Neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease, frontotemporal dementia, and multiple sclerosis, conceived as a chronic neuroinflammatory and neurodegenerative disease, challenge traditional treatment paradigms with their complex, overlapping cognitive and motor impairments affecting individuals’ autonomy, participation, and quality of life. Yet, rehabilitation approaches often treat these domains separately. These conditions have typically been approached through parallel treatment strategies, often isolating cognitive rehabilitation from motor recovery. Recent behavioral neuroscience, neurorehabilitation, and technological innovation point toward the need for integrated, multidomain interventions that reflect the real-life complexity of human functioning. There is tight interdependence between these domains, putting forward a rethinking of how we conceptualize and respond to neurodegeneration.

Recent research has shown that motor and cognitive systems are tightly interconnected through shared neural networks. Dual-task interference, executive control over movement, and goal-oriented behaviors are just a few examples of this interaction. New rehabilitation technologies, such as robotics, virtual reality, wearable sensors, and serious games, are increasingly designed to address this integration. By combining motor training with embedded cognitive stimulation, real-time biofeedback, and adaptive environments, they support a multimodal approach to care, aligned with the biopsychosocial model promoted by the International Classification of Functioning, Disability and Health (ICF).

Despite promising advances, key questions remain. We still lack a clear understanding of the mechanisms by which integrated cognitive-motor rehabilitation influences neuroplasticity and functional outcomes. Clinical trials directly comparing single- vs. multidomain strategies are scarce. Moreover, standardization of outcome measures that capture real-life functional gains is urgently needed.

By embracing a multidomain and person-centered perspective, rehabilitation can go beyond symptom management, promoting meaningful engagement, functional autonomy, and improved quality of life throughout the care continuum, not just at endpoints.

This Research Topic proposes an integrated perspective, where neurodegeneration is addressed not as isolated deficits, but as a multidomain disruption of human functioning, requiring equally integrated therapeutic strategies. It aims to investigate the behavioral and neural mechanisms underpinning cognitive-motor interactions; dual-task interference and executive control over movement; and how these insights inform rehabilitation approaches grounded in goal-directed behavior.

The project will highlight mechanisms, effectiveness, and translational potential of integrated cognitive-motor rehabilitation strategies in neurodegenerative disorders. By focusing on multidomain and technology-supported approaches, we seek to understand whether and how these interventions can mitigate functional decline, enhance neuroplasticity, and improve real-life outcomes for people living with neurodegenerative conditions or, as per MS, neuroinflammatory diseases with a neurodegenerative component.

We welcome submissions that bridge behavioral neuroscience, rehabilitation, and neurotechnology within a person-centered framework. Topics of interest include:

• Neural and behavioral mechanisms underlying cognitive-motor integration in neurodegeneration

• Dual-task interference,

• Executive control over movement,

• Goal-directed behaviors in degenerative conditions.

• Comparative studies of multidomain vs. single-domain rehabilitation protocols

• Role of neurotechnologies (robotics, VR, serious games, BCIs) in delivering integrated rehab

• Dual-task and multimodal paradigms applied to real-life functional training

• Preclinical and translational studies investigating cognitive-motor interactions

• Rehabilitation strategies promoting participation, autonomy, and quality of life

• Person-centered assessment tools and outcome measures aligned with the ICF.

The project is intentionally designed to bring together researchers from behavioral neuroscience, neurology, neurorehabilitation, and neurorobotics. We welcome contributions from interdisciplinary teams combining clinical, technological, and behavioral expertise, with a strong focus on translating impact and real-world relevance.

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Rethinking neurodegeneration through multidomain neurorehabilitation and neurotechnologies