Editor's evaluation: Internal neural states influence the short-term effect of monocular deprivation in human adults
Year: 2022
Type: peer-review
Abstract: Article Figures and data Abstract Editor's evaluation Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract The adult human visual system maintains the ability to be altered by sensory deprivation. What has not been considered is whether the internal neural states modulate visual sensitivity to short-term monocular deprivation. In this study we manipulated the internal neural state and reported changes in intrinsic neural oscillations with a patched eye open or closed. We investigated the influence of eye open/eye closure on the unpatched eye's contrast sensitivity and ocular dominance (OD) shifts induced by short-term monocular deprivation. The results demonstrate that internal neural states influence not only baseline contrast sensitivity but also the extent to which the adult visual system can undergo changes in ocular dominance. Editor's evaluation The authors report the results of three experiments assessing how one or both eyes open under a patch influence resting EEG activity, contrast sensitivity, and binocular balance in normally sighted subjects. Their results suggest that the state of eye-opening temporarily, but significantly, influences shifts in ocular dominance with relevance for the treatment of binocular visual disorders such as amblyopia that are treated with periodic monocular occlusion. The evidence supporting their conclusions is solid and the findings are important for the field. https://doi.org/10.7554/eLife.83815.sa0 Decision letter Reviews on Sciety eLife's review process Introduction Recent studies have shown that when one eye is deprived of its input for a short period of time (30 min to 2.5 hr), visual brain mechanisms undergo a neural change that results in not only a change in visual sensitivity but also interocular balance (i.e., ocular dominance) (Lunghi et al., 2011; Zhou et al., 2013a). However, unlike the long-term neuroplastic changes by abnormal visual experience in critical period, such change peaks immediately after patch removal and remains for up to 30–90 min (Lunghi et al., 2011; Zhou et al., 2013a), which we call as short-term monocular deprivation effect. A number of results suggest that this short-term monocular deprivation effect mainly involves V1 (the primary visual cortex), these include intrinsic optical imaging in monkeys (Begum and Tso, 2015), and magnetoencephalography (MEG) studies (Chadnova et al., 2017), electroencephalogram (EEG) studies (Lunghi et al., 2015a; Zhou et al., 2015), functional magnetic resonance imaging (fMRI) studies (Binda et al., 2018), magnetic resonance spectroscopy (MRS) studies (Lunghi et al., 2015b) and psychophysics studies (Zhou et al., 2014) in human adults. The role played by a number of exogenous factors have been investigated, namely image properties (Zhou et al., 2014; Zhou et al., 2017), exercise (Lunghi and Sale, 2015c), visual pathology (Lunghi et al., 2019b), body mass index (Lunghi et al., 2019a). What is not known is whether there is a role played by internal neural states in modulating this short-term monocular deprivation effect. It is well known that there are characteristic differences in resting-state brain activity in the absence of visual stimulation, for example, when the two eyes are open vs. closed in the dark, there is a significant decrease in occipital alpha oscillations called the Berger effect. There are power and coherence changes of a broad spectrum in the Δ, θ, α1, α2, β1, β2, and γ frequency bands that are presumed to be correlates of the switching of involuntary preliminary attention from internally directed attention specific for the eyes closed state to externally directed attention specific for the eyes open state (Boytsova and Danko, 2010). FMRI studies have shown that eyes open rest conditions are associated with larger activation of the visual cortex but smaller activation of the lateral geniculate nucleus (Marx et al., 2004). In the eyes closed state, activations of the ocular motor-related brain areas are larger, including the prefrontal eye fields, parietal and frontal eye fields, cerebellar vermis, thalamus, and basal ganglia (Marx et al., 2004). It has been argued that eye closure can alter the processing mode of the sensory system by decoupling geniculostriate processing in favor of enhanced thalamocortical coupling in non-visual brain areas (Brodoehl et al., 2015). While it remains an important question whether this type of intrinsic regulation can modulate visual sensitivity, it is a difficult question to answer because any comparison between eyes open and eyes closed conditions necessarily excludes the ability to measure visual sensitivity using external