Theta Burst Stimulation for Schizophrenia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Brief Assessment of Cognition (BACS) Composite T Score
研究概览
简要总结
Purpose and objective Schizophrenia is a chronic debilitating illness with cognitive deficits that cause serious impairment in psychosocial recovery and with few treatments to remediate these deficits. One area that holds great promise for the development of novel, effective therapies is noninvasive brain stimulation. The investigators have used one form of brain stimulation, transcranial magnetic stimulation (TMS), for some time to modulate and enhance cognitive function in the brain, especially working memory (WM) function, which has a central role in most executive processing that occurs in the brain. Theta burst stimulation (TBS) is a paradigm of TMS which has been shown to effectively modulate WM. Moreover, TBS can modulate gamma neural oscillations in the brain and neural activity, both of which have been implicated in the physiology of WM and pathophysiology of the disease process in schizophrenia, making these measures highly valuable for assessing physiological effects of TBS on cognition, quality of life and cortical inhibition. The purpose of this study is to evaluate the effect of TBS on WM in patients with schizophrenia, to develop evidence for potential brain stimulation techniques to treat cognitive deficits in schizophrenia.
Study activities and population group: Study subjects will be inpatient schizophrenic individuals with minimal positive symptoms and predominant cognitive deficits at Duke University Hospital. In an initial session they will be screened and taught a WM task. Following this, one TBS session will follow in which TBS will target dorsolateral prefrontal cortex. They will perform the WM task before, with and after the TBS, with an expected pre-post enhancement of WM performance.
Implications - There is a great need for treatments for cognitive deficits in schizophrenia. The results of this study will serve to generate pilot data for a much larger grant to develop a TBS therapy for remediating such cognitive deficits.
详细描述
Purpose of the study Aim1: Evaluate the effect of theta burst stimulation (TBS) on working memory (WM) in patients with schizophrenia. Hypothesis 1 - There will be significant improvement in WM compared to baseline with one session of TBS.
Background and Significance Schizophrenia is an illness known to have cognitive deficits, with a chronic and variable course. There is extensive research on cognitive deficits, with working memory, processing speed and verbal memory being some of the domains affected. Some modalities of treatment that have been tried to reverse these cognitive deficits are medications and cognitive behavioral therapy with minimal benefits. A few studies have shown modulation of working memory with routine repetitive transcranial magnetic stimulation at frequencies not exceeding 10 to 20 Hz of stimulation. Other studies have shown the working memory to be related to gamma oscillations. A few studies have also shown that transcranial magnetic stimulation (TMS) modulates these gamma oscillations as well. There is an extensive body of literature that shows that working memory has contributions from theta and gamma oscillations in the brain. Theta burst stimulation (TBS) is a form of transcranial magnetic stimulation (TMS), that entrains gamma and theta frequencies in the brain. It could be the most appropriate form of brain stimulation for improving cognition in schizophrenia patients because it has been shown to modulate brain oscillations in small samples of patients. The area for targeting would be the dorsolateral prefrontal cortex which is the site of origin of the gamma oscillations and plays a significant role in working memory.
Design and Procedures The study is designed to be a pilot one evaluating the effect of TBS on WM in patients with schizophrenia. The investigators plan to screen 20 subjects to have 10 participants. Working memory will be tested using delayed match sample task (DMS) and brief assessment of cognition in schizophrenia battery (BACS).
Transcranial Magnetic Stimulation (TMS) administration The patient would be transported from the inpatient unit to the TMS lab following screening and consent process. They would be accompanied by nursing staff. During their visit to the TMS lab a sample TMS session including motor threshold determination will be conducted. Subjects would be allowed to practice the DMS task to allow for the ceiling in practice effect of the task. The BACS would be administered before and after the TMS session.
Treatment Sessions Subjects would be administered left sided theta burst stimulation (TBS).The subject will be seated in a chair. A 64-channel electrode cap may be applied to the head for EEG recording. Electromyogram (EMG) electrodes will be applied to the right hand for motor evoked potential (MEP) recording. Subjects will perform the DMS task while sitting in the chair during the TMS session. EEG and EMG will be recorded throughout the treatment sessions. For theta burst stimulation the active motor threshold would be 80 % as used in most theta burst studies detailed in this review. Subjects would receive theta burst stimulation comprising 50 Hz bursts given at 3 to 5 Hz for close to 10 minutes which comprises 60 trains and 1800 pulses. The subject will be monitored until MEPs return to baseline. A side effects checklist will be completed at the beginning and at the end of the experimental session. All sessions will be performed by one of the protocol investigators, or by a trained and accredited research assistant supervised by the protocol investigators.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 18-65 years of age with schizophrenia or schizoaffective disorder
- •No other mental health diagnoses
- •Right handed males and females
- •May have mild positive symptoms (score of </= 21)
- •May have negative symptoms
- •Ability to provide informed consent
- •No restriction on concomitant medications given
排除标准
- •Intellectual disability
- •Any organic brain illness Presence of dementia symptoms or traumatic brain injury Primary diagnosis of substance use Seizure disorder Actively symptomatic with PANSS positive symptom sub-scale >
- •Concurrently receiving electroconvulsive therapy (ECT)
结局指标
主要结局
Brief Assessment of Cognition (BACS) Composite T Score
时间窗: 30 minutes
Performance on tasks included in the Brief Assessment of Cognition in Schizophrenia (BACS) battery, task performed and results recorded on IPAD. The mean change from baseline in total cognitive score on the BACS was calculated as a weighted average of T-scores (normalized for age) from BACS subtests including Verbal Memory, Digit Sequencing, Token Motor, Symbol Coding, Semantic Fluency, Letter Fluency, and Tower of London. The minimum and maximum values possible for this composite T-score of the change from baseline were -131 and 131, respectively. Higher values (positive changes from baseline) indicate better performance.
次要结局
- Change in Gamma and Theta Oscillations as Measured by EEG(one session, approximately 30 minutes)