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

Recent Publications

Cameron, IGM, Wallace DL, Al-Zughoul A, Kayser AS, D'Esposito M.  2018.  Effects of tolcapone and bromocriptine on cognitive stability and flexibility., 2018 Feb 09. Psychopharmacology. Abstract

The prefrontal cortex (PFC) and basal ganglia (BG) have been associated with cognitive stability and cognitive flexibility, respectively. We hypothesized that increasing PFC dopamine tone by administering tolcapone (a catechol-O-methyltransferase (COMT) inhibitor) to human subjects should promote stability; conversely, increasing BG dopamine tone by administering bromocriptine (a D2 receptor agonist) should promote flexibility.

Scimeca, JM, Kiyonaga A, D'Esposito M.  2018.  Reaffirming the Sensory Recruitment Account of Working Memory., 2018 Mar. Trends in cognitive sciences. 22(3):190-192.
Hwang, K, Shine JM, D'Esposito M.  2018.  Frontoparietal Activity Interacts With Task-Evoked Changes in Functional Connectivity., 2018 Feb 03. Cerebral cortex (New York, N.Y. : 1991). Abstract

Flexible interactions between brain regions enable neural systems to adaptively transfer and process information. However, the neural substrates that regulate adaptive communications between brain regions are understudied. In this human fMRI study, we investigated this issue by tracking time-varying, task-evoked changes in functional connectivity between localized occipitotemporal regions while participants performed different tasks on the same visually presented stimuli. We found that functional connectivity between ventral temporal and the primary visual regions selectively increased during the processing of task-relevant information. Further, additional task demands selectively strengthen these targeted connectivity patterns. To identify candidate regions that contribute to this increase in inter-regional coupling, we regressed the task-specific time-varying connectivity strength between primary visual and occipitotemporal regions against voxel-wise activity patterns elsewhere in the brain. This allowed us to identify a set of frontal and parietal regions whose activity increased as a function of task-evoked functional connectivity. These results suggest that frontoparietal regions may provide top-down biasing signals to influence task-specific interactions between brain regions.

Hwang, K, Bertolero M, Liu W, D'Esposito M.  2017.  The human thalamus is an integrative hub for functional brain networks., 2017 Apr 27. The Journal of neuroscience : the official journal of the Society for Neuroscience. Abstract

The thalamus is globally connected with distributed cortical regions, yet the functional significance of this extensive thalamocortical connectivity remains largely unknown. By performing graph-theoretic analyses on thalamocortical functional connectivity data collected from human participants, we found that most thalamic subdivisions display network properties capable of integrating multimodal information across diverse cortical functional networks. From a meta-analysis of a large dataset of functional brain imaging experiments, we further found that the thalamus is involved in multiple cognitive functions. Finally, we found that focal thalamic lesions in humans have widespread distal effects, disrupting the modular organization of cortical functional networks. This converging evidence suggests that the human thalamus is a critical hub region that could integrate diverse information being processed throughout the cerebral cortex, as well as maintain the modular structure of cortical functional networks.SIGNIFICANCE STATEMENTThe thalamus is traditionally viewed as a passive relay station of information from sensory organs or subcortical structures to the cortex. However, the thalamus has extensive connections with the entire cerebral cortex, which can also serve to integrate information processing between cortical regions. In this study, we demonstrate that multiple thalamic subdivisions displays network properties capable of integrating information across multiple functional brain networks. Moreover, the thalamus is engaged by tasks requiring multiple cognitive functions. These findings support the idea that the thalamus is involved in integrating information across cortical networks.

Berry, AS, Shah VD, Furman DJ, White RL, Baker SL, O'Neil JP, Janabi M, D'Esposito M, Jagust WJ.  2017.  Dopamine Synthesis Capacity is Associated with D2/3 Receptor Binding but not Dopamine Release., 2017 Aug 17. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. Abstract

Positron Emission Tomography (PET) imaging allows the estimation of multiple aspects of dopamine function including dopamine synthesis capacity, dopamine release, and D2/3 receptor binding. Though dopaminergic dysregulation characterizes a number of neuropsychiatric disorders including schizophrenia and addiction, there has been relatively little investigation into the nature of relationships across dopamine markers within healthy individuals. Here we used PET imaging in 40 healthy adults to compare, within individuals, estimates of dopamine synthesis capacity (Ki) using 6-[(18)F]fluoro-l-m-tyrosine ([(18)F]FMT; a substrate for aromatic amino acid decarboxylase), baseline D2/3 receptor binding potential using [(11)C]raclopride (a weak competitive D2/3 receptor antagonist), and dopamine release using [(11)C]raclopride paired with oral methylphenidate administration. Methylphenidate increases synaptic dopamine by blocking the dopamine transporter. We estimated dopamine release by contrasting baseline D2/3 receptor binding and D2/3 receptor binding following methylphenidate. Analysis of relationships among the three measurements within striatal regions of interest revealed a positive correlation between [(18)F]FMT Ki and the baseline (placebo) [(11)C]raclopride measure, such that participants with greater synthesis capacity showed higher D2/3 receptor binding potential. In contrast, there was no relationship between [(18)F]FMT and methylphenidate-induced [(11)C]raclopride displacement. These findings shed light on the nature of regulation between pre- and postsynaptic dopamine function in healthy adults, which may serve as a template from which to identify and describe alteration with disease.Neuropsychopharmacology accepted article preview online, 17 August 2017. doi:10.1038/npp.2017.180.