Elsevier

Brain Research

Volume 1369, 19 January 2011, Pages 74-88
Brain Research

Research Report
Neuroanatomical changes due to hearing loss and chronic tinnitus: A combined VBM and DTI study

https://doi.org/10.1016/j.brainres.2010.10.095Get rights and content

Abstract

Subjective tinnitus is the perception of sound in the absence of an external source. Tinnitus is often accompanied by hearing loss but not everyone with hearing loss experiences tinnitus. We examined neuroanatomical alterations associated with hearing loss and tinnitus in three groups of subjects: those with hearing loss with tinnitus, those with hearing loss without tinnitus and normal hearing controls without tinnitus. To examine changes in gray matter we used structural MRI scans and voxel-based morphometry (VBM) and to identify changes in white matter tract orientation we used diffusion tensor imaging (DTI). A major finding of our study was that there were both gray and white matter changes in the vicinity of the auditory cortex for subjects with hearing loss alone relative to those with tinnitus and those with normal hearing. We did not find significant changes in gray or white matter in subjects with tinnitus and hearing loss compared to normal hearing controls. VBM analysis revealed that individuals with hearing loss without tinnitus had gray matter decreases in anterior cingulate and superior and medial frontal gyri relative to those with hearing loss and tinnitus. Region-of-interest analysis revealed additional decreases in superior temporal gyrus for the hearing loss group compared to the tinnitus group. Investigating effects of hearing loss alone, we found gray matter decreases in superior and medial frontal gyri in participants with hearing loss compared to normal hearing controls. DTI analysis showed decreases in fractional anisotropy values in the right superior and inferior longitudinal fasciculi, corticospinal tract, inferior fronto-occipital tract, superior occipital fasciculus, and anterior thalamic radiation for the hearing loss group relative to normal hearing controls. In attempting to dissociate the effect of tinnitus from hearing loss, we observed that hearing loss rather than tinnitus had the greatest influence on gray and white matter alterations.

Research highlights

► Ninety percent of those with tinnitus have some hearing loss. ► Only 40% of those with hearing loss have tinnitus. ► Structural brain changes are associated with either hearing loss or tinnitus. ► Most extensive gray and white matter changes were found in hearing loss alone. ► Minimal structural changes were found in hearing loss with tinnitus.

Introduction

Tinnitus, from the Latin word tinnire for “to ring,” is a phantom perception of sound when no such sound is present externally. Although most incidences of tinnitus are temporary, chronic subjective tinnitus occurs in 4–15% of the general population, with the prevalence increasing in those above 50 years of age to almost 20% (Moller, 2007). Broadly speaking, about 90% of individuals with chronic tinnitus have some form of hearing loss; however, only about 30–40% of those with hearing loss develop tinnitus (Davis and Rafaie, 2000, Lockwood et al., 2002, Moller, 2007). For instance, Barnea et al. (1990) found that 8% of patients with tinnitus had normal hearing thresholds (defined as better than or equal to 20 dB HL) up to 8000 Hz. As reported by the National Center for Health Statistics (Adams et al., 1999) tinnitus affects about 12% of the men between the ages of 65–74 years and the prevalence of hearing impairment in the tinnitus population is between 80 and 90%. Hearing loss affects about 35% of men between the ages of 65–74 years. This means, approximately 65–70% of those with hearing loss in the 65–75 years range do not suffer from tinnitus. The prevalence of hearing loss is lower in the 45–64 years range; however, the percentage of those with tinnitus in the hearing impaired group is similar. Although there have been several brain imaging studies investigating neural bases of tinnitus, few have examined its relationship with hearing loss, and the exact mechanisms and brain regions associated with tinnitus remain poorly understood. In the present study, we investigated structural gray and white matter changes related to tinnitus and hearing loss and attempted to dissociate them from changes due to hearing loss alone. Spatial patterns of structural change are a means of studying long-term functional changes associated with chronic tinnitus or hearing loss and are indicative of potential mechanisms causing such changes. We used voxel-based morphometry (VBM) to compare the volume and concentration of gray matter between tinnitus and non-tinnitus groups at the voxel-level using high-resolution magnetic resonance imaging (MRI). Further, we used diffusion tensor imaging (DTI) to investigate changes in organization of white matter tracts between tinnitus and non-tinnitus groups.

