Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-28T04:12:55.693Z Has data issue: false hasContentIssue false
  • English
  • Français

HIV Infection Is Associated with Impaired Striatal Function during Inhibition with Normal Cortical Functioning on Functional MRI

Published online by Cambridge University Press:  05 October 2015

Stéfan du Plessis ,
Matthijs Vink ,
John A. Joska ,
Eleni Koutsilieri ,
Asif Bagadia ,
Dan J Stein  and
Robin Emsley
Stéfan du Plessis*
Affiliation:
Department of Psychiatry, 2nd Floor Clinical Building, Faculty of Heath Sciences, University of Stellenbosch, Fransie van Zijl Avenue, Tygerberg, Cape Town, South Africa
Matthijs Vink
Affiliation:
Brain Center Rudolf Magnus, CG Utrecht, The Netherlands
John A. Joska
Affiliation:
Department of Psychiatry, University of Cape Town, J-Block, Groote Schuur Hospital, Observatory, Cape Town
Eleni Koutsilieri
Affiliation:
Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany
Asif Bagadia
Affiliation:
Department of Radiology, 5th Floor Clinical Building, Faculty of Heath Sciences, University of Stellenbosch, Fransie van Zijl Avenue, Tygerberg, Cape Town, South Africa
Dan J Stein
Affiliation:
Department of Psychiatry, University of Cape Town, J-Block, Groote Schuur Hospital, Observatory, Cape Town Medical Research Council (Unit on Anxiety and Stress Disorders), 2nd Floor Clinical Building, Faculty of Heath Sciences, University of Stellenbosch, Tygerberg, Cape Town, South Africa
Robin Emsley
Affiliation:
Department of Psychiatry, 2nd Floor Clinical Building, Faculty of Heath Sciences, University of Stellenbosch, Fransie van Zijl Avenue, Tygerberg, Cape Town, South Africa
*
Correspondence and reprint requests to: Stéfan du Plessis, Department of Psychiatry, 2nd Floor Clinical Building, Faculty of Heath Sciences, University of Stellenbosch, Fransie van Zijl Avenue, Tygerberg, Cape Town, 7505 South Africa. E-mail: stefandup@sun.ac.za
Get access Rights & Permissions [Opens in a new window]

Abstract

The aim of the present study was to investigate the effect of HIV infection on cortical and subcortical regions of the frontal-striatal system involved in the inhibition of voluntary movement. Functional MRI (fMRI) studies suggest that human immunodeficiency virus (HIV) infection is associated with frontostriatal dysfunction. While frontostriatal systems play a key role in behavioral inhibition, there are to our knowledge no fMRI studies investigating the potential impact of HIV on systems involved during the inhibition of voluntary movement. A total of 17 combined antiretroviral therapy (cART) naïve HIV+ participants as well as 18 age, gender, ethnic, education matched healthy controls performed a modified version of the stop-signal paradigm. This paradigm assessed behavior as well as functional brain activity associated with motor execution, reactive inhibition (outright stopping) and proactive inhibition (anticipatory response slowing before stopping). HIV+ participants showed significantly slower responses during motor execution compared to healthy controls, whereas they had normal proactive response slowing. Putamen hypoactivation was evident in the HIV+ participants based on successful stopping, indicating subcortical dysfunction during reactive inhibition. HIV+ participants showed normal cortical functioning during proactive inhibition. Our data provide evidence that HIV infection is associated with subcortical dysfunction during reactive inhibition, accompanied by relatively normal higher cortical functioning during proactive inhibition. This suggests that HIV infection may primarily involve basic striatal-mediated control processes in cART naïve participants. (JINS, 2015, 21, 722–731)