visual inputs. Using the short-term monocular deprivation paradigm described above where one eye is deprived of its visual input for a short period of time, we have been able to assess the role of the internal state (comparing eyes open with eyes close behind the deprivation patch) for visual sensitivity and changes in binocular balance in adult humans. In particular, we directly compare the monocular deprivation effects, as assessed by changes in EEG power, steady-state visually evoked potentials (SSVEPs), and contrast sensitivity, during the period when the patched eye (PE) is kept either open or closed behind the patch. We derive contrast gain and ocular dominance changes that occur as a result of patching one eye for a 2.5 hr period when the eye behind the patch is either open or closed. The results show that the short-term monocular deprivation effect can be modulated by the internal state in the absence of visual stimulation and is greater when the eye behind the occlude is kept open (i.e., eye-open state). Results The immediate effects of open vs. close of the PE on intrinsic neural oscillations and the unpatched eye's sensitivity To investigate whether there is an internal state difference in intrinsic neural oscillations when only one eye is open or closed, we recruited 20 normal adults and measured the amplitudes of their alpha oscillations at the resting state with the two eyes closed, two eyes open, monocular patching with the PE open, and monocular patching with the PE closed. Here, we focused on the alpha oscillation because it is the strongest intrinsic neural oscillation in the brain, which is the hallmark of internal state changes (Boytsova and Danko, 2010). Figure 1a shows the amplitude spectrum averaged across subjects for the four conditions. Figure 1b shows the average amplitude at the alpha peak frequency. Similar to previous reports (Boytsova and Danko, 2010), alpha amplitude was significantly lower when two eyes are open compared to closed (t(19) = –2.272, p=0.035, two-tailed paired samples t-test with Holm-Bonferroni correction (Holm, 1979), number of comparisons k=2). Importantly, in the monocular patching conditions, the alpha amplitude was significantly lower when the PE remaining open as compared to the PE being kept closed (t(19) = –3.944, p<0.001, with Holm-Bonferroni correction, k=2). There were also weak signals in the beta band (Figure 1a, 20 Hz), but without significant changes in the eye-open than eye-closed condition. Figure 1 Download asset Open asset The immediate effects of open vs. close of the patched eye (PE). (a) The amplitude spectrum averaged across subjects between 2 and 30 Hz for four conditions (two eyes open: red dashed line; two eyes closed: black dashed lines; PE open: red solid line; PE closed: black solid line). Shaded area indicates one standard error of the mean (SEM) across 20 subjects. (b) The normalized amplitude at the alpha peak frequency. Each dot represents one subject. Error bars represent one SEM across 20 subjects. (c) The average amplitude of steady-state visually evoked potential (SSVEP) and peak alpha. Each dot represents each observer. Error bars represent one SEM across 20 subjects. (d) The contrast sensitivity of the unpatched eye (UPE). Each dot represents one observer. Error bars represent one SEM across 18 subjects. The black star indicates the significance of the two-tailed paired samples t-test with Holm-Bonferroni correction, *: p<0.05; ***: p<0.001. Figure 1—source data 1 Related to Figure 1a. https://cdn.elifesciences.org/articles/83815/elife-83815-fig1-data1-v2.xlsx Download elife-83815-fig1-data1-v2.xlsx Figure 1—source data 2 Related to Figure 1b. https://cdn.elifesciences.org/articles/83815/elife-83815-fig1-data2-v2.xlsx Download elife-83815-fig1-data2-v2.xlsx Figure 1—source data 3 Related to Figure 1c. https://cdn.elifesciences.org/articles/83815/elife-83815-fig1-data3-v2.xlsx Download elife-83815-fig1-data3-v2.xlsx Figure 1—source data 4 Related to Figure 1d. https://cdn.elifesciences.org/articles/83815/elife-83815-fig1-data4-v2.xlsx Download elife-83815-fig1-data4-v2.xlsx We further measured SSVEP to a sinewave plaid at 24% contrast counterphase flickering at 7.5 Hz, and the contrast sensitivity of the unpatched eye (UPE) for both PE-open and -closed conditions. The results in Figure 1c show stronger SSVEP (t(19) = 2.737, p=0.026, with Holm-Bonferroni correction, k=2) and weaker alpha oscillations (t(19) = –2.683, p=0.015, with Holm-Bonferroni correction, k=2) for the PE-open condition compared with the PE-closed condition. As shown by Figure 1d, the contrast sensitivity of the UPE with PE open was also higher than that with PE closed (t(17) = 2.667, p=0.016). We calculated the difference between the eye-open and eye-closed conditions as: (closed-open)/open, for