Intracranial Mapping of a Cortical Tinnitus System using Residual Inhibition

Tinnitus can occur when damage to the peripheral auditory system leads to spontaneous brain activity that is interpreted as sound [1Jastreboff P.J. Phantom auditory perception (tinnitus): mechanisms of generation and perception.Neurosci. Res. 1990; 8: 221-254Crossref PubMed Scopus (1146) Google Scholar, 2Roberts L.E. Eggermont J.J. Caspary D.M. Shore S.E. Melcher J.R. Kaltenbach J.A. Ringing ears: the neuroscience of tinnitus.J. Neurosci. 2010; 30: 14972-14979Crossref PubMed Scopus (433) Google Scholar]. Many abnormalities of brain activity are associated with tinnitus, but it is unclear how these relate to the phantom sound itself, as opposed to predisposing factors or secondary consequences [3Noreña A.J. Farley B.J. Tinnitus-related neural activity: theories of generation, propagation, and centralization.Hear. Res. 2013; 295: 161-171Crossref PubMed Scopus (140) Google Scholar]. Demonstrating "core" tinnitus correlates (processes that are both necessary and sufficient for tinnitus perception) requires high-precision recordings of neural activity combined with a behavioral paradigm in which the perception of tinnitus is manipulated and accurately reported by the subject. This has been previously impossible in animal and human research. Here we present extensive intracranial recordings from an awake, behaving tinnitus patient during short-term modifications in perceived tinnitus loudness after acoustic stimulation (residual inhibition) [4Roberts L.E. Residual inhibition.Prog. Brain Res. 2007; 166: 487-495Crossref PubMed Scopus (52) Google Scholar], permitting robust characterization of core tinnitus processes. As anticipated, we observed tinnitus-linked low-frequency (delta) oscillations [5Llinás R.R. Ribary U. Jeanmonod D. Kronberg E. Mitra P.P. Thalamocortical dysrhythmia: A neurological and neuropsychiatric syndrome characterized by magnetoencephalography.Proc. Natl. Acad. Sci. USA. 1999; 96: 15222-15227Crossref PubMed Scopus (1011) Google Scholar, 6Weisz N. Moratti S. Meinzer M. Dohrmann K. Elbert T. Tinnitus perception and distress is related to abnormal spontaneous brain activity as measured by magnetoencephalography.PLoS Med. 2005; 2: e153Crossref PubMed Scopus (307) Google Scholar, 7Kahlbrock N. Weisz N. Transient reduction of tinnitus intensity is marked by concomitant reductions of delta band power.BMC Biol. 2008; 6: 4Crossref PubMed Scopus (70) Google Scholar, 8Sedley W. Teki S. Kumar S. Barnes G.R. Bamiou D.-E. Griffiths T.D. Single-subject oscillatory γ responses in tinnitus.Brain. 2012; 135: 3089-3100Crossref PubMed Scopus (60) Google Scholar, 9Adjamian P. Sereda M. Zobay O. Hall D.A. Palmer A.R. Neuromagnetic indicators of tinnitus and tinnitus masking in patients with and without hearing loss.J. Assoc. Res. Otolaryngol. 2012; 13: 715-731Crossref PubMed Scopus (84) Google Scholar], thought to be triggered by low-frequency bursting in the thalamus [10Jeanmonod D. Magnin M. Morel A. Low-threshold calcium spike bursts in the human thalamus. Common physiopathology for sensory, motor and limbic positive symptoms.Brain. 1996; 119: 363-375Crossref PubMed Scopus (297) Google Scholar, 11Kalappa B.I. Brozoski T.J. Turner J.G. Caspary D.M. Single unit hyperactivity and bursting in the auditory thalamus of awake rats directly correlates with behavioural evidence of tinnitus.J. Physiol. 2014; 592: 5065-5078Crossref PubMed Scopus (104) Google Scholar]. Contrary to expectation, these delta changes extended far beyond circumscribed auditory cortical regions to encompass almost all of auditory cortex, plus large parts of temporal, parietal, sensorimotor, and limbic cortex. In discrete auditory, parahippocampal, and inferior parietal "hub" regions [12De Ridder D. Vanneste S. Weisz N. Londero A. Schlee W. Elgoyhen A.B. Langguth B. An integrative model of auditory phantom perception: tinnitus as a unified percept of interacting separable subnetworks.Neurosci. Biobehav. Rev. 2014; 44: 16-32Crossref PubMed Scopus (259) Google Scholar], these delta oscillations interacted with middle-frequency (alpha) and high-frequency (beta and gamma) activity, resulting in a coherent system of tightly coupled oscillations associated with high-level functions including memory and perception.