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

Recent Publications

Nee, DE, D'Esposito M.  2016.  The hierarchical organization of the lateral prefrontal cortex., 2016. eLife. 5 Abstract

Higher-level cognition depends on the lateral prefrontal cortex (LPFC), but its functional organization has remained elusive. An influential proposal is that the LPFC is organized hierarchically whereby progressively rostral areas of the LPFC process/represent increasingly abstract information facilitating efficient and flexible cognition. However, support for this theory has been limited. Here, human fMRI data revealed rostral/caudal gradients of abstraction in the LPFC. Dynamic causal modeling revealed asymmetrical LPFC interactions indicative of hierarchical processing. Contrary to dominant assumptions, the relative strength of efferent versus afferent connections positioned mid LPFC as the apex of the hierarchy. Furthermore, cognitive demands induced connectivity modulations towards mid LPFC consistent with a role in integrating information for control operations. Moreover, the strengths of these dynamics were related to trait-measured higher-level cognitive ability. Collectively, these results suggest that the LPFC is hierarchically organized with the mid LPFC positioned to synthesize abstract and concrete information to control behavior.

Rahnev, D, Nee DE, Riddle J, Larson AS, D'Esposito M.  2016.  Causal evidence for frontal cortex organization for perceptual decision making., 2016 May 9. Proceedings of the National Academy of Sciences of the United States of America. Abstract

Although recent research has shown that the frontal cortex has a critical role in perceptual decision making, an overarching theory of frontal functional organization for perception has yet to emerge. Perceptual decision making is temporally organized such that it requires the processes of selection, criterion setting, and evaluation. We hypothesized that exploring this temporal structure would reveal a large-scale frontal organization for perception. A causal intervention with transcranial magnetic stimulation revealed clear specialization along the rostrocaudal axis such that the control of successive stages of perceptual decision making was selectively affected by perturbation of successively rostral areas. Simulations with a dynamic model of decision making suggested distinct computational contributions of each region. Finally, the emergent frontal gradient was further corroborated by functional MRI. These causal results provide an organizational principle for the role of frontal cortex in the control of perceptual decision making and suggest specific mechanistic contributions for its different subregions.

Wallace, DL, Aarts E, d'Oleire Uquillas F, Dang LC, Greer SM, Jagust WJ, D'Esposito M.  2015.  Genotype status of the dopamine-related catechol-O-methyltransferase (COMT) gene corresponds with desirability of "unhealthy" foods., 2015 May 8. Appetite. Abstract

The role of dopamine is extensively documented in weight regulation and food intake in both animal models and humans. Yet the role of dopamine has not been well studied in individual differences for food desirability. Genotype status of the dopamine-related catechol-O-methyltransferase (COMT) gene has been shown to influence dopamine levels, with greater COMT enzymatic activity in val/val individuals corresponding to greater degradation of dopamine. Decreased dopamine has been associated with poorer cognitive control and diminished goal-directed behavior in various behavioral paradigms. Additionally, dopaminergic-rich regions such as the frontal cortex and dorsal striatum have been shown to be important for supporting food-related decision-making. However, the role of dopamine, as assessed by COMT genotype status, in food desirability has not been fully explored. Therefore, we utilized an individual's COMT genotype status (n=61) and investigated food desirability based on self-rated "healthy" and "unhealthy" food perceptions. Here we found val/val individuals (n=19) have greater desirability for self-rated "unhealthy" food items, but not self-rated "healthy" food items, as compared to val/met (n=24) and met/met (n=18) individuals (p<0.005). Utilizing an objective health measure for the food items, we also found val/val and val/met individuals have greater desirability for objectively defined "unhealthy" food items, as compared to met/met individuals (p<0.01). This work further substantiates a role of dopamine in food-related behaviors and more specifically in relationship to food desirability for "unhealthy" food items.

Sadaghiani, S, Poline J-B, Kleinschmidt A, D'Esposito M.  2015.  Ongoing dynamics in large-scale functional connectivity predict perception., 2015 Jun 23. Proceedings of the National Academy of Sciences of the United States of America. Abstract

Most brain activity occurs in an ongoing manner not directly locked to external events or stimuli. Regional ongoing activity fluctuates in unison with some brain regions but not others, and the degree of long-range coupling is called functional connectivity, often measured with correlation. Strength and spatial distributions of functional connectivity dynamically change in an ongoing manner over seconds to minutes, even when the external environment is held constant. Direct evidence for any behavioral relevance of these continuous large-scale dynamics has been limited. Here, we investigated whether ongoing changes in baseline functional connectivity correlate with perception. In a continuous auditory detection task, participants perceived the target sound in roughly one-half of the trials. Very long (22-40 s) interstimulus intervals permitted investigation of baseline connectivity unaffected by preceding evoked responses. Using multivariate classification, we observed that functional connectivity before the target predicted whether it was heard or missed. Using graph theoretical measures, we characterized the difference in functional connectivity between states that lead to hits vs. misses. Before misses compared with hits and task-free rest, connectivity showed reduced modularity, a measure of integrity of modular network structure. This effect was strongest in the default mode and visual networks and caused by both reduced within-network connectivity and enhanced across-network connections before misses. The relation of behavior to prestimulus connectivity was dissociable from that of prestimulus activity amplitudes. In conclusion, moment to moment dynamic changes in baseline functional connectivity may shape subsequent behavioral performance. A highly modular network structure seems beneficial to perceptual efficiency.

Daffner, KR, Gale SA, Barrett AM, Boeve BF, Chatterjee A, Coslett BH, D'Esposito M, Finney GR, Gitelman DR, Hart JJ, Lerner AJ, Meador KJ, Pietras AC, Voeller KS, Kaufer DI.  2015.  Improving clinical cognitive testing: Report of the AAN Behavioral Neurology Section Workgroup., 2015 Jul 10. Neurology. Abstract

To evaluate the evidence basis of single-domain cognitive tests frequently used by behavioral neurologists in an effort to improve the quality of clinical cognitive assessment.