Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Epilepsy Behav. 2013 Nov;29(2):400-6. doi: 10.1016/j.yebeh.2013.08.028. Epub 2013 Oct 3.
Alterations in neuronal circuitry are recognized as an important substrate of many neurological disorders, including epilepsy. Patients with the developmental brain malformation of periventricular nodular heterotopia (PNH) often have both seizures and dyslexia, and there is evidence to suggest that aberrant neuronal connectivity underlies both of these clinical features. We used task-based functional MRI (fMRI) to determine whether heterotopic nodules of gray matter in this condition are integrated into functional cortical circuits. Blood oxygenation level-dependent (BOLD) fMRI was acquired in eight participants with PNH during the performance of reading-related tasks. Evidence of neural activation within heterotopic gray matter was identified, and regions of cortical coactivation were then mapped systematically. Findings were correlated with resting-state functional connectivity results and with performance on the fMRI reading-related tasks. Six participants (75%) demonstrated activation within at least one region of gray matter heterotopia. Cortical areas directly overlying the heterotopia were usually coactivated (60%), as were areas known to have functional connectivity to the heterotopia in the task-free resting state (73%). Six of seven (86%) primary task contrasts resulted in heterotopia activation in at least one participant. Activation was most commonly seen during rapid naming of visual stimuli, a characteristic impairment in this patient population. Our findings represent a systematic demonstration that heterotopic gray matter can be metabolically coactivated in a neuronal migration disorder associated with epilepsy and dyslexia. Gray matter nodules were most commonly coactivated with the anatomically overlying cortex and other regions with resting-state connectivity to heterotopia. These results have broader implications for understanding the network pathogenesis of both seizures and reading disabilities.
神经元回路的改变被认为是许多神经疾病的重要基础，包括癫痫。患有脑室周围结节性异位（PNH）发育性脑畸形的患者经常既有癫痫发作又有诵读困难，有证据表明异常的神经元连接是这两种临床特征的基础。我们使用基于任务的功能磁共振成像（fMRI）来确定这种情况下的异位灰质结节是否整合到功能皮质回路中。在进行与阅读相关的任务时，我们在八名 PNH 患者中采集了血氧水平依赖（BOLD）fMRI。确定了异位灰质内的神经激活证据，然后系统地绘制了皮质共激活区域图。结果与静息状态功能连接结果和 fMRI 阅读相关任务的表现相关。六名参与者（75%）在至少一个异位灰质区域显示出激活。异位灰质正上方的皮质区域通常被共激活（60%），而在静息状态下与异位灰质具有功能连接的区域（73%）也是如此。在七个（86%）主要任务对比中，有六个导致至少一个参与者的异位激活。在快速命名视觉刺激期间最常见激活，这是该患者群体的特征性损伤。我们的发现代表了对代谢共激活与癫痫和诵读困难相关的神经元迁移障碍中的异位灰质的系统演示。灰质结节最常见与解剖上覆盖的皮质以及与异位灰质具有静息状态连接的其他区域共激活。这些结果对理解癫痫发作和阅读障碍的网络发病机制具有更广泛的意义。
