Superficial White Matter Brain Alterations Discriminate Tinnitus in Older Adults

Abstract

Subjective tinnitus is the perception of sound in the absence of an external source, with a neurobiological basis that remains poorly understood. Importantly, tinni-tus prevalence increases with aging, reaching up to 25 % in adults aged above 65 years. This study examines white matter tract alterations in older adults with tinnitus using diffusion magnetic resonance imaging. The research involved 96 individuals from the Chilean ANDES cohort, including 56 patients with tinnitus and 40 controls. Thirty-six deep white matter (DWM) and 84 superficial white matter (SWM) bundles were segmented. For each bundle, we extracted four diffu-sion tensor imaging metrics: axial diffusivity (AD), mean diffusivity (MD), radial diffusivity (RD), and fractional anisotropy (FA). With these features, we trained an Extreme Gradient Boosting classifier to predict tinnitus, achieving an AUC of 0.93, highlighting the relevance of AD. Key DWM bundles included the ante-rior arcuate fasciculus, inferior longitudinal fasciculus, and cingulum short fibers (right hemisphere), and the superior motor thalamic radiation (left hemisphere). Significant SWM bundles in the left hemisphere included the superior parietal, cuneus, lingual, superior temporal, caudal middle frontal, precentral, fusiform, postcentral, supramarginal, rostral middle frontal, and superior frontal regions. Tinnitus patients showed decreased AD, MD, and RD, and increased FA, sug-gesting microstructural reorganization. These changes may reflect adaptive or maladaptive plasticity. Increased FA could signal compensatory responses, while decreased AD might indicate axonal damage. Meanwhile, the decrease in MD and RD could indicate an increase in myelin integrity. This is the first study to investigate SWM bundle alterations in tinnitus patients.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

The authors acknowledge the financial support of ANID (Agencia Nacional de Investigacion y Desarrollo), Chile: Doctorado Nacional/2019-21191506 (Doctoral scholarship, L.L.G.R.); Doctorado Nacional/2022-21221090 (Doctoral scholarship, S.P.M.R.); FONDECYT 1221665 (Research grant, P.G.); FONDECYT 1220607 (Research grant, P.H.D.); Basal Centers AFB240002 (AC3E, Research Center, P.G., P.H.D.); and FB210017 (CENIA, Research Center, P.G.). ANDES Database. Presbycusis Neuroimaging Data were contributed by the collaborative research team at the Neuroscience Department, Facultad de Medicina, Universidad de Chile, Santiago, Chile; and the Otolaryngology Department, Hospital Clınico de la Universidad de Chile, Santiago, Chile. The study (Principal Investigators: Paul H. Delano and Carolina Delgado) was supported by the Proyecto Anillo ACT1403, ANID BASAL AFB240002, FONDEF ID20I10371, FONDECYT grants (1221696, 1220607, 3230557) and Fundacion Guillermo Puelma.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Clinical Hospital of the University of Chile (Date: 12 November 2014/No OAIC752/15). Informed consent was obtained from all individual participants included in the study.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

All data produced in the present study are available upon reasonable request to the authors.

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