Brain Regions Responsible for Tinnitus Distress and Loudness: A Resting-State fMRI Study

Subjective tinnitus is characterized by the perception of phantom sound without an external auditory stimulus. We hypothesized that abnormal functionally connected regions in the central nervous system might underlie the pathophysiology of chronic subjective tinnitus. Statistical significance of functional connectivity (FC) strength is affected by the regional autocorrelation coefficient (AC). In this study, we used resting-state functional MRI (fMRI) and measured regional mean FC strength (mean cross-correlation coefficient between a region and all other regions without taking into account the effect of AC (rGC) and with taking into account the effect of AC (rGCa) to elucidate brain regions related to tinnitus symptoms such as distress, depression and loudness. Consistent with previous studies, tinnitus loudness was not related to tinnitus-related distress and depressive state. Although both rGC and rGCa revealed similar brain regions where the values showed a statistically significant relationship with tinnitus-related symptoms, the regions for rGCa were more localized and more clearly delineated the regions related specifically to each symptom. The rGCa values in the bilateral rectus gyri were positively correlated and those in the bilateral anterior and middle cingulate gyri were negatively correlated with distress and depressive state. The rGCa values in the bilateral thalamus, the bilateral hippocampus, and the left caudate were positively correlated and those in the left medial superior frontal gyrus and the left posterior cingulate gyrus were negatively correlated with tinnitus loudness. These results suggest that distinct brain regions are responsible for tinnitus symptoms. The regions for distress and depressive state are known to be related to depression, while the regions for tinnitus loudness are known to be related to the default mode network and integration of multi-sensory information.

[1]  Lisa D. Nickerson,et al.  The hypnotic zolpidem increases the synchrony of BOLD signal fluctuations in widespread brain networks during a resting paradigm , 2013, NeuroImage.

[2]  C. Rorden,et al.  Stereotaxic display of brain lesions. , 2000, Behavioural neurology.

[3]  W. Delb,et al.  Tinnitus: Distinguishing between Subjectively Perceived Loudness and Tinnitus-Related Distress , 2012, PloS one.

[4]  P. Dijk,et al.  Neural correlates of human somatosensory integration in tinnitus , 2010, Hearing Research.

[5]  Michael W. Cole,et al.  Global Connectivity of Prefrontal Cortex Predicts Cognitive Control and Intelligence , 2012, The Journal of Neuroscience.

[6]  Harold Burton,et al.  Altered networks in bothersome tinnitus: a functional connectivity study , 2012, BMC Neuroscience.

[7]  G. Lindberg,et al.  Differences in resting state regional cerebral blood flow assessed with 99mTc-HMPAO SPECT and brain atlas matching between depressed patients with and without tinnitus , 2002, Nuclear medicine communications.

[8]  M. Czisch,et al.  Benzodiazepines Counteract Rostral Anterior Cingulate Cortex Activation Induced by Cholecystokinin-Tetrapeptide in Humans , 2013, Biological Psychiatry.

[9]  P. Larson,et al.  Tinnitus modulation by deep brain stimulation in locus of caudate neurons (area LC) , 2010, Neuroscience.

[10]  P. Dechent,et al.  Neural correlates of tinnitus related distress: An fMRI-study , 2013, Hearing Research.

[11]  T. Nihashi,et al.  Functional connectivity of epileptogenic focus: detection and relationship with default mode network , 2012, 2012 ICME International Conference on Complex Medical Engineering (CME).

[12]  Simon B. Eickhoff,et al.  An improved framework for confound regression and filtering for control of motion artifact in the preprocessing of resting-state functional connectivity data , 2013, NeuroImage.

[13]  Barry Horwitz,et al.  Neuroanatomical changes due to hearing loss and chronic tinnitus: A combined VBM and DTI study , 2011, Brain Research.

[14]  Danielle S Bassett,et al.  Genetic Influences on Cost-Efficient Organization of Human Cortical Functional Networks , 2011, The Journal of Neuroscience.

[15]  Karl J. Friston,et al.  Frequency-Specific Coupling in the Cortico-Cerebellar Auditory System , 2008, Journal of neurophysiology.

