Neural response to working memory demand predicts neurocognitive deficits in HIV

Abstract

Human immunodeficiency virus (HIV) continues to have adverse effects on cognition and the brain in many infected people, despite a reduced incidence of HIV-associated dementia with combined antiretroviral therapy (cART). Working memory is often affected, along with attention, executive control, and cognitive processing speed. Verbal working memory (VWM) requires the interaction of each of the cognitive component processes along with a phonological loop for verbal repetition and rehearsal. HIV-related functional brain response abnormalities during VWM are evident in functional MRI (fMRI), though the neural substrate underlying these neurocognitive deficits is not well understood. The current study addressed this by comparing 24 HIV+ to 27 demographically matched HIV-seronegative (HIV−) adults with respect to fMRI activation on a VWM paradigm (n-back) relative to performance on two standardized tests of executive control, attention and processing speed (Stroop and Trail Making A–B). As expected, the HIV+ group had deficits on these neurocognitive tests compared to HIV− controls, and also differed in neural response on fMRI relative to neuropsychological performance. Reduced activation in VWM task-related brain regions on the 2-back was associated with Stroop interference deficits in HIV+ but not with either Trail Making A or B performance. Activation of the posterior cingulate cortex (PCC) of the default mode network during rest was associated with Hopkins Verbal Learning Test-2 (HVLT-2) learning in HIV+. These effects were not observed in the HIV− controls. Reduced dynamic range of neural response was also evident in HIV+ adults when activation on the 2-back condition was compared to the extent of activation of the default mode network during periods of rest. Neural dynamic range was associated with both Stroop and HVLT-2 performance. These findings provide evidence that HIV-associated alterations in neural activation induced by VWM demands and during rest differentially predict executive-attention and verbal learning deficits. That the Stroop, but not Trail Making was associated with VWM activation suggests that attentional regulation difficulties in suppressing interference and/or conflict regulation are a component of working memory deficits in HIV+ adults. Alterations in neural dynamic range may be a useful index of the impact of HIV on functional brain response and as a fMRI metric in predicting cognitive outcomes.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

References

  1. Ances BM, Roc AC, Korczykowski M, Wolf RL, Kolson DL (2008) Combination antiretroviral therapy modulates the blood oxygen level-dependent amplitude in human immunodeficiency virus-seropositive patients. J Neuro-Oncol 14(5):418–424

    CAS  Google Scholar 

  2. Ances B, Vaida F, Ellis R, Buxton R (2011) Test-retest stability of calibrated BOLD-fMRI in HIV− and HIV+ subjects. NeuroImage 54(3):2156–2162. https://doi.org/10.1016/j.neuroimage.2010.09.081

    Article  PubMed  Google Scholar 

  3. Ances BM, Ortega M, Vaida F, Heaps J, Paul R (2012a) Independent effects of HIV, aging, and HAART on brain volumetric measures. J Acquir Immune Defic Syndr 59(5):469–477. https://doi.org/10.1097/QAI.0b013e318249db17

    Article  PubMed Central  PubMed  Google Scholar 

  4. Ances BM, Benzinger TL, Christensen JJ, Thomas J, Venkat R, Teshome M, Aldea P, Fagan AM, Holtzman DM, Morris JC, Clifford DB (2012b) 11C-PiB imaging of human immunodeficiency virus-associated neurocognitive disorder. Arch Neurol 69(1):72–77. https://doi.org/10.1001/archneurol.2011.761

    Article  PubMed Central  PubMed  Google Scholar 

  5. Anderson AM, Harezlak J, Bharti A, Mi D, Taylor MJ, Daar ES, Schifitto G, Zhong J, Alger JR, Brown MS, Singer EJ, Campbell TB, McMahon DD, Buchthal S, Cohen R, Yiannoutsos C, Letendre SL, Navia BA, HIV Neuroimaging Consortium (2015) Plasma and cerebrospinal fluid biomarkers predict cerebral injury in HIV-infected individuals on stable combination antiretroviral therapy. J Acquir Immune Defic Syndr 69(1):29–35. https://doi.org/10.1097/QAI.0000000000000532

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69(18):1789–1799. https://doi.org/10.1212/01.WNL.0000287431.88658.8b

