小脑蚓部间歇性 theta 爆发刺激增强以阴性症状为主的精神分裂症患者额-小脑静息状态功能连接：一项随机对照试验。
Intermittent theta burst stimulation of cerebellar vermis enhances fronto-cerebellar resting state functional connectivity in schizophrenia with predominant negative symptoms: A randomized controlled trial.
机构信息
Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India.
Department of Neuro Imaging and Interventional Radiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India.
出版信息
Schizophr Res. 2021 Dec;238:108-120. doi: 10.1016/j.schres.2021.10.005. Epub 2021 Oct 12.
OBJECTIVE
Negative symptoms of schizophrenia are substantially disabling and treatment resistant. Novel treatments like repetitive transcranial magnetic stimulation (TMS) need to be examined for the same using the experimental medicine approach that incorporates tests of mechanism of action in addition to clinical efficacy in trials.
METHODS
Study was a double-blind, parallel, randomized, sham-controlled trial recruiting schizophrenia with at least a moderate severity of negative symptoms. Participants were randomized to real or sham intermittent theta burst stimulation (iTBS) under MRI-guided neuro-navigation, targeting the cerebellar vermis area VII-B, at a stimulus intensity of 100% active motor threshold, two sessions/day for five days (total = 6000 pulses). Assessments were conducted at baseline (T0), day-6 (T1) and week-6 (T2) after initiation of intervention. Main outcomes were, a) Scale for the Assessment of Negative Symptoms (SANS) score (T0, T1, T2), b) fronto-cerebellar resting state functional connectivity (RSFC) (T0, T1).
RESULTS
Thirty participants were recruited in each arm. Negative symptoms improved in both arms (p < 0.001) but was not significantly different between the two arms (p = 0.602). RSFC significantly increased between the cerebellar vermis and the right inferior frontal gyrus (p = 0.033), right pallidum (p = 0.042) and right frontal pole (p = 0.047) in the real arm with no change in the sham arm.
CONCLUSION
Cerebellar vermal iTBS engaged a target belonging to the class of cerebello-subcortical-cortical networks, implicated in negative symptoms of schizophrenia. However, this did not translate to a superior clinical efficacy. Future trials should employ enhanced midline cerebellar TMS stimulation parameters for longer durations that can potentiate and translate biological changes into clinical effects.
目的
精神分裂症的阴性症状严重致残且治疗抵抗。需要采用实验医学方法来检查新型治疗方法，如重复经颅磁刺激（TMS），该方法除了临床试验中的临床疗效外，还需要结合作用机制的测试。
方法
这项研究是一项双盲、平行、随机、假对照试验，招募了至少有中度严重阴性症状的精神分裂症患者。参与者随机分为真刺激或假刺激间歇性经颅磁刺激（iTBS），在 MRI 引导的神经导航下，靶向小脑蚓部 VII-B 区，刺激强度为 100%主动运动阈值，每天两次，连续五天（共 6000 个脉冲）。评估在干预开始前的基线（T0）、第 6 天（T1）和第 6 周（T2）进行。主要结果是：a）阴性症状评定量表（SANS）评分（T0、T1、T2），b）额-小脑静息状态功能连接（RSFC）（T0、T1）。
结果
每个臂招募了 30 名参与者。两组的阴性症状均有所改善（p<0.001），但两组之间无显著差异（p=0.602）。真刺激组小脑蚓部与右侧额下回（p=0.033）、右侧苍白球（p=0.042）和右侧额极（p=0.047）之间的 RSFC显著增加，而假刺激组则无变化。
结论
小脑蚓部 iTBS 刺激了属于小脑-皮质下-皮质网络的靶点，该网络与精神分裂症的阴性症状有关。然而，这并没有转化为更好的临床疗效。未来的试验应该采用增强的中线小脑 TMS 刺激参数，持续更长时间，以增强和转化生物学变化为临床效果。
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