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Johnson, M. R.

Publications and source records attributed to Johnson, M. R..

2 recordsLinked to original sources

Not-so-working memory: Drift in fMRI pattern representations during maintenance predicts errors in a visual working memory task

Working memory (WM) is critical to many aspects of cognition, but it frequently fails. Much WM research has focused on capacity limits, but even for single, simple features, the fidelity of individual representations is limited. Why is this? We used fMRI and a pattern-based index of \"representational drift\" to investigate how ongoing changes in brain activity patterns throughout the WM maintenance period predicted performance, using a delayed-match-to-sample task for a single item with a single critical feature: orientation. In trials where the target and probe stimuli matched, participants incorrectly reported more non-matches when their activity patterns drifted away from the target. In trials where the target and probe did not match, participants incorrectly reported more matches when their activity patterns drifted towards the probe. Our results suggest that WM errors are not simply due to unstructured noise, but also drift within representation space that can be indexed by neuroimaging.

neuroscience

A Systems-Level Framework For Drug Discovery Identifies Csf1R As A Novel Anti-Epileptic Drug Target

The identification of mechanistically novel drug targets is highly challenging, particularly for diseases of the central nervous system. To address this problem we developed and experimentally validated a new computational approach to drug target identification that combines gene-regulatory information with a causal reasoning framework (\"causal reasoning analytical framework for target discovery\" - CRAFT). Starting from gene expression data, CRAFT provides a predictive functional genomics framework for identifying membrane receptors with a direction-specified influence over network expression. As proof-of-concept we applied CRAFT to epilepsy, and predicted the tyrosine kinase receptor Csf1R as a novel therapeutic target for epilepsy. The predicted therapeutic effect of Csf1R blockade was validated in two pre-clinical models of epilepsy using a small molecule inhibitor of Csf1R. These results suggest Csf1R blockade as a novel therapeutic strategy in epilepsy, and highlight CRAFT as a systems-level framework for predicting mechanistically new drugs and targets. CRAFT is applicable to disease settings other than epilepsy.

systems biology