要了解大脑的认知功能,就必须了解神经元是如何在局部、不同脑区以及整个大脑的大规模范围内相互连接的。局部处理和全局整合之间的平衡为复杂的处理模式提供了支持,这些模式是高阶认知功能的基础,同时确保了大脑的灵活性、稳健性和功能多样化。在这种情况下,网络范式为研究脑区之间的相互作用以及使用强大的计算工具解释功能网络的复杂拓扑结构提供了理论框架。本文回顾了研究大脑功能网络的当前技术水平,并总结了用于量化网络特征的方法进展。同时概述了主要的神经成像技术,探讨了目前有关认知功能和功能障碍的核心大规模网络的知识。
前言
对脑功能网络的全面表征不仅产生了对正常认知过程的大量描述,而且还产生了对不同网络功能障碍在异常和神经障碍(如抑郁症、癫痫、精神分裂症、自闭症和脑震荡后综合征)中所起作用的新见解。本文根据脑功能网络科学的最新发展,探讨了理解认知的神经基础的技术现状,脑功能网络已成为揭示分布式大脑系统内部和之间相互作用如何产生认知的主要范式。这是因为涉及认知处理不同方面的大规模脑网络之间的相互作用对于更深入地了解认知的神经基础至关重要。
功能神经成像技术在网络发现中的应用
神经成像技术的优缺点
连续波fNIRS是一种相对较新的技术,它结合了功能磁共振成像在空间分辨率方面的优势,但依赖于生物发色团的不同吸收特性,而不是血红蛋白的顺磁性。通过在光源和探测器对之间传递近红外光(700-900nm)来实现这一点,这些探测器对通常位于头皮上,距离范围为2cm到5cm。虽然fNIRS具有便携性和易用性特点,以及对头部运动伪影的敏感性相对较低,但它仅限于对皮层的表层进行采样,这与提供全脑测量的fMRI不同。
多模态方法
网络建模和分析方法
脑网络是认知功能的基础
脑网络:节点和边缘
图3.用不同的传感技术测量脑功能网络的典型步骤。
节点定义
此外,对于EEG和MEG,信号可以通过带通滤波技术分解成典型的频段。一旦与皮层源对应的信号被重建,这既可以在传感器水平也可以在源水平上完成。EEG/MEG频段分为delta(1-4Hz)、theta(4-8Hz)、alpha(8-13Hz)和beta(>13Hz),而更高频的活动(通常高于30Hz)称为gamma活动。在这些类型的分析中,在每个频段内都构建了不同的功能连通性网络,从而实现多层网络分析,如图4所示。
图4.通过对测量数据(最常见的是EEG和MEG)进行频域分解,多层网络形式可用于研究大脑活动。不同的层代表不同频段的脑功能网络,或者不同的层可能表示不同的数据形式。
边缘定义
表1.常用功能连接测量的列表。
脑网络的统计意义
选择合适的阈值通常具有挑战性。为了避免选择任意的阈值,可以考虑一个阈值范围,并在结果中重复所需的统计分析。这通常会产生多次统计检验,因此需要进行多个检验的校正。或者将所研究的网络测量值在阈值范围内进行整合,得到曲线下面积(AUC),然后对AUC进行统计检验。
大规模功能网络与认知
大脑区域作为大规模功能网络的一部分发挥着特定的作用。研究最多的网络包括默认模式网络(DMN),突显网络(SN),中央执行网络(CEN)和注意网络(背侧(DAN)和腹侧(VAN))(图5)。有证据支持这样一种观点,即结构/解剖网络只对功能连接起约束作用,而不完全决定功能连接。
图5.在认知中起主要作用的大规模网络。
图6.三重网络模型广泛用于描述默认模式网络、突显网络和中央执行网络之间的动态相互作用。
默认模式网络(DMN)
