Personalized brain stimulation of memory networks

Available online 13 September 2022Background: The finding that transcranial magnetic stimulation (TMS) can enhance memory performance via stimulation of parietal sites within the Cortical-Hippocampal Network counts as one of the most exciting findings in this field in the past decade. However, the first independent effort aiming to fully replicate this finding found no discernible influence of TMS on memory performance. Objective: We examined whether this might relate to interindividual spatial variation in brain connectivity architecture, and the capacity of personalisation methodologies to overcome the noise inherent across independent scanners and cohorts. Methods: We implemented recently detailed personalisation methodology to retrospectively compute individual-specific parietal targets and then examined relation to TMS outcomes. Results: Closer proximity between actual and novel fMRI-personalized targets associated with greater improvement in memory performance. Conclusion: These findings demonstrate the potential importance of aligning brain stimulation targets according to individual-specific differences in brain connectivity, and extend upon recent findings in prefrontal cortex.Robin F.H. Cash, Joshua Hendrikse, Kavisha B Fernando, Sarah Thompson, Chao Suo, Alex Fornito, Murat Yücel, Nigel C. Rogasch, Andrew Zalesky, James P. Coxo

The effects of NMDA receptor blockade on TMS-evoked EEG potentials from prefrontal and parietal cortex

Measuring the brain's response to transcranial magnetic stimulation (TMS) with electroencephalography (EEG) offers unique insights into the cortical circuits activated following stimulation, particularly in non-motor regions where less is known about TMS physiology. However, the mechanisms underlying TMS-evoked EEG potentials (TEPs) remain largely unknown. We assessed TEP sensitivity to changes in excitatory neurotransmission mediated by n-methyl-d-aspartate (NMDA) receptors following stimulation of non-motor regions. In fourteen male volunteers, resting EEG and TEPs from prefrontal (PFC) and parietal (PAR) cortex were measured before and after administration of either dextromethorphan (NMDA receptor antagonist) or placebo across two sessions in a double-blinded pseudo-randomised crossover design. At baseline, there were amplitude differences between PFC and PAR TEPs across a wide time range (15-250 ms), however the signals were correlated after ~80 ms, suggesting early peaks reflect site-specific activity, whereas late peaks reflect activity patterns less dependent on the stimulated sites. Early TEP peaks were not reliably altered following dextromethorphan compared to placebo, although findings were less clear for later peaks, and low frequency resting oscillations were reduced in power. Our findings suggest that early TEP peaks (<80 ms) from PFC and PAR reflect stimulation site specific activity that is largely insensitive to changes in NMDA receptor-mediated neurotransmission.Nigel C. Rogasch, Carl Zipser, Ghazaleh Darmani, Tuomas P. Mutanen, Mana Biabani, Christoph Zrenner, Debora Desideri, Paolo Belardinelli, Florian Müller-Dahlhaus, Ulf Zieman

Mindfulness meditators show altered distributions of early and late neural activity markers of attention in a response inhibition task

Attention is vital for optimal behavioural performance in every-day life. Mindfulness meditation has been shown to enhance attention. However, the components of attention altered by meditation and the related neural activities are underexplored. In particular, the contributions of inhibitory processes and sustained attention are not well understood. To address these points, 34 meditators were compared to 28 age and gender matched controls during electroencephalography (EEG) recordings of neural activity during a Go/Nogo response inhibition task. This task generates a P3 event related potential, which is related to response inhibition processes in Nogo trials, and attention processes across both trial types. Compared with controls, meditators were more accurate at responding to Go and Nogo trials. Meditators showed a more frontally distributed P3 to both Go and Nogo trials, suggesting more frontal involvement in sustained attention rather than activity specific to response inhibition. Unexpectedly, meditators also showed increased positivity over the right parietal cortex prior to visual information reaching the occipital cortex (during the pre-C1 window). Both results were positively related to increased accuracy across both groups. The results suggest that meditators show altered engagement of neural regions related to attention, including both higher order processes generated by frontal regions, and sensory anticipation processes generated by poster regions. This activity may reflect an increased capacity to modulate a range of neural processes in order to meet task requirements. This increased capacity may underlie the improved attentional function observed in mindfulness meditators.Neil W. Bailey, Gabrielle Freedman, Kavya Raj, Caley M. Sullivan, Nigel C. Rogasch, Sung W. Chung, Kate E. Hoy, Richard Chambers, Craig Hassed, Nicholas T. Van Dam, Thomas Koenig, Paul B. Fitzgeral