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Badhwar A, Tam A, Dansereau C, Orban P, Hoffstaedter F, Bellec P (2017) Resting-state network dysfunction in Alzheimer’s disease: a systematic review and meta-analysis. Alzheimers Dement (Amst) 8:73–85. https://doi.org/10.1016/j.dadm.2017.03.007

    Article  Google Scholar 

  8. Becker JT, Sanders J, Madsen SK et al (2011) Subcortical brain atrophy persists even in HAART-regulated HIV disease. Brain Imaging Behav 5(2):77–85. https://doi.org/10.1007/s11682-011-9113-8

    Article  PubMed Central  PubMed  Google Scholar 

  9. Becker JT, Maruca V, Kingsley LA et al (2012) Factors affecting brain structure in men with HIV disease in the post-HAART era. Neuroradiology 54(2):113–121. https://doi.org/10.1007/s00234-011-0854-2

    Article  PubMed  Google Scholar 

  10. Benedict RHBSA, Groninger L, Brandt J (1998) Hopkins Verbal Learning Test Revised: normative data and analysis of inter-form and test-retest reliability. Clin Neuropsychol 12(1):43–55. https://doi.org/10.1076/clin.12.1.43.1726

    Article  Google Scholar 

  11. Blackstone K, Moore DJ, Franklin DR, Clifford DB, Collier AC, Marra CM, Gelman BB, McArthur JC, Morgello S, Simpson DM, Ellis RJ, Atkinson JH, Grant I, Heaton RK (2012) Defining neurocognitive impairment in HIV: deficit scores versus clinical ratings. Clin Neuropsychol 26(6):894–908. https://doi.org/10.1080/13854046.2012.694479

    Article  CAS  PubMed  Google Scholar 

  12. Blazer DG, Yaffe K, Liverman CT, eds (2015) Cognitive aging: progress in understanding and opportunities for action. Washington (DC)

  13. Caldwell JZ, Gongvatana A, Navia BA et al (2014) Neural dysregulation during a working memory task in human immunodeficiency virus-seropositive and hepatitis C coinfected individuals. J Neuro-Oncol 20(4):398–411

    CAS  Google Scholar 

  14. Chang L, Ernst T, Leonido-Yee M, Walot I, Singer E (1999) Cerebral metabolite abnormalities correlate with clinical severity of HIV-1 cognitive motor complex. Neurology 52(1):100–108. https://doi.org/10.1212/WNL.52.1.100

    Article  CAS  PubMed  Google Scholar 

  15. Chang L, Speck O, Miller EN, Braun J, Jovicich J, Koch C, Itti L, Ernst T (2001) Neural correlates of attention and working memory deficits in HIV patients. Neurology 57(6):1001–1007. https://doi.org/10.1212/WNL.57.6.1001

    Article  CAS  PubMed  Google Scholar 

  16. 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. Ann Neurol 56(2):259–272. https://doi.org/10.1002/ana.20190

    Article  PubMed  Google Scholar 

  17. Chang L, Yakupov R, Nakama H, Stokes B, Ernst T (2008) Antiretroviral treatment is associated with increased attentional load-dependent brain activation in HIV patients. J NeuroImmune Pharmacol 3(2):95–104. https://doi.org/10.1007/s11481-007-9092-0

    Article  CAS  PubMed  Google Scholar 

  18. Chang L, Holt JL, Yakupov R, Jiang CS, Ernst T (2013) Lower cognitive reserve in the aging human immunodeficiency virus-infected brain. Neurobiol Aging 34(4):1240–1253. https://doi.org/10.1016/j.neurobiolaging.2012.10.012

    Article  PubMed  Google Scholar 

  19. Clark US, Cohen RA (2010) Brain dysfunction in the era of combination antiretroviral therapy: implications for the treatment of the aging population of HIV-infected individuals. Curr Opin Investig Drugs 11(8):884–900

    PubMed Central  CAS  PubMed  Google Scholar 

  20. Clifford DB (2008) HIV-associated neurocognitive disease continues in the antiretroviral era. Top HIV Med. 16(2):94–98

    PubMed  Google Scholar 

  21. Cohen RA, Boland R, Paul R, Tashima KT, Schoenbaum EE, Celentano DD, Schuman P, Smith DK, Carpenter CCJ (2001) Neurocognitive performance enhanced by highly active antiretroviral therapy in HIV-infected women. AIDS 15(3):341–345. https://doi.org/10.1097/00002030-200102160-00007

