Reversing pathological neural activity using targeted plasticity

Abstract

Neuronal plasticity, the process by which the human brain changes as a result of experience, is thought to be the source of several chronic neurological conditions, including tinnitus. Using a rodent model for noise-induced tinnitus, Engineer et al. find that reversing neural plasticity induced by the tinnitus can correct perceptual impairment. Repeatedly pairing tones with a brief stimulation of the vagus nerve sharpens auditory neuron tuning and eliminates the physiological and behavioural signs of tinnitus. This proof of principle suggests that simply restoring normal neural activity to circuits that have been pathologically modified could provide a benefit in conditions involving aberrant neural plasticity. Neuronal plasticity is thought to be the source of several chronic neurological conditions, including tinnitus. Using a rodent model for noise-induced tinnitus, this study finds that reversing neural plasticity induced by the tinnitus can correct perceptual impairments caused by the ailment. Pairing tones with stimulation of the vagus nerve sharpened auditory neuron tuning and eliminated the physiological as well as behavioural correlates of the tinnitus. This proof of principle suggests that simply restoring normal neural activity to circuits that have been pathologically modified could provide a benefit in those ailments involving aberrant neural plasticity. 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 tinnitus1,2,3. 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, respectively1,4. Direct electrical or transcranial magnetic stimulation of sensory cortex can temporarily disrupt these phantom sensations5. 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.