The D'Esposito Lab is a cognitive neuroscience research laboratory within the
Helen Wills Neuroscience Institute
and the Department of Psychology.

Recent Publications

Louis, CC, D'Esposito M, Moser JS.  2021.  Investigating interactive effects of worry and the catechol-o-methyltransferase gene (COMT) on working memory performance., 2021 Jun 25. Cognitive, affective & behavioral neuroscience. Abstract

Extant research indicates that worry is associated with reduced working memory. It remains unclear, however, what mechanisms contribute to impaired performance in worriers. Critically, dopamine in the prefrontal cortex heavily influences the stability of mental representations during working memory tasks, yet no research has probed its role in associations between worry and working memory. To address this gap, the current study was designed to examine the moderating role of dopamine on the association between worry and working memory, using the catechol-o-methyltransferase (COMT) gene as a proxy for basal levels of dopamine. Across four assessments, we examined within- and between-person variation in worry and its interactive effects with COMT to predict working memory performance. Within-person variation in worry interacted with COMT to predict accuracy, such that higher worry across time predicted less accuracy for homozygous Val carriers but not Met carriers. Our findings demonstrate that basal dopamine plays an important role in how increases in worry across time for an individual negatively impact working memory performance.

Westphal, AJ, Ballard ME, Rodriguez N, Vega TA, D'Esposito M, Kayser AS.  2021.  Working memory, cortical dopamine tone, and frontoparietal brain recruitment in post-traumatic stress disorder: a randomized controlled trial., 2021 Jul 12. Translational psychiatry. 11(1):389. Abstract

Post-traumatic stress disorder (PTSD) leads to impairments in both cognitive and affective functioning. Animal work suggests that chronic stress reduces dopamine tone, and both animal and human studies argue that changes in dopamine tone influence working memory, a core executive function. These findings give rise to the hypothesis that increasing cortical dopamine tone in individuals with greater PTSD symptomatology should improve working memory performance. In this pharmacological functional magnetic resonance imaging (fMRI) study, 30 US military veterans exhibiting a range of PTSD severity completed an emotional working memory task. Each subject received both placebo and the catechol-O-methyl transferase inhibitor tolcapone, which increases cortical dopamine tone, in randomized, double-blind, counterbalanced fashion. Mnemonic discriminability (calculated with d', an index of the detectability of working memory signals) and response bias were evaluated in the context of task-related brain activations. Subjects with more severe PTSD showed both greater tolcapone-mediated improvements in d' and larger tolcapone-mediated reductions in liberally-biased responding for fearful stimuli. FMRI revealed that tolcapone augmented activity within bilateral frontoparietal control regions during the decision phase of the task. Specifically, tolcapone increased cortical responses to fearful relative to neutral stimuli in higher severity PTSD subjects, and reduced cortical responses to fearful stimuli for lower severity PTSD subjects. Moreover, tolcapone modulated prefrontal connectivity with areas overlapping the default mode network. These findings suggest that enhancing cortical dopamine tone may represent an approach to remediating cognitive and affective dysfunction in individuals with more severe PTSD symptoms.

Levine, B, Rosenbaum SR, Solbakk A-K, D'Esposito M.  2021.  Introduction to the Special Issue., 2021 Jul 16. Journal of cognitive neuroscience. :1.
Miller, JA, D'Esposito M, Weiner KS.  2021.  Using Tertiary Sulci to Map the "Cognitive Globe" of Prefrontal Cortex., 2021 Aug 01. Journal of cognitive neuroscience. 33(9):1698-1715. Abstract

Stuss considered the human PFC as a "cognitive globe" [Stuss, D. T., & Benson, D. F. Neuropsychological studies of the frontal lobes. Psychological Bulletin, 95, 3-28, 1984] on which functions of the frontal lobe could be mapped. Here, we discuss classic and recent findings regarding the evolution, development, function, and cognitive role of shallow indentations or tertiary sulci in PFC, with the goal of using tertiary sulci to map the "cognitive globe" of PFC. First, we discuss lateral PFC (LPFC) tertiary sulci in classical anatomy and modern neuroimaging, as well as their development, with a focus on those within the middle frontal gyrus. Second, we discuss tertiary sulci in comparative neuroanatomy, focusing on primates. Third, we summarize recent findings showing the utility of tertiary sulci for understanding structural-functional relationships with functional network insights in ventromedial PFC and LPFC. Fourth, we revisit and update unresolved theoretical perspectives considered by C. Vogt and O. Vogt (Allgemeinere ergebnisse unserer hirnforschung. Journal für Psychologie und Neurologie, 25, 279-462, 1919) and F. Sanides (Structure and function of the human frontal lobe. Neuropsychologia, 2, 209-219, 1964) that tertiary sulci serve as landmarks for cortical gradients. Together, the consideration of these classic and recent findings indicate that tertiary sulci are situated in a unique position within the complexity of the "cognitive globe" of PFC: They are the smallest and shallowest of sulci in PFC, yet can offer insights that bridge spatial scales (microns to networks), modalities (functional connectivity to behavior), and species. As such, the map of tertiary sulci within each individual participant serves as a coordinate system specific to that individual on which functions may be further mapped. We conclude with new theoretical and methodological questions that, if answered in future research, will likely lead to mechanistic insight regarding the structure and function of human LPFC.

Menon, V, D'Esposito M.  2021.  The role of PFC networks in cognitive control and executive function., 2021 Aug 18. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. Abstract

Systems neuroscience approaches with a focus on large-scale brain organization and network analysis are advancing foundational knowledge of how cognitive control processes are implemented in the brain. Over the past decade, technological and computational innovations in the study of brain connectivity have led to advances in our understanding of how brain networks function, inspiring new conceptualizations of the role of prefrontal cortex (PFC) networks in the coordination of cognitive control. In this review, we describe six key PFC networks involved in cognitive control and elucidate key principles relevant for understanding how these networks implement cognitive control. Implementation of cognitive control in a constantly changing environment depends on the dynamic and flexible organization of PFC networks. In this context, we describe major empirical and theoretical models that have emerged in recent years and describe how their functional architecture and dynamic organization supports flexible cognitive control. We take an overarching view of advances made in the past few decades and consider fundamental issues regarding PFC network function, global brain dynamics, and cognition that still need to be resolved. We conclude by clarifying important future directions for research on cognitive control and their implications for advancing our understanding of PFC networks in brain disorders.