Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02134, USA; Department of Radiology, Harvard Medical School, Boston, MA, USA.
Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands; Department of (Neuro)Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Neuroimage. 2013 Jul 15;75:195-203. doi: 10.1016/j.neuroimage.2013.02.067. Epub 2013 Mar 16.
Connectivity and network analysis in neuroscience has been applied to multiple spatial scales, but the links between these different scales have rarely been investigated. In tumor-related epilepsy, altered network topology is related to behavior, but the molecular basis of these observations is unknown. We elucidate the associations between microscopic features of brain tumors, local network topology, and functional patient status. We hypothesize that expression of proteins related to tumor-related epilepsy is directly correlated with network characteristics of the tumor area. Glioma patients underwent magnetoencephalography, and functional network topology of the tumor area was used to predict tissue protein expression patterns of tumor tissue collected during neurosurgery. Protein expression and network topology were interdependent; in particular between-module connectivity was selectively associated with two epilepsy-related proteins. Total number of seizures was related to both the role of the tumor area in the functional network and to protein expression. Importantly, classification of protein expression was predicted by between-module connectivity with up to 100% accuracy. Thus, network topology may serve as an intermediate level between molecular features of tumor tissue and symptomatology in brain tumor patients, and can potentially be used as a non-invasive marker for microscopic tissue characteristics.
神经科学中的连接性和网络分析已经应用于多个空间尺度,但这些不同尺度之间的联系很少被研究。在与肿瘤相关的癫痫中,网络拓扑的改变与行为有关,但这些观察结果的分子基础尚不清楚。我们阐明了脑肿瘤的微观特征、局部网络拓扑和患者功能状态之间的关联。我们假设与肿瘤相关的癫痫相关蛋白的表达与肿瘤区域的网络特征直接相关。接受磁共振成像检查的神经胶质瘤患者,利用肿瘤区域的功能网络拓扑来预测在神经外科手术中收集的肿瘤组织的组织蛋白表达模式。蛋白表达和网络拓扑是相互依存的;特别是模块间连接性与两种与癫痫相关的蛋白选择性相关。癫痫发作的总次数与肿瘤区域在功能网络中的作用以及蛋白表达有关。重要的是,蛋白表达的分类可以通过模块间连接性以高达 100%的准确率进行预测。因此,网络拓扑可以作为肿瘤组织的分子特征与脑肿瘤患者症状之间的中间水平,并可能作为微观组织特征的非侵入性标志物。