Neuroscience Program, Center for Health Sciences, Biosciences Division, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025, USA.
Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Brain Imaging Behav. 2022 Aug;16(4):1776-1793. doi: 10.1007/s11682-022-00645-6. Epub 2022 Mar 16.
Expression of executive dysfunctions is marked by substantial heterogeneity in people living with HIV infection (PLWH) and attributed to neuropathological degradation of frontostriatal circuitry with age and disease. We compared the neurophysiology of executive function in older PLWH and Parkinson's disease (PD), both affecting frontostriatal systems. Thirty-one older PLWH, 35 individuals with PD, and 28 older healthy controls underwent executive task-activated fMRI, neuropsychological testing, and a clinical motor exam. fMRI task conditions distinguished cognitive control operations, invoking a lateral frontoparietal network, and motor control operations, activating a cerebellar-precentral-medial prefrontal network. HIV-specific findings denoted a prominent sensorimotor hypoactivation during cognitive control and striatal hypoactivation during motor control related to CD4 T cell count and HIV disease duration. Activation deficits overlapped for PLWH and PD, relative to controls, in dorsolateral frontal, medial frontal, and middle cingulate cortices for cognitive control, and in limbic, frontal, parietal, and cerebellar regions for motor control. Thus, despite well-controlled HIV infection, frontostriatal and sensorimotor activation deficits occurred during executive control in older PLWH. Overlapping activation deficits in posterior cingulate and hippocampal regions point toward similarities in mesocorticolimbic system aberrations among older PLWH and PD. The extent of pathophysiology in PLWH was associated with variations in immune system health, neural signature consistent with subclinical parkinsonism, and mild neurocognitive impairment. The failure to adequately engage these pathways could be an early sign for cognitive and motor functional decline in the aging population of PLWH.
执行功能障碍的表现形式在感染人类免疫缺陷病毒（HIV）的患者（PLWH）中存在显著的异质性，这归因于额纹状体回路的神经病理学退化，与年龄和疾病有关。我们比较了老年 PLWH 和帕金森病（PD）的执行功能神经生理学，这两种疾病都影响额纹状体系统。31 名老年 PLWH、35 名 PD 患者和 28 名老年健康对照者接受了执行任务激活 fMRI、神经心理学测试和临床运动检查。fMRI 任务条件区分了认知控制操作，调用了外侧额顶网络，以及运动控制操作，激活了小脑-前中央-内侧前额叶网络。HIV 特异性发现表明，在认知控制期间存在明显的感觉运动激活不足，在运动控制期间存在纹状体激活不足，与 CD4 T 细胞计数和 HIV 疾病持续时间有关。与对照组相比，PLWH 和 PD 的激活缺陷重叠，在认知控制方面，包括背外侧额叶、内侧额叶和中扣带回皮质；在运动控制方面，包括边缘、额叶、顶叶和小脑区域。因此，尽管 HIV 得到了很好的控制，老年 PLWH 在执行控制期间仍存在额纹状体和感觉运动激活缺陷。后扣带回和海马区域的重叠激活缺陷表明，在老年 PLWH 和 PD 中，中边缘皮质系统异常存在相似之处。PLWH 的病理生理学程度与免疫系统健康的变化、与亚临床帕金森病一致的神经特征以及轻度神经认知障碍有关。未能充分利用这些途径可能是 PLWH 老年人群认知和运动功能下降的早期迹象。
