Noise-Assisted Instantaneous Coherence Analysis of Brain Connectivity

Characterizing brain connectivity between neural signals is key to understanding brain function. Current measures such as coherence heavily rely on Fourier or wavelet transform, which inevitably assume the signal stationarity and place severe limits on its time-frequency resolution. Here we addressed these issues by introducing a noise-assisted instantaneous coherence (NAIC) measure based on multivariate mode empirical decomposition (MEMD) coupled with Hilbert transform to achieve high-resolution time frequency representation of neural coherence. In our method, fully data-driven MEMD, together with Hilbert transform, is first employed to provide time-frequency power spectra for neural data. Such power spectra are typically sparse and of high resolution, that is, there usually exist many zero values, which result in numerical problems for directly computing coherence. Hence, we propose to add random noise onto the spectra, making coherence calculation feasible. Furthermore, a statistical randomization procedure is designed to cancel out the effect of the added noise. Computer simulations are first performed to verify the effectiveness of NAIC. Local field potentials collected from visual cortex of macaque monkey while performing a generalized flash suppression task are then used to demonstrate the usefulness of our NAIC method to provide highresolution time-frequency coherence measure for connectivity analysis of neural data

Structure-Function Network Mapping and Its Assessment via Persistent Homology

Understanding the relationship between brain structure and function is a fundamental problem in network neuroscience. This work deals with the general method of structure-function mapping at the whole-brain level. We formulate the problem as a topological mapping of structure-function connectivity via matrix function, and find a stable solution by exploiting a regularization procedure to cope with large matrices. We introduce a novel measure of network similarity based on persistent homology for assessing the quality of the network mapping, which enables a detailed comparison of network topological changes across all possible thresholds, rather than just at a single, arbitrary threshold that may not be optimal. We demonstrate that our approach can uncover the direct and indirect structural paths for predicting functional connectivity, and our network similarity measure outperforms other currently available methods. We systematically validate our approach with (1) a comparison of regularized vs. non-regularized procedures, (2) a null model of the degree-preserving random rewired structural matrix, (3) different network types (binary vs. weighted matrices), and (4) different brain parcellation schemes (low vs. high resolutions). Finally, we evaluate the scalability of our method with relatively large matrices (2514x2514) of structural and functional connectivity obtained from 12 healthy human subjects measured non-invasively while at rest. Our results reveal a nonlinear structure-function relationship, suggesting that the resting-state functional connectivity depends on direct structural connections, as well as relatively parsimonious indirect connections via polysynaptic pathways

Single-Trial Decoding of Bistable Perception Based on Sparse Nonnegative Tensor Decomposition

The study of the neuronal correlates of the spontaneous alternation in perception elicited by bistable visual stimuli is promising for understanding the mechanism of neural information processing and the neural basis of visual perception and perceptual decision-making. In this paper, we develop a sparse nonnegative tensor factorization-(NTF)-based method to extract features from the local field potential (LFP), collected from the middle temporal (MT) visual cortex in a macaque monkey, for decoding its bistable structure-from-motion (SFM) perception. We apply the feature extraction approach to the multichannel time-frequency representation of the intracortical LFP data. The advantages of the sparse NTF-based feature extraction approach lies in its capability to yield components common across the space, time, and frequency domains yet discriminative across different conditions without prior knowledge of the discriminating frequency bands and temporal windows for a specific subject. We employ the support vector machines (SVMs) classifier based on the features of the NTF components for single-trial decoding the reported perception. Our results suggest that although other bands also have certain discriminability, the gamma band feature carries the most discriminative information for bistable perception, and that imposing the sparseness constraints on the nonnegative tensor factorization improves extraction of this feature

Two-Stage Fine-Tuning: A Novel Strategy for Learning Class-Imbalanced Data

Classification on long-tailed distributed data is a challenging problem, which suffers from serious class-imbalance and hence poor performance on tail classes with only a few samples. Owing to this paucity of samples, learning on the tail classes is especially challenging for the fine-tuning when transferring a pretrained model to a downstream task. In this work, we present a simple modification of standard fine-tuning to cope with these challenges. Specifically, we propose a two-stage fine-tuning: we first fine-tune the final layer of the pretrained model with class-balanced reweighting loss, and then we perform the standard fine-tuning. Our modification has several benefits: (1) it leverages pretrained representations by only fine-tuning a small portion of the model parameters while keeping the rest untouched; (2) it allows the model to learn an initial representation of the specific task; and importantly (3) it protects the learning of tail classes from being at a disadvantage during the model updating. We conduct extensive experiments on synthetic datasets of both two-class and multi-class tasks of text classification as well as a real-world application to ADME (i.e., absorption, distribution, metabolism, and excretion) semantic labeling. The experimental results show that the proposed two-stage fine-tuning outperforms both fine-tuning with conventional loss and fine-tuning with a reweighting loss on the above datasets.Comment: 20 pages, 6 figure

Leveraging GPT-4 for Food Effect Summarization to Enhance Product-Specific Guidance Development via Iterative Prompting

