Lessons learned from an fMRI-guided rTMS study on performance in a numerical Stroop task.

The Stroop task is a well-established tool to investigate the influence of competing visual categories on decision making. Neuroimaging as well as rTMS studies have demonstrated the involvement of parietal structures, particularly the intraparietal sulcus (IPS), in this task. Given its reliability, the numerical Stroop task was used to compare the effects of different TMS targeting approaches by Sack and colleagues (Sack AT 2009), who elegantly demonstrated the superiority of individualized fMRI targeting. We performed the present study to test whether fMRI-guided rTMS effects on numerical Stroop task performance could still be observed while using more advanced techniques that have emerged in the last decade (e.g., electrical sham, robotic coil holder system, etc.). To do so we used a traditional reaction time analysis and we performed, post-hoc, a more advanced comprehensive drift diffusion modeling approach. Fifteen participants performed the numerical Stroop task while active or sham 10 Hz rTMS was applied over the region of the right intraparietal sulcus (IPS) showing the strongest functional activation in the Incongruent > Congruent contrast. This target was determined based on individualized fMRI data collected during a separate session. Contrary to our assumption, the classical reaction time analysis did not show any superiority of active rTMS over sham, probably due to confounds such as potential cumulative rTMS effects, and the effect of practice. However, the modeling approach revealed a robust effect of rTMS on the drift rate variable, suggesting differential processing of congruent and incongruent properties in perceptual decision-making, and more generally, illustrating that more advanced computational analysis of performance can elucidate the effects of rTMS on the brain where simpler methods may not.

High transmission of endemic human coronaviruses before and during the COVID-19 pandemic in adolescents in Cebu, Philippines.

Background: SARS-CoV-2, the causative agent of COVID-19, is a betacoronavirus belonging to the same genus as endemic human coronaviruses (hCoVs) OC43 and HKU1 and is distinct from alpha hCoVs 229E and NL63. In a study of adolescents in the Philippines, we evaluated the seroprevalence to hCoVs, whether pre-pandemic hCoV immunity modulated subsequent risk of SARS-CoV-2 infection, and if SARS-CoV-2 infection affected the transmission of the hCoVs. Methods: From 499 samples collected in 2021 and screened by SARS-CoV-2 receptor binding domain (RBD) enzyme-linked immunosorbent assay (ELISA), we randomly selected 59 SARS-CoV-2 negative and 61 positive individuals for further serological evaluation. We measured RBD and spike antibodies to the four hCoVs and SARS-CoV-2 by ELISA in samples from the same participants collected pre-pandemic (2018-2019) and mid-pandemic (2021), before COVID-19 vaccination. Results: We observed over 72% seropositivity to the four hCoVs pre-pandemic. Binding antibodies increased with age to 229E and OC43, suggesting endemic circulation, while immunity was flat across ages for HKU1 and NL63. During the COVID-19 pandemic, antibody level increased significantly to the RBDs of OC43, NL63, and 229E and spikes of all four hCoVs in both SARS-CoV-2 negative and positive adolescents. Those aged 12-15 years old in 2021 had higher antibodies to RBD and spike of OC43, NL63, and 229E than adolescents the same age in 2019, further demonstrating intense transmission of the hCoVs during the pandemic. Conclusions: We observe a limited impact of the COVID-19 pandemic on endemic hCoV transmission. This study provides insight into co-circulation of hCoVs and SARS-CoV-2.

Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history.

The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with a single infection or multiple vaccine exposures, or both. We measured their neutralization titers against 15 natural variants and 7 variants with engineered spike mutations and analyzed antigenic diversity. Antigenic maps of primary infection sera showed that Omicron sublineages BA.2, BA.4/BA.5, and BA.2.12.1 are distinct from BA.1 and more similar to Beta/Gamma/Mu variants. Three mRNA COVID-19 vaccinations increased neutralization of BA.1 more than BA.4/BA.5 or BA.2.12.1. BA.1 post-vaccination infection elicited higher neutralization titers to all variants than three vaccinations alone, although with less neutralization to BA.2.12.1 and BA.4/BA.5. Those with BA.1 infection after two or three vaccinations had similar neutralization titer magnitude and antigenic recognition. Accounting for antigenic differences among variants when interpreting neutralization titers can aid the understanding of complex patterns in humoral immunity that informs the selection of future COVID-19 vaccine strains.