Skip to main content

Advertisement

SpringerLink
Log in

Functional Brain Abnormalities During Finger-Tapping in HIV-Infected Older Adults: A Magnetoencephalography Study

  • ORIGINAL ARTICLE
  • Published:
Journal of Neuroimmune Pharmacology Aims and scope Submit manuscript

Abstract

Despite the availability of combination antiretroviral therapy, at least mild cognitive dysfunction is commonly observed in HIV-infected patients, with an estimated prevalence of 35–70 %. Neuropsychological studies of these HIV-associated neurocognitive disorders (HAND) have documented aberrations across a broad range of functional domains, although the basic pathophysiology remains unresolved. Some of the most common findings have been deficits in fine motor control and reduced psychomotor speed, but to date no neuroimaging studies have evaluated basic motor control in HAND. In this study, we used magnetoencephalography (MEG) to evaluate the neurophysiological processes that underlie motor planning in older HIV-infected adults and a matched, uninfected control group. MEG is a noninvasive and direct measure of neural activity with good spatiotemporal precision. During the MEG recording, participants fixated on a central crosshair and performed a finger-tapping task with the dominant hand. All MEG data was corrected for head movements, preprocessed, and imaged in the time-frequency domain using beamforming methodology. All analyses focused on the pre-movement beta desynchronization, which is known to be an index of movement planning. Our results demonstrated that HIV-1-infected patients have deficient beta desynchronization relative to controls within the left/right precentral gyri, and the supplementary motor area. In contrast, HIV-infected persons showed abnormally strong beta responses compared to controls in the right dorsolateral prefrontal cortex and medial prefrontal areas. In addition, the amplitude of beta activity in the primary and supplementary motor areas correlated with scores on the Grooved Pegboard test in HIV-infected adults. These results demonstrate that primary motor and sensory regions may be particularly vulnerable to HIV-associated damage, and that prefrontal cortices may serve a compensatory role in maintaining motor performance levels in infected patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Ances BM, Sisti D, Vaida F, Liang CL, Leontiev O, Perthen JE et al (2009) Resting cerebral blood flow: a potential biomarker of the effects of HIV in the brain. Neurology 73:702–708

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M et al (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799

    Article  PubMed  CAS  Google Scholar 

  • Antiretroviral Therapy Cohort Collaboration (2008) Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet 372:293–299

    Article  Google Scholar 

  • Arendt G, Hefter H, Jablonowski H (1993) Acoustically evoked event-related potentials in HIV- associated dementia. Electroenceph Clin Neurophysiol 86:152–160

    Article  PubMed  CAS  Google Scholar 

  • Becker JT, Bajo R, Fabrizio M, Sudre G, Cuesta P, Aizenstein HJ et al (2012a) Functional connectivity measured with magnetoencephalography identifies persons with HIV disease. Brain Imaging Behav 6(3):366–373

    Article  PubMed  Google Scholar 

  • Becker JT, Fabrizio M, Sudre G, Haridis A, Ambrose T, Aizenstein HJ et al (2012b) Potential utility of resting-state magnetoencephalography as a biomarker of CNS abnormality in HIV disease. J Neurosci Methods 206(2):176–182

    Article  PubMed  Google Scholar 

  • Chang L, Speck O, Miller EN, Braun J, Jovicich J, Koch C et al (2001) Neural correlates of attention and working memory deficits in HIV patients. Neurology 57:1001–1007

    Article  PubMed  CAS  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(2):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  PubMed  CAS  Google Scholar 

  • Cheney PD, Riazi M, Marcario JM (2008) Behavioral and neurophysiological hallmarks of simian immunodeficiency virus infection in macaque monkeys. J Neurovirol 14(4):301–308

    Article  PubMed  CAS  Google Scholar 

  • Cheyne D, Bells S, Ferrari P, Gaetz W, Bostan AC (2008) Self-paced movements induce high- frequency gamma oscillations in primary motor cortex. NeuroImage 42:332–342

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Deeks SG (2009) Immune dysfunction, inflammation, and accelerated aging in patients on antiretroviral therapy. Top HIV Med 17:118–123

    PubMed  Google Scholar 

  • Dore GJ, McDonald A, Li Y, Kaldor JM, Brew BJ, National HIV Surveillance Committee (2003) Marked improvement in survival following AIDS dementia complex in the era of highly active antiretroviral therapy. AIDS 17:1539–1545

    Article  PubMed  Google Scholar 

  • Egan VG, Chiswick A, Brettle R, Goodwin G (1993) The Edinburgh cohort of HIV-positive drug users: the relationship between auditory P3 latency, cognitive function and self-related mood. Psychol Med 23:613–622

    Article  PubMed  CAS  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(9):1343–1349

    Article  PubMed  CAS  Google Scholar 

  • Ernst T, Yakupov R, Nakama H, Crocket G, Cole M, Watters M et al (2009) Declined neural efficiency in cognitively stable human immunodeficiency virus patients. Ann Neurol 65:316–325

