Tobias Egner - US grants

DESCRIPTION (provided by applicant): 'Cognitive control'describes the ability to configure, maintain, and adjust sets of processing strategies (task-sets), which underpins flexible, goal-directed behavior. The overarching goal of this proposal is to improve our understanding of the neural mechanisms mediating this behavioral flexibility. This represents a central challenge in the neurosciences that bears major clinical relevance, as many psychiatric and neurological conditions are characterized by impaired cognitive control. Our general strategy for achieving this goal is to fractionate the multifarious concept of cognitive control into experimentally tractable component processes, and to harness behavioral, neuroimaging, and neuro-disruptive techniques to probe their neural underpinnings and interrelations. As a point of departure we focus on conflict-driven control ('conflict adaptation'), a component mechanism of cognitive control that serves the function of task-set maintenance. Here, the monitoring of processing conflicts, arising from simultaneous activation of incompatible stimulus or response representations, is thought to provide a signal for reinforcing the top-down biasing processes that comprise the current task-set, thus ensuring that levels of biasing remain commensurate with task difficulty. We pursue two specific aims: first, to gain a more profound understanding of the neural mechanisms underlying conflict adaptation itself, and second, to position this conflict-driven control mechanism within the wider framework of other types of control processes that, in combination, facilitate flexible behavior. Two studies will address the first aim. Study 1.1 will examine the hypothesis that conflict-driven control is organized in a parallel architecture of multiple conflict adaptation loops, which resolve different types of conflict independently. For this purpose, we will define neural substrates of conflict adaptation to independently varied sources of conflict, using functional magnetic resonance imaging (fMRI), followed by fMRI-guided transcranial magnetic stimulation (TMS), to test whether distinct sources of top-down control play dissociable causal roles in resolving different conflicts. Study 1.2 will closely characterize the time-course of conflict adaptation processes. To address the second aim, three additional studies will assess how conflict adaptation interacts with other component mechanisms of cognitive control. Study 2.1 pursues this goal by contrasting the transient conflict adaptation mechanism with a more sustained form of control, by combining fMRI with an orthogonal manipulation of phasic and tonic levels of conflict. Study 2.2 contrasts the reactive nature of conflict adaptation with proactively recruited control, derived from explicit cues regarding forthcoming conflict. Finally, study 2.3 examines the relation between neural mechanisms underlying conflict-driven reinforcement of task-set with those that mediate detection of task-change and task-set reconfiguration, in a conflict task-switching paradigm. This research program has the potential to significantly enhance our understanding of how the human brain supports flexible, goal-directed behavior, and to highlight possible failure modes in this ability. PUBLIC HEALTH RELEVANCE: The proposed research is designed to elucidate neural mechanisms of 'cognitive control', the ability to generate, maintain, and adjust sets of goal-directed processing strategies, which lies at the heart of the type of flexible behavior that distinguishes humans from other animals, including other primates. We pursue this goal by combining experimental tasks that tax various component processes of cognitive control to differing degrees with measurements of brain activity (and functional connectivity between brain regions), as well as with stimulation techniques that temporarily inhibit function in a specific brain region, so that we can pinpoint which aspect of cognitive control is mediated by which brain region (or which set of interacting brain regions). The knowledge gained from this work will enhance our understanding of how the healthy brain mediates flexible, goal-directed behavior, and will provide more precise ideas of how neural mechanisms of cognitive control might be disrupted in psychiatric and neurological conditions.

