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Catecholamine-Driven Low-Dimensional Brain Dynamics and Cognitive Task Performance

Presented During:

Neuroscience Frontiers: Exploring Cognitive Dynamics and Brain Connectivity  
Monday, June 24, 2024: 5:45 PM - 7:00 PM
COEX  
Room: Hall D 2  

Poster No:

936 

Submission Type:

Abstract Submission 

Authors:

Gabriel Wainstein1, Christopher Whyte1, Eli Müller1, Daniella Furmann2, Mark D'esposito2, Sharon Naismith1, Mac Shine3

Institutions:

1University of Sydney, Sydney, NSW, 2University of California, Berkeley, CA, 3University of Sydney, Sydney, NA

First Author:

Gabriel Wainstein  
University of Sydney
Sydney, NSW

Co-Author(s):

Christopher Whyte  
University of Sydney
Sydney, NSW
Eli Müller  
University of Sydney
Sydney, NSW
Daniella Furmann  
University of California
Berkeley, CA
Mark D'esposito  
University of California
Berkeley, CA
Sharon Naismith  
University of Sydney
Sydney, NSW
Mac Shine  
University of Sydney
Sydney, NA

Introduction:

Cognitive flexibility underlies our ability to adapt to new and unexpected conditions in our environment. Genetic variations, such as the COMT Val158Met polymorphism, are known to influence this executive function. This study investigates the effects of the COMT genotype and the administration of tolcapone, a COMT inhibitor, on cognitive flexibility, utilizing fMRI and novel large-scale dynamic system analysis to explore underlying neural mechanisms (shine et al,. 2016; Munn et all., 2021).
Supporting Image: Figure1_final.png
 

Methods:

Eighty participants were genotyped for the COMT Val158Met polymorphism and randomly assigned to receive either tolcapone or a placebo in a double-blind trial. Participants engaged in a cognitive task requiring rule switching, designed to probe cognitive flexibility. We conducted functional connectivity analysis to define large-scale network modules and network integration, principal component regression to identify networks involved in task execution, and energy landscape representations to visualize state transitions during task performance.

Results:

Functional connectivity analysis revealed significant modularity influenced by COMT genotype and drug interaction, with tolcapone markedly affecting Val allele carriers (Figure 2 A-C). Principal component regression highlighted distinct involvement of control and default mode networks (PC2) and the engagement of dorsal attention networks (PC3) in task execution (Figure 2D). Energy landscapes showed that higher network integration, as induced by tolcapone in Val carriers, corresponded to reduced switch costs, indicative of more efficient cognitive state transitions (Figure 2E).
Supporting Image: Figure2_end.png
 

Conclusions:

Our findings suggest that the COMT Val158Met polymorphism and pharmacological intervention with tolcapone synergistically modulate cognitive flexibility. The enhanced network integration and reduced switch costs in Val carriers treated with tolcapone point to a genotype-specific enhancement of cognitive flexibility. These insights and framework advance our understanding of the neurogenetic basis of executive functions and have potential implications for personalized interventions in disorders characterized by impaired cognitive flexibility.

Higher Cognitive Functions:

Executive Function, Cognitive Control and Decision Making 1

Modeling and Analysis Methods:

Activation (eg. BOLD task-fMRI)

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Subcortical Structures
Transmitter Systems

Physiology, Metabolism and Neurotransmission :

Pharmacology and Neurotransmission 2

Keywords:

Cognition
Data analysis
Dopamine
FUNCTIONAL MRI
Neurotransmitter
Noradrenaline
Norpinephrine

1|2Indicates the priority used for review

Provide references using author date format

Munn, B. R., Müller, E. J., Wainstein, G., & Shine, J. M. (2021). The ascending arousal system shapes neural dynamics to mediate awareness of cognitive states. Nature communications, 12(1), 6016.

Shine, J. M., Bissett, P. G., Bell, P. T., Koyejo, O., Balsters, J. H., Gorgolewski, K. J., ... & Poldrack, R. A. (2016). The dynamics of functional brain networks: integrated network states during cognitive task performance. Neuron, 92(2), 544-554.