Higher order cognition (e.g., remembering past events, carrying on a conversation, reasoning and problem solving) depends critically on two broad classes of memory function, working memory (WM) and long-term memory (LTM). LTM refers to the cumulative record of our past experiences and WM refers to the information from perception and LTM that is currently active, along with the set of reflective processes that maintain and manipulate this information. WM allows us to keep something in mind after the initiating stimulus disappears, make connections and comparisons between events, have control over what we think about, formulate intentions, and make plans. Thus, WM is cognitive system that comprises both mnemonic processes (i.e. storage and rehearsal) as well as non-mnemonic processes (i.e. executive control processes). Furthermore, WM processes have a large impact on LTM, being essential for the """"""""encoding"""""""" and storage of LTM memories, as well as other cognitive systems such as language and perception. Thus, a modern conceptualization of WM emphasizes a system that allows for the active maintenance of relevant information necessary for goal-directed behavior. Neuronal recordings in monkeys, and physiological and lesion studies in humans have shown that prefrontal cortex (PFC) is critical for WM, and current theories have postulated that it is type of representations maintained in PFC that provides the basis for cognitive control. In this proposal, we seek to further characterize PFC representations, as well as investigate the interaction between the PFC and posterior regions during the active maintenance of relevant information. Cognitive theories have long been influenced by neuropsychological patient studies, while recent developments have been greatly influenced by breakthroughs in other technology such as functional MRI (fMRI), event-related potential (ERP) recording and transcranial stimulation (TMS). The current proposal will utilize fMRI, ERP and TMS to precisely characterize, both cognitively and neurally, the role of PFC in cognitive control. Basic knowledge about the functional organization of PFC gained from this work is of central clinical significance, and can provide substantial insights into the nature of a large number of disorders associated with the frontal lobes such as traumatic brain injury, schizophrenia, and attention-deficit hyperactivity disorder (ADHD), as well as a structural and degenerative brain diseases including Parkinson's and Alzheimer's disease. ? ? ?

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
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Cognitive Neuroscience Study Section (COG)
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Glanzman, Dennis L
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University of California Berkeley
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Lorenc, Elizabeth S; Sreenivasan, Kartik K; Nee, Derek E et al. (2018) Flexible Coding of Visual Working Memory Representations during Distraction. J Neurosci 38:5267-5276
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Nee, Derek Evan; D'Esposito, Mark (2016) The hierarchical organization of the lateral prefrontal cortex. Elife 5:
Bahlmann, Jörg; Aarts, Esther; D'Esposito, Mark (2015) Influence of motivation on control hierarchy in the human frontal cortex. J Neurosci 35:3207-17
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Sadaghiani, Sepideh; D'Esposito, Mark (2015) Functional Characterization of the Cingulo-Opercular Network in the Maintenance of Tonic Alertness. Cereb Cortex 25:2763-73
Sadaghiani, Sepideh; Poline, Jean-Baptiste; Kleinschmidt, Andreas et al. (2015) Ongoing dynamics in large-scale functional connectivity predict perception. Proc Natl Acad Sci U S A 112:8463-8

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