Functional Brain Connectivity Prior to the COVID-19 Outbreak Moderates the Effects of Coping and Perceived Stress on Mental Health Changes: A First Year of COVID-19 Pandemic Follow-up Study.

BACKGROUND: The COVID-19 pandemic provides a unique opportunity to investigate the psychological impact of a global major adverse situation. Our aim was to examine, in a longitudinal prospective study, the demographic, psychological, and neurobiological factors associated with interindividual differences in resilience to the mental health impact of the pandemic. METHODS: We included 2023 healthy participants (age: 54.32 ± 7.18 years, 65.69% female) from the Barcelona Brain Health Initiative cohort. A linear mixed model was used to characterize the change in anxiety and depression symptoms based on data collected both pre-pandemic and during the pandemic. During the pandemic, psychological variables assessing individual differences in perceived stress and coping strategies were obtained. In addition, in a subsample (n = 433, age 53.02 ± 7.04 years, 46.88% female) with pre-pandemic resting-state functional magnetic resonance imaging available, the system segregation of networks was calculated. Multivariate linear models were fitted to test associations between COVID-19-related changes in mental health and demographics, psychological features, and brain network status. RESULTS: The whole sample showed a general increase in anxiety and depressive symptoms after the pandemic onset, and both age and sex were independent predictors. Coping strategies attenuated the impact of perceived stress on mental health. The system segregation of the frontoparietal control and default mode networks were found to modulate the impact of perceived stress on mental health. CONCLUSIONS: Preventive strategies targeting the promotion of mental health at the individual level during similar adverse events in the future should consider intervening on sociodemographic and psychological factors as well as their interplay with neurobiological substrates.

Corrigendum to "Prefrontal reactivity to TMS perturbation as a toy model of mental health outcomes during the COVID-19 pandemic"[Heliyon 8 (8), (August 2022) Article e10208].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e10208.].

Prefrontal reactivity to TMS perturbation as a toy model of mental health outcomes during the COVID-19 pandemic.

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 timepoints 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 response, as exemplified by the COVID-19 pandemic.

Loneliness experience through COVID-19 pandemic and lockdown is related with resting-state brain networks functional connectivity

Background The reduction in social interactions often associated with old age frequently initiates or aggravates loneliness, increasing the risk of a number of diseases including depression and dementia (Mushtaq et al., JCDR. 2014;8(9):E01?WE4.). Loneliness has been related to particular patterns of brain resting-state networks (RSNs;Spreng et al., Nat Commun. 2020;11(1):6393). However, the role of RSNs in a resilient response to reductions of social interactions remains unknown and the COVID-19 pandemic provides a unprecedent opportunity to investigate it. Method Repeated loneliness assessments were collected by the Barcelona Brain Health Initiative (BBHI;www.bbhi.cat/en/) using the short UCLA Loneliness Scale (Russell et al., J Pers Assess. 1978;42(3):290?294). Two timepoints were measured over two years prior to COVID-19 outbreak and four thereafter (March, April, June and October 2020). We used baseline resting-state functional magnetic resonance imaging (rs-fMRI), from 281 participants (mean age 53.91±7.35;137 women), acquired within 1-2 years prior to the pandemic to compute resting-state functional connectivity (rs-FC) for each pair of nodes defined by the Schaefer-Yeo atlas. Then, we utilized partial least squares (PLS) analysis for the decomposition of two multivariate sets (i.e., rs-FC and loneliness scores) into latent variables of maximal covariation. Result We identified two latent trajectories significantly correlated with two latent connectivity patterns, each of them describing approximately opposite baseline rs-FC and loneliness levels during the months with the most severe restrictions (i.e., March and April). The first latent trajectory showed greater baseline loneliness improving during the pandemic, associated with higher within-network connectivity in the limbic and salience networks. The second trajectory captured individuals with baseline loneliness levels similar to the average population, improving in March, at the beginning of outbreak, and worsening in April, which was related to lower baseline within-network connectivity in the DMN and higher in the dorsal attention and visual circuits. Conclusion Present findings reveal specific associations between RSNs? functional connectivity and opposite changes in feelings of loneliness during an unanticipated period of severe social restrictions. Specifically, lower rs-FC of limbic networks combined with high connectivity of salience system at baseline suggested greater resilience to the negative impact during the pandemic on loneliness.

