Transcranial magnetic stimulation of left temporoparietal cortex and medication-resistant auditory hallucinations

BACKGROUND: Neuroimaging studies suggest that auditory hallucinations (AHs) of speech arise, at least in part, from activation of brain areas underlying speech perception. One-hertz repetitive transcranial magnetic stimulation (rTMS) produces sustained reductions in cortical activation. Recent results of 4-day administration of 1-Hz rTMS to left temporoparietal cortex were superior to those of sham stimulation in reducing AHs. We sought to determine if a more extended trial of rTMS could significantly reduce AHs that were resistant to antipsychotic medication. METHODS: Twenty-four patients with schizophrenia or schizoaffective disorder and medication-resistant AHs were randomly allocated to receive rTMS or sham stimulation for 9 days at 90% of motor threshold. Patients receiving sham stimulation were subsequently offered an open-label trial of rTMS. Neuropsychological assessments were administered at baseline and during and following each arm of the trial. RESULTS: Auditory hallucinations were robustly improved with rTMS relative to sham stimulation. Frequency and attentional salience were the 2 aspects of hallucinatory experience that showed greatest improvement. Duration of putative treatment effects ranged widely, with 52% of patients maintaining improvement for at least 15 weeks. Repetitive transcranial magnetic stimulation was well tolerated, without evidence of neuropsychological impairment. CONCLUSIONS: These data suggest that the mechanism of AHs involves activation of the left temporoparietal cortex. One-hertz rTMS deserves additional study as a possible treatment for this syndrome.     

低频重复经颅磁刺激治疗精神分裂症慢性幻听的疗效及随访研究

目的研究低频重复经颅磁刺激（rTMS）对精神分裂症难治性慢性幻听症状的疗效。方法将46例精神分裂症伴慢性幻听患者随机分为研究组（23例）和对照组（23例）。研究组在原有抗精神病药物种类及剂量不变的同时给予经左侧颞顶叶的2周共10次低频（1Hz）rTMS刺激,对照组采用假rTMS刺激。治疗前后对两组分别进行AHRS听幻觉量表及临床疗效总评量表（CGI）评定幻听症状的变化,并对治疗有效者于3个月后随访。结果研究组治疗前、后AHRS评分分别为（8．1±2．5）和（3．5±1．5）;对照组为（7．8±2．6）和（6．5±2．1）,研究组疗效明显优于对照组（F=20．3,P〈0．05）。所有患者均完成试验,未见有严重的副反应出现。结论低频rTMS治疗精神分裂症难治性慢性幻听症状,疗效肯定且安全性好。     

Transcranial magnetic stimulation of left temporoparietal cortex in three patients reporting hallucinated "voices".

BACKGROUND: Prior studies suggest that auditory hallucinations of "voices" arise from activation of speech perception areas of the cerebral cortex. Low frequency transcranial magnetic stimulation (TMS) can reduce cortical activation. METHODS: We have studied three schizophrenic patients reporting persistent auditory hallucinations to determine if low frequency TMS could curtail these experiences. One hertz stimulation of left temporoparietal cortex was compared with sham stimulation using a double-blind, cross-over design. RESULTS: All three patients demonstrated greater improvement in hallucination severity following active stimulation compared to sham stimulation. Two of the three patients reported near total cessation of hallucinations for > or = 2 weeks. CONCLUSIONS: TMS may advance our understanding of the mechanism and treatment of auditory hallucinations.     

低频重复经颅磁刺激治疗精神分裂症顽固性幻听的临床研究

目的：研究左侧颞顶区低频（1Hz）重复经颅磁刺激（rTMS）治疗伴有顽固性言语性幻听的精神分裂症的疗效。方法：将35例伴有顽固言语性幻听的精神分裂症患者随机分为研究组18例和对照组17例。在原有抗精神病药种类及剂量不变的基础上,研究组给予左侧颞顶区频率为1Hz的真性rTMS刺激2周共10次,对照组给予相应的假性刺激。两组治疗前后均采用阳性与阴性症状量表（PANSS）评定其总体临床症状及幻听的变化,并进行威斯康星卡片分类测验（WCST）及听觉注意力测验（CPT）。结果：35例患者均完成治疗,研究组治疗前后幻听评分分别为（4．89±1．18）分和（3．00±1．75）分,对照组治疗前后幻听评分分别为（4．88±1．11）分和（4．24±1．20）分（F=7．72,P=0．009）。研究组有效率77．8％显著优于对照组41．2％（P=0．041）。治疗后两组问PANSS评分除阴性症状外其他各项评分改善差异均有显著性（P〈0．05）。WCST和CFF评分治疗后两组间差异无显著性（P〉0．05）。结论：左侧颞顶区rTMS对于幻听具有较肯定的治疗作用,并且能够改善精神分裂症患者的总体精神病性症状。在一定程度上能够改善患者的认知功能,但尚无确切疗效。     

