Altered striatal intrinsic functional connectivity in pediatric anxiety

Abstract

Anxiety disorders are among the most common psychiatric disorders of adolescence. Behavioral and task-based imaging studies implicate altered reward system function, including striatal dysfunction, in adolescent anxiety. However, no study has yet examined alterations of the striatal intrinsic functional connectivity in adolescent anxiety disorders. The current study examines striatal intrinsic functional connectivity (iFC), using six bilateral striatal seeds, among 35 adolescents with anxiety disorders and 36 healthy comparisons. Anxiety is associated with abnormally low iFC within the striatum (e.g., between nucleus accumbens and caudate nucleus), and between the striatum and prefrontal regions, including subgenual anterior cingulate cortex, posterior insula and supplementary motor area. The current findings extend prior behavioral and task-based imaging research, and provide novel data implicating decreased striatal iFC in adolescent anxiety. Alterations of striatal neurocircuitry identified in this study may contribute to the perturbations in the processing of motivational, emotional, interoceptive, and motor information seen in pediatric anxiety disorders. This pattern of the striatal iFC perturbations can guide future research on specific mechanisms underlying anxiety.

Reduced neural differentiation of rewards and punishment during passive avoidance learning in adolescents with generalized anxiety disorder

“…Adolescents with GAD, relative to comparison adolescents, showed reduced differential responding to received reward relative to punishment (manifesting as reduced responses to reward) within caudate, putamen, midcingulate/paracentral lobule, and superior and middle frontal gyrus. This is compatible with previous work with adolescents with GAD reporting reduced responses to reward within caudate/putamen (Benson et al, 2015), reduced ventral striatal activity relative to controls during risky relative to safe choices for monetary rewards (Galvan & Peris, 2014) and reduced within‐striatum and striatum to frontal cortex correlated activity via connectivity analysis (Dorfman et al, 2016). Notably, the results are similar to our previous findings with adults with GAD and comparison individuals using a very similar task (White et al, 2017).…”

“…Induced anticipatory anxiety has also been associated with reduced expected value signaling in the ventral striatum in healthy adults (Engelmann et al, 2015). Similarly, adults with GAD showed reduced striatal responses to received reward in an instrumental learning task (White et al, 2017) and reduced within‐striatum and striatum to frontal cortex correlated activity via connectivity analysis (Dorfman et al, 2016). In addition, they have been found to show reduced modulation of the striatum and medial frontal cortex when considering rewarding future emotional events (Blair et al, 2017).…”

Adolescent anxiety disorders and the developing brain: comparing neuroimaging findings in adolescents and adults

“…49 Motivation processing: striatum, amygdala and prefrontal cortex The nucleus accumbens of the striatum evaluates stimuli in terms of motivational values, and the dorsal striatum integrates and transmits information to the prefrontal and motor cortices. 50 Reward representations are available to the ventral striatum that participates in forming motivational and goal-oriented behaviours. The amygdala actively regulates the striatum.…”

“…99 Patients with anxiety disorders also show altered prefrontal-striatal functional connectivity. 50 The prefrontal-striatum connectivity in adults with anxiety disorders is increased, 100 whereas that in adolescents with anxiety disorders may decrease in response to unexpected positive feedback. 30 The abnormal development of dopaminergic neurons in the amygdala, the prefrontal cortex, the hippocampus and the striatum during adolescence alters one's exposure to hormonal influences, which may increase the risk of mental illness.…”

Functional Connectivity of the Nucleus Accumbens across Variants of Callous-Unemotional Traits: A Resting-State fMRI Study in Children and Adolescents

“…From childhood to adulthood, the resting-state functional connectivity between the NAcc and frontal regions (including perigenual and subgenual anterior cingulate cortex, ventromedial prefrontal cortex, and orbitofrontal cortex) linearly decreases, whereas its connectivity with the posterior insula shows a quadratic effect (Fareri et al, 2015 ), highlighting its potential role in the development of various psychopathologies. In fact, a growing body of literature show that functional connectivity of the NAcc is associated with numerous psychopathologies during adolescence such as anxiety and depressive symptoms (Dorfman et al, 2016 ; Pan et al, 2017 ), impulsive decision-making (Costa Dias et al, 2013 ), substance misuse (Huntley et al, 2020 ; Morales et al, 2021 ), and social problems (Fareri et al, 2017 ). Thus, the maturational deficits in motivational processes are thought play a major role in our understanding of externalizing problems in children and adolescents (Bjork & Pardini, 2015 ).…”