Brain and vascular integrity related to cognitive and motor flexibility in autism: a study protocol

Introduction: Autism spectrum disorder, or autism, is a common neurodevelopmental condition characterized by socio-communicative problems together with restrictive and repetitive behaviors. Typically, the latter is manifested as deficits in behavioral flexibility, i.e. changing routine behaviors to adapt to environmental changes. Despite noticeable difficulties with flexible behavior in autism, there is to date not adequate knowledge about the intricacies of such challenges and neurobiological processes that may subserve them. This study aims to investigate both cognitive and motor flexibility in autistic compared with neurotypical adults using a novel combination of detailed methods for brain imaging and behavioral investigations in relation to probabilistic reversal learning (PRL) paradigms. In addition, the experiences of autistic adults on flexible behavior in education and everyday activities will be explored. Methods and analysis: Differences in cognitive flexibility between autistic (n[≥]20) and neurotypical (n[≥]20) adults (18-35 years) will be investigated in terms of brain activations, measured by functional magnetic resonance imaging (fMRI), during two-choice PRL performance (cognitive task). In addition, group differences in microcirculation as measured by arterial spin labelling (ASL) will be evaluated. Group differences in motor flexibility will be investigated as expressed in movement planning and execution (spatio-temporal parameters), measured by a robotic manipulandum platform (KinArm End-Point Robot), during two-choice PRL performance (motor task). Semi-structured interviews will be conducted individually with autistic participants (n=15). Questions concern own experiences of cognitive and motor behavior, and strategies used to support flexibility in these behaviors. Data from this qualitative approach will be analyzed by thematic analysis. Ethics and dissemination: Ethical approval has been obtained from the Swedish Ethical Review Authority (ref:2025-07939-01) and the study will be conducted in accordance with the Declaration of Helsinki, the European Union General Data Protection Regulation (GDPR) and national guidelines for the storing of personal data. The different investigations included are well-established, non-invasive and safe. Study outcomes will be published in peer-reviewed international scientific journals (open access), presented at national and international conferences, and to any interested audience/stakeholders.