Learning and plasticity in the human brain

本研究的主要目标是：i）在神经系统损伤或功能障碍的背景下建立大脑处理的差异; ii）确定学习诱导的可塑性改善这种变化的负面后果的潜力。在过去的一年里，我们主要关注自闭症谱系障碍（ASD）和截肢的影响，以及建立伴随学习/训练的大脑结构变化。 1)躯体感觉输入丧失（方案08-M-0052，NCT 00623818） 截肢后，超过90%的人报告他们失去的肢体有幻肢感，通常是疼痛感（幻肢痛或PLP）。目前的一种理论认为，PLP是皮层重组的直接结果，是适应不良可塑性的一个例子。镜子疗法已被用作PLP的治疗。在这种治疗过程中，患者在看镜子的同时移动他们完整的肢体，使其看起来好像他们缺失的肢体在移动。我们目前正在研究截肢的神经后果以及镜像治疗对大脑活动的影响。我们继续招募单侧截肢者，并在四周内用功能磁共振成像监测大脑活动，同时截肢者接受镜像治疗。我们正试图确定PLP的存在是否与躯体感觉和运动皮层的皮层重组相关（类似于我们在黄斑变性参与者中观察到的），以及镜像疗法是否通过减少皮层重组的程度而起作用。 2)自闭症谱系障碍（方案10-M-0027，NCT 01031407） 我们一直在研究自闭症谱系障碍（ASD）的运动处理，决策和注意力，这些过程得到了特征良好的大脑网络的支持。 以前，我们报道了ASD运动处理受损的证据。通过改变允许做出判断的时间，我们发现ASD中的运动处理比匹配的对照参与者弱，但仅在短时间内。我们使用fMRI进行了一项脑成像研究，并发现ASD参与者对运动刺激的反应减少，即使在皮层视觉处理的最早阶段（初级视觉皮层，V1）。此外，与行为数据一致，仅在短刺激持续时间下观察到这种效应（Robertson et al，2014，Brain）。 我们还研究了大脑皮层兴奋和抑制之间的潜在不平衡，这是许多自闭症神经生物学模型的核心组成部分。双眼竞争，即视觉刺激分别呈现给双眼以相互竞争并产生交替的视觉感受的趋势，被认为反映了兴奋性和抑制性皮层动力学的推拉。 我们发现ASD中双眼竞争交替的速率较慢，并且该速率可预测自闭症神经病学的临床测量，支持非典型皮质动力学可能是自闭症的一些症状的基础的观点（Robertson等人，2013，Journal of Neuroscience）。 3)学习/培训（方案93-M-0170，NCT 00001360） 我们正在对学习不同任务（例如运动序列）的参与者进行长期纵向研究，以确定大脑的结构特性如何随时间变化。在为期四周的时间里，参与者接受了两项不同任务的培训，我们在培训过程中收集了大量的功能和结构MRI数据。 确定成人皮质可塑性的性质、程度和后果，为神经系统损伤或功能障碍后的康复性脑治疗提供了重要的见解。

The primary goals of this research are i) to establish differences in brain processing in the context of nervous system damage or dysfunction, and ii) to determine the potential for learning-induced plasticity to ameliorate the negative consequences of such changes. Over the past year we have primarily focused on Autism Spectrum Disorders (ASD) and the impact of amputation, and on establishing the structural brain changes that accompany learning/training. 1) Loss of somatosensory input (Protocol 08-M-0052, NCT00623818) Following limb amputation, over 90% of people report phantom sensations in their missing limb, often painful sensations (Phantom Limb Pain, or PLP). One current theory suggests that PLP is a direct result of cortical reorganization, an example of maladaptive plasticity. Mirror therapy has been used as a treatment for PLP. During this therapy, patients move their intact limb while looking in a mirror, making it seem as if their missing limb is moving. We are currently investigating the neural consequences of amputation and the impact of mirror therapy on brain activity over time. We are continuing to recruit unilateral limb amputees and monitoring brain activity with fMRI over a period of four weeks while the amputees undergo mirror therapy. We are trying to establish whether the presence of PLP correlates with cortical reorganization in the somatosensory and motor cortex (similar to that observed in our participants with macular degeneration) and whether the mirror therapy works by reducing the extent of cortical reorganization. 2) Autism Spectrum Disorders (Protocol 10-M-0027, NCT01031407) We have been investigating motion processing, decision-making and attention in Autism Spectrum Disorders (ASD), processes that are supported by well-characteristic brain networks. Previously, we reported evidence for impaired motion processing in ASD. By varying the time allowed to make judgments, we found that motion processing in ASD was weaker then in matched control participants, but only at short durations. We followed up these results with a brain imaging study using fMRI, and found that responses to motion stimuli were reduced in ASD participants even in the earliest stages of cortical visual processing (primary visual cortex, V1). Further, consistent with the behavioral data, this effect was observed only at short stimulus durations (Robertson et al, 2014, Brain). We also investigated potential imbalance between excitation and inhibition in cortex, which has been a central component of many models of autistic neurobiology. Binocular rivalry, the tendency for visual stimuli presented separately to the two eyes to compete with each other and produce an alternating percept, is thought to reflect the push and pull of excitatory and inhibitory cortical dynamics. We found a slower rate of binocular rivalry alternations in ASD, and the rate was predictive of clinical measures of autistic symptomatology, supporting the notion that atypical cortical dynamics may underlie some of the symptoms of autism (Robertson et al, 2013, Journal of Neuroscience). 3) Learning/training (Protocol 93-M-0170, NCT00001360) We are conducting a long-term longitudinal study of participants learning different tasks (e.g. motor sequences) to determine how structural properties of the brain change over time. Over a period of four weeks, participants are trained in two different tasks and we collect extensive functional and structural MRI data over the course of training. Establishing the nature, degree and consequences of plasticity in the adult cortex provides important insights into the potential for rehabilitative brain therapies following injury or dysfunction in the nervous system.