with risk-sensitive skin conductance responses. Going beyond previous studies, we applied methods with high-temporal resolution to account for the temporal properties of the sympathetic activity. Preceding skin conductance peaks, we observed decreased occipital cortex oscillatory power and a relationship between the oscillatory power decrease and the skin conductance peak amplitude. Our study suggests an interaction between attention and emotion such as threat perception reflected in skin conductance responses.

Pulsed Facilitation of Corticospinal Excitability by the Sensorimotor µ-Alpha Rhythm.

Alpha oscillations (8-14 Hz) are assumed to gate information flow in the brain by means of pulsed inhibition; that is, the phasic suppression of cortical excitability and information processing once per alpha cycle, resulting in stronger net suppression for larger alpha amplitudes due to the assumed amplitude asymmetry of the oscillation. While there is evidence for this hypothesis regarding occipital alpha oscillations, it is less clear for the central sensorimotor µ-alpha rhythm. Probing corticospinal excitability via transcranial magnetic stimulation (TMS) of the primary motor cortex and the measurement of motor evoked potentials (MEPs), we have previously demonstrated that corticospinal excitability is modulated by both amplitude and phase of the sensorimotor µ-alpha rhythm. However, the direction of this modulation, its proposed asymmetry, and its underlying mechanisms remained unclear. We therefore used real-time EEG-triggered single- and paired-pulse TMS in healthy humans of both sexes to assess corticospinal excitability and GABA-A-receptor mediated short-latency intracortical inhibition (SICI) at rest during spontaneous high amplitude µ-alpha waves at different phase angles (peaks, troughs, rising and falling flanks) and compared them to periods of low amplitude (desynchronized) µ-alpha. MEP amplitude was facilitated during troughs and rising flanks, but no phasic suppression was observed at any time, nor any modulation of SICI. These results are best compatible with sensorimotor µ-alpha reflecting asymmetric pulsed facilitation but not pulsed inhibition of motor cortical excitability. The asymmetric excitability with respect to rising and falling flanks of the µ-alpha cycle further reveals that voltage differences alone cannot explain the impact of phase.SIGNIFICANCE STATEMENT The pulsed inhibition hypothesis, which assumes that alpha oscillations actively inhibit neuronal processing in a phasic manner, is highly influential and has substantially shaped our understanding of these oscillations. However, some of its basic assumptions, in particular its asymmetry and inhibitory nature, have rarely been tested directly. Here, we explicitly investigated the asymmetry of modulation and its direction for the human sensorimotor µ-alpha rhythm. We found clear evidence of pulsed facilitation, but not inhibition, in the human motor cortex, challenging the generalizability of the pulsed inhibition hypothesis and advising caution when interpreting sensorimotor µ-alpha changes in the sensorimotor system. This study also demonstrates how specific assumptions about the neurophysiological underpinnings of cortical oscillations can be experimentally tested noninvasively in humans.

The non-transcranial TMS-evoked potential is an inherent source of ambiguity in TMS-EEG studies.

Transcranial Magnetic Stimulation (TMS) excites populations of neurons in the stimulated cortex, and the resulting activation may spread to connected brain regions. The distributed cortical response can be recorded with electroencephalography (EEG). Since TMS also stimulates peripheral sensory and motor axons and generates a loud "click" sound, the TMS-evoked EEG potentials (TEPs) reflect not only neural activity induced by transcranial neuronal excitation but also neural activity due to somatosensory and auditory processing. In 17 healthy young individuals, we systematically assessed the contribution of multisensory peripheral stimulation to TEPs using a TMS-compatible EEG system. Real TMS was delivered with a figure-of-eight coil over the left para-median posterior parietal cortex or superior frontal gyrus with the coil being oriented perpendicularly or in parallel to the target gyrus. We also recorded the EEG responses evoked by realistic sham stimulation over the posterior parietal and superior frontal cortex, mimicking the auditory and somatosensory sensations evoked by real TMS. We applied state-of-the-art procedures to attenuate somatosensory and auditory confounds during real TMS, including the placement of a foam layer underneath the coil and auditory noise masking. Despite these precautions, the temporal and spatial features of the cortical potentials evoked by real TMS at the prefrontal and parietal site closely resembled the cortical potentials evoked by realistic sham TMS, both for early and late TEP components. Our findings stress the need to include a peripheral multisensory control stimulation in the design of TMS-EEG studies to enable a dissociation between truly transcranial and non-transcranial components of TEPs.

Frontoparietal Structural Connectivity Mediates the Top-Down Control of Neuronal Synchronization Associated with Selective Attention.

