Auditory network plasticity in tinnitus across the adult lifespan: Insights from fMRI and structural connectivity

Tinnitus, the perception of sound without an external source, is increasingly recognized as a disorder of large-scale brain networks rather than isolated auditory dysfunction. Aging introduces widespread neurobiological changes including cortical atrophy, reduced inhibitory control, and altered connectivity that may distinctly shape the neural basis of tinnitus across the adult lifespan. This study investigates age-specific brain network alterations in chronic subjective tinnitus using resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI). Sixty tinnitus patients and sixty age-matched controls were stratified into younger (19-35 years) and older (45-65 years) cohorts. We assessed spontaneous activity via amplitude of low-frequency fluctuations (ALFF), local functional connectivity using local correlation (LCOR), and structural-functional coupling through voxel-wise correlations between ALFF and fractional anisotropy (FA). Younger tinnitus patients exhibited hyperactivity in auditory and limbic regions, alongside reduced prefrontal and occipital regulation, suggesting heightened sensory salience and impaired habituation. In contrast, older patients showed increased activation in frontal and cerebellar regions but diminished integration in default mode and attention-related cortices, indicating compensatory recruitment constrained by age-related decline. Structure-function coupling revealed more diffuse and adaptive correlations in younger patients, while older adults exhibited focal and limited coupling, particularly in temporal and occipital regions. Network alterations were differentially modulated by tinnitus severity and anxiety across age groups. These findings reveal distinct, age-contingent neural signatures of tinnitus, emphasizing the role of aging in modulating brain network plasticity and underscoring the need for lifespan-informed models in tinnitus research.