Cortical map plasticity as a function of vagus nerve stimulation rate.

BACKGROUND: Repeatedly pairing a brief train of vagus nerve stimulation (VNS) with an external event can reorganize the sensory or motor cortex. A 30 Hz train of sixteen VNS pulses paired with a tone significantly increases the number of neurons in primary auditory cortex (A1) that respond to tones near the paired tone frequency. The effective range of VNS pulse rates for driving cortical map plasticity has not been defined. OBJECTIVE/HYPOTHESIS: This project investigated the effects of VNS rate on cortical plasticity. We expected that VNS pulse rate would affect the degree of plasticity caused by VNS-tone pairing. METHODS: Rats received sixteen pulses of VNS delivered at a low (7.5 Hz), moderate (30 Hz), or high (120 Hz) rate paired with 9 kHz tones 300 times per day over a 20 day period. RESULTS: More A1 neurons responded to the paired tone frequency in rats from the moderate rate VNS group compared to naïve controls. The response strength was also increased in these rats. In contrast, rats that received high or low rate VNS failed to exhibit a significant increase in the number of neurons tuned to sounds near 9 kHz. CONCLUSION: Our results demonstrate that the degree of cortical plasticity caused by VNS-tone pairing is an inverted-U function of VNS pulse rate. The apparent high temporal precision of VNS-tone pairing helps identify optimal VNS parameters to achieve the beneficial effects from restoration of sensory or motor function.

Cortical Map Plasticity as a Function of Vagus Nerve Stimulation Intensity.

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, 75% 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.

Degraded auditory processing in a rat model of autism limits the speech representation in non-primary auditory cortex.

Although individuals with autism are known to have significant communication problems, the cellular mechanisms responsible for impaired communication are poorly understood. Valproic acid (VPA) is an anticonvulsant that is a known risk factor for autism in prenatally exposed children. Prenatal VPA exposure in rats causes numerous neural and behavioral abnormalities that mimic autism. We predicted that VPA exposure may lead to auditory processing impairments which may contribute to the deficits in communication observed in individuals with autism. In this study, we document auditory cortex responses in rats prenatally exposed to VPA. We recorded local field potentials and multiunit responses to speech sounds in primary auditory cortex, anterior auditory field, ventral auditory field. and posterior auditory field in VPA exposed and control rats. Prenatal VPA exposure severely degrades the precise spatiotemporal patterns evoked by speech sounds in secondary, but not primary auditory cortex. This result parallels findings in humans and suggests that secondary auditory fields may be more sensitive to environmental disturbances and may provide insight into possible mechanisms related to auditory deficits in individuals with autism.