Department of Anatomy and Neurosciences, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam 1081 HV, The Netherlands.
Cancer Center Amsterdam, Imaging and Biomarkers, Brain Tumor Center Amsterdam, Amsterdam 1081 HV, The Netherlands.
Brain. 2022 Oct 21;145(10):3654-3665. doi: 10.1093/brain/awac180.
It is unclear why exactly gliomas show preferential occurrence in certain brain areas. Increased spiking activity around gliomas leads to faster tumour growth in animal models, while higher non-invasively measured brain activity is related to shorter survival in patients. However, it is unknown how regional intrinsic brain activity, as measured in healthy controls, relates to glioma occurrence. We first investigated whether gliomas occur more frequently in regions with intrinsically higher brain activity. Second, we explored whether intrinsic cortical activity at individual patients' tumour locations relates to tumour and patient characteristics. Across three cross-sectional cohorts, 413 patients were included. Individual tumour masks were created. Intrinsic regional brain activity was assessed through resting-state magnetoencephalography acquired in healthy controls and source-localized to 210 cortical brain regions. Brain activity was operationalized as: (i) broadband power; and (ii) offset of the aperiodic component of the power spectrum, which both reflect neuronal spiking of the underlying neuronal population. We additionally assessed (iii) the slope of the aperiodic component of the power spectrum, which is thought to reflect the neuronal excitation/inhibition ratio. First, correlation coefficients were calculated between group-level regional glioma occurrence, as obtained by concatenating tumour masks across patients, and group-averaged regional intrinsic brain activity. Second, intrinsic brain activity at specific tumour locations was calculated by overlaying patients' individual tumour masks with regional intrinsic brain activity of the controls and was associated with tumour and patient characteristics. As proposed, glioma preferentially occurred in brain regions characterized by higher intrinsic brain activity in controls as reflected by higher offset. Second, intrinsic brain activity at patients' individual tumour locations differed according to glioma subtype and performance status: the most malignant isocitrate dehydrogenase-wild-type glioblastoma patients had the lowest excitation/inhibition ratio at their individual tumour locations as compared to isocitrate dehydrogenase-mutant, 1p/19q-codeleted glioma patients, while a lower excitation/inhibition ratio related to poorer Karnofsky Performance Status, particularly in codeleted glioma patients. In conclusion, gliomas more frequently occur in cortical brain regions with intrinsically higher activity levels, suggesting that more active regions are more vulnerable to glioma development. Moreover, indices of healthy, intrinsic excitation/inhibition ratio at patients' individual tumour locations may capture both tumour biology and patients' performance status. These findings contribute to our understanding of the complex and bidirectional relationship between normal brain functioning and glioma growth, which is at the core of the relatively new field of 'cancer neuroscience'.
目前尚不清楚为什么神经胶质瘤在某些大脑区域更易发生。在动物模型中,神经胶质瘤周围的尖峰活动增加会导致肿瘤生长更快,而无创性测量到的大脑活动较高与患者的生存时间较短有关。然而,目前尚不清楚健康对照中测量的区域固有大脑活动与神经胶质瘤的发生有何关系。我们首先研究了神经胶质瘤是否更频繁地发生在固有大脑活动较高的区域。其次,我们探讨了个体患者肿瘤位置的固有皮质活动是否与肿瘤和患者特征有关。在三个横断面队列中,共纳入了 413 名患者。创建了个体肿瘤掩模。通过在健康对照中获取静息状态脑磁图并对 210 个皮质脑区进行源定位,评估了固有区域大脑活动。大脑活动的操作性定义为:(i)宽带功率;和(ii)功率谱非周期性分量的偏移,这两者均反映了基础神经元群体的神经元尖峰。我们还评估了(iii)功率谱非周期性分量的斜率,它被认为反映了神经元兴奋/抑制比。首先,通过将患者的肿瘤掩模串联起来获得的组水平区域性神经胶质瘤发生与组平均区域性固有大脑活动之间计算了相关系数。其次,通过将患者的个体肿瘤掩模与对照的区域固有大脑活动叠加来计算特定肿瘤位置的固有大脑活动,并将其与肿瘤和患者特征相关联。正如预期的那样,胶质瘤更易发生在固有大脑活动较高的脑区,这反映了更高的偏移量。其次,个体肿瘤位置的固有大脑活动根据神经胶质瘤亚型和表现状态而有所不同:与异柠檬酸脱氢酶突变型、1p/19q 缺失型神经胶质瘤患者相比,最恶性的异柠檬酸脱氢酶野生型神经胶质母细胞瘤患者的个体肿瘤位置的兴奋/抑制比最低,而较低的兴奋/抑制比与较差的 Karnofsky 表现状态有关,尤其是在缺失型神经胶质瘤患者中。总之,胶质瘤更常发生在固有活动水平较高的皮质脑区,这表明更活跃的区域更容易发生神经胶质瘤的发展。此外,患者个体肿瘤位置的健康、固有兴奋/抑制比的指数可能同时捕获肿瘤生物学和患者表现状态。这些发现有助于我们理解正常大脑功能与神经胶质瘤生长之间复杂而双向的关系,这是相对较新的“癌症神经科学”领域的核心。
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