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

摘要语义记忆反映了一个人对世界和个人经历的事实信息的认识，而语义加工更广泛地与获取这些存储知识的行为有关。尽管从损伤研究和神经影像学范式中已经了解了大量关于语义处理的知识，但涉及这些过程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，语言优势型前颞叶（ATL）功能障碍与类别相关的命名问题有关，而非优势型前颞叶功能障碍与视觉识别和熟悉判断的类别相关缺陷有关。分类相关缺陷经常出现在TLE患者术前，并在许多患者术后急剧恶化。我们的数据表明，几乎所有成年TLE患者都表现出这种下降，而许多早发患者则没有（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，一些患者经历了职业和/或社会功能的严重损害；许多人经历了伴随的情绪/精神困扰。然而，这些缺陷几乎没有被癫痫外科界所认识到。我们的数据表明，这些命名、识别和熟悉的缺陷反映了“断开综合症”，作为功能的核心组成部分（例如，语言、视觉处理、语义知识），尽管在我们的测量要求它们之间的相互作用时发生任务失败，但它们似乎完好无损。我们还提供了几个不同的例子来证明改变任务需求可以促进或阻碍绩效。例如，有命名缺陷的患者在提供多项选择识别格式时通常会选择正确的物体名称，但几分钟后出现的同一视觉图像又无法自发地命名。研究表明，ATL和白质（WM）通路中的神经区域将它们与其他关键的大脑区域连接起来，是我们识别和命名某些物体类别的能力的基础。由于弥散张量成像（DTI）和皮层下电刺激WM图谱显示，这些束的损伤足以导致识别和命名缺陷，我们认为这些WM束的破坏（由于术前癫痫发作或手术切除相关的生理变化）导致了TLE患者的这些缺陷。因此，我们建议使用DTI来确定类别相关命名和视觉识别性能与WM通路之间的关系，这些通路位于包含这些过程的神经回路的核心。如果我们能够识别关键的WM通路，在未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）来避免这些通路，从而防止命名，面部/物体识别和复杂语义学习方面的破坏性缺陷。我们将通过确定穿越每个大脑半球TL区域的哪些束与基线表现密切相关，以及通过检查哪些束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，为接受涉及前tl手术的患者进行手术。这与NIH治疗癫痫的目标是一致的，即改善癫痫患者的临床结果，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影响。在后续的研究中，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，以有效地分析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缺乏），以确保该程序在个体层面得到验证，并转化为常规临床应用。我们也希望这个项目将使我们的研究方案转化为一种与类别相关的命名和识别性能的临床测量方法，可以在整个癫痫外科社区传播，因为目前还没有这种类型的测量方法。最后，我们的研究对神经科学也有内在价值，因为我们可以在绘制语义记忆系统的神经回路方面取得重大进展，这在健康对照或患有其他神经系统疾病的患者中是不可能的。

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.