DESCRIPTION (provided by applicant): An accurate interpretation of the visual environment is crucial to our survival. However, visual perception is faced with two major constraints. First, computational limitations of the visual system render it impossible to simultaneously analyze all aspects of our surroundings with high fidelity. To meet this challenge, vision relies on mechanisms of attention, prioritizing the processing of those aspects of the environment deemed most relevant to our wellbeing. Second, visual information is inherently ambiguous, as many distinct objects can cast an identical retinal image, while a single object can cast many different images. The brain meets this challenge by exploiting statistical regularities in the environment to form perceptual expectations, providing context- sensitive guidance regarding the most probable visual data. Though expectation and attention are closely interwoven in everyday life, they have typically either been investigated in isolation or confounded with each other, such that their relation remains poorly understood. We here argue that the disentangling of the twin influences of attention (stimulus relevance) and expectation (stimulus probability) on perception is a key to major advances in our understanding of visual cognition, including the resolution of longstanding debates in the attention literature (does attention act in an additive o a multiplicative fashion? Does attention act early or late?). Moreover, this question is deeply relevant to clinical conditions in which attentive and predictive processes appear to be deficient, such as attention deficit hyperactivity disorder and schizophrenia. The overall goal of this projec is to determine the computational and neural mechanisms of expectation and attention in visual cognition. We break down this goal into three specific aims. Firstly, we will dissect the computational mechanisms by which expectation and attention modulate visual perception, by examining the timing (early vs. late) and nature (additive vs. multiplicative) of their respective influences on signal detection and visual neural responses. Secondly, we will determine whether and how attention and expectation interact in their modulation of visual processing. Finally, we will exploit the computational metrics developed in this work to lay the foundations for translational computational neuropsychiatry applications, by linking individual differences in attention and expectation model parameters in healthy subjects to variance in personality traits that constitute known risk-factors for clinical diseases whose etiology involves deficits in attentive and predictive processing. These aims will be addressed with a combination of computational simulations, psychophysical testing, self- report, functional magnetic resonance imaging (fMRI), electro-, and magneto-encephalography (EEG, MEG). The proposed work bridges traditionally segregated research on attention and expectation, and advances our knowledge of how humans make sense of, and prioritize, their visual environment. It is furthermore directly relevant to improving our understanding of potential 'failure modes' of visual cognition in patient populations who have difficulty with controlling attention or with accurately predicting and interpreting sensory information.

Project Summary/Abstract Adaptive behavior requires the ability to keep a current task set in mind and shield it from distraction (cognitive stability), as well as to update task sets in response to changing requirements (cognitive flexibility). Cognitive stability and flexibility are complementary but opponent processing modes, as greater stability comes at the cost of lower flexibility, and vice versa. Importantly, neither a stable nor a flexible mental state is inherently beneficial; rather, it is the adaptation of one?s flexibility level to varying environmental demands ? or meta-flexibility - that produces optimal cognition. Accordingly, adopting a contextually optimal set point in the stability/flexibility trade-off is considered a challenging (and poorly understood) ?cognitive control dilemma?, and this ability is severely impaired in many psychiatric disorders. Therefore, understanding the neural mechanisms that mediate meta-flexibility is of great significance to both basic and clinical brain science. However, whereas individual differences and externally (e.g., drug-) induced changes in flexibility set points have been studied with some success, it is not presently known how the brain produces strategic meta-flexibility, i.e., learning to adapt one?s flexibility level to changing contexts. While a budding behavioral literature shows that people strategically adapt their readiness to switch tasks in line with changes in contextual switch-likelihood, no study to date has examined the neural mechanisms underlying these dynamic, learned changes in cognitive flexibility. Therefore, the overall goal of this proposal is to foster a new understanding of strategic meta-flexibility. We triangulate this goal via 3 strategic aims: in aim 1 we delineate the neural loci and mechanisms of meta-flexibility by combining proactive (Study 1) and reactive (Study 2) cognitive flexibility learning protocols with functional magnetic resonance imaging (fMRI) and a suite of cutting-edge analysis approaches, including brain state ?pinging? and representational similarity (RSA), multivoxel pattern (MVPA), and dynamic functional connectivity (dFC) analyses. In aim 2, we then move on to determine the learning processes that guide the above mechanisms of strategic shifts in switch-readiness. Here, we use model-based fMRI, multivariate measures of neural memory reinstatement, and fMRI-guided model-based transcranial magnetic stimulation (TMS) to test how both ?incremental? reinforcement learning (RL) (Studies 3 and 4) and episodic reinstatement (Study 5) may contribute to guiding strategic meta-flexibility. Having established the basic brain mechanisms of strategic meta-flexibility, in aim 3 we then examine its potential clinical significance as a transdiagnostic cognitive endophenotype, by leveraging large-scale online data collection to relate individual differences in strategic meta-flexibility to variance in clinically relevant self-report measures (Study 6). We thus lay the foundation for a potential computational psychiatry of cognitive meta-flexibility. In sum, this proposal is the first systematic research program into neurocognitive mechanisms of strategic meta-flexibility, the ability to adapt switch-readiness to suit changing contexts. This innovative project will significantly enhance our understanding of how task-switching is regulated, and help identify potential failure modes of meta-flexibility in health and disease.