Short-term plasticity in the human visual thalamus
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Evaluation Summary:
This paper will be of interest to the large class of neuroscientists who investigate brain plasticity. It identifies short-term plasticity in a subcortical region, the ventral division of the pulvinar, following monocular deprivation in adult humans. The work is believed to extend our research focus on the topic of ocular dominance plasticity from mainly the cortex to a larger brain network including the subcortical stages of visual processing. This is an intriguing possibility, but further evidence is required to fully support the claims.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)
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Abstract
While there is evidence that the visual cortex retains a potential for plasticity in adulthood, less is known about the subcortical stages of visual processing. Here, we asked whether short-term ocular dominance plasticity affects the human visual thalamus. We addressed this question in normally sighted adult humans, using ultra-high field (7T) magnetic resonance imaging combined with the paradigm of short-term monocular deprivation. With this approach, we previously demonstrated transient shifts of perceptual eye dominance and ocular dominance in visual cortex (Binda et al., 2018). Here, we report evidence for short-term plasticity in the ventral division of the pulvinar (vPulv), where the deprived eye representation was enhanced over the nondeprived eye. This vPulv plasticity was similar as previously seen in visual cortex and it was correlated with the ocular dominance shift measured behaviorally. In contrast, there was no effect of monocular deprivation in two adjacent thalamic regions: dorsal pulvinar and Lateral Geniculate Nucleus. We conclude that the visual thalamus retains potential for short-term plasticity in adulthood; the plasticity effect differs across thalamic subregions, possibly reflecting differences in their corticofugal connectivity.
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Author Response:
Reviewer #1 (Public Review):
Strength:
Based on the previously published data (Binda et al., 2018), the authors focused their analysis on two subcortical ROIs, ventral pulvinar and LGN, and disclosed short-term ocular dominance plasticty in the ventral pulvinar but not in the LGN following monocular deprivation. The analysis method is generally sound, and the writing is clear. They primarily performed an FFT analysis, combining two more traditional analyses. The main finding in the ventral pulvinar was supported by all the three methods.
Weakness:
Although the paper does have strengths in principle, the weaknesses of the paper are the insufficient analyses and some writings that might potentially bias the main conclusion.
We thank this referee for their comments. We implemented new analyses and thoroughly …
Author Response:
Reviewer #1 (Public Review):
Strength:
Based on the previously published data (Binda et al., 2018), the authors focused their analysis on two subcortical ROIs, ventral pulvinar and LGN, and disclosed short-term ocular dominance plasticty in the ventral pulvinar but not in the LGN following monocular deprivation. The analysis method is generally sound, and the writing is clear. They primarily performed an FFT analysis, combining two more traditional analyses. The main finding in the ventral pulvinar was supported by all the three methods.
Weakness:
Although the paper does have strengths in principle, the weaknesses of the paper are the insufficient analyses and some writings that might potentially bias the main conclusion.
We thank this referee for their comments. We implemented new analyses and thoroughly revised our introduction and discussion, as specified in response to your specific comments below.
Line 72: Bourne & Morrone's (2017) review paper introduces the connectivity between the early visual cortex and ventrolateral subdivision of lateral Pulvinar. That is perhaps why the authors hypothesize that ventral Pulvinar may support ocular dominance plasticity. However, readers may wonder why it is the ventral Pulvinar but not the dorsal if they are not familiar with that review paper. For example, I was a little confused when I first read this paper.
A related question thus arises. Did the authors try the similar analysis on the dorsal division of Pulvinar? Showing the results there (even if they are negative) may help further understand the function of Pulvinar.
The Bourne and Morrone paper was certainly one motivation for studying short-term plasticity in the pulvinar, and primarily in its ventral portion. However, there were other considerations, which are now better outlined in the introduction. Mainly, ventral pulvinar is more tightly connected with posterior visual cortex than the dorsal pulvinar; this implies that passively viewed stimuli (such as the ones we used) are more likely to excite the ventral than the dorsal pulvinar; it also implies that ventral pulvinar is more likely to receive and relay signals from cortical areas affected by monocular deprivation (which we previously located in the occipital cortex, and mainly in its ventral aspect). These considerations originally led us to focus on ventral pulvinar. However, we acknowledge that both ventral and dorsal pulvinar divisions take part in cortico-thalamic loops modulating visual perception. We therefore embraced the opportunity to analyze responses in a mid-dorsal pulvinar region (where we found no effect of monocular deprivation). We completely agree that direct comparison of these two subregions is relevant for understanding the function of the pulvinar in this perceptual phenomenon.