Repetitive transcranial magnetic stimulation (rTMS) in autism spectrum disorder: protocol for a multicentre randomised controlled clinical trial

Introduction There are no well-established biomedical treatments for the core symptoms of autism spectrum disorder (ASD). A small number of studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, may improve clinical and cognitive outcomes in ASD. We describe here the protocol for a funded multicentre randomised controlled clinical trial to investigate whether a course of rTMS to the right temporoparietal junction (rTPJ), which has demonstrated abnormal brain activation in ASD, can improve social communication in adolescents and young adults with ASD. Methods and analysis This study will evaluate the safety and efficacy of a 4-week course of intermittent theta burst stimulation (iTBS, a variant of rTMS) in ASD. Participants meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (n=150, aged 14–40 years) will receive 20 sessions of either active iTBS (600 pulses) or sham iTBS (in which a sham coil mimics the sensation of iTBS, but no active stimulation is delivered) to the rTPJ. Participants will undergo a range of clinical, cognitive, epi/genetic, and neurophysiological assessments before and at multiple time points up to 6 months after iTBS. Safety will be assessed via a structured questionnaire and adverse event reporting. The study will be conducted from November 2020 to October 2024. Ethics and dissemination The study was approved by the Human Research Ethics Committee of Monash Health (Melbourne, Australia) under Australia’s National Mutual Acceptance scheme. The trial will be conducted according to Good Clinical Practice, and findings will be written up for scholarly publication. Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12620000890932)

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.Nigel C. Rogasch, Mana Biabani, Tuomas P. Mutane

Regulating consumer use of transcranial direct current stimulation devices

Abstract not availableAnne-Maree Farrell, Adrian Carter, Nigel C Rogasch, Paul B Fitzgeral

Non-invasive brain stimulation in the treatment of post-stroke aphasia: a scoping review

Published online: 13 Oct 2023. OnlinePublPurpose: Aphasia is an acquired language impairment that commonly results from stroke. Non-invasive brain stimulation (NIBS) might accelerate aphasia recovery trajectories and has seen mounting popularity in recent aphasia rehabilitation research. The present review aimed to: (1) summarise all existing literature on NIBS as a post-stroke aphasia treatment; and (2) provide recommendations for future NIBS-aphasia research. Materials and methods: Databases for published and grey literature were searched using scoping review methodology. 278 journal articles, conference abstracts/posters, and books, and 38 items of grey literature, were included for analysis. Results: Quantitative analysis revealed that ipsilesional anodal transcranial direct current stimulation and contralesional 1-Hz repetitive transcranial magnetic stimulation were the most widely used forms of NIBS, while qualitative analysis identified four key themes including: the roles of the hemispheres in aphasia recovery and their relationship with NIBS; heterogeneity of individuals but homogeneity of subpopulations; individualisation of stimulation parameters; and much remains under-explored in the NIBS-aphasia literature. Conclusions: Taken together, these results highlighted systemic challenges across the field such as small sample sizes, inter-individual variability, lack of protocol optimisation/standardisation, and inadequate focus on aphasiology. Four key recommendations are outlined herein to guide future research and refine NIBS methods for post-stroke aphasia treatment.Ellen E. R. Williams, Sabrina Sghirripa, Nigel C. Rogasch, Brenton Hordacre and Stacie Attril

Does predictive cueing of presentation time modulate alpha power and facilitate visual working memory performance in younger and older adults?