    Article  CAS  PubMed  Google Scholar 

  22. Cohen RA, Harezlak J, Gongvatana A et al (2010a) Cerebral metabolite abnormalities in human immunodeficiency virus are associated with cortical and subcortical volumes. J Neuro-Oncol 16(6):435–444

    CAS  Google Scholar 

  23. Cohen RA, Harezlak J, Schifitto G et al (2010b) Effects of nadir CD4 count and duration of human immunodeficiency virus infection on brain volumes in the highly active antiretroviral therapy era. J Neuro-Oncol 16(1):25–32

    CAS  Google Scholar 

  24. Cohen RA, de la Monte S, Gongvatana A, Ombao H, Gonzalez B, Devlin KN, Navia B, Tashima KT (2011) Plasma cytokine concentrations associated with HIV/hepatitis C coinfection are related to attention, executive and psychomotor functioning. J Neuroimmunol 233(1–2):204–210. https://doi.org/10.1016/j.jneuroim.2010.11.006

    Article  CAS  PubMed  Google Scholar 

  25. Crum-Cianflone NF, Moore DJ, Letendre S, Poehlman Roediger M, Eberly L, Weintrob A, Ganesan A, Johnson E, del Rosario R, Agan BK, Hale BR (2013) Low prevalence of neurocognitive impairment in early diagnosed and managed HIV-infected persons. Neurology 80(4):371–379. https://doi.org/10.1212/WNL.0b013e31827f0776

    Article  PubMed Central  PubMed  Google Scholar 

  26. Devlin KN, Gongvatana A, Clark US, Chasman JD, Westbrook ML, Tashima KT, Navia B, Cohen RA (2012) Neurocognitive effects of HIV, hepatitis C, and substance use history. J Int Neuropsychol Soc 18(1):68–78. https://doi.org/10.1017/S1355617711001408

    Article  PubMed  Google Scholar 

  27. Ellis RJ, Badiee J, Vaida F, Letendre S, Heaton RK, Clifford D, Collier AC, Gelman B, McArthur J, Morgello S, McCutchan JA, Grant I, CHARTER Group (2011) CD4 nadir is a predictor of HIV neurocognitive impairment in the era of combination antiretroviral therapy. AIDS 25(14):1747–1751. https://doi.org/10.1097/QAD.0b013e32834a40cd

    Article  CAS  PubMed  Google Scholar 

  28. Ernst T, Chang L, Arnold S (2003) Increased glial metabolites predict increased working memory network activation in HIV brain injury. NeuroImage 19(4):1686–1693. https://doi.org/10.1016/S1053-8119(03)00232-5

    Article  CAS  PubMed  Google Scholar 

  29. Ernst T, Yakupov R, Nakama H, Crocket G, Cole M, Watters M, Ricardo-Dukelow ML, Chang L (2009) Declined neural efficiency in cognitively stable human immunodeficiency virus patients. Ann Neurol 65(3):316–325. https://doi.org/10.1002/ana.21594

    Article  PubMed Central  PubMed  Google Scholar 

  30. Fennema-Notestine C, Ellis RJ, Archibald SL et al (2013) Increases in brain white matter abnormalities and subcortical gray matter are linked to CD4 recovery in HIV infection. J Neuro-Oncol 19(4):393–401

    CAS  Google Scholar 

  31. Filippi CG, Ulug AM, Ryan E, Ferrando SJ, van Gorp W (2001) Diffusion tensor imaging of patients with HIV and normal-appearing white matter on MR images of the brain. Ajnr 22(2):277–283

    CAS  PubMed  Google Scholar 

  32. Fox MD, Zhang D, Snyder AZ, Raichle ME (2009) The global signal and observed anticorrelated resting state brain networks. J Neurophysiol 101(6):3270–3283. https://doi.org/10.1152/jn.90777.2008

    Article  PubMed Central  PubMed  Google Scholar 

  33. Golden CJ (1972) Stroop color and word test. Chicago, Stoelting

    Google Scholar 

  34. Gongvatana A, Schweinsburg BC, Taylor MJ et al (2009) White matter tract injury and cognitive impairment in human immunodeficiency virus-infected individuals. J Neuro-Oncol 15(2):187–195