    Article  PubMed  Google Scholar 

  • Fein G, Biggines CA, MacKay S (1995) Alcohol abuse and HIV infection have additive effects on frontal cortex function as measured by auditory evoked potential P3a latency. Biol Psychiat 37:183–195

    Article  PubMed  CAS  Google Scholar 

  • Fox HS, Weed MR, Huitron-Resendiz S, Baig J, Horn TF, Dailey PJ et al (2000) Antiviral treatment normalizes neurophysiological but not movement abnormalities in simian immunodeficiency virus-infected monkeys. J Clin Invest 106(1):37–45

    Article  PubMed  CAS  Google Scholar 

  • Gaetz W, Macdonald M, Cheyne D, Snead OC (2010) Neuromagnetic imaging of movement- related cortical oscillations in children and adults: age predicts post-movement beta rebound. NeuroImage 51:792–807

    Article  PubMed  CAS  Google Scholar 

  • Gaetz W, Edgar JC, Wang DJ, Roberts TP (2011) Relating MEG measured motor cortical oscillations to resting γ-aminobutyric acid (GABA) concentration. NeuroImage 55:616–621

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Gelman BB, Lisinicchia JG, Chen T, Johnson KM, Jennings K, Freeman DH Jr, Soukup VM (2012) Prefrontal dopaminergic and enkephalinergic synaptic accommodation in HIV-associated neurocognitive disorders and encephalitis. J Neuroimmune Pharmacol 7(3):686–700

    Article  PubMed  Google Scholar 

  • Goodin DS, Aminoff MJ, Chernoff DN, Hollander H (1990) Long latency event-related potentials in patients infected with human immunodeficiency virus. Ann Neurol 27:414–419

    Article  PubMed  CAS  Google Scholar 

  • Gross J, Kujala J, Hamalainen M, Timmermann L, Schnitzler A, Salmelin R (2001) Dynamic imaging of coherent sources: studying neural interactions in the human brain. Proc Natl Acad Sci U S A 98:694–699

    Article  PubMed  CAS  Google Scholar 

  • Hardy DJ, Vance DE (2009) The neuropsychology of HIV/AIDS in older adults. Neuropsychol Rev 19:263–272

    Article  PubMed  Google Scholar 

  • Heaton RK, Clifford DB, Franklin DR Jr, Woods SP, Ake C, Vaida F et al (2010) HIV- associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 75:2087–2096

    Article  PubMed  Google Scholar 

  • Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S et al (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  PubMed  CAS  Google Scholar 

  • Hillebrand A, Singh KD, Holliday IE, Furlong PL, Barnes GR (2005) A new approach to neuroimaging with magnetoencephalography. Hum Brain Mapp 25:199–211

    Article  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 

  • Janssen RS, Cornblath DR, Epstein LG, McArthur J, Price RW (1991) Nomenclature and research case definitions for neurological manifestations of human immunodeficiency virus type-1 (HIV-1) infection. Report of a Working Group of the American Academy of Neurology AIDS Task Force. Neurology 41:778–785

    Article  Google Scholar 

  • Johnson R (1988) The amplitude of the P300 component of the event-related potentials: review and synthesis. In: Ackles P, Jennings JR, Coles MGH (eds) Advances in psychophysiology: a research annual, 3rd edn. JAI Press Inc, Greenwich, pp 69–137

    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 6:101–114, Review

    Article  Google Scholar 

  • Jurkiewicz MT, Gaetz WC, Bostan AC, Cheyne D (2006) Post-movement beta rebound is generated in motor cortex: evidence from neuromagnetic recordings. NeuroImage 32:1281–1289

    Article  PubMed  Google Scholar 

  • Melrose RJ, Tinaz S, Castelo JM, Courtney MG, Stern CE (2008) Compromised fronto-striatal functioning in HIV: an fMRI investigation of semantic event sequencing. Behav Brain Res 188(2):337–347

    Article  PubMed  Google Scholar 

  • Ollo C, Johnson R, Grafman J (1991) Signs of cognitive change in HIV disease: an event- related brain potential study. Neurology 41:209–215

    Article  PubMed  CAS  Google Scholar 

  • Papp N, Ktonas P (1977) Critical evaluation of complex demodulation techniques for the quantification of bioelectrical activity. Biomed Sci Instrum 13:135–143

    PubMed  CAS  Google Scholar 

  • Polich J (1998) P300 clinical utility and control of variability. J Clin Neurophysiol 15:14–33

    Article  PubMed  CAS  Google Scholar 

  • Polich J, Ehlers CL, Otis S, Mandell AJ, Bloom FE (1986) P300 latency reflects the degree of cognitive decline in dementing illness. Electroenceph Clin Neurophysiol 63:138–144

    Article  PubMed  CAS  Google Scholar 

  • Polich J, Ilan A, Poceta JS, Mitler MM, Darko DF (2000) Neuroelectric assessment of HIV: EEG, ERP, and viral load. Int J Psychophysiol 38(1):97–108

