NMDA receptor dysfunction disrupts history biases in working memory

The NMDA receptor (NMDAR) subserves memory mechanisms at several timescales, including sustained delay activity and different temporal components of synaptic potentiation. We investigated behavioral and electrophysiological working memory alterations in a delayed response task in two diseases linked to hypofunctional NMDARs: schizophrenia and autoimmune anti-NMDAR encephalitis. We report a markedly reduced influence of previous stimuli on to-be remembered working memory contents, while memory accuracy was preserved. Moreover, decoding analyses showed a limited temporal generalization of memory codes between trials in patients' EEG. In spiking network simulations of our memory task, we conclude that changes in cortical excitation quickly affect memory performance and cannot account for disrupted between trial interference. In contrast, our modeling supports alterations in NMDAR-dependent memory mechanisms operating on longer timescales, such as short-term potentiation. 

Heike Stein, who is completing her PhD studies with Albert Compte at IDIBAPS (Barcelona), will be presenting her work. For more information, see the corresponding biorxiv paper.