Exploring Behavior-Relevant and Disentangled Neural Dynamics with Generative Diffusion Models

Understanding the neural basis of behavior is a fundamental goal in neuroscience. Current research in large-scale neuro-behavioral data analysis often relies on decoding models, which quantify behavioral information in neural data but lack details on behavior encoding. This raises an intriguing scientific question: ``how can we enable in-depth exploration of neural representations in behavioral tasks, revealing interpretable neural dynamics associated with behaviors''. However, addressing this issue is challenging due to the varied behavioral encoding across different brain regions and mixed selectivity at the population level. To tackle this limitation, our approach, named ``BeNeDiff'', first identifies a fine-grained and disentangled neural subspace using a behavior-informed latent variable model. It then employs state-of-the-art generative diffusion models to synthesize behavior videos that interpret the neural dynamics of each latent factor. We validate the method on multi-session datasets containing widefield calcium imaging recordings across the dorsal cortex. Through guiding the diffusion model to activate individual latent factors, we verify that the neural dynamics of latent factors in the disentangled neural subspace provide interpretable quantifications of the behaviors of interest. At the same time, the neural subspace in BeNeDiff demonstrates high disentanglement and neural reconstruction quality.

Paper

Similar papers

Peer review

Reviewer HCYS7/10 · confidence 4/52024-06-15

Summary

This study presents BeNeDiff that integrates behavior-informed latent variable models with state-of-the-art generative diffusion models to investigate neural dynamics during behavioral tasks. The methodology involves identifying fine-grained and disentangled neural subspaces and synthesizing behavior videos to provide interpretable quantifications of neural activity related to specific behaviors. The authors validate their approach using multi-session widefield calcium imaging datasets, demonstrating high levels of neural disentanglement and reconstruction quality.

Strengths

1. Using wide-field calcium imaging for neural-behavior analysis is both innovative and interesting. 2. The approach of employing a behavior LVM for latent factor disentanglement, followed by a video diffusion model for behavior encoding, is both clear and impressive. 3. Especially, using $Z$ produced by LVM as learning target for the classifier in video diffusion model is quiet important, avoiding the issue of "label leakage" which maybe introduced by classifier-free guidance generation. 4. The paper is well-organized, and the disentanglement results and behavior encoding results are both meaningful and useful.

Weaknesses

1. This work primarily relies on a behavior LVM for neural activity disentanglement, which can be influenced by the newly introduced total correlation (TC) penalty term with $\beta$ weighted. The impact of this penalty should be considered through ablation studies. **Not a Weakness**: There is significant research combining behavioral labels with latent variables of neural activity [1,2], considering the effects of different disentanglement algorithms on behavior encoding would further enhance this study. [1] Zhou, Ding, and Xue-Xin Wei. "Learning identifiable and interpretable latent models of high-dimensional neural activity using pi-VAE." Advances in Neural Information Processing Systems 33 (2020): 7234-7247. [2] Schneider, Steffen, Jin Hwa Lee, and Mackenzie Weygandt Mathis. "Learnable latent embeddings for joint behavioural and neural analysis." Nature 617.7960 (2023): 360-368.

Questions

I have no question.

Rating

7

Confidence

4

Soundness

3

Presentation

4

Contribution

3

Limitations

see WeaKnesses part.

Reviewer CLKJ6/10 · confidence 3/52024-07-12

Summary

The paper proposed BeNeDiff to learn disentangled neural trajectories together with a generative diffusion mode for behavior. BeNeDiff leverages beta-VAE for learning of disentangled space space Additional behavior generation module is applied for interpretation of the neural subspace. It is interesting to see that the learned latent latent trajectory is separated for different behavior types. The qualitative results and quantitative results demonstrate the superior of the proposed method.

Strengths

1.The disentangle property of neural latent space is significant compared to previous methods based on the quantitative metric. 2.The idea leveraging diffusion model to interpret learned neural subspace is interesting.

