Skip to main content

Unveiling Hidden Neural Codes: SIMPL – A Scalable and Fast Approach for Optimizing Latent Variables and Tuning Curves in Neural Population Data

Dr. Rishabh Pathak
This research paper presents SIMPL (Scalable Iterative Maximization of Population-coded Latents), a novel, computationally efficient algorithm designed to refine the estimation of latent variables and tuning curves from neural population activity. Latent variables in neural data represent essential low-dimensional quantities encoding behavioral or cognitive states, which neuroscientists seek to identify to understand brain computations better. Background and Motivation Traditional approaches commonly assume the observed behavioral variable as the latent neural code. However, this assumption can lead to inaccuracies because neural activity sometimes encodes internal cognitive states differing subtly from observable behavior (e.g., anticipation, mental simulation). Existing latent variable models face challenges such as high computational cost, poor scalability to large datasets, limited expressiveness of tuning models, or difficulties interpreting complex neural network-based functio...
Post a Comment

Acetylation status during neurodegeneration, memory functions and aging: use of epigenetic modulators in Alzheimer’s diseases?

Image
Dr. Rishabh Pathak

Acetylation status, particularly histone acetylation, plays a crucial role in regulating gene expression, synaptic plasticity, memory functions, and neurodegenerative processes in the context of aging and Alzheimer's disease (AD). Epigenetic modulators, including histone acetyltransferases (HATs) and histone deacetylases (HDACs), can dynamically regulate acetylation levels and impact neuronal function. Here is an overview of the acetylation status during neurodegeneration, memory functions, aging, and the potential use of epigenetic modulators in Alzheimer's disease:


1.      Acetylation Status in Neurodegeneration:

o    Altered Histone Acetylation:

§  Neurodegenerative diseases, including AD, are associated with dysregulation of histone acetylation patterns, leading to aberrant gene expression and neuronal dysfunction.

§  Changes in histone acetylation levels can influence the expression of genes involved in neuroinflammation, oxidative stress, protein aggregation, and synaptic impairment.

o    Role of HDACs:

§  Overactivity of HDACs in neurodegenerative conditions can result in chromatin condensation, transcriptional silencing of neuroprotective genes, and exacerbation of disease pathology.

§  Targeting HDACs with specific inhibitors has emerged as a potential therapeutic strategy to restore histone acetylation balance and mitigate neurodegeneration-associated processes.

2.     Acetylation Status in Memory Functions:

o    Synaptic Plasticity and Memory Formation:

§  Histone acetylation dynamics play a critical role in regulating synaptic plasticity mechanisms, such as long-term potentiation (LTP) and long-term memory formation.

§  Acetylation of histones at specific gene loci involved in memory consolidation and synaptic strength is essential for proper cognitive function.

o    Epigenetic Regulation of Memory:

§  Epigenetic modulators, including HATs and HDACs, modulate the acetylation status of histones and non-histone proteins, influencing memory processes and cognitive performance.

3.     Acetylation Status in Aging:

o    Age-Related Changes in Acetylation:

§  Aging is associated with alterations in histone acetylation patterns, impacting gene expression profiles, cellular senescence, and cognitive decline.

§  Dysregulation of acetylation status during aging can contribute to neurodegenerative changes, synaptic dysfunction, and memory deficits.

o    Potential Role of Epigenetic Modulators:

§  Modulating histone acetylation through epigenetic modulators may offer a strategy to counteract age-related epigenetic alterations, enhance cognitive function, and promote healthy brain aging.

4.    Use of Epigenetic Modulators in Alzheimer's Disease:

o    Therapeutic Potential:

§  Epigenetic modulators, such as HDAC inhibitors, have shown promise in preclinical studies and clinical trials for AD by targeting aberrant histone acetylation patterns and gene expression changes.

§  Restoring histone acetylation balance with epigenetic modulators may help alleviate neurodegenerative processes, enhance synaptic plasticity, and improve memory functions in AD patients.

In summary, understanding the acetylation status during neurodegeneration, memory functions, and aging provides insights into the molecular mechanisms underlying these processes. Utilizing epigenetic modulators, particularly those targeting histone acetylation, holds therapeutic potential for addressing epigenetic dysregulation in Alzheimer's disease and other age-related cognitive disorders. Further research into the specific mechanisms of acetylation regulation and the development of targeted epigenetic therapies may offer new avenues for treating neurodegenerative diseases and age-related cognitive decline.

