Treatment of refractory auditory hallucinations in schizophrenia by rTMS: Positive impact of negative double blind controlled study

Background: Several studies reported on the effectiveness of 1 Hz repeated transcranial magnetic stimulation (rTMS) over the temporoparietal cortex (TPC) on refractory auditory hallucinations (AH) in schizophrenia but little is known about the long-term therapeutic effect of this tool. Aim: The aim of this study was to evaluate rTMS’ impact on auditory hallucinations (AH) and cognitive functions in patients with schizophrenia with a three-month follow-up. Methods: In a randomized double blind sham controlled study, 26 patients with refractory schizophrenia received 1 Hz rTMS applied on TPC for four weeks. rTMS was given to patients over one month with five rTMS sessions each week. Patients were evaluated via AHRS (Auditory Hallucination Rating Scale, Hoffman et al.), PANSS (Positive and Negative Syndrome Scale, Kay et al. 1988), and CGI (Clinical Global Impression) before treatment by rTMS every week during the first month, and every month until the third month. Results: Neither clinical nor cognitive differences were found between rTMS and placebo. Conclusion: 1 Hz rTMS using parameters mentioned above has no statistically significant effect on AH;although evidences about the potential benefit of rTMS in the treatment of AH negative results suggest the need for further studies in this area.

Transcranial direct current stimulation for auditory verbal hallucinations:a systematic review of clinical trials

Transcranial direct current stimulation(tDCS)has been reportedly beneficial for different neurodegenerative disorders.tDCS has been reported as a potential adjunctive or alternative treatment for auditory verbal hallucination(AVH).This study aims to review the effects of tDCS on AVH in patients with schizophrenia through combining the evidence from randomized clinical trials(RCTs).The databases of PsycINFO(2000–2019),PubMed(2000–2019),EMBASE(2000–2019),CINAHL(2000–2019),Web of Science(2000–2019),and Scopus(2000–2019)were systematically searched.The clinical trials with RCT design were selected for final analysis.A total of nine RCTs were eligible and included in the review.Nine RCTs were included in the final analysis.Among them,six RCTs reported a significant reduction of AVH after repeated sessions of tDCS,whereas three RCTs did not show any advantage of active tDCS over sham tDCS.The current studies showed an overall decrease of approximately 28%of AVH after active tDCS and 10%after sham tDCS.The tDCS protocols targeting the sensorimotor frontal-parietal network showed greater treatment effects compared with the protocols targeting other regions.In this regard,cathodal tDCS over the left temporoparietal area showed inhibitory effects on AVHs.The most effective tDCS protocol on AVHs was twice-daily sessions(2 mA,20-minute duration)over 5 consecutive days(10 sessions)with the anode over the left dorsolateral prefrontal cortex and the cathode over the left temporal area.Some patient-specific and diseasespecific factors such as young age,nonsmoking status,and higher frequencies of AVHs seemed to be the predictors of treatment response.Taken together,the results of tDCS as an alternative treatment option for AVH show controversy among current literatures,since not all studies were positive.However,the studies targeting the same site of the brain showed that the tDCS could be a promising treatment option to reduce AVH.Further RCTs,with larger sample sizes,should be conducted to reach a conclusion on the efficacy of tDCS for AVH and to develop an effective therapeutic protocol for clinical setting.

Repetitive transcranial magnetic stimulation for hallucination in schizophrenia spectrum disorders A meta-analysis

