Functional and Structural Optical Brain Imaging

我们正在使用功能性近红外光谱（fNIRS）在两个不同的研究方向上研究大脑活动：1)儿童认知能力的发展轨迹；2)fNIRS使用先前使用功能磁共振成像评估的认知任务的有效性。在发育研究方面，我们继续与Audrey Thurm博士（NIMH）和Nathan Fox博士（马里兰大学）就婴儿镜像神经元网络（IRB # 18-CH-0001）进行合作。镜像神经元网络（MNN）与典型人类婴儿出现的复杂社会行为的发展有关（例如，复杂的模仿，解码情绪状态）。在临床行为缺陷被发现之前，对MNN发展进行建模将创建一个敏感的社会沟通发展偏差测量。我们完成了40名成人受试者的数据收集，这些受试者接受了运动观察和执行范式，同时通过EEG/fNIRS测量了他们的大脑活动。MNN激活已经与脑电图的Mu抑制相关联。利用EEG（具有高时间分辨率）结合fNIRS，将提供基于血流动力学激活的更精确的神经活动空间分辨率来研究MNN。在该议定书范围内，目前正在编写/提交若干手稿。我们对当前fNIRS研究行动观测网络的文献进行了综述。本综述的目的是评估和批判使用近红外光谱（fNIRS）研究健康成人动作观察网络的方法学和分析方法。除了作为规划镜像神经元项目经验方法的重要准备步骤外，我们认为将这些文献整合到综述论文中是对该领域的重要贡献，可以鼓励其他研究人员考虑将fNIRS测量整合到这些类型的研究中。稿件将于2020年9月前提交给《神经影像》杂志。此外，我们还在30名受试者的子样本中研究了fNIRS用于MNS（也称为行动观察网络- AON）研究的可行性。结果表明，包括双侧顶叶上小叶（SPL）、双侧顶叶下小叶（IPL）、右侧边缘上区域（SMG）和右侧角回（AG）在内的顶叶区域是人类AON的候选区域。此外，我们还证明了该范式对自闭症亚临床水平的差异很敏感，这可以用于未来对行动理解和行动表征缺陷的临床人群（即自闭症谱系障碍（ASD））的研究。这项工作目前正在修订中，将于2020年10月前提交出版。正在使用连接性方法进行额外的分析，以确定观察条件和执行条件的增加在个人级别上是否不同。为此，我们正在研究所有受试者活动的相关性。我们发现8个区域内连接，包括左右中央前区、中央后区、角区、右边缘上区、左顶叶下区和左顶叶上区；7个区域之间连接，包括中央前区和中央后区（两侧）、右中央前区和左顶叶上区、左边缘上区和左角区、左顶叶下区和左中央后区、左顶叶下区和左顶叶上区、左中央后区和左顶叶上区，以及左中央后区和左顶叶上区。它们可能是MNN的候选者。这些连接满足以下条件：1)在行动观察任务和行动执行任务中具有较强的连通性；2)在两个任务中的连通性之间具有显著的相关性。此外，为了使用并发信号（EEG和fNIRS）充分表征MNN网络，我们正在进行多模态多集数据融合分析，目的是让模态充分相互作用。在综合数据集上应用mCCA后，我们观察到与先前文献一致的结果。动作执行/观察显示了类似的活动模式，表明当受试者执行动作时，左半球区域（中央旁区域、中央前区域、顶叶下上部区域）的大脑活动更高。在观察条件下，还发现大脑左侧区域，即中央后、中央旁、中央前和顶叶上、下区域的大脑活动也较高。这一初步分析是非常相关的，因为它是第一个使用不同的脑指标（血流动力学反应函数和电活动）来表征人脑中MNN的报告。由于我们的试点研究验证了MNN范式，我们现在开始招募正常发育的婴儿（9-12个月）（n=60）。一旦我们在这个样本中的一部分婴儿中测试了范式，我们将开始招募有风险的婴儿。我们继续与国家儿童医学中心的Andrea Gropman博士合作，研究尿素循环障碍（UCD）儿童的发育缺陷，特别是以高氨（HA）为特征的鸟氨酸转氨基甲酰酶缺乏症（OTCD）。已知HA会导致执行功能和工作记忆受损。监测OTCD的进展和研究神经认知生物标志物对于检查OTCD的潜在脑功能至关重要。我们使用近红外光谱（fNIRS）检查了OTCD人群和有和没有OTCD的异卵双胞胎PFC的血流动力学。结果显示，在对照组和OTCD患者之间，左侧PFC激活存在差异，其中对照组在执行Stroop任务时显示出更高的任务相关激活增加。OTCD患者也表现出双侧PFC激活增加。当双胞胎执行N-Back工作记忆任务时，我们量化了总血红蛋白的血流动力学变化。我们的初步结果表明，与对照组相比，OTCD兄弟姐妹在极低频段（<0.03 Hz，与大脑自动调节机制有关）的变化更高，可能是由于HA的影响。功能连通性（FC）分析还显示，随着任务负荷的增加，OTCD兄弟姐妹的半球间FC降低。最后，作为我们正在进行的fNIRS校准协议（irb# 10-CH-0198）的一部分，一份手稿目前正在神经科学前沿进行修改和重新提交阶段。通过使用同时收集的前额叶皮层功能近红外光谱（fNIRS）和高频心率变异性（HF-HRV；来源于心电图），我们研究了在行为灵活性任务（走/不走任务）中前额叶激活和副交感神经系统活动（测量的HF-HRV）之间的联系。这些措施之间的关系之前已经被神经内脏整合模型描述过（Thayer & Lane, 2000）；然而，迄今为止还没有研究同时审查这些措施。这些数据是在38名健康成人对照中收集的，他们处于休息状态，并在执行/不执行任务期间进行。然后比较基线期和任务期的HF-HRV和前额叶fNIRS激活的时间过程，以确定它们是否随时间而相关。结果表明，在休息时，HF-HRV与前额叶激活呈负相关，这与之前在单独的休息状态下收集HF-HRV和大脑活动的研究一致（Allen et al., 2015）。这些结果支持了神经内脏整合模型的原则，以及fNIRS在未来研究该模型及其与认知功能关系的应用。

We are using functional near infrared spectroscopy (fNIRS) to study brain activity in 2 distinct lines of research:1) developmental trajectories of cognitive abilities in children and 2) validity of fNIRS using cognitive tasks previously evaluated using fMRI. Under the developmental studies, we have continued the collaboration with Dr. Audrey Thurm (NIMH) and Dr. Nathan Fox (University of Maryland), on the mirror neuron network in infants (IRB # 18-CH-0001). The mirror neuron network (MNN) is associated with the development of sophisticated social behaviors that emerge in typical human infants (e.g., complex imitation, decoding emotional states). Modeling MNN development will create a sensitive measure of deviations in social communication development before clinical behavioral deficits can be detected. We have finished data collection in adult pilot subjects (N=40) who underwent a motor observation and execution paradigm while their brain activity measured through EEG/fNIRS simultaneously. MNN