Treating Working Memory Deficits in Patients With Schizophrenia Using Repetitive Transcranial Magnetic Stimulation (rTMS)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 122
- 试验地点
- 1
- 主要终点
- The primary outcome measure will be the performance on the N-back working memory task.
研究概览
简要总结
Deficits in working memory (WM) performance are the most significant cognitive impairments in schizophrenia (SCZ). It has also been shown that WM performance is contingent on the cortex synchronization, a process that relies on brain inhibition. Repetitive Transcranial Magnetic Stimulation (rTMS) has been demonstrated as an effective treatment for patients with SCZ and has been shown to increase brain inhibition and improve cognitive performance. In this study the investigators intend to:
- evaluate rTMS as a treatment for WM deficits in SCZ
- evaluate rTMS as a method to increase WM performance in healthy individuals
- determine if improvements in WM performance are related to enhanced synchronization of brain networks
- determine whether genetic polymorphisms predict cortical function and treatment response
- evaluate the influence of rTMS treatment on brain structure.
详细描述
To directly investigate whether enhanced gamma synchrony mediates rTMS enhancement of WM in patients with SCZ, and in healthy individuals the investigators propose the following study. The relationship between the improvements in WM performance and increased gamma synchrony following rTMS over the DLPFC will be investigated. Moreover, using statistical models, the investigators will further examine whether increased gamma synchrony mediates WM improvement in these patients. Therefore, in this study the investigators hope to clarify the neurophysiological mechanisms through which rTMS exerts its therapeutic effects on WM performance and develop rTMS as a novel therapeutic tool to enhance the treatment options available for one of the core cognitive deficits in this disorder.
There is considerable evidence to support the fact that WM deficits in schizophrenia are heritable and have a strong genetic component. This evidence emerges from genetic association studies, and studies demonstrating that unaffected relatives of schizophrenia patients also suffer WM deficits. Therefore, treatment response to rTMS may be at least partly contingent on genetic variation within each individual. In particular, GABAergic genes that code for GABAergic proteins which largely determine cortical inhibition may play a key role in treatment response to rTMS over the DLPFC. However, several other gene systems that interact with the GABAergic system may also play a role, and would also merit investigation. Similarly brain structure may also determine treatment response. For instance, volume or thickness of the DLPFC and DLPFC related circuitry has been shown to play a role in WM performance, and therefore, may be a biomarker of treatment response.
Objective 1: To improve WM in patients with SCZ, and in healthy individuals using rTMS.
Hypothesis 1:20 Hz rTMS over the DLPFC will be superior to sham stimulation in improving WM performance in patients with SCZ, and healthy individuals.
Objective 2: To evaluate if high frequency rTMS results in enhanced gamma synchrony SCZ and healthy individuals.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •for Schizophrenia Subjects:
- •Voluntary and competent to consent
- •SCID-IV Diagnosis of Schizophrenia or Schizoaffective Disorder
- •Between the ages of 18 and 85
- •Inclusion Criteria for Healthy Subjects:
- •voluntary and competent to consent
- •between the ages of 18-85
- •considered a healthy individual free of psychopathology based on the Personality Assessment Inventory
- •right-handed determined by the TMS screening and demographic form
- •self-reported non-smoker
- •do not have a self-reported concomitant major medical or neurologic illness
- •if a woman of childbearing potential, must be on an effective means of birth control determined through completion of the TMS screening and demographic form.
排除标准
- •for both Healthy Controls and Schizophrenia Subjects:
- •Have a DSM-IV history of substance abuse or dependence in the last 6 months
- •Have a concomitant major and unstable medical or neurologic illness
- •Have a history of seizures
- •Have a first degree relative with a history of a seizure disorder
- •Are pregnant
- •Have any clinically significant EEG activity indicating an increased risk of seizure, as confirmed by a neurologist.
研究组 & 干预措施
Active rTMS
Active treatment will be delivered at an intensity that is 90% of the RMT. Stimulation will be delivered at either 20 Hz or 10 Hz, depending on the patients' tolerance to the stimulation, with 50 stimulation trains of 30 stimuli each (i.e., 1500 stimuli) and an intertrain interval of 30 sec. 25 trains will be applied to to the left or right hemisphere followed by the other hemisphere.
干预措施: repetitive Transcranial Magnetic Stimulation (Device)
Sham rTMS
Sham stimulation will be delivered using the same stimulation parameters and at the site of active treatment, but with only the side-edge resting on the scalp. The coil will be angled 45 degrees away from the skull in a single-wing tilt position. This method produces sound and some somatic sensation (e.g., contraction of scalp muscles) similar to those of active stimulation, but with minimal direct brain effects.
干预措施: repetitive Transcranial Magnetic Stimulation (Device)
结局指标
主要结局
The primary outcome measure will be the performance on the N-back working memory task.
时间窗: 4 weeks
Specifically, we will evaluate if rTMS results in changes to the number of correct answers, omissions and errors as well as reaction times.
次要结局
- Increase in gamma band synchrony(4 weeks)
- Brain Imaging Changes(4 weeks)
研究者
Z. J. Daskalakis
Chair, Temerty Centre for Therapeutic Brain Intervention
Centre for Addiction and Mental Health