Scott, J. N. | Search bioRxiv

bioRxiv2024

Test-Retest Reliability and repeatability of Behavioral and Electrophysiological Markers in an Eriksen Flanker Task

Cognitive control processes, specifically interference control and error monitoring, are often impaired across neuropsychiatric disorders and have been proposed as transdiagnostic markers of psychopathology and important treatment targets. Accurately probing them, however, requires understanding the psychometric properties of the measures used to assess cognitive control, including their intra- and interindividual stability over time. Using an Eriksen Flanker Task, we tested behavioral and electrophysiological readouts of cognitive control in 36 healthy individuals (26 female, 10 male, M age{+/-}SD=33.18{+/-}14.49, range=19-68) and evaluated their test-retest reliability across 48 hours by calculating Pearson correlations and Intraclass Correlation Coefficients (ICCs) to assess group-level stability. Moreover, we assessed repeatability through Coefficients of Variation (CVs) and Bland-Altman statistics, to investigate the degree of change in participants absolute scores. We found satisfactory-to-excellent test-retest reliability for most cognitive control measures, with condition-specific metrics generally being more reliable than difference scores. Regarding repeatability, we observed considerable intraindividual variability in absolute scores over time, which differed widely between participants. These results demonstrate that measurements of cognitive control may display substantial intraindividual variability across sessions despite demonstrating high test-retest reliability and vice versa. Our findings expand the current literature by providing novel information about the stability of behavioral and physiological markers of cognitive control over time. Moreover, they may have important implications for the application and evaluation of clinical interventions by highlighting the usefulness of considering repeatability measures in addition to the more commonly reported test-retest reliability metrics, when tracking changes over time in clinically relevant processes within single individuals.

neuroscience↗

bioRxiv2022

An Ultralong Bovine CDRH3 that Targets a Conserved, Cryptic Epitope on SARS-CoV and SARS-CoV-2

The ability of broadly neutralising antibodies to target conserved epitopes gives them huge potential as antibody-based therapeutics, particularly in the face of constant viral antigen evolution. Certain bovine antibodies are highly adept at binding conserved, glycosylated epitopes, courtesy of their ultralong complementarity determining region (CDR)H3. Here, we used a SARS-naive, bovine ultralong CDRH3 library and mammalian cell display, to isolate a bovine paratope that engages the SARS-CoV and SARS-CoV-2 receptor-binding domain (RBD). This neutralises viruses pseudo-typed with SARS-CoV Spike protein but not by competition with RBD binding to ACE2. Instead, using differential hydrogen-deuterium exchange mass spectrometry and site-directed mutagenesis, we demonstrate that this ultralong CDRH3 recognises a rarely identified, conserved, cryptic epitope that overlaps the target of pan-sarbecovirus antibodies (7D6/6D6). The epitope is glycan-shielded and becomes accessible only transiently via inter-domain movements. This represents the first bovine anti-sarbecovirus paratope and highlights the power of this approach in identifying novel tools to combat emerging pathogens.

molecular biology↗