MRI STUDIES OF BRAIN FUNCTION AND METABOLISM

CBDB的功能核磁共振小组由具有神经学、精神病学、物理学、生物学和核磁共振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，包括研究正常人和神经精神障碍患者的大脑功能和新陈代谢。在过去的一年里，S小组的主要工作仍然是研究神经精神病学任务中的认知激活，以及使用磁共振波谱成像(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S病患者的大脑代谢物[N乙酰天冬氨酸、胆碱和肌酸]进行成像。从这些研究中发现了几个有趣的发现：1)工作记忆潜在网络的关键节点存在容量限制。精神分裂症患者达到这一能力的时间更早，但在他们的能力限制下，表现出正常的生理关系。2)在一项双盲安慰剂对照研究中，右旋苯丙胺对运动能力和前额叶皮质激活的影响在整个组中是不同的。它只在那些在基线时工作记忆容量相对较低的受试者中提高了表现，而在基线时工作记忆容量相对较高的受试者中，它会恶化表现。在表现恶化的受试者中，信号变化相对大于表现有改善的受试者。右旋安非他明的这种异质性效应可以通过与右旋安非他明的作用相互作用的遗传变异来解释。探索这一假说的进一步研究正在进行中。3)无论是优势手运动还是非优势手运动，同侧皮质运动区都会被招募，但在不太熟悉和不那么自动的任务中，这一点似乎更明显，无论涉及的是手还是大脑半球。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，他们显著减少了感觉运动皮质的功能偏侧化。一个更大的数据库正在收集中，以评估这一现象是否代表了与精神分裂症有关的大脑表型。5)精神分裂症患者背外侧前额叶皮质相对NAA浓度较低预示着基底节D-2结合电位较高，6)双相情感障碍患者海马区NAA测定值选择性降低，提示该皮质区存在神经元病理改变，为双相情感障碍的病理生理机制提供了进一步的证据。7)新生大鼠海马区损伤在青春期后前额叶皮质出现特异性神经元缺陷，表现为NAA水平降低。由于以前对啮齿动物的研究报告了新生海马区的损伤导致符合精神分裂症现象学的生化和行为异常，这些发现提供了进一步的证据，表明海马区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。在接下来的几年里，研究将继续在以下领域进行：临床测试和优化时间和空间分辨率的成像方案，通过药物操作对神经精神病学任务期间认知激活的大脑研究，以及绘制有精神分裂症、帕金森氏病等神经精神疾病风险的家庭成员的大脑功能和新陈代谢图。可以想象，可以识别可能用于连锁研究的遗传风险标记。-脑功能、核磁共振、精神分裂症、神经精神障碍、认知-人类受试者

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