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Decreased MEG beta oscillations in HIV-infected older adults during the resting state

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Abstract

The introduction of combination antiretroviral therapy significantly reduced the prevalence of the most severe form of HIV-associated neurocognitive disorders (HAND). Despite this decline, 35–70 % of HIV-infected patients continue to develop mild motor and cognitive impairments. Although neuropsychological studies have shown that HAND affects a wide array of cognitive functions, a formal diagnosis is still based on the exclusion of opportunistic infections and other common ailments, as no specific tests or biomarkers are currently available. In this study, we used magnetoencephalography (MEG) to measure neural activity during the resting-state in 15 HIV-infected older patients and a demographically matched group of 15 uninfected controls. MEG is a noninvasive and direct measure of neural activity with excellent spatiotemporal resolution. All MEG data were coregistered to structural magnetic resonance images, corrected for head motion, fitted to a regional-level source model, and subjected to spectral analyses to quantify population-level neural oscillatory activity. We found that HIV-infected persons exhibited decreased beta oscillations in the supplementary motor area bilaterally, paracentral lobule, posterior cingulate, and bilateral regions of the superior parietal lobule relative to healthy controls. Beta oscillations in the posterior cingulate, a critical component of the default mode network, were also positively correlated with patient scores on the memory recall aspect of the Hopkins Verbal Learning Test-Revised. These results demonstrate that chronic HIV infection does not uniformly disturb cortical function, and that neuronal populations in dorsomedial motor and parietal cortices are especially affected. These findings also suggest that resting-state MEG recordings may hold significant promise as a functional biomarker for identifying HAND and monitoring disease progression.

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References

  • Adamson DC, McArthur JC, Dawson TM, Dawson VL (1999) Rate and severity of HIV-associated dementia (HAD): correlations with Gp41 and iNOS. Mol Med 5:98–109

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ances BM, Sisti D, Vaida F, Liang CL, Leontiev O, Perthen JE, Buxton RB, Benson D, Smith DM, Little SJ, Richman DD, Moore DJ, Ellis RJ, Group H (2009) Resting cerebral blood flow: a potential biomarker of the effects of HIV in the brain. Neurology 73:702–708

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ances BM, Vaida F, Yeh MJ, Liang CL, Buxton RB, Letendre S, McCutchan JA, Ellis RJ (2010) HIV infection and aging independently affect brain function as measured by functional magnetic resonance imaging. J Infect Dis 201:336–340

    Article  PubMed Central  PubMed  Google Scholar 

  • Ances B, Vaida F, Ellis R, Buxton R (2011) Test–retest stability of calibrated BOLD-fMRI in HIV− and HIV+ subjects. Neuroimage 54:2156–2162

    Article  PubMed Central  PubMed  Google Scholar 

  • Andrews-Hanna JR, Reidler JS, Sepulcre J, Poulin R, Buckner RL (2010) Functional–anatomic fractionation of the brain’s default network. Neuron 65:550–562

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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 69:1789–1799

    Article  CAS  PubMed  Google Scholar 

  • Becker JT, Bajo R, Fabrizio M, Sudre G, Cuesta P, Aizenstein HJ, Lopez OL, Wolk D, Parkkonen L, Maestu F, Bagic A (2012a) Functional connectivity measured with magnetoencephalography identifies persons with HIV disease. Brain Imaging Behav 6:366–373

    Article  PubMed Central  PubMed  Google Scholar 

  • Becker JT, Cuesta P, Fabrizio M, Sudre G, Vergis EN, Douaihy A, Bajo R, Schubert A, Lopez OL, Parkkonen L, Maestu F, Bagic A (2012b) Brain structural and functional recovery following initiation of combination antiretroviral therapy. J Neurovirol 18:423–427

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Becker JT, Fabrizio M, Sudre G, Haridis A, Ambrose T, Aizenstein HJ, Eddy W, Lopez OL, Wolk DA, Parkkonen L, Bagic A (2012c) Potential utility of resting-state magnetoencephalography as a biomarker of CNS abnormality in HIV disease. J Neurosci Methods 206:176–182

    Article  PubMed Central  PubMed  Google Scholar 

  • Bouwman FH, Skolasky RL, Hes D, Selnes OA, Glass JD, Nance-Sproson TE, Royal W, Dal Pan GJ, McArthur JC (1998) Variable progression of HIV-associated dementia. Neurology 50:1814–1820

    Article  CAS  PubMed  Google Scholar 

  • Buckner RL, Vincent JL (2007) Unrest at rest: default activity and spontaneous network correlations. Neuroimage 37:1091–1096, discussion 1097–9

    Article  PubMed  Google Scholar 

  • Buckner RL, Andrews-Hanna JR, Schacter DL (2008) The brain’s default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 1124:1–38

    Article  PubMed  Google Scholar 

  • Carey CL, Woods SP, Rippeth JD, Gonzalez R, Moore DJ, Marcotte TD, Grant I, Heaton RK, Group H (2004) Initial validation of a screening battery for the detection of HIV-associated cognitive impairment. Clin Neuropsychol 18:234–248

    Article  PubMed  Google Scholar 

  • 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 57:1001–1007

    Article  CAS  PubMed  Google Scholar 

  • 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 56:259–272

    Article  PubMed  Google Scholar 

  • 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 3:95–104

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cohen RA, Harezlak J, Schifitto G, Hana G, Clark U, Gongvatana A, Paul R, Taylor M, Thompson P, Alger J, Brown M, Zhong J, Campbell T, Singer E, Daar E, McMahon D, Tso Y, Yiannoutsos CT, Navia B (2010) Effects of nadir CD4 count and duration of human immunodeficiency virus infection on brain volumes in the highly active antiretroviral therapy era. J Neurovirol 16:25–32

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cysique LA, Brew BJ (2009) Neuropsychological functioning and antiretroviral treatment in HIV/AIDS: a review. Neuropsychol Rev 19:169–185

    Article  PubMed  Google Scholar 

  • Ernst T, Chang L, Jovicich J, Ames N, Arnold S (2002) Abnormal brain activation on functional MRI in cognitively asymptomatic HIV patients. Neurology 59:1343–1349

    Article  CAS  PubMed  Google Scholar 

  • 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 65:316–325

    Article  PubMed Central  PubMed  Google Scholar 

  • Ernst T, Jiang CS, 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. J Magn Reson Imaging 32:1045–1053

    Article  PubMed Central  PubMed  Google Scholar 

  • Fox MD, Raichle ME (2007) Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci 8:700–711

    Article  CAS  PubMed  Google Scholar 

  • Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME (2005) The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A 102:9673–9678

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Franzen JD, Heinrichs-Graham E, White ML, Wetzel MW, Knott NL, Wilson TW (2013) Atypical coupling between posterior regions of the default mode network in attention-deficit/hyperactivity disorder: a pharmaco-magnetoencephalography study. J Psychiatry Neurosci 38:120054

    Google Scholar 

  • Gannon P, Khan MZ, Kolson DL (2011) Current understanding of HIV-associated neurocognitive disorders pathogenesis. Curr Opin Neurol 24:275–283

    Article  PubMed Central  PubMed  Google Scholar 

  • Greicius MD, Menon V (2004) Default-mode activity during a passive sensory task: uncoupled from deactivation but impacting activation. J Cogn Neurosci 16:1484–1492

    Article  PubMed  Google Scholar 

  • Heaton RK, Clifford DB, Franklin DR Jr, Woods SP, Ake C, Vaida F, Ellis RJ, Letendre SL, Marcotte TD, Atkinson JH, Rivera-Mindt M, Vigil OR, Taylor MJ, Collier AC, Marra CM, Gelman BB, McArthur JC, Morgello S, Simpson DM, McCutchan JA, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I, Group C (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 75:2087–2096

    Article  PubMed Central  PubMed  Google Scholar 

  • Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S, Corkran SH, Duarte NA, Clifford DB, Woods SP, Collier AC, Marra CM, Morgello S, Mindt MR, Taylor MJ, Marcotte TD, Atkinson JH, Wolfson T, Gelman BB, McArthur JC, Simpson DM, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I, Group C, Group H (2011) HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol 17:3–16

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hoechstetter K, Bornfleth H, Weckesser D, Ille N, Berg P, Scherg M (2004) BESA source coherence: a new method to study cortical oscillatory coupling. Brain Topogr 16:233–238

    Article  PubMed  Google Scholar 

  • Jernigan TL, Archibald SL, Fennema-Notestine C, Taylor MJ, Theilmann RJ, Julaton MD, Notestine RJ, Wolfson T, Letendre SL, Ellis RJ, Heaton RK, Gamst AC, Franklin DR Jr, Clifford DB, Collier AC, Gelman BB, Marra C, McArthur JC, McCutchan JA, Morgello S, Simpson DM, Grant I, Group C (2011) Clinical factors related to brain structure in HIV: the CHARTER study. J Neurovirol 17:248–257

    Article  PubMed Central  PubMed  Google Scholar 

  • Joska JA, Gouse H, Paul RH, Stein DJ, Flisher AJ (2010) Does highly active antiretroviral therapy improve neurocognitive function? A systematic review. J Neurovirol 16:101–114

    Article  CAS  PubMed  Google Scholar 

  • Koenigs M, Barbey AK, Postle BR, Grafman J (2009) Superior parietal cortex is critical for the manipulation of information in working memory. J Neurosci 29:14980–14986

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL (2001) A default mode of brain function. Proc Natl Acad Sci U S A 98:676–682

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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 21:1915–1921

    Article  PubMed  Google Scholar 

  • Simioni S, Cavassini M, Annoni JM, Rimbault Abraham A, Bourquin I, Schiffer V, Calmy A, Chave JP, Giacobini E, Hirschel B, Du Pasquier RA (2010) Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS 24:1243–1250

    PubMed  Google Scholar 

  • Taulu S, Simola J (2006) Spatiotemporal signal space separation method for rejecting nearby interference in MEG measurements. Phys Med Biol 51:1759–1768

    Article  CAS  PubMed  Google Scholar 

  • Taulu S, Simola J, Kajola M (2005) Applications of the signal space separation method (SSS). IEEE Trans Signal Process 53:3359–3372

    Article  Google Scholar 

  • Thomas JB, Brier MR, Snyder AZ, Vaida FF, Ances BM (2013) Pathways to neurodegeneration: effects of HIV and aging on resting-state functional connectivity. Neurology 80:1186–1193

    Article  PubMed  Google Scholar 

  • 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 102:15647–15652

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wilson TW, Fox HS, Robertson KR, Sandkovsky U, O’Neill J, Heinrichs-Graham E, Knott NL, Swindells S (2013a) Abnormal MEG oscillatory activity during visual processing in the prefrontal cortices and frontal eye-fields of the aging HIV brain. PLoS One 8:e66241

    Article  PubMed Central  PubMed  Google Scholar 

  • Wilson TW, Franzen JD, Heinrichs-Graham E, White ML, Knott NL, Wetzel MW (2013b) Broadband neurophysiological abnormalities in the medial prefrontal region of the default-mode network in adults with ADHD. Hum Brain Mapp 34:566–574

    PubMed  Google Scholar 

  • Wilson TW, Heinrichs-Graham E, Robertson KR, Sandkovsky U, O’Neill J, Knott NL, Fox HS, Swindells S (2013c) Functional brain abnormalities during finger-tapping in HIV-infected older adults: a magnetoencephalography study. J Neuroimmune Pharmacol 8(4):965–974

    Article  PubMed  Google Scholar 

  • Woods SP, Scott JC, Dawson MS, Morgan EE, Carey CL, Heaton RK, Grant I, Group HIVNRC (2005) Construct validity of Hopkins Verbal Learning Test-Revised component process measures in an HIV-1 sample. Arch Clin Neuropsychol 20:1061–1071

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by NIH grant P30 MH062261 (HSF). The Center for Magnetoencephalography at the University of Nebraska Medical Center was founded through an endowment from an anonymous donor. We would like to thank our participants for volunteering. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflicts of interest

KMB, EHG, HSF, JO’N, and TWW have no biomedical financial interests or potential conflicts of interest to report. KRR has served as a consultant for Abbott and GlaxoSmithKline. USS has served as a consultant for Merck and has received research grant support from Pfizer, Behring, and GlaxoSmithKline for research unrelated to this study. SS reports receiving grant support to the University of Nebraska Medical Center from GlaxoSmithKline and Pfizer for research unrelated to this study.

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Authors and Affiliations

  1. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA

    Katherine M. Becker, Howard S. Fox & Tony W. Wilson

  2. Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA

    Uriel Sandkovsky, Jennifer O’Neill & Susan Swindells

  3. Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, USA

    Tony W. Wilson

  4. Center for Magnetoencephalography, University of Nebraska Medical Center, Omaha, NE, USA

    Katherine M. Becker, Elizabeth Heinrichs-Graham & Tony W. Wilson

  5. Department of Psychology, University of Nebraska-Omaha, Omaha, NE, USA

    Elizabeth Heinrichs-Graham

  6. Department of Neurology, University of North Carolina School of Medicine, Chapel Hill, NC, USA

    Kevin R. Robertson

  7. Center for Magnetoencephalography, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 988422 Nebraska Medical Center, Omaha, NE, 68198, USA

    Tony W. Wilson

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  1. Katherine M. Becker
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Correspondence to Tony W. Wilson.

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Becker, K.M., Heinrichs-Graham, E., Fox, H.S. et al. Decreased MEG beta oscillations in HIV-infected older adults during the resting state. J. Neurovirol. 19, 586–594 (2013). https://doi.org/10.1007/s13365-013-0220-8

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