Lindberg Påvel G, Térémetz Maxime, Charron Sylvain, Kebir Oussama, Saby Agathe, Bendjemaa Narjes, Lion Stéphanie, Crépon Benoît, Gaillard Raphaël, Oppenheim Catherine, Krebs Marie-Odile, Amado Isabelle
FR3636 CNRS, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; INSERM U894, Centre de Psychiatrie et Neurosciences, Paris, France; Institut de Psychiatrie-GDR 3557 de Psychiatrie, France.
FR3636 CNRS, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; INSERM U894, Centre de Psychiatrie et Neurosciences, Paris, France; Institut de Psychiatrie-GDR 3557 de Psychiatrie, France.
Cortex. 2016 Dec;85:1-12. doi: 10.1016/j.cortex.2016.09.019. Epub 2016 Sep 30.
Inhibition is considered a key mechanism in schizophrenia. Short-latency intracortical inhibition (SICI) in the motor cortex is reduced in schizophrenia and is considered to reflect locally deficient γ-aminobutyric acid (GABA)-ergic modulation. However, it remains unclear how SICI is modulated during motor inhibition and how it relates to neural processing in other cortical areas. Here we studied motor inhibition Stop signal task (SST) in stabilized patients with schizophrenia (N = 28), healthy siblings (N = 21) and healthy controls (n = 31) matched in general cognitive status and educational level. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) were used to investigate neural correlates of motor inhibition. SST performance was similar in patients and controls. SICI was modulated by the task as expected in healthy controls and siblings but was reduced in patients with schizophrenia during inhibition despite equivalent motor inhibition performance. fMRI showed greater prefrontal and premotor activation during motor inhibition in schizophrenia. Task-related modulation of SICI was higher in subjects who showed less inhibition-related activity in pre-supplementary motor area (SMA) and cingulate motor area. An exploratory genetic analysis of selected markers of inhibition (GABRB2, GAD1, GRM1, and GRM3) did not explain task-related differences in SICI or cortical activation. In conclusion, this multimodal study provides direct evidence of a task-related deficiency in SICI modulation in schizophrenia likely reflecting deficient GABA-A related processing in motor cortex. Compensatory activation of premotor areas may explain similar motor inhibition in patients despite local deficits in intracortical processing. Task-related modulation of SICI may serve as a useful non-invasive GABAergic marker in development of therapeutic strategies in schizophrenia.
抑制作用被认为是精神分裂症的关键机制。精神分裂症患者运动皮层的短潜伏期皮层内抑制（SICI）降低，被认为反映了局部γ-氨基丁酸（GABA）能调节功能不足。然而，目前尚不清楚SICI在运动抑制过程中是如何被调节的，以及它与其他皮层区域的神经处理有何关系。在此，我们对精神分裂症稳定期患者（N = 28）、健康同胞（N = 21）和健康对照者（n = 31）进行了运动抑制停止信号任务（SST）研究，这些参与者在一般认知状态和教育水平上相匹配。采用经颅磁刺激（TMS）和功能磁共振成像（fMRI）来研究运动抑制的神经相关性。患者和对照者的SST表现相似。在健康对照者和同胞中，SICI如预期那样受任务调节，但在精神分裂症患者中，尽管运动抑制表现相当，但在抑制过程中SICI降低。fMRI显示，精神分裂症患者在运动抑制期间前额叶和运动前区激活增强。在辅助运动区（SMA）和扣带回运动区显示出较少抑制相关活动的受试者中，SICI的任务相关调节更高。对选定的抑制标记物（GABRB2、GAD1、GRM1和GRM3）进行的探索性基因分析未能解释SICI或皮层激活的任务相关差异。总之，这项多模态研究提供了直接证据，表明精神分裂症患者存在与任务相关的SICI调节缺陷，这可能反映了运动皮层中与GABA-A相关的处理功能不足。运动前区的代偿性激活可能解释了尽管患者皮层内处理存在局部缺陷，但仍能实现类似的运动抑制。SICI的任务相关调节可能作为精神分裂症治疗策略开发中一种有用的非侵入性GABA能标记物。