Weaknesses

1.It is unclear to me if the behavior video generation part is trained together with the disentangled subspace learning. It seems true based on the figure, but didn't see how they are optimized together from text. 2.it is interesting to learn the disentangled neural space. Some visualization of the learned latent space is beneficial. 3.Additional ablation study on different contribution of the loss function could be performed.

Questions

1.How training and testing data are split? Are they session wise or random? How the method can be generalized to different sessions or animals? 2.Does the learned latent trajectory show some clustering property, or somehow organized, could you visualize it? 3.For session 3.2, $c$ is better to be described as it is first mentioned in eq.5. Does the number of class is equals to feature dimension D and the same as the number of the behavior classes"? 4.To get figure 4, which latent variable do you use, $\hat{Z}$ or $Z$? 5.For fig.6, and fig.7, could you show the difference of the ground truth frame with the same behavior type as comparison.

Rating

6

Confidence

3

Soundness

3

Presentation

2

Contribution

3

Limitations

It could be better the paper include more analyze on the learned latent trajectory and see if it could provide some scientific insight.

Authorsrebuttal2024-08-12

Synthesizing Videos with Behavior Classifier Latents

Dear Reviewer CLKJ, We thank you for the valuable response. We agree that incorporating behavior labels can be helpful for learning a disentangled neural subspace. However, we note that our neural LVM module in BeNeDiff maintains a high neural data reconstruction rate (as shown in Table 1 of the manuscript), thereby preserving the neural dynamics in the latent trajectories. It is true that we can train a probabilistic behavior classifier (a behavior decoder from neural data $\mathbf{X}$ to behavior labels $\mathbf{U}$) to approximate the conditional distribution $p(\mathbf{U} \mid \mathbf{X})$ and derive latent variables $\mathbf{Z}'$ from it. The $\mathbf{Z}'$ would also be disentangled. However, such $\mathbf{Z}'$ lacks physical or semantic meaning, as there is no reconstruction of the neural data, making it unable to interpret neural dynamics or provide any scientific insights. We further trained a diffusion model guided by $\mathbf{Z}'$ and presented the visualization results. We have sent the AC a comment linking to an anonymous repository containing these synthesized video results. In accordance with this year’s NeurIPS guidelines, please have the AC forward it to you. We observe that while the synthesized videos by activating each latent factor does show some specificity to a particular behavior of interest, **the overall video results are quite chaotic and do not align with the ground-truth behavioral trajectories.** **The behavior movements are overly drastic and contain many unnatural distortions** compared to the videos generated by the neural latent trajectories in BeNeDiff. These videos will be included in the supplementary materials of the revised manuscript. Additionally, we have included the videos generated by BeNeDiff and the ground-truth behavior videos in the anonymous repository provided to the AC for comparison. Looking ahead, our future research aims to generalize BeNeDiff to settings where the latent (feature) dimension is larger than the number of behavior classes. We hope that these responses and the above rebuttals address your concerns and will be considered when determining the final review score.

Reviewer o3cJ5/10 · confidence 3/52024-07-15

Summary

The authors implement a VAE with behavioral labels to identify behavior-specific latent variables. They use these latents to then create a generative model for experimental video. They focus on the application of their model to a wide-field cortical recordings of a mouse during an experimental visual task. They show that their model identifies disentangled behaviorally relevant latents and can create experimental video where identifiable behavioral elements are generated from specific neural latents.

Strengths

I see two primary contributions in this paper that make it appropriate for a Neurips audience. 1) The use of Total correlation measures to disentangle latents in a VAE framework in neuroscience. 2) Using generative video diffusion models to identify what video features relate to individual neural latents. Both of these are interesting applications of existing methods but they are applied in a clever way to neural data and I think these would be of interest to a computational neuroscience audience.