Selective attention and working memory (WM) are vulnerable to age-related decline. Older adults perform worse on, and are less able to modulate alpha power (8–12 Hz) than younger adults in tasks involving cues about ‘where’ or ‘when’ a memory set will appear. However, no study has investigated whether alpha power is modulated by cues predicting the presentation time of a memory set. Here, we recorded electroencephalography while 24 younger (18–33 years) and 23 older (60–77 years) adults completed a modified delay match-to-sample task where participants were cued to the duration of a memory set (0.1 s or 0.5 s). We found: (1) predictive cues increased WM storage; (2) no differences in preparatory alpha power between predictive and neutral cue types, but preparatory alpha suppression was weaker in older adults; (3) retention period oscillatory power differed between presentation times, but these differences were no longer present when comparing trial types from the onset of the memory set; and (4) oscillatory power in the preparatory and retention periods were unrelated to performance. Our results suggest that preparatory alpha power is not modulated by predictive cues towards presentation time, however, reductions in alpha/beta power during visual WM retention may be linked to encoding, rather than retention.Sabrina Sghirripa, Lynton Graetz, Nigel C. Rogasch, John G. Semmler, Mitchell R. Goldsworth

The correspondence between EMG and EEG measures of changes in cortical excitability following transcranial magnetic stimulation

First published: 18 February 2021Key points: TMS is commonly used to study excitatory/inhibitory neurotransmission in cortical circuits. Changes in cortical excitability following TMS are typically measured from hand (using EMG; limited to motor cortex) or scalp (using EEG), however it is unclear whether these two measures represent the same activity when assessing motor cortex. We found that TMS-EMG and TMS-EEG measures of motor cortex excitability are differentially impacted by sensory confounds at different time points masking any actual relationship between them in the time domain. In the frequency domain, local high-frequency oscillations in EEG recordings were minimally confounded by sensory artefacts and demonstrated strong correlations with EMG measures of cortical excitability across time, regardless of TMS intensity or waveform. Therefore, despite the effects of sensory artefacts, the two measures of motor cortex excitability share a response component, suggesting that they index a similar cortical activity and perhaps the same neuronal population.AbstractTranscranial 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, sub- and 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. This article is protected by copyright. All rights reserved.Mana Biabani, Alex Fornito, James P. Coxon, Ben D. Fulcher, Nigel C. Rogasc

Resting state functional connectivity measures correlate with the response to anodal transcranial direct current stimulation

Responses to non-invasive brain stimulation are highly variable between subjects. Resting state functional connectivity was investigated as a marker of plasticity induced by anodal transcranial direct current stimulation (tDCS). Twenty-six healthy adults (15 male, 26.4 ± 6.5 years) were tested. Experiment 1 investigated whether functional connectivity could predict modulation of corticospinal excitability following anodal tDCS. Experiment 2 determined test-retest reliability of connectivity measures. Three minutes of electroencephalography was recorded and connectivity was quantified with the debiased weighted phase lag index. Anodal (1 mA, 20 min) or sham tDCS was applied to the left primary motor cortex (M1), with a change in motor evoked potential amplitude recorded from the right first dorsal interosseous used as a marker of tDCS response. Connectivity in the high beta frequency (20-30 Hz) between an electrode approximating the left M1 (C3) and electrodes overlying the left parietal cortex was a strong predictor of tDCS response (cross-validated R²  = 0.69). Similar relationships were observed for alpha (8-13 Hz; R²  = 0.64), theta (4-7 Hz; R²  = 0.53), and low beta (14-19 Hz; R²  = 0.58) frequencies, however, test-retest reliability of connectivity measures was strongest for the high beta frequency model (ICC = 0.65; good reliability). Further investigation of the high beta model found that greater connectivity between C3 and a cluster of electrodes approximately overlying the left parietal cortex was associated with stronger responses to anodal (rho = 0.61, P = 0.03), but not sham tDCS (rho = 0.43, P = 0.14). Functional connectivity is a strong predictor of the neuroplastic response to tDCS and may be one important characteristic to assist targeted tDCS application.Brenton Hordacre, Bahar Moezzi, Mitchell R. Goldsworthy, Nigel C. Rogasch, Lynton J. Graetz and Michael C. Riddin