Clinical and demographic information of the participants with a history of dense bilateral congenital cataracts (CC) as well as demographic information and visual acuity of age-matched normally sighted control participants (SC). NA indicates that patient’s data for the field were not available. FFL: Fixating and Following Light; CF: Counting Fingers; PL: Perceiving Light. Duration of visual deprivation was calculated by subtracting the date of birth from the date of surgery on the first eye (and thus corresponds to the age at surgery). Time since surgery was calculated by subtracting the date of surgery on the first eye from the date of testing. Visual acuity on the date of testing was measured binocularly with the Freiburg Vision Test (FrACT) (Bach 1996). The second group comprised of 10 normally sighted individuals (SC group, 8 males, Mean Age = 26.3 years, Range = 12 – 41.8). Participants across the two groups were age matched (t(9) = -0.12, p = 0.91). Congenital cataract-reversal individuals were clinically screened at the LV Prasad Eye Institute.

Voxel placement for Magnetic Resonance Spectroscopy and electrode placement for Electroencephalography.

a. Position of the frontal cortex (top) and visual cortex (bottom) voxels in a single subject. Skull-stripped figures output from SPM12. b. Electrode montage according to the 10/20 electrode system with marked occipital electrodes preselected for analyses, and frontal electrodes used for control analyses.

Quality metrics for Magnetic Resonance Spectroscopy data.

Mean quality metrics in each group are reported with the standard deviation in parentheses. The displayed quality metrics for Signal-to-Noise Ratio, Full-Width Half Maxima and Fit Error are those output by Gannet 3.0: Signal-to-noise-ratio (SNR), was calculated in GannetFit.m by estimating the noise in the GABA+/Glx/NAA signal across acquisitions and by dividing the absolute peak height of the GABA+/Glx/NAA signal by the estimated noise; Full-width-half-maxima (FWHM), is defined as the width of the peak in Hertz (Hz); and Fit Error, is defined as the standard deviation of the residual of the GABA+/Glx/NAA peak fit. The Fit Error is expressed as a percentage of the GABA+/Glx peak height. The Cramer-Rao Lower Bound is reported as output by TARQUIN 4.3.11 for the NAA signal (not calculated for GABA+ Glx as these metabolites were quantified using Gannet 3.0). Prior to in-vivo scanning, we confirmed the GABA+ and GABA+/Glx quantification quality with phantom testing (Henry et al., 2011; Jenkins et al., 2019). Imaging sequences were robust in identifying differences of 0.02 mM in GABA concentration; the known vs. measured concentrations of both GABA (r = 0.81, p = 0.004) and GABA/Glx (r = 0.71, p = 0.019) showed significant agreement. This 0.02 mM difference was documented by Weaver et al. (2013) between the occipital cortices of early blind and sighted individuals. The detailed procedure and results are described in Supplementary Material S7. The spectra from all individual subjects are shown in Supplementary Material S8.

Edited spectra obtained from Magnetic Resonance Spectroscopy (MRS).

a. Average edited spectra showing GABA+ and edited Glx peaks in the visual cortices of normally sighted individuals (SC, green) and individuals with reversed congenital cataracts (CC, red) are shown. Edited MRS DIFF spectra are separately displayed for the eyes open (EO), and eyes closed (EC) conditions using dashed and solid lines respectively. The standard error of the mean is shaded. Water-normalized GABA+, water-normalized Glx, and Glx/GABA+ concentration distributions for each group and condition are depicted as violin plots on the right. The solid black lines indicate mean values, and dotted lines indicate median values. The coloured lines connect values of individual participants across conditions. b. Corresponding average edited MRS spectra and water-normalized GABA+, water-normalized Glx and Glx/GABA+ concentration distributions measured from the frontal cortex are displayed. c. Correlations between visual cortex Glx/GABA+ concentrations in the visual cortex of CC individuals and visual acuity in logMAR units are depicted for the eyes closed (EC, left) and eyes open (EO, right) conditions. The 95% confidence intervals (CI) of the correlation coefficients (r) are reported.

Full spectrum and aperiodic activity of the electroencephalogram (EEG).

a. EEG spectra across O1 and O2 with the corresponding aperiodic (1/f) fits for normally sighted individuals (SC, blue, left) and individuals with reversed congenital cataracts (CC, red, right). Spectra of EEG recordings are displayed for the eyes closed (EC) and eyes opened (EO) conditions, as well as while viewing stimuli that changed in luminance (LU). Shaded regions represent the standard error of the mean. b. Aperiodic intercept (top) and slope (bottom) value distributions for each group and condition are displayed as violin plots. Solid black lines indicate mean values, dotted black lines indicate median values. Coloured lines connect values of individual participants across conditions.

Exploratory correlation analyses between the aperiodic intercept (1-20 Hz) and glutamate/glutamine (Glx) concentration in the visual cortex.

Correlations between water-normalized Glx concentration and aperiodic intercept are shown for the eyes closed (EC, left), eyes open (EO, middle) and visual stimulation (LU, right) conditions for sighted controls (SC, green, top) and individuals with reversed congenital cataracts (CC, red, bottom). The reported adjusted p values (p-adj) are Bonferroni corrected for multiple comparisons. The 95% confidence intervals (CI) of the correlation coefficients (r) are reported.