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

Recent Publications

Iyer, KK, Hwang K, Hearne LJ, Muller E, D'Esposito M, Shine JM, Cocchi L.  2022.  Focal neural perturbations reshape low-dimensional trajectories of brain activity supporting cognitive performance., 2022 01 10. Nature communications. 13(1):4. Abstract

The emergence of distributed patterns of neural activity supporting brain functions and behavior can be understood by study of the brain's low-dimensional topology. Functional neuroimaging demonstrates that brain activity linked to adaptive behavior is constrained to low-dimensional manifolds. In human participants, we tested whether these low-dimensional constraints preserve working memory performance following local neuronal perturbations. We combined multi-session functional magnetic resonance imaging, non-invasive transcranial magnetic stimulation (TMS), and methods translated from the fields of complex systems and computational biology to assess the functional link between changes in local neural activity and the reshaping of task-related low dimensional trajectories of brain activity. We show that specific reconfigurations of low-dimensional trajectories of brain activity sustain effective working memory performance following TMS manipulation of local activity on, but not off, the space traversed by these trajectories. We highlight an association between the multi-scale changes in brain activity underpinning cognitive function.

Ciampa, CJ, Parent JH, Harrison TM, Fain RM, Betts MJ, Maass A, Winer JR, Baker SL, Janabi M, Furman DJ, D'Esposito M, Jagust WJ, Berry AS.  2022.  Associations among locus coeruleus catecholamines, tau pathology, and memory in aging., 2022 Jan 15. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. Abstract

The locus coeruleus (LC) is the brain's major source of the neuromodulator norepinephrine, and is also profoundly vulnerable to the development of Alzheimer's disease (AD)-related tau pathology. Norepinephrine plays a role in neuroprotective functions that may reduce AD progression, and also underlies optimal memory performance. Successful maintenance of LC neurochemical function represents a candidate mechanism of protection against the propagation of AD-related pathology and may facilitate the preservation of memory performance despite pathology. Using [F]Fluoro-m-tyrosine ([F]FMT) PET imaging to measure catecholamine synthesis capacity in LC regions of interest, we examined relationships among LC neurochemical function, AD-related pathology, and memory performance in cognitively normal older adults (n = 49). Participants underwent [C]Pittsburgh compound B and [F]Flortaucipir PET to quantify β-amyloid (n = 49) and tau burden (n = 42) respectively. In individuals with substantial β-amyloid, higher LC [F]FMT net tracer influx (Ki) was associated with lower temporal tau. Longitudinal tau-PET analyses in a subset of our sample (n = 30) support these findings to reveal reduced temporal tau accumulation in the context of higher LC [F]FMT Ki. Higher LC catecholamine synthesis capacity was positively correlated with self-reported cognitive engagement and physical activity across the lifespan, established predictors of successful aging measured with the Lifetime Experiences Questionnaire. LC catecholamine synthesis capacity moderated tau's negative effect on memory, such that higher LC catecholamine synthesis capacity was associated with better-than-expected memory performance given an individual's tau burden. These PET findings provide insight into the neurochemical mechanisms of AD vulnerability and cognitive resilience in the living human brain.

Toker, D, Pappas I, Lendner JD, Frohlich J, Mateos DM, Muthukumaraswamy S, Carhart-Harris R, Paff M, Vespa PM, Monti MM, Sommer FT, Knight RT, D'Esposito M.  2022.  Consciousness is supported by near-critical slow cortical electrodynamics., 2022 Feb 15. Proceedings of the National Academy of Sciences of the United States of America. 119(7) Abstract

Mounting evidence suggests that during conscious states, the electrodynamics of the cortex are poised near a critical point or phase transition and that this near-critical behavior supports the vast flow of information through cortical networks during conscious states. Here, we empirically identify a mathematically specific critical point near which waking cortical oscillatory dynamics operate, which is known as the edge-of-chaos critical point, or the boundary between stability and chaos. We do so by applying the recently developed modified 0-1 chaos test to electrocorticography (ECoG) and magnetoencephalography (MEG) recordings from the cortices of humans and macaques across normal waking, generalized seizure, anesthesia, and psychedelic states. Our evidence suggests that cortical information processing is disrupted during unconscious states because of a transition of low-frequency cortical electric oscillations away from this critical point; conversely, we show that psychedelics may increase the information richness of cortical activity by tuning low-frequency cortical oscillations closer to this critical point. Finally, we analyze clinical electroencephalography (EEG) recordings from patients with disorders of consciousness (DOC) and show that assessing the proximity of slow cortical oscillatory electrodynamics to the edge-of-chaos critical point may be useful as an index of consciousness in the clinical setting.

Farahani, FV, Karwowski W, D'Esposito M, Betzel RF, Douglas PK, Sobczak AM, Bohaterewicz B, Marek T, Fafrowicz M.  2022.  Diurnal variations of resting-state fMRI data: A graph-based analysis., 2022 Apr 24. NeuroImage. :119246. Abstract

Circadian rhythms (lasting approximately 24 hours) control and entrain various physiological processes, ranging from neural activity and hormone secretion to sleep cycles and eating habits. Several studies have shown that time of day (TOD) is associated with human cognition and brain functions. In this study, utilizing a chronotype-based paradigm, we applied a graph theory approach on resting-state functional MRI (rs-fMRI) data to compare whole-brain functional network topology between morning and evening sessions and between morning-type (MT) and evening-type (ET) participants. Sixty-two individuals (31 MT and 31 ET) underwent two fMRI sessions, approximately 1 hour (morning) and 10 hours (evening) after their wake-up time, according to their declared habitual sleep-wake pattern on a regular working day. In the global analysis, the findings revealed the effect of TOD on functional connectivity (FC) patterns, including increased small-worldness, assortativity, and synchronization across the day. However, we identified no significant differences based on chronotype categories. The study of the modular structure of the brain at mesoscale showed that functional networks tended to be more integrated with one another in the evening session than in the morning session. Local/regional changes were affected by both factors (i.e., TOD and chronotype), mostly in areas associated with somatomotor, attention, frontoparietal, and default networks. Furthermore, connectivity and hub analyses revealed that the somatomotor, ventral attention, and visual networks covered the most highly connected areas in the morning and evening sessions: the latter two were more active in the morning sessions, and the first was identified as being more active in the evening. Finally, we performed a correlation analysis to determine whether global and nodal measures were associated with subjective assessments across participants. Collectively, these findings contribute to an increased understanding of diurnal fluctuations in resting brain activity and highlight the role of TOD in future studies on brain function and the design of fMRI experiments.

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.