Center for Brain Science and Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
J Neurosci. 2011 Oct 19;31(42):15086-91. doi: 10.1523/JNEUROSCI.0007-11.2011.
The blood oxygenation level-dependent (BOLD) signal serves as the basis for human functional MRI (fMRI). Knowledge of the properties of the BOLD signal, such as how linear its response is to sensory stimuli, is essential for the design and interpretation of fMRI experiments. Here, we combined the cell-type and site-specific causal control provided by optogenetics and fMRI (opto-fMRI) in mice to test the linearity of BOLD signals driven by locally induced excitatory activity. We employed high-resolution mouse fMRI at 9.4 tesla to measure the BOLD response, and extracellular electrophysiological recordings to measure the effects of stimulation on single unit, multiunit, and local field potential activity. Optically driven stimulation of layer V neocortical pyramidal neurons resulted in a positive local BOLD response at the stimulated site. Consistent with a linear transform model, this locally driven BOLD response summated in response to closely spaced trains of stimulation. These properties were equivalent to responses generated through the multisynaptic method of driving neocortical activity by tactile sensory stimulation, and paralleled changes in electrophysiological measures. These results illustrate the potential of the opto-fMRI method and reinforce the critical assumption of human functional neuroimaging that--to first approximation--the BOLD response tracks local neural activity levels.
血氧水平依赖 (BOLD) 信号是人类功能磁共振成像 (fMRI) 的基础。了解 BOLD 信号的特性，例如其对感觉刺激的响应有多线性，对于 fMRI 实验的设计和解释至关重要。在这里，我们结合了光遗传学和 fMRI（光磁共振成像）在小鼠中的细胞类型和特定部位的因果控制，以测试由局部诱导的兴奋活动驱动的 BOLD 信号的线性度。我们在 9.4 特斯拉的高分辨率小鼠 fMRI 中测量 BOLD 响应，以及细胞外电生理记录来测量刺激对单个单位、多单位和局部场电位活动的影响。用光刺激 V 层新皮层锥体神经元会在刺激部位产生正的局部 BOLD 响应。与线性变换模型一致，这种局部驱动的 BOLD 响应在紧密间隔的刺激序列中累积。这些特性与通过触觉感觉刺激驱动新皮层活动的多突触方法产生的响应等效，并与电生理测量的变化平行。这些结果说明了光磁共振成像方法的潜力，并强化了人类功能神经影像学的关键假设，即 BOLD 响应大致跟踪局部神经活动水平。
