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Menon, R. N.

Publications and source records attributed to Menon, R. N..

3 recordsLinked to original sources

Memory Consolidation with Orthogonal Gradients for avoiding Catastrophic Forgetting

The memory consolidation process enables the accumulation of recent and remote memories in the long-term memory store. In general, the deep network models of memory suffer from forgetting old information while learning new information, called catastrophic forgetting/interference. The human brain overcomes this problem quite effectively, a problem that continues to challenge current deep neural network models. We propose a regularization-based model to solve the problem of catastrophic forgetting. According to the proposed training mechanism, the network parameters are constrained to vary in a direction orthogonal to the average of the error gradients corresponding to the previous tasks. We also ensure that the constraint used in parameter updating satisfies the locality principle. The proposed models performance is compared with Elastic Weight Consolidation on standard datasets such as permuted MNIST and split MNIST on classification tasks using fully connected networks, and Convolution-based networks. The model performance is also compared to an autoencoder on split MNIST dataset, and to complex core50 dataset on two types of classification tasks with EWC. The proposed model gives a new view on plasticity at the neuronal level. In the proposed model, the parameter updating is controlled by the neuronal level plasticity rather than synapse level plasticity as in other standard models. The biological plausibility of the proposed model is discussed by linking the extra parameters to synaptic tagging, which represents the state of the synapse involved in Long Term Potentiation (LTP).

neuroscience↗

Resting state functional connectivity in relapsing remitting multiple sclerosis with mild disability - a data driven, whole brain multivoxel pattern analysis study

BackgroundMultivoxel pattern analysis (MVPA) has emerged as a powerful unbiased approach for generating seed regions of interest (ROIs) in resting-state functional connectivity (RSFC) analysis in a data-driven manner. Studies exploring RSFC in multiple sclerosis have produced diverse and often incongruent results. ObjectivesThe aim of the present study was to investigate RSFC differences between persons with relapsing-remitting multiple sclerosis (RRMS) and healthy controls (HC). MethodsWe performed a whole-brain connectome-wide MVPA in 50 RRMS patients with expanded disability status scale [≤]4 and 50 age and gender-matched HCs. ResultsSignificant group differences were noted in RSFC in three clusters distributed in the following regions; anterior cingulate gyrus, right middle frontal gyrus, and frontal medial cortex. Whole-brain seed-to-voxel RSFC characterization of these clusters as seed ROIs revealed network-specific abnormalities, specifically in the anterior cingulate cortex and the default mode network. ConclusionsThe network-wide RSFC abnormalities we report agree with the previous findings in RRMS, the cognitive and clinical implications of which are discussed herein. IMPACT STATEMENTThis study investigated resting state functional connectivity (RSFC) in relapsing remitting multiple sclerosis (RRMS) persons with mild disability (expanded disability status scale [≤]4). Whole-brain connectome-wide multivoxel pattern analysis (MVPA) was used for assessing RSFC. Compared to healthy controls (HC), we were able to identify three regions of interest for significant differences in connectivity patterns, which were then extracted as a mask for whole-brain seed-to-voxel analysis. A reduced connectivity was noted in the RRMS group, particularly in the anterior cingulate cortex and the default mode network regions, providing insights into the RSFC abnormalities in RRMS.

neuroscience↗

A novel role for SHARPIN in Amyloid-beta- mediated macrophage function in Alzheimers disease

INTRODUCTIONDefective immune cell-mediated clearance of amyloid-beta (A{beta}) and A{beta}-associated inflammatory activation of immune cells are key contributors of A{beta} accumulation and neurodegeneration in Alzheimers disease (AD), however, the underlying mechanisms remain elusive.\n\nMETHODSDifferentiated THP-1 cells treated with A{beta} and AD patient-derived macrophages were used as in-vitro model. The role of SHARPIN was analysed in differentiated THP-1 cells using siRNA-mediated knockdown followed by immunoblotting, ELISA, real-time PCR, immunoprecipitation and flow cytometry. Differentiated SHSY5Y cells were used to study inflammation-mediated apoptosis.\n\nRESULTSSHARPIN was found to regulate A{beta}-phagocytosis and NLRP3 expression in THP-1 derived macrophages. Further, it was found to promote macrophage polarization to an M1 (pro-inflammatory) phenotype resulting in enhanced inflammation and associated neuronal death, demonstrated using in-vitro culture systems. SHARPIN expression by blood-derived macrophages was further found to be higher in the early stages of AD, which correlates with A{beta}40/42 concentration in the plasma and age of the study subjects.\n\nDISCUSSIONThe novel protein, SHARPIN has been shown to play critical roles in regulation of A{beta}-phagocytosis and inflammation in AD and the mechanism by which SHARPIN is activated by A{beta} in macrophages has been elucidated.

molecular biology↗