Hostname: page-component-7c8c6479df-xxrs7 Total loading time: 0 Render date: 2024-03-28T15:53:08.705Z Has data issue: false hasContentIssue false

HIV Infection Is Associated with Attenuated Frontostriatal Intrinsic Connectivity: A Preliminary Study

Published online by Cambridge University Press:  31 March 2015

Jonathan C. Ipser
Affiliation:
Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa
Gregory G. Brown*
Affiliation:
Department of Psychiatry, University of California, San Diego, California
Amanda Bischoff-Grethe
Affiliation:
Department of Psychiatry, University of California, San Diego, California
Colm G. Connolly
Affiliation:
Department of Psychiatry, University of California, San Francisco, California
Ronald J. Ellis
Affiliation:
Department of Psychiatry, University of California, San Diego, California Department of Neurosciences, University of California, San Diego, California
Robert K. Heaton
Affiliation:
Department of Psychiatry, University of California, San Diego, California
Igor Grant
Affiliation:
Department of Psychiatry, University of California, San Diego, California
Translational Methamphetamine AIDS Research Center (TMARC) Group
Affiliation:
Department of Psychiatry, University of California, San Diego, California
*
Correspondence and reprint requests to: Gregory Brown, SDVAMC, 3350 La Jolla Village Drive, San Diego, CA 92161-116A. E-mail: gbrown@ucsd.edu

Abstract

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. (JINS, 2015, 21, 1–11)