[16]  B. Biswal,et al.  Functional connectivity in the motor cortex of resting human brain using echo‐planar mri , 1995, Magnetic resonance in medicine.

[17]  Mark A. Chevillet,et al.  Dysregulation of Limbic and Auditory Networks in Tinnitus , 2011, Neuron.

[18]  Dirk De Ridder,et al.  Structural brain changes in tinnitus: Grey matter decrease in auditory and non-auditory brain areas , 2009, NeuroImage.

[19]  P. Goodwin,et al.  The loudness of tinnitus. , 1980, Acta oto-laryngologica.

[20]  Berthold Langguth,et al.  Tinnitus and insomnia. , 2007, Progress in brain research.

[21]  Arthur W Toga,et al.  Anterior cingulate, gyrus rectus, and orbitofrontal abnormalities in elderly depressed patients: an MRI-based parcellation of the prefrontal cortex. , 2004, The American journal of psychiatry.

[22]  Keith A. Johnson,et al.  Cortical Hubs Revealed by Intrinsic Functional Connectivity: Mapping, Assessment of Stability, and Relation to Alzheimer's Disease , 2009, The Journal of Neuroscience.

[23]  Sven Vanneste,et al.  Tinnitus: network pathophysiology-network pharmacology , 2012, Front. Syst. Neurosci..

[24]  B. Langguth,et al.  Tinnitus severity, depression, and the big five personality traits. , 2007, Progress in brain research.

[25]  D. Tank,et al.  Brain magnetic resonance imaging with contrast dependent on blood oxygenation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[26]  S. Rombouts,et al.  Consistent resting-state networks across healthy subjects , 2006, Proceedings of the National Academy of Sciences.

[27]  Ilka A. Haala,et al.  Neural correlates of transmeatal cochlear laser (TCL) stimulation in healthy human subjects , 2007, Neuroscience Letters.

[28]  D. Schacter,et al.  The Brain's Default Network , 2008, Annals of the New York Academy of Sciences.

[29]  Marco Congedo,et al.  The neural correlates of tinnitus-related distress , 2010, NeuroImage.

[30]  C. Nagata,et al.  Prevalence of Tinnitus in Community-Dwelling Japanese Adults , 2011, Journal of epidemiology.

[31]  T. Brozoski,et al.  Effect of Tinnitus Retraining Therapy on the Loudness and Annoyance of Tinnitus: A Controlled Trial , 2011, Ear and hearing.

[32]  Julio Artieda,et al.  Activation of Human Cerebral and Cerebellar Cortex by Auditory Stimulation at 40 Hz , 2002, The Journal of Neuroscience.

[33]  Talma Hendler,et al.  Global Functional Connectivity Deficits in Schizophrenia Depend on Behavioral State , 2011, The Journal of Neuroscience.

[34]  M. Meikle,et al.  Tinnitus: clinical measurement. , 2003, Otolaryngologic clinics of North America.

[35]  J. Henry,et al.  Psychoacoustic measures of tinnitus. , 2000, Journal of the American Academy of Audiology.

[36]  Van Te Chow,et al.  Handbook of applied hydrology : a compendium of water-resources technology , 1964 .

[37]  D. De Ridder,et al.  Neuroimaging and Neuromodulation: Complementary Approaches for Identifying the Neuronal Correlates of Tinnitus , 2012, Front. Syst. Neurosci..

[38]  Robert A Levine,et al.  Tinnitus, diminished sound-level tolerance, and elevated auditory activity in humans with clinically normal hearing sensitivity. , 2010, Journal of neurophysiology.

[39]  J B Spitzer,et al.  Development of the Tinnitus Handicap Inventory. , 1996, Archives of otolaryngology--head & neck surgery.

[40]  Bharat B. Biswal,et al.  Competition between functional brain networks mediates behavioral variability , 2008, NeuroImage.

[41]  Kazuhiro Shinosaki,et al.  Variance and Autocorrelation of the Spontaneous Slow Brain Activity , 2012, PloS one.