all five measurements: contrast sensitivity, SSVEP amplitude, peak alpha amplitude in the SSVEP sessions (αSSVEP), peak alpha amplitude in the resting state when both eyes open/closed (αBi), and PE open/closed (αmono). Compared to the PE condition, the contrast sensitivity and SSVEP amplitude of the UPE were immediately decreased by 7.5% and 12.3%, whereas the amplitudes of αSSVEP, αBi, and αmono were immediately enhanced by 18.1%, 6.2%, and 23.3%, respectively, in the PE-closed condition. As shown in Figure 2, a positive correlation of the effect of eye open vs. eye close was found between contrast sensitivity and SSVEP amplitude (r=0.665, p=0.013), and between peak alpha amplitudes in the SSVEP sessions and resting state (αSSVEP vs. αBi: r=0.558, p=0.011; αSSVEP vs. αmono: r=0.643, p=0.002; αBi vs. αmono: r=0.468, p=0.037). No significant correlation was found between other pairs of measurements (all p>0.05). Figure 2 Download asset Open asset Correlations of the effects of eye open vs. eye close between different measurements. (a) Correlation between contrast sensitivity and SSVEP amplitude. (b) Correlation between peak alpha amplitude in the SSVEP sessions (αSSVEP) and the resting state when both eyes open/closed (αBi). (c) Correlation between peak alpha amplitude in the resting state when both eyes open/closed (αBi) and the resting state when PE open/closed (αmono). (d) Correlation between peak alpha amplitude in the SSVEP sessions (αSSVEP) and the resting state when PE open/closed (αmono). The difference of the eye-open and eye-closed conditions was calculated as: (closed-open)/open. Each dot represents one observer. Figure 2—source data 1 Related to Figure 2a, b, c and d. https://cdn.elifesciences.org/articles/83815/elife-83815-fig2-data1-v2.xlsx Download elife-83815-fig2-data1-v2.xlsx The aftereffects of 2.5-hr monocular patching on contrast sensitivity So far, we have shown that the alpha power is stronger if the eye behind a monocular patch is closed than when the eye behind the patch is open, which occurred in both the resting state and the SSVEP sessions. The effects of the PE-closed condition were to inhibit the SSVEP power and the sensitivity of the UPE during patching. One interesting question is whether such inhibition would influence the contrast gain changes of each eye after a short-term monocular deprivation (i.e., the aftereffects of 2.5 hr monocular patching)? We measured monocular contrast sensitivity as the inverse of contrast threshold. After 2.5 hr of monocular patching in the PE-open condition, the contrast sensitivity of the UPE changed from 103.086±6.961 (mean ± SE) before patching to 70.017±6.236 immediately after removal of the patch. This means that the short-term monocular deprivation temporally decreased the contrast sensitivity of the UPE by 32.1%. In contrast, the contrast sensitivity of the UPE decreased from 90.324±6.791 to 69.324±4.685 after 2.5 hr of monocular patching in the PE-closed condition. This implies that the aftereffect of 2.5 hr of monocular patching on monocular contrast sensitivity was 34.5% less in the PE-closed condition than that in the PE-open condition. Then, to normalize the change of contrast sensitivity for each eye at different conditions, we calculated the individual change of monocular contrast sensitivity in decibels (dB), where dB = 20 × log10(contrast sensitivity at post-measure session/contrast sensitivity at baseline). In Figure 3, we plot the average change of monocular contrast sensitivity after 2.5 hr of monocular patching where the PE remains open (sections M1&M3) and where the PE is kept closed (sections M2&M4) as open red triangle symbols and filled black triangle symbols (UPE: dashed line with inverted triangle; PE: solid line with regular triangle), respectively. The contrast sensitivity of the UPE becomes smaller for both of the two monocular deprivation conditions (for eye-closed patching, F(2,22) = 17.213, p<0.001, partial η2=0.610; for eye-open patching, F(2,22) = 24.371, p<0.001, partial η2=0.689; one-way repeated-measures within-subjects analysis of variance [ANOVA]), while the contrast sensitivity of the PE becomes larger or does not change (for eye-closed patching, F(2,22) = 0.447, p=0.645, partial η2=0.039; for eye-open patching, F(2,22) = 5.267, p=0.014, partial η2=0.324; one-way repeated-measures within-subjects ANOVA). Figure 3 Download asset Open asset The change in monocular contrast sensitivity as a result of the monocular deprivation. The change in monocular contrast sensitivity as a result of the monocular deprivation was compared when the eye behind the patch remained open (the eye-open condition: red lines and open triangles) and when the eye behind the patch was kept closed (the eye-closed condition: black lines and filled triangles) for