 

Categories:

Comments

Post a Comment

Popular posts from this blog

Relation of Model Complexity to Dataset Size

Dr. Rishabh Pathak
Core Concept The relationship between model complexity and dataset size is fundamental in supervised learning, affecting how well a model can learn and generalize. Model complexity refers to the capacity or flexibility of the model to fit a wide variety of functions. Dataset size refers to the number and diversity of training samples available for learning. Key Points 1. Larger Datasets Allow for More Complex Models When your dataset contains more varied data points , you can afford to use more complex models without overfitting. More data points mean more information and variety, enabling the model to learn detailed patterns without fitting noise. Quote from the book: "Relation of Model Complexity to Dataset Size. It’s important to note that model complexity is intimately tied to the variation of inputs contained in your training dataset: the larger variety of data points your dataset contains, the more complex a model you can use without overfitting....
Post a Comment
Read more

Linear Models

Dr. Rishabh Pathak
1. What are Linear Models? Linear models are a class of models that make predictions using a linear function of the input features. The prediction is computed as a weighted sum of the input features plus a bias term. They have been extensively studied over more than a century and remain widely used due to their simplicity, interpretability, and effectiveness in many scenarios. 2. Mathematical Formulation For regression , the general form of a linear model's prediction is: y^ ​ = w0 ​ x0 ​ + w1 ​ x1 ​ + … + wp ​ xp ​ + b where; y^ ​ is the predicted output, xi ​ is the i-th input feature, wi ​ is the learned weight coefficient for feature xi ​ , b is the intercept (bias term), p is the number of features. In vector form: y^ ​ = wTx + b where w = ( w0 ​ , w1 ​ , ... , wp ​ ) and x = ( x0 ​ , x1 ​ , ... , xp ​ ) . 3. Interpretation and Intuition The prediction is a linear combination of features — each feature contributes prop...
Post a Comment
Read more

Uncertainty Estimates from Classifiers

Dr. Rishabh Pathak
1. Overview of Uncertainty Estimates Many classifiers do more than just output a predicted class label; they also provide a measure of confidence or uncertainty in their predictions. These uncertainty estimates help understand how sure the model is about its decision , which is crucial in real-world applications where different types of errors have different consequences (e.g., medical diagnosis). 2. Why Uncertainty Matters Predictions are often thresholded to produce class labels, but this process discards the underlying probability or decision value. Knowing how confident a classifier is can: Improve decision-making by allowing deferral in uncertain cases. Aid in calibrating models. Help in evaluating the risk associated with predictions. Example: In medical testing, a false negative (missing a disease) can be worse than a false positive (extra test). 3. Methods to Obtain Uncertainty from Classifiers 3.1 ...
Post a Comment
Read more

Ensembles of Decision Trees

Dr. Rishabh Pathak
1. What are Ensembles? Ensemble methods combine multiple machine learning models to create more powerful and robust models. By aggregating the predictions of many models, ensembles typically achieve better generalization performance than any single model. In the context of decision trees, ensembles combine multiple trees to overcome limitations of single trees such as overfitting and instability. 2. Why Ensemble Decision Trees? Single decision trees: Are easy to interpret but tend to overfit training data, leading to poor generalization,. Can be unstable because small variations in data can change the structure of the tree significantly. Ensemble methods exploit the idea that many weak learners (trees that individually overfit or only capture partial patterns) can be combined to form a strong learner by reducing variance and sometimes bias. 3. Two Main Types of Tree Ensembles (a) Random Forests Random forests are ensembles con...
Post a Comment
Read more

Predicting Probabilities

Dr. Rishabh Pathak
1. What is Predicting Probabilities? The predict_proba method estimates the probability that a given input belongs to each class. It returns values in the range [0, 1] , representing the model's confidence as probabilities. The sum of predicted probabilities across all classes for a sample is always 1 (i.e., they form a valid probability distribution). 2. Output Shape of predict_proba For binary classification , the shape of the output is (n_samples, 2) : Column 0: Probability of the sample belonging to the negative class. Column 1: Probability of the sample belonging to the positive class. For multiclass classification , the shape is (n_samples, n_classes) , with each column corresponding to the probability of the sample belonging to that class. 3. Interpretation of predict_proba Output The probability reflects how confidently the model believes a data point belongs to each class. For example, in ...
Post a Comment
Read more