    Google Scholar 

  35. Gongvatana A, Cohen RA, Correia S et al (2011) Clinical contributors to cerebral white matter integrity in HIV-infected individuals. J Neuro-Oncol 17(5):477–486

    Google Scholar 

  36. Gongvatana A, Harezlak J, Buchthal S et al (2013) Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy. J Neuro-Oncol 19(3):209–218

    CAS  Google Scholar 

  37. Haddow LJ, Dudau C, Chandrashekar H, et al (2014) Cross-sectional study of unexplained white matter lesions in HIV positive individuals undergoing brain magnetic resonance imaging. AIDS Patient Care STDS

  38. Harezlak J, Buchthal S, Taylor M, Schifitto G, Zhong J, Daar E, Alger J, Singer E, Campbell T, Yiannoutsos C, Cohen R, Navia B, HIV Neuroimaging Consortium (2011) Persistence of HIV-associated cognitive impairment, inflammation, and neuronal injury in era of highly active antiretroviral treatment. AIDS 25(5):625–633. https://doi.org/10.1097/QAD.0b013e3283427da7

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Harezlak J, Cohen R, Gongvatana A, et al (2014) Predictors of CNS injury as measured by proton magnetic resonance spectroscopy in the setting of chronic HIV infection and CART. J Neurovirol 20(3):294-303. https://doi.org/10.1007/s13365-014-0246-6

  40. Heaton RK, Grant I, Butters N, White DA, Kirson D, Atkinson JH, McCutchan JA, Taylor MJ, Kelly MD, Ellis RJ, Wolfson T, Velin R, Marcotte TD, Hesselink JR, Jernigan TL, Chandler J, Wallace M, Abramson I, THE HNRC GROUP (1995) The HNRC 500—neuropsychology of HIV infection at different disease stages. HIV Neurobehavioral Research Center. J Int Neuropsychol Soc 1(3):231–251. https://doi.org/10.1017/S1355617700000230

    Article  CAS  PubMed  Google Scholar 

  41. Heaton RK, Miller SW, Taylor MJ (2004) Grant, I. Revised Comprehensive Norms for an Expanded Halstead-Reitan Battery: Demographically Adjusted Neuropsychological Norms for African American and Caucasian Adults. Lutz, Fl: Psychological Assessment Resources

  42. Heaton RK, Clifford DB, Franklin DR Jr et al (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 75(23):2087–2096. https://doi.org/10.1212/WNL.0b013e318200d727

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Heaton RK, Franklin DR, Ellis RJ et al (2011) HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neuro-Oncol 17(1):3–16

    CAS  Google Scholar 

  44. Heindel WC, Jernigan TL, Archibald SL, Achim CL, Masliah E, Wiley CA (1994) The relationship of quantitative brain magnetic resonance imaging measures to neuropathologic indexes of human immunodeficiency virus infection. Arch Neurol 51(11):1129–1135. https://doi.org/10.1001/archneur.1994.00540230067015

    Article  CAS  PubMed  Google Scholar 

  45. Jernigan TL, Archibald SL, Fennema-Notestine C et al (2011) Clinical factors related to brain structure in HIV: the CHARTER study. J Neuro-Oncol 17(3):248–257

    Google Scholar 

  46. Kim H (2016) Default network activation during episodic and semantic memory retrieval: a selective meta-analytic comparison. Neuropsychologia 80:35–46. https://doi.org/10.1016/j.neuropsychologia.2015.11.006

    Article  PubMed  Google Scholar 

  47. Letendre SL, Ellis RJ, Everall I, Ances B, Bharti A, McCutchan JA (2009) Neurologic complications of HIV disease and their treatment. Top HIV Med 17(2):46–56

    PubMed Central  PubMed  Google Scholar 

  48. Lezak MD (1995) Neuropsychological assessment (3rd ed.), 3rd edn. Oxford University Press, New York

    Google Scholar 

  49. Liu Y, Tang XP, McArthur JC, Scott J, Gartner S (2000) Analysis of human immunodeficiency virus type 1 gp160 sequences from a patient with HIV dementia: evidence for monocyte trafficking into brain. J Neuro-Oncol 6(Suppl 1):S70–S81

