MRI STUDIES OF BRAIN FUNCTION AND METABOLISM

CBDB的功能MRI组由神经病学、精神病学、物理学、生物学和MRI技术的多学科专家组成。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，该小组的主要工作是继续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病患者的脑代谢物[乙酰天冬氨酸（NAA）、胆碱和肌酸]进行成像。从这些研究中得出了几个有趣的发现：1)在工作记忆的假定网络的关键节点中存在容量限制。精神分裂症患者更快达到这种能力，但在他们的能力限制下表现出正常的生理关系。在一项双盲安慰剂对照研究中，右旋安非他明对各组表现和前额皮质激活的影响是不均匀的。它只改善了那些基线工作记忆容量相对较低的受试者的表现，而在基线工作记忆容量相对较高的受试者中，它使他们的表现恶化。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。右旋安非他明的这些异质效应可以用与右旋安非他明作用相互作用的遗传变异来解释。进一步的研究正在探索这一假设。3)同侧皮质运动区在优势手和非优势手运动中都被调动，但在不太熟悉和不太自动的任务中，无论涉及的是哪只手或哪个半球，这种调动似乎更多。4)对精神分裂症患者及其兄弟姐妹的数据的初步分析表明，与对照组相比，他们的感觉运动皮层的功能侧化明显减少。正在收集一个更大的数据库，以评估这种现象是否代表一种与精神分裂症相关的大脑表型。5)相对较低的NAA在背外侧前额叶皮层的浓度预示着精神分裂症患者基底神经节中较高的D-2结合电位。6)双相情感障碍患者在海马区表现出选择性的NAA减少，这表明该皮质区域存在神经元病理，并进一步证明海马参与双相情感障碍的病理生理。7)大鼠海马新生期病变产生青春期后前额皮质特异性神经元缺损，NAA水平降低证明了这一点。由于先前的啮齿动物研究报道了新生儿海马病变诱导与精神分裂症现象一致的生化和行为异常，这些发现进一步证明了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中发挥作用。未来几年的研究将继续进行临床测试和优化成像方案，提高空间和时间分辨率，在神经精神任务中使用药理操作对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（如精神分裂症、帕金森病等）中绘制脑功能和代谢图。这是可以想象的遗传风险标记，可能用于连锁研究，可以确定。-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