Schneider, V. | bioRxiv Science

bioRxiv2023

Bypassing Striatal Learning Mechanisms Using Delayed Feedback to Circumvent Learning Deficits in TBI

ObjectiveFeedback facilitates learning by guiding and modifying behaviors through an action-outcome contingency. As the majority of existing studies have focused on immediate presentation of feedback, the impact of delayed feedback on learning is understudied. Prior work demonstrated that learning from immediate and delayed feedback employed distinct brain regions in healthy individuals, and compared to healthy individuals, individuals with traumatic brain injury (TBI) are impaired in learning from immediate feedback. The goal of the current investigation was to assess the effects of delayed vs. immediate feedback on learning in individuals with TBI and examine brain networks associated with delayed and immediate feedback processing. SettingNon-profit research organization. ParticipantsTwenty-eight individuals with moderate-to-severe TBI. DesignParticipants completed a paired-associate word learning task while undergoing MRI. During the task, feedback was presented either immediately, after a delay, or not at all (control condition). Main measuresLearning performance accuracy; confidence ratings; post-task questionnaire, blood-oxygen-level dependent signal. ResultsBehavioral data showed that delayed feedback resulted in better learning performance than immediate feedback and no feedback. In addition, participants reported higher confidence in their performance during delayed feedback trials. During delayed vs. immediate feedback processing, greater activation was observed in the superior parietal and angular gyrus. Activation in these areas has been previously associated with successful retrieval and greater memory confidence. ConclusionThe observed results might be explained by delayed feedback processing circumventing the striatal dopaminergic regions responsible for learning from immediate feedback that are impaired in TBI. Additionally, delayed feedback evokes less of an affective reaction than immediate feedback, which likely benefited memory performance. Indeed, compared to delayed feedback, positive or negative immediate feedback was more likely to be rated as rewarding or punishing, respectively. Findings have significant implications for TBI rehabilitation and suggest that delaying feedback during rehabilitation might recruit brain regions that lead to better functional outcomes.

neuroscience↗

bioRxiv2021

Personalized genome assembly for accurate cancer somatic mutation discovery using cancer-normal paired reference samples

The use of personalized genome assembly as a reference for detecting the full spectrum of somatic events from cancers has long been advocated but never been systematically investigated. Here we address the critical need of assessing the accuracy of somatic mutation detection using personalized genome assembly versus the standard human reference assembly (i.e. GRCh38). We first obtained massive whole genome sequencing data using multiple sequencing technologies, and then performed de novo assembly of the first tumor-normal paired genomes, both nuclear and mitochondrial, derived from the same donor with triple negative breast cancer. Compared to standard human reference assembly, the haplotype phased chromosomal-scale personalized genome was best demonstrated with individual specific haplotypes for some complex regions and medical relevant genes. We then used this well-assembled personalized genome as a reference for read mapping and somatic variant discovery. We showed that the personalized genome assembly results in better alignments of sequencing reads and more accurate somatic mutation calls. Direct comparison of mitochondrial genomes led to discovery of unreported nonsynonymous somatic mutations. Our findings provided a unique resource and proved the necessity of personalized genome assembly as a reference in improving somatic mutation detection at personal genome level not only for breast cancer reference samples, but also potentially for other cancers.

bioinformatics↗