Paquette, S. | bioRxiv Science

bioRxiv2021

Proteomic portraits reveal evolutionarily conserved and divergent responses to spinal cord injury

Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of CSF and serum samples from 111 acute SCI patients and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at six months with an AUC of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response, and establish the CSF abundance of glial fibrillary acidic protein (GFAP) as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.

neuroscience↗

bioRxiv2019

Music perception in acquired prosopagnosia: An anterior temporal syndrome for faces, voices, and music

BackgroundAcquired prosopagnosia is often associated with other deficits, such as dyschromatopsia and topographagnosia, from damage to adjacent perceptual networks. A recent study showed that some subjects with developmental prosopagnosia also have congenital amusia, but problems with music perception have not been described in the acquired variant.\n\nObjectiveOur goal was to determine if music perception was also impaired in subjects with acquired prosopagnosia, and if so, its anatomic correlate.\n\nMethodsWe studied eight subjects with acquired prosopagnosia, all of whom had extensive neuropsychological and neuroimaging testing. They performed a battery of tests evaluating pitch and rhythm processing, including the Montreal Battery for the Evaluation of Amusia.\n\nResultsThree of eight subjects with acquired prosopagnosia had impaired musical pitch perception while rhythm perception was spared. Two of the three also showed reduced musical memory. These three reported alterations in their emotional experience of music: one reported music anhedonia and aversion, while the remaining two had changes consistent with musicophilia. The lesions of these three subjects affected the right or bilateral temporal poles as well as the right amygdala and insula. None of the three prosopagnosic subjects with lesions limited to the inferior occipitotemporal cortex had impaired pitch perception or musical memory, or reported changes in music appreciation.\n\nConclusionTogether with the results of our previous studies of voice recognition, these findings indicate an anterior temporal agnosia syndrome that can include the amnestic variant of prosopagnosia, phonagnosia, and various alterations in music perception, including acquired amusia, reduced musical memory, and altered emotional responses to music.

neuroscience↗