Metaplasticity: Dark exposure boosts local excitability and visual plasticity in adult human cortex

Abstract

An interlude of dark exposure for about 1 week is known to shift excitatory/inhibitory (E/I) balance of the mammalian visual cortex, promoting plasticity and accelerating visual recovery in animals that have experienced cortical lesions during development. However, the translational impact of our understanding of dark exposure from animal studies to humans remains elusive. Here, we used magnetic resonance spectroscopy as a probe for E/I balance in the primary visual cortex (V1) to determine the effect of 60 min of dark exposure, and measured binocular combination as a behavioural assay to assess visual plasticity in 14 normally sighted human adults. To induce neuroplastic changes in the observers, we introduced 60 min of monocular deprivation, which is known to temporarily shift sensory eye balance in favour of the previously deprived eye. We report that prior dark exposure for 60 min strengthens local excitability in V1 and boosts visual plasticity in normal adults. However, we show that it does not promote plasticity in amblyopic adults. Nevertheless, our findings are surprising, given the fact that the interlude is very brief. Interestingly, we find that the increased concentration of the excitatory neurotransmitter is not strongly correlated with the enhanced functional plasticity. Instead, the absolute degree of change in its concentration is related to the boost, suggesting that the dichotomy of cortical excitation and inhibition might not explain the physiological basis of plasticity in humans. We present the first evidence that an environmental manipulation that shifts cortical E/I balance can also act as a metaplastic facilitator for visual plasticity in humans. KEY POINTS: A brief interlude (60 min) of dark exposure increased the local concentration of glutamine/glutamate but not that of GABA in the visual cortex of adult humans. After dark exposure, the degree of the shift in sensory eye dominance in favour of the previously deprived eye from short-term monocular deprivation was larger than that from only monocular deprivation. The neurochemical and behavioural measures were associated: the magnitude of the shift in the concentration of glutamine/glutamate was correlated with the boost in perceptual plasticity after dark exposure. Surprisingly, the increase in the concentration of glutamine/glutamate was not correlated with the perceptual boost after dark exposure, suggesting that the physiological mechanism of how E/I balance regulates plasticity is not deterministic. In other words, an increased excitation did not unilaterally promote plasticity.

Keywords: E/I balance; amblyopia; dark exposure; magnetic resonance spectroscopy; metaplasticity; visual plasticity.