Diagnostic validity and safety of high-gamma language mapping with intracranial EEG

为了避免耐药性癫痫手术后的术后语言障碍， 刺激映射（ESM）被广泛依赖于定位语言皮层，但ESM通常在- 放电（AD）、癫痫发作、不自主运动和疼痛，可能限制标测并影响患者 安全为代价的此外，无害环境管理很耗时，而且通常只能产生全有或全无的结果，因此提供的见解有限 刺激部位的功能。最后，高达30%的患者在切除术后会出现语言功能障碍 由ESM指导。这些限制促使了基于任务相关的可替代映射方法。 高伽马频率（150 -200 Hz）的功率变化，与神经元数量高度相关 发射率变化。虽然高伽马映射（HGM）克服了ESM的上述限制， 其临床验证仅限于在具有显著变化的小病例系列中进行ESM-HGM比较 在不同中心的技术中，产生不一致的结果，方法之间存在无法解释的差异。 此外，HGM和ESM都没有被前瞻性地验证用于预测术后语言 硬膜下皮层电图（ECoG）或立体脑电图（sEEG）的损伤，越来越安全 ECoG的替代品）。这项研究的总体目标是使用一个由三个大型学术机构组成的小型联盟， 癫痫手术中心，以证明iEEG HGM对ECoG和 sEEG在221例患者的前瞻性系列中，使用创新的基于浏览器的床边HGM系统， 标准化方法并在各中心之间共享数据。这项研究将检验HGM可以准确地 预测术后语言结果，但需要与用于 紧急状态管理首先，使用传统的方法来解释HGM结果，我们将测试HGM之间的一致性， 和ESM，并比较其安全性和可行性。基于以前的研究，我们预测HGM将是一种 良好但不完美的ESM结果预测器。然而，我们预测，由于ESM相关的癫痫发作和 由于标测持续时间的差异，HGM将更安全，患者耐受性更好。第二，我们将测试模型 试图解释和调和HGM关于ESM的假阴性和假阳性，我们将 测试这些模型是否包含功能激活（HGM）和有效连接（测量） 皮质-皮质诱发电位（CCEP）可以更好地预测ESM结果。第三，我们将发展和 根据解剖范围和体积预测术后语言结果的测试模型 皮质切除相对于HGM和ESM结果，使用体素病变症状匹配（VLSM）。以来 临床决策目前基于ESM，临床医生将对HGM不知情，我们预测， 当切除HGM+电极时，语言缺陷的百分比将显著更高。这项研究将直接 对神经外科手术语言映射的临床实践产生了深远的影响， 对人类语言网络的结构和动态有价值的见解。

To avoid post-operative language impairments after surgery for drug-resistant epilepsy, electrical cortical stimulation mapping (ESM) is widely relied upon to localize language cortex, but ESM often elicits after- discharges (ADs), seizures, involuntary movements, and pain, which can limit mapping and impact patient safety. Furthermore, ESM is time-consuming and usually produces all-or-none results, providing limited insight into the function of stimulated sites. Finally, up to 30% of patients can have language dysfunction after resections that are guided by ESM. These limitations have motivated an alternative mapping method based on task-related power changes in high-gamma frequencies (≈50-200 Hz), which are highly correlated with neuronal population firing rate changes. Although high-gamma mapping (HGM) overcomes the aforementioned limitations of ESM, its clinical validation has been limited to ESM-HGM comparisons in small case series with significant variations in technique across centers, yielding inconsistent results, with unexplained discrepancies between methods. Moreover, neither HGM nor ESM have been prospectively validated for predicting post-operative language impairments with either subdural electrocorticography (ECoG) or stereo-EEG (sEEG, increasingly a safer alternative to ECoG). The overall objective of this study is to use a small consortium of three large academic epilepsy surgery centers to demonstrate the diagnostic validity and safety of iEEG HGM for both ECoG and sEEG in a prospective series of 221 patients, using an innovative browser-based bedside HGM system to standardize methods and share data across centers. This study will test the hypothesis that HGM can accurately predict post-surgical language outcomes but requires a different framework for interpretation than that used for ESM. First, using traditional methods for interpreting HGM results, we will test the concordance between HGM and ESM, and compare their safety and feasibility. Based on previous studies, we predict that HGM will be a good, but imperfect, predictor of ESM results. However, we predict that due to ESM-related seizures and differences in mapping duration, HGM will be safer and better tolerated by patients. Second, we will test models that attempt to explain and reconcile HGM false negatives and false positives with respect to ESM, and we will test whether these models, incorporating both functional activation (HGM) and effective connectivity (measured with cortico-cortical evoked potentials, or CCEPs) can better predict ESM results. Third, we will develop and test models for prediction of post-operative language outcomes, based on the anatomical extent and volume of cortical resection with respect to HGM and ESM results, using voxel-lesion-symptom matching (VLSM). Since clinical decisions are currently based on ESM and clinicians will be blinded to HGM, we predict that the incidence of language deficits will be significantly higher when HGM+ electrodes are resected. This study will have a direct and profound impact on the clinical practice of language mapping for neurosurgical procures, while contributing valuable insights into the structure and dynamics of human language networks.