Department of Psychology, University of Michigan, Ann Arbor, United States.
Kavli Foundation, Oxnard, United States.
Neuroimage Clin. 2017 Jun 27;15:801-811. doi: 10.1016/j.nicl.2017.06.032. eCollection 2017.
Neurofibromatosis Type 1 (NF1) is a genetic disorder that disrupts central nervous system development and neuronal function. Cognitively, NF1 is characterized by difficulties with executive control and visuospatial abilities. Little is known about the neural substrates underlying these deficits. The current study utilized Blood-Oxygen-Level-Dependent (BOLD) functional MRI (fMRI) to explore the neural correlates of spatial working memory (WM) deficits in patients with NF1.
BOLD images were acquired from 23 adults with NF1 (age = 32.69; 61% male) and 25 matched healthy controls (age = 33.08; 64% male) during an in-scanner visuo-spatial WM task. Whole brain functional and psycho-physiological interaction analyses were utilized to investigate neural activity and functional connectivity, respectively, during visuo-spatial WM performance. Participants also completed behavioral measures of spatial reasoning and verbal WM.
Relative to healthy controls, participants with NF1 showed reduced recruitment of key components of WM circuitry, the left dorsolateral prefrontal cortex and right parietal cortex. In addition, healthy controls exhibited greater simultaneous deactivation between the posterior cingulate cortex (PCC) and temporal regions than NF1 patients. In contrast, NF1 patients showed greater PCC and bilateral parietal connectivity with visual cortices as well as between the PCC and the cerebellum. In NF1 participants, increased functional coupling of the PCC with frontal and parietal regions was associated with better spatial reasoning and WM performance, respectively; these relationships were not observed in controls.
Dysfunctional engagement of WM circuitry, and aberrant functional connectivity of 'task-negative' regions in NF1 patients may underlie spatial WM difficulties characteristic of the disorder.
神经纤维瘤病 1 型（NF1）是一种遗传疾病，会破坏中枢神经系统的发育和神经元功能。认知方面，NF1 的特征是执行控制和视空间能力困难。对于这些缺陷的神经基础知之甚少。目前的研究利用血氧水平依赖（BOLD）功能磁共振成像（fMRI）来探索 NF1 患者空间工作记忆（WM）缺陷的神经相关性。
从 23 名 NF1 成年患者（年龄=32.69；61%为男性）和 25 名匹配的健康对照组（年龄=33.08；64%为男性）中采集 BOLD 图像，他们在扫描仪内进行视觉空间 WM 任务时。利用全脑功能和心理生理交互分析分别研究视觉空间 WM 表现期间的神经活动和功能连接。参与者还完成了空间推理和言语 WM 的行为测量。
与健康对照组相比，NF1 患者的 WM 回路的关键组成部分，即左侧背外侧前额叶皮层和右侧顶叶皮层的招募减少。此外，与 NF1 患者相比，健康对照组在后扣带回皮层（PCC）和颞叶之间表现出更大的同时去激活。相比之下，NF1 患者表现出与视觉皮层以及 PCC 和小脑之间更大的 PCC 和双侧顶叶连接。在 NF1 参与者中，PCC 与额叶和顶叶区域的功能耦合增加与空间推理和 WM 表现分别相关；这些关系在对照组中没有观察到。
NF1 患者 WM 回路的功能障碍和“任务负性”区域的异常功能连接可能是该疾病特征的空间 WM 困难的基础。