A pilot double-blind sham-controlled trial of repetitive transcranial magnetic stimulation for patients with refractory schizophrenia treated with clozapine

Schizophrenia is a complex and heterogeneous psychiatric disorder. Auditory verbal hallucinations occur in 50-70% of patients with schizophrenia and are associated with significant distress, decreased quality of life and impaired social functioning. This study aimed to investigate the effects of active compared with sham 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied to the left temporal-parietal cortex in patients with schizophrenia treated with clozapine. Symptom dimensions that were evaluated included general psychopathology, severity of auditory hallucinations, quality of life and functionality. Seventeen right-handed patients with refractory schizophrenia experiencing auditory verbal hallucinations and treated with clozapine were randomly allocated to receive either active rTMS or sham stimulation. A total of 384 min of rTMS was administered over 20 days using a double-masked, sham-controlled, parallel design. There was a significant reduction in Brief Psychiatric Rating Scale (BPRS) scores in the active group compared with the sham group. There was no significant difference between active and sham rTMS on Quality of Life Scale (QLS), Auditory Hallucinations Rating Scale (AHRS), Clinical Global Impressions (CGI) and functional assessment staging (FAST) scores. Compared with sham stimulation, active rTMS of the left temporoparietal cortex in clozapine-treated patients showed a positive effect on general psychopathology. However, there was no effect on refractory auditory hallucinations. Further studies with larger sample sizes are needed to confirm these findings.     

Slow transcranial magnetic stimulation can rapidly reduce resistant auditory hallucinations in schizophrenia.

BACKGROUND: Almost a quarter of patients with schizophrenia present with resistant auditory verbal hallucinations (AVH), a phenomenon that may relate to activation of brain areas underlying speech perception. Repetitive transcranial magnetic stimulation (rTMS) at 1 Hz reduces cortical activation, and recent results have shown that 1-Hz left temporoparietal rTMS may reduce AVH. The aim of this study was to replicate recent data and investigate whether low-frequency rTMS with a high total stimulation number delivered in a shorter 5-day block produces similar benefit. METHODS: Ten right-handed schizophrenia patients with resistant AVH received 5 days of active rTMS and 5 days of sham rTMS (2,000 stimulations per day at 90% of motor threshold) over the left temporoparietal cortex in a double-blind crossover design. The two weeks of stimulation were separated by a 1-week washout period. RESULTS: AVH were robustly improved (56%) by 5 days active rTMS, whereas no variation was observed after sham. Seven patients were responders to active treatment, five of whom maintained improvement for at least 2 months. CONCLUSIONS: These data confirm the efficiency of low-frequency rTMS applied to the left temporoparietal cortex, compared with sham stimulation, in reducing resistant AVH. This improvement can be obtained in only 5 days without serious initial adverse events.     

Low frequency repetitive transcranial magnetic stimulation improves source monitoring deficit in hallucinating patients with schizophrenia

Auditory hallucinations have been associated with a disruption in monitoring one's own speech suggesting an autonoetic agnosia in schizophrenia. This deficit can be measured by a source monitoring task. Low frequency transcranial magnetic stimulations (rTMS) applied to the left temporoparietal cortex can inhibit cortical areas involved both in autonoetic agnosia (which means 'the inability to identify self-generated mental events') and in auditory hallucinations (AH) phenomena. Although improvements in AH have been repeatedly reported following rTMS treatment, effects on autonoetic agnosia measured by source monitoring have never been investigated. We aimed to investigate the relation between improvements in AH and source monitoring performance after rTMS treatment. Twenty four right-handed refractory schizophrenic patients with hallucinations randomly received sham or active 10.0001-Hz rTMS to the left temporoparietal cortex and performed 2 source monitoring tasks requiring discrimination between silent- and overt-reading words before and after rTMS sessions. Compared to sham, active rTMS significantly improved AH. Source monitoring performances and the improvements tended to correlate, which would support a specific relation between autonoetic agnosia and auditory hallucinations.     

