MRI STUDIES OF BRAIN FUNCTION AND METABOLISM

脑功能和新陈代谢的 MRI 研究

• 批准号: 6290578
• 负责人: Daniel Martin Weinberger
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6290578
• 关键词: aspartate; brain metabolism; cerebrovascular disorders; clinical research; dementia; dextroamphetamine; diagnosis design /evaluation; disease /disorder model; disease /disorder proneness /risk; functional magnetic resonance imaging; human subject; ketamine; memory; mental disorder diagnosis; neuromuscular disorder; neurophysiology; neuropsychology; schizophrenia

The functional MRI group of CBDB consists of multidisciplinary specialists with expertise in neurology, psychiatry, physics, biology and MRI techniques. This group pursues a variety of research agendas involving study of brain function and metabolism in normals and patients with neuropsychiatric disorder. The lion’s share of the effort of this group over the last year has continued to be in studies of cognitive activation during neuropsychiatric tasks and imaging of brain metabolites [N acetyl aspartate (NAA), choline and creatine] using magnetic resonance spectroscopic imaging (MRSI) in normal individuals, patients with schizophrenia and their unaffected siblings, animal models of schizophrenia, and in patients with Parkinson’s disease. Several interesting findings have emerged from these studies: 1) There is a capacity constraint in the key nodes of the putative network underlying working memory. Patients with schizophrenia reach this capacity sooner, but within their capacity constraints show normal physiological relationships. Beyond capacity they become paradoxically hyper-frontal while controls decreased dorsolateral prefrontal cortical (DLPFC) activity 2) In a double blinded placebo controlled study, the effect of dextroamphetamine on performance and prefrontal cortical activation was heterogeneous across the group. It improved performance only in those subjects who had relatively low working memory capacity at baseline, whereas in subjects that had relatively high working memory capacity at baseline it worsened performance. In subjects whose performance deteriorated, signal change was relatively greater than in subjects who had an improvement in performance. These heterogeneic effects of dextroamphetamine may be explained by genetic variations that interact with the effects of dextroamphetamine. Further studies are in progress to explore this hypothesis. 3) Ipsilateral cortical motor areas are recruited during both dominant and non-dominant hand movements, but this appears to be more so in less familiar and less automatic tasks regardless of the hand or hemisphere involved. 4) Preliminary analysis of data from patients with schizophrenia and their siblings show that they have significantly reduced functional lateralization of the sensorimotor cortex when compared with controls. A larger database is being collected to evaluate if this phenomenon represents a brain ‘phenotype’ associated with schizophrenia. 5) Lower relative NAA concentrations in the dorsolateral prefrontal cortex predict a higher D-2 binding potential in the basal ganglia of patients with schizophrenia, 6) Patients with bipolar disorder show a selective reduction of NAA measures in the hippocampal region suggesting a neuronal pathology in this cortical area and adding further evidence for hippocampal involvement in the pathophysiology of bipolar disorder. 7) Neonatal lesions of the hippocampus of rats produced post pubertal emergence of specific neuronal deficits in the prefrontal cortex as evidenced by reduced NAA levels. Since previous studies in rodents have reported that neonatal lesions of the hippocampus induce biochemical and behavioral abnormalities consistent with the phenomenology of schizophrenia, these findings provide further evidence that aberrant development of the hippocampal and prefrontal systems could play a role in the pathophysiology of schizophrenia. Studies in the upcoming years will continue in the realm of clinical testing and optimization of imaging protocols with improved spatial and temporal resolution, of brain studies of cognitive activation during neuropsychiatric tasks with pharmacological manipulations, and mapping brain function and metabolism in family members who are at risk for neuropsychiatric illnesses such as schizophrenia, Parkinsons disease, etc. It is conceivable that a genetic risk marker, possibly of use in linkage studies, could be identified. - Brain function, MRI, Schizophrenia, neuropsychiatric disorders, cognition - Human Subjects

CBDB的功能性MRI组由具有神经病学、精神病学、物理学、生物学和MRI技术专业知识的多学科专家组成。该小组从事各种研究议程，包括正常人和神经精神障碍患者的脑功能和代谢研究。在过去的一年里，该小组的最大努力份额继续在神经精神任务期间的认知激活研究和使用磁共振光谱成像（MRSI）对正常人，精神分裂症患者及其未受影响的兄弟姐妹，精神分裂症动物模型和帕金森病患者进行脑代谢物[N乙酰天冬氨酸（NAA），胆碱和肌酸]成像。研究发现：1）工作记忆网络的关键节点存在容量限制。精神分裂症患者更快地达到这种能力，但在他们的能力限制范围内，表现出正常的生理关系。除了能力，他们变得矛盾的超额叶，而控制减少背外侧前额叶皮层（DLPFC）活动2）在双盲安慰剂对照研究中，苯丙胺对性能和前额叶皮层激活的影响在整个组中是异质的。它只改善了那些在基线时工作记忆容量相对较低的受试者的表现，而在基线时工作记忆容量相对较高的受试者中，它恶化了表现。在表现恶化的受试者中，信号变化相对大于表现改善的受试者。这些异源效应的苯丙胺可能是解释的遗传变异的影响相互作用的苯丙胺。进一步的研究正在进行中，以探讨这一假设。3)同侧皮质运动区在优势和非优势手部运动期间都被招募，但这似乎在不太熟悉和自动化程度较低的任务中更是如此，无论涉及的手或半球如何。4)对精神分裂症患者及其兄弟姐妹数据的初步分析表明，与对照组相比，他们的感觉运动皮层功能侧化显著减少。正在收集一个更大的数据库，以评估这种现象是否代表与精神分裂症相关的大脑表型。5)较低的相对NAA浓度在背外侧前额叶皮质预测较高的D-2结合电位在基底神经节的精神分裂症患者，6）双相情感障碍患者表现出选择性减少的NAA措施，在海马区，这表明在这个皮质区的神经元病理，并增加了进一步的证据海马参与双相情感障碍的病理生理。7)新生儿海马病变的大鼠青春期后出现特定的神经元缺损的前额叶皮质所证明的NAA水平降低。由于以前的研究在啮齿动物中已经报道，新生儿海马病变诱导的生化和行为异常与精神分裂症的现象学一致，这些研究结果提供了进一步的证据，海马和前额叶系统的异常发育可能在精神分裂症的病理生理学中发挥作用。未来几年的研究将继续在临床测试和优化成像协议的领域，提高空间和时间分辨率，在神经精神任务期间用药理学操作进行认知激活的大脑研究，以及在有神经精神疾病风险的家庭成员中绘制大脑功能和代谢，如精神分裂症，帕金森病等。可能用于联系研究。- 脑功能，MRI，精神分裂症，神经精神疾病，认知-人类受试者