Type
Research Articles
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

Alexander, G.E., DeLong, M.R., & Strick, P.L. (1986). Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annual Review of Neuroscience, 9, 357381.Google Scholar
American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: American Psychiatric Association.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, 59(5), 469477.Google Scholar
Arnsten, A.F. (2007). Catecholamine and second messenger influences on prefrontal cortical networks of “representational knowledge”: A rational bridge between genetics and the symptoms of mental illness. Cerebral Cortex, 17(Suppl 1), i6i15.Google Scholar
Backman, L., Karlsson, S., Fischer, H., Karlsson, P., Brehmer, Y., Rieckmann, A., … Nyberg, L. (2011). Dopamine D(1) receptors and age differences in brain activation during working memory. Neurobiology of Aging, 32(10), 18491856.Google Scholar
Barclay, T.R., Hinkin, C.H., Castellon, S.A., Mason, K.I., Reinhard, M.J., Marion, S.D., … Durvasula, R.S. (2007). Age-associated predictors of medication adherence in HIV-positive adults: Health beliefs, self-efficacy, and neurocognitive status. Health Psychology, 26(1), 4049. doi: 10.1037/0278-6133.26.1.40 Google Scholar
Beck, A.T., Steer, R.A., & Brown, G.K. (1996). Manual for the Beck Depression Inventory-II. San Antonio, TX: Psychological Corporation.Google Scholar
Becker, J.T., Bajo, R., Fabrizio, M., Sudre, G., Cuesta, P., Aizenstein, H.J., … Bagic, A. (2012). Functional connectivity measured with magnetoencephalography identifies persons with HIV disease. Brain Imaging and Behavior, 6(3), 366373.Google Scholar
Benjamini, Y., & Hochberg, Y. (1995). Controlling the false discovery rate: A practical and powerful approach to multiple testing. Journal of the Royal Statistical Society . Series B (Methodological), 57(1), 289300.CrossRefGoogle Scholar
Berger, J.R., Kumar, M., Kumar, A., Fernandez, J.B., & Levin, B. (1994). Cerebrospinal fluid dopamine in HIV-1 infection. AIDS, 8(1), 6771.Google Scholar
Biswal, B.B., Mennes, M., Zuo, X.N., Gohel, S., Kelly, C., Smith, S.M., … Milham, M.P. (2010). Toward discovery science of human brain function. Proceedings of the National Academy of Sciences of the United States of America, 107(10), 47344739.Google Scholar
Brew, B.J., Crowe, S.M., Landay, A., Cysique, L.A., & Guillemin, G. (2009). Neurodegeneration and ageing in the HAART era. Journal of Neuroimmune Pharmacology, 4(2), 163174.Google Scholar
Buckner, R.L., Krienen, F.M., Yeo, B.T. (2013). Opportunities and limitations of intrinsic functional connectivity MRI. Natural Neuroscience, 16(7), 832837.Google Scholar
Burdo, T.H., Lackner, A., & Williams, K.C. (2013). Monocyte/macrophages and their role in HIV neuropathogenesis. Immunological Reviews, 254(1), 102113.Google Scholar
Carey, C.L., Woods, S.P., Gonzalez, R., Conover, E., Marcotte, T.D., Grant, I., … HNRC Group. (2004). Predictive validity of global deficit scores in detecting neuropsychological impairment in HIV infection. Journal of Clinical and Experimental Neuropsychology, 26(3), 307319.Google Scholar
Casaletto, K.B., Cattie, J., Franklin, D.R., Moore, D.J., Woods, S.P., Grant, I., … HNRP Group. (2014). The wide range achievement test-4 reading subtest “holds” in HIV-infected individuals. Journal of Clinical and Experimental Neuropsychology, 36(9), 9921001.Google Scholar
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), 10011007.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), 259272.Google Scholar
Cheatwood, J.L., Reep, R.L., & Corwin, J.V. (2003). The associative striatum: Cortical and thalamic projections to the dorsocentral striatum in rats. Brain Research, 968(1), 114.Google Scholar
Cieslik, E.C., Zilles, K., Caspers, S., Roski, C., Kellermann, T.S., Jakobs, O., … Eickhoff, S.B. (2013). Is there “one” DLPFC in cognitive action control? Evidence for heterogeneity from co-activation-based parcellation. Cerebral Cortex, 23(11), 26772689.CrossRefGoogle Scholar
