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Reversing pathological neural activity using targeted 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.

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Figure 1: VNS–tone pairing causes map plasticity.
Figure 2: VNS/multiple tone pairing eliminates the behavioural correlate of tinnitus.
Figure 3: VNS/multiple tone pairing reverses map distortion.
Figure 4: Neurophysiological properties of naive, sham and therapy rats.

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We would like to thank A. Kuzu, J. Omana, D. Vuppala, H. Rasul, M. Fink, E. Hanacik, R. Miller and C. Walker for help with rat behavioural training. We would also like to thank J. Eggermont, A. Møller, C. Bauer, J. Fritz, H. Reed, C. Engineer, A. Reed, M. Brosch, R. Rennaker, R. Beitel, V. Miller, C. McIntyre, G. White, P. Pandya, R. Tyler and D. deRidder for suggestions about earlier versions of the manuscript. This work was supported by the James S. McDonnell Foundation, the Texas Advanced Research Program, the National Institute for Deafness and other Communication Disorders, and MicroTransponder Inc.

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Authors and Affiliations



N.D.E., J.R.R., J.D.S., S.P.S. and M.S.B. did the behaviour training sessions, noise exposure and auditory brainstem response recordings. N.D.E., J.R.R., J.D.S., W.A.V. and J.A.S. did cortical microelectrode mappings. J.A.S. did the A1 mapping surgeries. S.P.S. and N.D.E. did all the VNS implant surgeries. M.P.K. and N.D.E. designed the experiments, wrote the manuscript and performed data analysis. All authors discussed the paper and commented on the manuscript.

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Correspondence to Navzer D. Engineer.

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Competing interests

N.D.E. is a full-time employee of MicroTransponder Inc (Austin, Texas), which develops therapies using neurostimulation. M.P.K. is a consultant and shareholder of MicroTransponder Inc.

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Engineer, N., Riley, J., Seale, J. et al. Reversing pathological neural activity using targeted plasticity. Nature 470, 101–104 (2011).

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