Abstract Music’s role in modulating brain structure, particularly in neurodegenerative contexts such as Alzheimer’s Disease (AD), has been increasingly recognized. While previous studies have hinted at the potential neuroplastic benefits of musical engagement and training, the mechanisms through which music impacts structural connectivity in neurodegenerative pathways remain underexplored. We aimed to examine the impact of music perception skills, active musical engagement, and musical training on structural connectivity in areas relating to memory, emotion, and learning in individuals with worsening memory impairment, investigating the potential neuroplastic effects of music. Employing diffusion tensor imaging (DTI) based structural connectivity and graph theoretical analysis, we investigated brain topological features in 78 participants aged 42 to 85 with a range of memory impairments. Participants were assessed for musical training, engagement, and perception skills. The study analyzed regional and local network topological metrics to examine the influence of musical activities on graph metrics, while controlling for stages of objective memory impairment (SOMI) and diagnosis, separately. This study aimed to elucidate the effects of musical perception skills, active musical engagement, and musical training on structural connectivity within memory, emotion, and learning-related brain areas in individuals with varying degrees of memory impairment. We found enhanced structural connectivity of the right hippocampus and the right posterior cingulate cortex was associated with stronger local network metrics, such as clustering coefficient and betweenness centrality, with increased music perception skills like melody and beat perception. Musical training specifically impacted the clustering coefficient of the right hippocampus and the node degree of the right mid cingulate gyrus. Active musical engagement influenced the eigenvector centrality of the right hippocampus. Furthermore, musical training was associated with enhanced global metrics, such as global efficiency and characteristic path length. Our study integrates diffusion magnetic resonance imaging (MRI) and graph theoretical analysis to reveal significant effects of musical activities on structural connectivity in key brain regions. The results highlight the potential of musical activities to serve as a non-invasive modulatory tool for cognitive resilience, especially in memory impairment and neurodegeneration contexts. These insights contribute to the understanding of delaying AD onset and aiding early-stage patients through music-based interventions, emphasizing the importance of musical engagement in maintaining cognitive and brain health.
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