Cole, D.M., Smith, S.M., & Beckmann, C.F. (2010). Advances and pitfalls in the analysis and interpretation of resting-state FMRI data. Frontiers in Systems Neuroscience, 4, 8.Google Scholar
Connolly, C.G., Bischoff-Grethe, A., Jordan, S.J., Woods, S.P., Ellis, R.J., Paulus, M.P., … Translational Methamphetamine, Aids Research Center Group. (2014). Altered functional response to risky choice in HIV infection. PLoS One, 9(10), e111583.CrossRefGoogle ScholarPubMed
Cox, R.W. (1996). AFNI: Software for analysis and visualization of functional magnetic resonance neuroimages. Computers and Biomedical Research, 29(3), 162173.CrossRefGoogle ScholarPubMed
Damoiseaux, J.S., Rombouts, S.A., Barkhof, F., Scheltens, P., Stam, C.J., Smith, S.M., & Beckmann, C.F. (2006). Consistent resting-state networks across healthy subjects. Proceedings of the National Academy of Sciences of the United States of America, 103(37), 1384813853.Google Scholar
Del Re, A.C. (2013). compute.es: Compute Effect Sizes. R package version 0.2-2. Retrieved from http://cran.r-project.org/web/packages/compute.es Google Scholar
Di Martino, A., Scheres, A., Margulies, D.S., Kelly, A.M.C., Uddin, L.Q., Shehzad, Z., … Milham, M.P. (2008). Functional connectivity of human striatum: A resting state FMRI study. Cerebral Cortex, 18(12), 27352747.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), 13431349.Google Scholar
Ernst, T., Jiang, C.S., Nakama, H., Buchthal, S., & Chang, L. (2010). Lower brain glutamate is associated with cognitive deficits in HIV patients: A new mechanism for HIV-associated neurocognitive disorder. Journal of Magnetic Resonance Imaging, 32(5), 10451053.CrossRefGoogle ScholarPubMed
Feil, J., Sheppard, D., Fitzgerald, P.B., Yucel, M., Lubman, D.I., & Bradshaw, J.L. (2010). Addiction, compulsive drug seeking, and the role of frontostriatal mechanisms in regulating inhibitory control. Neuroscience and Biobehavioral Reviews, 35(2), 248275.Google Scholar
Fjell, A.M., & Walhovd, K.B. (2010). Structural brain changes in aging: Courses, causes and cognitive consequences. Reviews in the Neurosciences, 21(3), 187221.CrossRefGoogle ScholarPubMed
Fritz, C.O., Morris, P.E., & Richler, J.J. (2012). Effect size estimates: Current use, calculations, and interpretation. Journal of Expimental Psychology . General, 141(1), 218.Google Scholar
Greve, D.N., Brown, G.G., Mueller, B.A., Glover, G., & Liu, T.T. (2013). A survey of the sources of noise in fMRI. Psychometrika, 78(3), 396416.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: CHARTER Study. Neurology, 75(23), 20872096.Google Scholar
Heaton, R.K., Franklin, D.R., Ellis, R.J., McCutchan, J.A., Letendre, S.L., Leblanc, S., … Group, H. N. R. C. (2011). HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: Differences in rates, nature, and predictors. Journal of Neurovirology, 17(1), 316.Google Scholar
Hedges, L.V., & Olkin, L.I. (1985). Statistical methods for meta-analysis. Orlando, FL: Academic Press.Google Scholar
Hestad, K., McArthur, J.H., Dal Pan, G.J., Selnes, O.A., Nance-Sproson, T.E., Aylward, E., … McArthur, J.C. (1993). Regional brain atrophy in HIV-1 infection: Association with specific neuropsychological test performance. Acta Neurologica Scandinavica, 88(2), 112118.Google Scholar
Heyes, M.P., Saito, K., & Markey, S.P. (1992). Human macrophages convert L-tryptophan into the neurotoxin quinolinic acid. The Biochemical Journal . 283(Pt 3), 633635.Google Scholar
Hothorn, T., Hornik, K., van de Wiel, M.A., & Zeileis, A. (2008). Implementing a class of permutation tests: The coin Package. Journal of Statistical Software, 28(8), 123. http://www.jstatsoft.org/v28/i08/ Google Scholar
Itoh, K., Mehraein, P., & Weis, S. (2000). Neuronal damage of the substantia nigra in HIV-1 infected brains. Acta Neuropathologica, 99(4), 376384.Google Scholar
Jernigan, T.L., Archibald, S., Hesselink, J.R., Atkinson, J.H., Velin, R.A., McCutchan, J.A., … Grant, I. (1993). Magnetic resonance imaging morphometric analysis of cerebral volume loss in human immunodeficiency virus infection. The HNRC Group. Archives of Neurology, 50(3), 250255.Google Scholar
Jernigan, T.L., Gamst, A.C., Archibald, S.L., Fennema-Notestine, C., Mindt, M.R., Marcotte, T.D., … Grant, I. (2005). Effects of methamphetamine dependence and HIV infection on cerebral morphology. American Journal of Psychiatry, 162(8), 14611472.Google Scholar
Kalichman, S.C., Rompa, D., & Cage, M. (2000). Distinguishing between overlapping somatic symptoms of depression and HIV disease in people living with HIV-AIDS. Journal of Nervous and Mental Disease, 188(10), 662670.Google Scholar
Kamishina, H., Yurcisin, G.H., Corwin, J.V., & Reep, R.L. (2008). Striatal projections from the rat lateral posterior thalamic nucleus. Brain Research, 1204, 2439.Google Scholar
Kaul, M., & Lipton, S.A. (1999). Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis. Proceedings of the National Academy of Sciences of the United States of America, 96(14), 82128216.Google Scholar
Kessler, R.C., & Ustun, T.B. (2004). The World Mental Health (WMH) Survey Initiative Version of the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI). International Journal of Methods in Psychiatric Research, 13(2), 93121.Google Scholar
Kieburtz, K., Ketonen, L., Cox, C., Grossman, H., Holloway, R., Booth, H., … Caine, E.D. (1996). Cognitive performance and regional brain volume in human immunodeficiency virus type 1 infection. Archives of Neurology, 53(2), 155158.CrossRefGoogle ScholarPubMed
Kumar, A.M., Fernandez, J.B., Singer, E.J., Commins, D., Waldrop-Valverde, D., Ownby, R.L., & Kumar, M. (2009). Human immunodeficiency virus type 1 in the central nervous system leads to decreased dopamine in different regions of postmortem human brains. Journal of Neurovirology, 15(3), 257274.Google Scholar
Lancaster, J.L., Woldorff, M.G., Parsons, L.M., Liotti, M., Freitas, C.S., Rainey, L., … Fox, P.T. (2000). Automated Talairach atlas labels for functional brain mapping. Human Brain Mapping, 10(3), 120131.Google Scholar
Larsson, M., Hagberg, L., Forsman, A., & Norkrans, G. (1991). Cerebrospinal fluid catecholamine metabolites in HIV-infected patients. Journal of Neuroscience Research, 28(3), 406409.Google Scholar
Lieberman, M.D., & Cunningham, W.A. (2009). Type I and Type II error concerns in fMRI research: Re-balancing the scale. Social Cognitive and Affective Neuroscience, 4(4), 423428.CrossRefGoogle ScholarPubMed
MacDonald, S.W.S., Karlsson, S., Rieckmann, A., Nyberg, L., & Bäckman, L. (2012). Aging-related increases in behavioral variability: Relations to losses of dopamine D1 receptors. Journal of Neuroscience, 32(24), 81868191.Google Scholar
Margulies, D.S., Vincent, J.L., Kelly, C., Lohmann, G., Uddin, L.Q., Biswal, B.B., … Petrides, M. (2009). Precuneus shares intrinsic functional architecture in humans and monkeys. Proceedings of the National Academy of Sciences of the United States of America, 106(47), 2006920074.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), 337347.CrossRefGoogle ScholarPubMed
Nakano, K., Kayahara, T., Tsutsumi, T., & Ushiro, H. (2000). Neural circuits and functional organization of the striatum. Journal of Neurology, 247(Suppl 5), V1V15.Google Scholar
Nath, A. (2002). Human immunodeficiency virus (HIV) proteins in neuropathogenesis of HIV dementia. The Journal of Infectious Diseases, 186(Suppl 2), S193S198.Google Scholar
Parent, A., & Hazrati, L.N. (1995). Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop. Brain Research. Brain Research Reviews, 20(1), 91127.Google Scholar
Plessis, S.D., 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(6), 803811.Google Scholar
Potkin, S.G., Turner, J.A., Brown, G.G., McCarthy, G., Greve, D.N., Glover, G.H., … Fbirn. (2009). Working memory and DLPFC inefficiency in schizophrenia: The FBIRN study. Schizophrenia Bulletin, 35(1), 1931.Google Scholar
