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Rogasch, N. C.

Publications and source records attributed to Rogasch, N. C..

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Designing and comparing cleaning pipelines for TMS-EEG data: a theoretical overview and practical example

Combining transcranial magnetic stimulation (TMS) with electroencephalography (EEG) is growing in popularity as a method for probing the reactivity and connectivity of neural circuits in basic and clinical research. However, using EEG to measure the neural responses to TMS is challenging due to the unique artifacts introduced by combining the two techniques. In this paper, we overview the artifacts present in TMS-EEG data and the offline cleaning methods used to suppress these unwanted signals. We then describe how open science practices, including the development of open-source toolboxes designed for TMS-EEG analysis (e.g., TESA - the TMS-EEG signal analyser), have improved the availability and reproducibility of TMS-EEG cleaning methods. We provide theoretical and practical considerations for designing TMS-EEG cleaning pipelines and then give an example of how to compare different pipelines using TESA. We show that changing even a single step in a pipeline designed to suppress decay artifacts results in TMS-evoked potentials (TEPs) with small differences in amplitude and spatial topography. The variability in TEPs resulting from the choice of cleaning pipeline has important implications for comparing TMS-EEG findings between research groups which use different online and offline approaches. Finally, we discuss the challenges of validating cleaning pipelines and recommend that researchers compare outcomes from TMS-EEG experiments using multiple pipelines to ensure findings are not related to the choice of cleaning methods. We conclude that the continued improvement, availability, and validation of cleaning pipelines is essential to ensure TMS-EEG reaches its full potential as a method for studying human neurophysiology. HighlightsO_LIConcurrent TMS-EEG is challenging due to artifacts in the recorded signals. C_LIO_LIWe overview offline methods for cleaning TEPs and provide tips on pipeline design. C_LIO_LIWe use TESA to compare pipelines and show changing a single step alters TEPs. C_LIO_LIWe discuss the challenges in validating pipelines for TMS-EEG analysis. C_LIO_LIWe suggest using multiple pipelines to minimise the impact of method choice on TEPs. C_LI

neuroscience↗

The influence of somatosensory and auditory evoked potentials on concurrent transcranial-magnetic stimulation electroencephalography recordings

BackgroundTranscranial magnetic stimulation (TMS) evoked potentials (TEPs) can be used to index cortical excitability. However, it remains unclear to what extent TEPs reflect somatosensory and auditory-evoked potentials which arise from the scalp sensation and click of the TMS coil, as opposed to transcranial stimulation of cortical circuits. ObjectivesThe present study had two aims; a) to determine the extent to which sensory potentials contaminate TEPs using a spatially matched sham condition, and b) to determine whether sensory potentials reflect auditory or somatosensory potentials alone, or a combination of the two. MethodsTwenty healthy participants received active or sham stimulation, with the latter consisting of the click of a sham coil combined with scalp electrical stimulation. Earplugs/headphones were used to suppress the TMS click noise. Two additional control conditions i) electrical stimulation alone and ii) auditory stimulation alone were included in a subset of 13 participants. ResultsSignals from active and sham stimulation were correlated in spatial and temporal domains, especially >70ms post-stimulation. Relative to auditory or electrical stimulation alone, combined (sham) stimulation resulted in a) larger evoked responses b) stronger correlations with active stimulation and c) a signal that could not be explained by the linear sum of electrical and auditory stimulation alone. ConclusionsSensory potentials can confound data interpretations of TEPs at timepoints >70ms post-TMS, while earlier timepoints appear reflective of cortical excitability. Furthermore, contamination of TEPs cannot be explained by auditory or somatosensory potentials alone, but instead reflects a non-linear interaction between both sources. Future studies may benefit from controlling for sensory contamination using sham conditions that are spatially matched to active TMS, and which consist of combined auditory and somatosensory stimulation.

