Ernst T, Chang L, Arnold S
Medical Department, Brookhaven National Laboratory, Building 490, P.O. Box 5000, Upton, NY 11973-5000, USA.
Neuroimage. 2003 Aug;19(4):1686-93. doi: 10.1016/s1053-8119(03)00232-5.
Deficits in attention and working memory are common in human immuno deficiency virus type 1 (HIV-1)-infected patients, but the pathophysiology of these deficits is poorly understood. Modern neuroimaging techniques, such as proton magnetic resonance spectroscopy ((1)H MRS) and functional MRI (fMRI), can assess some of the processes underlying HIV brain injury. To evaluate the model that attentional deficits in early HIV brain disease are related to brain inflammation, (1)H MRS and fMRI were performed in 14 HIV-positive subjects [acquired immunodeficiency syndrome (AIDS) dementia complex stage 1 or less]. Increasing attentional load on three working memory tasks was assessed with fMRI, and the concentrations of brain metabolites were measured with (1)H MRS in the frontal gray and white matter, and basal ganglia. Metabolite concentrations were correlated with fMRI blood oxygenation level-dependent (BOLD) signals, using a random-effects linear regression model in SPM99. Several positive correlations were observed between the BOLD signal strength in the working memory network (posterior parietal cortex and lateral prefrontal cortex) and the concentrations of frontal white matter and basal ganglia metabolites that are predominant in glial cells (choline-containing compounds, myo-inositol, and total creatine). In contrast, BOLD signals in the working memory network were not correlated with the concentration of N-acetyl compounds, which are markers of neuronal viability, or with metabolite concentrations in the frontal gray matter. These findings are consistent with previous results that mild HIV brain injury is associated with increased glial activation without major involvement of neuronal abnormalities. We propose that the inflammatory glial abnormalities reduce the efficiency of neural processing, and necessitate compensatory increases in attention in patients, and associated BOLD signals, to perform a given task. The same mechanism may also contribute to cognitive dysfunction in other brain diseases that involve inflammation.
注意力和工作记忆缺陷在人类免疫缺陷病毒1型（HIV-1）感染患者中很常见，但这些缺陷的病理生理学机制尚不清楚。现代神经影像学技术，如质子磁共振波谱（（1）H MRS）和功能磁共振成像（fMRI），可以评估HIV脑损伤的一些潜在过程。为了评估早期HIV脑病中注意力缺陷与脑炎症相关的模型，对14名HIV阳性受试者（获得性免疫缺陷综合征（AIDS）痴呆复合征1期或以下）进行了（1）H MRS和fMRI检查。通过fMRI评估了三个工作记忆任务中注意力负荷的增加情况，并使用（1）H MRS测量了额叶灰质和白质以及基底神经节中的脑代谢物浓度。使用SPM99中的随机效应线性回归模型，将代谢物浓度与fMRI血氧水平依赖（BOLD）信号进行相关分析。在工作记忆网络（顶叶后皮质和前额叶外侧皮质）中的BOLD信号强度与额叶白质和基底神经节中以胶质细胞为主的代谢物浓度（含胆碱化合物、肌醇和总肌酸）之间观察到了一些正相关。相比之下，工作记忆网络中的BOLD信号与作为神经元活力标志物的N-乙酰化合物浓度或额叶灰质中的代谢物浓度无关。这些发现与先前的结果一致，即轻度HIV脑损伤与胶质细胞激活增加有关，而神经元异常未起主要作用。我们提出，炎症性胶质细胞异常会降低神经处理效率，患者需要增加注意力及相关的BOLD信号来完成给定任务。相同的机制也可能导致其他涉及炎症的脑部疾病出现认知功能障碍。