A systematic review and meta-analysis of the use of repetitive transcranial magnetic stimulation for auditory hallucinations treatment in refractory schizophrenic patients

Background. The use of repetitive transcranial magnetic stimulation (rTMS) remains a promising therapeutic tool in the treatment of schizophrenia. Symptoms such as auditory hallucinations (AH) find contradictory results in many studies. Here we present an up-to-date systematic review and meta-analysis of rTMS in the treatment of AH in schizophrenia. Methods. We searched Pubmed-MEDLINE from 1999 to 2013 for double-blinded randomized sham-controlled trials that applied slow rTMS on the left temporoparietal cortex and assessed the outcome results using Hallucination Change Scale or Auditory Hallucination Rating Scale or Scale for Auditory Hallucinations (SAH). We identified 10 studies suitable for the meta-analysis. Results. We found a positive sized effect in favor of rTMS [random-effects model Hedges’ g = 0.011, I-squared = 58.1%]. There was some variability between study effect sizes, but the sensitivity analysis concluded that none of them had sufficient weight to singularly alter the results of our meta-analysis. Discussion. rTMS appears to be an effective treatment for AH. The left temporoparietal cortex seems to be the area in which rTMS is effective. Although meta-analysis is a powerful analytical tool, more studies must be conducted in order to obtain a more expressive sample size to perform a more accurate analytical approach.     

不同部位低频重复经颅磁刺激治疗顽固性幻听起效时间和安全性的双盲对照研究

目的 初步探讨背外侧前额叶和左侧颞顶叶低频重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)治疗精神分裂症顽固性幻听的疗效(起效时间)和安全性.方法 36例伴有顽固性幻听的精神分裂症患者随机分为三组,分别为背外侧前额叶rTMS治疗组(n1 =12)、左侧颞顶叶rTMS治疗组(n2=14)及对照组(假性刺激)(n3=10),背外侧前额叶rTMS治疗组、左侧颞顶叶rTMS治疗组分别给予10次1 Hz rTMS真性刺激,对照组给予假刺激,治疗期间维持原有抗精神病药种类及剂量不变.采用阳性和阴性症状量表(Positive and Negative Syndrome Scale,PANSS)评定临床症状,不良反应症状量表(Treatment Emergent Symptom Scale,TESS)、纯音听力测试评估副反应.结果 两个真性治疗组疗效均明显优于假性治疗组,与基线比较,背外侧前额叶组第4次评估、左侧颞顶叶组第7次评估出现统计学差异,两个治疗组比较差异无统计学意义.无论治疗组、对照组均未观察到明显的副反应.结论 1 Hz背外侧前额叶、左侧颞顶叶低频重复经颅磁刺激治疗精神分裂症顽固性幻听均有效,且安全性高.     

Should we treat auditory hallucinations with repetitive transcranial magnetic stimulation? A metaanalysis

Objective: Abnormal activations of neural networks implicated in auditory stimuli processing are hypothesized to generate auditory hallucinations (AH) in schizophrenia spectrum disorders. Because repetitive transcranial magnetic stimulation (rTMS) has the potential to modulate neural network activity, several studies have explored its use in treating medication-resistant AH, with mixed results in small-to-medium patient samples. Our aim is to apply a metaanalytic approach to exploring the efficacy of rTMS in treating medication-resistant AH. Method: A search of the electronic databases for studies comparing low-frequency (1 Hz) rTMS over the left temporoparietal cortex to sham stimulation in patients suffering from medication- resistant AH was performed. Our search was completed by cross-referencing the articles, searching the Current Controlled Trials website, and direct contact with relevant researchers. Results: From 265 possible abstracts, 6 parallel-arm, double-blind placebo-controlled and 4 crossover controlled trials, all randomized, matched the inclusion and exclusion criteria (n = 232). The primary outcome measure (effect of active treatment on AH at the end of the treatment) was tested with a random effect model and reached a significant homogeneous ES estimate (Hedges' g = 0.514; P = 0.001; 95CI%, 0.225 to 0.804; Q = 13.022; P = 0.162). Conclusions: We found that low-frequency rTMS over the left temporoparietal cortex has a medium ES action on medication-resistant AH. This result has implications for understanding the pathophysiology of psychotic symptoms (specifically AH) and supports the use of rTMS as a complementary treatment approach in patients suffering from treatment-resistant AH.     

