NEUROmetabolic Mechanisms of COGnitive Training in Schizophrenia
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 168
- 主要终点
- Change in DPX Task Performance
研究概览
简要总结
This study will examine brain metabolic and excitatory/inhibitory mechanisms related to cognitive and visual functioning in adults with schizophrenia and healthy control participants.
Participants will complete behavioral assessments, cognitive testing, electroencephalography, magnetic resonance imaging, and magnetic resonance spectroscopy assessments. After baseline assessments, participants will be randomly assigned to one of two computerized cognitive training programs: perceptual discrimination training or cognitive control training. Each training program will include approximately 10 hours of training over 2 to 6 weeks.
The study will evaluate changes in cognitive and visual task performance, EEG measures, and brain metabolite concentrations before and after cognitive training. Some participants may also complete optional extended baseline assessments before cognitive training.
详细描述
Schizophrenia is associated with cognitive and visual impairments that can persist across the lifespan and are not fully addressed by current antipsychotic treatments. These impairments may be related to disruptions in brain metabolism and excitatory/inhibitory balance. This study is designed to better understand neurochemical and neurophysiological mechanisms of cognitive and visual functioning in schizophrenia and to evaluate whether these mechanisms change following cognitive training.
The study will enroll adults with schizophrenia or schizoaffective disorder and demographically similar healthy control participants. Participants will complete baseline clinical assessments, cognitive and visual tasks, electroencephalography, structural magnetic resonance imaging, and magnetic resonance spectroscopy. Magnetic resonance spectroscopy will be used to measure brain metabolite concentrations, including metabolites related to brain metabolism and excitatory/inhibitory function.
After baseline assessments, participants will be randomly assigned to one of two computerized cognitive training programs: perceptual discrimination training or cognitive control training. Both training programs are delivered through the BrainHQ platform and include approximately 10 hours of training over a 2- to 6-week period. Perceptual discrimination training focuses on visual stimulus discrimination, signal-to-noise resolution, and attentional control. Cognitive control training focuses on maintaining cognitive context in working memory during response selection.
After completing cognitive training, participants will return for follow-up assessments, including repeat clinical assessments, cognitive and visual tasks, EEG, MRI, and magnetic resonance spectroscopy. Participants may also choose to complete an optional extended baseline component with additional baseline scanning visits before cognitive training.
The primary outcomes include behavioral performance on the DPX task variant, EEG variables related to excitatory/inhibitory balance, and magnetic resonance spectroscopy measures of neurometabolite concentrations. Secondary outcomes include symptom and functioning measures such as the Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, Scale for the Assessment of Positive Symptoms, World Health Organization Disability Assessment Schedule, and Global Functioning Social/Role scales.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
盲法说明
This is an open-label study. Participants and study staff will know which computerized cognitive training intervention is assigned.
入排标准
- 年龄范围
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All participants (healthy control and SZ):
- •Age: 18-79
- •Have given written informed consent
- •Be able to read and write in English
- •General health status: Participants should be in good general physical health (no major neurological disorder or head injury with prolonged unconsciousness, and no current moderate or severe substance use disorder)
- •Geographic location: Minnesota counties that are approximately within 1 hour driving distance to Twin Cities, including, but not limited to, Hennepin, Ramsey, Washington, Anoka, Wright, Carver, Scott, Dakota, Sherburn
- •Agree to refrain from using recreational drugs for 1 week prior to each scanning session, including, but not limited to, marijuana
- •For people with schizophrenia (SZ):
- •Current DSM-5 diagnosis of schizophrenia or schizoaffective disorder. Participants should be in stable psychiatric health, evidenced by no suicide attempt or psychiatric hospitalization within the past 1 month. (Initial diagnosis will be assessed using SCID 5 or MINI-7, and confirmation of ongoing SZ status and symptom changes will be monitored at each major timepoint using BPRS.)
- •All SZ must have achieved clinical stability, defined as outpatient status for at least one month prior to study participation, plus stable doses of psychiatric medications for at least 1 month prior to study participation (as reported by participants and confirmed via medication list (procured by participants via their own medical or pharmacy records) and/or current pill bottle labels).