    CAS  Google Scholar 

  50. Martin EM, Robertson LC, Edelstein HE, Jagust WJ, Sorensen DJ, Giovanni DS, Chirurgi VA (1992a) Performance of patients with early HIV-1 infection on the Stroop task. J Clin Exp Neuropsychol 14(5):857–868. https://doi.org/10.1080/01688639208402867

    Article  CAS  PubMed  Google Scholar 

  51. Martin E, Sorenson D, Edelstein H et al (1992b) Decision-making speed in HIV-infection: a preliminary report. AIDS 6(1):109–113. https://doi.org/10.1097/00002030-199201000-00015

    Article  CAS  PubMed  Google Scholar 

  52. Martin EM, Pitrak DL, Pursell KJ, Andersen BR, Mullane KM, Novak RM (1998) Information processing and antiretroviral therapy in HIV-1 infection. J Int Neuropsychol Soc 4(4):329–335

    CAS  PubMed  Google Scholar 

  53. Martin EM, Pitrak DL, Novak RM, Pursell KJ, Mullane KM (1999) Reaction times are faster in HIV-seropositive patients on antiretroviral therapy: a preliminary report. J Clin Exp Neuropsychol 21(5):730–735. https://doi.org/10.1076/jcen.21.5.730.867

    Article  CAS  PubMed  Google Scholar 

  54. Martin EM, DeHaan S, Vassileva J, Gonzalez R, Weller J, Bechara A (2013) Decision making among HIV+ drug using men who have sex with men: a preliminary report from the Chicago Multicenter AIDS Cohort Study. J Clin Exp Neuropsychol 35(6):573–583. https://doi.org/10.1080/13803395.2013.799122

    Article  PubMed Central  PubMed  Google Scholar 

  55. McArthur JC, McDermott MP, McClernon D, St Hillaire C, Conant K, Marder K, Schifitto G, Selnes OA, Sacktor N, Stern Y, Albert SM, Kieburtz K, deMarcaida JA, Cohen B, Epstein LG (2004) Attenuated central nervous system infection in advanced HIV/AIDS with combination antiretroviral therapy. Arch Neurol 61(11):1687–1696. https://doi.org/10.1001/archneur.61.11.1687

    Article  PubMed  Google Scholar 

  56. McMurtray A, Nakamoto B, Shikuma C, Valcour V (2008) Cortical atrophy and white matter hyperintensities in HIV: the Hawaii Aging with HIV Cohort Study. J Stroke Cerebrovasc Dis 17(4):212–217. https://doi.org/10.1016/j.jstrokecerebrovasdis.2008.02.005

    Article  PubMed Central  PubMed  Google Scholar 

  57. Muller-Oehring EM, Schulte T, Rosenbloom MJ, Pfefferbaum A, Sullivan EV (2010) Callosal degradation in HIV-1 infection predicts hierarchical perception: a DTI study. Neuropsychologia 48(4):1133–1143. https://doi.org/10.1016/j.neuropsychologia.2009.12.015

    Article  PubMed  Google Scholar 

  58. Olsen WL, Longo FM, Mills CM, Norman D (1988) White matter disease in AIDS: findings at MR imaging. Radiology 169(2):445–448. https://doi.org/10.1148/radiology.169.2.3174991

    Article  CAS  PubMed  Google Scholar 

  59. Paul RH, Yiannoutsos CT, Miller EN et al (2007) Proton MRS and neuropsychological correlates in AIDS dementia complex: evidence of subcortical specificity. J Neuropsychiatry Clin Neurosci 19(3):283–292. https://doi.org/10.1176/jnp.2007.19.3.283

    Article  PubMed  Google Scholar 

  60. Paul RH, Ernst T, Brickman AM, Yiannoutsos CT, Tate DF, Cohen RA, Navia BA, ACTG 301 team, ACTG 700 team, HIV MRS Consortium (2008) Relative sensitivity of magnetic resonance spectroscopy and quantitative magnetic resonance imaging to cognitive function among nondemented individuals infected with HIV. J Int Neuropsychol Soc 14(5):725–733. https://doi.org/10.1017/S1355617708080910

    Article  PubMed  Google Scholar 

  61. Pfefferbaum A, Sullivan EV, Hedehus M, Lim KO, Adalsteinsson E, Moseley M (2000) Age-related decline in brain white matter anisotropy measured with spatially corrected echo-planar diffusion tensor imaging. Magn Reson Med 44(2):259–268. https://doi.org/10.1002/1522-2594(200008)44:2<259::AID-MRM13>3.0.CO;2-6

