Semantic Deficits in Temporal Lobe Epilepsy Surgical Patients May Represent A Str

描述(申请人提供)：颞叶癫痫手术患者的语义缺陷可能代表着结构性连接问题：用扩散成像进行探索抽象语义记忆反映了一个人对关于世界和一个人的经历的事实信息的知识，而语义处理更广泛地涉及访问这些存储的知识的行为。虽然已经从损伤研究和神经成像范式中了解了大量关于语义加工的知识，但关于参与这些过程的神经机制和概念信息在大脑中的表征仍然存在很大的不确定性。我们对颞叶癫痫(TLE)手术患者的研究表明，语言显性前颞叶(ATL)功能障碍与类别相关的命名问题有关，而非显性ATL功能障碍与类别相关的视觉识别和熟悉判断缺陷有关。TLE患者在手术前经常出现与类别相关的缺陷，并且在许多患者手术后急剧恶化。我们的数据表明，几乎所有成人起病的TLE患者都表现出这样的下降，而许多早发患者没有(可能反映了后者的功能重组)。初步数据表明，由于这些限制，一些患者经历了职业和/或社会功能的严重损害；许多患者伴随而来的是情绪/精神痛苦。然而，癫痫外科社区实际上并没有意识到这些缺陷。我们的数据表明，这些命名、识别和熟悉度的缺陷反映了“脱节综合症”，因为功能的核心组成部分(例如，语言、视觉处理、语义知识)似乎完好无损，尽管当我们的测量需要它们之间的交互时，任务失败会发生。我们还提供了几个不同的例子，证明改变任务需求可以促进或阻碍性能。例如，有命名缺陷的患者通常在提供多项选择识别格式时选择正确的对象名称，但再次无法自发地命名仅几分钟后呈现的相同视觉图像。研究表明，ATL中的神经区域和连接它们与其他关键大脑区域的白质(WM)通路是我们识别和命名某些对象类别的能力的基础。由于弥散张量成像(DTI)和皮质下电刺激标测的WM表明，这些束的损害足以导致识别和命名缺陷，我们认为这些WM束的破坏(由于与术前癫痫发作或手术横断相关的生理变化)导致了TLE患者的这些缺陷。因此，我们建议使用DTI来确定与类别相关的命名和视觉识别性能以及位于包含这些过程的神经回路的核心的WM通路之间的关系。如果我们能够识别关键的WM通路，未来就可以确保神经外科医生通过改变手术方法或使用替代技术(例如伽玛刀、反应刺激映射)来避免这些通路，从而防止在命名、人脸/物体识别和复杂语义学习方面的毁灭性缺陷。我们将通过确定哪些横跨每个大脑半球TL区域的区域与基线表现密切相关，并通过检查在观察到类别相关缺陷时哪些区域受到影响来展示关键路径。我们的研究代表着朝着理解这些回路迈出的重要一步，并将使我们能够创建术前“扩散成像图”，以指导手术干预结合隐形技术或术中MRI对接受手术涉及前交叉韧带的患者进行。这与NIH治疗癫痫的目标一致，即改善癫痫患者的临床结果，并对接受其他神经外科干预的患者和TLS疾病具有更广泛的影响。在随后的研究中，我们希望将扩散成像技术与功能连接范式相结合，以研究支持这些认知功能的更广泛的神经回路。目前的K02奖励机制将为Drane博士提供必要的培训，以便有效地分析通过这些神经成像工具获得的数据，同时进一步确定WM对这些认知技能的贡献。我们认为，临床研究人员必须熟练掌握这些先进的扩散成像技术(考虑到它们在大多数临床环境中都不存在)，以确保该程序在个人层面得到验证，并转化为常规临床使用。我们也希望这个项目将使我们的研究方案能够将我们的研究方案转变为与类别相关的命名和识别性能的临床测量，可以在整个癫痫外科社区传播，因为目前还没有这类测量方法可用。最后，我们的研究对神经科学也具有内在价值，因为我们可以在绘制语义记忆系统的神经回路方面取得巨大进展，这在健康对照组或其他神经系统疾病患者中是不可能的。

DESCRIPTION (provided by applicant): Semantic Deficits in Temporal Lobe Epilepsy Surgical Patients may represent a Structural Connectivity Problem: Exploration with Diffusion Imaging Abstract Semantic memory reflects one's knowledge of factual information about the world and one's experiences, while semantic processing more broadly relates to the act of accessing this stored knowledge. Although a great deal has been learned about semantic processing from both lesion studies and neuroimaging paradigms, great uncertainty remains regarding the neural mechanisms involved in these processes and the representation of conceptual information in the brain. Our research with temporal lobe epilepsy (TLE) surgical patients demonstrates that language dominant anterior temporal lobe (ATL) dysfunction is associated with category-related naming problems while nondominant ATL dysfunction is associated with category-related deficits in visual recognition and familiarity judgments. Category-related deficits are frequently present preoperatively in TLE patients, and worsen dramatically in many patients following surgery. Our data suggests nearly all adult onset TLE patients exhibit such declines while many of the early onset patients do not (likely reflecting reorganization of function in the latter group). Preliminary data indicate that some patients experience significant compromise of vocational and/or social functioning due to these limitations; with many experiencing concomitant emotional/psychiatric distress. Nevertheless, these deficits have gone virtually unrecognized by the epilepsy surgical community. Our data indicate that these naming, recognition, and familiarity deficits reflect "disconnection syndromes," as core components of functioning (e.g., language, visual processing, semantic knowledge) appear intact despite task failures occurring when our measures require interaction between them. We also present