A further related question. Did the authors check different divisions of LGN? Different parts of LGN may have different connectivity patterns, too. LGN receives direct and robust feedback from the cortex. There are different feedback connectivities between the layers of LGN and the layers of V1. For example, in macaque monkey, cells in cortical layer 6A were reported to project to the LGN P layers (or neighboring K layers, K3-K6) while cells in 6B were reported to project primarily to the LGN M (or neighboring K layers, K1-K3). In the present work, the BOLD response was calculated and reported only for the entire LGN, without separating its different layers. Not clear if different layers of LGN would show distinct BOLD response patterns.
Given the spatial resolution of our functional MR acquisitions, it was not possible to reliably discriminate responses in single LGN layers, but it was possible to separate two subregions within LGN (which we did based on an independent template): one more medial and ventral that primarily includes magnocellular layers, and the other (larger) with the parvocellular layers (we did not attempt to isolate the contribution of koniocellular neurons). Analyzing these separately confirmed the lack of monocular deprivation effects in both divisions. These results are included in an additional figure (Figure 2 - Supplement 2).
What about the phase results? The current manuscript only reports the amplitude results for the FFT analysis.
Thank you for raising this point. As shown in Figure 1D, response phases (the delay of the BOLD response) differed across regions of interest – in line with previous evidence that the hemodynamic delay differs across subcortical ROIs. Quantifying ROIs responses by FFT amplitude is one way to factor out these differences in response dynamics. Besides reporting analyses of FFT amplitude, we also report analyses of phase values, which we found unaffected by monocular deprivation.
Line 272: With Bold results, one cannot clarify the effect is feedforward or feedback, as the authors also proposed. Therefore, for now it seems not safe to say the plasticity originates in the pulvinar. Also at line 58, it is not clear why the authors propose that possibility in the Introduction. Input signals of each monocular pathway do not converge until they reach the visual cortex. Cortical changes of neural activity may be fed back to LGN though. Without feedback modulations from the cortex, it is hard to imagine why ocular dominance plasticity can originate at LGN.
Apologies for the lack of clarity on this point.
In principle, monocular deprivation could affect responses through monocular contrast adaptation. If this were the case, deprivation effects could emerge before any binocular interaction, in LGN or even in the retina. Another possibility (more common in the literature) is that monocular deprivation acts through inter-ocular interactions. Even in this case, modulations could still originate within the thalamus (e.g. through connections across LGN layers or through other thalamic nuclei, such as the TRN). Alternatively, they could generate within the cortex and be inherited by the thalamus (and impact vPulv more strongly than LGN, due to the relative importance of cortical and retinal inputs in the two regions). Given the relative sparseness of inter-ocular interactions in the thalamus vs. the cortex, we agree that the latter is the most likely scenario – although it is important to acknowledge that BOLD data cannot discriminate between these hypotheses.
Reviewer #2 (Public Review):
While this is an interesting paper using a clever behavioral paradigm to induce and measure short-term ocular dominance plasticity in humans, there are some limitations of the current manuscript, which limit the strength of claims made about the relative roles of the visual pulvinar and LGN in this plasticity:
1. Established major differences between LGN and vPulv properties and connectivity: LGN relay neurons receive their strongest driving input from a single eye, and are considered monocular. While there may be cross-talk between eye-specific information at the level of the LGN (because of intrinsic circuitry, cortical input, or both), this stands in stark contrast with vPulv neurons, which are largely binocular and receive their driving input from a range of visual cortical areas. A concise review of the literature on these subjects would help better define the hypotheses, and modulate the interpretation of results obtained.
2. A key animal study previously showed how binocular rivalry correlated with changes in LGN versus vPulv firing rates (Wilke et al. Proceedings of the National Academy of Sciences Jun 2009, 106 (23) 9465-9470) presenting results that dramatically parallel those reported here, and also in the context of binocular rivalry - a discussion of those findings and their implications for the present paradigm seems necessary and useful for interpretation of findings.
3. Other fMRI work in humans reporting strong BOLD signal modulation in the LGN associated with periods of perceptual dominance and suppression during binocular rivalry should also be reported and discussed (Haynes JD, Deichmann R, Rees G. 2005. Eye-specific effects of binocular rivalry in the human lateral geniculate nucleus. Nature 438(7067):496-499; Wunderlich K, Schneider KA, Kastner S. 2005. Neural correlates of binocular rivalry in the human lateral geniculate nucleus. Nat Neurosci 8(11):1595-1602).
