TMS-Evoked Prefrontal Perturbation as a Toy Model of Brain Resilience to Stress During the COVID-19 Pandemic

Abstract

Psychosocial hardships associated with the COVID-19 pandemic led many individuals to suffer adverse mental health consequences, however, others show no negative effects. We hypothesized that the electroencephalographic (EEG) response to transcranial magnetic stimulation (TMS) could serve as a toy-model of an individual's capacity to resist psychological stress, in this case linked to the COVID-19 pandemic. We analyzed data from 74 participants who underwent mental health monitoring and concurrent electroencephalography with transcranial magnetic stimulation of the left dorsolateral prefrontal cortex (L-DLPFC) and left inferior parietal lobule (L-IPL). Within the following 19 months, mental health was reassessed at three time points during lock-down confinement and different phases of de-escalation in Spain. Compared with participants who remained stable, those who experienced increased mental distress showed, months earlier, significantly larger late EEG responses locally after L-DLPFC stimulation (but not globally nor after L-IPL stimulation). This response, together with years of formal education, was significantly predictive of mental health status during the pandemic. These findings reveal that the effect of TMS perturbation offers a predictive toy model of psychosocial stress resilience, as exemplified by the COVID-19 pandemic, and point to the L-DLPFC as a promising target for resilience promotion.

Keywords: COVID-19; TMS; brain; perturbation.

Figure 1

Schematic Illustration of the toy-model approach in the study design. MRI-guided single pulse TMS perturbation is used to experimentally model as the stressor, captured by evoked EEG reactivity, and measured at local and global levels. We examined whether this ‘toy-model’ can predict the eventual impact of the COVID-19 on mental health assessed months later. We further hypothesized the stressor would be moderated by demographic and individual factors such as years of formal education. Modified from Pascual-Leone and Bartrés-Faz 6.

Figure 2

Results of permutation testing of the difference between resilient and vulnerable individuals on the TMS evoked EEG time-series. A) shows the significant differences at the local EEG time-series during L-DLPFC stimulation in grey horizontal bands, while the horizontal green band highlights the cluster surviving correction for multiple comparisons. B) shows the topographical distribution in source space of the response to L-DLPFC stimulation during the green shaded time-window in A, for both groups and their difference. C) depicts the results of permutation testing for the control stimulation of the L-IPL. D) shows the topographical distribution for the same time window as B, for both groups and their difference. Red and blue contours along the plot lines in A and C depict the standard error of the mean. DLPFC, dorsolateral prefrontal cortex; IPL, inferior parietal lobule

Figure 3

Scatter plots illustrating the linear relationship between the predictors and the response variable in the reduced model. Black line in each plot depicts the least squares regression line; shaded grey contours depict 95% confidence intervals. The response variable depicted here in the y-axis is Box-Cox transformed (λ=−0.078). PHQ-4, four item patient health questionnaire; DLPFC, dorsolateral prefrontal cortex; AUC, area under the curve.

Figure 4

Timeline of relevant events for the study cohort. According to the Spanish Government state of alarm dictation orders and subsequent de-escalation (https://www.boe.es/eli/es/rd/2020/03/14/463/con). 1st, 2nd and 3rd indicate the three PHQ-4 based mental health monitoring timepoints during the pandemic. PHQ-4, four item patient health questionnaire; COVID-19, coronavirus diesease 2019; TMS-EEG, transcraneal magnetic stimulation with concurrent electroencephalography.