PROJECT SUMMARY The brain constantly makes decisions based on perceptual input as well as internal signals, quickly weighing and processing information, leading to goal-directed behavior. One key aspect crucial to all these processes is communication: the transfer of information from one brain network to the next. However, we are only beginning to understand how the brain accomplishes this. Here we propose to study exactly this question. The overarching goal of this project is to elucidate how the brain sets up the functional neural architecture involved in working memory and decision- making. We argue that brain oscillations in the beta frequency band (15–30 Hz) play a critical role in forming flexible neural ensembles. We propose a novel theoretical framework, delineating how the beta rhythm flexibly sets up transient networks, linking neuronal circuits that are relevant to current task demands, especially in terms of endogenous information processing (e.g., working memory, decision-making). In this view, beta provides the scaffolding for information transfer, routing information through the brain by temporarily connecting relevant nodes such that exchange of information can take place. We propose that the beta rhythm briefly activates a neural ensemble, allowing it to broadcast its message—encoded in (population) spike activity—such that it can be efficiently and effectively received. To test this framework, we here aim to: 1) examine the role of beta oscillations in dynamic neural ensemble formation and its relation to behavioral performance, 2) identify the underlying circuit-level physiology of beta-mediated ensemble formation, and 3) establish the generality of beta-mediated ensemble formation and identify non- invasive biomarkers. We will use a combination of EEG recordings in healthy human subjects, and intracranial electrophysiology and optogenetic neuromodulation in awake-behaving rodents. Both human subjects and animals will perform a spatial working-memory paradigm, critically allowing vertical integration across recording levels. Human subjects will additionally perform working-memory tasks in different sensory modalities and at higher levels of abstraction to guarantee generalizability of results, and to allow for identification of biomarkers to be used in future patient studies. This approach is designed to answer core mechanistic questions: how are local ensembles formed and how are these modulated? Critically, we will determine the effect of these mechanisms on behavior. The project will provide fundamental insights that will set the stage for further detailed investigations in healthy human subjects and patients with impaired beta functioning and cognitive impairment, such as in Parkinson’s disease and schizophrenia.

PROJECT NARRATIVE We will study brain oscillations in the beta frequency band, testing a new framework proposing that these rhythms provide the scaffolding for information transfer in the brain. Critically, we will use neuromodulation methods to test for causal effects of these brain rhythms on behavior. This research project is designed to answer core mechanistic questions regarding a crucial brain operation underlying perception and cognition, and will set the stage for further detailed investigations in patients with idiosyncratic beta patterns and potentially related cognitive impairments (e.g., in Parkinson’s disease and schizophrenia).