scholarly journals Bayesian inference for biophysical neuron models enables stimulus optimization for retinal neuroprosthetics

Author(s):  
Jonathan Oesterle ◽  
Christian Behrens ◽  
Cornelius Schröder ◽  
Thoralf Herrmann ◽  
Thomas Euler ◽  
...  

ABSTRACTMulticompartment models have long been used to study the biophysical mechanisms underlying neural information processing. However, it has been challenging to infer the parameters of such models from data. Here, we build on recent advances in Bayesian simulation-based inference to estimate the parameters of detailed models of retinal neurons whose anatomical structure was based on electron microscopy data. We demonstrate how parameters of a cone, an OFF- and an ON-cone bipolar cell model can be inferred from standard two-photon glutamate imaging with simple light stimuli. The inference method starts with a prior distribution informed by literature knowledge and yields a posterior distribution over parameters highlighting parameters consistent with the data. This posterior allows determining how well parameters are constrained by the data and to what extent changes in one parameter can be compensated for by changes in another. To demonstrate the potential of such data-driven mechanistic neuron models, we created a simulation environment for external electrical stimulation of the retina as used in retinal neuroprosthetic devices. We used the framework to optimize the stimulus waveform to selectively target OFF- and ON-cone bipolar cells, a current major problem of retinal neuroprothetics. Taken together, this study demonstrates how a data-driven Bayesian simulation-based inference approach can be used to estimate parameters of complex mechanistic models with high-throughput imaging data.

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jonathan Oesterle ◽  
Christian Behrens ◽  
Cornelius Schröder ◽  
Thoralf Hermann ◽  
Thomas Euler ◽  
...  

While multicompartment models have long been used to study the biophysics of neurons, it is still challenging to infer the parameters of such models from data including uncertainty estimates. Here, we performed Bayesian inference for the parameters of detailed neuron models of a photoreceptor and an OFF- and an ON-cone bipolar cell from the mouse retina based on two-photon imaging data. We obtained multivariate posterior distributions specifying plausible parameter ranges consistent with the data and allowing to identify parameters poorly constrained by the data. To demonstrate the potential of such mechanistic data-driven neuron models, we created a simulation environment for external electrical stimulation of the retina and optimized stimulus waveforms to target OFF- and ON-cone bipolar cells, a current major problem of retinal neuroprosthetics.


1967 ◽  
Vol 12 (11) ◽  
pp. 558-559
Author(s):  
STEPHAN L. CHOROVER

Author(s):  
Laure Fournier ◽  
Lena Costaridou ◽  
Luc Bidaut ◽  
Nicolas Michoux ◽  
Frederic E. Lecouvet ◽  
...  

Abstract Existing quantitative imaging biomarkers (QIBs) are associated with known biological tissue characteristics and follow a well-understood path of technical, biological and clinical validation before incorporation into clinical trials. In radiomics, novel data-driven processes extract numerous visually imperceptible statistical features from the imaging data with no a priori assumptions on their correlation with biological processes. The selection of relevant features (radiomic signature) and incorporation into clinical trials therefore requires additional considerations to ensure meaningful imaging endpoints. Also, the number of radiomic features tested means that power calculations would result in sample sizes impossible to achieve within clinical trials. This article examines how the process of standardising and validating data-driven imaging biomarkers differs from those based on biological associations. Radiomic signatures are best developed initially on datasets that represent diversity of acquisition protocols as well as diversity of disease and of normal findings, rather than within clinical trials with standardised and optimised protocols as this would risk the selection of radiomic features being linked to the imaging process rather than the pathology. Normalisation through discretisation and feature harmonisation are essential pre-processing steps. Biological correlation may be performed after the technical and clinical validity of a radiomic signature is established, but is not mandatory. Feature selection may be part of discovery within a radiomics-specific trial or represent exploratory endpoints within an established trial; a previously validated radiomic signature may even be used as a primary/secondary endpoint, particularly if associations are demonstrated with specific biological processes and pathways being targeted within clinical trials. Key Points • Data-driven processes like radiomics risk false discoveries due to high-dimensionality of the dataset compared to sample size, making adequate diversity of the data, cross-validation and external validation essential to mitigate the risks of spurious associations and overfitting. • Use of radiomic signatures within clinical trials requires multistep standardisation of image acquisition, image analysis and data mining processes. • Biological correlation may be established after clinical validation but is not mandatory.


2021 ◽  
Vol 7 (22) ◽  
pp. eabe7547
Author(s):  
Meenakshi Khosla ◽  
Gia H. Ngo ◽  
Keith Jamison ◽  
Amy Kuceyeski ◽  
Mert R. Sabuncu

Naturalistic stimuli, such as movies, activate a substantial portion of the human brain, invoking a response shared across individuals. Encoding models that predict neural responses to arbitrary stimuli can be very useful for studying brain function. However, existing models focus on limited aspects of naturalistic stimuli, ignoring the dynamic interactions of modalities in this inherently context-rich paradigm. Using movie-watching data from the Human Connectome Project, we build group-level models of neural activity that incorporate several inductive biases about neural information processing, including hierarchical processing, temporal assimilation, and auditory-visual interactions. We demonstrate how incorporating these biases leads to remarkable prediction performance across large areas of the cortex, beyond the sensory-specific cortices into multisensory sites and frontal cortex. Furthermore, we illustrate that encoding models learn high-level concepts that generalize to task-bound paradigms. Together, our findings underscore the potential of encoding models as powerful tools for studying brain function in ecologically valid conditions.


Author(s):  
Hans Liljenström

AbstractWhat is the role of consciousness in volition and decision-making? Are our actions fully determined by brain activity preceding our decisions to act, or can consciousness instead affect the brain activity leading to action? This has been much debated in philosophy, but also in science since the famous experiments by Libet in the 1980s, where the current most common interpretation is that conscious free will is an illusion. It seems that the brain knows, up to several seconds in advance what “you” decide to do. These studies have, however, been criticized, and alternative interpretations of the experiments can be given, some of which are discussed in this paper. In an attempt to elucidate the processes involved in decision-making (DM), as an essential part of volition, we have developed a computational model of relevant brain structures and their neurodynamics. While DM is a complex process, we have particularly focused on the amygdala and orbitofrontal cortex (OFC) for its emotional, and the lateral prefrontal cortex (LPFC) for its cognitive aspects. In this paper, we present a stochastic population model representing the neural information processing of DM. Simulation results seem to confirm the notion that if decisions have to be made fast, emotional processes and aspects dominate, while rational processes are more time consuming and may result in a delayed decision. Finally, some limitations of current science and computational modeling will be discussed, hinting at a future development of science, where consciousness and free will may add to chance and necessity as explanation for what happens in the world.


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