大量的脑部疾病与DMN的功能障碍有关。这些疾病包括AD、自闭症、注意缺陷多动障碍、双相情感障碍、抑郁症、癫痫、情绪障碍、帕金森病和创伤后应激障碍。然而,关于DMN的临床意义,需要指出的是,很少有研究报告DMN内的连通性中断(主要是神经退行性疾病,如AD),而大多数研究将疾病与DMN与其他大规模网络(如CEN和SN)之间的不平衡联系起来。然而,DMN在清醒镇静下似乎持续存在,其后扣带皮层成分的活动有局灶性降低。最后,虽然上述大多数观察结果都是基于人类研究,但应该注意的是,关于DMN一般特征的确凿性证据也在非人类哺乳动物中存在。
突显网络(SN)
大量的研究也强调了SN在健康大脑认知过程中的作用。举几个例子,最近一项涉及图论指标的研究显示,随着认知负荷的增加,SN和CEN中的功能连接显著增加,而DMN中的功能连接显著减少。此外,由于错误往往在正常的认知行为中很突出,最近的研究调查了大脑的错误监测系统与SN之间的联系。研究结果发现,源于AI的加工可以检测错误信号并将其传递给ACC,然后以前馈方式传递给感觉运动区域。
中央执行网络(CEN)
注意网络
在大规模功能网络的背景下,引起广泛兴趣的另一个领域是注意过程和潜在的神经机制。目前用于研究注意网络的两个最有影响力的模型是Posner和Petersen在90年代初提出的三个子系统模型以及Corbetta和Shulman提出的双网络模型。
三个子系统模型已被证明对应于不同脑区的协同功能活动:(i)警报子系统,负责获得和维持警觉状态和警惕性,它位于脑干蓝斑部位,通过去甲肾上腺素通路投射到额叶和顶叶皮层区域;(ii)定向子系统,将显性和隐形注意力引导到刺激上,位于腹内侧额叶皮层(vFC)、颞顶交界处(TPJ)、额叶视区(FEF)和顶内沟/顶叶上叶(IPS/SPL);(iii)执行控制子系统,它涉及对目标的检测,以及为意识加工检测和选择刺激。该子系统涉及大量区域,包括ACC、AI和纹状体(图7)。
图7.典型的大脑注意网络。
Posner模型中的第三个子系统是执行控制子系统,它对各种任务中目标检测和选择过程中的自发响应提供自上而下的控制。该系统进一步分为两个独立的执行控制网络:(i)额顶网络,与上述定向子网络不同,由背侧额叶皮层(dFC),IPS,IPL,楔前叶和内侧扣带皮层(mCC)内的节点组成;(ii)扣带回-盖部网络,由前额叶皮层(aPFC)、dACC、AI和fO中的节点组成(图7b)。这两个系统相对独立地在任务执行期间实现自上而下的控制。扣带回-盖部网络和SN在解剖拓扑结构方面有很大程度的重叠,一些研究表明它们实际上是同一个神经网络的一部分。许多功能障碍都与执行控制系统有关,包括焦虑、抑郁、精神分裂症和强迫症。
总结
本文回顾了用于描述脑功能网络的主要概念和技术,介绍了有关大规模功能网络在认知中的作用。可以看到,基于网络的脑科学为在多个尺度上研究神经活动提供了一个框架,它不仅被应用于基础神经科学,而且越来越多地应用于临床和转化研究。网络结构存在于大脑的所有组织层面,从细胞(单个神经元和突触)到全脑区域和系统水平。本文将重点放在分析全脑水平及其各个解剖区域和功能系统的相互作用的方法上,目的是提供有关建模步骤的系统观点,同时也描述大规模网络组织,这在基于模型的认知功能和功能障碍研究中越来越流行。此外,随着多模态神经成像方法的日益普及,预计多层网络方法的使用将成为常态。例如,同时获取的fMRI-EEG提供了有关不同神经生物学机制以及高时空分辨率,多层网络是用来解释这种多模态、多尺度数据的数学模型。多层网络已在EEG研究中得到了应用,它们被用于优化描述同时发生在不同频段上的功能相互作用,从而有可能揭示不同神经机制的功能耦合。
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