THE NEUROANATOMICAL BASIS OF SOCIAL-AFFECTIVE DEFICITS IN AUTISM

自闭症的神经病理学发现一直涉及到海马体和杏仁核，这两个关键的边缘系统结构在许多皮质区域都有特定但广泛的联系。虽然海马体在陈述性和短期记忆过程中具有重要功能，但杏仁核与情绪、恐惧、焦虑有关，对于与人和环境的社会互动至关重要。在自闭症患者中，个人在陈述性记忆和社会情绪方面存在困难。 以及情绪化行为。尽管海马体和杏仁核是许多 正在进行的研究表明，这两个关键大脑区域的直接和间接皮质连接在自闭症中还没有得到很好的研究。因此，本研究将研究六个关键的皮质区域，包括额叶的两个区域(内侧和眼眶额叶皮质)，扣带回的三个区域(扣带回和脾后皮质)，以及梭状回中的颞叶梭形面区，每个区域都与海马、杏仁核或两者都有重要联系。假设是这些边缘皮质内的回路发生了改变，导致了自闭症患者的社会情感行为缺陷。细胞结构和皮质细胞构筑将通过六个大脑皮层的细胞病理学标准尼氏染色进行研究。因为现在看来苯二氮卓类药物结合的异常 已经确定了海马区的位置和GABA-A受体，将使用各种方法研究六个皮质区域的GABA能。免疫细胞化学将量化皮质GABA能中间神经元的亚群，并利用针对三种类型的GABA能转运体(摄取部位)的抗体来评估功能活性。此外，体外多浓度配体结合将定量结合苯二氮类药物和GABA-A位点以及三种类型的5-羟色胺能受体的结合密度和亲和力，这是与自闭症谱系有关的另一种递质系统。最后，动态 自闭症患者的大脑状态将利用针对两种类型的神经胶质细胞的抗体进行评估：小胶质细胞和星形胶质细胞。神经病变部位的小胶质细胞聚集将成为研究的重点，并假设自闭症是一个持续的过程，而不是静态的障碍。

Neuropathological findings in autism have consistently implicated the hippocampus and amygdala, two key limbic system structures with specific but wide-ranging connections throughout many cortical regions. While the hippocampus has important functions in declarative and short term memory processes, the amygdala in contrast has been implicated in emotions, fear, anxiety and is critically important for social interaction with 3eers and the environment, in autism, individuals have difficulties with declarative memory and with socioemotional and affective behavior. Although the hippocampus and amygdala are the subject of many ongoing research studies, the direct and indirect cortical connectivity of these two key brain areas have not been well studied in autism. Thus, the present study will investigate six key cortical areas including two in the frontal lobe (medial and orbital frontal cortex), three areas in the cingulate gyrus (anterior and posterior cingulate and retrosplenial cortex) and the temporal lobe fusiform face area in the fusiform gyrus, each of which have important connections with either the hippocarnpus, amygdala or both. The hypothesis is that the circuitry within these limbic cortices is altered contributing to the social affective behavioral deficits in autism. The cellular structure and cortical cytoarchitecture will be studied via standard Nissl stains for cellular pathology in the six cortices. Since it now appears that abnormalities in benzodiazepine binding sites and GABA-A receptors have been identified in the hippocampus, the GABAergic will be investigated in the six cortical areas using a variety of methods. Immunocytochemistry will quantify subpopulations of cortical GABAergic intemeurons and assess the functional activity utilizing antibodies dierected against three types of GABAergic transporters (uptake sites). In addition, in vitro multiple concentration ligand binding will quantify the density of binding and affinity to bind benzodiazepine and GABA-A sites as well as three types of serotonergic receptors, another transmitter system implicated in autistic spectrum. Finally, the dynamic state within the brain of autistic individuals will be assessed utilizing antibodies toward two types of neuroglia: microglia and astrocytes. Microglial aggregations at sites of neuropathological changes wilt be a focus of the study with the hypothesis that autism is an ongoing process and not a static disorder.