Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain

Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS.

脑深部电刺激（Deep Brain Stimulation, DBS）是治疗神经及精神疾病的极具前景的疗法，但其作用机制与经电极向脑部施加电场的效应仍有待阐明。目前针对DBS效应的研究主要依托电生理与神经化学实验手段，但这类方法无法在全脑尺度上探究DBS相关的神经响应。要可视化DBS的全脑效应，需借助功能性磁共振成像（functional Magnetic Resonance Imaging, fMRI）这类功能成像技术，该技术可反映全脑容积内的血氧水平依赖（blood oxygen level dependent, BOLD）信号变化。为了可视化DBS诱导的BOLD响应，我们研发了一款与MRI兼容的电极，并设计了在fMRI扫描期间实施DBS的采集方案。本研究旨在验证：fMRI同步DBS技术能否用于研究海马区DBS的局部及全脑效应，以及剖析不同刺激强度诱导的神经变化。实验中，7只大鼠经立体定向手术，在右侧海马区植入定制的MRI兼容DBS电极。我们采用区组设计范式，施加高频泊松分布电刺激。数据通过独立成分分析（Independent Component Analysis, ICA）进行处理，经多重比较校正后p值<0.05的簇被判定为具有统计学显著性。研究结果显示，实时海马区DBS可根据刺激强度的不同，在海马区及其他中脑边缘结构中诱发双侧BOLD响应。综上，同步DBS与fMRI技术可用于检测不同刺激强度下脑环路激活引发的局部及全脑响应，该技术有望为临床前及临床场景下的DBS相关脑部变化探索提供强有力的研究工具。