Chang L, Yakupov R, Nakama H, Stokes B, Ernst T
Department of Medicine, Division of Neurology, John A. Burns School of Medicine, University of Hawaii at Manoa, The Queen's Medical Center University Tower, 1356 Lusitana Street, Honolulu, HI 96813, USA.
J Neuroimmune Pharmacol. 2008 Jun;3(2):95-104. doi: 10.1007/s11481-007-9092-0. Epub 2007 Oct 13.
The purpose of this paper was to determine whether antiretroviral medications, especially the nucleoside analogue reverse transcriptase inhibitors, lead to altered brain activation due to their potential neurotoxic effects in patients with human immunodeficiency virus (HIV) infection.
Forty-two right-handed men were enrolled in three groups: seronegative controls (SN, n = 18), HIV subjects treated with antiretroviral medications (HIV+ARV, n = 12), or not treated with antiretroviral medications (HIV+NARV, n = 12). Each subject performed a set of visual attention tasks with increasing difficulty or load (tracking two, three or four balls) during functional magnetic resonance imaging.
HIV subjects, both groups combined, showed greater load-dependent increases in brain activation in the right frontal regions compared to SN (p-corrected = 0.006). HIV+ARV additionally showed greater load-dependent increases in activation compared to SN in bilateral superior frontal regions (p-corrected = 0.032) and a lower percent accuracy on the performance of the most difficult task (tracking four balls). Region of interest analyses further demonstrated that SN showed load-dependent decreases (with repeated trials despite increasing difficulty), while HIV subjects showed load-dependent increases in activation with the more difficult tasks, especially those on ARVs.
These findings suggest that chronic ARV treatments may lead to greater requirement of the attentional network reserve and hence less efficient usage of the network and less practice effects in these HIV patients. As the brain has a limited reserve capacity, exhausting the reserve capacity in HIV+ARV would lead to declined performance with more difficult tasks that require more attention.
本文旨在确定抗逆转录病毒药物,尤其是核苷类似物逆转录酶抑制剂,是否因其对人类免疫缺陷病毒(HIV)感染患者的潜在神经毒性作用而导致大脑激活改变。
42名右利手男性被纳入三组:血清阴性对照组(SN,n = 18)、接受抗逆转录病毒药物治疗的HIV受试者(HIV+ARV,n = 12)或未接受抗逆转录病毒药物治疗的HIV受试者(HIV+NARV,n = 12)。在功能磁共振成像期间,每个受试者执行一组难度或负荷逐渐增加的视觉注意力任务(跟踪两个、三个或四个球)。
与SN相比,两组HIV受试者在右侧额叶区域的大脑激活随负荷增加的幅度更大(p校正 = 0.006)。与SN相比,HIV+ARV在双侧额上区域的激活随负荷增加的幅度更大(p校正 = 0.032),并且在最困难任务(跟踪四个球)的表现上准确率较低。感兴趣区域分析进一步表明,SN表现出随负荷增加的激活减少(尽管难度增加但试验重复),而HIV受试者在执行更困难任务时,尤其是接受抗逆转录病毒药物治疗的患者,表现出随负荷增加的激活增加。
这些发现表明,长期抗逆转录病毒治疗可能导致这些HIV患者对注意力网络储备的需求增加,从而导致该网络的使用效率降低和练习效果减弱。由于大脑的储备能力有限,HIV+ARV组耗尽储备能力会导致在需要更多注意力的更困难任务上表现下降。