PMID- 32512402 OWN - NLM STAT- MEDLINE DCOM- 20210329 LR - 20210329 IS - 2213-1582 (Electronic) IS - 2213-1582 (Linking) VI - 27 DP - 2020 TI - Adolescents at clinical high risk for psychosis show qualitatively altered patterns of activation during rule learning. PG - 102286 LID - S2213-1582(20)30123-6 [pii] LID - 10.1016/j.nicl.2020.102286 [doi] LID - 102286 AB - BACKGROUND: The ability to flexibly apply rules to novel situations is a critical aspect of adaptive human behavior. While executive function deficits are known to appear early in the course of psychosis, it is unclear which specific facets are affected. Identifying whether rule learning is impacted at the early stages of psychosis is necessary for truly understanding the etiology of psychosis and may be critical for designing novel treatments. Therefore, we examined rule learning in healthy adolescents and those meeting criteria for clinical high risk (CHR) for psychosis. METHODS: 24 control and 22 CHR adolescents underwent rapid, high-resolution fMRI while performing a paradigm which required them to apply novel or practiced task rules. RESULTS: Previous work has suggested that practiced rules rely on rostrolateral prefrontal cortex (RLPFC) during rule encoding and dorsolateral prefrontal cortex (DLPFC) during task performance, while novel rules show the opposite pattern. We failed to replicate this finding, with greater activity for novel rules during performance. Comparing the HC and CHR group, there were no statistically significant effects, but an effect size analysis found that the CHR group showed less activation during encoding and greater activation during performance. This suggests the CHR group may use less efficient reactive control to retrieve task rules at the time of task performance, rather than proactively during rule encoding. CONCLUSIONS: These findings suggest that flexibility is qualitatively altered in the clinical high risk state, however, more data is needed to determine whether these deficits predict disease progression. CI - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Orr, Joseph M AU - Orr JM AD - Department of Psychological and Brain Sciences, Texas A&M University, College Station, TX, United States; Texas A&M Institute for Neuroscience, Texas A&M University, College Station, TX, United States. Electronic address: joseph.orr@tamu.edu. FAU - Lopez, Jesus AU - Lopez J AD - Department of Psychological and Brain Sciences, Texas A&M University, College Station, TX, United States. Electronic address: jesusjlopez619@tamu.edu. FAU - Imburgio, Michael J AU - Imburgio MJ AD - Department of Psychological and Brain Sciences, Texas A&M University, College Station, TX, United States. Electronic address: mimburgi@tamu.edu. FAU - Pelletier-Baldelli, Andrea AU - Pelletier-Baldelli A AD - Department of Psychiatry, UNC-Chapel Hill School of Medicine, Chapel Hill, NC, United States. Electronic address: andrea_baldelli@med.unc.edu. FAU - Bernard, Jessica A AU - Bernard JA AD - Department of Psychological and Brain Sciences, Texas A&M University, College Station, TX, United States; Texas A&M Institute for Neuroscience, Texas A&M University, College Station, TX, United States. Electronic address: jessica.bernard@tamu.edu. FAU - Mittal, Vijay A AU - Mittal VA AD - Department of Psychiatry, Northwestern University, Evanston, IL, United States; Medical Social Sciences, Northwestern University, Evanston, IL, United States; Institute for Policy Research (IPR), Northwestern University, Evanston, IL, United States; Institute for Innovations in Developmental Sciences (DevSci), Northwestern University, Evanston, IL, United States. Electronic address: vijay.mittal@northwestern.edu. LA - eng GR - F31 MH100821/MH/NIMH NIH HHS/United States GR - F32 DA034412/DA/NIDA NIH HHS/United States GR - F32 MH102898/MH/NIMH NIH HHS/United States GR - R01 MH094650/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200526 PL - Netherlands TA - Neuroimage Clin JT - NeuroImage. Clinical JID - 101597070 SB - IM MH - Adolescent MH - Brain/*physiopathology MH - Brain Mapping/methods MH - Executive Function/*physiology MH - Female MH - Humans MH - Learning/*physiology MH - Magnetic Resonance Imaging/methods MH - Male MH - Prefrontal Cortex/physiopathology MH - Psychotic Disorders/*physiopathology MH - Risk PMC - PMC7281799 OTO - NOTNLM OT - Executive function OT - High risk OT - Imaging OT - Psychosis OT - Rule learning OT - fMRI EDAT- 2020/06/09 06:00 MHDA- 2021/03/30 06:00 PMCR- 2020/05/26 CRDT- 2020/06/09 06:00 PHST- 2020/01/19 00:00 [received] PHST- 2020/05/17 00:00 [revised] PHST- 2020/05/19 00:00 [accepted] PHST- 2020/06/09 06:00 [pubmed] PHST- 2021/03/30 06:00 [medline] PHST- 2020/06/09 06:00 [entrez] PHST- 2020/05/26 00:00 [pmc-release] AID - S2213-1582(20)30123-6 [pii] AID - 102286 [pii] AID - 10.1016/j.nicl.2020.102286 [doi] PST - ppublish SO - Neuroimage Clin. 2020;27:102286. doi: 10.1016/j.nicl.2020.102286. Epub 2020 May 26.