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. 2025 May 16:13:RP98143.
doi: 10.7554/eLife.98143.

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

Rashi Pant  1 , Kabilan Pitchaimuthu  1   2 , José P Ossandón  1 , Idris Shareef  3   4 , Sunitha Lingareddy  5 , Jürgen Finsterbusch  6 , Ramesh Kekunnaya  3 , Brigitte Röder  1   3
Affiliations

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

Rashi Pant et al. Elife. .

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 10 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 on early visual experience in humans. First, participants underwent MRS scanning at rest with their eyes open 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.

Keywords: cataract models; excitatory/inhibitory balance; human; neuroscience; plasticity; sensitive periods; visual deprivation; visual development.

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Conflict of interest statement

RP, KP, JO, IS, JF, RK, BR No competing interests declared, SL is the Managing Director Radiology at Lucid Medical Diagnostics, Hyderabad, India

Figures

Figure 1.
Figure 1.. 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.
Figure 2.
Figure 2.. 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 colored 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.
Figure 3.
Figure 3.. 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. Colored lines connect values of individual participants across conditions.
Figure 4.
Figure 4.. 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.
Appendix 1—figure 1.
Appendix 1—figure 1.. Visual acuity in normally sighted individuals (SC) and congenital cataract-reversal (CC individuals).
Binocularly measured visual acuity distributions in logarithmic of minimum angle of resolution (logMAR) are displayed as violin plots. Solid black lines indicate mean values, dotted black lines indicate median values.
Appendix 1—figure 2.
Appendix 1—figure 2.. Edited (DIFF) spectrum metabolites quantified via Osprey.
Water-normalized and tissue corrected GABA+, water-normalized and tissue-corrected Glx, and Glx/GABA+ concentration distributions from the visual cortex are depicted as violin plots for each group and condition (left to right). The solid black lines indicate mean values, and dotted lines indicate median values. The colored lines connect values of individual participants across conditions. Results for congenitally cataract-reversal individuals (CC) and for normally sighted controls (SC) are shown in blue and red, respectively. EC = Eyes closed, EO = Eyes open.,
Appendix 1—figure 3.
Appendix 1—figure 3.. OFF spectrum metabolites quantified via Osprey.
Water-normalized NAA concentration distributions from the visual cortex are depicted as violin plots for each group and condition (left to right). The solid black lines indicate mean values, and dotted lines indicate median values. The colored lines connect values of individual participants across conditions. For abbreviations see Appendix 1—figure 2.
Appendix 1—figure 4.
Appendix 1—figure 4.. Tissue fractions for Magnetic Resonance Spectroscopy voxels.
The fractions of white matter (yellow), grey matter (grey) and cerebrospinal fluid (blue) are displayed for the eyes open (EO), and eyes closed (EC) conditions in the congenital cataract-reversal group (CC) and the normally sighted control group (SC). Tissue fractions were separately calculated for the visual (left) and frontal (right) cortex voxels.
Appendix 1—figure 5.
Appendix 1—figure 5.. Cr-normalized edited (DIFF) spectrum metabolites.
Creatine (Cr)-normalized GABA+, Cr-normalized Glx, and Glx/GABA+ concentration distributions from the visual cortex are depicted as violin plots for each group and condition (left to right). The solid black lines indicate mean values, and dotted lines indicate median values. The colored lines connect values of individual participants across conditions.
Appendix 1—figure 6.
Appendix 1—figure 6.. Phantom testing of GABA concentrations.
Plots depicting the correlation between known and measured concentrations from phantom scans of Gamma-Aminobutyric Acid (GABA; left) and the ratio of GABA to Glutamate/Glutamine (GABA/Glx, right) concentration. In the left panel, previously reported GABA concentration from the visual cortex of congenitally blind individuals (Weaver et al., 2013) is marked with a vertical dotted line.
Appendix 1—figure 7.
Appendix 1—figure 7.. Edited spectra of participants showing GABA+ and Glx peaks.
Individual participants’ edited spectra and the respective model fits for congenital cataract-reversal (CC, left) and normally sighted control (SC, right) individuals. Spectra are shown as output by GannetFit.m for the eyes closed and eyes open conditions for each subject.
Appendix 1—figure 8.
Appendix 1—figure 8.. Aperiodic fits for normally sighted control (SC, top) and congenital cataract-reversal (CC, bottom) individuals at occipital electrodes during rest with eyes closed.
Solid black lines indicate the power spectral density, red lines indicate the aperiodic (1 /f) fit in the 1–20 Hz range, excluding alpha frequencies.
Appendix 1—figure 9.
Appendix 1—figure 9.. Aperiodic fits for normally sighted control (SC, top) and congenital cataract-reversal (CC, bottom) individuals at occipital electrodes during rest with eyes open.
