Peattie Alexander R D, Manktelow Anne E, Sahakian Barbara J, Menon David K, Stamatakis Emmanuel A
Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Box 93, Hills Road, Cambridge CB2 0QQ, UK.
Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Box 165, Hills Road, Cambridge CB2 0QQ, UK.
J Clin Med. 2024 Jan 29;13(3):771. doi: 10.3390/jcm13030771.
(1) : Traumatic brain injury (TBI) often results in cognitive impairments, including in visuospatial planning and executive function. Methylphenidate (MPh) demonstrates potential improvements in several cognitive domains in patients with TBI. The Tower of London (TOL) is a visuospatial planning task used to assess executive function. (2) : Volunteers with a history of TBI ( = 16) participated in a randomised, double-blinded, placebo-controlled, fMRI study to investigate the neurobiological correlates of visuospatial planning and executive function, on and off MPh. (3) : Healthy controls (HCs) ( = 18) and patients on placebo (TBI-placebo) differed significantly in reaction time ( < 0.0005) and accuracy ( < 0.0001) when considering all task loads, but especially for high cognitive loads for reaction time ( < 0.001) and accuracy ( < 0.005). Across all task loads, TBI-MPh were more accurate than TBI-placebo ( < 0.05) but remained less accurate than HCs ( < 0.005). TBI-placebo substantially improved in accuracy with MPh administration (TBI-MPh) to a level statistically comparable to HCs at low ( = 0.443) and high ( = 0.175) cognitive loads. Further, individual patients that performed slower on placebo at low cognitive loads were faster with MPh ( < 0.05), while individual patients that performed less accurately on placebo were more accurate with MPh at both high and low cognitive loads ( < 0.005). TBI-placebo showed reduced activity in the bilateral inferior frontal gyri (IFG) and insulae versus HCs. MPh normalised these regional differences. MPh enhanced within-network connectivity (between parietal, striatal, insula, and cerebellar regions) and enhanced beyond-network connectivity (between parietal, thalamic, and cerebellar regions). Finally, individual changes in cerebellar-thalamic ( < 0.005) and cerebellar-parietal ( < 0.05) connectivity with MPh related to individual changes in accuracy with MPh. (4) : This work highlights behavioural and neurofunctional differences between HCs and patients with chronic TBI, and that adverse differences may benefit from MPh treatment.
(1)：创伤性脑损伤（TBI）常导致认知障碍，包括视觉空间规划和执行功能方面的障碍。哌醋甲酯（MPh）在TBI患者的几个认知领域显示出潜在的改善作用。伦敦塔任务（TOL）是一项用于评估执行功能的视觉空间规划任务。(2)：有TBI病史的志愿者（n = 16）参与了一项随机、双盲、安慰剂对照的功能磁共振成像（fMRI）研究，以探究服用和未服用MPh时视觉空间规划和执行功能的神经生物学相关性。(3)：在考虑所有任务负荷时，健康对照组（HCs）（n = 18）和服用安慰剂的患者（TBI-安慰剂组）在反应时间（p < 0.0005）和准确性（p < 0.0001）上有显著差异，尤其是在高认知负荷下的反应时间（p < 0.001）和准确性（p < 0.005）方面。在所有任务负荷下，TBI-MPh组比TBI-安慰剂组更准确（p < 0.05），但仍不如HCs组准确（p < 0.005）。服用MPh（TBI-MPh）后，TBI-安慰剂组的准确性有显著提高，在低（p = 0.443）和高（p = 0.175）认知负荷下，其准确性在统计学上与HCs组相当。此外，在低认知负荷下服用安慰剂时表现较慢的个体患者，服用MPh后速度更快（p < 0.05），而在高、低认知负荷下服用安慰剂时准确性较低的个体患者，服用MPh后准确性更高（p < 0.005）。与HCs相比，TBI-安慰剂组双侧额下回（IFG）和脑岛的活动减少。MPh使这些区域差异恢复正常。MPh增强了网络内连接（顶叶、纹状体、脑岛和小脑区域之间），并增强了网络间连接（顶叶、丘脑和小脑区域之间）。最后，服用MPh时小脑-丘脑连接（p < 0.005）和小脑-顶叶连接（p < 0.05）的个体变化与服用MPh时准确性的个体变化相关。(4)：这项研究突出了HCs与慢性TBI患者之间的行为和神经功能差异，且这些不利差异可能受益于MPh治疗。
