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（clinical high risk，缩写为HRD）是指发生在 精神病发作，是深入研究的对象。对行为的关注是由行为的证据驱动的。 和大脑水平的损伤，在许多人经历他们的减弱精神病症状， 类似于在首发和慢性精神分裂症（SZ）中发现的：我们的工作和其他人的工作表明， 这些人的大脑功能和认知能力都有缺陷，这让人想起在SZ中发现的缺陷。为 例如，在深圳发现的增加的默认模式网络（DMN）连接也在CHR中被确定。 经期为减轻或预防疾病发展提供了最大的希望，但有效的治疗方案是 仍然缺乏。 这项R61/33研究的首要目标是对基于实时功能性MRI的 神经反馈（rt-NFB），辅以正念（rt-NFB+M），以影响大脑连接和临床， 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皮层（MPFC-PCC）的超连通性， MPFC-背外侧前额叶皮层（DLPFC）的反相关性在随机分配的受试者中 至真实-rt-NFB+M（N=24）或假手术/对照-rt-NFB +M（N=24）条件。扫描30名健康对照 一次将作为额外的对照组。还将评估MPFC和DLPFC中的神经递质 使用磁共振波谱将细胞水平测量与脑网络测量相关联。MPFC- 在真实的rt-NFB+M中，PCC连接减少和MPFC-DLPFC增加了NFB后的相关性 组，将是R61 GO标准。在R33阶段，我们将在独立样本中重复R61结果 在真实的fMRI NFB+M条件下，比较rt-NFB+M（N=51）与冥想的效果。 仅（N=30 μ g），检查4个疗程的剂量反应，以及网络连接之间的关系 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 工作记忆（WM）和注意力，干预后，在rt-NFB+M和冥想组。这 该提案建立在我们在SZ中成功使用rt-NFB来调节DMN连接并减轻症状的基础上。 作为该领域的首批研究者之一，我们证明了以DMN为目标的rt-NFB降低了其超连接性， SZ;反过来，与rt-NFB后幻听减少相关。MPFC-DLPFC增加 在一项单独的研究中，还观察到了与MPFC GABA增加相关的关系。 此外，我们还观察到DMN-DLPFC的增加与药理学或 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， 具有最少异常大脑模式的SZ从我们的rt-NFB干预中受益最多，我们认为采用 RT-NFB在改变疾病轨迹方面将是非常有效的。