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.

精神病状态的临床高风险 (CHR) 是指之前发生的有症状的动态时期 精神病的发作，是深入研究的课题。对 CHR 的关注是由行为证据驱动的 许多经历减轻精神病症状的人的大脑水平受损 与第一集和慢性精神分裂症（SZ）中发现的类似：我们和其他人的工作表明 CHR 个体在大脑功能和认知方面都表现出缺陷，让人想起在 SZ 中发现的情况。为了 例如，在 CHR 中也发现了 SZ 中增加的默认模式网络 (DMN) 连接性。人权委员会 这段时期最有希望减轻或预防疾病的发展，但有效的治疗选择是 仍然缺乏。 这项 R61/33 研究的首要目标是基于实时功能 MRI 的早期功效测试 神经反馈（rt-NFB），辅以正念（rt-NFB+M），影响大脑连接性和临床和 神经认知（NP）结果。在R61阶段，我们将检查rt-NFB+M靶向DMN的功效 减少内侧前额叶和后扣带皮层 (MPFC-PCC) 的超连接性并增加 将被随机分配的 CHR 受试者中 MPFC-背外侧前额叶皮层 (DLPFC) 反相关性 到真实-rt-NFB+M (N=24) 或假/对照-rt-NFB+M (N=24) 条件。扫描三十个健康对照 一次将作为额外的对照组。 MPFC 和 DLPFC 中的神经递质也将被评估 使用磁共振波谱将细胞水平测量与大脑网络测量联系起来。 MPFC- 在实际 rt-NFB+M 中，PCC 连接性减少和 MPFC-DLPFC 增加了 NFB 后的反相关性 组，将是 R61 GO 标准。在 R33 阶段，我们将在独立样本中复制 R61 结果 真实 fMRI NFB+M 条件下的 51 CHR，比较 rt-NFB+M (N=51 CHR) 与冥想的效果 仅 (N=30 CHR)，检查 4 个会话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学的变化，特别是在 rt-NFB+M 组和仅冥想组的干预后工作记忆 (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 连接并缓解症状的基础上。 作为该领域的先行者之一，我们证明了针对 DMN 的 rt-NFB 降低了其超连接性 SZ 其中；反过来，与 rt-NFB 后幻听减少有关。增加 MPFC-DLPFC 在另一项研究中还观察到了反相关性，并与 MPFC GABA 的增加相关。 此外，我们观察到由于药理学或药物作用，DMN-DLPFC 反相关性增加 行为干预与改善 WM 和注意力有关。由于我们的初步数据表明 异常大脑模式最少的 SZ 从我们的 rt-NFB 干预中受益最多，我们相信采用 CHR 中的 rt-NFB 将非常有效地改变疾病轨迹。