    Article  CAS  PubMed  Google Scholar 

  62. Pfefferbaum A, Rosenbloom MJ, Adalsteinsson E, Sullivan EV (2007) Diffusion tensor imaging with quantitative fibre tracking in HIV infection and alcoholism comorbidity: synergistic white matter damage. Brain J Neurol 130(Pt 1):48–64. https://doi.org/10.1093/brain/awl242

    Article  Google Scholar 

  63. Pomara N, Crandall DT, Choi SJ, Johnson G, Lim KO (2001) White matter abnormalities in HIV-1 infection: a diffusion tensor imaging study. Psychiatry Res 106(1):15–24. https://doi.org/10.1016/S0925-4927(00)00082-2

    Article  CAS  PubMed  Google Scholar 

  64. Ragin AB, Wu Y, Storey P, Cohen BA, Edelman RR, Epstein LG (2005) Diffusion tensor imaging of subcortical brain injury in patients infected with human immunodeficiency virus. J Neuro-Oncol 11(3):292–298

    Google Scholar 

  65. Ragin AB, Du H, Ochs R, Wu Y, Sammet CL, Shoukry A, Epstein LG (2012) Structural brain alterations can be detected early in HIV infection. Neurology 79(24):2328–2334. https://doi.org/10.1212/WNL.0b013e318278b5b4

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. Reitan, R. (1958) Validity of the Trail Making Test as an indicator of organic brain damage. Perceptual and Motor Skills 8:271-276. https://doi.org/10.2466/PMS.8.7.271-276

  67. Robertson KR, Smurzynski M, Parsons TD, Wu K, Bosch RJ, Wu J, McArthur JC, Collier AC, Evans SR, Ellis RJ (2007) The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS 21(14):1915–1921. https://doi.org/10.1097/QAD.0b013e32828e4e27

    Article  PubMed  Google Scholar 

  68. Sacktor N, McDermott MP, Marder K et al (2002) HIV-associated cognitive impairment before and after the advent of combination therapy. J Neuro-Oncol 8(2):136–142

    Google Scholar 

  69. Segura B, Jurado MA, Freixenet N, Falcon C, Junque C, Arboix A (2009) Microstructural white matter changes in metabolic syndrome: a diffusion tensor imaging study. Neurology 73(6):438–444. https://doi.org/10.1212/WNL.0b013e3181b163cd

    Article  CAS  PubMed  Google Scholar 

  70. Seider TR, Gongvatana A, Woods AJ et al (2016) Age exacerbates HIV-associated white matter abnormalities. J Neuro-Oncol 22(2):201–212

    Google Scholar 

  71. Sexton CE, Kalu UG, Filippini N, Mackay CE, Ebmeier KP (2011) A meta-analysis of diffusion tensor imaging in mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging 32(12):2322 e2325–2322 e2318

    Article  Google Scholar 

  72. Sun B, Abadjian L, Rempel H, Calosing C, Rothlind J, Pulliam L (2010) Peripheral biomarkers do not correlate with cognitive impairment in highly active antiretroviral therapy-treated subjects with human immunodeficiency virus type 1 infection. J Neuro-Oncol 16(2):115–124

    CAS  Google Scholar 

  73. Tam A, Dansereau C, Badhwar A, Orban P, Belleville S, Chertkow H, Dagher A, Hanganu A, Monchi O, Rosa-Neto P, Shmuel A, Wang S, Breitner J, Bellec P, Alzheimer's Disease Neuroimaging Initiative (2015) Common effects of amnestic mild cognitive impairment on resting-state connectivity across four independent studies. Front Aging Neurosci 7:242. https://doi.org/10.3389/fnagi.2015.00242

    Article  PubMed Central  PubMed  Google Scholar 

  74. Tate DF, Conley J, Paul RH, Coop K, Zhang S, Zhou W, Laidlaw DH, Taylor LE, Flanigan T, Navia B, Cohen R, Tashima K (2010) Quantitative diffusion tensor imaging tractography metrics are associated with cognitive performance among HIV-infected patients. Brain Imaging Behav 4(1):68–79. https://doi.org/10.1007/s11682-009-9086-z

