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Fear conditioning has been proposed to represent a central pathway for the development and maintenance of this disorder; however, its neural substrates remain elusive. The present study aimed to investigate the neural correlates of fear conditioning in PD\/AG patients.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291713000792_sec_a2\" sec-type=\"methods\"><jats:title>Method<\/jats:title><jats:p>The blood oxygen level-dependent (BOLD) response was measured using fMRI during a fear conditioning task. Indicators of differential conditioning, simple conditioning and safety signal processing were investigated in 60 PD\/AG patients and 60 matched healthy controls.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291713000792_sec_a3\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>Differential conditioning was associated with enhanced activation of the bilateral dorsal inferior frontal gyrus (IFG) whereas simple conditioning and safety signal processing were related to increased midbrain activation in PD\/AG patients versus controls. Anxiety sensitivity was associated positively with the magnitude of midbrain activation.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291713000792_sec_a4\" sec-type=\"conclusion\"><jats:title>Conclusions<\/jats:title><jats:p>The results suggest changes in top-down and bottom-up processes during fear conditioning in PD\/AG that can be interpreted within a neural framework of defensive reactions mediating threat through distal (forebrain) <jats:italic>versus<\/jats:italic> proximal (midbrain) brain structures. Evidence is accumulating that this network plays a key role in the aetiopathogenesis of panic disorder.<\/jats:p><\/jats:sec>","DOI":"10.1017\/s0033291713000792","type":"journal-article","created":{"date-parts":[[2013,4,23]],"date-time":"2013-04-23T14:26:06Z","timestamp":1366727166000},"page":"381-394","source":"Crossref","is-referenced-by-count":54,"title":["Altered top-down and bottom-up processing of fear conditioning in panic disorder with agoraphobia"],"prefix":"10.1017","volume":"44","author":[{"given":"U.","family":"Lueken","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Straube","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Reinhardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. 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