Real time neurofeedback, its neurotransmitter underpinnings, and therapeutic effects, in clinical high risk individuals

临床高危个体的实时神经反馈、其神经递质基础和治疗效果

• 批准号: 10645480
• 负责人: Alexander Peter Lin
• 金额: $ 121.45万
• 依托单位: BOSTON VA RESEARCH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-17 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10645480
• 关键词: Adopted; Attention; Attenuated; Auditory Hallucination; Behavior Therapy; Behavioral; Benchmarking; Brain; Chronic Schizophrenia; Clinical; Cognition; Cognitive; Control Groups; Crossover Design; Data; Development; Disease; Dose; Functional Magnetic Resonance Imaging; Future; Glutamates; Goals; Grant; Impairment; Individual; Intervention; Magnetic Resonance Spectroscopy; Measures; Medial; Meditation; Meta-Analysis; Motor Cortex; Names; Neurocognitive; Neuropsychology; Neurotransmitters; Outcome; Patients; Pattern; Phase; Prefrontal Cortex; Process; Psychoses; Randomized; Research; Rest; Risk; Sampling; Scanning; Schizophrenia; Short-Term Memory; Source; Superior temporal gyrus; Symptoms; Testing; Therapeutic Effect; Time; Work; behavior measurement; brain abnormalities; brain dysfunction; cingulate cortex; clinical high risk for psychosis; cognitive change; comparison group; effective therapy; efficacy evaluation; efficacy testing; experience; first episode schizophrenia; gamma-Aminobutyric Acid; high risk; high risk population; improved; mindfulness; mindfulness meditation; neural network; neurochemistry; neurofeedback; pharmacologic; post intervention; prevent; prodromal psychosis; psychotic; psychotic symptoms; reduce symptoms; response

Clinical high risk (CHR) for psychosis states are symptomatic, dynamic periods that occur before psychosis onset and are subjects of intensive research. The focus on CHR is driven by evidence of behavioral and brain level impairments in many individuals experiencing their attenuated psychotic symptoms which are similar to those found in first episode and chronic schizophrenia (SZ): our work, and that of others, demonstrated that CHR individuals show deficits in both brain function and cognition reminiscent of those found in SZ. For example, increased default mode network (DMN) connectivity found in SZ was also identified in CHR. The CHR period offers the most hope for mitigating or preventing disease development yet effective treatment options are still lacking. The overarching goal of this R61/33 study is early efficacy testing of the real-time functional MRI-based neurofeedback (rt-NFB), aided by mindfulness (rt-NFB+M), to impact both brain connectivity and clinical and neurocognitive (NP) outcomes. In the R61 phase, we will examine the efficacy of rt-NFB+M targeting the DMN to reduce medial prefrontal and posterior cingulate cortex (MPFC-PCC) hyperconnectivity and to increase MPFC-dorsolateral prefrontal cortex (DLPFC) anti-correlations in CHR subjects who will be randomly assigned to either real-rt-NFB+M (N=24) or sham/control -rt-NFB+M (N=24) condition. Thirty healthy controls scanned once will serve as an additional control group. Neurotransmitters in MPFC and DLPFC will also be assessed using magnetic resonance spectroscopy to relate cellular level measures to brain network measures. MPFC- PCC connectivity reductions and MPFC-DLPFC increased anticorrelation, post-NFB, in the real rt-NFB+M group, will be the R61 GO criteria. In the R33 phase, we will replicate R61 results in an independent sample of 51 CHR in the real-fMRI NFB+M condition, compare the effects of rt-NFB+M (N=51 CHR) versus meditation only (N=30 CHR), examine dose-response over 4 sessions, and the relationship between network connectivity and glutamate (Glu) and GABA changes, as well as clinical and neuropsychological changes, especially in working memory (WM) and attention, post-intervention, in both rt-NFB+M and in the meditation only group. This proposal builds on our successful use of rt-NFB in SZ to modulate the DMN connectivity and mitigate symptoms. As one of the first in the field, we demonstrated that rt-NFB targeting the DMN reduced its hyper-connectivity in SZ which; in turn, was associated with auditory hallucinations reduction after rt-NFB. Increased MPFC-DLPFC anticorrelations were also observed and associated with increases in MPFC GABA in a separate study. Furthermore, we have observed that increases in DMN-DLPFC anticorrelations due to pharmacological or behavioral interventions are associated with improved WM and attention. Since our preliminary data suggest that SZ with the least abnormal brain patterns benefited most from our rt-NFB intervention, we believe that adopting the rt-NFB in CHR will be highly effective in altering the disease trajectory.

精神错乱状态的临床高危(CHR)是发生在以下情况之前的有症状的动态时期 精神病的发病，是深入研究的对象。对CHR的关注是由行为证据驱动的 以及许多经历精神症状减弱的个体的大脑水平损害，这些症状是 与在首发和慢性精神分裂症(SZ)中发现的类似：我们和其他人的工作表明 CHR患者在大脑功能和认知方面都表现出缺陷，这让人想起在SZ发现的那些人。为 例如，在SZ发现的增加的默认模式网络(DMN)连通性也在CHR中发现。Chr. 这一时期为缓解或预防疾病的发展带来了最大的希望，但有效的治疗选择是 还是不够用。 这项R61/33研究的首要目标是基于实时功能磁共振的早期疗效测试 神经反馈(RT-NFB)，辅助正念(RT-NFB+M)，影响大脑连通性和临床和 神经认知(NP)结果。在R61阶段，我们将检查RT-NFB+M靶向DMN的疗效 减少内侧前额叶和后扣带回(MPFC-PCC)的过度连接并增加 随机分配的慢性阻塞性肺疾病受试者mPFC-背外侧前额叶皮质(DLPFC)的反相关性 至Real-RT-NFB+M(N=24)或Sham/Control-RT-NFB+M(N=24)状态。对30名健康对照进行了扫描 ONCE将作为额外的对照组。还将评估MPFC和DLPFC中的神经递质 使用磁共振光谱学将细胞水平的测量与大脑网络的测量联系起来。MPFC- 在真实RT-NFB+M中，PCC连接性减少和MPFC-DLPFC在NFB后增加了反相关性 小组，将是R61围棋的标准。在R33阶段，我们将在独立样本中复制R61结果 在Real-fMRI NFB+M条件下，比较RT-NFB+M(N=51CHR)和冥想的效果 仅(N=30chr)，检查4个疗程的剂量-反应以及网络连接之间的关系 和谷氨酸(Glu)和GABA的变化，以及临床和神经心理的变化，尤其是在 干预后，RT-NFB+M组和仅冥想组的工作记忆(WM)和注意力。这 该提案建立在我们在深圳成功使用RT-NFB来调节DMN连接和缓解症状的基础上。 作为该领域的首批人员之一，我们证明了针对DMN的RT-NFB降低了其在 SZ，进而与RT-NFB后幻听的减少有关。增加MPFC-DLPFC 在另一项单独的研究中，还观察到了与MPFC GABA增加有关的抗癌作用。 此外，我们观察到DMN-DLPFC抗相关性的增加是由于药物或 行为干预与改善WM和注意力有关。因为我们的初步数据显示 大脑模式异常最少的深圳从我们的RT-NFB干预中受益最大，我们相信采用 CHR中的RT-NFB将在改变疾病轨迹方面非常有效。