The Mind Research Network/Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM.
Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque, NM.
Schizophr Bull. 2019 Apr 25;45(3):552-561. doi: 10.1093/schbul/sby086.
Inhibitory failure represents a core dysfunction in patients with schizophrenia (SP), which has predominantly been tested in the literature using reactive (ie, altering behavior after a stimulus) rather than proactive (ie, purposefully changing behavior before a stimulus) response inhibition tasks. The current study replicates/extends our previous findings of SP exhibiting sensorimotor cortex (SMC) hyperactivity and connectivity abnormalities in independent samples of patients and controls. Specifically, 49 clinically well-characterized SP and 54 matched healthy controls (HC) performed a proactive response inhibition task while undergoing functional magnetic resonance imaging and resting-state data collection. Results indicated that the majority of SP (84%) and HC (88%) successfully inhibited all overt motor responses following a cue, eliminating behavioral confounds frequently present in this population. Observations of left SMC hyperactivity during proactive response inhibition, reduced cortical connectivity with left SMC, and increased connectivity between left SMC and ventrolateral thalamus were replicated for SP relative to HC in the current study. Similarly, negative symptoms (eg, motor retardation) were again associated with SMC functional and connectivity abnormalities. In contrast, findings of a negative blood oxygenation level-dependent response in the SMC of HC did not replicate. Collectively, current and previous findings suggest that SMC connectivity abnormalities may be more robust relative to evoked hemodynamic signals during proactive response inhibition. In addition, there is strong support that these SMC abnormalities are a key component of SP pathology, along with dysfunction within other sensory cortices, and may be associated with certain clinical deficits such as negative symptoms.
抑制失败代表精神分裂症(SP)患者的核心功能障碍,该障碍主要通过反应性(即刺激后改变行为)而不是主动性(即在刺激前有目的地改变行为)抑制任务在文献中进行测试。本研究在独立的 SP 患者和对照组样本中复制/扩展了我们之前发现的 SP 表现出感觉运动皮层(SMC)过度活跃和连接异常的研究结果。具体来说,49 名临床特征明确的 SP 和 54 名匹配的健康对照组(HC)在进行功能磁共振成像和静息态数据采集的同时执行主动反应抑制任务。结果表明,大多数 SP(84%)和 HC(88%)在收到提示后成功抑制了所有明显的运动反应,消除了该人群中经常存在的行为混淆因素。在当前研究中,与 HC 相比,观察到 SP 在主动反应抑制期间左侧 SMC 过度活跃,左侧 SMC 与皮质的连接减少,以及左侧 SMC 与腹外侧丘脑之间的连接增加。同样,负面症状(例如,运动迟缓)与 SMC 的功能和连接异常再次相关。相比之下,HC 的 SMC 中负血氧水平依赖反应的发现没有复制。总的来说,当前和以前的研究结果表明,SMC 连接异常在主动反应抑制期间相对于诱发的血液动力学信号可能更为稳健。此外,有强有力的证据表明,这些 SMC 异常是 SP 病理学的关键组成部分,与其他感觉皮层的功能障碍一起,并且可能与某些临床缺陷(如负面症状)相关。