title: Reversing pathological neural activity using targeted plasticity.
abstract: Brain changes in response to nerve damage or cochlear trauma can generate pathological neural activity that is believed to be responsible for many types of chronic pain and tinnitus. Several studies have reported that the severity of chronic pain and tinnitus is correlated with the degree of map reorganization in somatosensory and auditory cortex, respectively. Direct electrical or transcranial magnetic stimulation of sensory cortex can temporarily disrupt these phantom sensations. However, there is as yet no direct evidence for a causal role of plasticity in the generation of pain or tinnitus. Here we report evidence that reversing the brain changes responsible can eliminate the perceptual impairment in an animal model of noise-induced tinnitus. Exposure to intense noise degrades the frequency tuning of auditory cortex neurons and increases cortical synchronization. Repeatedly pairing tones with brief pulses of vagus nerve stimulation completely eliminated the physiological and behavioural correlates of tinnitus in noise-exposed rats. These improvements persisted for weeks after the end of therapy. This method for restoring neural activity to normal may be applicable to a variety of neurological disorders.
authors.affiliation: Cortical Plasticity Laboratory, Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, Texas 75080, USA. navzer@utdallas.edu
authors.forename: Navzer D
authors.initials: ND
authors.lastname: Engineer
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Riley
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Seale
authors.forename: Will A
authors.initials: WA
authors.lastname: Vrana
authors.forename: Jai A
authors.initials: JA
authors.lastname: Shetake
authors.forename: Sindhu P
authors.initials: SP
authors.lastname: Sudanagunta
authors.forename: Michael S
authors.initials: MS
authors.lastname: Borland
authors.forename: Michael P
authors.initials: MP
authors.lastname: Kilgard
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001307:Auditory Perception / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005260:Female; D008959:Models, Neurological; D009473:Neuronal Plasticity / Q000502:physiology*; D009622:Noise / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014012:Tinnitus / Q000209:etiology / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D014630:Vagus Nerve / Q000502:physiology