Solid black lines indicate the power spectral density, red lines indicate the aperiodic (1 /f) fit in the 1–20 Hz range, excluding alpha frequencies.
Appendix 1—figure 10.
Appendix 1—figure 10.. Aperiodic fits for normally sighted control (SC, top) and congenital cataract-reversal (CC, bottom) individuals at occipital electrodes during visual stimulation.
Solid black lines indicate the power spectral density, red lines indicate the aperiodic (1 /f) fit in the 1–20 Hz range, excluding alpha frequencies.
Appendix 1—figure 11.
Appendix 1—figure 11.. Effect of visual deprivation history on GABA+ concentration.
Correlations between visual cortex GABA+ concentration and chronological age of the congenital cataract-reversal (CC, red) and normally sighted individuals (SC, blue, see left panel). Second to fourth panels depict correlations between visual cortex GABA+ concentration and duration of visual deprivation, time since surgery and visual acuity in the CC individuals, respectively. Correlations were separately calculated for the eyes open (EO, top row) and eyes closed (EC, bottom row) conditions. The 95% confidence intervals (CI) of the correlation coefficients (r) are reported.
Appendix 1—figure 12.
Appendix 1—figure 12.. Effect of visual deprivation history on Glx concentration.
Correlations between visual cortex Glx concentration and chronological age of the congenital cataract-reversal (CC, red) and normally sighted individuals (SC, blue, see left panel). Second to fourth panels depict correlations between visual cortex Glx concentration and duration of visual deprivation, time since surgery and visual acuity in the CC individuals, respectively. Correlations were separately calculated for the eyes open (EO, top row) and eyes closed (EC, bottom row) conditions. The 95% confidence intervals (CI) of the correlation coefficients (r) are reported.
Appendix 1—figure 13.
Appendix 1—figure 13.. Effect of visual deprivation history on Glx/GABA concentration.
Correlations between visual cortex Glx/GABA+ concentration and chronological age of the congenital cataract-reversal (CC, red) and normally sighted individuals (SC, blue, see left panel). Second to fourth panels depict correlations between visual cortex Glx/GABA+ concentration and duration of visual deprivation, time since surgery and visual acuity in the CC individuals, respectively. Correlations were separately calculated for the eyes open (EO, top row) and eyes closed (EC, bottom row) conditions. The 95% confidence intervals (CI) of the correlation coefficients (r) are reported.
Appendix 1—figure 14.
Appendix 1—figure 14.. OFF spectra obtained from Magnetic Resonance Spectroscopy (MRS).
(a) The average spectra show NAA peaks in the visual cortices of normally sighted individuals (SC, green) and individuals with reversed congenital cataracts (CC, red) are shown. Spectra are displayed for the eyes open (EO), and eyes closed (EC) conditions. The standard error of the mean is shaded. NAA concentration distributions for each group and condition are demonstrated as violin plots on the right. The solid black lines indicate mean values, and dotted lines indicate median values. The colored lines connect values of individual participants across conditions. (b) Corresponding average MRS spectra and NAA concentration distributions measured from the frontal cortex are displayed.
Appendix 1—figure 15.
Appendix 1—figure 15.. Aperiodic intercept (top) and slope (bottom) for congenital cataract-reversal (CC, red) and age-matched normally sighted control (SC, blue) individuals in frontal electrodes.
Distributions of these parameters are displayed as violin plots for three conditions; at rest with eyes closed (EC), at rest with eyes open (EO) and during visual stimulation (LU). Aperiodic parameters were calculated across electrodes Fp1 and Fp2. Solid black lines indicate mean values, dotted black lines indicate median values. Colored lines connect values of individual participants across conditions.
Appendix 1—figure 16.
Appendix 1—figure 16.. Effect of visual deprivation history on aperiodic intercept.
Correlations between aperiodic intercept at occipital electrodes and chronological age of the congenital cataract-reversal (CC, red) and normally sighted individuals (SC, blue, see left panel). Second to fourth panels depict correlations between aperiodic intercept and duration of visual deprivation, time since surgery and visual acuity in the CC individuals, respectively. Correlations were separately calculated for the aperiodic intercept while participants viewed stimuli that changed in luminance (LU, top row) and the eyes open (EO, middle row) and eyes closed (EC, bottom row) conditions. The 95% confidence intervals (CI) of the correlation coefficients (r) are reported.
Appendix 1—figure 17.
Appendix 1—figure 17.. Effect of visual deprivation history on aperiodic slope.
Correlations between aperiodic slope across occipital electrodes and chronological age of the congenital cataract-reversal (CC, red) and normally sighted individuals (SC, blue, see left panel). Second to fourth panels depict correlations between aperiodic slope and duration of visual deprivation, time since surgery and visual acuity in the CC individuals, respectively. Correlations separately calculated for the aperiodic slope while participants viewed flickering stimuli (LU, top row) and the eyes open (EO, middle row) and eyes closed (EC, bottom row) conditions. The 95% confidence intervals (CI) of the correlation coefficients (r) are reported.
