title: Hyperactivity of caudate, parahippocampal, and prefrontal regions during working memory in never-medicated persons at clinical high-risk for psychosis.
abstract: 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-naïve 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 naïve 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-naïve 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.
authors.affiliation: 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.
authors.forename: Heidi W
authors.initials: HW
authors.lastname: Thermenos
authors.affiliation: Harvard Medical School, Boston, MA, USA; Department of Psychiatry, McLean Hospital, Belmont, MA, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Juelich
authors.affiliation: Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Samantha R
authors.initials: SR
authors.lastname: DiChiara
authors.affiliation: Harvard Medical School, Boston, MA, USA; Massachusetts Mental Health Center Division of Public Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Raquelle I
authors.initials: RI
authors.lastname: Mesholam-Gately
authors.affiliation: Harvard Medical School, Boston, MA, USA; Massachusetts Mental Health Center Division of Public Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Woodberry
authors.affiliation: Harvard Medical School, Boston, MA, USA; Massachusetts Mental Health Center Division of Public Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Wojcik
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Nikos
authors.initials: N
authors.lastname: Makris
authors.affiliation: Harvard Medical School, Boston, MA, USA; Massachusetts Mental Health Center Division of Public Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Matcheri S
authors.initials: MS
authors.lastname: Keshavan
authors.affiliation: McGovern Institute for Brain Research, Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Whitfield-Gabrieli
authors.affiliation: 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.
authors.forename: Tsung-Ung W
authors.initials: TU
authors.lastname: Woo
authors.affiliation: Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Petryshen
authors.affiliation: 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.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Goldstein
authors.affiliation: 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.
authors.forename: Martha E
authors.initials: ME
authors.lastname: Shenton
authors.affiliation: 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.
authors.forename: Robert W
authors.initials: RW
authors.lastname: McCarley
authors.affiliation: 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.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
mesh_terms: D000293:Adolescent; D000328:Adult; D001931:Brain Mapping; D016022:Case-Control Studies; D002421:Caudate Nucleus / Q000000981:diagnostic imaging*; D003072:Cognition Disorders / Q000209:etiology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D020534:Parahippocampal Gyrus / Q000000981:diagnostic imaging*; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging*; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology*; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: Clinical high risk; Prodrome; Psychosis; Working memory; fMRI