Role of Neuroimaging in HIV-Associated Neurocognitive Disorders

 

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Abstract

Human immunodeficiency virus (HIV) enters the brain soon after seroconversion and can cause HIV-associated neurocognitive disorders (HAND). Although the more severe and progressive forms of HAND are less prevalent due to combination antiretroviral therapy (cART), ∼ 40% of HIV-infected (HIV+) patients continue to have cognitive impairment. Some HIV+ individuals who have effective plasma HIV-1 RNA suppression with cART still develop HAND. It is often difficult to diagnose HAND in the outpatient setting as detailed neuropsychological performance testing is required. Additional biomarkers that are relatively easy to obtain and clinically relevant are needed for assessing HIV-associated neuropathologic changes. Recently developed noninvasive magnetic resonance imaging (MRI) techniques have great potential to serve as biomarkers. The authors review the application of some of these neuroimaging techniques, magnetic resonance spectroscopy (MRS), volumetric MRI, diffusion tensor imaging (DTI), functional MRI (fMRI), in HIV+ individuals. Each of the neuroimaging methods offers unique insight into mechanisms underlying neuroHIV, could monitor disease progression, and may assist in evaluating the efficacy of particular cART regimens. It is hoped that considerable progress will continue to occur such that some of these neuroimaging methods will be incorporated across multiple sites and included in future HAND guidelines.

• References

• 1 Letendre SL, Ellis RJ, Everall I, Ances B, Bharti A, McCutchan JA. Neurologic complications of HIV disease and their treatment. Top HIV Med 2009; 17 (2) 46-56
  PubMedGoogle Scholar
• 2 Justice AC. HIV and aging: time for a new paradigm. Curr HIV/AIDS Rep 2010; 7 (2) 69-76
  CrossrefPubMedGoogle Scholar
• 3 Holt JL, Kraft-Terry SD, Chang L. Neuroimaging studies of the aging HIV-1-infected brain. J Neurovirol 2012; 18 (4) 291-302
  CrossrefPubMedGoogle Scholar
• 4 Aberg JA, Kaplan JE, Libman H , et al; HIV Medicine Association of the Infectious Diseases Society of America. Primary care guidelines for the management of persons infected with human immunodeficiency virus: 2009 update by the HIV medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2009; 49 (5) 651-681
  CrossrefPubMedGoogle Scholar
• 5 Luther VP, Wilkin AM. HIV infection in older adults. Clin Geriatr Med 2007; 23 (3) 567-583 , vii
  CrossrefPubMedGoogle Scholar
• 6 Justice AC, Modur SP, Tate JP , et al; NA-ACCORD and VACS Project Teams. Predictive accuracy of the Veterans Aging Cohort Study index for mortality with HIV infection: a North American cross cohort analysis. J Acquir Immune Defic Syndr 2013; 62 (2) 149-163
  CrossrefPubMedGoogle Scholar
• 7 Heaton RK, Clifford DB, Franklin Jr DR , et al; CHARTER Group. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 2010; 75 (23) 2087-2096
  CrossrefPubMedGoogle Scholar
• 8 Antinori A, Arendt G, Becker JT , et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology 2007; 69 (18) 1789-1799
  CrossrefPubMedGoogle Scholar
• 9 Spudich S. HIV and neurocognitive dysfunction. Curr HIV/AIDS Rep 2013; 10 (3) 235-243
  CrossrefPubMedGoogle Scholar
• 10 Ellis RJ, Moore DJ, Childers ME , et al. Progression to neuropsychological impairment in human immunodeficiency virus infection predicted by elevated cerebrospinal fluid levels of human immunodeficiency virus RNA. Arch Neurol 2002; 59 (6) 923-928
  CrossrefPubMedGoogle Scholar