neuroscience↗

Age differences in aperiodic neural activity measured with resting EEG

Previous research using electroencephalography (EEG) and magnetoencephalography (MEG) has shown that neural oscillatory activity within the alpha band (8-12 Hz) becomes slower and lower in amplitude with advanced age. However, most studies have focused on quantifying age-related differences in periodic oscillatory activity with little consideration of the influence of aperiodic activity on these measures. The aim of this study was to investigate age differences in aperiodic activity inherent in the resting EEG signal. We assessed aperiodic activity in 85 healthy younger adults (mean age: 22.2 years, SD: 3.9, age range: 18-35, 37 male) and 92 healthy older adults (mean age: 66.1 years, SD: 8.2, age range 50-86, 53 male) by fitting the 1/f-like background activity evident in EEG power spectra using the fitting oscillations & one over f (FOOOF) toolbox. Across the scalp, the aperiodic exponent and offset were smaller in older compared to younger participants, reflecting a flatter 1/f-like slope and a downward broadband shift in the power spectra with age. Before correcting for aperiodic activity, older adults showed slower peak alpha frequency and reduced peak alpha power relative to younger adults. After correcting for aperiodic activity, peak alpha frequency remained slower in older adults; however, peak alpha power no longer differed statistically between age groups. The large sample size utilized in this study, as well as the depth of analysis, provides further evidence that the aperiodic component of the resting EEG signal is altered with aging and should be considered when investigating neural oscillatory activity.

neuroscience↗

No evidence for changes in GABA concentration, functional connectivity, or working memory following continuous theta burst stimulation over dorsolateral prefrontal cortex

Continuous theta burst stimulation (cTBS) is thought to reduce cortical excitability and modulate functional connectivity, possibly by altering cortical inhibition at the site of stimulation. However, most evidence comes from the motor cortex and it remains unclear whether similar effects occur following stimulation over other brain regions. We assessed whether cTBS over left dorsolateral prefrontal cortex altered gamma aminobutyric acid (GABA) concentration, functional connectivity and brain dynamics at rest, and brain activation and memory performance during a working memory task. Seventeen healthy individuals participated in a randomised, sham-controlled, cross-over experiment. Before and after either real or sham cTBS, magnetic resonance spectroscopy was obtained at rest to measure GABA concentrations. Functional magnetic resonance imaging (fMRI) was also recorded at rest and during an n-back working memory task to measure functional connectivity, regional brain activity (low-frequency fluctuations), and task-related patterns of brain activity. We could not find evidence for changes in GABA concentration (P=0.66, Bayes factor [BF10]=0.07), resting-state functional connectivity (P(FWE)>0.05), resting-state low-frequency fluctuations (P=0.88, BF10=0.04), blood-oxygen level dependent activity during the n-back task (P(FWE) >0.05), or working memory performance (P=0.13, BF10=0.05) following real or sham cTBS. Our findings add to a growing body of literature suggesting the effects of cTBS are highly variable between individuals and question the notion that cTBS is a universal inhibitory paradigm.

neuroscience↗

A single- and paired-pulse TMS-EEG investigation of the N100 and long interval cortical inhibition in autism spectrum disorder

BackgroundThere is evidence to suggest a disruption of gamma-aminobutyric acid (GABA) in autism spectrum disorder (ASD), but findings are mixed. Concurrent electroencephalography and transcranial magnetic stimulation (TMS-EEG) provides a novel method by which to probe GABA-mediated cortical inhibition. MethodsWith a particular focus on GABAB-ergic mechanisms, we investigated the N100 peak of the TMS evoked potential (TEP), as well as long interval cortical inhibition (LICIEEG) in adults with ASD (n = 23; 12 female) without intellectual disability, and a neurotypical comparison group (n =22; 12 female) matched for age, sex, and IQ. Seventy-five single-(spTMS) and 75 paired-(ppTMS; 100 ms inter-stimulus-interval) pulses were applied to the right primary motor cortex (M1), right temporoparietal junction (TPJ), and right dorsolateral prefrontal cortex (DLPFC) while EEG was recorded from 20 scalp electrodes. Additionally, electromyography (EMG) was used to investigate corticospinal inhibition following ppTMS to M1 (LICIEMG). ResultsThere were no group differences in the N100 amplitude or latency following spTMS. LICI outcomes following ppTMS, as measured by either EEG or EMG, also did not differ between groups. These findings were further supported by Bayesian analyses, which provided weak-moderate support for the null hypothesis. LimitationsData presented here reflect adults without intellectual disability, and the generalisability of these results is therefore limited. ConclusionsThe findings of this study argue against GABAB-ergic impairment in adults with ASD without intellectual disability, at least at the cortical regions examined. Further research investigating these mechanisms in ASD at various ages, with varying degrees of symptomatology, and at different brain sites is an important factor in understating the role of GABA in the neuropathophysiology of ASD.

