Neural mechanisms underlying the relationship between inhibitory control and noradrenergic system
Poster No:
726
Submission Type:
Abstract Submission
Authors:
Marcela Díaz Díaz1, Maria Paz Martinez-Molina2, Patricia Soto-Icaza2, Alejandra Figueroa-Vargas1, Mariana Ayala-Ochoa2, Victor Marquez2, Paulo Figueroa-Taiba2, Tomás Ossandón1, Pablo Billeke2
Institutions:
1Pontificia Universidad Católica de Chile, Santiago, Chile, 2Universidad del Desarrollo, Santiago, Chile
First Author:
Co-Author(s):
Introduction:
In daily life, successful goal-directed behavior depends on our ability to inhibit impulses or distractions (Diamond, 2013). When facing conflictive situations where automatic responses must be suppressed, conflict expectation emerges (Aron, 2010), increasing cognitive control demands.
The Go-NoGo paradigm is widely employed to study inhibitory control. Increasing the number of consecutive Go stimuli before a NoGo stimulus enhances conflict expectation, leading to longer reaction times (Zamorano et al., 2014). Fronto-medial theta oscillations, especially in the superior frontal gyrus (SFG), have been linked to conflict anticipation and its effects on performance (Dippel et al., 2017). Martinez-Molina et al. (2024) further showed that theta-band rhythmic stimulation intensifies these effects, increasing RTs and improving NoGo accuracy. Additionally, the locus coeruleus-noradrenergic (LC-NE) system supports cognitive control and attention. Its activity, measured indirectly via pupil diameter, increase with cognitive demands (Pfeffer et al., 2022), and its integrity correlates with better inhibitory performance (Tomassini et al., 2022). Prior evidence indicates that as NoGo stimuli become less frequent-thus increasing conflict-theta power and pupil diameter both rise (Dippel, 2017). In this study, we aim to clarify the neural mechanisms that link conflict expectation, inhibitory control, and the LC-NE system by examining how changes in pupil dynamics relate to fronto-medial theta oscillations.
The Go-NoGo paradigm is widely employed to study inhibitory control. Increasing the number of consecutive Go stimuli before a NoGo stimulus enhances conflict expectation, leading to longer reaction times (Zamorano et al., 2014). Fronto-medial theta oscillations, especially in the superior frontal gyrus (SFG), have been linked to conflict anticipation and its effects on performance (Dippel et al., 2017). Martinez-Molina et al. (2024) further showed that theta-band rhythmic stimulation intensifies these effects, increasing RTs and improving NoGo accuracy. Additionally, the locus coeruleus-noradrenergic (LC-NE) system supports cognitive control and attention. Its activity, measured indirectly via pupil diameter, increase with cognitive demands (Pfeffer et al., 2022), and its integrity correlates with better inhibitory performance (Tomassini et al., 2022). Prior evidence indicates that as NoGo stimuli become less frequent-thus increasing conflict-theta power and pupil diameter both rise (Dippel, 2017). In this study, we aim to clarify the neural mechanisms that link conflict expectation, inhibitory control, and the LC-NE system by examining how changes in pupil dynamics relate to fronto-medial theta oscillations.
Methods:
Thirty-two healthy participants (19 women; age range: 18-45 years, mean: 27 ± 7 years) performed a modified Go-NoGo task manipulating the number of consecutive Go trials before a NoGo to modulate conflict expectation. Behavioral data (RTs), electroencephalography (EEG), and pupillometry were recorded. We applied an integrative approach, combining cognitive computational modeling (Bayesian hierarchical drift-diffusion model), EEG time-frequency analyses, and pupil dilation indices to assess the interplay of conflict expectation and inhibitory control. Statistical comparisons on EEG and behavioral measures were conducted using non-parametric Wilcoxon tests with Bonferroni correction. A linear mixed-effects (LME) model was used to analyze pupil dilation, incorporating conflict expectation and previous error as fixed factors.