the PE (solid line with regular triangle) and UPE (dashed line with inverted triangle). The contrast sensitivity change in decibels (dB) was calculated as: 20 × log10(contrast sensitivity at post-measure session/contrast sensitivity at baseline). Error bars indicate one SEM across 12 subjects. Figure 3—source data 1 Related to Figure 3. https://cdn.elifesciences.org/articles/83815/elife-83815-fig3-data1-v2.xlsx Download elife-83815-fig3-data1-v2.xlsx We further calculated the contrast sensitivity ratio by dividing the contrast sensitivity of the PE into that of UPE for two patching conditions. The change of contrast sensitivity ratio after deprivation was shown in Figure 4a. If the UPE becomes weaker or PE becomes stronger, the contrast sensitivity ratio becomes more negative, otherwise, the ratio becomes more positive. We conducted a two-way repeated-measures ANOVA, with the patching conditions (two levels) and time points of measurements after deprivation (two levels) selected as within-subject factors. The results showed that there was significant difference between two time points (F(1,11) = 20.245, p<0.001, partial η2=0.648), no difference between two patching conditions (F(1,11) = 0.811, p=0.387, partial η2=0.069), and significant interaction of time point and condition (F(1,11) = 9.271, p=0.011, partial η2=0.457). Post hoc Bonferroni test showed that the contrast sensitivity ratio changes between the eye-open and eye-closed patching at 0' was significantly different (p=0.023, Figure 4b). Figure 4 Download asset Open asset The change in contrast sensitivity ratio as a result of the monocular deprivation. (a) The change in contrast sensitivity ratio as a result of the monocular deprivation was compared when the eye behind the patch remained open (the eye-open condition: red lines and open hexagons) and when the eye behind the patch was kept closed (the eye-closed condition: black lines and filled hexagons). The contrast sensitivity ratio was calculated as: contrast sensitivity of UPE/contrast sensitivity of PE. The contrast sensitivity ratio change was calculated as: contrast sensitivity ratio at post-measure session − contrast sensitivity ratio at baseline. Error bars indicate one SEM across 12 subjects. (b) The average change of the post-measure session at 0' was compared for each subject for the two patching conditions. The open square symbol represents the averaged results. The dash line is the equality line. The gray area indicates where the eye-open patching produced more patching effect than the eye-closed patching. Error bars represent one SEM across 12 subjects. The black star indicates the significance of the two-tailed paired samples t-test, *: p<0.05. Figure 4—source data 1 Related to Figure 4a and b. https://cdn.elifesciences.org/articles/83815/elife-83815-fig4-data1-v2.xlsx Download elife-83815-fig4-data1-v2.xlsx The aftereffects of 2.5-hr monocular patching on binocular combination Since the results show that the contrast gain changes from monocular deprivation in the PE-closed condition is smaller than that in the PE-open condition, we wondered whether such an effect could also modulate the changes of sensory eye dominance after short-term monocular deprivation? We directly tested this by monitoring changes of sensory eye dominance as a result of monocular deprivation using a binocular phase combination task. After 2.5 hr of monocular patching in the PE-open condition, binocular perceived phase changed from –0.196±0.215° (mean ± SE) before patching to –14.196±3.184° immediately after removal of the patch. In contrast, in the PE-closed condition, binocular perceived phase changed from –0.214±0.308° to –6.357±1.962°. This means that the change in sensory eye dominance, as reflected by the binocular perceived phase, was 56.1% less in the PE-closed condition than that in the PE-open condition. The average change of perceived phase after patching where the patched (dominant) eye remains open (section B1) and where the patched (dominant) eye is kept closed (section B2) is plotted in Figure 5a as open red square symbols and filled black square symbols, respectively. The perceived phase changes in a more minus direction for both of the two monocular deprivation conditions. This means that after a 2.5 hr monocular patching, the contribution of PE to the binocularly fused percept becomes stronger. One-way repeated-measures within-subjects ANOVA showed that the binocular perceived phase significantly varied from baseline to post-measure sessions: for eye-closed patching, F(3.022,39.509)=7.126, p<0.001, partial η2=0.354; for eye-open patching, F(5,65) = 11.420, p<0.001, partial η2=0.468. These results indicate that the PE, which was the dominant eye, was significantly strengthened after both the eye-open patching (section