Segregating domain-general from emotional context-specific inhibitory control systems - ventral striatum and orbitofrontal cortex serve as emotion-cognition integration hubs

Abstract

Inhibitory control hierarchically regulates cognitive and emotional systems in the service of adaptive goal-directed behavior across changing task demands and environments. While previous studies convergently determined the contribution of prefrontal-striatal systems to general inhibitory control, findings on the specific circuits that mediate the context-specific impact of inhibitory control remained inconclusive. Against this background we employed an evaluated emotional Go/No Go task with fMRI in a large cohort of subjects (N = 250) to segregate brain systems and circuits that mediate domain-general from emotion-specific inhibition control. Particularly during a positive emotional context, behavioral results showed a lower accuracy for No Go trials and a faster response time for Go trials. While the dorsal striatum and lateral frontal regions were involved in inhibitory control irrespective of emotional context, activity in the ventral striatum (VS) and medial orbitofrontal cortex (mOFC) varied as a function of emotional context. On the voxel-wise network level, limbic and striatal systems generally exhibited highest changes in global brain connectivity during inhibitory control, while global brain connectivity of the left mOFC was less suppressed during emotional contexts. Functional connectivity analyses moreover revealed that negative coupling between the VS with inferior frontal gyrus (IFG)/insula and mOFC varied as a function of emotional context. Together these findings indicated separable domain general systems as well emotional context-specific inhibitory brain systems which specifically encompass the VS and its connections with frontal regions.

Angiotensin II regulates the neural expression of subjective fear in humans - precision pharmaco-neuroimaging approach

“…The conventional mass univariate activation and connectivity analyses revealed that AT1R blockade specifically attenuated left dlPFC reactivity and amygdala-vACC connectivity in response to fearful oddballs. The dlPFC represents a functionally heterogenous region and has been involved in several domains related to fear processing, including implicit and explicit cognitive regulation of negative affect and task-irrelevant distractors (Beauregard, Lévesque, & Bourgouin, 2001; Delgado, Nearing, LeDoux, & Phelps, 2008; Kim & Hamann, 2007; Lévesque et al, 2003; C. Liu et al, 2021; Ochsner, Bunge, Gross, & Gabrieli, 2002; Ochsner et al, 2004; Phan et al, 2004; Zhuang et al, 2021) rapid attention towards salient stimuli, including threat-related stimuli (Clarke et al, 2020; Peers, Simons, & Lawrence, 2013; Sagliano, D’Olimpio, Izzo, & Trojano, 2017) and the conscious subjective experience of emotional states including fear (Kroes et al, 2019; LeDoux & Pine, 2016). In accordance with this functional characterization of the dlPFC in neuroimaging studies lesion and non-invasive brain stimulation studies have provided more causal evidence for an involvement in the fear-related process.…”

The right inferior frontal gyrus as pivotal node and effective regulator of the basal ganglia-thalamocortical response inhibition circuit

“…Participants N=250 healthy right-handed participants were enrolled in the current study and underwent a validated Go/NoGo fMRI paradigm. The data has been previously used to examine undirected functional connectivity within domain-general and emotion-specific inhibitory brain systems (Zhuang et al, 2021) and was part of larger neuroimaging project examining pain empathy (Li et al, 2018;Zhou et al, 2020), emotional face memory (Liu et al, 2022) and mirror neuron processing (Xu et al, 2022). After quality assessment n=218 subjects were included (104 males, Supplementary Materials).…”

“…In our previous study we demonstrated that subjects exhibited more errors during inhibitory control (i.e., NoGo>Go) as well as faster responses in positive Go contexts and lower accuracy in positive NoGo contexts (Zhuang et al, 2021). Given that sex-differences were examined in the DCM model the present analyses additionally examined sex-differences on accuracy and reaction times (Supplementary Materials).…”

“…A validated mixed event-related block design linguistic emotional Go/NoGo fMRI paradigm was employed (Goldstein et al, 2007;Protopopescu et al, 2005, details see Zhuang et al, 2021). Participants were required to make responses as accurately and quickly as possible based on orthographical cues, i.e.…”

“…Each Go block encompassed 18 normal font words (100% Go trials) while each NoGo block encompassed 12 normal font words (66.7% Go trials) and 6 italicized font words (33.3% NoGo trials). Further details in (Zhuang et al, 2021) and Supplementary Materials.…”