TMS-induced EEG perturbation as a marker of psychological resilience to deleterious mental health effects during the COVID-19 pandemic

Background Social, economic and psychological hardships associated with the COVID-19 pandemic are expected to result in a global burden on mental health outcomes. However, while some individuals suffer from increasing distress and reduced quality of life, others will show no negative effects. A better understanding of brain mechanisms subtending resilience would be helpful in informing future recommendations to individuals and societies facing the present pandemic and future similar events. Here, we compared neurophysiological brain markers between individuals who exhibited resilience or vulnerability to pandemic associated psychological stress. Method 23 participants from the longitudinal study cohort of the Barcelona Brain Health Initiative (Cattaneo et al., Front. Aging Neurosci. 2018;10:321) who underwent concurrent transcranial magnetic stimulation with electroencephalography (TMS-EEG), were classified as either resilient (n=16) or non-resilient (n=7), based on their scoring in the PHQ-4 questionnaire (Kroenke et al., Psychosomatics 2009;50(6):613?21) along four timepoints;one before COVID-19 outbreak and three spanning 2.5 months during the pandemic. Individuals maintaining a score below 3 across all timepoints were deemed resilient, while those scoring below 3 before pandemic but higher than 2 at any pandemic timepoint were considered non-resilient. TMS-EEG data was collected by delivering 120 single TMS pulses to the dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobule (IPL). TMS evoked global mean field amplitude and local response at the stimulation site were computed. Result Figure 1 depicts time-series for DLPFC and IPL responses for both groups of subjects. Overall, non-resilient individuals exhibited a larger global response to TMS perturbation during DLPFC stimulation, as well as larger local current density estimates during IPL stimulation. Conclusion These preliminary results revealed that non-resilient individuals were more susceptible to TMS perturbation, shown by global DLPFC and local IPL reactivity. Notably, these targets are nodes of the default mode and cognitive control networks affected by stress (van Oort et al., Neurosci. Biobehav. Rev. 2017;83:281?97), and the left frontal cortex has been proposed as a cognitive resilience hub (Franzmeier et al., J. Alzheimer?s Dis. 2017;59(4):1381?92.). Future studies should investigate and confirm the possibility that these nodes constitute a shared neurophysiological substrate for psychological and cognitive resilience.

Human Brain Resilience: A Call to Action.

At present, resilience refers to a highly heterogeneous concept with ill-defined determinants, mechanisms, and outcomes. This call for action argues for the need to define resilience as a person-centered multidimensional metric, informed by a dynamic lifespan perspective and combining observational and interventional experimental studies to identify specific neural markers and correlated behavioral measures. The coronavirus disease 2019 (COVID-19) pandemic highlights the urgent need of such an effort with the ultimate goal of defining a new vital sign, an individual index of resilience, as a life-long metric with the capacity to predict an individual's risk for disability in the face of a stressor, insult, injury, or disease. ANN NEUROL 2021;90:336-349.

The paradoxical effect of COVID-19 outbreak on loneliness.

As in previous periods of quarantine, lockdown confinement measures dictated to control SARS-CoV-2 would be expected to negatively affect mental health. We investigated the immediate effects (over a 10 day period) of a strict nationwide stay-at-home order imposed in Spain, one of the countries most affected by the COVID-19 pandemic. Focusing our analysis on the feelings of loneliness, we obtained our measures within a social context characterised by strong and continuous public and governmental support for increasing social bonds and cooperation in order to face the common public threat. Leveraging data from the Barcelona Brain Health Initiative, a prospective population-based study cohort, the short UCLA Loneliness Scale was administered to 1604 participants 2 years and 1 year before the stay-at-home lockdown and repeated, on average, 10 days after the official confinement order issued by the Spanish government. Ratings of loneliness remained stable during the 2 years before lockdown; however, they decreased significantly during the early stages of home confinement. This effect was particularly significant for the item 'feeling excluded from others' and was also observed among individuals who were confined alone. Overall, the results suggest that gestures and manifestations of appreciation by people for the labour and efforts of certain individuals, along with official campaigns designed to promote feelings of inclusion and belonging, may have beneficial effects on feelings of loneliness, a negative emotional state strongly regarded as a risk factor for impaired mental and general health status. Further assessments during the later stages of home confinement are now warranted.