MRI-targeted repetitive transcranial magnetic stimulation of Heschl's gyrus for refractory auditory hallucinations

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has shown promise as a treatment for refractory auditory hallucinations (AH) in Schizophrenia. Most previous studies have examined the effect of low frequency, left-sided stimulation (LFL) (1 Hz) to the temporoparietal cortex (TPC). Priming stimulation (6 Hz) prior to LFL stimulation (hereby simply referred to as priming) has been shown to enhance the neurophysiological effects of LFL rTMS alone and, as such, may lead to greater attenuation of AH.ObjectiveTherefore, this study evaluated the efficacy of priming rTMS and LFL rTMS compared to sham rTMS using MRI targeting of Heschl’s gyrus (HG) within the TPC of subjects with SCZ experiencing refractory auditory hallucinations (AH).MethodsSubjects between the ages of 18 and 65 were recruited from a tertiary care university hospital. Fifty-four subjects with medication resistant AH were randomized to receive LFL, priming, or sham rTMS for 20 treatments. The primary outcome was reduction of hallucinatory symptoms as indexed by response rates on the Psychotic Symptoms Rating Scale (PSYRATS).ResultsThe response rates did not differ among the three treatment groups using an intention to treat analysis. The response rates did not differ in any of the secondary outcome measures. The treatment was well tolerated with minimal adverse effects including no changes in cognition during the study.ConclusionThese findings suggest that neither priming nor LFL rTMS of Heschl’s gyrus are effective at ameliorating refractory AH in schizophrenia.ClinicalTrials.gov Identifier: NCT01386918     

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 January1985 to May 2012.Key words were"transcranial magnetic stimulation","TMS","repetitive transcranial magnetic stimulation",and"hallucination".STUDY SELECTION:Selected studies were randomized controlled trials assessing therapeutic efficacy 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 repetitive transcranial magnetic stimulation versus sham stimulation was statistically significant(MD=–0.42,95%CI:–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%CI: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 repetitive 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.     

An evoked auditory response fMRI study of the effects of rTMS on putative AVH pathways in healthy volunteers

Background

Auditory verbal hallucinations (AVH) are the most prevalent symptom in schizophrenia. They are associated with increased activation within the temporoparietal cortices and are refractory to pharmacological and psychological treatment in approximately 25% of patients. Low frequency repetitive transcranial magnetic stimulation (rTMS) over the temporoparietal cortex has been demonstrated to be effective in reducing AVH in some patients, although results have varied. The cortical mechanism by which rTMS exerts its effects remain unknown, although data from the motor system is suggestive of a local cortical inhibitory effect. We explored neuroimaging differences in healthy volunteers between application of a clinically utilized rTMS protocol and a sham rTMS equivalent when undertaking a prosodic auditory task.

Method

Single-blind placebo controlled fMRI study of 24 healthy volunteers undertaking an auditory temporoparietal activation task, who received either right temporoparietal rTMS or sham RTMS.

Results

The main effect of group was bilateral inferior parietal deactivation following real rTMS. An interaction of group and task type showed deactivation during real rTMS in the right superior temporal gyrus (STG), left thalamus, left postcentral gyrus and cerebellum. However, the left parietal lobe showed an increase in activation following right sided real rTMS, but this increase was specific to a non-linguistic, tone-sequence task.

Conclusion

rTMS does cause local inhibitory effects, not only in the underlying region of application, but also in functionally connected cortical regions. However, there is also a related, task dependent, increase in activation within selected cortical areas in the contralateral hemisphere; these are likely to reflect compensatory mechanisms, and such cortical activation may in some cases contribute to, or retard, some of the therapeutic effects seen with rTMS.     

