Integrating Neuropsychological and Neurobiological Approaches to Cognitive Impairment: Innovations in Neuromodulation and Digital Rehabilitation Strategies

This doctoral thesis delves into the investigation of cognitive impairment, i.e., a decrease in one's perceptual, learning, memory, or thinking abilities. Cognitive impairment is prevalent in numerous neurological and non-neurological conditions and heavily impacts the individual's life and socio-economic well-being. Accurate neuropsychological assessment of cognitive difficulties is pivotal for effective diagnosis, prognosis, and treatment planning. Research studies have increasingly investigated possible neural and biological correlates of cognitive impairment to enhance diagnostic accuracy and evaluate treatment efficacy. This thesis wedges into this topic by exploring cognitive impairment and its rehabilitation across different patient populations, addressing both traditional neuropsychological approaches and innovative neuromodulatory and digital solutions. The first section of the thesis reviews the literature on cognitive impairment, offering insights into differential diagnosis and clinical management of patients with cognitive impairment. The first chapter also investigates two domains highly relevant to the individual's independence, i.e., numerical competence and financial abilities, as well as their cognitive and neural correlates, indicating distinct patterns of deficits across various patient groups. The second section examines non-pharmacological interventions for cognitive impairment, including traditional cognitive rehabilitation, non-invasive brain stimulation (NIBS) techniques, and new technological solutions like serious games and telemedicine. These interventions showed promising results in improving cognitive outcomes and fostering a personalized medicine approach by increasing patient motivation and treatment adherence. The third and last section of this thesis focuses on the combination of digital cognitive training with prismatic adaptation, a widespread neuropsychological procedure that has been suggested to exert neuromodulatory effects on cortical excitability. The effects of this combined intervention were explored in neurological patients, taking into account changes in clinical, cognitive, neurofunctional, and neurobiological levels. Preliminary findings suggest that the combined treatment may improve clinical and cognitive outcomes. Moreover, prismatic adaptation seems to enhance the effects of cognitive training by promoting functional reorganization of brain networks and neuroplastic mechanisms, though different mechanisms may also be involved depending on the underlying pathology (cerebrovascular vs. neurodegenerative). In conclusion, this thesis significantly contributes to the understanding of cognitive impairment and the neurobiological mechanisms involved in its rehabilitation, offering new insights to support the integration of neuropsychological and neurobiological approaches in the care of patients with cognitive impairment.