PMID- 26965745 OWN - NLM STAT- MEDLINE DCOM- 20170102 LR - 20181113 IS - 1573-2509 (Electronic) IS - 0920-9964 (Print) IS - 0920-9964 (Linking) VI - 173 IP - 1-2 DP - 2016 May TI - Hyperactivity of caudate, parahippocampal, and prefrontal regions during working memory in never-medicated persons at clinical high-risk for psychosis. PG - 1-12 LID - S0920-9964(16)30078-0 [pii] LID - 10.1016/j.schres.2016.02.023 [doi] AB - BACKGROUND: Deficits in working memory (WM) are a core feature of schizophrenia (SZ) and other psychotic disorders. We examined brain activity during WM in persons at clinical high risk (CHR) for psychosis. METHODS: Thirty-seven CHR and 34 healthy control participants underwent functional MRI (fMRI) on a 3.0T scanner while performing an N-back WM task. The sample included a sub-sample of CHR participants who had no lifetime history of treatment with psychotropic medications (n=11). Data were analyzed using SPM8 (2-back>0-back contrast). Pearson correlations between brain activity, symptoms, and WM performance were examined. RESULTS: The total CHR group and medication-naive CHR sub-sample were comparable to controls in most demographic features and in N-back WM performance, but had significantly lower IQ. Relative to controls, medication-naive CHR showed hyperactivity in the left parahippocampus (PHP) and the left caudate during performance of the N-back WM task. Relative to medication-exposed CHR, medication naive CHR exhibited hyperactivity in the left caudate and the right dorsolateral prefrontal cortex (DLPFC). DLPFC activity was significantly negatively correlated with WM performance. PHP, caudate and DLPFC activity correlated strongly with symptoms, but results did not withstand FDR-correction for multiple comparisons. When all CHR participants were combined (regardless of medication status), only trend-level PHP hyperactivity was observed in CHR relative to controls. CONCLUSIONS: Medication-naive CHR exhibit hyperactivity in regions that subserve WM. These regions are implicated in studies of schizophrenia and risk for psychosis. Results emphasize the importance of medication status in the interpretation of task - induced brain activity. CI - Copyright (c) 2016 Elsevier B.V. All rights reserved. FAU - Thermenos, Heidi W AU - Thermenos HW AD - Harvard Medical School, Boston, MA, USA; Massachusetts Mental Health Center Division of Public Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. Electronic address: hthermen@bidmc.harvard.edu. FAU - Juelich, Richard J AU - Juelich RJ AD - Harvard Medical School, Boston, MA, USA; Department of Psychiatry, McLean Hospital, Belmont, MA, USA. FAU - DiChiara, Samantha R AU - DiChiara SR AD - Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. FAU - Mesholam-Gately, Raquelle I AU - Mesholam-Gately RI AD - Harvard Medical School, Boston, MA, USA; Massachusetts Mental Health Center Division of Public Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA. FAU - Woodberry, Kristen A AU - Woodberry KA AD - Harvard Medical School, Boston, MA, USA; Massachusetts Mental Health Center Division of Public Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA. FAU - Wojcik, Joanne AU - Wojcik J AD - Harvard Medical School, Boston, MA, USA; Massachusetts Mental Health Center Division of Public Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA. FAU - Makris, Nikos AU - Makris N AD - Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. FAU - Keshavan, Matcheri S AU - Keshavan MS AD - Harvard Medical School, Boston, MA, USA; Massachusetts Mental Health Center Division of Public Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA. FAU - Whitfield-Gabrieli, Susan AU - Whitfield-Gabrieli S AD - McGovern Institute for Brain Research, Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge, MA, USA. FAU - Woo, Tsung-Ung W AU - Woo TU AD - Harvard Medical School, Boston, MA, USA; Massachusetts Mental Health Center Division of Public Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA; Laboratory of Cellular Neuropathology, McLean Hospital, Belmont, MA, USA. FAU - Petryshen, Tracey L AU - Petryshen TL AD - Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. FAU - Goldstein, Jill M AU - Goldstein JM AD - Harvard Medical School, Boston, MA, USA; Department of Medicine, Division of Women's Health, Connor's Center for Women's Health & Gender Biology, Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, USA. FAU - Shenton, Martha E AU - Shenton ME AD - Harvard Medical School, Boston, MA, USA; Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; VA Boston Healthcare System, Brockton, MA, USA. FAU - McCarley, Robert W AU - McCarley RW AD - Harvard Medical School, Boston, MA, USA; Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; VA Boston Healthcare System, Brockton, MA, USA. FAU - Seidman, Larry J AU - Seidman LJ AD - Harvard Medical School, Boston, MA, USA; Massachusetts Mental Health Center Division of Public Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. LA - eng GR - K23 MH102358/MH/NIMH NIH HHS/United States GR - UL1RR025758/RR/NCRR NIH HHS/United States GR - S10 RR021110/RR/NCRR NIH HHS/United States GR - S10 RR019307/RR/NCRR NIH HHS/United States GR - P50 MH080272/MH/NIMH NIH HHS/United States GR - P41 RR014075/RR/NCRR NIH HHS/United States GR - M01 RR001032/RR/NCRR NIH HHS/United States GR - UO1 MH081928/MH/NIMH NIH HHS/United States GR - 1S10RR019307/RR/NCRR NIH HHS/United States GR - 1S10RR023043/RR/NCRR NIH HHS/United States GR - P41EB015896/EB/NIBIB NIH HHS/United States GR - 1S10RR023401/RR/NCRR NIH HHS/United States GR - M01RR01032/RR/NCRR NIH HHS/United States GR - S10RR021110/RR/NCRR NIH HHS/United States GR - UL1 RR025758/RR/NCRR NIH HHS/United States GR - P50MH080272/MH/NIMH NIH HHS/United States GR - S10 RR023043/RR/NCRR NIH HHS/United States GR - P41RR14075/RR/NCRR NIH HHS/United States GR - P41 EB015896/EB/NIBIB NIH HHS/United States GR - U01 MH081928/MH/NIMH NIH HHS/United States GR - S10 RR023401/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20160307 PL - Netherlands TA - Schizophr Res JT - Schizophrenia research JID - 8804207 RN - S88TT14065 (Oxygen) SB - IM MH - Adolescent MH - Adult MH - Brain Mapping MH - Case-Control Studies MH - Caudate Nucleus/*diagnostic imaging MH - Cognition Disorders/*etiology MH - Female MH - Humans MH - Image Processing, Computer-Assisted MH - Magnetic Resonance Imaging MH - Male MH - Memory, Short-Term/physiology MH - Neuropsychological Tests MH - Oxygen/blood MH - Parahippocampal Gyrus/*diagnostic imaging MH - Prefrontal Cortex/*diagnostic imaging MH - Psychiatric Status Rating Scales MH - Psychotic Disorders/*complications/diagnostic imaging/*pathology MH - Statistics as Topic MH - Young Adult PMC - PMC4836956 MID - NIHMS767563 OTO - NOTNLM OT - Clinical high risk OT - Prodrome OT - Psychosis OT - Working memory OT - fMRI EDAT- 2016/03/12 06:00 MHDA- 2017/01/04 06:00 PMCR- 2017/05/01 CRDT- 2016/03/12 06:00 PHST- 2015/10/06 00:00 [received] PHST- 2016/02/09 00:00 [revised] PHST- 2016/02/11 00:00 [accepted] PHST- 2016/03/12 06:00 [entrez] PHST- 2016/03/12 06:00 [pubmed] PHST- 2017/01/04 06:00 [medline] PHST- 2017/05/01 00:00 [pmc-release] AID - S0920-9964(16)30078-0 [pii] AID - 10.1016/j.schres.2016.02.023 [doi] PST - ppublish SO - Schizophr Res. 2016 May;173(1-2):1-12. doi: 10.1016/j.schres.2016.02.023. Epub 2016 Mar 7.