Division of Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.
Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany.
Brain. 2021 Oct 22;144(9):2837-2851. doi: 10.1093/brain/awab170.
Because of its involvement in a wide variety of cardiovascular, metabolic and behavioural functions, the hypothalamus constitutes a potential target for neuromodulation in a number of treatment-refractory conditions. The precise neural substrates and circuitry subserving these responses, however, are poorly characterized to date. We sought to retrospectively explore the acute sequelae of hypothalamic region deep brain stimulation and characterize their neuroanatomical correlates. To this end we studied-at multiple international centres-58 patients (mean age: 68.5 ± 7.9 years, 26 females) suffering from mild Alzheimer's disease who underwent stimulation of the fornix region between 2007 and 2019. We catalogued the diverse spectrum of acutely induced clinical responses during electrical stimulation and interrogated their neural substrates using volume of tissue activated modelling, voxel-wise mapping, and supervised machine learning techniques. In total 627 acute clinical responses to stimulation-including tachycardia, hypertension, flushing, sweating, warmth, coldness, nausea, phosphenes, and fear-were recorded and catalogued across patients using standard descriptive methods. The most common manifestations during hypothalamic region stimulation were tachycardia (30.9%) and warmth (24.6%) followed by flushing (9.1%) and hypertension (6.9%). Voxel-wise mapping identified distinct, locally separable clusters for all sequelae that could be mapped to specific hypothalamic and extrahypothalamic grey and white matter structures. K-nearest neighbour classification further validated the clinico-anatomical correlates emphasizing the functional importance of identified neural substrates with area under the receiving operating characteristic curves between 0.67 and 0.91. Overall, we were able to localize acute effects of hypothalamic region stimulation to distinct tracts and nuclei within the hypothalamus and the wider diencephalon providing clinico-anatomical insights that may help to guide future neuromodulation work.
由于其参与了广泛的心血管、代谢和行为功能，下丘脑构成了许多治疗抵抗性疾病中神经调节的潜在靶点。然而，迄今为止，这些反应的确切神经基质和回路仍知之甚少。我们试图回顾性地探讨下丘脑区域深部脑刺激的急性后果，并描述其神经解剖学相关性。为此，我们在多个国际中心研究了 58 名（平均年龄：68.5±7.9 岁，26 名女性）患有轻度阿尔茨海默病的患者，他们在 2007 年至 2019 年间接受了穹窿区域的刺激。我们记录了电刺激过程中急性诱导的临床反应的多样谱，并使用组织激活建模、体素映射和监督机器学习技术探讨了它们的神经基质。总共记录并分类了 627 例急性刺激反应，包括心动过速、高血压、潮红、出汗、温暖、寒冷、恶心、闪光、恐惧等，这些反应在患者之间使用标准描述性方法进行了记录和分类。下丘脑区域刺激时最常见的表现是心动过速（30.9%）和温暖（24.6%），其次是潮红（9.1%）和高血压（6.9%）。体素映射确定了所有后遗症的独特、局部可分离的簇，可以映射到特定的下丘脑和下丘脑外灰质和白质结构。最近邻分类进一步验证了临床解剖相关性，强调了识别的神经基质的功能重要性，其接受者操作特征曲线下面积在 0.67 到 0.91 之间。总的来说，我们能够将下丘脑区域刺激的急性效应定位到下丘脑内和更广泛的间脑的不同束和核，提供临床解剖学见解，这可能有助于指导未来的神经调节工作。
