title: HIV infection is associated with attenuated frontostriatal intrinsic connectivity: a preliminary study.
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.
authors.affiliation: 1Department of Psychiatry and Mental Health,University of Cape Town,Cape Town,South Africa.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Ipser
authors.affiliation: 2Department of Psychiatry,University of California,San Diego,California.
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Brown
authors.affiliation: 2Department of Psychiatry,University of California,San Diego,California.
authors.forename: Amanda
authors.initials: A
authors.lastname: Bischoff-Grethe
authors.affiliation: 3Department of Psychiatry,University of California,San Francisco,California.
authors.forename: Colm G
authors.initials: CG
authors.lastname: Connolly
authors.affiliation: 2Department of Psychiatry,University of California,San Diego,California.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.affiliation: 2Department of Psychiatry,University of California,San Diego,California.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Heaton
authors.affiliation: 2Department of Psychiatry,University of California,San Diego,California.
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
mesh_terms: D000328:Adult; D000367:Age Factors; D016022:Case-Control Studies; D003342:Corpus Striatum / Q000098:blood supply / Q000473:pathology*; D005260:Female; D005625:Frontal Lobe / Q000098:blood supply / Q000473:pathology*; D015658:HIV Infections / Q000150:complications / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000098:blood supply / Q000473:pathology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D012146:Rest; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: Dopamine
references.citation: Brain Connect. 2011;1(3):207-17
references.pmid: 22433049
references.citation: J Neurol. 2000 Sep;247 Suppl 5:V1-15
references.pmid: 11081799
references.citation: Neuropsychol Rev. 2009 Jun;19(2):152-68
references.pmid: 19462243
references.citation: Neurosci Biobehav Rev. 2010 Nov;35(2):248-75
references.pmid: 20223263
references.citation: J Nerv Ment Dis. 2000 Oct;188(10):662-70
references.pmid: 11048815
references.citation: Rev Neurosci. 2010;21(3):187-221
references.pmid: 20879692
references.citation: Brain Res. 2008 Apr 14;1204:24-39
references.pmid: 18342841
references.citation: Neurol Sci. 2011 Oct;32(5):773-85
references.pmid: 21667095
references.citation: Acta Neuropathol. 1991;82(1):39-44
references.pmid: 1950477
references.citation: Immunol Rev. 2013 Jul;254(1):102-13
references.pmid: 23772617
references.citation: Neurobiol Aging. 2011 Oct;32(10):1849-56
references.pmid: 19962789
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4734-9
references.pmid: 20176931
references.citation: J Exp Psychol Gen. 2012 Feb;141(1):2-18
references.pmid: 21823805
references.citation: Brain Imaging Behav. 2012 Sep;6(3):366-73
references.pmid: 22328062
references.citation: J Magn Reson Imaging. 2010 Nov;32(5):1045-53
references.pmid: 21031507
references.citation: J Neurophysiol. 2010 Jan;103(1):297-321
references.pmid: 19889849
references.citation: Health Psychol. 2007 Jan;26(1):40-9
references.pmid: 17209696
references.citation: J Infect Dis. 2002 Dec 1;186 Suppl 2:S193-8
references.pmid: 12424697
references.citation: Soc Cogn Affect Neurosci. 2009 Dec;4(4):423-8
references.pmid: 20035017
references.citation: Front Syst Neurosci. 2010 Apr 06;4:8
references.pmid: 20407579
references.citation: J Neurosci. 2012 Jun 13;32(24):8186-91
references.pmid: 22699899
references.citation: Neurology. 2001 Sep 25;57(6):1001-7
references.pmid: 11571324
references.citation: J Neurovirol. 2009 May;15(3):257-74