B1) and the eye-closed patching (section B2). Figure 5 Download asset Open asset The change in ocular dominance as a result of the monocular deprivation in binocular combination. (a) The change in ocular dominance as a result of the monocular deprivation using phase combination task was compared for monocular patching where the eye behind the patch remained open (the eye-open condition – red lines and open squares) and when the eye behind the patch was closed (the eye-closed condition – black lines and filled squares). The perceived phase change was calculated as: perceived phase at post-measure session − perceived phase at baseline. Error bars indicate one SEM across 14 subjects. (b) The average change (degrees) of four post-measure sessions (0', 3', 6', 9') using the binocular phase combination task was compared for each subject for the two patching conditions. The open square symbol represents the averaged results. The dash line is the equality line. The gray area indicates where the eye-open patching produced more cumulated shift of ocular dominance than that of the eye-closed patching. Error bars represent one SEM across 14 subjects. The black star indicates the significance of the two-tailed paired samples t-test, **: p<0.001. Figure 5—source data 1 Related to Figure 5a and b. https://cdn.elifesciences.org/articles/83815/elife-83815-fig5-data1-v2.xlsx Download elife-83815-fig5-data1-v2.xlsx One interesting result, which is also obvious in Figure 5a, is that the ocular dominance changes as a result of monocular deprivation are stronger in the eye-open condition than that in the eye-closed condition. A two-way repeated-measures within-subjects ANOVA also showed that the magnitude of the change of the perceived phase was significantly different between these two patching conditions (i.e., eye-open vs. eye-closed): F(1,13) = 10.265, p=0.007, partial η2=0.441; the interaction between patching condition (i.e., eye-open vs. eye-closed) and the post-measure sessions (i.e., from 0' to 30') was not significant: F(4,52) = 1.553, p=0.201, partial η2=0.107, indicating the different patching impacts between the eye-open and eye-closed patching was consistent within 30 min after the removal of the patch. To further show the difference between these two patching conditions, we plotted individual averages of the perceived phase change of four post-measure sessions (0', 3', 6', 9') with eye-closed condition (section B2) as a function of that with eye-open condition (section B1) in Figure 5b. All subjects' data, except two, located above the equality line, indicating stronger patching effect in the eye-open condition than in the eye-closed condition. A two-tailed paired samples t-test also showed that there was a significant difference between these two conditions: t(13) = –3.276, p=0.006. The aftereffects of 2.5-hr monocular patching on binocular rivalry Similar patching induced ocular dominance shifts were found using the binocular rivalry task (sections B3&B4, Figure 6a, red and black circles) showing a distinct increase in the dominance of the PE after either eye-open patching (section B3; Figure 6a, red circles) or eye-closed patching (section B4; Figure 6a, black circles). One-way repeated-measures within-subjects ANOVA also showed that the eye dominance ratio significantly varied from baseline to post-measure sessions: for eye-closed patching, F(5,65) = 17.047, p<0.001, partial η2=0.567; for eye-open patching, F(5,65) = 34.987, p<0.001, partial η2=0.729. After 2.5 hr of monocular patching in the PE-open condition, the eye dominance ratio changed from 0.946±0.035 (mean ± SE) before patching to 0.459±0.061 immediately after removal of the patch. In contrast, in the PE-closed condition, the eye dominance ratio changed from 0.922±0.042 to 0.508±0.075. This means that the change in sensory eye dominance, as reflected by the binocular rivalry, was 6.9% less in the PE-closed condition than that in the PE-open condition. The magnitude of the eye dominance ratio shift was also significantly different between the two patching conditions: F(1,13) = 5.256, p=0.039, partial η2=0.288, without significant interaction between patching condition (i.e., eye-open vs. eye-closed) and the post-measure sessions (i.e., from 0' to 30'): F(4,52) = 2.009, p=0.107, partial η2=0.134 (two-way repeated-measures ANOVA). In Figure 6b, the average of the perceived phase change of four post-measure sessions (0', 3', 6', 9') was compared for each subject for the eye-open and eye-closed patching conditions. All subjects, except three, showing stronger change in the eye-open condition than that in the eye-closed condition. A Wilcoxon signed-rank test also showed that there was a significant difference between two conditions: Z=–2.103, p=0.035. Figure 6 Download asset Open asset The