Keywords

BrainInhibitionDementiafMRIPutamenHIV
Type
Research Articles
Information
Journal of the International Neuropsychological Society , Volume 21 , Issue 9 , October 2015 , pp. 722 - 731
Copyright
Copyright © The International Neuropsychological Society 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Amin, J., Kaye, M., Skidmore, S., Pillay, D., Cooper, D.A., & Dore, G.J. (2004). HIV and hepatitis C coinfection within the CAESAR study. HIV Medicine, 5(3), 174–179. http://doi.org/10.1111/j.1468-1293.2004.00207.x Google Scholar
An, S.F., Groves, M., Gray, F., & Scaravilli, F. (1999). Early entry and widespread cellular involvement of HIV-1 DNA in brains of HIV-1 positive asymptomatic individuals. Journal of Neuropathology and Experimental Neurology, 58(11), 1156–1162 Google Scholar
Ances, B.M., Ortega, M., Vaida, F., Heaps, J., & Paul, R. (2012). Independent effects of HIV, aging, and HAART on brain volumetric measures. Journal of Acquired Immune Deficiency Syndromes (1999), 59(5), 469–477. http://doi.org/10.1097/QAI.0b013e318249db17 Google Scholar
Ances, B.M., Roc, A.C., Korczykowski, M., Wolf, R.L., & Kolson, D.L. (2008). Combination antiretroviral therapy modulates the blood oxygen level–dependent amplitude in human immunodeficiency virus-seropositive patients. Journal of Neurovirology, 14(5), 418–424. http://doi.org/10.1080/13550280802298112 Google Scholar
Ances, B.M., Roc, A.C., Wang, J., Korczykowski, M., Okawa, J., Stern, J., & Detre, J.A. (2006). Caudate blood flow and volume are reduced in HIV+ neurocognitively impaired patients. Neurology, 66(6), 862–866. http://doi.org/10.1212/01.wnl.0000203524.57993.e2 Google Scholar
Ances, B.M., Sisti, D., Vaida, F., Liang, C.L., Leontiev, O., Perthen, J.E., & Ellis, R.J. (2009). Resting cerebral blood flow: A potential biomarker of the effects of HIV in the brain. Neurology, 73(9), 702–708. http://doi.org/10.1212/WNL.0b013e3181b59a97 Google Scholar
Ances, B.M., Vaida, F., Cherner, M., Yeh, M.J., Liang, C.L., Gardner, C., & Buxton, R.B. (2011). HIV and chronic methamphetamine dependence affect cerebral blood flow. Journal of Neuroimmune Pharmacology, 6(3), 409–419. http://doi.org/10.1007/s11481-011-9270-y CrossRefGoogle ScholarPubMed
Ances, B.M., Vaida, F., Yeh, M.J., Liang, C.L., Buxton, R.B., Letendre, S., & McCutchan, J.A. (2010). HIV infection and aging independently affect brain function as measured by functional magnetic resonance imaging. The Journal of Infectious Diseases, 201(3), 336–340. http://doi.org/10.1086/649899 Google Scholar
Aron, A.R. (2011). From reactive to proactive and selective control: Developing a richer model for stopping inappropriate responses. Biological Psychiatry, 69(12), e55–e68 Google Scholar
Bari, A., Eagle, D.M., Mar, A.C., Robinson, E.S.J., & Robbins, T.W. (2009). Dissociable effects of noradrenaline, dopamine, and serotonin uptake blockade on stop task performance in rats. Psychopharmacology, 205(2), 273–283. http://doi.org/10.1007/s00213-009-1537-0 Google Scholar
Carey, C.L., Woods, S.P., Gonzalez, R., Conover, E., Marcotte, T.D., Grant, I., & Heaton, R.K. (2004). Predictive validity of global deficit scores in detecting neuropsychological impairment in HIV infection. Journal of Clinical and Experimental Neuropsychology, 26(3), 307–319. http://doi.org/10.1080/13803390490510031 Google Scholar
Castellon, S.A., Hinkin, C.H., Wood, S., & Yarema, K.T. (1998). Apathy, depression, and cognitive performance in HIV-1 infection. The Journal of Neuropsychiatry and Clinical Neurosciences, 10(3), 320–329 Google Scholar
Castelo, J.M.B., Sherman, S.J., Courtney, M.G., Melrose, R.J., & Stern, C.E. (2006). Altered hippocampal-prefrontal activation in HIV patients during episodic memory encoding. Neurology, 66(11), 1688–1695. http://doi.org/10.1212/01.wnl.0000218305.09183.70 CrossRefGoogle ScholarPubMed
Chang, L., Holt, J.L., Yakupov, R., Jiang, C.S., & Ernst, T. (2013). Lower cognitive reserve in the aging human immunodeficiency virus-infected brain. Neurobiology of Aging, 34(4), 1240–1253. http://doi.org/10.1016/j.neurobiolaging.2012.10.012 CrossRefGoogle ScholarPubMed
Chang, L., Speck, O., Miller, E.N., Braun, J., Jovicich, J., Koch, C., & Ernst, T. (2001). Neural correlates of attention and working memory deficits in HIV patients. Neurology, 57(6), 1001–1007 CrossRefGoogle ScholarPubMed
Chang, L., Tomasi, D., Yakupov, R., Lozar, C., Arnold, S., Caparelli, E., &&Ernst, T. (2004). Adaptation of the attention network in human immunodeficiency virus brain injury. Annals of Neurology, 56(2), 259–272. http://doi.org/10.1002/ana.20190 CrossRefGoogle ScholarPubMed
Chang, L., Yakupov, R., Nakama, H., Stokes, B., & Ernst, T. (2007). Antiretroviral treatment is associated with increased attentional load-dependent brain activation in HIV patients. Journal of Neuroimmune Pharmacology, 3(2), 95–104. http://doi.org/10.1007/s11481-007-9092-0 Google Scholar
Eagle, D.M., Baunez, C., Hutcheson, D.M., Lehmann, O., Shah, A.P., & Robbins, T.W. (2007). Stop-signal reaction-time task performance: Role of prefrontal cortex and subthalamic nucleus. Cerebral Cortex, 18(1), 178–188. http://doi.org/10.1093/cercor/bhm044 Google Scholar
Eagle, D.M., Tufft, M.R.A., Goodchild, H.L., & Robbins, T.W. (2007). Differential effects of modafinil and methylphenidate on stop-signal reaction time task performance in the rat, and interactions with the dopamine receptor antagonist cis-flupenthixol. Psychopharmacology, 192(2), 193–206. http://doi.org/10.1007/s00213-007-0701-7 Google Scholar
Ernst, T., Chang, L., Jovicich, J., Ames, N., & Arnold, S. (2002). Abnormal brain activation on functional MRI in cognitively asymptomatic HIV patients. Neurology, 59(9), 1343–1349 Google Scholar
Fox, M.P., & Rosen, S. (2010). Patient retention in antiretroviral therapy programs up to three years on treatment in sub-Saharan Africa, 2007-2009: Systematic review. Tropical Medicine & International Health, 15, 1–15. http://doi.org/10.1111/j.1365-3156.2010.02508.x Google Scholar
Frank, M.J. (2005). Dynamic dopamine modulation in the basal ganglia: A neurocomputational account of cognitive deficits in medicated and nonmedicated Parkinsonism. Journal of Cognitive Neuroscience, 17(1), 51–72. http://doi.org/10.1016/S0028-3932(02)00068-4 Google Scholar
Gauggel, S., Rieger, M., & Feghoff, T.-A. (2004). Inhibition of ongoing responses in patients with Parkinson’s disease. Journal of Neurology, Neurosurgery, and Psychiatry, 75(4), 539–544 Google Scholar
Geissler, A., Gartus, A., Foki, T., Tahamtan, A.R., Beisteiner, R., & Barth, M. (2007). Contrast-to-noise ratio (CNR) as a quality parameter in fMRI. Journal of Magnetic Resonance Imaging, 25(6), 1263–1270. http://doi.org/10.1002/jmri.20935 Google Scholar
Giesen, von, H.J., Antke, C., Hefter, H., Wenserski, F., Seitz, R.J., & Arendt, G. (2000). Potential time course of human immunodeficiency virus type 1-associated minor motor deficits: Electrophysiologic and positron emission tomography findings. Archives of Neurology, 57(11), 1601–1607 Google Scholar
Grant, I. (2008). Neurocognitive disturbances in HIV. International Review of Psychiatry, 20(1), 33–47. http://doi.org/10.1080/09540260701877894 Google Scholar
Hardy, D.J., & Hinhn, C.H. (2002). Reaction time performance in adults with HIV/AIDS. Journal of Clinical and Experimental Neuropsychology, 24(7), 912–929 Google Scholar
