Front Cover -- TINNITUS AND HYPERACUSIS -- TINNITUS AND HYPERACUSIS: Facts, Theories, and Clinical Implications -- Copyright -- Contents -- Preface -- Abbreviations in the main text -- 1 - Tinnitus, hyperacusis, and hearing loss -- 1.1 Introduction -- 1.2 Acquired hearing loss -- 1.2.1 Human data -- 1.2.2 Animal data -- 1.3 Loudness recruitment -- 1.3.1 Auditory nerve responses and recruitment -- 1.3.2 Central nervous system and recruitment -- 1.4 Noise-induced temporary threshold shifts -- 1.4.1 Animal data -- 1.4.2 Human findings -- 1.4.2.1 Autopsy material -- 1.4.2.2 Human ABR data -- 1.5 Noise exposure not causing PTS or TTS -- 1.6 Tinnitus pitch, loudness, and hearing loss -- 1.6.1 Tinnitus pitch -- 1.6.2 Tinnitus loudness -- 1.7 Summary -- References -- 2 - Epidemiology, etiology, and genetics -- 2.1 Prevalence of tinnitus and hyperacusis -- 2.1.1 Overall prevalence -- 2.1.2 Co-occurrence of tinnitus and hyperacusis -- 2.1.3 Tinnitus and auditory hallucinations -- 2.1.4 Co-occurrence of tinnitus and chronic pain -- 2.2 Etiology -- 2.2.1 Hidden hearing loss -- 2.2.2 Acquired hearing loss -- 2.2.3 Blast injury and concussions -- 2.2.3.1 Mechanisms -- 2.2.3.2 Military -- 2.2.3.3 Sports -- 2.2.4 Somatic injury -- 2.2.5 Stress -- 2.2.6 Ménière's disease -- 2.2.7 Tinnitus risk in common diseases -- 2.2.8 Tinnitus and aging -- 2.3 Genetics -- 2.3.1 Hereditary aspects -- 2.3.2 Genome studies -- 2.3.2.1 Candidate gene studies -- 2.3.2.2 Genome-wide association studies -- 2.3.3 Epigenetic factors possibly contributing to tinnitus -- 2.4 Summary -- References -- 3 - Physiological markers of tinnitus and hyperacusis -- 3.1 Spontaneous neural activity. Noise or information carrier? -- 3.1.1 Auditory nerve fibers -- 3.1.2 Spontaneous firing in auditory cortex -- 3.2 Spike-firing synchrony -- 3.2.1 Sparse cross-correlation in auditory cortex

3.2.2 Epidural versus intracortical spike-based receptive fields -- 3.3 Brain rhythms -- 3.3.1 Ultra-slow fluctuations -- 3.3.2 Delta -- 3.3.3 Theta -- 3.3.4 Alpha -- 3.3.5 Beta -- 3.3.6 Gamma -- 3.4 Thalamocortical oscillations -- 3.5 Spike-LFP and EEG/MEG correlation and networks in human cortex -- 3.5.1 Correlation -- 3.5.2 Resting state networks -- 3.6 Auditory-evoked potentials -- 3.6.1 The auditory brainstem response -- 3.6.2 The auditory steady-state response -- 3.6.3 The longer latency obligatory responses -- 3.6.4 The event-related responses -- 3.6.5 Evoked magnetic fields -- 3.7 Summary -- References -- 4 - Substrates of tinnitus and hyperacusis in the animal auditory system -- 4.1 Spontaneous firing activity in general -- 4.2 Effects of salicylate and noise exposure in auditory pathways -- 4.3 Cell types and afferent pathways -- 4.3.1 The ventral cochlear nucleus -- 4.3.2 The dorsal cochlear nucleus -- 4.4 Hyperacusis -- 4.4.1 Evidence from single units and cortical oscillations -- 4.4.2 Behavioral signs of hyperacusis and tinnitus -- 4.4.3 Putative different pathways for igniting hyperacusis and tinnitus -- 4.4.4 A role for the reticular formation and cerebellum in tinnitus and hyperacusis -- 4.5 Neurotransmitters, neuromodulators, and immediate early genes -- 4.5.1 Neurotransmitters -- 4.5.1.1 Glutamate -- 4.5.1.2 Glycine -- 4.5.1.3 GABA -- 4.5.2 Neuromodulators -- 4.5.2.1 Acetylcholine -- 4.5.2.2 Serotonin -- 4.5.3 Immediate early genes -- 4.5.3.1 Noise exposure -- 4.5.3.2 Salicylate administration -- 4.6 Summary -- References -- 5 - Evoked potentials and neuroimaging in humans with tinnitus -- 5.1 Auditory-evoked potentials and tinnitus -- 5.1.1 Subcortical -- 5.1.2 Cortical -- 5.1.2.1 Obligatory-evoked potentials -- 5.1.2.2 Event-related potentials -- 5.2 Brain structure, rhythms, and networks -- 5.2.1 Structural brain changes