activation has already been associated with Mu suppression using EEG. By using EEG (with high temporal resolution) in conjunction with fNIRS will provide a more precise spatial resolution of neural activity based on hemodynamic activation to investigate the MNN. Within this protocol several manuscripts are currently under preparation/ submission. We conducted a review on the current fNIRS literature examining the action-observation network. The purpose of the review was to assess and critique the methodological and analytic approaches that have been used to study the action-observation network in healthy adults using fNIRS. In addition to being an important preparatory step in planning our empirical approach for our mirror neuron project, we felt that integrating this literature into a review paper was an important contribution to the field that could encourage other researchers to consider integration fNIRS measurement into these types of studies. The manuscript will be submitted to Neuroimage by September 2020. In addition, we have also examined the feasibility of fNIRS for the study of MNS (also referred to action-observation network- AON) in a subsample of 30 subjects. Overall, our results indicated that the parietal regions, including bilateral superior parietal lobule (SPL), bilateral inferior parietal lobule (IPL), right supra-marginal region (SMG) and right angular gyrus (AG) are candidate regions of the human AON. Moreover, we demonstrated that the paradigm is sensitive to differences in subclinical levels of autistic traits, which can be used in future studies with clinical populations who present deficits in action understanding and action representation, namely autism spectrum disorders (ASD). This work in now under revision and will be submitted to publication by October 2020. Additional analysis is being conducted using a connectivity approach to determine if increases in observation and execution conditions are distinct at an individual level. For this purpose, we are examining the correlation of activity across all subjects. We found 8 within region connections including the right and left precentral, postcentral, and angular, right supramarginal, left parietal inferior, and left parietal superior regions, and 7 between regions connections including precentral and postcentral (both sides), right precentral and left parietal superior, left supramarginal and left angular, left parietal inferior and left postcentral, left parietal inferior and left parietal superior, and left postcentral and left parietal superior, which can potentially be candidates of the MNN. These connections satisfy conditions of 1) having a strong connectivity in both action-observation and action-execution task and 2) a significant correlation between the connectivity during both tasks. Furthermore, to fully characterize the MNN network using concurrent signals (EEG and fNIRS) we are conducting multimodal multiset data-fusion analysis with the goal of letting the modalities fully interact. After applying mCCA on the integrated datasets we observed consistent results with previous literature. Action execution/observation showed a similar pattern of activity across regions of interest indicating higher brain activity in regions in the left hemisphere (paracentral region, precentral region, and parietal inferior and superior regions) while subjects were performing an