- •All participants should have symptom ratings below a rating of 7 "extremely severe" on a severity scale of 1-7 on the BPRS and/or below grade 3 on longitudinal assessment defined by (as determined by the PI):
- •Grade 1: Worsening of 1 point on any item within each BPRS factor
- •Grade 2: Worsening of 2 points on any item within each BPRS factor
- •Grade 3: Worsening of 3+ points on any item within each BPRS factor, or a change to a rating of extremely severe
- •Grade 4: Suicide attempt with intent to die
排除标准
- •Exclusion criteria for both groups are:
- •Presence of major neurological disorder
- •Conditions preventing MR scanning or other MRI contraindications:
- •Implanted devices or ferromagnetic objects, current pregnancy (positive pregnancy test on day of MRI scanning or currently breast-feeding), etc. Significant movement disorders including tardive dyskinesia that could disrupt MRI and MRS recordings. Medically significant condition considered unsuitable for the current study (e.g., epilepsy, etc.)
- •Estimated IQ < 70
- •Other relevant comorbidity (e.g., epilepsy, developmental disability) or visual impairment
- •Presence of current substance use disorder (moderate or severe; excluding caffeine and nicotine), as measured by the MINI-7 or SCID 5 based on DSM-5 criteria.
- •For healthy controls, additionally:
- •Personal or immediate first-degree family history of a psychotic or mood disorder. Specifically, current or past history of meeting DSM-5 criteria for schizophrenia spectrum or other psychotic disorders, or Bipolar I or II Disorder, major depressive disorder, posttraumatic stress disorder, panic disorder, obsessive compulsive disorder, dysthymic disorder. Those with a first or second-degree relative with a current or past history of meeting DSM-5 criteria for schizophrenia or other psychotic disorders or bipolar I or II disorder, because they might have an underlying genetic susceptibility for psychosis symptoms.
- •Presence of symptoms of the following DSM-5 disorders (as assessed by the MINI-7 or SCID 5):
- •Major Depressive Episode
- •Suicidality
- •Manic and Hypomanic Episodes
- •Panic disorder
- •Obsessive-Compulsive Disorder
- •Posttraumatic Stress Disorder
- •Alcohol Use Disorder
- •Substance Use Disorder (Non-Alcoholic)
- •Psychotic Disorders and Mood Disorders with Psychotic Features
- •Medication or substance induced psychosis
- •Major Depressive Disorder (MDD)
- •MDD with Psychotic Features
- •Bipolar I
- •Bipolar II
- •Other Specified Bipolar and Related Disorder
结局指标
主要结局
Change in DPX Task Performance
时间窗: Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component
Behavioral performance on the DPX task variant will be assessed as a measure of cognitive control. Trial-by-trial behavioral data will be used to derive observed behavioral and computational metrics of cognitive control. The DPX task variant consists of a series of pattern sequences. One pattern is designated the "A" cue followed by the "X" cue, which requires one response (AX, 60-70% of trials, e.g. respond with the left button), while other pattern sequences require a different response (AY or BX, 12-15% of trials each, or BY, 6-10% of trials, e.g. respond with the right button). Given the strong expectation that X's evoke a valid response, BX trials place demands on cognitive control via the fidelity (stability, memory) of the "B" cue representation to overcome this tendency. Unit of Measure: Mean and standard deviation for BX trial error rate
Number of participants with pre/post EEG data
时间窗: Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component
The final sample size (participants with resting electroencephalography before and after intervention) will be reported to facilitate future analyses of change in EEG variables, which could include phase synchrony, slope of the spectral power density indexing excitatory/inhibitory balance, and/or prefrontal/parietal theta as a measure of perceptual noise. Units of Measure: Number of participants with pre/post EEG data
Number of participants with pre/post Magnetic Resonance Spectroscopy data
时间窗: Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component
Magnetic resonance spectroscopy (MRS) will be used to measure neurometabolite concentrations, including but not limited to glutamate, GABA, glutathione, and glucose. MRS measurements will be collected from prefrontal and occipital cortex. The final sample size (participants with MRS before and after intervention) will be reported to facilitate future analyses of change in MRS variables. Units of Measure: Number of participants with pre/post MRS data
次要结局
- Change in Brief Psychiatric Rating Scale Score(Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component)
- Change in Positive Symptom Scores(Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component)
- Change in Negative Symptom Scores(Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component)
- Change in World Health Organization Disability Assessment Schedule Score(Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component)
- Change in Global Functioning Role Scale Score(Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component)