Heaton, R.K., Clifford, D.B., Franklin, D.R. Jr, Woods, S.P., Ake, C., Vaida, F., … CHARTER group (2010). HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy. Neurology, 75, 2087–2095 Google Scholar
Hinkin, C.H., Castellon, S.A., Hardy, D.J., Granholm, E., & Siegle, G. (1999). Computerized and traditional Stroop task dysfunction in HIV-1 infection. Neuropsychology, 13(2), 306–316 Google Scholar
Holt, J.L., Kraft-Terry, S.D., & Chang, L. (2012). Neuroimaging studies of the aging HIV-1-infected brain. Journal of Neurovirology, 18(4), 291–302. http://doi.org/10.1007/s13365-012-0114-1 Google Scholar
Joska, J.A., Westgarth-Taylor, J., Myer, L., Hoare, J., Thomas, K.G.F., Combrinck, M., & Flisher, A.J. (2010). Characterization of HIV-associated neurocognitive disorders among individuals starting antiretroviral therapy in South Africa. AIDS and Behavior, 15(6), 1197–1203. http://doi.org/10.1007/s10461-010-9744-6 Google Scholar
Kellogg, S.H., McHugh, P.F., Bell, K., Schluger, J.H., Schluger, R.P., LaForge, K.S., & Kreek, M.J. (2003). The Kreek-McHugh-Schluger-Kellogg scale: A new, rapid method for quantifying substance abuse and its possible applications. Drug and Alcohol Dependence, 69(2), 137–150 Google Scholar
Langford, T.D., Letendre, S.L., Marcotte, T.D., Ellis, R.J., McCutchan, J.A., Grant, I., … HNRC Group (2002). Severe, demyelinating leukoencephalopathy in AIDS patients on antiretroviral therapy. AIDS, 16(7), 1019–1029 Google Scholar
Logan, G.D., & Cowan, W.B. (1984). On the ability to inhibit thought and action: A theory of an act of control. Psychological Review, 91(3), 295–327. http://doi.org/10.1037/0033-295X.91.3.295 Google Scholar
Logan, G.D., Cowan, W.B., & Davis, K.A. (1984). On the ability to inhibit simple and choice reaction time responses: A model and a method. Journal of Experimental Psychology: Human Perception and Performance, 10(2), 276–291. http://doi.org/10.1037/0096-1523.10.2.276 Google Scholar
Meade, C.S., Lowen, S.B., MacLean, R.R., Key, M.D., & Lukas, S.E. (2011). fMRI brain activation during a delay discounting task in HIV-positive adults with and without cocaine dependence. Psychiatry Research: Neuroimaging, 192(3), 167–175. http://doi.org/10.1016/j.pscychresns.2010.12.011 Google Scholar
Melrose, R.J., Tinaz, S., Castelo, J.M.B., Courtney, M.G., & Stern, C.E. (2008). Compromised fronto-striatal functioning in HIV: An fMRI investigation of semantic event sequencing. Behavioural Brain Research, 188(2), 337–347. http://doi.org/10.1016/j.bbr.2007.11.021 Google Scholar
Miller, E.N., Satz, P., & Visscher, B. (1991). Computerized and conventional neuropsychological assessment of HIV-1-infected homosexual men. Neurology, 41(10), 1608–1616 Google Scholar
Mink, J.W. (1996). The basal ganglia: Focused selection and inhibition of competing motor programs. Progress in Neurobiology, 50(4), 381–425 Google Scholar
Navia, B.A., Jordan, B.D., & Price, R.W. (1986). The AIDS dementia complex: I. Clinical features. Annals of Neurology, 19(6), 517–524. http://doi.org/10.1002/ana.410190602 Google Scholar
Oldfield, R.C. (1971). The assessment and analysis of handedness: The Edinburgh inventory. Neuropsychologia, 9(1), 97–113 Google Scholar
Ortega, M., Brier, M.R., & Ances, B.M. (2015). Effects of HIV and combination antiretroviral therapy on cortico-striatal functional connectivity. AIDS, 29(6), 703–712. http://doi.org/10.1097/QAD.0000000000000611 Google Scholar
Paul, R., Flanigan, T., Tashima, K., Cohen, R., Lawrence, J., Alt, E., & Hinkin, C. (2005). Apathy correlates with cognitive function but not CD4 status in patients with human immunodeficiency virus. Journal of Neuropsychiatry and Clinical Neurosciences, 17(1), 114 CrossRefGoogle Scholar