[42]  J P Rauschecker,et al.  Consensus for tinnitus patient assessment and treatment outcome measurement: Tinnitus Research Initiative meeting, Regensburg, July 2006. , 2007, Progress in Brain Research.

[43]  A. Lozano,et al.  Deep Brain Stimulation for Treatment-Resistant Depression , 2005, Neuron.

[44]  D. Hall,et al.  The mechanisms of tinnitus: Perspectives from human functional neuroimaging , 2009, Hearing Research.

[45]  Abraham Z. Snyder,et al.  Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion , 2012, NeuroImage.

[46]  D. De Ridder,et al.  The neural network of phantom sound changes over time: a comparison between recent‐onset and chronic tinnitus patients , 2011, The European journal of neuroscience.

[47]  A. Simmons,et al.  Structural neuroimaging studies in major depressive disorder. Meta-analysis and comparison with bipolar disorder. , 2011, Archives of general psychiatry.

[48]  D. Hall,et al.  Re-examining the relationship between audiometric profile and tinnitus pitch , 2011, International journal of audiology.

[49]  Changwei W. Wu,et al.  Brain activation in patients with idiopathic hyperacusis. , 2009, American journal of otolaryngology.

[50]  K. Burchiel,et al.  Deep Brain Stimulation Effects in Patients with Tinnitus , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[51]  Y. Chan Tinnitus: etiology, classification, characteristics, and treatment. , 2009, Discovery medicine.

[52]  M. Hamilton A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.

[53]  Winfried Schlee,et al.  Abnormal resting-state cortical coupling in chronic tinnitus , 2009, BMC Neuroscience.

[54]  M. Fox,et al.  The global signal and observed anticorrelated resting state brain networks. , 2009, Journal of neurophysiology.

[55]  Stephen M. Smith,et al.  fMRI resting state networks define distinct modes of long-distance interactions in the human brain , 2006, NeuroImage.

[56]  R. Burkard,et al.  The functional anatomy of the normal human auditory system: responses to 0.5 and 4.0 kHz tones at varied intensities. , 1999, Cerebral cortex.

[57]  P. Larson,et al.  Deep Brain Stimulation in Area LC Controllably Triggers Auditory Phantom Percepts , 2012, Neurosurgery.

[58]  Mert R. Sabuncu,et al.  The influence of head motion on intrinsic functional connectivity MRI , 2012, NeuroImage.

[59]  J. Eggermont,et al.  Ringing Ears: The Neuroscience of Tinnitus , 2010, The Journal of Neuroscience.

[60]  T. Hackett Information flow in the auditory cortical network , 2011, Hearing Research.

[61]  Mark A. Elliott,et al.  Impact of in-scanner head motion on multiple measures of functional connectivity: Relevance for studies of neurodevelopment in youth , 2012, NeuroImage.

[62]  Athena Demertzi,et al.  Auditory Resting-State Network Connectivity in Tinnitus: A Functional MRI Study , 2012, PloS one.

[63]  A Axelsson,et al.  Tinnitus--a study of its prevalence and characteristics. , 1989, British journal of audiology.

[64]  Dustin Scheinost,et al.  The intrinsic connectivity distribution: A novel contrast measure reflecting voxel level functional connectivity , 2012, NeuroImage.

[65]  W. Hiller,et al.  When Tinnitus Loudness and Annoyance Are Discrepant: Audiological Characteristics and Psychological Profile , 2007, Audiology and Neurotology.

[66]  M. Meikle,et al.  The Perceived Severity of Tinnitus: Some Observations Concerning a Large Population of Tinnitus Clinic Patients , 1984, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[67]  Berthold Langguth,et al.  Structural brain changes in tinnitus: grey matter decrease in auditory and non-auditory brain areas , 2009 .

[68]  B. Horwitz,et al.  Discrimination Task Reveals Differences in Neural Bases of Tinnitus and Hearing Impairment , 2011, PloS one.

[69]  B. Langguth,et al.  Neural correlates of tinnitus duration and Distress: A positron emission tomography study , 2013, Human brain mapping.