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

Recent Publications

Miller, JA, Voorhies WI, Lurie DJ, D'Esposito M, Weiner KS.  2021.  Overlooked tertiary sulci serve as a meso-scale link between microstructural and functional properties of human lateral prefrontal cortex., 2021 Jan 15. The Journal of neuroscience : the official journal of the Society for Neuroscience. Abstract

Understanding the relationship between neuroanatomy and function in portions of cortex that perform functions largely specific to humans such as lateral prefrontal cortex (LPFC) is of major interest in systems and cognitive neuroscience. When considering neuroanatomical-functional relationships in LPFC, shallow indentations in cortex known as tertiary sulci have been largely unexplored. Here, by implementing a multi-modal approach and manually defining 936 neuroanatomical structures in 72 hemispheres (in both males and females), we show that a subset of these overlooked tertiary sulci serve as a meso-scale link between microstructural (myelin content) and functional (network connectivity) properties of human LPFC in individual participants. For example, the () is a tertiary sulcus with three components that differ in their myelin content, resting state connectivity profiles, and engagement across meta-analyses of 83 cognitive tasks. Further, generating microstructural profiles of myelin content across cortical depths for each component and the surrounding middle frontal gyrus (MFG) shows that both gyral and sulcal components of the MFG have greater myelin content in deeper compared to superficial layers and that the myelin content in superficial layers of the gyral components is greater than sulcal components. These findings support a classic, yet largely unconsidered theory that tertiary sulci may serve as landmarks in association cortices, as well as a modern cognitive neuroscience theory proposing a functional hierarchy in LPFC. As there is a growing need for computational tools that automatically define tertiary sulci throughout cortex, we share probabilistic sulcal maps with the field.: Lateral prefrontal cortex (LPFC) is critical for functions that are thought to be specific to humans compared to other mammals. However, relationships between fine-scale neuroanatomical structures largely specific to hominoid cortex and functional properties of LPFC remain elusive. Here, we show that these structures, which have been largely unexplored throughout history, surprisingly serve as markers for anatomical and functional organization in human LPFC. These findings have theoretical, methodological, developmental, and evolutionary implications for improved understanding of neuroanatomical-functional relationships not only in LPFC, but also in association cortices more broadly. Finally, these findings ignite new questions regarding how morphological features of these neglected neuroanatomical structures contribute to functions of association cortices that are critical for human-specific aspects of cognition.

Cook, PF, Hoard VA, Dolui S, deB Frederick B, Redfern R, Dennison SE, Halaska B, Bloom J, Kruse-Elliott KT, Whitmer ER, Trumbull EJ, Berns GS, Detre JA, D'Esposito M, Gulland FMD, Reichmuth C, Johnson SP, Field CL, Inglis BA.  2021.  An MRI protocol for anatomical and functional evaluation of the California sea lion brain., 2021 Feb 10. Journal of neuroscience methods. :109097. Abstract

Domoic acid (DOM) is a neurotoxin produced by some harmful algae blooms in coastal waters. California sea lions (Zalophus californianus) exposed to DOM often strand on beaches where they exhibit a variety of symptoms, including seizures. These animals typically show hippocampal atrophy on MRI scans.

Miller, JA, D'Esposito M, Weiner KS.  2021.  Using Tertiary Sulci to Map the "Cognitive Globe" of Prefrontal Cortex., 2021 Mar 03. Journal of cognitive neuroscience. :1-18. Abstract

Stuss considered the human prefrontal cortex (pFC) as a "cognitive globe" [Stuss, D. T., & Benson, D. F. Neuropsychological studies of the frontal lobes. , , 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. , , 279-462, 1919) and F. Sanides (Structure and function of the human frontal lobe. , , 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.

Eichenbaum, A, Pappas I, Lurie D, Cohen JR, D'Esposito M.  2021.  Differential contributions of static and time-varying functional connectivity to human behavior., 2021. Network neuroscience (Cambridge, Mass.). 5(1):145-165. Abstract

Measures of human brain functional connectivity acquired during the resting-state track critical aspects of behavior. Recently, fluctuations in resting-state functional connectivity patterns-typically averaged across in traditional analyses-have been considered for their potential neuroscientific relevance. There exists a lack of research on the differences between traditional "static" measures of functional connectivity and newly considered "time-varying" measures as they relate to human behavior. Using functional magnetic resonance imagining (fMRI) data collected at rest, and a battery of behavioral measures collected outside the scanner, we determined the degree to which each modality captures aspects of personality and cognitive ability. Measures of time-varying functional connectivity were derived by fitting a hidden Markov model. To determine behavioral relationships, static and time-varying connectivity measures were submitted separately to canonical correlation analysis. A single relationship between static functional connectivity and behavior existed, defined by measures of personality and stable behavioral features. However, two relationships were found when using time-varying measures. The first relationship was similar to the static case. The second relationship was unique, defined by measures reflecting trialwise behavioral variability. Our findings suggest that time-varying measures of functional connectivity are capable of capturing unique aspects of behavior to which static measures are insensitive.

Kimbrough, A, Lurie DJ, Collazo A, Kreifeldt M, Sidhu H, Macedo GC, D'Esposito M, Contet C, George O.  2020.  Brain-wide functional architecture remodeling by alcohol dependence and abstinence., 2020 Jan 14. Proceedings of the National Academy of Sciences of the United States of America. 117(4):2149-2159. Abstract2020_kimbrough.pdf

Alcohol abuse and alcohol dependence are key factors in the development of alcohol use disorder, which is a pervasive societal problem with substantial economic, medical, and psychiatric consequences. Although our understanding of the neurocircuitry that underlies alcohol use has improved, novel brain regions that are involved in alcohol use and novel biomarkers of alcohol use need to be identified. The present study used a single-cell whole-brain imaging approach to 1) assess whether abstinence from alcohol in an animal model of alcohol dependence alters the functional architecture of brain activity and modularity, 2) validate our current knowledge of the neurocircuitry of alcohol abstinence, and 3) discover brain regions that may be involved in alcohol use. Alcohol abstinence resulted in the whole-brain reorganization of functional architecture in mice and a pronounced decrease in modularity that was not observed in nondependent moderate drinkers. Structuring of the alcohol abstinence network revealed three major brain modules: 1) extended amygdala module, 2) midbrain striatal module, and 3) cortico-hippocampo-thalamic module, reminiscent of the three-stage theory. Many hub brain regions that control this network were identified, including several that have been previously overlooked in alcohol research. These results identify brain targets for future research and demonstrate that alcohol use and dependence remodel brain-wide functional architecture to decrease modularity. Further studies are needed to determine whether the changes in coactivation and modularity that are associated with alcohol abstinence are causal features of alcohol dependence or a consequence of excessive drinking and alcohol exposure.