Neil W. Bailey

Removing artefacts from TMS-EEG recordings using independent component analysis: Importance for assessing prefrontal and motor cortex network properties

INTRODUCTION The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) is emerging as a powerful tool for causally investigating cortical mechanisms and networks. However, various artefacts contaminate TMS-EEG recordings, particularly over regions such as the dorsolateral prefrontal cortex (DLPFC). The aim of this study was to substantiate removal of artefacts from TMS-EEG recordings following stimulation of the DLPFC and motor cortex using independent component analysis (ICA). METHODS 36 healthy volunteers (30.8 ± 9 years, 9 female) received 75 single TMS pulses to the left DLPFC or left motor cortex while EEG was recorded from 57 electrodes. A subset of 9 volunteers also received 50 sham pulses. The large TMS artefact and early muscle activity (-2 to ~15 ms) were removed using interpolation and the remaining EEG signal was processed in two separate ICA runs using the FastICA algorithm. Five sub-types of TMS-related artefacts were manually identified: remaining muscle artefacts, decay artefacts, blink artefacts, auditory-evoked potentials and other noise-related artefacts. The cause of proposed blink and auditory-evoked potentials was assessed by concatenating known artefacts (i.e. voluntary blinks or auditory-evoked potentials resulting from sham TMS) to the TMS trials before ICA and evaluating grouping of resultant independent components (ICs). Finally, we assessed the effect of removing specific artefact types on TMS-evoked potentials (TEPs) and TMS-evoked oscillations. RESULTS Over DLPFC, ICs from proposed muscle and decay artefacts correlated with TMS-evoked muscle activity size, whereas proposed TMS-evoked blink ICs combined with voluntary blinks and auditory ICs with auditory-evoked potentials from sham TMS. Individual artefact sub-types characteristically distorted each measure of DLPFC function across the scalp. When free of artefact, TEPs and TMS-evoked oscillations could be measured following DLPFC stimulation. Importantly, characteristic TEPs following motor cortex stimulation (N15, P30, N45, P60, N100) could be recovered from artefactual data, corroborating the reliability of ICA-based artefact correction. CONCLUSIONS Various different artefacts contaminate TMS-EEG recordings over the DLPFC and motor cortex. However, these artefacts can be removed with apparent minimal impact on neural activity using ICA, allowing the study of TMS-evoked cortical network properties.

Analysing concurrent transcranial magnetic stimulation and electroencephalographic data: A review and introduction to the open-source TESA software

ABSTRACT The concurrent use of transcranial magnetic stimulation with electroencephalography (TMS–EEG) is growing in popularity as a method for assessing various cortical properties such as excitability, oscillations and connectivity. However, this combination of methods is technically challenging, resulting in artifacts both during recording and following typical EEG analysis methods, which can distort the underlying neural signal. In this article, we review the causes of artifacts in EEG recordings resulting from TMS, as well as artifacts introduced during analysis (e.g. as the result of filtering over high‐frequency, large amplitude artifacts). We then discuss methods for removing artifacts, and ways of designing pipelines to minimise analysis‐related artifacts. Finally, we introduce the TMS–EEG signal analyser (TESA), an open‐source extension for EEGLAB, which includes functions that are specific for TMS–EEG analysis, such as removing and interpolating the TMS pulse artifact, removing and minimising TMS‐evoked muscle activity, and analysing TMS‐evoked potentials. The aims of TESA are to provide users with easy access to current TMS–EEG analysis methods and to encourage direct comparisons of these methods and pipelines. It is hoped that providing open‐source functions will aid in both improving and standardising analysis across the field of TMS–EEG research. HIGHLIGHTSTMS pulses result in numerous artifacts in concurrent EEG recordings.We review the origins of these artifacts and methods for removing them.We also introduce TESA, an open‐source EEGLAB extension for TMS‐EEG analysis.

The effect of transcranial Direct Current Stimulation on gamma activity and working memory in schizophrenia

Working memory impairments in schizophrenia have been strongly associated with abnormalities in gamma oscillations within the dorsolateral prefrontal cortex (DLFPC). We recently published the first ever study showing that anodal transcranial Direct Current Stimulation (tDCS) to the left DLPFC was able to significantly improve working memory performance in schizophrenia. In the current paper we present a secondary analysis from this study, specifically looking at the effect of tDCS on gamma activity and its relationship to working memory. In a repeated measures design we assessed the impact of anodal tDCS (1mA, 2mA, sham) on gamma activity in the left DLPFC at three time-points post-stimulation (0min, 20min, 40min). EEG data was available for 16 participants in the 2mA condition, 13 in the 1mA condition and 12 in the sham condition. Following 2mA stimulation we found a significant increase in gamma event-related synchronisation in the left DLPFC, this was in the context of a significantly improved working memory performance. There was also a significant decrease in gamma event-related synchronisation, with no changes in working memory, following sham stimulation. The current study provides preliminary evidence that tDCS may enhance working memory in schizophrenia by restoring normal gamma oscillatory function.