Functional brain imaging studies in humans have provided evidence for a distributed network of cortical regions associated with tinnitus (Giraud et al., 1999, Lockwood et al., 2001, Lockwood et al., 2002, Mirz et al., 2000a, Mirz et al., 2000b, Smits et al., 2007). There have been three studies to date investigating the gross anatomical changes in gray matter in individuals with tinnitus (Landgrebe et al., 2009, Muhlau et al., 2006, Schneider et al., 2009). The previous studies using VBM (Landgrebe et al., 2009, Muhlau et al., 2006) provide evidence for gray matter changes in individuals with tinnitus and normal hearing relative to a normal hearing non-tinnitus control group in both the auditory and limbic systems. The specific structures within these systems identified by the two studies are different. Muhlau et al. found gray matter increases in the thalamus and gray matter decreases in the subcallosal frontal cortex, while Landgrebe and colleagues detected gray matter decreases in the right inferior colliculus and the left hippocampus for the tinnitus participants relative to controls. Whereas the thalamus and inferior colliculus are prominent and necessary junctures in the central auditory system, subcallosal frontal cortex and the hippocampus are associated with processing of emotion and memory, respectively, and are part of the limbic system. The patient demographics in both studies were similar. However, there may be other contributory factors for the different results: there were some differences in the patient characteristics related to laterality of perceived tinnitus (majority in both studies perceived the tinnitus as bilateral, a minority perceived it as lateralized) and personality traits or depressive symptoms (8 patients had mild-to-moderate depressive symptoms in the Landgrebe study but not in the Muhlau study). Therefore, although these studies are informative, they present contradictory results and cannot necessarily be generalized to the larger tinnitus population with hearing loss. In contrast, Schneider et al. (2009)'s study included those with hearing loss in addition to tinnitus. Using individual morphological segmentation, Schneider et al. (2009) found gray matter reductions in medial Heschl's gyrus for those with tinnitus relative to controls without tinnitus (29 out of the 42 control participants had normal hearing). The study also found some evidence for an association between volume reduction and hearing loss, dependent on the tinnitus status, musical training of the participant and the degree of symmetry of their hearing loss. The study concentrated on Heschl's gyrus and did not include non-primary auditory cortex regions in its investigation. Thus, there remains the outstanding question about the extent and type of gray matter changes in the auditory and non-auditory processing areas due to hearing loss and tinnitus.

Animal studies, much like human studies, have mainly focused on the functional consequences of hearing loss or tinnitus along the central auditory processing pathway. These studies have implicated physiological changes in the dorsal cochlear nucleus (Kaltenbach et al., 2000), the inferior colliculus (Chen and Jastreboff, 1995, Wang et al., 2002), thalamus (Basta et al., 2005, Basta et al., 2008), and the auditory cortices (Basta et al., 2008, Eggermont and Kenmochi, 1998). A few animal studies investigating structural changes after hearing loss found reduced cell density in the brain stem, specifically in the dorsal cochlear nucleus, superior olive and the inferior colliculus (Kim et al., 1997), and medial geniculate body of the thalamus and the primary auditory cortex (Basta et al., 2005).

The first study to investigate white matter microstructural integrity in persons with tinnitus was a pilot study (Lee et al., 2007), but there have been other DTI investigations focused on sensorineural hearing loss (Chang et al., 2004, Lee et al., 2004, Lin et al., 2008). Chang et al. (2004) focused their attention on the central auditory pathways, primarily in the brainstem region, by performing partial-brain diffusion tensor imaging and doing a further focused region-of-interest analysis. They found significantly reduced fractional anisotropy (FA) values for participants with hearing loss in the fiber tracts passing through the superior olivary nucleus, lateral lemniscus, inferior colliculus and auditory radiation regions. FA is a measure of the degree of diffusion directionality, and is sensitive to changes in white matter microstructure; a large FA value implies that white matter tracts are oriented in the same direction and a lower FA value indicates loss of white matter or that white matter tracts are disorganized and radiating in all directions. The subjects were of both genders, ranged in age from 8 to 85 years with mild-to-severe hearing loss and 2 of the 10 subjects had unilateral hearing loss while the remaining 8 had bilateral hearing loss. The heterogeneity of the subject population severely limits interpretation and generalization of the study. Lin et al. (2008) studied three groups of patients: those with bilateral hearing loss, those with unilateral hearing loss and those with partial hearing loss. They focused their investigation on two ROIs in the lateral lemniscus and the inferior colliculus where they found decreased FA values for all patients. This suggests that hearing loss may be associated with uniform changes in white matter orientation; however, it is not clear how such changes will occur when hearing loss is accompanied by chronic tinnitus, and whether such white matter changes occur in other brain areas, particularly in neocortex.

The intent of the present study was to investigate the effect of chronic tinnitus and hearing loss on the brain's gross anatomy and dissociate these changes from those due to hearing loss alone. Our specific focus was the region around the primary auditory cortex and auditory processing pathways, leading into and out of the primary auditory cortex. Our hypothesis was that there are distinct spatial patterns of gray and white matter changes that are related to hearing loss or tinnitus. Based on previous studies, we expected that there are tinnitus-related volumetric changes in gray matter in inferior colliculus, parts of the thalamus, and subcallosal frontal cortex. Based on previous DTI studies of sensorineural hearing loss, we expected changes in orientation of subcortical white matter tracts in the anterior thalamic radiation and lateral lemniscus.