Appendix 1—figure 18.
Appendix 1—figure 18.. Correlation between aperiodic slope and Glx/GABA+ concentration.
Correlations between the aperiodic slope and visual cortex Glx/GABA+ concentration measured at rest with eyes closed (EC) (left panels) and eyes open (EO) (middle panels), and the correlation between aperiodic slope measured while subjects viewed flickering stimuli (LU) and visual cortex Glx/GABA+ concentration measured in the EO condition (right panels), are depicted. Correlations were calculated separately for normally sighted control (SC, blue, top row) and congenital cataract-reversal (CC, red, bottom row) individuals. The 95% confidence intervals (CI) of the correlation coefficients (r) are reported.
Appendix 1—figure 19.
Appendix 1—figure 19.. Correlation between aperiodic intercept and Glx/GABA+ concentration.
Correlations between the aperiodic intercept and visual cortex Glx/GABA+ concentration measured at rest with eyes closed (EC) (left panels) and eyes open (EO) (middle panels), and the correlation between aperiodic intercept measured while subjects viewed flickering stimuli (LU) and visual cortex Glx/GABA+ concentration measured in the EO condition (right panels), are depicted. Correlations were calculated separately for normally sighted control (SC, blue, top row) and congenital cataract-reversal (CC, red, bottom row) individuals. The 95% confidence intervals (CI) of the correlation coefficients (r) are reported.
Appendix 1—figure 20.
Appendix 1—figure 20.. Correlation between aperiodic slope and GABA+ concentration.
Correlations between the aperiodic slope and visual cortex GABA+ concentration measured at rest with eyes closed (EC) (left panels) and eyes open (EO) (middle panels), and the correlation between aperiodic slope measured while subjects viewed flickering stimuli (LU) and visual cortex GABA+ concentration measured in the EO condition (right panels), are depicted. Correlations were calculated separately for normally sighted control (SC, blue, top row) and congenital cataract-reversal (CC, red, bottom row) individuals. The 95% confidence intervals (CI) of the correlation coefficients (r) are reported.
Appendix 1—figure 21.
Appendix 1—figure 21.. Correlation between aperiodic intercept and GABA+ concentration.
Correlations between the aperiodic intercept and visual cortex GABA+ concentration measured at rest with eyes closed (EC) (left panels) and eyes open (EO) (middle panels), and the correlation between aperiodic intercept measured while subjects viewed flickering stimuli (LU) and visual cortex GABA+ concentration measured in the EO condition (right panels), are depicted. Correlations were calculated separately for normally sighted control (SC, blue, top row) and congenital cataract-reversal (CC, red, bottom row) individuals. The 95% confidence intervals (CI) of the correlation coefficients (r) are reported.
Appendix 1—figure 22.
Appendix 1—figure 22.. Correlation between aperiodic slope and Glx concentration.
Correlations between the aperiodic slope and visual cortex Glx concentration measured at rest with eyes closed (EC) (left panels) and eyes open (EO) (middle panels), and the correlation between aperiodic slope measured while subjects viewed flickering stimuli (LU) and visual cortex Glx concentration measured in the EO condition (right panels), are depicted. Correlations were calculated separately for normally sighted control (SC, blue, top row) and congenital cataract-reversal (CC, red, bottom row) individuals. The 95% confidence intervals (CI) of the correlation coefficients (r) are reported.
Appendix 1—figure 23.
Appendix 1—figure 23.. Aperiodic offset and slope in the 1–20 Hz range from occipital electrodes in congenital cataract reversal (CC) and normally sighted control (SC) individuals of the present study (left) and additional 28 subjects of Ossandón et al., 2023.
Aperiodic intercepts (top) and slope (bottom) distributions for each group and condition are displayed as violin plots. Solid black lines indicate mean values, dotted black lines indicate median values. Colored lines connect values of individual participants across conditions.
Appendix 1—figure 24.
Appendix 1—figure 24.. Aperiodic-corrected alpha amplitude in congenital cataract-reversal and normally sighted individuals.
Aperiodic-corrected alpha amplitudes (8–14 Hz) distributions for each group and condition are displayed as violin plots. Solid black lines indicate mean values, dotted black lines indicate median values. Colored lines connect values of individual participants across conditions.
Author response image 1.
Author response image 1.. Power spectral density of one congenital cataract-reversal (CC) participant in the visual stimulation condition across all channels.
The reduced power at 30 Hz shows the effects of the anti-aliasing filter applied by EEGLAB’s pop_resample function.
See this image and copyright information in PMC

Update of

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