Thermenos Heidi W, Juelich Richard J, DiChiara Samantha R, Mesholam-Gately Raquelle I, Woodberry Kristen A, Wojcik Joanne, Makris Nikos, Keshavan Matcheri S, Whitfield-Gabrieli Susan, Woo Tsung-Ung W, Petryshen Tracey L, Goldstein Jill M, Shenton Martha E, McCarley Robert W, Seidman Larry J
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.
Harvard Medical School, Boston, MA, USA; Department of Psychiatry, McLean Hospital, Belmont, MA, USA.
Schizophr Res. 2016 May;173(1-2):1-12. doi: 10.1016/j.schres.2016.02.023. Epub 2016 Mar 7.
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.
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.
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.
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.
工作记忆（WM）缺陷是精神分裂症（SZ）和其他精神障碍的核心特征。我们研究了临床高危（CHR）精神病患者在工作记忆期间的大脑活动。
37名CHR参与者和34名健康对照者在3.0T扫描仪上接受功能磁共振成像（fMRI），同时执行N-回溯工作记忆任务。样本包括从未接受过精神药物治疗的CHR参与者子样本（n = 11）。使用SPM8（2-回溯>0-回溯对比）分析数据。检查大脑活动、症状和工作记忆表现之间的Pearson相关性。
CHR总组和未用药的CHR子样本在大多数人口统计学特征和N-回溯工作记忆表现方面与对照组相当，但智商显著较低。相对于对照组，未用药的CHR在执行N-回溯工作记忆任务期间，左侧海马旁回（PHP）和左侧尾状核表现出活动亢进。相对于接受过药物治疗的CHR，未用药的CHR在左侧尾状核和右侧背外侧前额叶皮质（DLPFC）表现出活动亢进。DLPFC活动与工作记忆表现显著负相关。PHP、尾状核和DLPFC活动与症状密切相关，但结果在多重比较的FDR校正后不成立。当所有CHR参与者合并（无论用药状态如何）时，相对于对照组，CHR中仅观察到趋势水平的PHP活动亢进。
未用药的CHR在支持工作记忆的区域表现出活动亢进。这些区域在精神分裂症和精神病风险研究中具有重要意义。结果强调了用药状态在解释任务诱发的大脑活动中的重要性。