5.2.1.1 Gray matter -- 5.2.1.2 White matter -- 5.2.2 Resting-state brain metabolism -- 5.2.3 Brain rhythms -- 5.2.4 Comparison of VBM and EEG -- 5.2.5 Neurochemistry -- 5.3 Brain networks in humans with tinnitus -- 5.3.1 MRI-based networks -- 5.3.1.1 Auditory network analyses -- 5.3.1.2 Tinnitus networks in animal models -- are they relevant for humans? -- 5.3.1.3 Whole brain network analyses -- 5.3.2 EEG-based networks -- 5.4 Summary -- References -- 6 - Tinnitus and hyperacusis: The nonclassical auditory system -- 6.1 Overview of brain areas activated by sound compared to resting state -- 6.2 The amygdala -- 6.2.1 Connectivity of the amygdala with the auditory system -- 6.2.2 Effects of noise exposure -- 6.2.3 Effects of salicylate -- 6.2.4 Effects of blast injury -- 6.3 The hippocampus -- 6.3.1 Effects of noise exposure -- 6.3.2 Effects of salicylate -- 6.4 Cingulate cortex -- 6.5 Human tinnitus and the limbic system -- 6.5.1 Structural changes in the limbic system -- 6.5.2 MRI-based functional connectivity -- 6.5.3 Effects of hearing loss on connectivity of the amygdala -- 6.5.4 EEG-based activity in tinnitus with neurological comorbidities -- 6.6 Comparison of animal and human data -- 6.7 Cerebellum -- 6.7.1 Animal data -- 6.7.1.1 Activity changes in tinnitus -- 6.7.1.2 Cerebellar interaction with the auditory system -- 6.7.2 Human studies -- 6.8 Summary -- References -- 7 - Tinnitus and the nonauditory brain -- 7.1 The nonauditory brain in cognition and perception -- 7.1.1 Connectivity of auditory and prefrontal cortex -- 7.1.2 Perception and cognition -- 7.2 Tinnitus-related changes in structural and functional MRI networks -- 7.2.1 Structural changes -- 7.2.1.1 Gray matter changes -- 7.2.1.2 White matter changes -- 7.2.2 fMRI-based functional network changes -- 7.3 EEG/MEG-based network connectivity changes in tinnitus

