Skip to main content Accessibility help
×
×
Home

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

  • Jonathan C. Ipser (a1), Gregory G. Brown (a2), Amanda Bischoff-Grethe (a2), Colm G. Connolly (a3), Ronald J. Ellis (a2) (a4), Robert K. Heaton (a2), Igor Grant (a2) and Translational Methamphetamine AIDS Research Center (TMARC) Group (a2)...
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)

Copyright
Corresponding author
Correspondence and reprint requests to: Gregory Brown, SDVAMC, 3350 La Jolla Village Drive, San Diego, CA 92161-116A. E-mail: gbrown@ucsd.edu
References
Hide All
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.
American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: American Psychiatric Association.
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.
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.
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.
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
Beck, A.T., Steer, R.A., & Brown, G.K. (1996). Manual for the Beck Depression Inventory-II. San Antonio, TX: Psychological Corporation.
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.
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.
Berger, J.R., Kumar, M., Kumar, A., Fernandez, J.B., & Levin, B. (1994). Cerebrospinal fluid dopamine in HIV-1 infection. AIDS, 8(1), 6771.
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.
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.
Buckner, R.L., Krienen, F.M., Yeo, B.T. (2013). Opportunities and limitations of intrinsic functional connectivity MRI. Natural Neuroscience, 16(7), 832837.
Burdo, T.H., Lackner, A., & Williams, K.C. (2013). Monocyte/macrophages and their role in HIV neuropathogenesis. Immunological Reviews, 254(1), 102113.
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.
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.
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.
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.
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.
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.
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.
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.
Cox, R.W. (1996). AFNI: Software for analysis and visualization of functional magnetic resonance neuroimages. Computers and Biomedical Research, 29(3), 162173.
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.
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
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.
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.
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.
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.
Fjell, A.M., & Walhovd, K.B. (2010). Structural brain changes in aging: Courses, causes and cognitive consequences. Reviews in the Neurosciences, 21(3), 187221.
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.
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.
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.
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.
Hedges, L.V., & Olkin, L.I. (1985). Statistical methods for meta-analysis. Orlando, FL: Academic Press.
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.
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.
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/
Itoh, K., Mehraein, P., & Weis, S. (2000). Neuronal damage of the substantia nigra in HIV-1 infected brains. Acta Neuropathologica, 99(4), 376384.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Larsson, M., Hagberg, L., Forsman, A., & Norkrans, G. (1991). Cerebrospinal fluid catecholamine metabolites in HIV-infected patients. Journal of Neuroscience Research, 28(3), 406409.
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.
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.
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.
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.
Nakano, K., Kayahara, T., Tsutsumi, T., & Ushiro, H. (2000). Neural circuits and functional organization of the striatum. Journal of Neurology, 247(Suppl 5), V1V15.
Nath, A. (2002). Human immunodeficiency virus (HIV) proteins in neuropathogenesis of HIV dementia. The Journal of Infectious Diseases, 186(Suppl 2), S193S198.
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.
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.
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.
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.
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/
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.
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.
Rosazza, C., & Minati, L. (2011). Resting-state brain networks: Literature review and clinical applications. Neurological Sciences, 32(5), 773785.
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.
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.
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.
Shapiro, S.S., & Wilk, M.B. (1965). An analysis of variance test for normality (complete samples). Biometrika, 52(3–4), 591611.
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.
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.
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.
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.
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.
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.
Wilkinson, G.S., & Robertson, G.J. (2006). WRAT 4 (4th ed.). Lutz, FL: Psychological Assessment Resources, Inc.
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.
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.
Woods, S.P., Moore, D.J., Weber, E., & Grant, I. (2009). Cognitive neuropsychology of HIV-associated neurocognitive disorders. Neuropsychology Review, 19(2), 152168.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Journal of the International Neuropsychological Society
  • ISSN: 1355-6177
  • EISSN: 1469-7661
  • URL: /core/journals/journal-of-the-international-neuropsychological-society
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords

Type Description Title
WORD
Supplementary materials

Ipser supplementary material S1
Table

 Word (86 KB)
86 KB

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed