A methodological assessment of studies that use voxel-based morphometry to study neural changes in tinnitus patients

Background The scientific understanding of tinnitus and its etiology has transitioned from thinking of tinnitus as solely a peripheral auditory problem to an increasing awareness that cortical networks may play a critical role in tinnitus percept or bother. With this change, studies that seek to use structural brain imaging techniques to better characterize tinnitus patients have become more common. These studies include using voxel-based morphometry (VBM) to determine if there are differences in regional gray matter volume in individuals who suffer from tinnitus and those who do not. However, studies using VBM in patients with tinnitus have produced inconsistent and sometimes contradictory results. Objective This paper is a systematic review of all of the studies to date that have used VBM to study regional gray matter volume in people with tinnitus, and explores ways in which methodological differences in these studies may account for their heterogeneous results. We also aim to provide guidance on how to conduct future studies using VBM to produce more reproducible results to further our understanding of disease processes such as tinnitus. Methods Studies about tinnitus and VBM were searched for using PubMed and Embase. These returned 15 and 25 results respectively. Of these, nine met the study criteria and were included for review. An additional 5 studies were identified in the literature as pertinent to the topic at hand and were added to the review, for a total of 13 studies. Results There was significant heterogeneity among the studies in several areas, including inclusion and exclusion criteria, software programs, and statistical analysis. We were not able to find publicly shared data or code for any study. Discussion The differences in study design, software analysis, and statistical methodology make direct comparisons between the different studies difficult. Especially problematic are the differences in the inclusion and exclusion criteria of the study, and the statistical design of the studies, both of which could radically alter findings. Thus, heterogeneity has complicated efforts to explore the etiology of tinnitus using structural MRI. Conclusion There is a pressing need to standardize the use of VBM when evaluating tinnitus patients. While some heterogeneity is expected given the rapid advances in the field, more can be done to ensure that there is internal validity between studies.