Paired Associative Stimulation in the Dorsolateral Prefrontal Cortex in Patients With Schizophrenia: a Combined Transcranial Magnetic Stimulation and Electroencephalography Study Across the Life Span
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Changes in working memory
研究概览
简要总结
The purpose of this study is to
- assess the effect of PAS in schizophrenia in the dorsolateral prefrontal cortex (DLPFC)
- assess the effect of PAS induced long-term potentiation (LTP) on the performance of patients with schizophrenia on a cognitive task related to DLFPC.
详细描述
Neuroplasticity refers to changes in the strength of communication between different neurons. Long-term potentiation (LTP) is one form of neuroplasticity and refers to the strengthening of such communication. LTP is believed to be a cellular substrate of learning and memory. Paired associative stimulation (PAS) is a transcranial magnetic stimulation (TMS) paradigm that is believed to induce LTP in human subjects. However, its effects have been shown to be minimal in patients with schizophrenia suggesting impaired LTP in schizophrenia. The lack of PAS effect in schizophrenia has been observed in the motor cortex (M1). Thus, the investigators propose to assess the effect of PAS in schizophrenia in the dorsolateral prefrontal cortex (DLPFC), an area of the brain that is especially relevant to learning and memory, and to the pathology in schizophrenia. The investigators also propose to assess the effect of PAS induced LTP on the performance of patients with schizophrenia on a cognitive task that is related to DLFPC.
Hypothesis 1: Patients with schizophrenia will have reduced PAS-LTP in DLPFC in comparison with healthy controls.
Hypothesis 2a: PAS-LTP in patients with schizophrenia and healthy controls randomized to PAS-25 and PAS-100 will correlate with performance on the N-back task at baseline (pre-PAS).
Hypothesis 2b: Healthy controls randomized to PAS-25 will perform better after one session of PAS-25 on the 1- and 7-day N-back task compared to healthy controls randomized to PAS-100.
Hypothesis 2c: Among healthy controls randomized to PAS-25, the magnitude of improvement on the 1- and 7-day N-back task (compared to pre-PAS) that is in excess of the magnitude of improvement on the 1- and 7-day N-back task among subjects randomized to PAS-100 will correlate with the degree of PAS-LTP.
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
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •for patients:
- •Age 18 or above
- •All races and ethnicities.
- •Females and males.
- •Meet DSM-IV TR criteria for a current diagnosis of schizophrenia or schizoaffective disorder.
- •Clinically stable as operationalized by (1) either having not been hospitalized within 3 months or having been hospitalized for 3 months or more prior to assessment, and (2) having had no change in antipsychotic medication dosage within the 4 weeks prior to assessment.
- •Willingness and ability to speak English
- •Willingness to provide informed consent
- •Corrected visual ability that enables reading of newspaper headlines and corrected hearing capacity that is adequate to respond to a raised conversational voice.
排除标准
- •for patients:
- •Meets criteria for a cognitive disorder secondary to a neurological or other medical disorder affecting the central nervous system (for example, multiple sclerosis, history of traumatic brain injury, stroke, untreated hypothyroidism).
- •Mini Mental Status Examination score of 17 and less because a subject with a very low MMSE score is unlikely to be able to compete the NP battery.
- •Diagnosis of bipolar disorder or current major depressive episode.
- •Meets diagnostic criteria for current alcohol or other drug dependence within 6 months of testing
- •Electroconvulsive Therapy (ECT) within 6 months of testing.
- •Left handedness.
- •Incompetency to consent
- •Inclusion Criteria for controls:
- •Age 18 or above
- •Willingness and ability to speak English
- •Willingness to provide informed consent
- •Corrected visual ability that enables reading of newspaper headlines and corrected hearing capacity that is adequate to respond to a raised conversational voice.
- •Exclusion Criteria for controls:
- •DSM IV TR psychiatric diagnosis except for simple phobias or an adjustment disorder.
- •Other neurological disorder affecting central nervous system.
- •Psychotropic medication except for sedative /hypnotics at a stable dose for at least 4 weeks.
- •Family history of a primary psychotic disorder in a first-degree relative.
- •Left handedness.
研究组 & 干预措施
PAS 25
In humans, paired associative stimulation (PAS-25) is a transcranial magnetic stimulation (TMS) protocol that has been shown to result in LTP-like plasticity (PAS-LTP) in the motor cortex (M1). PAS-LTP has been shown to be dependent on the NMDAR and to correlate significantly with performance on a motor learning task.
干预措施: Brain Stimulation via Transcranial Magnetic Stimulation (Other)
PAS 100
To control for non-specific effects of PAS protocol, the investigators will use a modified PAS protocol (PAS-100) that does not result in any neurophysiologic effects. Patients with schizophrenia and healthy controls will be assessed first with the N-back task and then randomized
干预措施: Brain Stimulation via Transcranial Magnetic Stimulation (Other)
结局指标
主要结局
Changes in working memory
时间窗: 1 day and 7 days post N-back task
The N-Back is a working memory task where the subject is presented with a sequence of stimuli (letters). The task consists of indicating when the current stimulus matches the one from n steps earlier in the sequence. The load factor n can be adjusted to make the task more or less difficult. Subjects are required to complete the 0, 1, 2 and 3 back at baseline, 1 day post PAS delivery and 7 days post PAS.
次要结局
未报告次要终点
研究者
Tarek Rajji
Principal Investigator
Centre for Addiction and Mental Health