Dissecting the Cognitive Roles of Hippocampus, Other Temporal Lobe Structures

描述(申请人提供)：累及前内侧颞叶(ATL)的癫痫手术通常会导致语言优势切除后的言语记忆和命名能力下降，以及非优势切除后的视觉记忆下降。我们已经展示了开放的ATL切除也经常导致对几种对象类型的识别或命名下降(例如， 名人)和相关功能(如专有名词流利性)。这些缺陷，以前没有被认为是临床风险，损害了功能状态，并加剧了记忆力下降的负担。我们认为这些缺陷反映了手术进入近侧TL时所造成的附带损伤。我们正在进行的NINDS K02奖使用DTI概率牵引术来确定下降是否源于特定脑白质(WM)路径的损害。这种K02为开发手术选择奠定了基础，通过保留这些功能下的关键路径来改善认知结果。初步数据显示，有几条WM路径与这些指标的基线表现有关，切除特定的纤维束会导致预测的下降。我们的R01方案使用了一种新颖的、微创的、MRI引导的激光消融技术，即选择性激光杏仁核海马区切开术(SLAH)，以直接测试我们的附带损伤假说。SLAH可消融至少50%的海马体和杏仁核，但由于其微创性质，不会直接损害WM。我们假设，仅限于这些结构的损伤不会导致命名和识别缺陷，这与我们的初步数据一致。这使我们能够评估流行的观点，即中层TL结构对这些过程是必不可少的，这一观点源于间接范式(fMRI/刺激标测)。我们的临床数据还表明，大多数SLAH患者没有经历情景记忆下降，这也与普遍认为的海马区功能相反。我们认为，SLAH的结果是：(A)保留了周围的近侧TL结构；(B)远离切除区的WM路径受到的直接和继发性退行性损害较少。我们预测接受SLAH的患者将不会经历命名和识别缺陷，并且将表现出比开放切除患者明显更好的结果。我们预测，包括在开放切除中的WM束将导致这些任务的性能下降，但不会导致海马区和杏仁核切除体积的下降。其次，我们评估了海马体和杏仁核对情景记忆功能的贡献，预测与SLAH相比，开放切除后更大的记忆缺陷。最后，我们将使用MRI弥散参数来探索未切除的WM束的继发性变化，预测SLAH术后这些参数比开放切除后有更大的改善。我们假设，这些未切除的脑束和对侧海马区扩散率的改善将与记忆得分的改善相关(对于SLAH队列来说，这一点最大)。总之，这项研究使我们能够：(A)将杏仁核和海马体与上皮层和TL WM通路对关键认知功能的贡献分离开来，以及(B)确定SLAH是否保留了经常受到开放切除影响的认知功能。

DESCRIPTION (provided by applicant): Epilepsy surgery involving the anteromedial temporal lobe (ATL) often results in verbal memory and naming decline following language dominant resection and in visual memory decline after nondominant resection. We have shown open ATL resections also frequently result in recognition or naming declines for several object types (e.g., famous persons) and related functions (e.g., proper noun fluency). These deficits, not previously recognized as clinical risks, compromise functional status and compound the burden of memory decline. We propose these deficits reflect collateral damage incurred when surgically accessing the mesial TL. Our ongoing NINDS K02 award uses DTI probabilistic tractography to determine if decline results from damage to specific white matter (WM) paths. This K02 is laying the groundwork for developing surgical options to improve cognitive outcome by sparing key paths underlying these functions. Preliminary data show several WM paths are related to baseline performance on these measures, and resection of specific tracts leads to predicted decline. Our R01 proposal uses a novel, minimally invasive, MRI-guided laser ablation technique, selective laser amygdalohippocampotomy (SLAH), to directly test our collateral damage hypothesis. SLAH ablates at least 50% of hippocampus and amygdala, but does not directly damage WM due to its minimally invasive nature. We hypothesize damage restricted to these structures will not lead to naming and recognition deficits, consistent with our preliminary data. This allows us to assess the popular view that mesial TL structures are essential to these processes, which has arisen from indirect paradigms (fMRI/stimulation mapping). Our clinical data also indicate most SLAH patients do not experience episodic memory decline, again contrary to prevailing views of hippocampal function. We propose better memory outcomes after SLAH results from: (a) sparing surrounding mesial TL structures; and (b) less direct and secondary degenerative damage to WM paths away from the resection zone. We predict patients undergoing SLAH will not experience naming and recognition deficits, and will exhibit a significantly better outcome than open resection patients. We predict WM tracts included in open resections will contribute to performance declines on these tasks, but not hippocampal and amygdalar resection volumes. Secondly, we evaluate the contribution of the hippocampus and amygdala to episodic memory functions, predicting greater memory deficits following open resection compared to SLAH. Lastly, we will explore secondary changes in non-resected WM tracts using MRI diffusion parameters, predicting greater improvement in these parameters after SLAH versus open resection. We hypothesize diffusivity improvements in these non-resected tracts and contralateral hippocampus will correlate with improved memory scores (greatest for the SLAH cohort). In sum, this research allows us to: (a) dissociate the contribution of amygdala and hippocampus from that of the overlying cortex and TL WM paths to key cognitive functions, and (b) determine if SLAH preserves cognitive functions frequently affected by open resections.