Weaknesses

Each of the primary contributions to neural LVM type models (the use of total correlation and the diffusion modeling) are not sufficiently benchmarked against competing approaches. It is unclear how this model compares to the others used in neuroscience. If the authors wanted to strengthen the case that their model is an important novel contribution for behaviorally-relevant latent disentangling, they could compare how total correlation VAE compares to other methods where behavioral labels are used to help disentangle the latent states. One important comparison that I would be curious to see that isn't cited would be the pi-VAE1, but the others the authors cite could be used. Specifically, these other models could be added to figures 4 and 5. The authors could also focus on how using video diffusion is a novel application in this setting. Again, some additional benchmarking with existing deep LVMs in neuroscience and some further discussion and emphasis as to how the diffusion methodology solves an important problem in neuroscience that perhaps existing methods cannot solve would strengthen this paper. Though the authors highlight the application of the model to this specific dataset as a contribution, this alone would be more appropriate for a more experimentally-focused venue. For neurips, the focus should be on the model advancements and their applications, not the significance of the dataset. 1 - Learning identifiable and interpretable latent models of high-dimensional neural activity using pi-VAE - Zhou and Wei

Questions

NA

Rating

5

Confidence

3

Soundness

2

Presentation

3

Contribution

3

Limitations

The authors only minimally discussed the limits of the ability of their model.

Authorsrebuttal2024-08-12

Thank you

Dear Reviewer o3cJ, We sincerely appreciate your positive evaluation of our method's contribution and additional benchmarking. We apologize for the confusion in the Introduction section and will clarify the model's generalizability across datasets when discussing the major contributions in the revised manuscript. We thank you once again for the valuable feedback and suggestions.

Reviewer HCYS2024-08-09

Thank you for the author's response. The new information meets my expectations, and I hope this content can be added to the supplementary materials. Thus, I maintain my original score.

Authorsrebuttal2024-08-09

Thank you

Dear Reviewer HCYS, Thank you for your timely response. We will include the ablation study of the hyperparameter $\beta$ within the total-correlation term and present the results in the appendix of the revised manuscript. Additionally, we will assess the generalizability of the video diffusion modeling (VDM) module to the pi-VAE and CEBRA neural LVM baselines (with the total-correlation penalty term) to discover neural dynamics in their learned disentangled subspace. The generated video results (similar to Figures 6 and 7 of the manuscript) will be added to the supplementary materials. We again appreciate your evaluation and recognition of our work.

Reviewer CLKJ2024-08-10

Thanks for the responses. The responses addressed most of my concerns. But towards Q2, if the number of latent factor $D$ and the number of behavior of interest are the same, use the class label as guidance would obviously be helpful to learn a disentangled latent space. Directly learning a classifier and use the latent from the classifier would also be disentangled. It would be good to provide the latent variables from the trained classifier to diffusion model to see if the behavior videos could be synthesized from these variables.

Authorsrebuttal2024-08-12

Thank you

Dear Reviewer CLKJ, We appreciate your positive feedback and the adjustment to your score. As mentioned in our previous response, we will include the video results synthesized from behavior classifier latents in the supplementary materials of the revised manuscript. Thank you once again for your valuable suggestions and comments.

Authorsrebuttal2024-08-10

Thank you

Dear Reviewer o3cJ, Thank you for your positive feedback and for adjusting your score. As mentioned in our rebuttal, we will incorporate the neural LVM module comparisons and the VDM module-generated video visualizations for multiple datasets into the appendix of the revised manuscript.

Reviewer o3cJ2024-08-10

Thank you for the response. I think with this added detail the paper's contribution is clearer and I'd suggest emphasizing and clarifying the contribution similarly in a revised manuscript. I also appreciate the additional benchmarking with the total correlation measure. I have adjusted my score accordingly. Regarding my comment about your emphasis on the data set - I did not mean to suggest that the analysis is specific to this dataset, but rather that your phrasing in the manuscript emphasizes the data set in-and-of-itself as a major contribution. The end of the introduction reads "To highlight our major contributions: (1) This is the first work to explore wide-field imaging of the dorsal cortex of mice during a decision-making task using neural subspace analysis," and on like 167 "However, our work is the first to discover interpretable and disentangled latent subspaces of wide-field imaging data". I agree that your methods are generally applicable across datasets and I believe, therefore, that the model and it's generality should be what is primarily emphasized when discussing the major contributions in the manuscript.

Program Chairsdecision2024-09-25

Decision

Accept (poster)

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