Measuring the impact of HIV on the fronto-striatal system

Du Plessis, Stefan (2016-12)

Thesis (PhD)--Stellenbosch University, 2016.

Thesis

ENGLISH SUMMARY : HIV infection remains a major contributor to the global health burden despite the introduction of effective prevention strategies and the effectiveness of combined antiretroviral therapy (cART). Of particular importance is the impact of HIV on the brain. While cART has been successful in treating the more severe forms HIV induced cognitive impairment, the minor forms of impairment are now more prevalent. There remains some controversy with regard to the latter. Being diagnosed in the absence of other symptoms, there is some doubt that this category of cognitive impairment is valid at all. As such, investigating HIV induced functional brain changes may be helpful in the study of these forms of impairment. Although functional magnetic resonance imaging (fMRI) studies have thus far shown various forms of functional impairment in the brain, how these impairments relate to one another is unclear. Many key aspects of HIV’s potential impact on the frontostriatal system remain unexplored. Our overall objective was therefore to investigate the early impact of HIV on the brain using fMRI as an objective measurement tool. First, we investigated the effects of HIV on the brain by performing a quantitative meta analysis of all suitable fMRI data. Next, we proceeded to investigate the fronto-striatal network based on the results of the meta-analysis by performing fMRI imaging in a sample of HIV+ participants and matched HIV negative controls. Participants performed a stop-signal anticipation and a monetary incentive delay task to investigate the impact of HIV on important sub-networks of the fronto-striatal system. Finally, we investigated the relationship between striatal dysfunction with structural brain changes. The results from the meta-analysis showed that HIV consistently affects the fronto-striatal system based on past fMRI studies. In subsequent studies, we demonstrated diminished functioning of the fronto-striatal networks involved in inhibition of voluntary movement as well as reward processing. Furthermore, this fronto-striatal dysfunction was also related to cortical atrophy often seen in HIV. Based on these findings, I therefore conclude that fronto-striatal dysfunction is a core component of HIV infection and needs to be considered in the assessment and management of all patients afflicted by this still very prevalent illness.

AFRIKAANSE OPSOMMING : MIV-infeksie dra by tot die globale gesondheid las, ten spyte van die bekendstelling van effektiewe voorkomende strategiee en die doeltreffendheid van gekombineerde antiretrovirale terapie (ART). Van besondere belang is die impak van MIV op die brein. Terwyl ART suksesvol was in die behandeling van die meer ernstige klassifikasie van MIV geassosieerde kognitiewe inkorting, is die subtiele klassifikasie van hierdie inkorting nou nog meer algemeen. Die diagnose van meer ernstige kognitiewe inkorting is tans nog kontroversieel. Sedert dit gediagnoseer word in die afwesigheid van funksionele inkorting, is daar tans twyfel of hierdie kategorie van kognitiewe inkorting geldig is. Dit is dus nodig om te bepaal of MIV wel opsig self funksionele veranderinge in die brein veroorsaak. Alhoewel funksionele magnetiese resonansbeelding (fMRI) studies tot dusver verskeie manifestasies van funksionele inkorting in die brein toon, is die verband tussen die fMRI abnormaliteite en die virus nog onduidelik. Die spesifieke impak van MIV op die frontale-striatale stelsel is nog onbekend. Ons hoof doelwit was dus om die vroee impak van MIV op die brein met behulp van fMRI as 'n objektiewe meetinstrument te ondersoek. Eerstens het ons die gevolge van MIV infeksie op die brein ondersoek deur 'n kwantitatiewe meta-analise van alle geskikte fMRI data uit te voer. Gebaseer op die resultate van ons metaanalise, het ons voortgegaan om die frontale-striatale netwerk te ondersoek deur die toepassing van fMRI beelding in 'n groep MIV + deelnemers asook MIV negatiewe kontroles. Deelnemers het 'n stop-sein afwagtings taak en 'n monetêre afwagtings taak voltooi om die Laastens, het ons die verhouding tussen striatale disfunksie en veranderinge in brein struktuur bestudeer. Die resultate van die meta-analise het getoon dat MIV ‘n beduidende invloed op die funksie van die frontale-striatale stelsel het. Verder het ons verminderde aktivering van die frontalestriatale netwerke wat betrokke is by die inhibisie van willekeurige beweging asook belonging prosessering gedemonstreer. Verder was hierdie fronto-striatale disfunksie ook verwant aan kortikale atrofie, ‘n bekende bevinding in MIV infeksie. Op grond van hierdie bevindinge, kan ons dus aflei dat fronto-striatale disfunksie 'n hoofkomponent is van MIV-infeksie. Hierdie brein disfunksie moet dus oorweeg word in die assessering en behandeling van MIV. impak van MIV op belangrike sub-netwerke van die frontale-striatale stelsel te ondersoek.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/100223
This item appears in the following collections: