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Erschienen in: Journal of NeuroVirology 3/2018

26.12.2017

Neural response to working memory demand predicts neurocognitive deficits in HIV

verfasst von: Ronald A. Cohen, S. Siegel, J. M. Gullett, E. Porges, A. J. Woods, H. Huang, Y. Zhu, K. Tashima, M.-Z. Ding

Erschienen in: Journal of NeuroVirology | Ausgabe 3/2018

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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.
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Literatur
Zurück zum Zitat 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 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
Zurück zum Zitat 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 CrossRefPubMedCentralPubMed 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​ CrossRefPubMedCentralPubMed
Zurück zum Zitat Blazer DG, Yaffe K, Liverman CT, eds (2015) Cognitive aging: progress in understanding and opportunities for action. Washington (DC) Blazer DG, Yaffe K, Liverman CT, eds (2015) Cognitive aging: progress in understanding and opportunities for action. Washington (DC)
Zurück zum Zitat 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 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
Zurück zum Zitat 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):884–900PubMedCentralPubMed 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):884–900PubMedCentralPubMed
Zurück zum Zitat Clifford DB (2008) HIV-associated neurocognitive disease continues in the antiretroviral era. Top HIV Med. 16(2):94–98PubMed Clifford DB (2008) HIV-associated neurocognitive disease continues in the antiretroviral era. Top HIV Med. 16(2):94–98PubMed
Zurück zum Zitat 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 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
Zurück zum Zitat 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 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
Zurück zum Zitat 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 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
Zurück zum Zitat 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):277–283PubMed 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):277–283PubMed
Zurück zum Zitat Golden CJ (1972) Stroop color and word test. Chicago, Stoelting Golden CJ (1972) Stroop color and word test. Chicago, Stoelting
Zurück zum Zitat 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 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
Zurück zum Zitat 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 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
Zurück zum Zitat 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 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
Zurück zum Zitat 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 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
Zurück zum Zitat 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 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
Zurück zum Zitat 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 CrossRefPubMed 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/​S135561770000023​0 CrossRefPubMed
Zurück zum Zitat 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 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
Zurück zum Zitat 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 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
Zurück zum Zitat 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 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
Zurück zum Zitat 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):46–56PubMedCentralPubMed 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):46–56PubMedCentralPubMed
Zurück zum Zitat Lezak MD (1995) Neuropsychological assessment (3rd ed.), 3rd edn. Oxford University Press, New York Lezak MD (1995) Neuropsychological assessment (3rd ed.), 3rd edn. Oxford University Press, New York
Zurück zum Zitat 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 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
Zurück zum Zitat 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):329–335PubMed 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):329–335PubMed
Zurück zum Zitat 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 CrossRefPubMed 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 CrossRefPubMed
Zurück zum Zitat 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 CrossRefPubMed 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/​S135561770808091​0 CrossRefPubMed
Zurück zum Zitat 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 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
Zurück zum Zitat 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 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
Zurück zum Zitat 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 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
Zurück zum Zitat Seider TR, Gongvatana A, Woods AJ et al (2016) Age exacerbates HIV-associated white matter abnormalities. J Neuro-Oncol 22(2):201–212 Seider TR, Gongvatana A, Woods AJ et al (2016) Age exacerbates HIV-associated white matter abnormalities. J Neuro-Oncol 22(2):201–212
Zurück zum Zitat 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 e2318CrossRef 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 e2318CrossRef
Zurück zum Zitat 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 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
Zurück zum Zitat Wendelken LA, Valcour V (2012) Impact of HIV and aging on neuropsychological function. J Neuro-Oncol 18(4):256–263 Wendelken LA, Valcour V (2012) Impact of HIV and aging on neuropsychological function. J Neuro-Oncol 18(4):256–263
Zurück zum Zitat 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):2720–2724PubMed 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):2720–2724PubMed
Metadaten
Titel
Neural response to working memory demand predicts neurocognitive deficits in HIV
verfasst von
Ronald A. Cohen
S. Siegel
J. M. Gullett
E. Porges
A. J. Woods
H. Huang
Y. Zhu
K. Tashima
M.-Z. Ding
Publikationsdatum
26.12.2017
Verlag
Springer International Publishing
Erschienen in
Journal of NeuroVirology / Ausgabe 3/2018
Print ISSN: 1355-0284
Elektronische ISSN: 1538-2443
DOI
https://doi.org/10.1007/s13365-017-0607-z

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