Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232-2310, USA.
Epilepsia. 2011 Sep;52(9):1741-9. doi: 10.1111/j.1528-1167.2011.03196.x. Epub 2011 Jul 29.
Mesial temporal lobe epilepsy (mTLE) is a chronic disorder with spontaneous seizures recurring for years, or even decades. Many structural and functional changes have been detected in both the seizure focus and distal regions throughout the brain over this duration that may reflect the development of epileptogenic networks. Resting state functional magnetic resonance imaging (fMRI) connectivity mapping has the potential to elucidate and quantify these networks. The network between the left and right hippocampus may very likely be one of the most susceptible to changes due to long-term seizure propagation effects. Therefore, the objective of this study was to quantify cross hippocampal influence in mTLE using high temporal resolution fMRI, and to determine its relationship with disease duration.
fMRI images were acquired in the resting (interictal) state with 500 ms temporal resolution across the temporal lobes of 19 mTLE patients (13 left, 6 right). The left and right hippocampi were identified on each subject's images using both structurally defined and functionally defined boundaries. The cross hippocampal influence was quantified in two ways for each pair of regions: (1) the nondirectional hippocampal functional connectivity calculated as the Pearson's correlation between the average time series in the left and the right hippocampus regions, and (2) the Granger causality (GC) laterality measure, which implies directional influence by determining temporal precedence. Each of these measures was correlated with age, age of onset, and disease duration across subjects to investigate relationship to disease progression.
The hippocampal connectivity was not significantly different between patients with left and right mTLE using either the structurally or the functionally defined regions. Across all patients, hippocampal connectivity was not correlated significantly with age of onset or duration of disease. However, as duration of disease increased after 10 years (nine patients), the hippocampal connectivity increased linearly. Using the functionally defined regions, the GC laterality was increased in the right mTLE over the left mTLE, indicating that the left hippocampus was influencing the right hippocampus more than the right influencing left. This was also positively correlated with age of onset. Furthermore, like hippocampal connectivity, the relationship between GC laterality and duration of disease changes after 10 years duration of disease. After this duration, the GC laterality was positive in the three of three patients with right mTLE (left influencing right), whereas the GC laterality was negative in five of six patients with left mTLE (right influencing left).
This study reveals a relationship between fMRI functional connectivity and causal influence of the left and right hippocampi and duration of disease in mTLE. During the interictal state, the interhemispheric hippocampal connectivity initially is disrupted and then linearly increases as the epilepsy progresses longer than 10 years. This increase in connectivity appears to be due to the hippocampus contralateral to the epileptogenic focus exerting more influence over the ipsilateral hippocampus. These findings may have implications in understanding the functional development of epileptic networks and possibly prediction of surgical outcome of mTLE.
内侧颞叶癫痫（MTLE）是一种慢性疾病，会出现自发性癫痫发作，反复发作数年甚至数十年。在这段时间内，大脑中的癫痫灶和远隔区域都检测到了许多结构和功能的变化，这些变化可能反映了致痫网络的发展。静息状态功能磁共振成像（fMRI）连接图具有阐明和量化这些网络的潜力。左、右海马体之间的网络很可能是最容易受到长期癫痫传播效应变化影响的网络之一。因此，本研究的目的是使用高时间分辨率 fMRI 量化 MTLE 中海马体之间的交叉影响，并确定其与疾病持续时间的关系。
使用 500ms 的时间分辨率在 19 例 MTLE 患者的颞叶范围内采集静息（发作间期）状态的 fMRI 图像（13 例左侧，6 例右侧）。使用结构定义和功能定义的边界在每个受试者的图像上识别左、右海马体。对于每对区域，以两种方式量化跨海马体的影响：（1）非定向海马体功能连接，计算为左、右海马体区域平均时间序列之间的 Pearson 相关系数；（2）格兰杰因果（GC）侧性度量，通过确定时间优先顺序来暗示定向影响。对每个受试者的这些指标与年龄、发病年龄和疾病持续时间进行相关性分析，以探讨与疾病进展的关系。
使用结构或功能定义的区域，左侧和右侧 MTLE 患者的海马体连接没有显著差异。在所有患者中，海马体连接与发病年龄或疾病持续时间均无显著相关性。然而，随着疾病持续时间超过 10 年（9 例患者），海马体连接呈线性增加。使用功能定义的区域，右侧 MTLE 的 GC 侧性比左侧 MTLE 增加，表明左海马体对右海马体的影响大于右海马体对左海马体的影响。这也与发病年龄呈正相关。此外，与海马体连接一样，GC 侧性与疾病持续时间的关系在疾病持续时间超过 10 年后发生变化。在此期间，3 例右侧 MTLE 患者（左影响右）的 GC 侧性为正，而 6 例左侧 MTLE 患者（右影响左）的 GC 侧性为负。
本研究揭示了 MTLE 中左、右海马体的 fMRI 功能连接和因果影响与疾病持续时间之间的关系。在发作间期，半球间海马体连接最初被破坏，然后随着癫痫持续时间超过 10 年而呈线性增加。这种连接的增加似乎是由于癫痫灶对侧的海马体对同侧海马体施加了更大的影响。这些发现可能对理解癫痫网络的功能发展以及预测 MTLE 的手术结果具有重要意义。
