Guiding transcranial brain stimulation by EEG/MEG to interact with ongoing brain activity and associated functions: A position paper

Abstract

Non-invasive transcranial brain stimulation (NTBS) techniques have a wide range of applications but also suffer from a number of limitations mainly related to poor specificity of intervention and variable effect size. These limitations motivated recent efforts to focus on the temporal dimension of NTBS with respect to the ongoing brain activity. Temporal patterns of ongoing neuronal activity, in particular brain oscillations and their fluctuations, can be traced with electro- or magnetoencephalography (EEG/MEG), to guide the timing as well as the stimulation settings of NTBS. These novel, online and offline EEG/MEG-guided NTBS-approaches are tailored to specifically interact with the underlying brain activity. Online EEG/MEG has been used to guide the timing of NTBS (i.e., when to stimulate): by taking into account instantaneous phase or power of oscillatory brain activity, NTBS can be aligned to fluctuations in excitability states. Moreover, offline EEG/MEG recordings prior to interventions can inform researchers and clinicians how to stimulate: by frequency-tuning NTBS to the oscillation of interest, intrinsic brain oscillations can be up- or down-regulated. In this paper, we provide an overview of existing approaches and ideas of EEG/MEG-guided interventions, and their promises and caveats. We point out potential future lines of research to address challenges.

Keywords: Brain oscillations; Electroencephalography; Magnetoencephalography; Non-invasive transcranial brain stimulation (NTBS); Temporally guided NTBS.

Figure 1

Principles of guiding non-invasive transcranial brain stimulation (NTBS) by electro- and/or magnetoencephalography (EEG/MEG). A. The main rationale is to consider oscillatory network activity as targets for intervention. B. This relies on the combination of TACS&MEG or rTMS&EEG for guiding and documenting the intervention by MEG or EEG and for interacting with brain oscillations by TACS or rTMS. C. Three approaches are outlined, which either use ongoing EEG readouts to trigger interventions by instantaneous power or phase (C1), tune rhythmic intervention to the frequency of ongoing oscillations for entraining them (C2), or trigger interventions by phase of entrained oscillations (C3). See text for details and Figs 2–4 for examples of each of these three approaches.

Figure 2

Triggering NTBS by instantaneous phase/power of underlying brain oscillations. A. Design: Single-pulse TMS was triggered online to recordings by automatic detection of slow oscillation (SO) up-and down-states during NREM sleep EEG. TMS was applied over the primary motor cortical hand area. B. Result. B1. Both the size of the motor evoked potentials (MEPs) in the hand muscle (left bar plot) and the TMS-evoked potentials (TEPs) in the EEG (right line plot) depended on brain state at time of TMS. B2. Single-trial correlations (MEPs) and post-hoc single-trial binning (TEPs) according to EEG amplitude (here up-states) revealed that both MEP size (left panel) and TEP amplitude (right panel) scale with the EEG amplitude (i.e., actual voltage) at the time of TMS. Reproduced from Bergmann et al. (2012a) with permission.

Figure 3

Tuning NTBS to frequency of underlying brain oscillations. A. Entrainment of brain oscillations by rTMS (A1) and TACS (A2) when stimulation is directed to posterior alpha oscillations. B. Functional consequences in terms of perception of these interventions (B1 and B2). A1. Short bursts of alpha-rTMS over right parietal cortex promotes right parietal alpha-oscillations (relative to sham rTMS), and B1. biases visual perception away from the contralateral to the ipsilateral visual field (relative to rTMS at control “flanker” frequencies). A2. Alpha-TACS entrains occipital alpha oscillations (relative to pre and post EEG measures), and B2. causes visual perception to co-cycle with the entrained alpha rhythm. Reproduced from Thut et al. (2011), Romei et al. (2010) and Helfrich et al. (2014b) with permission.

Figure 4

Combined frequency-tuning and phase-triggering. A. Design: Prefrontal cortex was stimulated in nine TACS conditions, including gamma-TACS bursts nested in theta-TACS cycles (i.e. a crossfrequency phase-power TACS protocol), while EEG and working memory performance was recorded. B. Theta-gamma TACS enhanced working memory performance. This effect depended on the timing of the gamma-bursts relative to the theta cycle (phase modulation, upper bar plot), as well as on the frequency of the gamma bursts (frequency modulation, middle bar plot) and could not be explained by gamma-burst stimulation simply repeated at a theta-rate without the presence of a theta TACS waveform (DC offset controls, lower bar plot). C. Prefrontal theta-gamma TACS enhanced global brain connectivity, relative to all other conditions (here illustrated for sham). Reproduced from Alekseichuk et al. (2016) with permission.

Figure 5

Control of NTBS. A. Open-loop stimulation. Neural activity is extracted by signal processing techniques (e.g. beamforming in EEG/MEG), directly from neural implants, or inferred from a peripheral proxy such as muscle activity. The relationship between neural activity and stimulation waveform is then calculated (offline) to determine the influence of stimulation on, for example, the phase and amplitude of the endogenous neural activity. B. Closed-loop stimulation. Neural activity is readout in real-time and processed to determine the appropriate form of stimulation on a moment-by-moment basis. On-line processing is technique dependent, such as targeting specific phase points via TMS, or providing continuous feedback via phase locking in the case of TACS. In either case, closed-loop stimulation requires knowledge of target parameters (such as the optimal choice of phase) that may come from an a priori hypothesis, or be determined empirically by open-loop stimulation. Fully-closed loop approaches aim to enhance (or suppress) neural synchrony within- or between- target populations.