局灶性脑损伤所致神经症状的网络定位

Network localization of neurological symptoms from focal brain lesions.

作者信息

Boes Aaron D, Prasad Sashank, Liu Hesheng, Liu Qi, Pascual-Leone Alvaro, Caviness Verne S, Fox Michael D

机构信息

1 Berenson-Allen Centre for Non-invasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Centre, 330 Brookline Ave, Boston, MA, 02215, USA 2 Department of Paediatric Neurology, Massachusetts General Hospital, Harvard Medical School, Mailcode: WACC 8-835, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA

3 Department of Neurology, Division of Neuro-Ophthalmology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston MA 02115, USA.

出版信息

Brain. 2015 Oct;138(Pt 10):3061-75. doi: 10.1093/brain/awv228. Epub 2015 Aug 10.

Abstract

A traditional and widely used approach for linking neurological symptoms to specific brain regions involves identifying overlap in lesion location across patients with similar symptoms, termed lesion mapping. This approach is powerful and broadly applicable, but has limitations when symptoms do not localize to a single region or stem from dysfunction in regions connected to the lesion site rather than the site itself. A newer approach sensitive to such network effects involves functional neuroimaging of patients, but this requires specialized brain scans beyond routine clinical data, making it less versatile and difficult to apply when symptoms are rare or transient. In this article we show that the traditional approach to lesion mapping can be expanded to incorporate network effects into symptom localization without the need for specialized neuroimaging of patients. Our approach involves three steps: (i) transferring the three-dimensional volume of a brain lesion onto a reference brain; (ii) assessing the intrinsic functional connectivity of the lesion volume with the rest of the brain using normative connectome data; and (iii) overlapping lesion-associated networks to identify regions common to a clinical syndrome. We first tested our approach in peduncular hallucinosis, a syndrome of visual hallucinations following subcortical lesions long hypothesized to be due to network effects on extrastriate visual cortex. While the lesions themselves were heterogeneously distributed with little overlap in lesion location, 22 of 23 lesions were negatively correlated with extrastriate visual cortex. This network overlap was specific compared to other subcortical lesions (P < 10(-5)) and relative to other cortical regions (P < 0.01). Next, we tested for generalizability of our technique by applying it to three additional lesion syndromes: central post-stroke pain, auditory hallucinosis, and subcortical aphasia. In each syndrome, heterogeneous lesions that themselves had little overlap showed significant network overlap in cortical areas previously implicated in symptom expression (P < 10(-4)). These results suggest that (i) heterogeneous lesions producing similar symptoms share functional connectivity to specific brain regions involved in symptom expression; and (ii) publically available human connectome data can be used to incorporate these network effects into traditional lesion mapping approaches. Because the current technique requires no specialized imaging of patients it may prove a versatile and broadly applicable approach for localizing neurological symptoms in the setting of brain lesions.

摘要

一种将神经症状与特定脑区相联系的传统且广泛应用的方法是,识别具有相似症状的患者在病变位置上的重叠情况,这一方法被称为病变映射。这种方法功能强大且具有广泛适用性,但当症状并非局限于单个区域,或者源于与病变部位相连的区域而非病变部位本身的功能障碍时,就会存在局限性。一种对这种网络效应敏感的更新方法涉及对患者进行功能神经成像,但这需要常规临床数据之外的专门脑部扫描,使得其通用性较差,并且在症状罕见或短暂出现时难以应用。在本文中,我们表明,传统的病变映射方法可以扩展到将网络效应纳入症状定位中,而无需对患者进行专门的神经成像。我们的方法包括三个步骤:(i)将脑损伤的三维体积转移到一个参考脑上;(ii)使用标准化连接组数据评估病变体积与大脑其他部分的内在功能连接性;(iii)重叠与病变相关的网络,以识别临床综合征共有的区域。我们首先在脑桥幻觉症中测试了我们的方法,脑桥幻觉症是一种皮层下病变后出现视幻觉的综合征,长期以来一直假设这是由于对纹外视觉皮层的网络效应所致。虽然病变本身分布不均,病变位置几乎没有重叠,但23个病变中有22个与纹外视觉皮层呈负相关。与其他皮层下病变相比(P < 10^(-5))以及相对于其他皮层区域(P < 0.01),这种网络重叠具有特异性。接下来,我们通过将其应用于另外三种病变综合征来测试我们技术的可推广性:中风后中枢性疼痛、幻听症和皮层下失语症。在每种综合征中,本身几乎没有重叠的异质性病变在先前与症状表达相关的皮层区域显示出显著的网络重叠(P < 10^(-4))。这些结果表明:(i)产生相似症状的异质性病变与参与症状表达的特定脑区具有功能连接性;(ii)公开可用的人类连接组数据可用于将这些网络效应纳入传统的病变映射方法中。由于当前技术不需要对患者进行专门成像,它可能被证明是一种在脑损伤情况下定位神经症状的通用且广泛适用的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a78/4671478/c02920bf6c7e/awv228fig1g.jpg

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