Overall, while the results advance the field by presenting evidence of changes in vPulv [but not LGN] activity in concert with changes in perceptual performance reflective of ocular dominance plasticity, they do not reach the level of evidence needed to claim that these changes (or lack thereof) are causal, even differentially so. Nonetheless, the insights provided are useful, especially if the authors could expand on their [albeit speculative] discussion of how differences in circuitry, connectivity and physiological properties of the vPulv versus LGN could underlie the observed phenomena.
We would like to thank this referee for their comments and literature suggestions.
We have revised our introduction to outline the predicted outcomes of our experiment, based on the known features of LGN and pulvinar. Briefly, LGN is mainly a monocular relay stage (although it also receives feedback from the cortex, and it hosts binocular interactions between layers or through other nuclei like TRN) while vPulv is mainly driven by binocular cortical efferents (although it includes a small retinorecipient region in its inferior aspect). If monocular deprivation acted through monocular-contrast adaptation, as some have suggested, its effects could emerge in LGN. If monocular deprivation depended on interocular inhibition, its effects could emerge at stages where binocular integration is possible: certainly in the visual cortex, possibly in the thalamus. Even if effects emerged in the visual cortex, they could be inherited by thalamic nuclei through cortico-fugal signals. And these effects should be less evident in LGN than in pulvinar, given the stronger impact of feed-forward vs. cortico-fugal signals in LGN than in pulvinar.
We acknowledge that the BOLD technique does not provide decisive evidence for or against any of these possibilities. The differential response in LGN and vPulv suggests that monocular deprivation effects are weaker where processing is more monocular and we interpret this to suggest that monocular deprivation effects are sensitive to binocular interactions. However, our results do not mean that LGN “lacks plasticity”. We explicitly acknowledge that, while we failed to reveal an effect of monocular deprivation in this region, such effect might have been revealed under different experimental conditions.
We agree that work by Wilke et al. is relevant. There is remarkable consistency between the two sets of findings, Wilke et al’s electrophysiology and our BOLD data, both showing that vPulv tracks changes in perception better than LGN. However, our findings generalize this beyond the context of binocular rivalry: we found that vPulv BOLD activity tracked the effects of deprivation, even if BOLD was measured during passive monocular stimulation, not during binocular rivalry. Our stimulation conditions (monocular and passive) might account for the divergence of our observations in LGN and Haynes et al.’s or Wunderlich et al.’s. Other methodological considerations could also be relevant; for example, we had the opportunity to use ROIs defined by independent studies based on both functional and anatomical criteria. Instead, earlier work had to rely on functional activations for ROIs definitions, and this could have inflated their LGN region of interest to include part of other nuclei, like vPulv (DeSimone, Viviano and Schneider 2015 made a similar suggestion for their own previous analyses of LGN).
Following the referees’ suggestions, we extended our analyses to a third thalamic region: dPulv. Our passive viewing paradigm did not elicit reliable activation of this region (which did not change with deprivation); this is again consistent with Wilke et al.’s findings, who showed that dPulv is only engaged during active reporting of perception, not during passive stimulation.
These considerations have been included in the manuscript, by completely revising our introduction and discussion.
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Evaluation Summary:
This paper will be of interest to the large class of neuroscientists who investigate brain plasticity. It identifies short-term plasticity in a subcortical region, the ventral division of the pulvinar, following monocular deprivation in adult humans. The work is believed to extend our research focus on the topic of ocular dominance plasticity from mainly the cortex to a larger brain network including the subcortical stages of visual processing. This is an intriguing possibility, but further evidence is required to fully support the claims.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)
-
Reviewer #1 (Public Review):
Strength:
Based on the previously published data (Binda et al., 2018), the authors focused their analysis on two subcortical ROIs, ventral pulvinar and LGN, and disclosed short-term ocular dominance plasticty in the ventral pulvinar but not in the LGN following monocular deprivation. The analysis method is generally sound, and the writing is clear. They primarily performed an FFT analysis, combining two more traditional analyses. The main finding in the ventral pulvinar was supported by all the three methods.Weakness:
Although the paper does have strengths in principle, the weaknesses of the paper are the insufficient analyses and some writings that might potentially bias the main conclusion.Line 72: Bourne & Morrone's (2017) review paper introduces the connectivity between the early visual cortex and …
Reviewer #1 (Public Review):
Strength:
Based on the previously published data (Binda et al., 2018), the authors focused their analysis on two subcortical ROIs, ventral pulvinar and LGN, and disclosed short-term ocular dominance plasticty in the ventral pulvinar but not in the LGN following monocular deprivation. The analysis method is generally sound, and the writing is clear. They primarily performed an FFT analysis, combining two more traditional analyses. The main finding in the ventral pulvinar was supported by all the three methods.Weakness:
Although the paper does have strengths in principle, the weaknesses of the paper are the insufficient analyses and some writings that might potentially bias the main conclusion.Line 72: Bourne & Morrone's (2017) review paper introduces the connectivity between the early visual cortex and ventrolateral subdivision of lateral Pulvinar. That is perhaps why the authors hypothesize that ventral Pulvinar may support ocular dominance plasticity. However, readers may wonder why it is the ventral Pulvinar but not the dorsal if they are not familiar with that review paper. For example, I was a little confused when I first read this paper.