• 11 Liner II KJ, Ro MJ, Robertson KR. HIV, antiretroviral therapies, and the brain. Curr HIV/AIDS Rep 2010; 7 (2) 85-91
  CrossrefPubMedGoogle Scholar
• 12 Marra CM, Zhao Y, Clifford DB , et al; AIDS Clinical Trials Group 736 Study Team. Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance. AIDS 2009; 23 (11) 1359-1366
  CrossrefPubMedGoogle Scholar
• 13 Robertson K, Liner J, Meeker RB. Antiretroviral neurotoxicity. J Neurovirol 2012; 18 (5) 388-399
  CrossrefPubMedGoogle Scholar
• 14 Hagberg L, Cinque P, Gisslen M , et al. Cerebrospinal fluid neopterin: an informative biomarker of central nervous system immune activation in HIV-1 infection. AIDS Res Ther 2010; 7: 15
  CrossrefPubMedGoogle Scholar
• 15 Mind Exchange Working G ; Mind Exchange Working Group. Assessment, diagnosis, and treatment of HIV-associated neurocognitive disorder: a consensus report of the mind exchange program. Clin Infect Dis 2013; 56 (7) 1004-1017
  CrossrefPubMedGoogle Scholar
• 16 Gannon P, Khan MZ, Kolson DL. Current understanding of HIV-associated neurocognitive disorders pathogenesis. Curr Opin Neurol 2011; 24 (3) 275-283
  CrossrefPubMedGoogle Scholar
• 17 Valcour V, Paul R, Chiao S, Wendelken LA, Miller B. Screening for cognitive impairment in human immunodeficiency virus. Clin Infect Dis 2011; 53 (8) 836-842
  CrossrefPubMedGoogle Scholar
• 18 Sperling RA, Aisen PS, Beckett LA , et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011; 7 (3) 280-292
  CrossrefPubMedGoogle Scholar
• 19 Sathekge M, Goethals I, Maes A, van de Wiele C. Positron emission tomography in patients suffering from HIV-1 infection. Eur J Nucl Med Mol Imaging 2009; 36 (7) 1176-1184
  CrossrefPubMedGoogle Scholar
• 20 Cysique LA, Moffat K, Moore DM , et al. HIV, vascular and aging injuries in the brain of clinically stable HIV-infected adults: a (1)H MRS study. PLoS ONE 2013; 8 (4) e61738
  CrossrefPubMedGoogle Scholar
• 21 Lentz MR, Kim WK, Kim H , et al. Alterations in brain metabolism during the first year of HIV infection. J Neurovirol 2011; 17 (3) 220-229
  CrossrefPubMedGoogle Scholar
• 22 Harezlak J, Buchthal S, Taylor M , et al; HIV Neuroimaging Consortium. Persistence of HIV-associated cognitive impairment, inflammation, and neuronal injury in era of highly active antiretroviral treatment. AIDS 2011; 25 (5) 625-633
  CrossrefPubMedGoogle Scholar
• 23 Descamps M, Hyare H, Stebbing J, Winston A. Magnetic resonance imaging and spectroscopy of the brain in HIV disease. J HIV Ther 2008; 13 (3) 55-58
  PubMedGoogle Scholar
• 24 Kantarci K. Proton MRS in mild cognitive impairment. J Magn Reson Imaging 2013; 37 (4) 770-777
  CrossrefPubMedGoogle Scholar
• 25 Valcour V, Chalermchai T, Sailasuta N , et al; RV254/SEARCH 010 Study Group. Central nervous system viral invasion and inflammation during acute HIV infection. J Infect Dis 2012; 206 (2) 275-282
  CrossrefPubMedGoogle Scholar
• 26 Sailasuta N, Ross W, Ananworanich J , et al; RV254/SEARCH 010 protocol teams. Change in brain magnetic resonance spectroscopy after treatment during acute HIV infection. PLoS ONE 2012; 7 (11) e49272
  CrossrefPubMedGoogle Scholar
• 27 Iannucci G, Rovaris M, Giacomotti L, Comi G, Filippi M. Correlation of multiple sclerosis measures derived from T2-weighted, T1-weighted, magnetization transfer, and diffusion tensor MR imaging. AJNR Am J Neuroradiol 2001; 22 (8) 1462-1467
  PubMedGoogle Scholar
• 28 Cardenas VA, Meyerhoff DJ, Studholme C , et al. Evidence for ongoing brain injury in human immunodeficiency virus-positive patients treated with antiretroviral therapy. J Neurovirol 2009; 15 (4) 324-333