Results:
Behaviorally, the Bayesian drift-diffusion model indicated a significant effect of conflict expectation on RTs (β = 52.3, p < 0.001), suggesting that higher conflict anticipation increases cognitive control demands. For pupil dilation, the LME model (N=13,743 observations) revealed significant positive effects of conflict expectation (β = 5.91, p = 0.0389) and previous error (perror; β = 4.26, p = 0.00022) on pupil size, indicating that both increased conflict expectation and recent errors increase the LC-NE system engagement (Figure 1). Time-frequency EEG analyses focused on fronto-medial electrodes showed that conditions associated with higher conflict expectation modulated theta power. Non-parametric Wilcoxon tests with Bonferroni correction confirmed these differences, aligning with the notion that theta oscillations track inhibitory control needs (Figure 2).
Conclusions:
Participants adapt their behavior in anticipation of conflict, evidenced by slower responses when expecting challenging tasks demands. This adaptive mechanism suggests that cognitive resources are dynamically allocated based on increasing expectations, engaging inhibitory control processes before the presentation of a conflicting stimulus. In addition, the modulation of frontal theta activity in the right lateral prefrontal cortex, together with changes in pupil dilation, highlights the interplay between these neural markers and the LC-NE system in shaping responses to conflict expectation. These results provide new insights into the underlying brain mechanisms that link inhibitory control and the noradrenergic system in the context of conflict expectation.
Higher Cognitive Functions:
Executive Function, Cognitive Control and Decision Making 1
Modeling and Analysis Methods:
Bayesian Modeling
EEG/MEG Modeling and Analysis 2
Keywords:
Other - Inhibitory control, conflict expectation, EEG, pupillometry, computational modeling, theta oscillations, Locus coeruleus - norepinephrine system
1|2Indicates the priority used for review
Abstract Information
By submitting your proposal, you grant permission for the Organization for Human Brain Mapping (OHBM) to distribute your work in any format, including video, audio print and electronic text through OHBM OnDemand, social media channels, the OHBM website, or other electronic publications and media.
The Open Science Special Interest Group (OSSIG) is introducing a reproducibility challenge for OHBM 2025. This new initiative aims to enhance the reproducibility of scientific results and foster collaborations between labs. Teams will consist of a “source” party and a “reproducing” party, and will be evaluated on the success of their replication, the openness of the source work, and additional deliverables. Click here for more information. Propose your OHBM abstract(s) as source work for future OHBM meetings by selecting one of the following options:
Please indicate below if your study was a "resting state" or "task-activation” study.
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Was this research conducted in the United States?
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.
Please indicate which methods were used in your research:
Provide references using APA citation style.
Diamond, A. (2013). Executive functions. In Annual Review of Psychology (Vol. 64, pp. 135–168). Annual Reviews Inc.
https://doi.org/10.1146/annurev-psych-113011-143750
Dippel, G., Mückschel, M., Ziemssen, T., & Beste, C. (2017). Demands on response inhibition processes determine modulations of theta band activity in superior frontal areas and correlations with pupillometry – Implications for the norepinephrine system during inhibitory control. NeuroImage, 157, 575–585. https://doi.org/10.1016/j.neuroimage.2017.06.037
Martínez-Molina, M. P., Valdebenito-Oyarzo, G., Soto-Icaza, P., Zamorano, F., Figueroa-Vargas, A., Carvajal-Paredes, P., Stecher, X., Salinas, C., Valero-Cabré, A., Polania, R., & Billeke, P. (2024). Lateral Prefrontal Theta Oscillations Causally Drive a Computational Mechanism Underlying Conflict Expectation and Adaptation. https://doi.org/10.1101/2024.04.30.591918
Pfeffer, T., Keitel, C., Kluger, D. S., Keitel, A., Russmann, A., Thut, G., Donner, T. H., & Gross, J. (2022). Coupling of pupil-and neuronal population dynamics reveals diverse influences of arousal on cortical processing. ELife, 11. https://doi.org/10.7554/ELIFE.71890
Tomassini, A., Hezemans, F. H., Ye, R., Tsvetanov, K. A., Wolpe, N., & Rowe, J. B. (2022). Prefrontal cortical connectivity mediates locus coeruleus noradrenergic regulation of inhibitory control in older adults. Journal of Neuroscience, 42(16), 3484-3493.
Zamorano, F., Billeke, P., Hurtado, J. M., López, V., Carrasco, X., Ossandón, T., & Aboitiz, F. (2014). Temporal constraints of behavioral inhibition: Relevance of inter-stimulus interval in a go-nogo task. PLoS ONE, 9(1). https://doi.org/10.1371/journal.pone.0087232