Functional and Structural Optical Brain Imaging

功能近红外光谱（fNIRS）用于研究两个领域的大脑活动：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thurm博士（NIMH）和Fox博士（UMD）就婴儿镜像神经元网络（MNN）进行合作。MNN与典型人类婴儿出现的复杂社会行为的发展有关。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。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。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。这项工作已于2021年8月发表在Plos One杂志上（Miguel et al., 2021）。正在使用连接性方法进行其他分析。这种方法的结果发表在《脑科学》杂志上（Nguyen et al., 2021）。我们的研究结果表明，在动作执行过程中，当参与者用右手执行一个动作时，左半球内多个区域间的连接是相关的（左中央前区、左中央后区、左顶叶下区以及左边缘上区和左角区之间的连接）。此外，为了利用并发信号（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，目的是利用每种神经成像模式的优势，即EEG的良好时间分辨率和fNIRS的更高焦点分辨率。我们将结构化稀疏多集CCA （ssmCCA）模型应用于我们的集成数据集，结果发现在动作执行/观察过程中，在感兴趣的区域中发现了相似的活动模式，表明当受试者执行运动动作时，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。这是首次将不同的脑指标（血流动力学反应功能和电活动）融合在一起来表征人脑的MNN，并指出左顶叶下区是动作执行和动作观察的主要激活脑区。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。这项工作已发表在《科学报告》杂志上（Dashtestani et al., 2022）。在研究了行动执行和行动观察过程中的大脑活动模式后，我们将想象条件与行动执行和行动观察联系起来。由于我们已经在我们的范式中实现了动作想象，所以我们也使用我们建立的ssmCCA方法来分析这种情况。增加这一条件的重要性在于，运动认知能力依赖于并通过对动作执行的心理预演和重演机制来实现。我们还发现左顶叶下区是整个想象条件下的主要贡献区。在运动想象任务中激活的其他大脑区域位于左半球，在执行和观察条件下与大脑区域相似，但在不同条件下它们的活动水平不同。虽然关于动作想象的文献不多，但我们的研究结果与其他研究结果是一致的。我们的发现支持了这样一种观点，即动作观察或动作想象激发了支持执行相同动作的相同的感觉-运动皮层网络。在这三种情况下，大脑活动如此相似，一个合理的原因是归因于一个动作的内部练习。这些结果已经在我们准备并计划于2022年10月提交的手稿中进行了广泛的讨论。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）。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。接下来的研究包括同时收集前额皮质的近红外光谱和高频心率变异性（HF-HRV）；在行为灵活性任务（去/不去任务）中，通过心电图来检查前额叶激活和副交感神经系统活动（测量HF-HRV）之间的联系。这些措施之间的关系先前已由神经内脏整合模型描述；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，并在去/不去的任务中进行。结果表明，在休息时，HF-HRV与前额叶激活负相关，这与先前在单独的休息状态下收集HF-HRV和大脑活动的研究一致。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。第二组对上述研究中使用的“走/不走”任务进行了二次数据分析，以检查在简单的“走/不走”任务和情绪“走/不走”任务期间前额叶的连通性。研究结果表明，无论是男性还是女性，更强的连通性都与简单任务的更好表现有关；然而，更强的连通性只与男性在情绪上的表现有关。这些发现显示了男性和女性在情绪行为抑制过程中的功能差异。

Functional near infrared spectroscopy (fNIRS) is used to study brain activity in 2 areas: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.Thurm (NIMH) and Dr. Fox (UMD), on the mirror neuron network (MNN) in infants. MNN is associated with the development of sophisticated social behaviors that emerge in typical human infants. 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. 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. 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 has been published in Plos One journal in August 2021(Miguel et al., 2021). Additional analysis is being conducted using a connectivity approach. Results from this approach was published in the journal of Brain Science (Nguyen et al., 2021).. Our results showed that during the action execution, while a participant was performing an action with the right hand several region-to-region connections within the left hemisphere were related (connections within the left precentral, left postcentral, left inferior parietal and be-tween the left supramarginal and left angular regions). 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 benefitting from each neuroimaging modalities strength, i.e. good temporal resolution of EEG and more focal resolution of fNIRS. We applied structured sparse multiset CCA (ssmCCA) model to our integrated dataset which resulted in finding similar activity patterns during action execution/observation 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 executing a motor action. This is the first report that fused distinct brain metrics (hemodynamic response function and electrical activity) to characterize the MNN in the human brain and pinpoints left inferior parietal region is the dominant activated brain area in both action execution and action observation. 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 work has been published in Scientific Reports journal (Dashtestani et al., 2022). After investigating brain activity patterns during action execution and action observation, we incorporate imagination condition in relation to action execution and action observation. Since we had implemented action imagination into our paradigm, this condition has also been analyzed using our established ssmCCA method. The importance of adding such condition lies in the belief that motor cognitive abilities depending on and achieved by the mechanism of mental rehearsal and re-enactment of action execution. Here, we also found left parietal inferior region is the main contributing area across imagination condition. Other brain regions activating during motor imagery task were located at the left hemisphere and were similar to the brain regions in both execution and observation conditions while their activity levels differ across each condition. Although there is not extensive literature on action imagination, the result of our work was in line with other studies. Our findings back up the idea that action observation or action imagination excites the same sensory-motor cortical network which supports execution of that same action. One plausible reason for such similarities between brain activities across those three conditions has been attributed to internal practice of an action. These results have been extensively discussed in a manuscript that we have prepared and planned to submit for publication by October 2022. 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). 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. Next study involves simultaneous collection fNIRS of the prefrontal cortex and high frequency heart rate variability (HF-HRV); as derived from EKG to examine 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; 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.. 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. 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. The second performed a secondary data analysis on the go/no-go task used in the above study to examine prefrontal connectivity during a simple go/no-go task and an emotional go/no-go task. Findings show that stronger connectivity was associated with better performance on the simple task in both males and females; however, stronger connectivity was only associated with better performance on the emotional go/no-go in males. These findings show functional differences during emotional behavior inhibition in males compared to females.