Efficacy and Mechanisms of Transcranial Direct Current Stimulation (tDCS) - Effects on Working Memory in Schizophrenia
试验速览
- 阶段
- 不适用
- 入组人数
- 128
- 试验地点
- 3
- 主要终点
- Change of dprime
研究概览
简要总结
Impairments of cognition are a core, severely disabling feature of schizophrenia leading to poor long-term outcome with no established treatment available.
Particularly impaired executive functions (e.g working memory) are frequently observed and are consistently associated with reduced activation of the dorsolateral prefrontal cortex (dlPFC). Deficits in those functions have been shown to be closely related to negative symptoms, thought disorder, and functional outcome in schizophrenia leading to the notion that frontal lobe dysfunction is crucially important in schizophrenic psychopathology.
Noninvasive brain stimulation like tDCS can enhance executive functions like working memory in healthy subjects as well as in patients. To identify the optimal parameters for this intervention in patients with schizophrenia, the investigators first test the effects of different polarities (anodal, cathodal), stimulation intensities (1mA, 2mA) and laterality (left, right) on working-memory performance (nback task) in a sham-controlled cross-over design (n=128). To elucidate mechanisms of action, oscillatory brain activity will be registered with electroencephalography (EEG).
These experiments will provide reliable data for an evidence-based development of new clinical interventions to improve treatment of cognitive deficits in patients with schizophrenia and thus enhance schizophrenia prevention and recovery.
详细描述
- Working hypothesis:
In patients with subacute schizophrenia, transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex (dlPFC) exerts lasting beneficial effects on working-memory performance. 2. Research question(s):
In patients with remitted early phase schizophrenia, this research project aims at providing evidence for:
i) immediate improvement of working-memory performance by application of tDCS to the dlPFC in patients with schizophrenia; ii) determination of the optimal stimulation polarity, dosage and localization; iii) neurophysiological mechanisms (modulation in oscillatory activity and functional connectivity) and predictors of tDCS effects; iv) modulating effect of gender on the malleability of executive functions with tDCS. 3. Previous work of the investigators:
The investigators have provided proof-of principle evidence for persisting improvement of cognitive planning by a polarity-specific learning-stage dependent coupling of training and stimulation. The investigators have demonstrated that working memory and deficient cognitive control can be enhanced with anodal tDCS in depression and that the effects of tDCS are modulated by genetic polymorphisms. The investigators were the first to show impaired cortical plasticity following tDCS in schizophrenia patients at different disease states. Finally, the investigators have just successfully finished the world-wide largest clinical trial investigating the efficacy of non-invasive brain stimulation (rTMS) on negative symptoms in schizophrenia (DFG 241/10-1, Falkai, Hasan). 4. Aims and work plan:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •diagnosed schizophrenia (DSM-V)
- •age (18 - 60 years)
- •right handedness
- •stable medication during 1 week of treatment and 1 week before
排除标准
- •history of seizures
- •metal device throughout the body
- •pregnancy
- •use of anticonvulsive medication
- •use of benzodiazepines more than 1 mg of Lorazepam equivalent
- •current substance abuse (nicotine excluded)
结局指标
主要结局
Change of dprime
时间窗: Assessment during stimulation in a n-back task at three specific timepoints during one week
dprime provides the separation between the means of the signal and the noise distributions, compared against the standard deviation of the signal plus noise distributions
次要结局
- Change of reaction time in n-back task(Assessment during stimulation in a n-back task at three specific timepoints during one week)
研究者
Christian Plewnia, MD
Prof. Dr.
University Hospital Tuebingen