Cochlear implants are neuroprosthetic devices that can provide hearing to deaf patients1. Despite signi cant bene ts offered by cochlear implants, there are highly variable outcomes in how quickly hearing is restored and perceptual accuracy after months or years of use2,3. Cochlear implant use is believed to require neuroplasticity within the central auditory system, and differential engagement of neuroplastic mechanisms might contribute to outcome variability4-7. Despite extensive studies on how cochlear implants activate the auditory system4,8-12, our understanding of cochlear implant-related neuroplasticity remains limited. One potent factor enabling plasticity is the neuromodulator norepinephrine from the brainstem locus coeruleus. Here we examined behavioral responses and neural activity in locus coeruleus and auditory cortex of deafened rats tted with multi-channel cochlear implants. Animals were trained on a reward-based auditory task, with considerable individual differences of learning rates and maximum performance. Photometry from locus coeruleus predicted when implanted subjects would begin responding to sounds and longer-term perceptual accuracy, which were augmented by optogenetic locus coeruleus stimulation. Auditory cortical responses to cochlear implant stimulation re ected behavioral performance, with enhanced responses to rewarded stimuli and decreased distinction between unrewarded stimuli. Adequate engagement of central neuromodulatory systems is thus a potential clinically-relevant target for optimizing neuroprosthetic device use. Main TextCochlear implants are major biomedical devices, and an exemplary success story of the application of foundational neuroscience research and use of brain-machine interface neuroprosthetics to treat a widespread neurological condition: hearing loss 1-5 . However, the auditory bene ts provided by a cochlear implant are not instantaneous, in contrast to the ampli cation of acoustic input provided by commercial hearing aids. Some patients acquire a degree of speech comprehension with the cochlear implant a few hours after activation, but many patients unfortunately require months or even years post-implantation to achieve optimum levels of speech perception 2,3 . There are many open questions about the behavioral characteristics of this adaptation process in human listeners and the underlying neurophysiological changes 13,14 . Measuring how cochlear implants activate the central auditory system or other brain areas is technically complicated due to signi cant limitations with imaging in patients with implanted metallic medical devices 15 . Historically there have also been considerable challenges with experimental animal models of cochlear implant use, especially with the aims of monitoring and manipulating neural activity in implanted freely-behaving subjects. Here we addressed these issues by utilizing our recently-developed system for studying behaviorally-and physiologically-validated cochlear implant use in rats 16 , and examined neuromodulation and plasti...

Cochlear implants are neuroprosthetic devices that can provide hearing to deaf patients1. Despite significant benefits offered by cochlear implants, there are highly variable outcomes in how quickly hearing is restored and perceptual accuracy after months or years of use2,3. Cochlear implant use is believed to require neuroplasticity within the central auditory system, and differential engagement of neuroplastic mechanisms might contribute to outcome variability4-7. Despite extensive studies on how cochlear implants activate the auditory system4,8-12, our understanding of cochlear implant-related neuroplasticity remains limited. One potent factor enabling plasticity is the neuromodulator norepinephrine from the brainstem locus coeruleus. Here we examined behavioral responses and neural activity in locus coeruleus and auditory cortex of deafened rats fitted with multi-channel cochlear implants. Animals were trained on a reward-based auditory task, with considerable individual differences of learning rates and maximum performance. Photometry from locus coeruleus predicted when implanted subjects would begin responding to sounds and longer-term perceptual accuracy, which were augmented by optogenetic locus coeruleus stimulation. Auditory cortical responses to cochlear implant stimulation reflected behavioral performance, with enhanced responses to rewarded stimuli and decreased distinction between unrewarded stimuli. Adequate engagement of central neuromodulatory systems is thus a potential clinically-relevant target for optimizing neuroprosthetic device use.