Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry & Psychology and Neuroscience, King's College of London, London, UK.
Department of Psychosis Studies, Institute of Psychiatry, Psychology &Neuroscience, King's College London, London, UK; Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK.
Psychoneuroendocrinology. 2021 Mar;125:105116. doi: 10.1016/j.psyneuen.2020.105116. Epub 2020 Dec 17.
Glucocorticoid receptor (GR) antagonism is a promising new treatment for cognitive dysfunction in psychiatric disorders but the effects of GR antagonism on cognition related brain activity is poorly understood. This study examines the effects of the GR and progesterone receptor antagonist mifepristone on the neural correlates of visuospatial learning and working memory in healthy male participants. The study used a pharmacological functional magnetic resonance imaging (fMRI) design to determine mifepristone effects on visuospatial paired associates learning (vPAL) and n-back working memory (WM) fMRI task related brain activations. 20 right-handed healthy male participants received 600 mg mifepristone or placebo on two separate imaging days and each participant performed fMRI tasks four hours later. The effect of mifepristone on task related brain activations was determined using Region of Interest (ROI) fMRI analyses and an exploratory whole brain voxel-wise fMRI task analyses was also conducted. The vPAL task ROI analysis found that mifepristone administration was significantly associated with decreased fusiform cortex activations in first and second encoding blocks (p = 0.007, p = 0.04) and decreased angular and precuneal cortices activations in the first recall block (p = 0.01, p = 0.02). There were no significant differences in fMRI brain activations associated with mifepristone administration in the n-back task ROI's (all p > 0.05). Mifepristone administration did not significantly affect fMRI brain activations in the whole brain voxel-wise analyses for both tasks. N-back and vPAL task reaction times and accuracy were similar in both mifepristone and placebo conditions (all p > 0.05). Our finding of decreased fusiform, angular and precuneal vPAL task related brain activity associated with mifepristone administration for the same behavioural performance as found in the placebo condition may represent improved efficiency of visuospatial memory encoding and recall. These findings provide evidence that mifepristone may enhance the efficiency of human visuospatial memory and calls for further studies in patient populations using an fMRI approach to provide proof of concept for new treatments.
糖皮质激素受体（GR）拮抗剂是治疗精神障碍认知功能障碍的一种有前途的新方法，但 GR 拮抗剂对认知相关脑活动的影响知之甚少。本研究旨在探讨 GR 和孕激素受体拮抗剂米非司酮对健康男性参与者的视觉空间学习和工作记忆相关脑活动的影响。该研究采用药理学功能磁共振成像（fMRI）设计，以确定米非司酮对视觉空间配对联想学习（vPAL）和 n-back 工作记忆（WM）fMRI 任务相关脑激活的影响。20 名右利手健康男性参与者在两天内分别接受 600mg 米非司酮或安慰剂治疗，之后每位参与者在四小时后进行 fMRI 任务。使用感兴趣区（ROI）fMRI 分析来确定米非司酮对任务相关脑激活的影响，同时还进行了探索性全脑体素水平 fMRI 任务分析。vPAL 任务 ROI 分析发现，米非司酮给药与第一和第二编码块中梭状回激活减少显著相关（p=0.007，p=0.04），第一回忆块中角回和楔前叶皮质激活减少（p=0.01，p=0.02）。在 n-back 任务 ROI 中，米非司酮给药与 fMRI 脑激活无显著差异（均 p>0.05）。在全脑体素水平分析中，米非司酮给药对两个任务的 fMRI 脑激活均无显著影响。在米非司酮和安慰剂条件下，n-back 和 vPAL 任务的反应时间和准确性相似（均 p>0.05）。我们发现，与安慰剂条件下的行为表现相比，米非司酮给药后 vPAL 任务相关的梭状回、角回和楔前叶皮质活动减少，这可能代表视觉空间记忆编码和回忆效率提高。这些发现为米非司酮可能增强人类视觉空间记忆效率提供了证据，并呼吁进一步在患者人群中使用 fMRI 方法进行研究，为新治疗方法提供概念验证。
