Neuropsychological, neuroimaging and electrophysiological research supports a crucial role of lateral prefrontal cortex (PFC) in executive control of human behavior. Altered PFC function underlies a host of debilitating developmental, neurological and psychiatric disorders. Despite significant progress in PFC research, the real-time processes supporting PFC control of human cognition remain undetermined. We propose that PFC uses oscillatory dynamics to implement cognitive control of task-dependent neural networks. To address this hypothesis we will use a unique combination of direct cortical recording in neurosurgical patients (Electrocorticography; ECoG) with superb spatio-temporal resolution and signal-to-noise ratio, along with cutting-edge analysis to define PFC-dependent neural networks supporting cognition. We will examine three tasks probing hallmarks of frontal lobe function (categorical perception, working memory and controlled vs. automatic attention) across three sensory modalities (audition, vision, touch) to address the generalizabilty of PFC dependent oscillatory network control. We will then examine the causality of the oscillatory dynamics observed with ECoG using scalp EEG and behavioral methods in patients with focal lesions centered in lateral PFC.
Aim 1 will use ECoG recording to define the role of PFC control of phase locking of low frequency neural oscillations between task dependent networks and whether cross frequency coupling (CFC) between high gamma oscillations (60-200 Hz) and low frequency oscillations tracks task performance.
Aim 2 is the most exploratory and draws from a recent finding in our laboratory demonstrating that an exquisite cortical microstructure observed at 4 mm cortical resolution supports categorical perception of phonemes in the temporal lobe. Using ECoG we propose to examine whether such a sub-centimeter microstructure extends to the PFC during cognitive control.
Aim 3 wil examine the causality of each oscillatory process in patients with either focal lateral PFC or posterior parietal cortex (PPC) damage. We predict that deficits in neural oscillations in the lesioned hemisphere wil correlate with behavioral deficits and reveal novel patterns of neuroplasticity in the non-lesioned hemisphere. In summary, the proposed work will define the role of PFC in both distributed and local network function in the support of human behavior.

Public Health Relevance

The research is relevant to public health because it aims to better delineate the mechanisms of PFC control of human behavior. It is well established that a host of disabling neurological, developmental and psychiatric conditions are linked to prefrontal dysfunction. This proposal aims to provide basic information on the role of prefrontal cortex in behavior. This work is essential to the NIH mission since it will provide novel insights into the neurophysiology of prefrontal control of cognition relevant to the understanding, diagnosis and potential treatment of many devastating clinical disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
High Priority, Short Term Project Award (R56)
Project #
2R56NS021135-26
Application #
8550163
Study Section
Special Emphasis Panel (SPC)
Program Officer
Babcock, Debra J
Project Start
1985-09-09
Project End
2013-08-31
Budget Start
2012-09-30
Budget End
2013-08-31
Support Year
26
Fiscal Year
2012
Total Cost
$462,294
Indirect Cost
$158,880
Name
University of California Berkeley
Department
Neurosciences
Type
Organized Research Units
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
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