  CrossrefPubMedGoogle Scholar
• 29 Mohamed MA, Barker PB, Skolasky RL , et al. Brain metabolism and cognitive impairment in HIV infection: a 3-T magnetic resonance spectroscopy study. Magn Reson Imaging 2010; 28 (9) 1251-1257
  CrossrefPubMedGoogle Scholar
• 30 Paul RH, Ernst T, Brickman AM , et al; ACTG 301 team; ACTG 700 team; HIV MRS Consortium. Relative sensitivity of magnetic resonance spectroscopy and quantitative magnetic resonance imaging to cognitive function among nondemented individuals infected with HIV. J Int Neuropsychol Soc 2008; 14 (5) 725-733
  PubMedGoogle Scholar
• 31 Yiannoutsos CT, Nakas CT, Navia BA ; proton MRS Consortium. Assessing multiple-group diagnostic problems with multi-dimensional receiver operating characteristic surfaces: application to proton MR Spectroscopy (MRS) in HIV-related neurological injury. Neuroimage 2008; 40 (1) 248-255
  CrossrefPubMedGoogle Scholar
• 32 Ernst T, Jiang CS, Nakama H, Buchthal S, Chang L. Lower brain glutamate is associated with cognitive deficits in HIV patients: a new mechanism for HIV-associated neurocognitive disorder. J Magn Reson Imaging 2010; 32 (5) 1045-1053
  CrossrefPubMedGoogle Scholar
• 33 Chang L, Ernst T, Leonido-Yee M , et al. Highly active antiretroviral therapy reverses brain metabolite abnormalities in mild HIV dementia. Neurology 1999; 53 (4) 782-789
  CrossrefPubMedGoogle Scholar
• 34 Tarasów E, Wiercińska-Drapało A, Jaroszewicz J , et al. Antiretroviral therapy and its influence on the stage of brain damage in patients with HIV - 1H MRS evaluation. Med Sci Monit 2004; 10 (Suppl. 03) 101-106
  PubMedGoogle Scholar
• 35 Schifitto G, Yiannoutsos CT, Ernst T , et al; ACTG 5114 Team. Selegiline and oxidative stress in HIV-associated cognitive impairment. Neurology 2009; 73 (23) 1975-1981
  CrossrefPubMedGoogle Scholar
• 36 Robertson KR, Su Z, Margolis DM , et al; A5170 Study Team. Neurocognitive effects of treatment interruption in stable HIV-positive patients in an observational cohort. Neurology 2010; 74 (16) 1260-1266
  CrossrefPubMedGoogle Scholar
• 37 Schweinsburg BC, Taylor MJ, Alhassoon OM , et al; HNRC Group. Brain mitochondrial injury in human immunodeficiency virus-seropositive (HIV+) individuals taking nucleoside reverse transcriptase inhibitors. J Neurovirol 2005; 11 (4) 356-364
  CrossrefPubMedGoogle Scholar
• 38 Klauschen F, Goldman A, Barra V, Meyer-Lindenberg A, Lundervold A. Evaluation of automated brain MR image segmentation and volumetry methods. Hum Brain Mapp 2009; 30 (4) 1310-1327
  CrossrefPubMedGoogle Scholar
• 39 Fjell AM, Westlye LT, Amlien I , et al. High consistency of regional cortical thinning in aging across multiple samples. Cereb Cortex 2009; 19 (9) 2001-2012
  CrossrefPubMedGoogle Scholar
• 40 Dal Pan GJ, McArthur JH, Aylward E , et al. Patterns of cerebral atrophy in HIV-1-infected individuals: results of a quantitative MRI analysis. Neurology 1992; 42 (11) 2125-2130
  CrossrefPubMedGoogle Scholar
• 41 Fennema-Notestine C, Ellis RJ, Archibald SL , et al; CHARTER Group. Increases in brain white matter abnormalities and subcortical gray matter are linked to CD4 recovery in HIV infection. J Neurovirol 2013; 19 (4) 393-401
  CrossrefPubMedGoogle Scholar
• 42 Jernigan TL, Archibald SL, Fennema-Notestine C , et al; CHARTER Group. Clinical factors related to brain structure in HIV: the CHARTER study. J Neurovirol 2011; 17 (3) 248-257
  CrossrefPubMedGoogle Scholar
