Single trial variability in neural activity during a working memory task: A window into multiple distinct information processing sequences

Successful encoding, maintenance, and retrieval of information stored in working memory requires persistent coordination of activity among multiple brain regions. It is generally assumed that the pattern of such coordinated activity remains consistent for a given task. Thus, to separate this task-relevant signal from noise, multiple trials of the same task are completed, and the neural response is averaged across trials to generate an event-related potential (ERP). However, from trial to trial, the neuronal activity recorded with electroencephalogram (EEG) is actually spatially and temporally diverse, conflicting with the assumption of a single pattern of activity for a given task. Here, we show that variability in neuronal activity among single time-locked trials arises from the presence of multiple forms of stimulus dependent synchronized activity (i.e., distinct ERPs). We develop a data-driven classification method based on community detection to identify three discrete spatio-temporal clusters, or subtypes, of trials with different patterns of activation that are further associated with differences in decision-making processes. These results demonstrate that differences in the patterns of neural activity during working memory tasks represent fluctuations in the engagement of distinct brain networks and cognitive processes, suggesting that the brain can choose from multiple mechanisms to perform a given task. Significance StatementWorking memory is a complex cognitive ability requiring coordinated activity among multiple brain regions to encode, maintain, and retrieve information. It is generally assumed that the pattern of coordination among brain regions remains consistent and one can average data across multiple trials of the same task. We instead show that there is significant variability in the patterns of brain activity among trials of the same task and develop a method to classify brain activity into distinct subtypes of responses, each with a different spatial and temporal pattern. The subtypes are associated with differences in decision-making processes, suggesting that the brain can use multiple mechanisms to perform a given task.