change in ocular dominance as a result of the monocular deprivation in binocular rivalry. (a) The change in ocular dominance as a result of the monocular deprivation using binocular rivalry task was compared when the eye behind the patch remained open (the eye-open condition: red lines and open circles) and when the eye behind the patch was kept closed (the eye-closed condition: black lines and filled circles). The eye dominance ratio was calculated as: dominant duration of UPE/dominant duration of PE. The eye dominance ratio change was calculated as: eye dominance ratio at post-measure session − eye dominance ratio at baseline. Error bars indicate one SEM across 14 subjects. (b) The average change of four post-measure sessions (0', 3', 6', 9') using the binocular rivalry task was compared for each subject for the two patching conditions. The open square symbol represents the averaged results. The dash line is the equality line. The gray area indicates where the eye-open patching produced more cumulated shift of ocular dominance than the eye-closed patching. Error bars represent one SEM across 14 subjects. The black star indicates the significance of the Wilcoxon signed-rank test, *: p<0.05. Figure 6—source data 1 Related to Figure 6a and b. https://cdn.elifesciences.org/articles/83815/elife-83815-fig6-data1-v2.xlsx Download elife-83815-fig6-data1-v2.xlsx Discussion In the absence of any visual stimulation, it is well accepted that the eyes open (REO) and eyes closed (REC) state, be it in the light or in the dark, can affect the resting state as reflected by changes in EEG spectral power and coherence in the Δ, θ, α1, α2, β1, β2, and γ frequency bands. Under complete darkness conditions, such changes cannot be related to exogenous visual stimulation, suggesting that the differences may be caused by the switching of involuntary preliminary attention from internally directed attention specific for the REC state to externally directed attention specific for the REO state (Boytsova and Danko, 2010). To our knowledge, we are the first to study the difference in brain state on visual sensitivity and changes in binocular balance in human adults. This was achieved by a monocular deprivation paradigm, with the PE that was being deprived of all visual input, being either open or closed. We show evidence that the PE-open and -closed states induce differences in alpha amplitude, which is quite similar with the differences in internal state when both eyes are open vs. when both eyes are closed. The elevation of alpha oscillations when closing the PE, both for the resting state and SSVEP sessions, results in a of contrast sensitivity of the UPE during deprivation of the other This internal state effect that these of sensitivity by internal state are at a binocular We also show that there is an of the aftereffect from short-term monocular the change in ocular dominance that results from such deprivation can be enhanced when the PE is kept open under the patch during the deprivation We show that this is for binocular combination and also binocular rivalry the mechanisms for these two are to be the involves interocular gain in visual cortex et al., and the involves interocular and influences from visual areas et al., The of the study is that we modulate the internal state with one eye open and its on visual processing for both monocular contrast and binocular combination. the of the internal states with one eye open or closed and assessing the visual sensitivity to the other eye, we can internal state with visual We found that the alpha amplitude by and in the resting state and during visual respectively, for the PE eye-closed condition compared to the PE eye-open condition. We demonstrate that both visual sensitivity and the regulation of binocular balance can be modulated by internal neural We showed that by the eye under the patch open, the immediate SSVEP amplitude and contrast sensitivity of UPE was the contrast gain and ocular dominance change when the occlude after 2.5 hr patching was It be that these changes are because contrast gain and ocular dominance to baseline after a period of However, there are differences in time between which may be to the that different may different of and In particular, the binocular perceived phase change in binocular combination which may on the of in the primary visual cortex et al., to to baseline within 30 min (Figure In contrast, changes in binocular rivalry, which more processing at as well as in the visual et al., at the post-measure session (Figure However, we measure further effects 30 it would be to that this would have This study the of the effects of only
Source: eLife
Author: Eric D Gaier
Institution: Boston Children's Hospital
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
OpenAlex ID: W4319663827