OBJECTIVE： This study assessed the efficacy and tolerability of repetitive transcranial magnetic stimulation for treatment of auditory hallucination of patients with schizophrenia spectrum disorders. DATA SOURCES： Online literature retrieval was conducted using PubMed, ISI Web of Science, EMBASE, Medline and Cochrane Central Register of Controlled Trials databases from January 1985 to May 2012. Key words were ＂transcranial magnetic stimulation＂, ＂TMS＂, ＂repetitive tran- scranial magnetic stimulation＂, and ＂hallucination＂. STUDY SELECTION： Selected studies were randomized controlled trials assessing therapeutic ef- ficacy of repetitive transcranial magnetic stimulation for hallucination in patients with schizophrenia spectrum disorders. Experimental intervention was low-frequency repetitive transcranial magnetic stimulation in left temporoparietal cortex for treatment of auditory hallucination in schizophrenia spectrum disorders. Control groups received sham stimulation. MAIN OUTCOME MEASURES： The primary outcome was total scores of Auditory Hallucinations Rating Scale, Auditory Hallucination Subscale of Psychotic Symptom Rating Scale, Positive and Negative Symptom Scale-Auditory Hallucination item, and Hallucination Change Scale. Secondary outcomes included response rate, global mental state, adverse effects and cognitive function. RESULTS： Seventeen studies addressing repetitive transcranial magnetic stimulation for treatment of schizophrenia spectrum disorders were screened, with controls receiving sham stimulation. All data were completely effective, involving 398 patients. Overall mean weighted effect size for repeti- tive transcranial magnetic stimulation versus sham stimulation was statistically significant （MD = -0.42, 95%C/： -0.64 to -0.20, P = 0.000 2）. Patients receiving repetitive transcranial magnetic stimulation responded more frequently than sham stimulation （OR = 2.94, 95%C/： 1.39 to 6.24, P =0.005）. No significant differences were found between active repetitive transcranial magnetic stimulation and sham stimulation for positive or negative symptoms. Compared with sham stimulation, active repeti- tive transcranial magnetic stimulation had equivocal outcome in cognitive function and commonly caused headache and facial muscle twitching. CONCLUSION： Repetitive transcranial magnetic stimulation is a safe and effective treatment for auditory hallucination in schizophrenia spectrum disorders,

精神分裂症幻听患者汉语听觉语言皮质定位的脑磁图研究

目的采用脑磁图(MEG)技术探讨男性精神分裂症幻听患者汉语听觉语言皮质的定位。方法给予13例精神分裂症幻听患者和14名正常对照组双耳男、女声各100对词义相关及不相关的二个字汉语词汇刺激,并由MEG设备记录刺激后产生的听觉诱发磁场,将MEG采集数据叠加到核磁共振上获得磁源性影像。结果①患者组10例汉语听觉语言皮质定位在大脑半球双侧颞中、上回后部、额下回后部,2例在右侧额下回后部,1例在左侧颞上回后部。对照组10名定位于左侧颞中、上回后部,即Wernicke区,2名定位于右侧颞中回后部,2名定位在双侧颞上回后部。患者组定位在双侧比例明显高于对照组(76.92%vs14.29%,2=2.88,P<0.05)。②无论男声或女声刺激,患者组与对照组的中枢三维坐标在X轴上差异均有统计学意义(P<0.05)。结论精神分裂症幻听患者的汉语语言皮质定位与正常人的位置不同,更靠近颞中、上回外侧部,这一改变可能是其听觉性语言认知功能障碍的神经病理学基础之一。

精神分裂症幻听患者初级听觉皮质的脑磁图研究

目的探讨在不同频率纯音刺激下男性精神分裂症幻听患者初级听觉皮质的脑磁图（MEG）定位。方法对均为右利手的10例男性精神分裂症幻听患者（研究组）和11名男性健康受试者（对照组），分别给予频率为0．5，2，4，8kHz的纯音刺激，强度90dB，持续200ms，刺激声间隔1s。用脑磁图设备记录刺激后产生的听觉诱发磁场，并将MEG资料叠加到核磁共振成像以获得磁源性影像。结果（1）对照组初级听觉皮质均定位于双侧颞横回；与对照组比较，研究组右侧初级听觉皮质位置更靠近颞横回外部，左侧明显偏向颞上回后外下部（P〈0．05）。（2）在分别给予2kHz和4kHz纯音刺激时，研究组大脑双侧M100潜伏期[2kHz：左（97±t6）ms，右（97±10）ms，4kHz：左（93±13）ms，右（99±14）ms]均短于对照组[2kHz：左（121±15）ms，右（113±6）ms，4kHz：左（113±13）ms，右（114±6）ms]（均P〈0．01），而波幅[2kHz：左（89±10）fT，右（118±37）fT，4kHz：左（81±9）fT，右（108±14）fT]高于对照组[2kHz：左（73±12）fT，右（79±13）fT，4kHz：左（69±14）fT，右（81±20）fT]（均P〈0．05—0．01）。结论男性精神分裂症幻听患者的初级听觉皮质位置与正常人不同，其M100波幅高，潜伏期短，这些功能及解剖结构的异常可能是精神分裂症幻听产生的病理生理机制之一。