Prefrontal cortical thinning in HIV infection is associated with impaired striatal functioning
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While cortical thinning has been associated with HIV infection, it is unclear whether this reflects a direct effect of the virus, whether it is related to disruption of subcortical function or whether it is better explained by epiphenomena, such as drug abuse or comorbid medical conditions. The present study investigated the relationship between cortical thickness and subcortical function in HIV+ patients. Specifically, we examined the relationship between prefrontal cortical thickness and striatal function. Twenty-three largely treatment naïve, non-substance abusing HIV+ participants and 19 healthy controls matched for age, gender, and educational status were included. Cortical morphometry was performed using FreeSurfer software analysis. Striatal function was measured during an fMRI stop-signal anticipation task known to engage the striatum. Any cortical regions showing significant thinning were entered as dependent variables into a single linear regression model which included subcortical function, age, CD4 count, and a measure of global cognitive performance as independent predictors. The only cortical region that was significantly reduced after correction for multiple comparisons was the right superior frontal gyrus. Striatal activity was found to independently predict superior frontal gyral cortical thickness. While cortical thinning in HIV infection is likely multifactorial, viral induced subcortical dysfunction appears to play a role.
KeywordsfMRI Cortex Atrophy HIV Inhibition Striatum
The authors would like to thank Dr Hetta Gouse from the University of Cape Town, as well as Prof Rob Paul from the University of Missouri-St. Louis, for their assistance in determining the neuropsychological assessment battery as well as giving input into the neuropsychological assessments. The authors would also like to thank Mr Teboho Linda from the University of Cape Town for assisting in the recruiting of participants. S.D.P has received support from a National Research Fund International Research Training Grant (IRTG 1522), as well as support from the Medical Research Council of South Africa, Biological Psychiatry Special Interest Group of the South African Society of Psychiatrists as well as the HIV research Trust (HIVRT14-049). M.V and A.B. have reported no biomedical financial interests or potential conflicts of interest. J.J has received support from the Medical Research Council of South Africa. E.K. is supported by an EDCTP Strategic Primary Grant (SP. 2011.41304.065.) as well as a “Verein für Parkinson-Forschung” grant. D.S. has received research grants and/or consultancy honoraria from Abbott, Astrazeneca, Biocodex, Eli-Lilly, GlaxoSmithKline, Jazz Pharmaceuticals, Johnson & Johnson, Lundbeck, Novartis, Orion, Pfizer, Pharmacia, Roche, Servier, Solvay, Sumitomo, Sun, Takeda, Tikvah, and Wyeth. He is supported by the MRC of South Africa. R.E. has participated in speakers/advisory boards and received honoraria from AstraZeneca, Bristol-Myers Squibb, Janssen, Lilly, Lundbeck, Servier and Otsuka. He has also received research funding from Janssen, Lundbeck, and AstraZeneca.
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Conflict of interest
The authors have no conflicts of interest to declare.
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