Development Of Cognitive Activation Tasks For Functional Neuroimaging

National Institute Of Mental Health

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Abstract

Last year we examined two components of working memory (WM): maintenance of information for a short period of time and manipulation of information necessary for higher cognitive functions, such as language, reasoning and problem solving. Earlier WM studies demonstrated that dorsolateral prefrontal cortex (DLPFC) activity increases as maintenance and load demand increases. This suggested a role of DLPFC in the active maintenance of information. Few studies have carefully disambiguated these two WM processes at the behavioral and physiological levels. Using functional magnetic resonance imaging (fMRI) and a block design of the Sternberg task, we mapped within the prefrontal cortex (PFC) locales that are selectively load sensitive, delay sensitive, or both. In considering the Sternberg task, WM load was manipulated by varying the memory set size (3, 5, or 8 letters) and the delay period between the string of letters and probe. The effect of memory maintenance was examined by employing two time delays between the letter set and probe stimuli. We found the DLPFC was strongly activated in load manipulation, whereas activation as a function of delay was restricted to the left premotor regions and Broca areas. Regions of PFC on the right were found to be exclusively affected by load. These results suggest the possibility that top-down modulation of attention or cognitive control at encoding and/or decision making may be mediated by these areas. [unreadable] [unreadable] Little is known about the distributed neuronal networks impacted by dopamine modulation in the component process of WM, although working memory is critically mediated by dopaminergic tuning of signal-to-noise in cortical neural assemblies. Here we used the COMT val158met genotype as an index of relative cortical dopamine bioavailability and tuning efficiency. In this new study, we examined the spatial and subprocess specificity by which dopamine modulation occurs within the prefrontal-parietal-striatal network during WM, thus empirically showing that dopamine plays a key role in updating and stabilizing new information at the neural systems level. To do this we employed a cognitive paradigm which allowed separation of the encoding from the response phases in subsequent image analyses. By doing this, we allowed for the isolation of cognitive processes of interest using planned contrasts of activations at the response phases. This paradigm incorporated various aspects of WM and cognitive control, along with a set of control tasks. Each set of WM or control tasks had in common a response phase, which required a sensorimotor response, numerical size determination, or a more complex task that included numerical computation as well as numerical size judgment. We found that temporal updating operations, engaged relatively specific dopaminergic tuning at the DLPFC. Manipulating and rapidly updating representations were sensitive to dopaminergic modulation of neural signaling in a larger prefrontal-parietal-striatal network. These findings add to the integration of dopaminergic signaling in basic cortical assemblies with their roles in specific human brain networks during the orchestration of information processing in WM.