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

Recent Publications

Toker, D, Sommer FT, D'Esposito M.  2020.  A simple method for detecting chaos in nature., 2020. Communications biology. 3:11. Abstract

Chaos, or exponential sensitivity to small perturbations, appears everywhere in nature. Moreover, chaos is predicted to play diverse functional roles in living systems. A method for detecting chaos from empirical measurements should therefore be a key component of the biologist's toolkit. But, classic chaos-detection tools are highly sensitive to measurement noise and break down for common edge cases, making it difficult to detect chaos in domains, like biology, where measurements are noisy. However, newer tools promise to overcome these limitations. Here, we combine several such tools into an automated processing pipeline, and show that our pipeline can detect the presence (or absence) of chaos in noisy recordings, even for difficult edge cases. As a first-pass application of our pipeline, we show that heart rate variability is not chaotic as some have proposed, and instead reflects a stochastic process in both health and disease. Our tool is easy-to-use and freely available.

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. Abstract

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.

Berry, AS, White RL, Furman DJ, Naskolnakorn JR, Shah VD, D'Esposito M, Jagust WJ.  2019.  Dopaminergic mechanisms underlying normal variation in trait anxiety., 2019 Feb 08. The Journal of neuroscience : the official journal of the Society for Neuroscience. Abstract

Trait anxiety has been associated with altered activity within corticolimbic pathways connecting the amygdala and rostral anterior cingulate cortex (rACC), which receive rich dopaminergic input. Though the popular culture uses the term "chemical imbalance" to describe the pathophysiology of psychiatric conditions such as anxiety disorders, we know little about how individual differences in human dopamine neurochemistry are related to variation in anxiety and activity within corticolimbic circuits. We addressed this issue by examining inter-individual variability in dopamine release at rest using [C]raclopride positron emission tomography (PET), functional connectivity between amygdala and rACC using resting-state functional magnetic resonance imaging (fMRI), and trait anxiety measures in healthy adult male and female humans. To measure endogenous dopamine release, we collected two [C]raclopride PET scans per participant. We contrasted baseline [C]raclopride D2/3 receptor binding and D2/3 receptor binding following oral methylphenidate administration. Methylphenidate blocks the dopamine transporter, which increases extracellular dopamine and leads to reduced [C]raclopride D2/3 receptor binding via competitive displacement. We found that individuals with higher dopamine release in the amygdala and rACC self-reported lower trait anxiety. Lower trait anxiety was also associated with reduced rACC-amygdala functional connectivity at baseline. Further, functional connectivity showed a modest negative relationship with dopamine release such that reduced rACC-amygdala functional connectivity was accompanied by higher levels of dopamine release in these regions. Together, these findings contribute to hypodopaminergic models of anxiety and support the utility of combining fMRI and PET measures of neurochemical function to advance our understanding of basic affective processes in humans.It is common wisdom that individuals vary in their baseline levels of anxiety. We all have a friend or colleague we know to be more "tightly wound" than others, or, perhaps, we are the ones marveling at others' ability to "just go with the flow." While such observations about individual differences within non-clinical populations are commonplace, the neural mechanisms underlying normal variation in trait anxiety have not been established. Using multimodal brain imaging in humans, this study takes initial steps in linking intrinsic measures of neuromodulator release and functional connectivity within regions implicated in anxiety disorders. Our findings suggest that in healthy adults, higher levels of trait anxiety may arise, at least in part, from reduced dopamine neurotransmission.

Gallen, CL, D'Esposito M.  2019.  Brain Modularity: A Biomarker of Intervention-related Plasticity., 2019 Feb 27. Trends in cognitive sciences. Abstract

Interventions using methods such as cognitive training and aerobic exercise have shown potential to enhance cognitive abilities. However, there is often pronounced individual variability in the magnitude of these gains. Here, we propose that brain network modularity, a measure of brain subnetwork segregation, is a unifying biomarker of intervention-related plasticity. We present work from multiple independent studies demonstrating that individual differences in baseline brain modularity predict gains in cognitive control functions across several populations and interventions, spanning healthy adults to patients with clinical deficits and cognitive training to aerobic exercise. We believe that this predictive framework provides a foundation for developing targeted, personalized interventions to improve cognition.

Sreenivasan, KK, D'Esposito M.  2019.  The what, where and how of delay activity., 2019 May 13. Nature reviews. Neuroscience. Abstract

Working memory is characterized by neural activity that persists during the retention interval of delay tasks. Despite the ubiquity of this delay activity across tasks, species and experimental techniques, our understanding of this phenomenon remains incomplete. Although initially there was a narrow focus on sustained activation in a small number of brain regions, methodological and analytical advances have allowed researchers to uncover previously unobserved forms of delay activity various parts of the brain. In light of these new findings, this Review reconsiders what delay activity is, where in the brain it is found, what roles it serves and how it may be generated.