Visual Functions Are Associated with Biomarker Changes in Alzheimer's Disease.

Background: While various biomarkers of Alzheimer's disease (AD) have been associated with general cognitive function, their association to visual-perceptive function across the AD spectrum warrant more attention due to its significant impact on quality of life. Thus, this study explores how AD biomarkers are associated with decline in this cognitive domain. Objective: To explore associations between various fluid and imaging biomarkers and visual-based cognitive assessments in participants across the AD spectrum. Methods: Data from participants (N = 1,460) in the Alzheimer's Disease Neuroimaging Initiative were analyzed, including fluid and imaging biomarkers. Along with the Mini-Mental State Examination (MMSE), three specific visual-based cognitive tests were investigated: Trail Making Test (TMT) A and TMT B, and the Boston Naming Test (BNT). Locally estimated scatterplot smoothing curves and Pearson correlation coefficients were used to examine associations. Results: MMSE showed the strongest correlations with most biomarkers, followed by TMT-B. The p-tau181/Aß1-42 ratio, along with the volume of the hippocampus and entorhinal cortex, had the strongest associations among the biomarkers. Conclusions: Several biomarkers are associated with visual processing across the disease spectrum, emphasizing their potential in assessing disease severity and contributing to progression models of visual function and cognition.

Multimodal imaging measures in the prediction of clinical response to deep brain stimulation for refractory depression: A machine learning approach.

OBJECTIVES: This study compared machine learning models using unimodal imaging measures and combined multi-modal imaging measures for deep brain stimulation (DBS) outcome prediction in treatment resistant depression (TRD). METHODS: Regional brain glucose metabolism (CMRGlu), cerebral blood flow (CBF), and grey matter volume (GMV) were measured at baseline using 18F-fluorodeoxy glucose (18F-FDG) positron emission tomography (PET), arterial spin labelling (ASL) magnetic resonance imaging (MRI), and T1-weighted MRI, respectively, in 19 patients with TRD receiving subcallosal cingulate (SCC)-DBS. Responders (n = 9) were defined by a 50% reduction in HAMD-17 at 6 months from the baseline. Using an atlas-based approach, values of each measure were determined for pre-selected brain regions. OneR feature selection algorithm and the naïve Bayes model was used for classification. Leave-out-one cross validation was used for classifier evaluation. RESULTS: The performance accuracy of the CMRGlu classification model (84%) was greater than CBF (74%) or GMV (74%) models. The classification model using the three image modalities together led to a similar accuracy (84%0 compared to the CMRGlu classification model. CONCLUSIONS: CMRGlu imaging measures may be useful for the development of multivariate prediction models for SCC-DBS studies for TRD. The future of multivariate methods for multimodal imaging may rest on the selection of complementing features and the developing better models.Clinical Trial Registration: ClinicalTrials.gov (#NCT01983904).

Simulation of neuroplasticity in a CNN-based in-silico model of neurodegeneration of the visual system.

The aim of this work was to enhance the biological feasibility of a deep convolutional neural network-based in-silico model of neurodegeneration of the visual system by equipping it with a mechanism to simulate neuroplasticity. Therefore, deep convolutional networks of multiple sizes were trained for object recognition tasks and progressively lesioned to simulate neurodegeneration of the visual cortex. More specifically, the injured parts of the network remained injured while we investigated how the added retraining steps were able to recover some of the model's object recognition baseline performance. The results showed with retraining, model object recognition abilities are subject to a smoother and more gradual decline with increasing injury levels than without retraining and, therefore, more similar to the longitudinal cognition impairments of patients diagnosed with Alzheimer's disease (AD). Moreover, with retraining, the injured model exhibits internal activation patterns similar to those of the healthy baseline model when compared to the injured model without retraining. Furthermore, we conducted this analysis on a network that had been extensively pruned, resulting in an optimized number of parameters or synapses. Our findings show that this network exhibited remarkably similar capability to recover task performance with decreasingly viable pathways through the network. In conclusion, adding a retraining step to the in-silico setup that simulates neuroplasticity improves the model's biological feasibility considerably and could prove valuable to test different rehabilitation approaches in-silico.

Dementia in Convolutional Neural Networks: Using Deep Learning Models to Simulate Neurodegeneration of the Visual System.

Although current research aims to improve deep learning networks by applying knowledge about the healthy human brain and vice versa, the potential of using such networks to model and study neurodegenerative diseases remains largely unexplored. In this work, we present an in-depth feasibility study modeling progressive dementia in silico with deep convolutional neural networks. Therefore, networks were trained to perform visual object recognition and then progressively injured by applying neuronal as well as synaptic injury. After each iteration of injury, network object recognition accuracy, saliency map similarity between the intact and injured networks, and internal activations of the degenerating models were evaluated. The evaluation revealed that cognitive function of the network progressively decreased with increasing injury load whereas this effect was much more pronounced for synaptic damage. The effects of neurodegeneration found for the in silico model are especially similar to the loss of visual cognition seen in patients with posterior cortical atrophy.

Modeling Neurodegeneration in silico With Deep Learning.

Deep neural networks, inspired by information processing in the brain, can achieve human-like performance for various tasks. However, research efforts to use these networks as models of the brain have primarily focused on modeling healthy brain function so far. In this work, we propose a paradigm for modeling neural diseases in silico with deep learning and demonstrate its use in modeling posterior cortical atrophy (PCA), an atypical form of Alzheimer's disease affecting the visual cortex. We simulated PCA in deep convolutional neural networks (DCNNs) trained for visual object recognition by randomly injuring connections between artificial neurons. Results showed that injured networks progressively lost their object recognition capability. Simulated PCA impacted learned representations hierarchically, as networks lost object-level representations before category-level representations. Incorporating this paradigm in computational neuroscience will be essential for developing in silico models of the brain and neurological diseases. The paradigm can be expanded to incorporate elements of neural plasticity and to other cognitive domains such as motor control, auditory cognition, language processing, and decision making.