Food effect summarization from New Drug Application (NDA) is an essential component of product-specific guidance (PSG) development and assessment. However, manual summarization of food effect from extensive drug application review documents is time-consuming, which arouses a need to develop automated methods. Recent advances in large language models (LLMs) such as ChatGPT and GPT-4, have demonstrated great potential in improving the effectiveness of automated text summarization, but its ability regarding the accuracy in summarizing food effect for PSG assessment remains unclear. In this study, we introduce a simple yet effective approach, iterative prompting, which allows one to interact with ChatGPT or GPT-4 more effectively and efficiently through multi-turn interaction. Specifically, we propose a three-turn iterative prompting approach to food effect summarization in which the keyword-focused and length-controlled prompts are respectively provided in consecutive turns to refine the quality of the generated summary. We conduct a series of extensive evaluations, ranging from automated metrics to FDA professionals and even evaluation by GPT-4, on 100 NDA review documents selected over the past five years. We observe that the summary quality is progressively improved throughout the process. Moreover, we find that GPT-4 performs better than ChatGPT, as evaluated by FDA professionals (43% vs. 12%) and GPT-4 (64% vs. 35%). Importantly, all the FDA professionals unanimously rated that 85% of the summaries generated by GPT-4 are factually consistent with the golden reference summary, a finding further supported by GPT-4 rating of 72% consistency. These results strongly suggest a great potential for GPT-4 to draft food effect summaries that could be reviewed by FDA professionals, thereby improving the efficiency of PSG assessment cycle and promoting the generic drug product development.Comment: 22 pages, 6 figure

Information Extraction From FDA Drug Labeling to Enhance Product-Specific Guidance Assessment Using Natural Language Processing

Towards the objectives of the UnitedStates Food and Drug Administration (FDA) generic drug science and research program, it is of vital importance in developing product-specific guidances (PSGs) with recommendations that can facilitate and guide generic product development. To generate a PSG, the assessor needs to retrieve supportive information about the drug product of interest, including from the drug labeling, which contain comprehensive information about drug products and instructions to physicians on how to use the products for treatment. Currently, although there are many drug labeling data resources, none of them including those developed by the FDA (e.g., Drugs@FDA) can cover all the FDA-approved drug products. Furthermore, these resources, housed in various locations, are often in forms that are not compatible or interoperable with each other. Therefore, there is a great demand for retrieving useful information from a large number of textual documents from different data resources to support an effective PSG development. To meet the needs, we developed a Natural Language Processing (NLP) pipeline by integrating multiple disparate publicly available data resources to extract drug product information with minimal human intervention. We provided a case study for identifying food effect information to illustrate how a machine learning model is employed to achieve accurate paragraph labeling. We showed that the pre-trained Bidirectional Encoder Representations from Transformers (BERT) model is able to outperform the traditional machine learning techniques, setting a new state-of-the-art for labelling food effect paragraphs from drug labeling and approved drug products datasets

Variance Entropy: A Method for Characterizing Perceptual Awareness of Visual Stimulus

Entropy, as a complexity measure, is a fundamental concept for time series analysis. Among many methods, sample entropy (SampEn) has emerged as a robust, powerful measure for quantifying complexity of time series due to its insensitivity to data length and its immunity to noise. Despite its popular use, SampEn is based on the standardized data where the variance is routinely discarded, which may nonetheless provide additional information for discriminant analysis. Here we designed a simple, yet efficient, complexity measure, namely variance entropy (VarEn), to integrate SampEn with variance to achieve effective discriminant analysis. We applied VarEn to analyze local field potential (LFP) collected from visual cortex of macaque monkey while performing a generalized flash suppression task, in which a visual stimulus was dissociated from perceptual experience, to study neural complexity of perceptual awareness. We evaluated the performance of VarEn in comparison with SampEn on LFP, at both single and multiple scales, in discriminating different perceptual conditions. Our results showed that perceptual visibility could be differentiated by VarEn, with significantly better discriminative performance than SampEn. Our findings demonstrate that VarEn is a sensitive measure of perceptual visibility, and thus can be used to probe perceptual awareness of a stimulus

Artificial Intelligence-Enabled End-To-End Detection and Assessment of Alzheimer’s Disease Using Voice

There is currently no simple, widely available screening method for Alzheimer’s disease (AD), partly because the diagnosis of AD is complex and typically involves expensive and sometimes invasive tests not commonly available outside highly specialized clinical settings. Here, we developed an artificial intelligence (AI)-powered end-to-end system to detect AD and predict its severity directly from voice recordings. At the core of our system is the pre-trained data2vec model, the first high-performance self-supervised algorithm that works for speech, vision, and text. Our model was internally evaluated on the ADReSSo (Alzheimer’s Dementia Recognition through Spontaneous Speech only) dataset containing voice recordings of subjects describing the Cookie Theft picture, and externally validated on a test dataset from DementiaBank. The AI model can detect AD with average area under the curve (AUC) of 0.846 and 0.835 on held-out and external test set, respectively. The model was well-calibrated (Hosmer-Lemeshow goodness-of-fit p-value = 0.9616). Moreover, the model can reliably predict the subject’s cognitive testing score solely based on raw voice recordings. Our study demonstrates the feasibility of using the AI-powered end-to-end model for early AD diagnosis and severity prediction directly based on voice, showing its potential for screening Alzheimer’s disease in a community setting