Cognitive control and executive function are similar terms used to describe our ability to direct thought and action based on our goals and intentions, rather than being driven automatically by the world around us. Given that working memory (WM) is a crucial component underlying cognitive control, increased knowledge about WM will be necessary to fully understand goal-directed behavior. Building on the progress we have made in the previous funding period, the overall aim of the current proposal is to further advance and refine our understanding of the neural mechanisms underlying working memory and cognitive control. In human subjects, two methods will be used ? functional MRI (fMRI) and transcranial magnetic stimulation (TMS), providing a convergent approach to test our hypotheses. Importantly, TMS allows for the establishment of the causality of the fMRI findings. We will also be implementing two new TMS approaches ? one that delivers stimulation simultaneously with fMRI, and the other that transmits TMS pulses to the brain at different oscillatory frequencies. Together, these novel methods will allow us to test hypotheses that could not be tested previously. We will specifically focus on identifying the neural mechanisms that underlie both WM storage and processing limits. We seek to understand these mechanisms at both the local level (e.g. how information is stored in posterior sensory cortex during WM) and the network (systems) level (e.g. how interactions between large-scale networks support WM processing). In particular, we seek to enter new territory by investigating the interactions between local and systems-level processing in the service of goal-directed behavior. Loss of cognitive control is marked by an over-dependence on external stimuli or strong associations to guide responses, causing a loss of adaptive, goal-directed behavior. Thus, basic knowledge about cognitive control can provide substantial insights into the nature of a large number of psychiatric and neurological disorders affecting these cognitive abilities such as schizophrenia, attention-deficit disorder, substance addiction, dementia, and traumatic brain injury. Furthermore, cognitive control deficits are challenging to treat, with few therapeutic interventions. Thus, s greater understanding of the neural mechanisms underlying cognitive control can lead to improved diagnosis and rehabilitation of many clinical disorders.

Public Health Relevance

The proposed research is relevant to public health because it will advance our understanding of the role of the frontal lobes in goal-directed behavior. Many psychiatric and neurological disorders such as schizophrenia dementia, stroke and traumatic brain injury affect frontal lobe function; and many other conditions such as attention-deficit disorder, substance addiction and normal aging, are proposed to involve selective dysfunction of frontal brain systems. The proposed research is also relevant to NIH's mission because it will lead to basic knowledge about frontal lobe function that can provide valuable insights into the understanding, diagnosis and treatment of a wide range of clinical conditions.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
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Cognition and Perception Study Section (CP)
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Rossi, Andrew
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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
Vogelsang, David A; D'Esposito, Mark (2018) Is There Evidence for a Rostral-Caudal Gradient in Fronto-Striatal Loops and What Role Does Dopamine Play? Front Neurosci 12:242
Nee, Derek Evan; D'Esposito, Mark (2017) Causal evidence for lateral prefrontal cortex dynamics supporting cognitive control. Elife 6:
Rahnev, Dobromir; Nee, Derek Evan; Riddle, Justin et al. (2016) Causal evidence for frontal cortex organization for perceptual decision making. Proc Natl Acad Sci U S A 113:6059-64
Nee, Derek Evan; D'Esposito, Mark (2016) The hierarchical organization of the lateral prefrontal cortex. Elife 5:
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
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
D'Esposito, Mark; Postle, Bradley R (2015) The cognitive neuroscience of working memory. Annu Rev Psychol 66:115-42
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
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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