neuroscience↗

Dynamical consequences of regional heterogeneity in the brains transcriptional landscape

Brain regions vary in their molecular and cellular composition, but how this heterogeneity shapes neuronal dynamics is unclear. Here, we investigate the dynamical consequences of regional heterogeneity using a biophysical model of whole-brain functional magnetic resonance imaging (MRI) dynamics in humans. We show that models in which transcriptional variations in excitatory and inhibitory receptor (E:I) gene expression constrain regional heterogeneity more accurately reproduce the spatiotemporal structure of empirical functional connectivity estimates than do models constrained by global gene expression profiles and MRI-derived estimates of myeloarchitecture. We further show that regional heterogeneity is essential for yielding both ignition-like dynamics, which are thought to support conscious processing, and a wide variance of regional activity timescales, which supports a broad dynamical range. We thus identify a key role for E:I heterogeneity in generating complex neuronal dynamics and demonstrate the viability of using transcriptional data to constrain models of large-scale brain function.

neuroscience↗

Assessing cerebellar-cortical connectivity using concurrent TMS-EEG: A Feasibility Study

BackgroundCombined single-pulse transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been used to probe the features of local networks in the cerebral cortex. Here we investigate whether we can use this approach to explore long-range connections between the cerebellum and cerebral cortex. ObjectiveTo assess the feasibility of using cerebellar TMS-EEG for the exploration of cerebellar-cerebral network dynamics. MethodsTen healthy adults received single-pulse suprathreshold TMS to the cerebellum and an occipital/parietal control site with double-cone and figure-of-eight coils while cerebral activity was recorded. A multisensory electrical control condition was used to simulate the sensation of the double-cone coil at the cerebellar site. Two cleaning pipelines were compared, and the spatiotemporal relationships of the EEG output between conditions were examined at sensor and source levels. ResultsCerebellar stimulation with the double-cone coil resulted in large artefacts in the EEG trace. The addition of SOUND filtering to the cleaning pipeline improved the signal such that further analyses could be undertaken. The cortical potentials evoked by the active TMS conditions showed strong relationships with the responses to the multisensory control condition after ~50 ms. A distinct parietal component at ~42 ms was found following cerebellar double-cone stimulation. ConclusionsCerebellar double-cone stimulation produces large artefacts in the EEG. Cerebellar-specific responses could not be reliably differentiated from sensory evoked potentials after ~50 ms. While evoked potentials differed across conditions at early latencies, it is unclear as to whether these represented TMS-related network activation of the cerebellarthalamocortical tract, or whether components were dominated by sensory contamination and/or coil-driven artefacts. Further work will be required to clarify the specific contribution of cerebellar-cortical connectivity to the observed early latency signals.

neuroscience↗

The effects of multi-day rTMS and cardiorespiratory fitness on working memory and local GABA concentration

Working memory (WM) refers to the capacity to temporarily retain and manipulate finite amounts of information; a critical process in complex behaviours such as reasoning, comprehension, and learning. This cognitive function is supported by a parietal-prefrontal network and linked to the activity of key neurotransmitters, such as gamma-aminobutyric acid (GABA). Impairments in WM are seen in a range of psychiatric and neurological disorders, and there are currently no effective treatments. In this study, we analysed secondary outcome measures from a trial investigating the effects of multi-day rTMS on cognition. Participants received four days of 20 Hz rTMS to an individualised region of left parietal cortex in one week, and an individualised region of pre-supplementary motor area (pre-SMA) in a separate week. We assessed changes to WM function before and after each week of stimulation (N = 39), and changes to GABA concentration before and after stimulation in week one using MR spectroscopy (N = 18 per stimulation condition). We hypothesised that parietal rTMS would enhance WM and alter GABA concentration at the site of stimulation, but this was not observed. Instead, we report some evidence of improved WM function following the first week of pre-SMA rTMS stimulation, and a generalised increase in GABA concentration across both parietal and pre-SMA voxels following pre-SMA rTMS. Additionally, we found that higher cardiorespiratory fitness was associated with greater WM improvement following pre-SMA stimulation. This study does not support the use of parietal multi-day rTMS for the enhancement of working memory. In contrast, the results suggest that increasing cardiorespiratory fitness may provide a novel approach to enhance the effects of pre-SMA rTMS on cognition.

neuroscience↗

The effects of regular aerobic exercise on hippocampal structure and function

Regular exercise has numerous benefits for brain health, including the structure and function of the hippocampus. The hippocampus plays a critical role in memory function, and is altered in a number of psychiatric disorders associated with memory impairments (e.g. depression and schizophrenia), as well as healthy ageing. While many studies have focussed on how regular exercise may improve hippocampal integrity in older individuals, less is known about these effects in young to middle-aged adults. Therefore, we assessed the associations of regular exercise and cardiorespiratory fitness with hippocampal structure and function in these age groups. We recruited 40 healthy young to middle-aged adults, comprised of two groups (n = 20) who self-reported either high or low levels of exercise, according to World Health Organisation guidelines. We assessed cardiorespiratory fitness using a graded exercise test (VO2max) and hippocampal structure via manual tracing of T1-weighted magnetic resonance images. We also assessed hippocampal function using magnetic resonance spectroscopy to derive estimates of NAA concentration and hippocampal-dependent associative memory and pattern separation tasks. We observed evidence of increased N-acetyl-aspartate concentration and associative memory performance in individuals engaging in high levels of exercise. However, no differences in hippocampal volume or pattern separation capacity were observed between groups. Cardiorespiratory fitness was positively associated with hippocampal volume (left, right, and bilateral), N-acetyl-aspartate concentration, and pattern separation. However, no association was observed between cardiorespiratory fitness and associative memory. Therefore, we provide evidence that higher levels of exercise and cardiorespiratory fitness are associated with improved hippocampal structure and function. Exercise may provide a low-risk, effective method of improving hippocampal integrity in an early-to-mid-life stage.

neuroscience↗

The role of alpha power in the suppression of anticipated distractors during verbal working memory

As working memory (WM) is limited in capacity, it is important to direct neural resources towards processing task-relevant information while ignoring distractors. Neural oscillations in the alpha frequency band (8-12 Hz) have been suggested to play a role in the inhibition of task-irrelevant information during WM, although results are mixed, possibly due to differences in the type of WM task employed. Here, we examined the role of alpha power in inhibition of anticipated distractors of varying strength using a modified Sternberg task where the encoding and retention periods were temporally separated. We recorded EEG while 20 young adults completed the task and found: 1) slower reaction times in strong distractor trials compared to weak distractor trials; 2) increased alpha power in posterior regions from baseline prior to presentation of a distractor regardless of condition; and 3) no differences in alpha power between strong and weak distractor conditions. Our results suggest that parieto-occipital alpha power is increased prior to a distractor. However we could not find evidence that alpha power is further modulated by distractor strength.

neuroscience↗

Modeling motor-evoked potentials from neural field simulations of transcranial magnetic stimulation

ObjectiveTo develop a population-based biophysical model of motor-evoked potentials (MEPs) following transcranial magnetic stimulation (TMS). MethodsWe combined an existing MEP model with population-based cortical modeling. Layer 2/3 excitatory and inhibitory neural populations, modeled with neural-field theory, are stimulated with TMS and feed layer 5 corticospinal neurons, which also couple directly but weakly to the TMS pulse. The layer 5 output controls mean motoneuron responses, which generate a series of single motor-unit action potentials that are summed to estimate a MEP. ResultsA MEP waveform was generated comparable to those observed experimentally. The model captured TMS phenomena including a sigmoidal input-output curve, common paired pulse effects (short interval intracortical inhibition, intracortical facilitation, long interval intracortical inhibition) including responses to pharmacological interventions, and a cortical silent period. Changes in MEP amplitude following theta burst paradigms were observed including variability in outcome direction. ConclusionsThe model reproduces effects seen in common TMS paradigms. SignificanceThe model allows population-based modeling of changes in cortical dynamics due to TMS protocols to be assessed in terms of changes in MEPs, thus allowing a clear comparison between population-based modeling predictions and typical experimental outcome measures. HighlightsO_LIA model of motor-evoked potential formation gives a realistic electromyogram in response to TMS. C_LIO_LIThe model reproduces effects of SICI, ICF and LICI. C_LIO_LIA link between existing neural field modeling and realistic outcome measures of TMS is provided. C_LI

biophysics↗

Load-dependent modulation of alpha oscillations during working memory encoding and retention in young and older adults

Working memory (WM) is vulnerable to age-related decline, particularly under high loads. Visual alpha oscillations contribute to WM performance in younger adults, and although alpha decreases in power and frequency with age, it is unclear if alpha activity supports WM in older adults. We recorded electroencephalography (EEG) while 24 younger (aged 18-35 years) and 30 older (aged 50-86) adults performed a modified Sternberg task with varying load conditions. Older adults demonstrated slower reaction times at all loads, but there were no significant age differences in accuracy. Regardless of age, alpha power decreased, and alpha frequency increased with load during encoding, and the magnitude of alpha suppression during retention was larger at higher loads. While alpha power during retention was lower than fixation in older, but not younger adults, the relative change from fixation was not significantly different between age groups. Individual differences in alpha power did not predict performance for either age groups or at any WM loads. Future research should elaborate the functional significance of alpha power and frequency changes that accompany WM performance in cognitive ageing.

neuroscience↗

Do TMS evoked responses measured from scalp and hand represent the same cortical mechanisms?

Transcranial magnetic stimulation (TMS) is a powerful tool to investigate cortical circuits. Changes in cortical excitability following TMS are typically assessed by measuring changes in either conditioned motor-evoked potentials (MEPs) following paired-pulse TMS over motor cortex or evoked potentials measured with electroencephalography following single-pulse TMS (TEPs). However, it is unclear whether these two measures of cortical excitability index the same cortical response. Twenty-four healthy participants received local and interhemispheric paired-pulse TMS over motor cortex with eight inter-pulse intervals, suband suprathreshold conditioning intensities, and two different pulse waveforms, while MEPs were recorded from a hand muscle. TEPs were also recorded in response to single-pulse TMS using the conditioning pulse alone. The relationships between TEPs and conditioned-MEPs were evaluated using metrics sensitive to both their magnitude at each timepoint and their overall shape across time. The impacts of undesired sensory potentials resulting from TMS pulse and muscle contractions were also assessed on both measures. Both conditioned-MEPs and TEPs were sensitive to re-afferent somatosensory activity following motor-evoked responses, but over different post-stimulus timepoints. Moreover, the amplitude of low-frequency oscillations in TEPs was strongly correlated with the sensory potentials, whereas early and local high-frequency responses showed minimal relationships. Accordingly, conditioned-MEPs did not correlate with TEPs in the time domain but showed high shape similarity with the amplitude of high-frequency oscillations in TEPs. Therefore, despite the effects of sensory confounds, the TEP and MEP measures share a response component, suggesting that they index a similar cortical response and perhaps the same neuronal populations.

neuroscience↗

Characterizing and minimizing the contribution of sensory inputs to TMS-evoked potentials

