Cognitive control and executive function are similar terms used to describe our ability to direct thought and action based on our goals and intentions, rather than being driven automatically by the world around us. Current theories of cognitive control propose that the prefrontal cortex (PFC) is a brain region that is critical for tis ability. The PFC has extensive, reciprocal projections to both cortical and subcortical regions and therefore is in a privileged position to be a source of top-down signals that could sculpt behavior. Building on the progress we have made in the previous funding period, the overall aim of the current proposal is to further advance and refine our understanding of the functional organization of PFC and the neural mechanisms by which the PFC can provide top-down signals that modulate incoming sensory information. We propose that the PFC stores the highest level of representations such as rules and goals, and it is the active maintenance of these representations that bias information processing elsewhere in the brain influencing how we ultimately make decisions and act. In humans, frontal lobe function has been extensively researched both through the careful study of neurological patients with focal lesions (usually due to stroke and traumatic brain injury) and using functional MRI (fMRI) with healthy young subjects. However, there has been surprisingly little work combining these two approaches. Lesion and fMRI methodologies can complement each other in significant ways, and so when combined can be a powerful approach for studying brain-behavior relationships. In this proposal, such a convergent approach will be implemented. Basic knowledge about PFC function and cognitive control can provide substantial insights into the nature of a large number of psychiatric and neurological disorders affecting PFC function such as schizophrenia, dementia, stroke and traumatic brain injury;as well as many other conditions such as attention-deficit disorder, substance addiction and normal aging, that are proposed to involve selective dysfunction of frontal brain systems. Moreover, cognitive and behavioral deficits from PFC damage are particularly challenging to treat. A greater understanding of frontal lobe function is necessary for developing effective therapeutic interventions.

Public Health Relevance

The proposed research is relevant to public health because it will advance our understanding of the role of the frontal lobes in goal-directed behavior. Many psychiatric and neurological disorders such as schizophrenia dementia, stroke and traumatic brain injury affect frontal lobe function;and many other conditions such as attention-deficit disorder, substance addiction and normal aging, are proposed to involve selective dysfunction of frontal brain systems. The proposed research is also relevant to NIH's mission because it will lead to basic knowledge about frontal lobe function that can provide valuable insights into the understanding, diagnosis and treatment of a wide range of clinical conditions.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Cognition and Perception Study Section (CP)
Program Officer
Rossi, Andrew
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Berkeley
Organized Research Units
United States
Zip Code
Gratton, Caterina; Lee, Taraz G; Nomura, Emi M et al. (2014) Perfusion MRI indexes variability in the functional brain effects of theta-burst transcranial magnetic stimulation. PLoS One 9:e101430
Cohen, Jessica R; Sreenivasan, Kartik K; D'Esposito, Mark (2014) Correspondence between stimulus encoding- and maintenance-related neural processes underlies successful working memory. Cereb Cortex 24:593-9
Sreenivasan, Kartik K; Vytlacil, Jason; D'Esposito, Mark (2014) Distributed and dynamic storage of working memory stimulus information in extrastriate cortex. J Cogn Neurosci 26:1141-53
Sreenivasan, Kartik K; Gratton, Caterina; Vytlacil, Jason et al. (2014) Evidence for working memory storage operations in perceptual cortex. Cogn Affect Behav Neurosci 14:117-28
Sreenivasan, Kartik K; Curtis, Clayton E; D'Esposito, Mark (2014) Revisiting the role of persistent neural activity during working memory. Trends Cogn Sci 18:82-9
Blumenfeld, Robert S; Bliss, Daniel P; Perez, Fernando et al. (2014) CoCoTools: open-source software for building connectomes using the CoCoMac anatomical database. J Cogn Neurosci 26:722-45
Blumenfeld, Robert S; Lee, Taraz G; D'Esposito, Mark (2014) The effects of lateral prefrontal transcranial magnetic stimulation on item memory encoding. Neuropsychologia 53:197-202
Vytlacil, Jason; Kayser, Andrew; Miyakawa, Asako et al. (2014) An approach for identifying brainstem dopaminergic pathways using resting state functional MRI. PLoS One 9:e87109
Kayser, Andrew S; D'Esposito, Mark (2013) Abstract rule learning: the differential effects of lesions in frontal cortex. Cereb Cortex 23:230-40
Chiong, Winston; Wilson, Stephen M; D'Esposito, Mark et al. (2013) The salience network causally influences default mode network activity during moral reasoning. Brain 136:1929-41

Showing the most recent 10 out of 68 publications