references.pmid: 19499455
references.citation: J Neurosci. 2011 Oct 5;31(40):14284-90
references.pmid: 21976513
references.citation: AIDS. 1994 Jan;8(1):67-71
references.pmid: 8011238
references.citation: J Acquir Immune Defic Syndr. 2012 Apr 15;59(5):469-77
references.pmid: 22269799
references.citation: Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13848-53
references.pmid: 16945915
references.citation: Behav Brain Res. 2008 Apr 9;188(2):337-47
references.pmid: 18242723
references.citation: J Neuroimmune Pharmacol. 2009 Jun;4(2):163-74
references.pmid: 19067177
references.citation: Neurology. 2013 Mar 26;80(13):1186-93
references.pmid: 23446675
references.citation: Schizophr Bull. 2009 Jan;35(1):19-31
references.pmid: 19042912
references.citation: PLoS One. 2013;8(6):e66241
references.pmid: 23840428
references.citation: J Neurosci Res. 1991 Mar;28(3):406-9
references.pmid: 1856886
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):20069-74
references.pmid: 19903877
references.citation: Psychometrika. 2013 Jul;78(3):396-416
references.pmid: 25106392
references.citation: J Neurophysiol. 2008 Dec;100(6):3328-42
references.pmid: 18799601
references.citation: Biochem J. 1992 May 1;283 ( Pt 3):633-5
references.pmid: 1534219
references.citation: Arch Neurol. 1996 Feb;53(2):155-8
references.pmid: 8639065
references.citation: Acta Neuropathol. 2000 Apr;99(4):376-84
references.pmid: 10787036
references.citation: Arch Neurol. 1993 Mar;50(3):250-5
references.pmid: 8442702
references.citation: J Clin Exp Neuropsychol. 2004 May;26(3):307-19
references.pmid: 15512922
references.citation: Neuroimage. 2014 Jan 1;84:320-41
references.pmid: 23994314
references.citation: AIDS. 2014 Mar 27;28(6):803-11
references.pmid: 24300546
references.citation: Neurology. 2002 Nov 12;59(9):1343-9
references.pmid: 12427881
references.citation: Brain Res Brain Res Rev. 1995 Jan;20(1):91-127
references.pmid: 7711769
references.citation: J Neurovirol. 2012 Feb;18(1):74-9
references.pmid: 22271019
references.citation: Am J Psychiatry. 2005 Aug;162(8):1461-72
references.pmid: 16055767
references.citation: Brain Res. 2003 Apr 4;968(1):1-14
references.pmid: 12644259
references.citation: J Neurosci. 1985 Mar;5(3):776-94
references.pmid: 2983048
references.citation: Int J Methods Psychiatr Res. 2004;13(2):93-121
references.pmid: 15297906
references.citation: Acta Neurol Scand. 1993 Aug;88(2):112-8
references.pmid: 8213054
references.citation: Neurology. 2010 Dec 7;75(23):2087-96
references.pmid: 21135382
references.citation: Hum Brain Mapp. 2000 Jul;10(3):120-31
references.pmid: 10912591
references.citation: J Neuroimmune Pharmacol. 2013 Sep;8(4):965-74
references.pmid: 23749418
references.citation: Cereb Cortex. 2007 Sep;17 Suppl 1:i6-15
references.pmid: 17434919
references.citation: Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):8212-6
references.pmid: 10393974
references.citation: J Neurovirol. 2011 Feb;17(1):3-16
references.pmid: 21174240
references.citation: Annu Rev Neurosci. 1986;9:357-81
references.pmid: 3085570
references.citation: Cereb Cortex. 2013 Nov;23(11):2677-89
references.pmid: 22918987
references.citation: Neuroreport. 1996 Mar 22;7(4):910-2
references.pmid: 8724671
references.citation: Cereb Cortex. 2008 Dec;18(12):2735-47
references.pmid: 18400794
references.citation: Cereb Cortex. 2009 Oct;19(10):2209-29
references.pmid: 19221144
references.citation: Comput Biomed Res. 1996 Jun;29(3):162-73
references.pmid: 8812068
references.citation: PLoS One. 2014;9(10):e111583
references.pmid: 25347679
references.citation: Neurobiol Aging. 2015 Jan;36(1):401-12
references.pmid: 25034343
references.citation: Ann Neurol. 2004 Aug;56(2):259-72
references.pmid: 15293278