The (Eigen)Value of Diffusion Tensor Imaging to Investigate Depression After Traumatic Brain Injury

Background: Many people with a traumatic brain injury (TBI), even mild to moderate, will develop major depression (MD). Recent studies of patients with MD suggest reduced fractional anisotropy (FA) in dorsolateral prefrontal cortex (DLPFC), temporal lobe tracts, midline, and capsule regions. Some of these pathways have also been found to have reduced FA in patients with TBI. It is unknown whether the pathways implicated in MD after TBI are similar to those with MD without TBI. This study sought to investigate whether there were specific pathways unique to TBI patients who develop MD. Methods: A sample of TBI‐MD subjects (N = 14), TBI‐no‐MD subjects (N = 12), MD‐no‐TBI (N = 26), and control subjects (no TBI or MD, N = 23), using a strict measurement protocol underwent psychiatric assessments and diffusion tensor brain Magnetic Resonance Imaging (MRI). Results: The findings of this study indicate that (1) TBI patients who develop MD have reduced axial diffusivity in DLPFC, corpus callosum (CC), and nucleus accumbens white matter tracts compared to TBI patients who do not develop MD and (2) MD patients without a history of TBI have reduced FA along the CC. We also found that more severe MD relates to altered radial diffusivity. Conclusions: These findings suggest that compromise to specific white matter pathways, including both axonal and myelination aspects, after a mild TBI underlie the susceptibility of these patients developing MD. Hum Brain Mapp 35:227–237, 2014.

The effect of γ-tACS on working memory performance in healthy controls

Transcranial Direct Current Stimulation (tDCS) has been widely investigated for its potential to enhance cognition, and in particular working memory, however to date standard approaches to stimulation have shown only modest effects. Alternative, more specialised, forms of current delivery may be better suited to cognitive enhancement. One such method is transcranial Alternating Current Stimulation (tACS) which delivers stimulation at a specific frequency and has been shown to entrain endogenous cortical oscillations which underlie cognitive functioning. To date there has been no comparison of the effects of tACS to those of tDCS on cognitive enhancement. In a randomised repeated-measures study design we assessed the effect of gamma (γ)-tACS, tDCS and sham tDCS on working memory in 18 healthy participants who attended three sessions held at least 72h apart. Pre- and post-stimulation working memory performance was assessed using the 2 and 3-back. Our findings indicated the presence of a selective improvement in performance on the 3-back task following γ-tACS compared with tDCS and sham stimulation. The current findings provide support for further and more detailed investigation of the role of γ-tACS as a more specialised approach to neuromodulation.

Cortical inhibitory deficits in premanifest and early Huntington's disease.

Although progress has been made towards understanding the gross cortical and subcortical pathology of Huntingtons disease (HD), there remains little understanding of the progressive pathophysiological changes that occur in the brain circuits underlying the disease. Transcranial magnetic stimulation (TMS) enables investigation of the functional integrity of cortico-subcortical pathways, yet it has not been widely applied in HD research to date. This study sought to characterise profiles of cortical excitability, including inhibition and facilitation, in groups of premanifest and symptomatic HD participants via the use of TMS. We also investigated the clinical, neurocognitive and psychiatric correlates of cortical excitability to better understand the development of phenotypic heterogeneity. The sample comprised 16 premanifest HD, 12 early symptomatic HD and 17 healthy control participants. Single- and paired-pulse TMS protocols were administered to the left primary motor cortex, with surface electromyography recorded from the abductor pollicis brevis muscle. Short-interval cortical inhibition was significantly reduced in symptomatic HD, compared with premanifest HD and controls, and was significantly correlated with pathological burden and neurocognitive performance. There was also reduced long-interval cortical inhibition in both premanifest and symptomatic HD, compared with controls, which was associated with pathological burden and psychiatric disturbances. Motor thresholds, cortical silent periods and intracortical facilitation did not differ across groups. Our results provide important new insights into pathophysiological changes in cortico-subcortical circuits across disease stages in HD. We propose that neurophysiological measures obtained via TMS have potential utility as endophenotypic biomarkers in HD, given their association with both pathological burden and clinical phenotype.

Impaired upper alpha synchronisation during working memory retention in depression and depression following traumatic brain injury.

Rates of major depressive disorder (MDD) following traumatic brain injury (TBI) are higher than in the general population. Individuals with depression following traumatic brain injury (TBI-MDD) exhibit working memory (WM) impairments. Electrophysiological evidence has suggested that parieto-occipital upper alpha synchronisation may enhance WM retention by inhibiting irrelevant processes. The current research assessed whether retention period WM parieto-occipital upper alpha activity is disrupted in groups with TBI-only (N=20), MDD (N=17), and TBI-MDD (N=15) compared to healthy controls (N=31). Behavioural data indicated poorer performance in MDD and TBI-MDD. Parietal-occipital upper alpha was reduced in the MDD and TBI-MDD groups, but was unaffected in TBI-only. These results suggest inhibitory deficits may account for WM impairments in MDD and TBI-MDD, and that for individuals with TBI-MDD it may be the depression rather than the TBI that impairs WM.

Volumetrics relate to the development of depression after traumatic brain injury

Previous research suggests that many people who sustain a traumatic brain injury (TBI), even of the mild form, will develop major depression (MD). We previously reported white matter integrity differences between those who did and did not develop MD after mild TBI. In this current paper, we aimed to investigate whether there were also volumetric differences between these groups, as suggested by previous volumetric studies in mild TBI populations. A sample of TBI-with-MD subjects (N=14), TBI-without-MD subjects (N=12), MD-without-TBI (N=26) and control subjects (no TBI or MD, N=23), received structural MRI brain scans. T1-weighted data were analysed using the Freesurfer software package which produces automated volumetric results. The findings of this study indicate that (1) TBI patients who develop MD have reduced volume in temporal, parietal and lingual regions compared to TBI patients who do not develop MD, and (2) MD patients with a history of TBI have decreased volume in the temporal region compared to those who had MD but without a history of TBI. We also found that more severe MD in those with TBI-with-MD significantly correlated with reduced volume in anterior cingulate, temporal lobe and insula. These findings suggest that volumetric reduction to specific regions, including parietal, temporal and occipital lobes, after a mild TBI may underlie the susceptibility of these patients developing major depression, in addition to altered white matter integrity.

Demonstration of short-term plasticity in the dorsolateral prefrontal cortex with theta burst stimulation: A TMS-EEG study

OBJECTIVES To examine the effects of intermittent TBS (iTBS) and continuous TBS (cTBS) on cortical reactivity in the dorsolateral prefrontal cortex. METHODS 10 healthy participants were stimulated with either iTBS, cTBS or sham at F3 electrode. Single- and paired-pulse TMS and concurrent electroencephalography (EEG) were used to assess change in cortical reactivity and long-interval intracortical inhibition (LICI) via TMS-evoked potentials (TEPs) and TMS-evoked oscillations. RESULTS Significant increases in N120 amplitudes (p<0.01) were observed following iTBS over prefrontal cortex. Changes in TMS-evoked theta oscillations and LICI of theta oscillations were also observed following iTBS (increase) and cTBS (decrease). Change in LICI of theta oscillations correlated with change in N120 amplitude following TBS (r=-0.670, p=0.001). CONCLUSIONS This study provides preliminary evidence that TBS produces direct changes in cortical reactivity in the prefrontal cortex. Combining TBS with TMS-EEG may be a useful approach to optimise stimulation paradigms prior to the conduct of clinical trials. SIGNIFICANCE TBS is able to modulate cortical reactivity and cortical inhibition in the prefrontal cortex.

Neural evidence that conscious awareness of errors is reduced in depression following a traumatic brain injury.

Impaired error awareness is related to poorer outcome following traumatic brain injury (TBI). Error awareness deficits are also found in major depressive disorder (MDD), but have not been examined in the MDD that follows a TBI (TBI-MDD). This study assessed neural activity related to error awareness in TBI-MDD. Four groups completed a response inhibition task while EEG was recorded- healthy controls (N = 15), MDD-only (N = 15), TBI-only (N = 16), and TBI-MDD (N = 12). Error related EEG activity was compared using powerful randomisation statistics that included all electrodes and time points. Participants with TBI-MDD displayed less frontally distributed neural activity, suggesting reduced contribution from frontal generating sources. Neural activity during this time window is thought to reflect conscious awareness of errors. The TBI-only and MDD-only groups did not differ from controls, and early error processing was unaffected, suggesting early error detection is intact.