Pence, B.W., Gaynes, B.N., Whetten, K., Eron, J.J., Ryder, R.W., & Miller, W.C. (2005). Validation of a brief screening instrument for substance abuse and mental illness in HIV-positive patients. Journal of Acquired Immune Deficiency Syndromes (1999), 40(4), 434–444 Google Scholar
Plessis, du, S., Vink, M., Joska, J.A., Koutsilieri, E., Bagadia, A., Stein, D.J., && Emsley, R. (2015). HIV infection results in ventral-striatal reward system hypo-activation during cue processing. AIDS, 29(11), 1335–1343. http://doi.org/10.1097/QAD.0000000000000680 Google Scholar
Plessis, du, S., Vink, M., Joska, J.A., Koutsilieri, E., Stein, D.J., & Emsley, R. (2014). HIV infection and the fronto-striatal system: A systematic review and meta-analysis of fMRI studies. AIDS, 28, 803–811. http://doi.org/10.1097/QAD.0000000000000151 Google Scholar
Reda, A.A., & Biadgilign, S. (2012). Determinants of adherence to antiretroviral therapy among HIV-infected patients in Africa. AIDS Research and Treatment, 2012(4), 1–8. http://doi.org/10.1155/2012/574656 Google Scholar
Sheehan, D.V., Lecrubier, Y., Sheehan, K.H., Amorim, P., Janavs, J., Weiller, E., & Dunbar, G.C. (1998). The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. The Journal of Clinical Psychiatry, 59(Suppl 20), 22–33; quiz 34–57Google Scholar
Stöcker, T., Schneider, F., Klein, M., Habel, U., Kellermann, T., Zilles, K., & Shah, N.J. (2005). Automated quality assurance routines for fMRI data applied to a multicenter study. Human Brain Mapping, 25(2), 237–246. http://doi.org/10.1002/hbm.20096 Google Scholar
Thomas, J.B., Brier, M.R., Snyder, A.Z., Vaida, F.F., & Ances, B.M. (2013). Pathways to neurodegeneration: Effects of HIV and aging on resting-state functional connectivity. Neurology, 80(13), 1186–1193. http://doi.org/10.1212/WNL.0b013e318288792b CrossRefGoogle ScholarPubMed
UNAIDS (2012). UNAIDS report on the global AIDS epidemic (pp. 1–106). Geneva: Joint United Nations Program on HIV/AIDS (UNAIDS) Google Scholar
van der Kouwe, A.J.W., Benner, T., Salat, D.H., & Fischl, B. (2008). Brain morphometry with multiecho MPRAGE. Neuroimage, 40(2), 559–569. http://doi.org/10.1016/j.neuroimage.2007.12.025 Google Scholar
Van Dijk, K.R.A., Sabuncu, M.R., & Buckner, R.L. (2012). The influence of head motion on intrinsic functional connectivity MRI. Neuroimage, 59(1), 431–438. http://doi.org/10.1016/j.neuroimage.2011.07.044 Google Scholar
Vink, M., Kahn, R.S., Raemaekers, M., van den Heuvel, M., Boersma, M., & Ramsey, N.F. (2005). Function of striatum beyond inhibition and execution of motor responses. Human Brain Mapping, 25(3), 336–344. http://doi.org/10.1002/hbm.20111 Google Scholar
Vink, M., Zandbelt, B.B., Gladwin, T., Hillegers, M., Hoogendam, J.M., van den Wildenberg, W.P.M., & Kahn, R.S. (2014). Frontostriatal activity and connectivity increase during proactive inhibition across adolescence and early adulthood. Human Brain Mapping, 35(9), 4415–4427. http://doi.org/10.1002/hbm.22483 Google Scholar
Wiley, C.A., Soontornniyomkij, V., Radhakrishnan, L., Masliah, E., Mellors, J., Hermann, S.A., & Achim, C.L. (1998). Distribution of brain HIV load in AIDS. Brain Pathology, 8(2), 277–284 Google Scholar
Zandbelt, B.B., & Vink, M. (2010). On the role of the striatum in response inhibition. PLoS One, 5(11), e13848. http://doi.org/10.1371/journal.pone.0013848 Google Scholar
Zandbelt, B.B., van Buuren, M., Kahn, R.S., & Vink, M. (2011). Reduced proactive inhibition in schizophrenia is related to corticostriatal dysfunction and poor working memory. Biological Psychiatry, 70, 1151–1158 CrossRefGoogle ScholarPubMed