7.4 Comparing functional connectivity changes in tinnitus and hearing loss -- 7.4.1 Changes in tinnitus -- 7.4.2 Changes in hearing loss -- 7.4.3 Comparison of the effects of tinnitus and hearing loss on functional connectivity -- 7.5 Connectivity changes of the nucleus accumbens -- 7.6 Transitions from no-tinnitus to tinnitus, and from acute to chronic tinnitus -- 7.6.1 Tinnitus prerequisites -- 7.6.2 Turning on tinnitus -- 7.6.3 From acute to chronic tinnitus -- 7.7 Summary -- References -- Further reading -- 8 - Loudness recruitment and hyperacusis: the central-gain model -- 8.1 Hyperacusis and related symptoms -- 8.1.1 Loudness hyperacusis and noise sensitivity -- 8.1.2 Pain hyperacusis -- 8.1.3 Phonophobia and misophonia -- 8.1.4 Psychoacoustic tests -- 8.2 Hyperacusis in common disorders -- 8.2.1 Autism spectrum disorder -- 8.2.2 Attention deficit and hyperactivity disorder -- 8.2.3 Mild traumatic brain injury -- 8.3 Loudness recruitment and increased central gain -- 8.4 Central gain and hyperacusis -- 8.4.1 Detection of hyperacusis in animals -- 8.4.1.1 The acoustic startle reflex -- 8.4.1.2 Operant conditioning methods with reaction time measures -- 8.4.2 Central gain enhancement in the animal auditory system -- 8.4.3 Central gain enhancement in animal limbic regions -- 8.5 Human studies of hyperacusis -- 8.5.1 Behavioral -- 8.5.2 Electrophysiology and neural imaging -- 8.5.2.1 EEG-based activity and connectivity -- 8.5.2.2 fMRI in the classical auditory system -- 8.6 Mechanisms of hyperacusis -- 8.6.1 Neural inhibition -- 8.6.1.1 Inhibitory interneurons in auditory cortex -- 8.6.1.2 Disruption of lateral inhibition after hearing loss -- 8.6.2 Homeostatic plasticity and central gain enhancement -- 8.6.3 The role of the olivocochlear system -- 8.6.4 A role for serotonin -- 8.7 Summary -- References -- 9 - Bottom-up tinnitus models

9.1 The neural synchrony model -- 9.1.1 Spontaneous versus sound-driven synchrony -- 9.1.2 Neural synchrony in noise-exposed animals -- 9.1.3 Neural synchrony in humans -- 9.1.4 What does synchrony explain and what is missing? -- 9.2 The cortical map reorganization and filling-in models -- 9.2.1 Tonotopic map reorganization in animals -- 9.2.2 Findings in humans -- 9.2.2.1 Neural imaging -- 9.2.2.2 Behavioral -- 9.2.3 The filling-in or phantom model -- 9.3 The maladaptive plasticity model -- 9.3.1 Neural mechanisms -- 9.3.2 Maladaptive changes underlying phantom pain and extrapolation to tinnitus -- 9.4 The central gain enhancement model and tinnitus -- 9.5 The insufficient central compensation model -- 9.5.1 The cortical inhibitory network -- 9.5.2 Role of neural gain -- 9.5.3 Disrupted auditory-frontostriatal connectivity -- 9.5.4 Is this model necessary and sufficient to explain tinnitus? -- 9.6 Summary -- References -- 10 - Top-down tinnitus models -- 10.1 The Jastreboff model -- 10.2 The thalamocortical dysrhythmia/global workspace model -- 10.2.1 Thalamocortical dysrhythmia -- 10.2.2 Is the thalamocortical dysrhythmia model feasible for tinnitus? -- 10.2.3 The global workspace addition -- 10.3 Noise cancellation by frontostriatal gating -- 10.3.1 Anatomy and function of the striatum -- 10.3.2 The NAc-TRN noise cancellation model -- 10.3.3 The NAc-TRN gating model in practice -- 10.3.4 The caudate as a gate in tinnitus perception -- 10.4 The increased central noise model -- 10.5 Interacting neural network models -- 10.5.1 An EEG-frequency bands model -- 10.5.2 An fMRI-based network model -- 10.6 The sensory predictive coding or Bayesian inference model -- 10.6.1 The Bayesian model -- 10.6.2 Neurophysiological correlates of prediction errors -- 10.6.3 A conceptual predictive coding model for tinnitus

10.6.4 A neurobiological substrate of predictive coding for tinnitus