several different examples demonstrating that altering task demands can facilitate or hinder performance. For example, patients with naming deficits typically select the correct object name when provided with a multiple choice recognition format, yet are again unable to spontaneously name the same visual image presented only minutes later. Research demonstrates that neural regions in the ATL and the white matter (WM) pathways that connect them to other key brain areas underlie our ability to recognize and name certain object categories. As diffusion tensor imaging (DTI) and subcortical electrostimulation mapping of the WM suggest that damage to these tracts is sufficient to cause recognition and naming deficits, we believe that the disruption of these WM tracts (due to physiological changes related to seizures preoperatively or surgical transection) contributes to these deficits in TLE patients. Therefore, we propose using DTI to determine the relationship between category-related naming and visual recognition performance and WM pathways that lie at the core of the neural circuits that subsume these processes. If we can identify the critical WM pathways, in the future it can be ensured that these are spared by the neurosurgeon by altering surgical approach or using alternative techniques (e.g., Gamma Knife, responsive stimulation mapping), thus preventing devastating deficits in naming, recognition of faces/objects, and complex semantic learning. We will demonstrate the key pathways by establishing which tracts that traverse the TL regions of each cerebral hemisphere are strongly correlated with baseline performance, and by examining which are compromised when category-related deficits are observed. Our study represents an important step towards understanding these circuits, and will allow us to create preoperative "diffusion imaging maps" to guide surgical intervention in conjunction with stealth technology or intraoperative MRI for patients undergoing surgery involving the anterior TLs. This is consistent with the NIH Curing Epilepsy goal of improving the clinical outcome of epilepsy patients, and has broader implications for patients undergoing other neurosurgical interventions and diseases of the TLs. In subsequent studies we hope to combine diffusion imaging techniques with functional connectivity paradigms in order to study the broader neural circuits involved in supporting these cognitive functions. The current K02 award mechanism will provide Dr. Drane with the necessary training to effectively analyze the data obtained with these neuroimaging tools, while further determining the contribution of WM to these cognitive skills. We feel it is imperative for a clinical researcher to be skilled in these advanced diffusion imaging techniques (given their absence in most clinical settings) in order to insure that this procedure gets validated at the level of the individual, and translated into regular clinical use. We also hope that this project will allow us to turn our research protocol into a clinical measure of category-related naming and recognition performance that can be disseminated throughout the epilepsy surgical community, as no measures of this type are currently available. Finally, our research also has intrinsic value to neuroscience, as we can make great strides in mapping the neural circuitry of the semantic memory system in a manner that is not possible in healthy controls or patients with other neurological diseases.