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Cognitive models of GAD<\/jats:styled-content> highlight the role of intolerance of uncertainty (IU<\/jats:styled-content>) in precipitating and maintaining worry, and it has been hypothesized that patients with GAD<\/jats:styled-content> exhibit decision\u2010making deficits under uncertain conditions. Improving understanding of the neural mechanisms underlying cognitive deficits associated with IU<\/jats:styled-content> may lead to the identification of novel rTMS<\/jats:styled-content> treatment targets and optimization of treatment parameters. The current report describes two interrelated studies designed to identify and verify a potential neural target for rTMS<\/jats:styled-content> treatment of GAD.<\/jats:p><\/jats:sec>Methods<\/jats:title>Study I explored the integrity of prefrontal cortex (PFC<\/jats:styled-content>) and amygdala neural networks, which underlie decision making under conditions of uncertainty, in GAD<\/jats:styled-content>. Individuals diagnosed with GAD<\/jats:styled-content> (n\u00a0<\/jats:italic>=\u00a0<\/jats:italic>31) and healthy controls (n\u00a0<\/jats:italic>=\u00a0<\/jats:italic>20) completed a functional magnetic resonance imaging (fMRI<\/jats:styled-content>) gambling task that manipulated uncertainty using high versus low error rates. In a subsequent randomized\u2010controlled trial (Study II<\/jats:styled-content>), a subset of the GAD<\/jats:styled-content> sample (n\u00a0<\/jats:italic>=\u00a0<\/jats:italic>16) completed the fMRI<\/jats:styled-content> gambling task again after 30 sessions of active versus sham rTMS<\/jats:styled-content> (1\u00a0Hz, right dorsolateral prefrontal cortex) to investigate the modulation of functional networks and symptoms.<\/jats:p><\/jats:sec>Results<\/jats:title>In Study I, participants with GAD<\/jats:styled-content> demonstrated impairments in PFC<\/jats:styled-content>\u2010PFC<\/jats:styled-content> and PFC<\/jats:styled-content>\u2010amygdala functional connectivity (FC<\/jats:styled-content>) mostly during the high uncertainty condition. In Study II<\/jats:styled-content>, one region of interest pair, dorsal anterior cingulate (ACC<\/jats:styled-content>) \u2013 subgenual ACC<\/jats:styled-content>, showed \u201cnormalization\u201d of FC<\/jats:styled-content> following active, but not sham, rTMS<\/jats:styled-content>, and neural changes were associated with improvement in worry symptoms.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>These results outline a possible treatment mechanism of rTMS<\/jats:styled-content> in GAD<\/jats:styled-content>, and pave the way for future studies of treatment optimization.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.1015","type":"journal-article","created":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T04:14:31Z","timestamp":1529640871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Neural functional architecture and modulation during decision making under uncertainty in individuals with generalized 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