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Here, we examined the neural underpinnings of emotion processing within and across patients (<jats:italic>N<\/jats:italic> =\u200944) receiving either ECT (<jats:italic>N<\/jats:italic> =\u200917, mean age: 36.8, 11.0 <jats:italic>SD<\/jats:italic>) or repeated subanesthetic (0.5\u2009mg\/kg) intravenous ketamine therapy (<jats:italic>N<\/jats:italic> =\u200927, mean age: 37.3, 10.8 <jats:italic>SD<\/jats:italic>) using a naturalistic study design. MRI and clinical data were collected before (TP1) and after treatment (TP2); healthy controls (<jats:italic>N<\/jats:italic> =\u200931, mean age: 34.5, 13.5 <jats:italic>SD<\/jats:italic>) completed one MRI session (TP1). An fMRI face\u2010matching task probed negative\u2010 and positive\u2010valence systems. Whole\u2010brain analysis, comparing neurofunctional changes within and across treatment groups, targeted brain regions involved in emotional facial processing, and included regions\u2010of\u2010interest analysis of amygdala responsivity. Main findings revealed a decrease in amygdalar reactivity after both ECT and ketamine for positive and negative emotional face processing (<jats:italic>p<\/jats:italic> &lt;\u2009.05 family wise\u2010error (FWE) corrected). Subthreshold changes were observed between treatments within the dorsolateral prefrontal cortex and insula (<jats:italic>p<\/jats:italic> &lt;\u2009.005, uncorrected). BOLD change for positive faces in the inferior parietal cortex significantly correlated with overall symptom improvement, and BOLD change in frontal regions correlated with anxiety for negative faces, and anhedonia for positive faces (<jats:italic>p<\/jats:italic> &lt;\u2009.05 FWE corrected). Both serial ketamine and ECT treatment modulate amygdala response, while more subtle treatment\u2010specific changes occur in the larger functional network. Findings point to both common and differential mechanistic upstream systems\u2010level effects relating to fast\u2010acting antidepressant response, and symptoms of anxiety and anhedonia, for the processing of emotionally valenced stimuli.<\/jats:p>","DOI":"10.1002\/hbm.24895","type":"journal-article","created":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T06:14:35Z","timestamp":1583129675000},"page":"1699-1710","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Modulation of amygdala reactivity following rapidly acting interventions for major depression"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9550-804X","authenticated-orcid":false,"given":"Joana R. 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