action. For the observation condition also higher brain activity was also found in left regions of the brain, namely the postcentral, paracentral, precentral, and parietal superior and inferior regions. This preliminary analysis is very relevant, as it is the first report that uses distinct brain metrics (hemodynamic response function and electrical activity) to characterize the MNN in the human brain. As our pilot study validates the MNN paradigm, we have now started recruiting typically developing infants (9-12 months) (n=60). Once we have tested the paradigm in a subset of infants in this sample, we will start recruiting infants at-risk. We have continued the collaboration with Dr. Andrea Gropman at Childrens National Medical Center examining developmental deficits in children with Urea Cycle Disorders (UCD), especifically Ornithine transcarbamylase deficiency (OTCD) characterized by presence of hyperammonia (HA). HA is known to cause impairments of executive function and working memory. Monitoring OTCD progression and investigating neurocognitive biomarkers can become critical in examining the underlying brain function in OTCD. Using fNIRS we examined the hemodynamics of PFC in OTCD population and fraternal twin with and without OTCD. Results revealed a distinction in left PFC activation between controls and patients with OTCD, where controls showed higher task related activation increase while performing the Stroop task. Subjects with OTCD also exhibited bilateral increase in PFC activation. We quantified the hemodynamic variations in total-hemoglobin, while twins performed the N-Back Working Memory task. Our preliminary results showed that the sibling with OTCD had higher variations in a very low frequency band (<0.03 Hz, related to mechanism of cerebral autoregulation) compared to the control sibling, possibly due to effect of HA. Functional connectivity (FC) analysis also revealed lower interhemispheric FC in an OTCD sibling as the task load increased. Lastly, as part of our ongoing fNIRS calibration protocol (IRB #10-CH-0198), one manuscript is currently in the revise and resubmit phase at Frontiers in Neuroscience. Through the use of simultaneously collected functional near-infrared spectroscopy (fNIRS) of the prefrontal cortex and high frequency heart rate variability (HF-HRV; as derived from electrocardiogram), we examined the connection between prefrontal activation and parasympathetic nervous system activity (as measured HF-HRV) during a behavioral flexibility task (the go/no-go task). The relationship between these measures has been previously described by the neurovisceral integration model (Thayer & Lane, 2000); however, no study to date had examined these measures simultaneously. These data were collected in 38 healthy adult controls at rest and during the go/no-go task. The time course of HF-HRV and prefrontal fNIRS activation over the baseline period and the task period were then compared to determine whether they were related over time. Results indicated that at rest, HF-HRV was negatively related to prefrontal activation, consistent with previous studies that had collected HF-HRV and brain activity during separate resting state sessions (Allen et al., 2015). These results support the tenets of the neurovisceral integration model and the utility of fNIRS in future studies examining the model and its relation to cognitive functions.