Ipser Jonathan C, Brown Gregory G, Bischoff-Grethe Amanda, Connolly Colm G, Ellis Ronald J, Heaton Robert K, Grant Igor
1Department of Psychiatry and Mental Health,University of Cape Town,Cape Town,South Africa.
2Department of Psychiatry,University of California,San Diego,California.
J Int Neuropsychol Soc. 2015 Mar;21(3):203-13. doi: 10.1017/S1355617715000156. Epub 2015 Mar 31.
HIV-associated cognitive impairments are prevalent, and are consistent with injury to both frontal cortical and subcortical regions of the brain. The current study aimed to assess the association of HIV infection with functional connections within the frontostriatal network, circuitry hypothesized to be highly vulnerable to HIV infection. Fifteen HIV-positive and 15 demographically matched control participants underwent 6 min of resting-state functional magnetic resonance imaging (RS-fMRI). Multivariate group comparisons of age-adjusted estimates of connectivity within the frontostriatal network were derived from BOLD data for dorsolateral prefrontal cortex (DLPFC), dorsal caudate and mediodorsal thalamic regions of interest. Whole-brain comparisons of group differences in frontostriatal connectivity were conducted, as were pairwise tests of connectivity associations with measures of global cognitive functioning and clinical and immunological characteristics (nadir and current CD4 count, duration of HIV infection, plasma HIV RNA). HIV - associated reductions in connectivity were observed between the DLPFC and the dorsal caudate, particularly in younger participants (<50 years, N=9). Seropositive participants also demonstrated reductions in dorsal caudate connectivity to frontal and parietal brain regions previously demonstrated to be functionally connected to the DLPFC. Cognitive impairment, but none of the assessed clinical/immunological variables, was also associated with reduced frontostriatal connectivity. In conclusion, our data indicate that HIV is associated with attenuated intrinsic frontostriatal connectivity. Intrinsic connectivity of this network may therefore serve as a marker of the deleterious effects of HIV infection on the brain, possibly via HIV-associated dopaminergic abnormalities. These findings warrant independent replication in larger studies.
与HIV相关的认知障碍很普遍,并且与大脑额叶皮质和皮质下区域的损伤一致。当前的研究旨在评估HIV感染与额纹状体网络内功能连接之间的关联,该神经回路被认为极易受到HIV感染。15名HIV阳性参与者和15名在人口统计学上匹配的对照参与者接受了6分钟的静息态功能磁共振成像(RS-fMRI)。额纹状体网络内连接性的年龄调整估计值的多变量组间比较来自于背外侧前额叶皮质(DLPFC)、背侧尾状核和感兴趣的丘脑背内侧区域的血氧水平依赖(BOLD)数据。进行了额纹状体连接性组间差异的全脑比较,以及连接性与整体认知功能、临床和免疫学特征(最低点和当前CD4细胞计数、HIV感染持续时间、血浆HIV RNA)测量值之间关联的成对检验。在DLPFC和背侧尾状核之间观察到与HIV相关的连接性降低,尤其是在较年轻的参与者(<50岁,N = 9)中。血清反应阳性的参与者还表现出背侧尾状核与先前证明与DLPFC功能相连的额叶和顶叶脑区之间的连接性降低。认知障碍,但没有一个评估的临床/免疫学变量,也与额纹状体连接性降低有关。总之,我们的数据表明HIV与额纹状体内在连接性减弱有关。因此,该网络的内在连接性可能作为HIV感染对大脑有害影响的一个标志物,可能是通过与HIV相关的多巴胺能异常。这些发现需要在更大规模的研究中进行独立验证。