Reply to: "Reflecting the causes of variability of EEG responses elicited by cerebellar TMS".

In their commentary on our recently published paper about electroencephalographic responses induced by cerebellar transcranial magnetic stimulation (Fong et al., 2023), Gassmann and colleagues (Gassmann et al., 2023b) try to explain the differences between our results and their own previous work on the same topic. We agree with them that many of the differences arise from our use of a different magnetic stimulation coil. However, two unresolved questions remain. (1) Which method is most likely to achieve optimal activation of cerebellar output? (2) To what extent are the evoked cerebellar responses contaminated by concomitant sensory input? We highlight the role of careful experimental design and of combining electrophysiological and behavioural data to obtain reliable TMS-EEG data.

EEG responses induced by cerebellar TMS at rest and during visuomotor adaptation.

BACKGROUND: Connections between the cerebellum and the cortex play a critical role in learning and executing complex behaviours. Dual-coil transcranial magnetic stimulation (TMS) can be used non-invasively to probe connectivity changes between the lateral cerebellum and motor cortex (M1) using the motor evoked potential as an outcome measure (cerebellar-brain inhibition, CBI). However, it gives no information about cerebellar connections to other parts of cortex. OBJECTIVES: We used electroencephalography (EEG) to investigate whether it was possible to detect activity evoked in any areas of cortex by single-pulse TMS of the cerebellum (cerebellar TMS evoked potentials, cbTEPs). A second experiment tested if these responses were influenced by the performance of a cerebellar-dependent motor learning paradigm. METHODS: In the first series of experiments, TMS was applied over either the right or left cerebellar cortex, and scalp EEG was recorded simultaneously. Control conditions that mimicked auditory and somatosensory inputs associated with cerebellar TMS were included to identify responses due to non-cerebellar sensory stimulation. We conducted a follow-up experiment that evaluated whether cbTEPs are behaviourally sensitive by assessing individuals before and after learning a visuomotor reach adaptation task. RESULTS: A TMS pulse over the lateral cerebellum evoked EEG responses that could be distinguished from those caused by auditory and sensory artefacts. Significant positive (P80) and negative peaks (N110) over the contralateral frontal cerebral area were identified with a mirrored scalp distribution after left vs. right cerebellar stimulation. The P80 and N110 peaks were replicated in the cerebellar motor learning experiment and changed amplitude at different stages of learning. The change in amplitude of the P80 peak was associated with the degree of learning that individuals retained following adaptation. Due to overlap with sensory responses, the N110 should be interpreted with caution. CONCLUSIONS: Cerebral potentials evoked by TMS of the lateral cerebellum provide a neurophysiological probe of cerebellar function that complements the existing CBI method. They may provide novel insight into mechanisms of visuomotor adaptation and other cognitive processes.

A causal framework to determine the effectiveness of dynamic quarantine policy to mitigate COVID-19.

Since the start of the pandemic caused by the novel coronavirus, COVID-19, more than 106 million people have been infected and global deaths have surpassed 2.4 million. In Chile, the government restricted the activities and movement of people, organizations, and companies, under the concept of dynamic quarantine across municipalities for a predefined period of time. Chile is an interesting context to study because reports to have a higher quantity of infections per million people as well as a higher number of polymerize chain reaction (PCR) tests per million people. The higher testing rate means that Chile has good measurement of the contagious compared to other countries. Further, the heterogeneity of the social, economic, and demographic variables collected of each Chilean municipality provides a robust set of control data to better explain the contagious rate for each city. In this paper, we propose a framework to determine the effectiveness of the dynamic quarantine policy by analyzing different causal models (meta-learners and causal forest) including a time series pattern related to effective reproductive number. Additionally, we test the ability of the proposed framework to understand and explain the spread over benchmark traditional models and to interpret the Shapley Additive Explanations (SHAP) plots. The conclusions derived from the proposed framework provide important scientific information for government policymakers in disease control strategies, not only to analyze COVID-19 but to have a better model to determine social interventions for future outbreaks.