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Principal Investigator: Robert Thomas Knight
Organization: UNIVERSITY OF CALIFORNIA BERKELEY
Fiscal Year: 2024
Award: $525,493
Funding agency: National Institute of Neurological Disorders and Stroke
Abstract
Prefrontal cortex (PFC) plays a pivotal role in distributed neural networks orchestrating human behavior.
Notably, PFC dysfunction is observed in numerous debilitating developmental, neurological and psychiatric
disorders. This emphasizes the need for improved knowledge of the physiology implementing goal-directed
behavior to better understand these devastating neuropsychological impairments. The last two decades have
seen an exponential increase of PFC research in animals and humans but numerous questions remain.
Intracranial EEG recording (iEEG) in humans provides a powerful method to assess the spatial-temporal
structure of network activity enabling imaging of both local and inter-areal dynamics. Local neural activation is
measured with high frequency activity (HFA; 70-200 Hz) and single-unit activity (SUA). Inter-areal interactions
are assessed using connectivity metrics including phase slope index, directional phase amplitude coupling,
Granger causality, mutual information and single-trial HFA latency onsets. We combine these local and
network approaches with iEEG recordings to address four core areas of PFC dependent function including
attention, working memory, learning and interpersonal communication. Aim 1 draws on our prior iEEG work
documenting lateral PFC-hippocampal theta band engagement in working memory (WM) and rhythmic PFC-
Parietal attentional sampling in the theta range. Here we test the hypothesis that shared and distinct theta
networks support WM and attention. Critically, we record from the same individual utilizing identical stimuli
differing only in task requirements. In a second study, we employ a naturalistic slot machine gambling task
positing that orbital PFC-insular- anterior cingulate interactions track wheel-spinning expectations
determining both satisfaction and the motivation to spin again. The slot machine expectation manipulation
we employ is banned in casinos given its powerful drive to continue gambling. Aim 2 assesses feedback-
based learning in two studies. One posits lateral PFC-hippocampal interactions in rule-based concept
learning, the other proposes a central role for orbital PFC-hippocampal interactions in flexibly responding to
changing outcome contingencies. Aim 3 proposes novel dual iEEG studies examining how interacting
humans exchange knowledge. One task requires transferring knowledge about items and a second
examines non-verbal social communication. Dual iEEG involves recording from two interacting patients and
preliminary data indicates synchrony between patients in PFC-hippocampal-anterior cingulate circuits during
knowledge exchange. Taken together, the proposed work will advance our understanding of how PFC
dependent networks support goal-directed human behavior.
Terms: <Address><Ammon Horn><Animals><Anterior><Area><Attention><Behavior><Behavioral><Brain><Brain Nervous System><Causality><Central Lobe><Clinical Treatment><Cognition><Communication><Cornu Ammonis><Coupling><Cyclicity><Data><Deceleration><Development><Diagnosis><Disabling><Disease><Disorder><Dysfunction><EEG><Electroencephalogram><Electroencephalography><Encephalon><Environment><Epilepsy><Epileptic Seizures><Epileptics><Etiology><Event><Expectancy><Feedback><Frequencies><Functional MRI><Functional Magnetic Resonance Imaging><Functional disorder><Gambling><Goals><Hippocampus><Human><Image><Immediate Memory><Impairment><Individual><Insula><Insula of Reil><Interpersonal Communication><Island of Reil><Knowledge><Lateral><Learning><Link><Literature><Location><Measures><Memory><Mental disorders><Mental health disorders><Methods><Mission><Modern Man><Motivation><NIH><National Institutes of Health><Nervous System Diseases><Nervous System Disorder><Neurologic><Neurologic Disorders><Neurological><Neurological Disorders><Neuropsychologies><Neuropsychology><Non-linear Dynamic><Non-linear Dynamics><Nonlinear Dynamic><Nonlinear Dynamics><Nonverbal Communication><Operative Procedures><Operative Surgical Procedures><Outcome><Outcome Measure><Parietal Lobe><Patients><Periodicity><Personal Communication><Persons><Phase><Physiology><Physiopathology><Play><Prefrontal Cortex><Psychiatric Disease><Psychiatric Disorder><Psychological reinforcement><Reinforcement><Reporting><Research><Reversal Learning><Rewards><Rhythmicity><Role><Sampling><Seizure Disorder><Sensory><Shapes><Short-Term Memory><Shortterm Memory><Site><Stimulus><Structure><Surgical><Surgical Interventions><Surgical Procedure><Testing><Texture><Transmission><Uncertainty><United States National Institutes of Health><Update><Work><causation><clinical research site><clinical site><cognitive burden><cognitive function><cognitive load><computer based prediction><developmental><developmental disease><developmental disorder><disease causation><doubt><epilepsia><epileptogenic><expectation><fMRI><flexibility><flexible><hippocampal><imaging><improved><indexing><insight><measurable outcome><mental illness><neural><neural network><neurological disease><neurophysiological><neurophysiology><neuropsychologic><non-speaking><non-verbal><non-verbal communication><non-vocal><novel><outcome measurement><paralinguistic behavior><parietal cortex><participant engagement><pathophysiology><patient engagement><predictive modeling><psychiatric illness><psychological disorder><satisfaction><social communication><social role><success><support network><surgery><transmission process><trial regimen><trial treatment><working memory>