Neuronal synchronization reflected by oscillatory brain activity has been strongly implicated in the mechanisms supporting selective gating. We here aimed at identifying the anatomical pathways in humans supporting the top-down control of neuronal synchronization. We first collected diffusion imaging data using magnetic resonance imaging to identify the medial branch of the superior longitudinal fasciculus (SLF), a white-matter tract connecting frontal control areas to parietal regions. We then quantified the modulations in oscillatory activity using magnetoencephalography in the same subjects performing a spatial attention task. We found that subjects with a stronger SLF volume in the right compared to the left hemisphere (or vice versa) also were the subjects who had a better ability to modulate right compared to left hemisphere alpha and gamma band synchronization, with the latter also predicting biases in reaction time. Our findings implicate the medial branch of the SLF in mediating top-down control of neuronal synchronization in sensory regions that support selective attention.

Combining non-invasive transcranial brain stimulation with neuroimaging and electrophysiology: Current approaches and future perspectives.

Non-invasive transcranial brain stimulation (NTBS) techniques such as transcranial magnetic stimulation (TMS) and transcranial current stimulation (TCS) are important tools in human systems and cognitive neuroscience because they are able to reveal the relevance of certain brain structures or neuronal activity patterns for a given brain function. It is nowadays feasible to combine NTBS, either consecutively or concurrently, with a variety of neuroimaging and electrophysiological techniques. Here we discuss what kind of information can be gained from combined approaches, which often are technically demanding. We argue that the benefit from this combination is twofold. Firstly, neuroimaging and electrophysiology can inform subsequent NTBS, providing the required information to optimize where, when, and how to stimulate the brain. Information can be achieved both before and during the NTBS experiment, requiring consecutive and concurrent applications, respectively. Secondly, neuroimaging and electrophysiology can provide the readout for neural changes induced by NTBS. Again, using either concurrent or consecutive applications, both "online" NTBS effects immediately following the stimulation and "offline" NTBS effects outlasting plasticity-inducing NTBS protocols can be assessed. Finally, both strategies can be combined to close the loop between measuring and modulating brain activity by means of closed-loop brain state-dependent NTBS. In this paper, we will provide a conceptual framework, emphasizing principal strategies and highlighting promising future directions to exploit the benefits of combining NTBS with neuroimaging or electrophysiology.

Transcranial magnetic stimulation of primary motor cortex elicits an immediate transcranial evoked potential.

BACKGROUND: Transcranial evoked potentials (TEPs) measured via electroencephalography (EEG) are widely used to study the cortical responses to transcranial magnetic stimulation (TMS). Immediate transcranial evoked potentials (i-TEPs) have been obscured by pulse and muscular artifacts. Thus, the TEP peaks that are commonly reported have latencies that are too long to be caused by direct excitation of cortical neurons. METHODS: In 25 healthy individuals, we recorded i-TEPs evoked by a single biphasic TMS pulse targeting the primary motor hand area (M1HAND) or parietal or midline control sites. Sampling EEG at 50 kHz enabled us to reduce the duration of the TMS pulse artifact to a few milliseconds, while minor adjustments of the TMS coil tilt or position enabled us to avoid cranial muscular twitches during the experiment. RESULTS: We observed an early positive EEG deflection starting after approx. 2 ms followed by a series of superimposed peaks with an inter-peak interval of ∼1.1-1.4 ms in multiple electrodes surrounding the stimulated sensorimotor region. This multi-peak i-TEP response was only evoked by TMS of the M1HAND region and was modified by changes in stimulation intensity and current direction. DISCUSSION: Single-pulse TMS of the M1HAND evokes an immediate local multi-peak response at the cortical site of stimulation. Our results suggest that the observed i-TEP patterns are genuine cortical responses evoked by TMS caused by synchronized excitation of pyramidal neurons in the targeted precentral cortex. This notion needs to be corroborated in future studies, including further investigations into the potential contribution of instrumental or physiological artifacts.

Network perturbation-based biomarkers of depression and treatment response.

Using concurrent TMS-EEG, Han et al.1 identified temporal and spectral signatures of depression in a prefrontal-orbitofrontal-hippocampal network, which renormalized after rTMS. This highlights the relevance of causal network perturbation for the assessment of disease-related network states and their therapeutic modulation.

Repetitive sensorimotor mu-alpha phase-targeted afferent stimulation produces no phase-dependent plasticity related changes in somatosensory evoked potentials or sensory thresholds.

