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

描述（由申请人提供）：颞叶癫痫手术患者的语义缺陷可能代表结构连接性问题：扩散成像探索摘要语义记忆反映了一个人对世界和经验的事实信息的知识，而语义处理更广泛地涉及访问此存储知识的行为。虽然已经从损伤研究和神经影像学范式中了解了大量关于语义处理的知识，但关于这些过程中涉及的神经机制和大脑中概念信息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，语言优势前颞叶（ATL）功能障碍与类别相关的命名问题有关，而非优势ATL功能障碍与视觉识别和熟悉性判断中的类别相关缺陷有关。TLE患者术前常出现分类相关缺陷，许多患者术后严重恶化。我们的数据表明，几乎所有成年发作的TLE患者表现出这种下降，而许多早发患者没有（可能反映了后一组的功能重组）。初步数据表明，由于这些限制，一些患者的职业和/或社会功能受到严重损害;许多患者伴随着情绪/精神困扰。然而，这些缺陷几乎没有被癫痫外科界所认识。 我们的数据表明，这些命名、识别和熟悉缺陷反映了“断开综合征”，作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，尽管当我们的措施需要它们之间的相互作用时会发生任务失败。我们还提出了几个不同的例子表明，改变任务要求可以促进或阻碍性能。例如，命名缺陷的患者通常选择正确的对象名称时，提供了一个多项选择识别格式，但再次无法自发命名相同的视觉图像仅几分钟后。研究表明，ATL中的神经区域以及将它们与其他关键大脑区域连接的白色物质（WM）通路是我们识别和命名某些对象类别的能力的基础。由于扩散张量成像（DTI）和皮层下电刺激映射的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束的中断（由于与癫痫发作或手术前横断相关的生理变化）有助于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和WM通路之间的关系，这些通路位于这些过程的神经回路的核心。如果我们能够确定关键的WM通路，将来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，反应性刺激映射），从而防止命名，面部/物体识别和复杂语义学习的破坏性缺陷。我们将通过确定哪些穿越每个大脑半球TL区域的束与基线表现密切相关，并通过检查哪些在观察到类别相关缺陷时受到损害，来证明关键通路。我们的研究代表了理解这些回路的重要一步，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的患者接受手术涉及前TL。这与NIH治愈癫痫的目标一致，即改善癫痫患者的临床结局，并对接受其他神经外科干预和TL疾病的患者具有更广泛的意义。 在随后的研究中，我们希望将联合收割机扩散成像技术与功能连接范例相结合，以研究支持这些认知功能的更广泛的神经回路。目前的K 02奖励机制将为Drane博士提供必要的培训，以有效地分析使用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弥散成像技术（鉴于大多数临床环境中缺乏这些技术），以确保该程序在个人水平上得到验证，并转化为常规临床使用。我们还希望，这个项目将使我们能够把我们的研究方案变成一个临床措施的类别相关的命名和识别性能，可以在整个癫痫外科社区传播，因为没有这种类型的措施目前可用。最后，我们的研究对神经科学也有内在价值，因为我们可以在映射语义记忆系统的神经回路方面取得重大进展，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.