BackgroundTranscranial magnetic stimulation (TMS) evokes voltage deflections in electroencephalographic (EEG) recordings, known as TMS-evoked potentials (TEPs), which are increasingly used to study brain dynamics. However, the extent to which TEPs reflect activity directly evoked by magnetic rather than sensory stimulation is unclear.\n\nObjectiveTo characterize and minimize the contribution of sensory inputs to TEPs.\n\nMethodsTwenty-four healthy participants received TMS over the motor cortex using two different intensities (below and above cortical motor threshold) and waveforms (monophasic, biphasic). TMS was also applied over the shoulder as a multisensory control condition. Common sensory attenuation measures, including coil padding and noise masking, were adopted. We examined spatiotemporal relationships between the EEG responses to the scalp and shoulder stimulations at sensor and source levels. Furthermore, we compared three different filters (independent component analysis, signal-space projection with source informed reconstruction (SSP-SIR) and linear regression) designed to attenuate the impact of sensory inputs on TEPs.\n\nResultsThe responses to the scalp and shoulder stimulations were correlated in both temporal and spatial domains, especially after [~]60 ms, regardless of the intensity and stimuli waveform. Among the three filters, SSP-SIR showed the best trade-off between removing sensory-related signals while preserving data not related to the control condition.\n\nConclusionsThe findings demonstrate that TEPs elicited by motor cortex TMS reflect a combination of transcranially and peripherally evoked brain responses despite adopting sensory attenuation methods during experiments, thereby highlighting the importance of adopting sensory control conditions in TMS-EEG studies. Offline filters may help to isolate the transcranial component of the TEP from its peripheral component, but only if these components express different spatiotemporal patterns. More realistic control conditions may help to improve the characterization and attenuation of sensory inputs to TEPs, especially in early responses.

neuroscience↗

Mindfulness meditators do not show differences in electrophysiological measures of error processing

Mindfulness meditation may improve attention and self-regulation. One component of attention and self-regulation that may allow these improvements is performance monitoring. Neural correlates of performance monitoring can be objectively measured with electroencephalogram (EEG) via the error related negativity (ERN) and error positivity (Pe). Previous research assessing the ERN and Pe in meditators has resulted in inconsistent findings; some have reported alteration in peak amplitudes from both very brief meditation practice and long-term meditation practice, while others have failed to provide evidence for differences in the ERN or Pe. However, recently developed EEG analysis techniques allow for more rigorous analyses than have been used in past investigations. The current study measured the ERN and Pe, as well as post-error alpha suppression, during a Go/Nogo task, and emotional and colour Stroop tasks. The measures were compared between 22 experienced meditators (mean of 8 years of practice) and 20 healthy controls. The results suggested no differences in the ERN, Pe, or post-error alpha suppression (all p > 0.05), even when varying multiple analysis parameters. The study showed equivalent statistical power to previous research, and > 85% power to detect medium effect sizes present in previous research. Bayes Factor analysis indicated the null hypotheses were > 3.5 more likely than any of the alternative hypotheses for the ERN or Pe. These results suggest that meditation may not alter neural activity related to error processing, despite prior research suggesting that it does.

neuroscience↗

Biophysical modeling of neural plasticity induced by transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is a widely used noninvasive brain stimulation method capable of inducing plastic reorganisation of cortical circuits in humans. Changes in neural activity following TMS are often attributed to synaptic plasticity (e.g long-term potentiation and depression; LTP/LTD). However, the precise way in which synaptic processes such as LTP/LTD modulate the activity of large populations of neurons, as stimulated en masse by TMS, are unclear. The recent development of biophysically-informed models, which capture the physiological properties of TMS-induced plasticity using mathematics, provide an excellent framework for reconciling synaptic and macroscopic plasticity. In this article, we overview the TMS paradigms used to induce plasticity, and their limitations. We then describe the development of biophysically-based numerical models of the mechanisms underlying LTP/LTD on population-level neuronal activity, and the application of these models to TMS plasticity paradigms, including theta burst and paired associative stimulation. Finally, we outline how modeling can complement experiment to improve mechanistic understandings and optimize outcomes of TMS-induced plasticity.\n\nAbbreviations

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