Phase-dependent plasticity has been proposed as a neurobiological mechanism by which oscillatory phase-amplitude cross-frequency coupling mediates memory process in the brain. Mimicking this mechanism, real-time EEG oscillatory phase-triggered transcranial magnetic stimulation (TMS) has successfully induced LTP-like changes in corticospinal excitability in the human motor cortex. Here we asked whether EEG phase-triggered afferent stimulation alone, if repetitively applied to the peaks, troughs, or random phases of the sensorimotor mu-alpha rhythm, would be sufficient to modulate the strength of thalamocortical synapses as assessed by changes in somatosensory evoked potential (SEP) N20 and P25 amplitudes and sensory thresholds (ST). Specifically, we applied 100 Hz triplets of peripheral electrical stimulation (PES) to the thumb, middle, and little finger of the right hand in pseudorandomized trials, with the afferent input from each finger repetitively and consistently arriving either during the cortical mu-alpha trough or peak or at random phases. No significant changes in SEP amplitudes or ST were observed across the phase-dependent PES intervention. We discuss potential limitations of the study and argue that suboptimal stimulation parameter choices rather than a general lack of phase-dependent plasticity in thalamocortical synapses are responsible for this null finding. Future studies should further explore the possibility of phase-dependent sensory stimulation.

Closing the loop between brain and electrical stimulation: towards precision neuromodulation treatments.

One of the most critical challenges in using noninvasive brain stimulation (NIBS) techniques for the treatment of psychiatric and neurologic disorders is inter- and intra-individual variability in response to NIBS. Response variations in previous findings suggest that the one-size-fits-all approach does not seem the most appropriate option for enhancing stimulation outcomes. While there is a growing body of evidence for the feasibility and effectiveness of individualized NIBS approaches, the optimal way to achieve this is yet to be determined. Transcranial electrical stimulation (tES) is one of the NIBS techniques showing promising results in modulating treatment outcomes in several psychiatric and neurologic disorders, but it faces the same challenge for individual optimization. With new computational and methodological advances, tES can be integrated with real-time functional magnetic resonance imaging (rtfMRI) to establish closed-loop tES-fMRI for individually optimized neuromodulation. Closed-loop tES-fMRI systems aim to optimize stimulation parameters based on minimizing differences between the model of the current brain state and the desired value to maximize the expected clinical outcome. The methodological space to optimize closed-loop tES fMRI for clinical applications includes (1) stimulation vs. data acquisition timing, (2) fMRI context (task-based or resting-state), (3) inherent brain oscillations, (4) dose-response function, (5) brain target trait and state and (6) optimization algorithm. Closed-loop tES-fMRI technology has several advantages over non-individualized or open-loop systems to reshape the future of neuromodulation with objective optimization in a clinically relevant context such as drug cue reactivity for substance use disorder considering both inter and intra-individual variations. Using multi-level brain and behavior measures as input and desired outcomes to individualize stimulation parameters provides a framework for designing personalized tES protocols in precision psychiatry.

TMS combined with EEG: Recommendations and open issues for data collection and analysis.

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.

The Brain Electrophysiological recording & STimulation (BEST) toolbox.

Non-invasive brain stimulation (NIBS) experiments involve many recurring procedures that are not sufficiently standardized in the community. Given the diversity in experimental design and experience of the investigators, automated but yet flexible data collection and analysis tools are needed to increase objectivity, reliability, and reproducibility of NIBS experiments. The Brain Electrophysiological recording and STimulation (BEST) Toolbox is a MATLAB-based, open-source software with graphical user interface that allows users to design, run, and share freely configurable multi-protocol, multi-session NIBS studies, including transcranial magnetic, electric, and ultrasound stimulation (TMS, tES, TUS). Interfacing with a variety of recording and stimulation devices, the BEST toolbox analyzes EMG and EEG data, and configures stimulation parameters on-the-fly to facilitate closed-loop protocols and real-time applications. Its functionality is continuously expanded and includes e.g., TMS motor hotspot search, threshold estimation, motor evoked potential (MEP) and TMS-evoked EEG potential (TEP) measurements, dose-response curves, paired-pulse and dual-coil TMS, rTMS interventions.

No robust online effects of transcranial direct current stimulation on corticospinal excitability.