Section snippets

Results

Three groups of subjects participated in the study: TIN (those with tinnitus and hearing loss), HL (those with hearing loss without tinnitus), and NH (normal hearing individuals without tinnitus). We conducted a structural MRI study to investigate both changes in gray matter using VBM and in white matter using DTI.

Discussion

Subjective tinnitus occurs frequently as a consequence of hearing impairment. The hearing loss can cause reorganization of the auditory nerve, the central auditory processing pathways and the cortex, possibly leading to tinnitus. However, the underlying neural mechanisms and changes associated with tinnitus are poorly understood and not everyone with hearing loss develops tinnitus. The aim of the present study was to investigate gray and white matter changes in individuals with tinnitus and

Subjects

All participants understood and signed a written consent for NIH/NINDS-NIDCD IRB Protocol 06-DC-0218 and were suitably compensated. They were recruited from the greater Washington, D.C. metropolitan area.

The tinnitus group (TIN) consisted of 8 male volunteers (age range = 42–64 years, mean = 56.13 years, SD = 7.04 years) with bilateral, mild-to-moderate hearing loss and chronic subjective tinnitus that had persisted for between 3 and 38 years at the time of their scan. The tinnitus percept was most

Acknowledgments

The research was supported by the NIH-NIDCD Intramural Research Program and a grant from the Tinnitus Research Consortium to FTH. We are grateful to Dr. Allen Braun of the Language Section and the Audiology clinic staff of NIDCD-NIH: Dr. H. J. Kim, Dr. C. Brewer, Nurse Practitioner S. Rudy, audiologist C. Zalewski, for their diligent efforts in screening the participants in the study. We thank Kathy Xu for her help in the initial stages of the DTI analysis and Christopher Grindrod for his

References (65)

  • J.A. Kaltenbach et al.

    Plasticity of spontaneous neural activity in the dorsal cochlear nucleus after intense sound exposure

    Hear. Res.

    (2000)
  • J. Kim et al.

    Degeneration of axons in the brainstem of the chinchilla after auditory overstimulation

    Hear. Res.

    (1997)
  • M. Kubicki et al.

    Voxel-based morphometric analysis of gray matter in first episode schizophrenia

    Neuroimage

    (2002)
  • M. Landgrebe et al.

    Structural brain changes in tinnitus: grey matter decrease in auditory and non-auditory brain areas

    Neuroimage

    (2009)
  • Y.J. Lee et al.

    Evaluation of white matter structures in patients with tinnitus using diffusion tensor imaging

    J. Clin. Neurosci.

    (2007)
  • J.A. Maldjian et al.

    An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets

    Neuroimage

    (2003)
  • F. Mirz et al.

    Positron emission tomography of cortical centers of tinnitus

    Hear. Res.

    (1999)
  • A.R. Moller

    Neural plasticity in tinnitus

    Prog. Brain Res.

    (2006)
  • A.R. Moller

    Tinnitus: presence and future

    Prog. Brain Res.

    (2007)
  • V.B. Penhune et al.

    The morphometry of auditory cortex in the congenitally deaf measured using MRI

    Neuroimage

    (2003)
  • P. Salgado-Pineda et al.

    Sustained attention impairment correlates to gray matter decreases in first episode neuroleptic-naive schizophrenic patients

    Neuroimage

    (2003)
  • P. Schneider et al.

    Reduced volume of Heschl's gyrus in tinnitus

    Neuroimage

    (2009)
  • S.M. Smith et al.

    Advances in functional and structural MR image analysis and implementation as FSL

    Neuroimage

    (2004)
  • S.M. Smith et al.

    Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data

    Neuroimage

    (2006)
  • M.A. Trivedi et al.

    Structural MRI discriminates individuals with Mild Cognitive Impairment from age-matched controls: a combined neuropsychological and voxel based morphometry study

    Alzheimers Dement.

    (2006)
  • J. Wang et al.

    Functional reorganization in chinchilla inferior colliculus associated with chronic and acute cochlear damage

    Hear. Res.

    (2002)
  • P.F. Adams et al.

    Current estimates from the National Health Interview Survey, 1996

    Vital. Health. Stat.

    (1999)
  • G. Andersson et al.

    Regional cerebral blood flow during tinnitus: a PET case study with lidocaine and auditory stimulation

    Acta Otolaryngol.

    (2000)
  • AnderssonJ.L.R. et al.

    Non-linear registration, aka spatial normalisation

  • AnderssonJ.L.R. et al.

    Non-linear optimisation

  • G. Barnea et al.

    Tinnitus with normal hearing sensitivity: extended high-frequency audiometry and auditory-nerve brain-stem-evoked responses

    Audiology

    (1990)
  • T.E. Behrens et al.

    Characterization and propagation of uncertainty in diffusion-weighted MR imaging

    Magn. Reson. Med.

    (2003)
  • Cited by (0)

    View full text