The ability to selectively facilitate or suppress the processing of information is essential for higher-order cognitive tasks such as working memory. Previous work has identified the prefrontal cortex (PFC) as the region modulating this processing. We propose that the PFC utilizes oscillatory mechanisms to communicate with and control network activity in lower-order cortical areas during cognition. The proposed work seeks to investigate the oscillatory interactions which allow the PFC to modulate cortical excitability i sensory areas during working memory. Knowledge of the neural mechanisms of PFC engagement in this process has both theoretical as well as translational implications and may lead to development of targeted rehabilitation methods to treat and monitor the progress of recovery for patients suffering from brain injury. This work will be carried out with two specific aims.
In Aim 1, we will utilize electrocorticography (ECoG) to investigate the role of oscillatory coupling in the prefrontal control of sensory cortex excitability. ECoG signals, which are obtained directly from the cortex of patients undergoing treatment for refractory epilepsy, will be recorded while subjects perform a multimodal working memory task requiring selective attention to stimuli in different sensory modalities. The ECoG method has many benefits compared with noninvasive recording methods including exceptionally high spatial and temporal resolutions as well as an enhanced signal to noise ratio. We hypothesize that the PFC uses oscillatory mechanisms to control and enhance network activity between PFC and lower-order cortical areas in order to facilitate the processing of relevant information, and this hypothesis will be tested by computing connectivity measures such as phase coherence, spectral Granger causality, and cross frequency coupling between electrodes during different task periods. Furthermore, we predict that greater levels of connectivity between PFC and sensory areas will be associated with better task performance, as well as with an increased modulation of alpha (~10Hz) oscillations, a putative index of cortical excitability, over sensory areas.
In Aim 2, we wll build on our findings from the previous aim and assess the causal role and reorganization of prefrontal cortex in modulating sensory processing utilizing electroencephalographic (EEG) recordings from patients with focal frontal lobe damage due to stroke as well as age-matched controls. EEG will be recorded while subjects perform a task similar to that used in Aim 1. We hypothesize that, concurrent with decreased task performance when attending to stimuli contralateral to damaged PFC, patients will show a decreased amount of alpha modulation over sensory areas ipsilateral to damaged PFC. We further predict that intact frontal cortex will compensate for lesioned cortex and that this compensation will be manifested through a greater level of connectivity between the intact frontal hemisphere and posterior sensory areas in patients compared with age-matched controls.

Public Health Relevance

This proposal will help to reveal the mechanisms utilized by the prefrontal cortex to communicate with and control other brain areas during working memory. A greater knowledge of these mechanisms is necessary to understand normal and disordered cognition in neurological and psychiatric patients. Further, insights into the physiological mechanisms of prefrontal control are critical to development of targeted rehabilitation methods to treat and monitor the progress of recovery for patients suffering from prefrontal cortex damage.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32NS082065-01A1
Application #
8596522
Study Section
Special Emphasis Panel (ZRG1-F02B-D (20))
Program Officer
Babcock, Debra J
Project Start
2013-07-01
Project End
2016-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$52,190
Indirect Cost
Name
University of California Berkeley
Department
Type
Other Domestic Higher Education
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Piai, Vitória; Anderson, Kristopher L; Lin, Jack J et al. (2016) Direct brain recordings reveal hippocampal rhythm underpinnings of language processing. Proc Natl Acad Sci U S A 113:11366-11371