• 43 Dewey J, Hana G, Russell T , et al; HIV Neuroimaging Consortium. Reliability and validity of MRI-based automated volumetry software relative to auto-assisted manual measurement of subcortical structures in HIV-infected patients from a multisite study. Neuroimage 2010; 51 (4) 1334-1344
  CrossrefPubMedGoogle Scholar
• 44 Heindel WC, Jernigan TL, Archibald SL, Achim CL, Masliah E, Wiley CA. The relationship of quantitative brain magnetic resonance imaging measures to neuropathologic indexes of human immunodeficiency virus infection. Arch Neurol 1994; 51 (11) 1129-1135
  CrossrefPubMedGoogle Scholar
• 45 Aylward EH, Henderer JD, McArthur JC , et al. Reduced basal ganglia volume in HIV-1-associated dementia: results from quantitative neuroimaging. Neurology 1993; 43 (10) 2099-2104
  CrossrefPubMedGoogle Scholar
• 46 Aylward EH, Brettschneider PD, McArthur JC , et al. Magnetic resonance imaging measurement of gray matter volume reductions in HIV dementia. Am J Psychiatry 1995; 152 (7) 987-994
  CrossrefPubMedGoogle Scholar
• 47 Stout JC, Ellis RJ, Jernigan TL , et al; HIV Neurobehavioral Research Center Group. Progressive cerebral volume loss in human immunodeficiency virus infection: a longitudinal volumetric magnetic resonance imaging study. Arch Neurol 1998; 55 (2) 161-168
  CrossrefPubMedGoogle Scholar
• 48 Heaps JM, Joska J, Hoare J , et al. Neuroimaging markers of human immunodeficiency virus infection in South Africa. J Neurovirol 2012; 18 (3) 151-156
  CrossrefPubMedGoogle Scholar
• 49 Thompson PM, Dutton RA, Hayashi KM , et al. Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4+ T lymphocyte decline. Proc Natl Acad Sci U S A 2005; 102 (43) 15647-15652
  CrossrefPubMedGoogle Scholar
• 50 Ances BM, Ortega M, Vaida F, Heaps J, Paul R. Independent effects of HIV, aging, and HAART on brain volumetric measures. J Acquir Immune Defic Syndr 2012; 59 (5) 469-477
  CrossrefPubMedGoogle Scholar
• 51 Ragin AB, Du H, Ochs R , et al. Structural brain alterations can be detected early in HIV infection. Neurology 2012; 79 (24) 2328-2334
  CrossrefPubMedGoogle Scholar
• 52 Cohen RA, Harezlak J, Schifitto G , et al. Effects of nadir CD4 count and duration of human immunodeficiency virus infection on brain volumes in the highly active antiretroviral therapy era. J Neurovirol 2010; 16 (1) 25-32
  CrossrefPubMedGoogle Scholar
• 53 Patel SH, Kolson DL, Glosser G , et al. Correlation between percentage of brain parenchymal volume and neurocognitive performance in HIV-infected patients. AJNR Am J Neuroradiol 2002; 23 (4) 543-549
  PubMedGoogle Scholar
• 54 Cohen RA, Harezlak J, Gongvatana A , et al; HIV Neuroimaging Consortium. Cerebral metabolite abnormalities in human immunodeficiency virus are associated with cortical and subcortical volumes. J Neurovirol 2010; 16 (6) 435-444
  CrossrefPubMedGoogle Scholar
• 55 Pfefferbaum A, Rosenbloom MJ, Sassoon SA , et al. Regional brain structural dysmorphology in human immunodeficiency virus infection: effects of acquired immune deficiency syndrome, alcoholism, and age. Biol Psychiatry 2012; 72 (5) 361-370
  CrossrefPubMedGoogle Scholar
• 56 Castelo JM, Courtney MG, Melrose RJ, Stern CE. Putamen hypertrophy in nondemented patients with human immunodeficiency virus infection and cognitive compromise. Arch Neurol 2007; 64 (9) 1275-1280
  CrossrefPubMedGoogle Scholar
• 57 Thames AD, Foley JM, Wright MJ , et al. Basal ganglia structures differentially contribute to verbal fluency: evidence from Human Immunodeficiency Virus (HIV)-infected adults. Neuropsychologia 2012; 50 (3) 390-395
  CrossrefPubMedGoogle Scholar