Successful suppression of musical hallucinations with low-frequency rTMS of the left temporo-parietal junction: A case report

BackgroundInhibitory low frequency repetitive transcranial magnetic stimulation (rTMS) of the temporo-parietal area has been applied to treat both auditory verbal hallucinations as well as tinnitus.ObjectiveWe hypothesized that 1 Hz rTMS to the left temporoparietal junction (TPJ) may be beneficial in alleviating musical hallucinations (MH), another condition with auditory experiences in the absence of an external source.MethodsHere we describe a patient with almost insufferable life-long MH with comorbid depression, who received inhibitory rTMS to the left TPJ as well as the right dorsolateral prefrontal cortex (DLPFC).ResultsThe intrusiveness and frequency of her MH as well as her depressive symptoms alleviated quickly and substantially, and once-a-week maintenance therapy with rTMS seemed to preserve this amelioration. Future studies will hopefully reveal whether this is a viable treatment approach for other patients suffering from MH with or without comorbid depression.     

Hearing Safety of Long-Term Treatment with Theta Burst Stimulation

BackgroundRepetitive transcranial magnetic stimulation (rTMS) for the experimental treatment of tinnitus or auditory hallucinations aims at a modulation of cortical activity in areas of auditory perception and processing. Continuous theta burst stimulation (cTBS) is a patterned rTMS paradigm with lower stimulation intensity and shorter stimulus duration that is increasingly used for the optimization of rTMS-treatment paradigms. Possible interference with physiological brain function and the noise emitted by the rTMS device might induce relevant unwanted impairment of hearing and speech perception.Objective/HypothesisHere, we investigate the audiological safety of long-term, bilateral cTBS for the treatment of auditory phantom perception.MethodsForty-eight patients with chronic tinnitus were treated for four weeks with bilateral continuous theta burst stimulation to the temporal (n = 16), temporoparietal (n = 16) or a non-cortical control (n = 16) site. Measurements in these patients were obtained before and four weeks after treatment. The rTMS-induced noise was measured at various frequency levels.ResultsNo evidence was found for auditory threshold shifts or alterations in the perception of speech in quiet or in background noise by bilateral, long-term theta burst stimulation to the temporal or temporoparietal cortex with a loudness of up to 84 dB SPL (A).ConclusionsTheta burst stimulation of the temporal and temporoparietal cortex appears to be safe with respect to hearing and speech perception. These data provide evidence for the audiological safety of rTMS in the experimental treatment of auditory phantom perception.     

Auditory/Verbal hallucinations, speech perception neurocircuitry, and the social deafferentation hypothesis.

Auditory/verbal hallucinations (AVHs) are comprised of spoken conversational speech seeming to arise from specific, nonself speakers. One hertz repetitive transcranial magnetic stimulation (rTMS) reduces excitability in the brain region stimulated. Studies utilizing 1-Hz rTMS delivered to the left temporoparietal cortex, a brain area critical to speech perception, have demonstrated statistically significant improvements in AVHs relative to sham simulation. A novel mechanism of AVHs is proposed whereby dramatic pre-psychotic social withdrawal prompts neuroplastic reorganization by the "social brain" to produce spurious social meaning via hallucinations of conversational speech. Preliminary evidence supporting this hypothesis includes a very high rate of social withdrawal emerging prior to the onset of frank psychosis in patients who develop schizophrenia and AVHs. Moreover, reduced AVHs elicited by temporoparietal 1-Hz rTMS are likely to reflect enhanced long-term depression. Some evidence suggests a loss of long-term depression following experimentally-induced deafferentation. Finally, abnormal cortico-cortical coupling is associated with AVHs and also is a common outcome of deafferentation. Auditory/verbal hallucinations (AVHs) of spoken speech or "voices" are reported by 60-80% of persons with schizophrenia at various times during the course of illness. AVHs are associated with high levels of distress, functional disability, and can lead to violent acts. Among patients with AVHs, these symptoms remain poorly or incompletely responsive to currently available treatments in approximately 25% of cases. For patients with AVHs who do respond to antipsychotic drugs, there is a very high likelihood that these experiences will recur in subsequent episodes. A more precise characterization of underlying pathophysiology may lead to more efficacious treatments.     