A related question thus arises. Did the authors try the similar analysis on the dorsal division of Pulvinar? Showing the results there (even if they are negative) may help further understand the function of Pulvinar.
A further related question. Did the authors check different divisions of LGN? Different parts of LGN may have different connectivity patterns, too. LGN receives direct and robust feedback from the cortex. There are different feedback connectivities between the layers of LGN and the layers of V1. For example, in macaque monkey, cells in cortical layer 6A were reported to project to the LGN P layers (or neighboring K layers, K3-K6) while cells in 6B were reported to project primarily to the LGN M (or neighboring K layers, K1-K3). In the present work, the BOLD response was calculated and reported only for the entire LGN, without separating its different layers. Not clear if different layers of LGN would show distinct BOLD response patterns.
What about the phase results? The current manuscript only reports the amplitude results for the FFT analysis.
Line 272: With Bold results, one cannot clarify the effect is feedforward or feedback, as the authors also proposed. Therefore, for now it seems not safe to say the plasticity originates in the pulvinar. Also at line 58, it is not clear why the authors propose that possibility in the Introduction. Input signals of each monocular pathway do not converge until they reach the visual cortex. Cortical changes of neural activity may be fed back to LGN though. Without feedback modulations from the cortex, it is hard to imagine why ocular dominance plasticity can originate at LGN.
-
Reviewer #2 (Public Review):
While this is an interesting paper using a clever behavioral paradigm to induce and measure short-term ocular dominance plasticity in humans, there are some limitations of the current manuscript, which limit the strength of claims made about the relative roles of the visual pulvinar and LGN in this plasticity:
1. Established major differences between LGN and vPulv properties and connectivity: LGN relay neurons receive their strongest driving input from a single eye, and are considered monocular. While there may be cross-talk between eye-specific information at the level of the LGN (because of intrinsic circuitry, cortical input, or both), this stands in stark contrast with vPulv neurons, which are largely binocular and receive their driving input from a range of visual cortical areas. A concise review of the …
Reviewer #2 (Public Review):
While this is an interesting paper using a clever behavioral paradigm to induce and measure short-term ocular dominance plasticity in humans, there are some limitations of the current manuscript, which limit the strength of claims made about the relative roles of the visual pulvinar and LGN in this plasticity:
1. Established major differences between LGN and vPulv properties and connectivity: LGN relay neurons receive their strongest driving input from a single eye, and are considered monocular. While there may be cross-talk between eye-specific information at the level of the LGN (because of intrinsic circuitry, cortical input, or both), this stands in stark contrast with vPulv neurons, which are largely binocular and receive their driving input from a range of visual cortical areas. A concise review of the literature on these subjects would help better define the hypotheses, and modulate the interpretation of results obtained.
2. A key animal study previously showed how binocular rivalry correlated with changes in LGN versus vPulv firing rates (Wilke et al. Proceedings of the National Academy of Sciences Jun 2009, 106 (23) 9465-9470) presenting results that dramatically parallel those reported here, and also in the context of binocular rivalry - a discussion of those findings and their implications for the present paradigm seems necessary and useful for interpretation of findings.
3. Other fMRI work in humans reporting strong BOLD signal modulation in the LGN associated with periods of perceptual dominance and suppression during binocular rivalry should also be reported and discussed (Haynes JD, Deichmann R, Rees G. 2005. Eye-specific effects of binocular rivalry in the human lateral geniculate nucleus. Nature 438(7067):496-499; Wunderlich K, Schneider KA, Kastner S. 2005. Neural correlates of binocular rivalry in the human lateral geniculate nucleus. Nat Neurosci 8(11):1595-1602).Overall, while the results advance the field by presenting evidence of changes in vPulv [but not LGN] activity in concert with changes in perceptual performance reflective of ocular dominance plasticity, they do not reach the level of evidence needed to claim that these changes (or lack thereof) are causal, even differentially so. Nonetheless, the insights provided are useful, especially if the authors could expand on their [albeit speculative] discussion of how differences in circuitry, connectivity and physiological properties of the vPulv versus LGN could underlie the observed phenomena.
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