• 58 Becker JT, Sanders J, Madsen SK , et al; Multicenter AIDS Cohort Study. Subcortical brain atrophy persists even in HAART-regulated HIV disease. Brain Imaging Behav 2011; 5 (2) 77-85
  CrossrefPubMedGoogle Scholar
• 59 Sullivan EV, Rosenbloom MJ, Rohlfing T, Kemper CA, Deresinski S, Pfefferbaum A. Pontocerebellar contribution to postural instability and psychomotor slowing in HIV infection without dementia. Brain Imaging Behav 2011; 5 (1) 12-24
  CrossrefPubMedGoogle Scholar
• 60 Li C, Zhang X, Komery A, Li Y, Novembre FJ, Herndon JG. Longitudinal diffusion tensor imaging and perfusion MRI investigation in a macaque model of neuro-AIDS: a preliminary study. Neuroimage 2011; 58 (1) 286-292
  CrossrefPubMedGoogle Scholar
• 61 Kallianpur KJ, Shikuma C, Kirk GR , et al. Peripheral blood HIV DNA is associated with atrophy of cerebellar and subcortical gray matter. Neurology 2013; 80 (19) 1792-1799
  CrossrefPubMedGoogle Scholar
• 62 Ragin AB, D'Souza G, Reynolds S , et al. Platelet decline as a predictor of brain injury in HIV infection. J Neurovirol 2011; 17 (5) 487-495
  CrossrefPubMedGoogle Scholar
• 63 Durazzo TC, Rothlind JC, Cardenas VA, Studholme C, Weiner MW, Meyerhoff DJ. Chronic cigarette smoking and heavy drinking in human immunodeficiency virus: consequences for neurocognition and brain morphology. Alcohol 2007; 41 (7) 489-501
  CrossrefPubMedGoogle Scholar
• 64 McMurtray A, Nakamoto B, Shikuma C, Valcour V. Small-vessel vascular disease in human immunodeficiency virus infection: the Hawaii aging with HIV cohort study. Cerebrovasc Dis 2007; 24 (2-3) 236-241
  CrossrefPubMedGoogle Scholar
• 65 Becker JT, Maruca V, Kingsley LA , et al; Multicenter AIDS Cohort Study. Factors affecting brain structure in men with HIV disease in the post-HAART era. Neuroradiology 2012; 54 (2) 113-121
  CrossrefPubMedGoogle Scholar
• 66 Towgood KJ, Pitkanen M, Kulasegaram R , et al. Mapping the brain in younger and older asymptomatic HIV-1 men: frontal volume changes in the absence of other cortical or diffusion tensor abnormalities. Cortex 2012; 48 (2) 230-241
  CrossrefPubMedGoogle Scholar
• 67 Valcour VG. HIV, aging, and cognition: emerging issues. Top Antivir Med 2013; 21 (3) 119-123
  PubMedGoogle Scholar
• 68 Tate DF, Sampat M, Harezlak J , et al; HIV Neuroimaging Consortium. Regional areas and widths of the midsagittal corpus callosum among HIV-infected patients on stable antiretroviral therapies. J Neurovirol 2011; 17 (4) 368-379
  CrossrefPubMedGoogle Scholar
• 69 Christensen A, Russ S, Rambaran N, Wright SW. Patient perspectives on opt-out HIV screening in a Guyanese emergency department. In Health 2012; 4 (3) 185-191
  PubMedGoogle Scholar
• 70 Turner MR, Modo M. Advances in the application of MRI to amyotrophic lateral sclerosis. Expert Opin Med Diagn 2010; 4 (6) 483-496
  CrossrefPubMedGoogle Scholar
• 71 Chanraud S, Zahr N, Sullivan EV, Pfefferbaum A. MR diffusion tensor imaging: a window into white matter integrity of the working brain. Neuropsychol Rev 2010; 20 (2) 209-225
  CrossrefPubMedGoogle Scholar
• 72 Wycoco V, Shroff M, Sudhakar S, Lee W. White matter anatomy: what the radiologist needs to know. Neuroimaging Clin N Am 2013; 23 (2) 197-216
  CrossrefPubMedGoogle Scholar
• 73 Gongvatana A, Cohen RA, Correia S , et al. Clinical contributors to cerebral white matter integrity in HIV-infected individuals. J Neurovirol 2011; 17 (5) 477-486
  CrossrefPubMedGoogle Scholar
• 74 Wu Y, Storey P, Cohen BA, Epstein LG, Edelman RR, Ragin AB. Diffusion alterations in corpus callosum of patients with HIV. AJNR Am J Neuroradiol 2006; 27 (3) 656-660
