Investigation Of Central Pathogenesis In Presbycusis Using Functional Magnetic Resonance Imaging

Presbycusis(PC)is the most common sensory deficit in the ageing population.Presbycusis is most often characterized by a progressive hearing loss at high frequencies and a poor speech discrimination,especially in a noisy environment.Presbycusis may cause serious influence to the quality of life of the elderly,and can lead to depression and other psychiatric disorders,which brings heavy pressure to the society.A large-scale sample study of our country has showed that presbycusis is the principal cause of hearing disability in the elderly.With the acceleration of population aging in our country,the number of patients with presbycusis will increase year by year.Therefore,it is crucial to investigate the central pathogenesis in presbycusis and provide the theoretical basis for preventing,treating and monitoring presbycusis.Hypofunction of the inner ear is the main reason for the peripheral component of presbycusis.However,poor speech discrimination and deteriorated temporal sound processing reflect a possible central component of presbycusis.Moreover,many studies have showed the existence of a central component of presbycusis.However,the central pathogenesis in presbycusis still remain unclear.In the past,because of the lack of effective measurement technology,it was very difficult for us to study the changes of metabolism in auditory cortex and the changes of auditory nerve pathways in patients with presbycusis in vivo.The development of neuroimaging,especially functional magnetic resonance imaging(fMRI),provides us a powerful tool to investigate presbycusis.Magnetic resonance spectroscopy(MRS)is a noninvasive technique that permits the estimation of the concentrations of various metabolites in the human brain in vivo.A widely used technique,diffusion tensor imaging(DTI),has been considered as the most effective method for characterizing white matter organization.Therefore,this study will combine two kinds of fMRI technology to investigate the central pathogenesis in presbycusis and provide the theoretical basis for preventing,treating and monitoring presbycusis.This study contains two parts,as follows:Part 1.Decreased auditory GABA+ concentrations in presbycusis demonstrated by edited magnetic resonance spectroscopyBACKGROUND AND PURPOSE:Gamma-aminobutyric acid(GABA)is the main inhibitory neurotransmitter in the central auditory system.Altered GABAergic neurotransmission has been found in both the inferior colliculus and the auditory cortex in animal models of presbycusis.Edited magnetic resonance spectroscopy(MRS),using the MEGA-PRESS sequence,is the most widely used technique for detecting GABA in the human brain.However,to date there has been a paucity of studies exploring changes to the GABA concentrations in the auditory region of patients with presbycusis.MATERIALS AND METHODS:In this study,sixteen patients with presbycusis(5 males/11 females,mean age 63.1± 2.6 years)and twenty healthy controls(6 males/14 females,mean age 62.5 ± 2.3 years)underwent audiological and MRS examinations.Pure tone audiometry from 0.125 to 8 kHz and tympanometry were used to assess the hearing abilities of all subjects.The pure tone average(PTA;the average of hearing thresholds at 0.5,1,2 and 4 kHz)was calculated.The MEGA-PRESS sequence was used to measure GABA+ concentrations in 4 x 3×3 cm3 volumes centered on the left and right Heschl’s gyri.RESULTS:GABA+ concentrations were significantly lower in the presbycusis group compared to the control group(left auditory regions:p = 0.002,right auditory regions:p＝0.008).Significant negative correlations were observed between PTA and GABA+ concentrations in the presbycusis group(r =-0.57,p = 0.02),while a similar trend was found in the control group(r =-0.40,p = 0.08).CONCLUSIONS:These results are consistent with a hypothesis of dysfunctional GABAergic neurotransmission in the central auditory system in presbycusis and suggest a potential treatment target for presbycusis.Part 2.Diffusion tensor imaging Analysis of Presbycusis Using Voxel-Based AnalysisBACKGROUND AND PURPOSE:Presbycusis is the most common sensory deficit in the aging population.A recent study reported using a DTI-based tractography technique to identify a lack of integrity in a portion of the auditory pathway in patients with presbycusis.The aim of our study was to investigate the white matter pathology of patients with presbycusis by using a voxel-based analysis that is highly sensitive to local intensity changes in DTI data.MATERIALS AND METHODS:Fifteen patients with presbycusis and 14 age-and sex-matched healthy controls were scanned on a 3T scanner.Fractional anisotropy,mean diffusivity,axial diffusivity,and radial diffusivity were obtained from the DTI data.Intergroup statistics were implemented on these measurements,which were transformed to Montreal Neurological Institute coordinates by using a nonrigid image registration method called large deformation diffeomorphic metric mapping.RESULTS:Increased axial diffusivity,radial diffusivity,and mean diffusivity and decreased fractional anisotropy were found near the right-side hearing-related areas in patients with presbycusis.Increased radial diffusivity and mean diffusivity were also found near a language-related area(Broca area)in patients with presbycusis.CONCLUSIONS:Our findings could be important for exploring reliable imaging evidence of presbycusis and could complement an ROI-based approach.