Transcranial direct current stimulation (tDCS) has been used for over twenty years to modulate cortical (particularly motor corticospinal) excitability both during (online) and outlasting (offline) the stimulation, with the former effects associated to the latter. However, tDCS effects are highly variable, partially because stimulation intensity is commonly not adjusted individually (in contrast to transcranial magnetic stimulation, TMS). In Experiment 1, we therefore explored an empirical approach of personalizing tDCS intensity for the primary motor cortex (M1) based on dose-response curves (DRCs), individually relating tDCS Intensity (in steps from 0.3 to 2.0 mA) and Polarity (anodal, cathodal) to the online modulation of concurrent TMS motor evoked potentials (MEP), assessing DRC reliability across two separate days. No robust DRCs could be observed, neither at the individual nor at the group level, with the only robust effect being a (paradoxical) MEP facilitation during cathodal tDCS at 2.0 mA, but no modulation at traditional intensities of or near 1 mA. In Experiment 2, we therefore attempted to replicate the classical bidirectional online MEP modulation during 1 mA tDCS that had been reported by several of the early seminal tDCS papers. We either closely recreated stimulation parameters and temporal protocol of these original studies (Experiment 2A) or slightly modernized them according to current standards (Experiment 2B). In neither experiment did we observed any significant online MEP modulation. We conclude that an empirical titration of individually effective tDCS intensities may not be feasible as online tDCS effects do not appear to be sufficiently robust.

A checklist for assessing the methodological quality of concurrent tES-fMRI studies (ContES checklist): a consensus study and statement.

Low-intensity transcranial electrical stimulation (tES), including alternating or direct current stimulation, applies weak electrical stimulation to modulate the activity of brain circuits. Integration of tES with concurrent functional MRI (fMRI) allows for the mapping of neural activity during neuromodulation, supporting causal studies of both brain function and tES effects. Methodological aspects of tES-fMRI studies underpin the results, and reporting them in appropriate detail is required for reproducibility and interpretability. Despite the growing number of published reports, there are no consensus-based checklists for disclosing methodological details of concurrent tES-fMRI studies. The objective of this work was to develop a consensus-based checklist of reporting standards for concurrent tES-fMRI studies to support methodological rigor, transparency and reproducibility (ContES checklist). A two-phase Delphi consensus process was conducted by a steering committee (SC) of 13 members and 49 expert panelists through the International Network of the tES-fMRI Consortium. The process began with a circulation of a preliminary checklist of essential items and additional recommendations, developed by the SC on the basis of a systematic review of 57 concurrent tES-fMRI studies. Contributors were then invited to suggest revisions or additions to the initial checklist. After the revision phase, contributors rated the importance of the 17 essential items and 42 additional recommendations in the final checklist. The state of methodological transparency within the 57 reviewed concurrent tES-fMRI studies was then assessed by using the checklist. Experts refined the checklist through the revision and rating phases, leading to a checklist with three categories of essential items and additional recommendations: (i) technological factors, (ii) safety and noise tests and (iii) methodological factors. The level of reporting of checklist items varied among the 57 concurrent tES-fMRI papers, ranging from 24% to 76%. On average, 53% of checklist items were reported in a given article. In conclusion, use of the ContES checklist is expected to enhance the methodological reporting quality of future concurrent tES-fMRI studies and increase methodological transparency and reproducibility.

Acute changes in motor cortical excitability during slow oscillatory and constant anodal transcranial direct current stimulation.

Transcranial oscillatory current stimulation has recently emerged as a noninvasive technique that can interact with ongoing endogenous rhythms of the human brain. Yet, there is still little knowledge on how time-varied exogenous currents acutely modulate cortical excitability. In ten healthy individuals we used on-line single-pulse transcranial magnetic stimulation (TMS) to search for systematic shifts in corticospinal excitability during anodal sleeplike 0.8-Hz slow oscillatory transcranial direct current stimulation (so-tDCS). In separate sessions, we repeatedly applied 30-s trials (two blocks at 20 min) of either anodal so-tDCS or constant tDCS (c-tDCS) to the primary motor hand area during quiet wakefulness. Simultaneously and time-locked to different phase angles of the slow oscillation, motor-evoked potentials (MEPs) as an index of corticospinal excitability were obtained in the contralateral hand muscles 10, 20, and 30 s after the onset of tDCS. MEPs were also measured off-line before, between, and after both stimulation blocks to detect any lasting excitability shifts. Both tDCS modes increased MEP amplitudes during stimulation with an attenuation of the facilitatory effect toward the end of a 30-s tDCS trial. No phase-locking of corticospinal excitability to the exogenous oscillation was observed during so-tDCS. Off-line TMS revealed that both c-tDCS and so-tDCS resulted in a lasting excitability increase. The individual magnitude of MEP facilitation during the first tDCS trials predicted the lasting MEP facilitation found after tDCS. We conclude that sleep slow oscillation-like excitability changes cannot be actively imposed on the awake cortex with so-tDCS, but phase-independent on-line as well as off-line facilitation can reliably be induced.