  PubMedGoogle Scholar
• 75 Thurnher MM, Castillo M, Stadler A, Rieger A, Schmid B, Sundgren PC. Diffusion-tensor MR imaging of the brain in human immunodeficiency virus-positive patients. AJNR Am J Neuroradiol 2005; 26 (9) 2275-2281
  PubMedGoogle Scholar
• 76 Pomara N, Crandall DT, Choi SJ, Johnson G, Lim KO. White matter abnormalities in HIV-1 infection: a diffusion tensor imaging study. Psychiatry Res 2001; 106 (1) 15-24
  CrossrefPubMedGoogle Scholar
• 77 Müller-Oehring EM, Schulte T, Rosenbloom MJ, Pfefferbaum A, Sullivan EV. Callosal degradation in HIV-1 infection predicts hierarchical perception: a DTI study. Neuropsychologia 2010; 48 (4) 1133-1143
  CrossrefPubMedGoogle Scholar
• 78 Stebbins GT, Smith CA, Bartt RE , et al. HIV-associated alterations in normal-appearing white matter: a voxel-wise diffusion tensor imaging study. J Acquir Immune Defic Syndr 2007; 46 (5) 564-573
  CrossrefPubMedGoogle Scholar
• 79 Ragin AB, Wu Y, Storey P, Cohen BA, Edelman RR, Epstein LG. Diffusion tensor imaging of subcortical brain injury in patients infected with human immunodeficiency virus. J Neurovirol 2005; 11 (3) 292-298
  CrossrefPubMedGoogle Scholar
• 80 Filippi CG, Ulug AM, Ryan E, Ferrando SJ, van Gorp W. Diffusion tensor imaging of patients with HIV and normal-appearing white matter on MR images of the brain. AJNR Am J Neuroradiol 2001; 22 (2) 277-283
  PubMedGoogle Scholar
• 81 Ragin AB, Storey P, Cohen BA, Edelman RR, Epstein LG. Disease burden in HIV-associated cognitive impairment: a study of whole-brain imaging measures. Neurology 2004; 63 (12) 2293-2297
  CrossrefPubMedGoogle Scholar
• 82 Ragin AB, Storey P, Cohen BA, Epstein LG, Edelman RR. Whole brain diffusion tensor imaging in HIV-associated cognitive impairment. AJNR Am J Neuroradiol 2004; 25 (2) 195-200
  PubMedGoogle Scholar
• 83 Pfefferbaum A, Rosenbloom MJ, Rohlfing T, Kemper CA, Deresinski S, Sullivan EV. Frontostriatal fiber bundle compromise in HIV infection without dementia. AIDS 2009; 23 (15) 1977-1985
  CrossrefPubMedGoogle Scholar
• 84 Hoare J, Westgarth-Taylor J, Fouche JP , et al. A diffusion tensor imaging and neuropsychological study of prospective memory impairment in South African HIV positive individuals. Metab Brain Dis 2012; 27 (3) 289-297
  CrossrefPubMedGoogle Scholar
• 85 Stubbe-Drger B, Deppe M, Mohammadi S , et al; German Competence Network HIV/AIDS. Early microstructural white matter changes in patients with HIV: a diffusion tensor imaging study. BMC Neurol 2012; 12: 23
  CrossrefPubMedGoogle Scholar
• 86 Du H, Wu Y, Ochs R , et al. A comparative evaluation of quantitative neuroimaging measurements of brain status in HIV infection. Psychiatry Res 2012; 203 (1) 95-99
  CrossrefPubMedGoogle Scholar
• 87 Zhu T, Zhong J, Hu R , et al. Patterns of white matter injury in HIV infection after partial immune reconstitution: a DTI tract-based spatial statistics study. J Neurovirol 2013; 19 (1) 10-23
  CrossrefPubMedGoogle Scholar
• 88 Wright PW, Heaps JM, Shimony JS, Thomas JB, Ances BM. The effects of HIV and combination antiretroviral therapy on white matter integrity. AIDS 2012; 26 (12) 1501-1508
  CrossrefPubMedGoogle Scholar
• 89 Chen Y, An H, Zhu H , et al. White matter abnormalities revealed by diffusion tensor imaging in non-demented and demented HIV+ patients. Neuroimage 2009; 47 (4) 1154-1162
  CrossrefPubMedGoogle Scholar
• 90 Rauch A, Rainer G, Logothetis NK. The effect of a serotonin-induced dissociation between spiking and perisynaptic activity on BOLD functional MRI. Proc Natl Acad Sci U S A 2008; 105 (18) 6759-6764
