Alahmadi Adnan A S, Pardini Matteo, Samson Rebecca S, D'Angelo Egidio, Friston Karl J, Toosy Ahmed T, Gandini Wheeler-Kingshott Claudia A M
Department of Diagnostic Radiology, Faculty of Applied Medical Science, King Abdulaziz University, Jeddah, Saudi Arabia.
NMR Research Unit, Department of Neuroinflammation, Queen Square MS Centre, UCL Queen Square Institute of Neurology, London, United Kingdom.
Front Cell Neurosci. 2021 Apr 26;15:616028. doi: 10.3389/fncel.2021.616028. eCollection 2021.
This study highlights the importance of looking beyond the main effect of movement to study alterations in functional response in the presence of central nervous system pathologies such as multiple sclerosis (MS). Data show that MS selectively affects regional BOLD (blood oxygenation level dependent) responses to variable grip forces (GF). It is known that the anterior and posterior BA 4 areas (BA 4a and BA 4p) are anatomically and functionally distinct. It has also been shown in healthy volunteers that there are linear (first order, typical of BA 4a) and nonlinear (second to fourth order, typical of BA 4p) BOLD responses to different levels of GF applied during a dynamic motor paradigm. After modeling the BOLD response with a polynomial expansion of the applied GFs, the particular case of BA 4a and BA 4p were investigated in healthy volunteers (HV) and MS subjects. The main effect of movement (zeroth order) analysis showed that the BOLD signal is greater in MS compared with healthy volunteers within both BA 4 subregions. At higher order, BOLD-GF responses were similar in BA 4a but showed a marked alteration in BA 4p of MS subjects, with those with greatest disability showing the greatest deviations from the healthy response profile. Therefore, the different behaviors in HV and MS could only be uncovered through a polynomial analysis looking beyond the main effect of movement into the two BA 4 subregions. Future studies will investigate the source of this pathophysiology, combining the present fMRI paradigm with blood perfusion and nonlinear neuronal response analysis.
本研究强调了在研究诸如多发性硬化症（MS）等中枢神经系统疾病存在时功能反应的改变时，超越运动的主要效应进行观察的重要性。数据表明，MS会选择性地影响对可变握力（GF）的局部血氧水平依赖（BOLD）反应。已知额叶和顶叶BA 4区（BA 4a和BA 4p）在解剖学和功能上是不同的。在健康志愿者中也已表明，在动态运动范式期间，对不同水平的GF存在线性（一阶，典型的BA 4a）和非线性（二阶至四阶，典型的BA 4p）BOLD反应。在用所施加的GFs的多项式展开对BOLD反应进行建模之后，在健康志愿者（HV）和MS受试者中研究了BA 4a和BA 4p的特殊情况。运动的主要效应（零阶）分析表明，在两个BA 4子区域内，MS患者的BOLD信号比健康志愿者更强。在更高阶时，BA 4a中的BOLD-GF反应相似，但MS受试者的BA 4p中显示出明显改变，残疾程度最高的患者与健康反应曲线的偏差最大。因此，只有通过超越运动主要效应进入两个BA 4子区域的多项式分析，才能揭示HV和MS中的不同行为。未来的研究将结合当前的功能磁共振成像范式与血液灌注和非线性神经元反应分析，研究这种病理生理学的根源。
