Peer review process
Not revised: This Reviewed Preprint includes the authors’ original preprint (without revision), an eLife assessment, public reviews, and a provisional response from the authors.
Read more about eLife’s peer review process.Editors
- Reviewing EditorSaad JbabdiUniversity of Oxford, Oxford, United Kingdom
- Senior EditorTimothy BehrensUniversity of Oxford, Oxford, United Kingdom
Reviewer #1 (Public review):
The manuscript by Choi and colleagues investigates the impact of variation in cortical geometry and growth on cortical surface morphology. Specifically, the study uses physical gel models and computational models to evaluate the impact of varying specific features/parameters of the cortical surface. The study makes use of this approach to address the topic of malformations of cortical development and finds that cortical thickness and cortical expansion rate are the drivers of differences in morphogenesis.
The study is composed of two main sections. First, the authors validate numerical simulation and gel model approaches against real cortical postnatal development in the ferret. Next, the study turns to modelling malformations in cortical development using modified tangential growth rate and cortical thickness parameters in numerical simulations. The findings investigate three genetically linked cortical malformations observed in the human brain to demonstrate the impact of the two physical parameters on folding in the ferret brain.
This is a tightly presented study that demonstrates a key insight into cortical morphogenesis and the impact of deviations from normal development. The dual physical and computational modeling approach offers the potential for unique insights into mechanisms driving malformations. This study establishes a strong foundation for further work directly probing the development of cortical folding in the ferret brain. One weakness of the current study is that the interpretation of the results in the context of human cortical development is at present indirect, as the modelling results are solely derived from the ferret. However, these modelling approaches demonstrate proof of concept for investigating related alterations more directly in future work through similar approaches to models of the human cerebral cortex.
Reviewer #2 (Public review):
Summary:
Based on MRI data of the ferret (a gyrencephalic non-primate animal, in whom folding happens postnatally), the authors create in vitro physical gel models and in silico numerical simulations of typical cortical gyrification. They then use genetic manipulations of animal models to demonstrate that cortical thickness and expansion rate are primary drivers of atypical morphogenesis. These observations are then used to explain cortical malformations in humans.
Strengths:
The paper is very interesting and original, and combines physical gel experiments, numerical simulations, as well as observations in MCD. The figures are informative, and the results appear to have good overall face validity.
Weaknesses:
On the other hand, I perceived some lack of quantitative analyses in the different experiments, and currently, there seems to be rather a visual/qualitative interpretation of the different processes and their similarities/differences.
Ideally, the authors also quantify local/pointwise surface expansion in the physical and simulation experiments, to more directly compare these processes. Time courses of eg, cortical curvature changes, could also be plotted and compared for those experiments.
I had a similar impression about the comparisons between simulation results and human MRI data. Again, face validity appears high, but the comparison appeared mainly qualitative.
I felt that MCDs could have been better contextualized in the introduction.