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 tinnitus1–3. 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.

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

“…Although chronic VNS is known to confer anxiolytic effects [99,100], this effect is not dependent on pairing with an extinction training regimen. Therefore, the absence of benefits of unpaired VNS is consistent with VNS therapies for sensory and motor dysfunction described above [32,59,61], and further supports enhancement of plasticity as a convergent mechanism that underlies the benefits of VNS therapy.…”

“…As detailed above, VNS paired with tones can drive specific plasticity to alter spectral and temporal response characteristics of central auditory neurons [32,34]. If map distortion and alterations in receptive field size contribute to tinnitus, in principle, VNS paired with the appropriate presentation of tones could drive plasticity to restore the normal characteristics of the circuitry and alleviate the percept of tinnitus ( Fig.…”

“…In an early investigation of the ability of VNS to enhance cortical plasticity, Engineer et al [32] examined whether left cervical VNS paired with the presentation of tones could drive reorganization of the tonotopic map in primary auditory cortex (Fig. 1A).…”

“…In response to noise-induced hearing loss, the CNS fails to receive input from a region of the damaged cochlea. This loss of input causes destabilization of the normal excitatory and inhibitory balance within central auditory circuits, which can lead to map distortion, increased receptive field size, and increased synchronous activity in quiet, all of which appear to contribute to the tinnitus percept [32].…”

“…2A). Engineer et al [32] sought to evaluate the ability of VNS-based targeted plasticity therapy to eliminate the behavioral correlate of chronic tinnitus in rats. The rationale for the therapy was based on increasing the number of cortical neurons tuned to frequencies other than the tinnitus frequency to reduce the overrepresented tinnitus frequency.…”