Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
Department of Clinical Engineering, Haukeland University Hospital, Bergen, Norway.
NMR Biomed. 2024 Mar;37(3):e5065. doi: 10.1002/nbm.5065. Epub 2023 Oct 28.
A recurring issue in functional neuroimaging is how to link task-driven haemodynamic blood oxygen level dependent functional MRI (BOLD-fMRI) responses to underlying neurochemistry at the synaptic level. Glutamate and γ-aminobutyric acid (GABA), the major excitatory and inhibitory neurotransmitters respectively, are typically measured with MRS sequences separately from fMRI, in the absence of a task. The present study aims to resolve this disconnect, developing acquisition and processing techniques to simultaneously assess GABA, glutamate and glutamine (Glx) and BOLD in relation to a cognitive task, at 3 T. Healthy subjects (N = 81) performed a cognitive task (Eriksen flanker), which was presented visually in a task-OFF, task-ON block design, with individual event onset timing jittered with respect to the MRS readout. fMRS data were acquired from the medial anterior cingulate cortex during task performance, using an adapted MEGA-PRESS implementation incorporating unsuppressed water-reference signals at a regular interval. These allowed for continuous assessment of BOLD activation, through T *-related changes in water linewidth. BOLD-fMRI data were additionally acquired. A novel linear model was used to extract modelled metabolite spectra associated with discrete functional stimuli, building on well established processing and quantification tools. Behavioural outcomes from the flanker task, and activation patterns from the BOLD-fMRI sequence, were as expected from the literature. BOLD response assessed through fMRS showed a significant correlation with fMRI, specific to the fMRS-targeted region of interest; fMRS-assessed BOLD additionally correlated with lengthening of response time in the incongruent flanker condition. While no significant task-related changes were observed for GABA+, a significant increase in measured Glx levels (~8.8%) was found between task-OFF and task-ON periods. These findings verify the efficacy of our protocol and analysis pipelines for the simultaneous assessment of metabolite dynamics and BOLD. As well as establishing a robust basis for further work using these techniques, we also identify a number of clear directions for further refinement in future studies.
功能神经影像学中的一个反复出现的问题是如何将任务驱动的血液氧合水平依赖功能磁共振成像 (BOLD-fMRI) 响应与突触水平的基础神经化学联系起来。谷氨酸和γ-氨基丁酸（GABA）分别是主要的兴奋性和抑制性神经递质，通常分别使用 MRS 序列在没有任务的情况下从 fMRI 中进行测量。本研究旨在解决这一脱节问题，开发采集和处理技术，以同时评估 GABA、谷氨酸和谷氨酰胺（Glx）以及与认知任务相关的 BOLD，在 3T 下进行。健康受试者（N=81）执行认知任务（Eriksen 侧翼），该任务以任务-OFF、任务-ON 块设计的视觉方式呈现，个体事件起始时间相对于 MRS 读出进行抖动。fMRS 数据在任务执行期间从内侧前扣带皮层采集，使用改编的 MEGA-PRESS 实现，每隔一段时间包含未抑制的水参考信号。这允许通过水线宽的 T *相关变化，连续评估 BOLD 激活。此外，还采集了 BOLD-fMRI 数据。使用新的线性模型提取与离散功能刺激相关的模型代谢物谱，基于成熟的处理和量化工具。来自侧翼任务的行为结果，以及来自 BOLD-fMRI 序列的激活模式，与文献中的预期一致。通过 fMRS 评估的 BOLD 响应与 fMRI 显著相关，与 fMRS 靶向的感兴趣区域特定相关；fMRS 评估的 BOLD 还与不一致侧翼条件下反应时间的延长相关。虽然没有观察到 GABA+的显著任务相关变化，但在任务-OFF 和任务-ON 期间测量的 Glx 水平显著增加（~8.8%）。这些发现验证了我们的协议和分析管道用于同时评估代谢物动力学和 BOLD 的有效性。除了为使用这些技术的进一步工作建立稳健的基础外，我们还确定了在未来研究中进一步改进的一些明确方向。