  CrossrefPubMedGoogle Scholar
• 91 Zhang D, Raichle ME. Disease and the brain's dark energy. Nat Rev Neurol 2010; 6 (1) 15-28
  CrossrefPubMedGoogle Scholar
• 92 Ogawa S. Finding the BOLD effect in brain images. Neuroimage 2012; 62 (2) 608-609
  CrossrefPubMedGoogle Scholar
• 93 Chang L, Speck O, Miller EN , et al. Neural correlates of attention and working memory deficits in HIV patients. Neurology 2001; 57 (6) 1001-1007
  CrossrefPubMedGoogle Scholar
• 94 Ances B, Vaida F, Ellis R, Buxton R. Test-retest stability of calibrated BOLD-fMRI in HIV- and HIV+ subjects. Neuroimage 2011; 54 (3) 2156-2162
  CrossrefPubMedGoogle Scholar
• 95 Ances BM, Roc AC, Korczykowski M, Wolf RL, Kolson DL. Combination antiretroviral therapy modulates the blood oxygen level-dependent amplitude in human immunodeficiency virus-seropositive patients. J Neurovirol 2008; 14 (5) 418-424
  CrossrefPubMedGoogle Scholar
• 96 Chang L, Tomasi D, Yakupov R , et al. Adaptation of the attention network in human immunodeficiency virus brain injury. Ann Neurol 2004; 56 (2) 259-272
  CrossrefPubMedGoogle Scholar
• 97 Ernst T, Chang L, Jovicich J, Ames N, Arnold S. Abnormal brain activation on functional MRI in cognitively asymptomatic HIV patients. Neurology 2002; 59 (9) 1343-1349
  CrossrefPubMedGoogle Scholar
• 98 Ernst T, Yakupov R, Nakama H , et al. Declined neural efficiency in cognitively stable human immunodeficiency virus patients. Ann Neurol 2009; 65 (3) 316-325
  CrossrefPubMedGoogle Scholar
• 99 Juengst SB, Aizenstein HJ, Figurski J, Lopez OL, Becker JT. Alterations in the hemodynamic response function in cognitively impaired HIV/AIDS subjects. J Neurosci Methods 2007; 163 (2) 208-212
  CrossrefPubMedGoogle Scholar
• 100 Maki PM, Cohen MH, Weber K , et al. Impairments in memory and hippocampal function in HIV-positive vs HIV-negative women: a preliminary study. Neurology 2009; 72 (19) 1661-1668
  CrossrefPubMedGoogle Scholar
• 101 Tracey I, Hamberg LM, Guimaraes AR , et al. Increased cerebral blood volume in HIV-positive patients detected by functional MRI. Neurology 1998; 50 (6) 1821-1826
  CrossrefPubMedGoogle Scholar
• 102 Du Plessis S, Vink M, Joska J, Koutsilieri E, Stein DJ, Emsley R. HIV infection and the fronto–striatal system: a systematic review and meta-analysis of fMRI studies. AIDS 2014; ; In press
  PubMedGoogle Scholar
• 103 Thomas JB, Brier MR, Snyder AZ, Vaida FF, Ances BM. Pathways to neurodegeneration: effects of HIV and aging on resting-state functional connectivity. Neurology 2013; 80 (13) 1186-1193
  CrossrefPubMedGoogle Scholar
• 104 Bonnet F, Amieva H, Marquant F , et al; S CO3 Aquitaine Cohort. Cognitive disorders in HIV-infected patients: are they HIV-related?. AIDS 2013; 27 (3) 391-400
  CrossrefPubMedGoogle Scholar
• 105 Fennema-Notestine C, Ellis RJ, Archibald SL , et al; CHARTER Group. Increases in brain white matter abnormalities and subcortical gray matter are linked to CD4 recovery in HIV infection. J Neurovirol 2013; 19 (4) 393-401
  CrossrefPubMedGoogle Scholar
• 106 Müller-Oehring EM, Schulte T, Rosenbloom MJ, Pfefferbaum A, Sullivan EV. Callosal degradation in HIV-1 infection predicts hierarchical perception: a DTI study. Neuropsychologia 2010; 48 (4) 1133-1143
  CrossrefPubMedGoogle Scholar
• 107 Pfefferbaum A, Rosenbloom MJ, Rohlfing T, Kemper CA, Deresinski S, Sullivan EV. Frontostriatal fiber bundle compromise in HIV infection without dementia. AIDS 2009; 23 (15) 1977-1985
  CrossrefPubMedGoogle Scholar