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

Abstract

Background: Combined 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. Objective: To assess the feasibility of using cerebellar TMS-EEG for the exploration of cerebellar-cerebral network dynamics. Methods: Ten 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. Results: Cerebellar 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. Conclusions: Cerebellar 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.

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

“…Further complicating matters, the presence and magnitude of these artifacts can depend on the hardware used to collect the data. While features of certain artifacts appear consistent between some hardware systems, there are published examples of changes in artifact profiles between different TMS devices (Rogasch et al, 2013), TMS coils (Fernandez et al, 2021), and EEG electrodes (Mancuso et al, 2021), as well as anecdotal evidence within the TMS-EEG community for differences between EEG amplifiers. The vast number of different hardware combinations used by different laboratories poses a genuine challenge for comparing data between groups, which may suffer from different, and in some cases unique, artifact profiles.…”

“…Finally, TMS results in a loud clicking sound, which evokes a prominent auditory potential with peaks at ∼100 and 200 ms (Nikouline et al, 1999). Importantly, sensory-evoked potentials can persist in TMS-EEG recordings even when online masking methods are used, like playing noise through earphones to mask the TMS click (Biabani et al, 2021, 2019; Conde et al, 2019; Fernandez et al, 2021; Gordon et al, 2018; Herring et al, 2015). Of note, whether sensory-evoked potentials like those resulting from the TMS coil click are considered artifacts is largely dependent on the goal of the study.…”

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

“…EEG was recorded using a DC-coupled, TMS-compatible amplifier (ActiChamp Plus, Brain Products, Germany) at a sampling rate of 25000 Hz [7]. Signals were recorded from 63 active electrodes, embedded in an elastic cap (ActiCap, Brain Products, Germany), in line with the 10-10 system.…”

“…Two kinds of sensory-evoked potentials may contribute to TEPs: auditory potentials elicited by the "clicking" of the TMS coil, and somatosensory potentials elicited by the "flicking" sensation on the skin. Several masking methods have been used to suppress these sensory inputs [4][5][6][7] . For example, white noise played through headphones has been used to mask the click sound [1,8], while a thin layer of foam placed between the TMS coil and EEG cap has been used to minimize the scalp sensation [9].…”

“…One limitation of previous sham conditions is the sensory components were not spatially matched to active TMS. For example, four studies induced auditory potentials by delivering active TMS at a distance from the scalp, and concurrently administered mild scalp electrical stimulation to induce somatosensory potentials [4,7,10,11], while another study used a sham condition where active TMS was delivered to the shoulder [5]. These studies typically demonstrated sensory contamination between ~60-250ms post-stimulation, with earlier timepoints (<60ms) less impacted by sensory contamination [5,6,10,12].…”