Altered visual cortex excitatory/inhibitory ratio following transient congenital visual deprivation in humans

Abstract

Non-human animal models have indicated that the ratio of excitation to inhibition (E/I) in neural circuits is experience dependent and changes across development. Here, we assessed 3T Magnetic Resonance Spectroscopy (MRS) and electroencephalography (EEG) markers of cortical E/I ratio in ten individuals who had been treated for dense bilateral congenital cataracts, after an average of 12 years of blindness, to test for dependence of the E/I ratio in humans on early visual experience. First, participants underwent MRS scanning at rest with their eyes opened and eyes closed, to obtain visual cortex Gamma-Aminobutyric Acid (GABA+) concentration, Glutamate/Glutamine (Glx) concentration and the concentration ratio of Glx/GABA+, as measures of inhibition, excitation, and E/I ratio respectively. Subsequently, EEG was recorded to assess aperiodic activity (1-20 Hz) as a neurophysiological measure of the cortical E/I ratio, during rest with eyes open and eyes closed, and during flickering stimulation. Across conditions, congenital cataract-reversal individuals demonstrated a significantly lower visual cortex Glx/GABA+ ratio, and a higher intercept and steeper aperiodic slope at occipital electrodes, compared to age-matched sighted controls. In the congenital cataract-reversal group, a lower Glx/GABA+ ratio was associated with better visual acuity, and Glx concentration correlated positively with the aperiodic intercept in the conditions with visual input. We speculate that these findings result from an increased E/I ratio of the visual cortex as a consequence of congenital blindness, which might require commensurately increased inhibition in order to balance the additional excitation from restored visual input. The lower E/I ratio in congenital cataract-reversal individuals would thus be a consequence of homeostatic plasticity.