The kynurenine pathway relates to post-acute COVID-19 objective cognitive impairment and PASC.

OBJECTIVE: To determine the prevalence and natural history of post-acute COVID-19 objective cognitive impairment and function, and their relationship to demographic, clinical factors, post-acute sequelae of COVID-19 (PASC), and biomarkers. METHODS: A total of 128 post-acute COVID-19 patients (age = 46 ± 15; 42% women, acute disease severity: not hospitalized: 38.6% mild: 0-1 symptoms, 52% 2+ symptoms; 9.4% hospitalized) completed standard cognition, olfaction, and mental health examinations 2-, 4-, and 12-month post diagnosis. Over the same time frame, WHO-defined PASC was determined. Blood cytokines, peripheral neurobiomarkers, and kynurenine pathway (KP) metabolites were measured. Objective cognitive function was demographically/practice corrected, and impairment prevalence was determined using the evidence-based Global Deficit Score method to detect at least mild cognitive impairment (GDS > 0.5). Linear mixed effect regression models with time effect (month post diagnosis) evaluated the relationships to cognition. RESULTS: Across the 12-month study period, mild to moderate cognitive impairment ranged from 16% to 26%, and 46.5% were impaired at least once. Impairment associated with poorer work capacity (p < 0.05), and 2-month objectively tested anosmia (p < 0.05). PASC with (p = 0.01) and without disability (p < 0.03) associated with acute COVID-19 severity. KP measures showed prolonged activation (2 to 8 months) (p < 0.0001) linked to IFN-beta in those with PASC. Of the blood analytes, only the KP metabolites (elevated quinolinic acid, 3-hydroxyanthranilic acid, kynurenine, the kynurenine/tryptophan ratio) associated (p < 0.001) with poorer cognitive performance and greater likelihood of impairment. PASC, independent of disability associated with abnormal kynurenine/tryptophan (p < 0.03). INTERPRETATION: The kynurenine pathway relates to post-acute COVID-19 objective cognitive impairment and PASC, thereby enabling biomarker and therapeutic possibilities.

Turning the Face Inversion Effect on Its Head: Violated Expectations of Orientation, Lighting, and Gravity Enhance N170 Amplitudes.

Face inversion effects occur for both behavioral and electrophysiological responses when people view faces. In EEG, inverted faces are often reported to evoke an enhanced amplitude and delayed latency of the N170 ERP. This response has been attributed to the indexing of specialized face processing mechanisms within the brain. However, inspection of the literature revealed that, although N170 is consistently delayed to a variety of face representations, only photographed faces invoke enhanced N170 amplitudes upon inversion. This suggests that the increased N170 amplitudes to inverted faces may have other origins than the inversion of the face's structure. We hypothesize that the unique N170 amplitude response to inverted photographed faces stems from multiple expectation violations, over and above structural inversion. For instance, rotating an image of a face upside-down not only violates the expectation that faces appear upright but also lifelong priors about illumination and gravity. We recorded EEG while participants viewed face stimuli (upright vs. inverted), where the faces were illuminated from above versus below, and where the models were photographed upright versus hanging upside-down. The N170 amplitudes were found to be modulated by a complex interaction between orientation, lighting, and gravity factors, with the amplitudes largest when faces consistently violated all three expectations. These results confirm our hypothesis that face inversion effects on N170 amplitudes are driven by a violation of the viewer's expectations across several parameters that characterize faces, rather than a disruption in the configurational disposition of its features.