Power, J.D., Mitra, A., Laumann, T.O., Snyder, A.Z., Schlaggar, B.L., & Petersen, S.E. (2014). Methods to detect, characterize, and remove motion artifact in resting state fMRI. Neuroimage, 84, 320341.Google Scholar
R Development Core Team. (2012). R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing. Retrieved from, http://www.R-project.org/ Google Scholar
Reyes, M.G., Faraldi, F., Senseng, C.S., Flowers, C., & Fariello, R. (1991). Nigral degeneration in acquired immune deficiency syndrome (AIDS). Acta Neuropathologica, 82(1), 3944.Google Scholar
Rieckmann, A., Karlsson, S., Fischer, H., & Bäckman, L. (2011). Caudate dopamine D1 receptor density is associated with individual differences in frontoparietal connectivity during working memory. Journal of Neuroscience, 31(40), 1428414290.Google Scholar
Rosazza, C., & Minati, L. (2011). Resting-state brain networks: Literature review and clinical applications. Neurological Sciences, 32(5), 773785.Google Scholar
Sardar, A.M., Czudek, C., & Reynolds, G.P. (1996). Dopamine deficits in the brain: The neurochemical basis of parkinsonian symptoms in AIDS. Neuroreport, 7(4), 910912.Google Scholar
Schweinsburg, B.C., Scott, J.C., Schweinsburg, A.D., Jacobus, J., Theilmann, R.J., Frank, L.R., … H.I.V. Neurobehavioral Research Center Group. (2012). Altered prefronto-striato-parietal network response to mental rotation in HIV. Journal of Neurovirology, 18(1), 7479.Google Scholar
Selemon, L.D., & Goldman-Rakic, P.S. (1985). Longitudinal topography and interdigitation of corticostriatal projections in the rhesus monkey. The Journal of Neuroscience, 5(3), 776794.CrossRefGoogle ScholarPubMed
Shapiro, S.S., & Wilk, M.B. (1965). An analysis of variance test for normality (complete samples). Biometrika, 52(3–4), 591611.Google Scholar
Shehzad, Z., Kelly, A.M., Reiss, P.T., Gee, D.G., Gotimer, K., Uddin, L.Q., … Milham, M.P. (2009). The resting brain: Unconstrained yet reliable. Cerebral Cortex, 19(10), 22092229.Google Scholar
Thomas, J.B., Brier, M.R., Ortega, M., Benzinger, T.L., & Ances, B.M. (2015). Weighted brain networks in disease: Centrality and entropy in human immunodeficiency virus and aging. Neurobiology of Aging, 36, 401412.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, 26, 11861193.Google Scholar
Van Dijk, K.R., Hedden, T., Venkataraman, A., Evans, K.C., Lazar, S.W., & Buckner, R.L. (2010). Intrinsic functional connectivity as a tool for human connectomics: Theory, properties, and optimization. Journal of Neurophysiology, 103(1), 297321.Google Scholar
Vincent, J.L., Kahn, I., Snyder, A.Z., Raichle, M.E., & Buckner, R.L. (2008). Evidence for a frontoparietal control system revealed by intrinsic functional connectivity. Journal of Neurophysiology, 100(6), 33283342.Google Scholar
Wang, X., Foryt, P., Ochs, R., Chung, J., Wu, Y., Parrish, T., & Ragin, A.B. (2011). Abnormalities in resting-state functional connectivity in early human immunodeficiency virus infection. Brain Connectivity, 1(3), 207217.Google Scholar
Wilkinson, G.S., & Robertson, G.J. (2006). WRAT 4 (4th ed.). Lutz, FL: Psychological Assessment Resources, Inc.Google Scholar
Wilson, T.W., Fox, H.S., Robertson, K.R., Sandkovsky, U., O’Neill, J., Heinrichs-Graham, E., … Swindells, S. (2013). Abnormal MEG oscillatory activity during visual processing in the prefrontal cortices and frontal eye-fields of the aging HIV brain. PLoS One, 8(6), e66241.Google Scholar
Wilson, T.W., Heinrichs-Graham, E., Robertson, K.R., Sandkovsky, U., O’Neill, J., Knott, N.L., … Swindells, S. (2013). Functional brain abnormalities during finger-tapping in HIV-infected older adults: A magnetoencephalography study. J Neuroimmune Pharmacology, 8(4), 965974.Google Scholar
Woods, S.P., Moore, D.J., Weber, E., & Grant, I. (2009). Cognitive neuropsychology of HIV-associated neurocognitive disorders. Neuropsychology Review, 19(2), 152168.Google Scholar
Supplementary material: File

Ipser supplementary material S1

Table

Download Ipser supplementary material S1(File)
File 85.5 KB