The broad goal of Project 1 is to advance understanding of the organization of lateral frontal cortex,both in terms of the regional distinctions that define its functional topography and the principles bywhich these regions interact to produce controlled behavior. The first set of experiments wasdesigned to test the hypothesis that frontal cortex is hierarchically organized, with progressively moreanterior regions processing higher-order representations. According to this hierarchical hypothesis,successive stages of processing lead to increased abstraction and complexity of representation alonga posterior-anterior gradient across frontal cortex. This hypothesis will be tested with two paradigmsand a variety of approaches: behavioral data from patients with focal PFC lesions, temporary lesionswith transcranial magnetic stimulation, intracortical recordings in humans prior to epilepsy surgery,and fMRI studies in adults and children. The second set of experiments focuses on the most anteriorpart of lateral frontal cortex, a region implicated in higher cognition about which relatively little isknown. Based on preliminary data, we have argued that this region is involved in the jointconsideration of multiple relationships between mental representations - a general function that canbe used to compare, evaluate, or integrate across concepts, or to coordinate several ongoing mentalprocesses. A variety of complementary techniques will be used to test whether anterior lateral frontalcortex is sensitive to the need to consider multiple relations between items. Basic knowledge aboutthe functional organization of frontal cortex gained from these proposed studies is of central clinicalsignificance, and can provide substantial insights into the nature of a large number of neurologicaldisorders associated with the frontal lobe dysfunction, such as stroke, traumatic brain injury, anddegenerative brain diseases including Parkinson's, Alzheimer's Disease, and frontotemporaldementia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
2P01NS040813-06
Application #
7475462
Study Section
Special Emphasis Panel (ZNS1-SRB-R (29))
Project Start
Project End
Budget Start
2008-03-15
Budget End
2009-02-28
Support Year
6
Fiscal Year
2008
Total Cost
$186,925
Indirect Cost
Name
University of California Berkeley
Department
Type
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Nee, Derek Evan; D'Esposito, Mark (2017) Causal evidence for lateral prefrontal cortex dynamics supporting cognitive control. Elife 6:
Baldo, Juliana V; Kacinik, Natalie A; Moncrief, Amber et al. (2016) You may now kiss the bride: Interpretation of social situations by individuals with right or left hemisphere injury. Neuropsychologia 80:133-141
Nee, Derek Evan; D'Esposito, Mark (2016) The hierarchical organization of the lateral prefrontal cortex. Elife 5:
Cohen, Jessica R; D'Esposito, Mark (2016) The Segregation and Integration of Distinct Brain Networks and Their Relationship to Cognition. J Neurosci 36:12083-12094
Fegen, David; Buchsbaum, Bradley R; D'Esposito, Mark (2015) The effect of rehearsal rate and memory load on verbal working memory. Neuroimage 105:120-31
Mackey, Allyson P; Miller Singley, Alison T; Wendelken, Carter et al. (2015) Characterizing Behavioral and Brain Changes Associated with Practicing Reasoning Skills. PLoS One 10:e0137627
Bahlmann, Jörg; Blumenfeld, Robert S; D'Esposito, Mark (2015) The Rostro-Caudal Axis of Frontal Cortex Is Sensitive to the Domain of Stimulus Information. Cereb Cortex 25:1815-26
Baldo, Juliana V; Paulraj, Selvi R; Curran, Brian C et al. (2015) Impaired reasoning and problem-solving in individuals with language impairment due to aphasia or language delay. Front Psychol 6:1523
Voytek, Bradley; Kayser, Andrew S; Badre, David et al. (2015) Oscillatory dynamics coordinating human frontal networks in support of goal maintenance. Nat Neurosci 18:1318-24
Murray, John D; Bernacchia, Alberto; Freedman, David J et al. (2014) A hierarchy of intrinsic timescales across primate cortex. Nat Neurosci 17:1661-3

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