    Article  PubMed Central  PubMed  Google Scholar 

  75. Thompson PM, Dutton RA, Hayashi KM, Toga AW, Lopez OL, Aizenstein HJ, Becker JT (2005) Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4+ T lymphocyte decline. Proc Natl Acad Sci U S A 102(43):15647–15652. https://doi.org/10.1073/pnas.0502548102

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Thompson PM, Dutton RA, Hayashi KM, Lu A, Lee SE, Lee JY, Lopez OL, Aizenstein HJ, Toga AW, Becker JT (2006) 3D mapping of ventricular and corpus callosum abnormalities in HIV/AIDS. NeuroImage 31(1):12–23. https://doi.org/10.1016/j.neuroimage.2005.11.043

    Article  PubMed  Google Scholar 

  77. Tomasi D, Chang L, de Castro CE, Telang F, Ernst T (2006) The human immunodeficiency virus reduces network capacity: acoustic noise effect. Ann Neurol 59(2):419–423. https://doi.org/10.1002/ana.20766

    Article  PubMed Central  PubMed  Google Scholar 

  78. Towgood KJ, Pitkanen M, Kulasegaram R, Fradera A, Kumar A, Soni S, Sibtain NA, Reed L, Bradbeer C, Barker GJ, Kopelman MD (2012) 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 48(2):230–241. https://doi.org/10.1016/j.cortex.2011.03.006

    Article  PubMed  Google Scholar 

  79. Tracey I, Hamberg LM, Guimaraes AR, Hunter G, Chang I, Navia BA, Gonzalez RG (1998) Increased cerebral blood volume in HIV-positive patients detected by functional MRI. Neurology 50(6):1821–1826. https://doi.org/10.1212/WNL.50.6.1821

    Article  CAS  PubMed  Google Scholar 

  80. Valcour VG, Shiramizu BT, Shikuma CM (2010) HIV DNA in circulating monocytes as a mechanism to dementia and other HIV complications. J Leukoc Biol 87(4):621–626. https://doi.org/10.1189/jlb.0809571

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. Valcour V, Sithinamsuwan P, Letendre S, Ances B (2011) Pathogenesis of HIV in the central nervous system. Curr HIV/AIDS Rep 8(1):54–61. https://doi.org/10.1007/s11904-010-0070-4

    Article  PubMed  Google Scholar 

  82. Wendelken LA, Valcour V (2012) Impact of HIV and aging on neuropsychological function. J Neuro-Oncol 18(4):256–263

    Google Scholar 

  83. Xuan A, Wang GB, Shi DP, Xu JL, Li YL (2013) Initial study of magnetic resonance diffusion tensor imaging in brain white matter of early AIDS patients. Chin Med J 126(14):2720–2724

    PubMed  Google Scholar 

  84. Yiannoutsos CT, Ernst T, Chang L, Lee PL, Richards T, Marra CM, Meyerhoff DJ, Jarvik JG, Kolson D, Schifitto G, Ellis RJ, Swindells S, Simpson DM, Miller EN, Gonzalez RG, Navia BA (2004) Regional patterns of brain metabolites in AIDS dementia complex. NeuroImage 23(3):928–935. https://doi.org/10.1016/j.neuroimage.2004.07.033

    Article  PubMed  Google Scholar 

  85. Zhang Y, Wang M, Li H, Zhang H, Shi Y, Wei F, Liu D, Liu K, Chen D (2012) Accumulation of nuclear and mitochondrial DNA damage in the frontal cortex cells of patients with HIV-associated neurocognitive disorders. Brain Res 1458:1–11. https://doi.org/10.1016/j.brainres.2012.04.001

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Ronald A. Cohen.

Ethics declarations

The study was approved by the Institutional Review Boards for the Miriam Hospital and Brown University and informed consent was obtained from each participant before enrollment.

Electronic supplementary material

Supplemental Figure 1

(DOCX 1178 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Cohen, R.A., Siegel, S., Gullett, J.M. et al. Neural response to working memory demand predicts neurocognitive deficits in HIV. J. Neurovirol. 24, 291–304 (2018). https://doi.org/10.1007/s13365-017-0607-z

Download citation

Keywords

  • HIV
  • Working memory
  • Functional MRI
  • Attention
  • Executive control
  • Stroop