N-Methyl-D-Aspartate Receptor-Antibody Encephalitis Impairs Maintenance of Attention to Items in Working Memory.

ABSTRACT

NMDA receptors (NMDARs) may be crucial to working memory (WM). Computational models predict that they sustain neural firing and produce associative memory, which may underpin maintaining and binding information, respectively. We test this in patients with antibodies to NMDAR (n = 10, female) and compare them with healthy control participants (n = 55, 20 male, 35 female). Patients were tested after recovery with a task that separates two aspects of WM sustaining attention and feature binding. Participants had to remember two colored arrows. Then attention was directed to one of them. After a variable delay, they reported the direction of either the same arrow (congruent cue) or of the other arrow (incongruent cue). We asked how congruency affected recall precision and measured types of error. Patients had difficulty in both sustaining attention to an item over time and feature binding. Controls were less precise after longer delays and incongruent cues. In contrast, patients did not benefit from congruent cues at longer delays [group × congruency (long condition); p = 0.041], indicating they could not sustain attention. Additionally, patients reported the wrong item (misbinding errors) more than controls after congruent cues [group × delay (congruent condition), main effect of group; p ≤ 0.001]. Our results suggest NMDARs are critical for both maintaining attention and feature binding.