A preliminary fMRI study of the effects on cortical activation of the treatment of refractory auditory hallucinations with rTMS

Three patients underwent fMRI during a word generation task before and after successful treatment of auditory hallucinations with rTMS and were compared to four control subjects. There was a significant increase and more normal task related brain activation in brain areas involved in language processing including left temporoparietal cortex after rTMS treatment.     

Treating auditory hallucinations by transcranial magnetic stimulation: a randomized controlled cross-over trial

BACKGROUND: In a previous functional magnetic resonance imaging study, the authors succeeded in demonstrating the activation of Heschl's gyrus during auditory hallucinations (AH). OBJECTIVES: This study aims to treat AH specifically by repetitive transcranial magnetic stimulation (rTMS). METHODS: 16 patients with AH were included in a randomized, cross-over, sham-controlled trial. 1 Hz rTMS was administered over the left and right temporo-parietal cortex and sham position, respectively, on 5 consecutive days; 900 stimuli each, strength 100% of motor threshold. Using the Psychotic Symptom Rating Scales (PSYRATS), the hallucinations during the stimulation periods and 4-week follow-ups were quantified. Electroencephalograms (EEG) were acquired before and after each period. RESULTS: Treatment responses were observed after left hemisphere rTMS only. The 5 patients who showed a response did so already after 2 days. However, group mean hallucination scores did not differ across treatment conditions. No significant changes were found in EEG after rTMS. CONCLUSIONS: A subgroup of patients suffering from AH benefits soon after treatment start from rTMS over the left superior temporal gyrus as revealed by the decrease of AH scores compared to right-sided and sham procedures.     

A Negative Pilot Study of Daily Bimodal Transcranial Direct Current Stimulation in Schizophrenia

BackgroundA small number of studies conducted to date have suggested that transcranial direct current stimulation (tDCS) applied to the temporoparietal cortex may reduce auditory hallucinations in patients with schizophrenia. Prefrontal brain stimulation with other methods, has also been shown to potentially improve the negative symptoms of this disorder.ObjectiveTo investigate the therapeutic potential of daily bimodal tDCS: anodal stimulation to the prefrontal cortex and cathodal stimulation to the temporoparietal junction in patients with persistent hallucinations and negative symptoms of schizophrenia.MethodsWe conducted two small randomized double-blind controlled trials comparing bimodal tDCS to sham stimulation. In one study, stimulation was provided unilaterally, in the second study it was provided bilaterally.ResultsNeither unilateral nor bilateral tDCS resulted in a substantial change in either hallucinations or negative symptoms. Stimulation was well tolerated without side-effects.ConclusionDaily tDCS does not appear to have substantial potential in the treatment of hallucinations or negative symptoms and further research should investigate higher doses of stimulation or more frequently applied treatment schedules.     

Transcranial magnetic stimulation in the treatment of schizophrenic symptoms: a double blind sham controlled study

BACKGROUND: Schizophrenia is a disabling disease with a significant proportion of patients experiencing persistent symptoms. Repetitive transcranial magnetic stimulation (rTMS) is a promising new therapeutic tool that could benefit to schizophrenic patients. In this study we sought to assess the efficacy of active rTMS compared to sham stimulation in the treatment of patients with schizophrenia. METHOD: Eighteen schizophrenic patients according to DSM-IV criteria were randomly allocated to receive active or sham rTMS for 10 days over the left temporoparietal cortex (80% of the motor threshold, 1Hz, five trains of 1 min). Psychopathological dimensions were measured with the positive and negative syndrome scale and clinical global impression at baseline and after 10 session of rTMS. RESULTS: All patients were improved at the end of the trial but no significant group differences were found. Patients receiving sham stimulation showed the same pattern of improvement compared to active condition on all the subscales of the positive and negative syndrome scale and clinical global impression scores (p>0.05). CONCLUSION: In our study, active rTMS failed to show superiority over sham stimulation in the treatment of schizophrenic symptoms. Although previous results have shown that rTMS reduces auditory hallucination, its efficacy on other positive schizophrenic symptoms is not yet established. Nevertheless, the results of our study, even though negative, provide further insights in the pathophysiology of schizophrenia.