Although sensory and motor systems support different functions, both systems exhibit experience-dependent cortical plasticity under similar conditions. If mechanisms regulating cortical plasticity are common to sensory and motor cortices, then methods generating plasticity in sensory cortex should be effective in motor cortex. Repeatedly pairing a tone with a brief period of vagus nerve stimulation (VNS) increases the proportion of primary auditory cortex responding to the paired tone (Engineer ND, Riley JR, Seale JD, Vrana WA, Shetake J, Sudanagunta SP, Borland MS, Kilgard MP. 2011. Reversing pathological neural activity using targeted plasticity. Nature. 470:101-104). In this study, we predicted that repeatedly pairing VNS with a specific movement would result in an increased representation of that movement in primary motor cortex. To test this hypothesis, we paired VNS with movements of the distal or proximal forelimb in 2 groups of rats. After 5 days of VNS movement pairing, intracranial microstimulation was used to quantify the organization of primary motor cortex. Larger cortical areas were associated with movements paired with VNS. Rats receiving identical motor training without VNS pairing did not exhibit motor cortex map plasticity. These results suggest that pairing VNS with specific events may act as a general method for increasing cortical representations of those events. VNS movement pairing could provide a new approach for treating disorders associated with abnormal movement representations.

Background Pairing sensory or motor events with vagus nerve stimulation (VNS) can reorganize sensory or motor cortex. Repeatedly pairing a tone with a brief period of VNS increases the proportion of primary auditory cortex (A1) responding to the frequency of the paired tone. However, the relationship between VNS intensity and cortical map plasticity is not known. Objective/Hypothesis The primary goal of this study was to determine the range of VNS intensities that can be used to direct cortical map plasticity. Methods The rats were exposed to a 9 kHz tone paired with VNS at intensities of 0.4, 0.8, 1.2, or 1.6 mA. Results In rats that received moderate (0.4-0.8 mA) intensity VNS, seventy-five percent more cortical neurons were tuned to frequencies near the paired tone frequency. A two-fold effective range is broader than expected based on previous VNS studies. Rats that received high (1.2-1.6 mA) intensity VNS had significantly fewer neurons tuned to the same frequency range compared to the moderate intensity group. Conclusion This result is consistent with previous results documenting that VNS is memory enhancing as a non-monotonic relationship of VNS intensity.

Cochlear implants provide good speech discrimination ability despite highly limited amount of information they transmit compared with normal cochlea. Noise vocoded speech, simulating cochlear implants in normal hearing listeners, have demonstrated that spectrally and temporally degraded speech contains sufficient cues to provide accurate speech discrimination. We hypothesized that neural activity patterns generated in the primary auditory cortex by spectrally and temporally degraded speech sounds will account for the robust behavioral discrimination of speech. We examined the behavioral discrimination of noise vocoded consonants and vowels by rats and recorded neural activity patterns from rat primary auditory cortex (A1) for the same sounds. We report the first evidence of behavioral discrimination of degraded speech sounds by an animal model. Our results show that rats are able to accurately discriminate both consonant and vowel sounds even after significant spectral and temporal degradation. The degree of degradation that rats can tolerate is comparable to human listeners. We observed that neural discrimination based on spatiotemporal patterns (spike timing) of A1 neurons is highly correlated with behavioral discrimination of consonants and that neural discrimination based on spatial activity patterns (spike count) of A1 neurons is highly correlated with behavioral discrimination of vowels. The results of the current study indicate that speech discrimination is resistant to degradation as long as the degraded sounds generate distinct patterns of neural activity.

Repeatedly pairing vagus nerve stimulation (VNS) with a tone or movement drives highly specific and long-lasting plasticity in auditory or motor cortex, respectively. Based on this robust enhancement of plasticity, VNS paired with rehabilitative training has emerged as a potential therapy to improve recovery, even when delivered long after the neurological insult. Development of VNS delivery paradigms that reduce therapy duration and maximize efficacy would facilitate clinical translation. The goal of the current study was to determine whether primary auditory cortex (A1) plasticity can be generated more quickly by shortening the interval between VNS-tone pairing events or by delivering fewer VNS-tone pairing events. While shortening the inter-stimulus interval between VNS-tone pairing events resulted in significant A1 plasticity, reducing the number of VNS-tone pairing events failed to alter A1 responses. Additionally, shortening the inter-stimulus interval between VNS-tone pairing events failed to normalize neural and behavioral responses following acoustic trauma. Extending the interval between VNS-tone pairing events yielded comparable A1 frequency map plasticity to the standard protocol, but did so without increasing neural excitability. These results indicate that the duration of the VNS-event pairing session is an important parameter that can be adjusted to optimize neural plasticity for different clinical needs.

Neurons at higher stations of each sensory system are responsive to feature combinations not present in lower levels. As a result, the activity of these neurons becomes less redundant than lower levels. We recorded responses to speech sounds from inferior colliculus and primary auditory cortex neurons of rats, and tested the hypothesis that primary auditory cortex neurons are more sensitive to combinations of multiple acoustic parameters compared to inferior colliculus neurons. We independently eliminated periodicity information, spectral information and temporal information in each consonant and vowel sound using a noise vocoder. This technique made it possible to test several key hypotheses about speech sound processing. Our results demonstrate that inferior colliculus responses are spatially arranged and primarily determined by the spectral energy and the fundamental frequency of speech, whereas primary auditory cortex neurons generate widely distributed responses to multiple acoustic parameters, and are not strongly influenced by the fundamental frequency of speech. We found no evidence that inferior colliculus or primary auditory cortex was specialized for speech features such as voice onset time or formants. The greater diversity of responses in primary auditory cortex compared to inferior colliculus may help explain how the auditory system can identify a wide range of speech sounds across a wide range of conditions without relying on any single acoustic cue.