    Article  PubMed  CAS  Google Scholar 

  • Pollock VE, Schneider L, Lyness S (1990) EEG amplitudes in health, late middle-aged, and elderly adults: normality of the distributions and correlations with age. Electroenceph Clin Neurophysiol 75:276–288

    Article  PubMed  CAS  Google Scholar 

  • Raymond LAM, Wallace D, Berman NEJ, Marcario J, Foresman L, Joag SV et al (1998) Auditory brainstem responses in a rhesus macaque model of neuro-AIDS. J Neuro Virol 4:512–520

    CAS  Google Scholar 

  • Raymond LAM, Wallace D, Berman NEJ, Marcario J, Foresman L, Joag SV et al (1999) Motor evoked potentials in a rhesus macaque model of neuro-AIDS. J Neuro Virol 5:217–231

    CAS  Google Scholar 

  • Raymond LAM, Wallace D, Zhou J, Raghavan R, Marcario JK, Johnson JK et al (2000) Sensory evoked potentials in SIV-infected monkeys with rapidly and slowly progressing disease. AIDS Res Hum Retroviruses 16:1163–1173

    Article  PubMed  CAS  Google Scholar 

  • Robertson KR, Smurzynski M, Parsons TD, Wu K, Bosch RJ, Wu J et al (2007) The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS 21:1915–1921

    Article  PubMed  Google Scholar 

  • Robertson K, Liner J, Heaton R (2009) Neuropsychological assessment of HIV-infected populations in international settings. Neuropsychol Rev 19:232–249

    Article  PubMed  Google Scholar 

  • Sacktor N, McDermott MP, Marder K, Schifitto G, Selnes OA, McArthur JC et al (2002) HIV- associated cognitive impairment before and after the advent of combination therapy. J Neurovirol 8:136–142

    Article  PubMed  Google Scholar 

  • Simioni S, Cavassini M, Annoni JM, Rimbault Abraham A, Bourquin I, Schiffer V et al (2010) Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS 24:1243–1250

    PubMed  Google Scholar 

  • Talairach G, Tournoux P (1988) Co-planar stereotaxic atlas of the human brain. Thieme, New York

    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  PubMed  CAS  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 

  • The Mind Exchange Working Group (2013) Assessment, diagnosis, and treatment of HIV-associated neurocognitive disorder: a consensus report of the mind exchange program. Clin Infect Dis. [Epub ahead of print] PubMed PMID: 23175555

  • 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  PubMed  CAS  Google Scholar 

  • Tozzi V, Balestra P, Bellagamba R, Corpolongo A, Salvatori MF, Visco-Comandini U et al (2007) Persistence of neuropsychologic deficits despite long-term highly active antiretroviral therapy in patients with HIV-related neurocognitive impairment: prevalence and risk factors. J Acquir Immune Defic Syndr 45:174–182

    Article  PubMed  Google Scholar 

  • Tzagarakis C, Ince NF, Leuthold AC, Pellizzer G (2010) Beta-band activity during motor planning reflects response uncertainty. J Neurosci 30:11270–11277

    Article  PubMed  CAS  Google Scholar 

  • van Veen BD, van Drongelen W, Yuchtman M, Suzuki A (1997) Localization of brain electrical activity via linearly constrained minimum variance spatial filtering. IEEE Trans Biomed Eng 44:867–880

    Article  PubMed  Google Scholar 

  • Wilson TW, Slason E, Asherin RM, Kronberg E, Reite ML, Teale PD, Rojas DC (2010) An extended motor network generates beta and gamma oscillatory perturbations during development. Brain Cogn 73:75–84

    Article  PubMed  Google Scholar 

  • Wilson TW, Slason E, Asherin RM, Kronberg E, Teale PD, Reite ML, Rojas DC (2011) Abnormal gamma and beta MEG activity during finger movements in early-onset psychosis. Dev Neuropsychol 36:596–613

    Article  PubMed  Google Scholar 

  • Woods SP, Moore DJ, Weber E, Grant I (2009) Cognitive neuropsychology of HIV-associated neurocognitive disorders. Neuropsychol Rev 19:152–168

    Article  PubMed  Google Scholar 

  • Yousry TA, Schmid UD, Alkadhi H, Schmidt D, Peraud A, Buettner A, Winkler P (1997) Localization of the motor hand area to a knob on the precentral gyrus. A new landmark. Brain 120:141–157

    Article  PubMed  Google Scholar 

Download references

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.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

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

    Tony W. Wilson & Howard S. Fox

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

    Tony W. Wilson

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

    Uriel Sandkovsky, Jennifer O’Neill & Susan Swindells

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

    Tony W. Wilson, Elizabeth Heinrichs-Graham & Nichole L. Knott

  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

Authors
  1. Tony W. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elizabeth Heinrichs-Graham
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kevin R. Robertson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Uriel Sandkovsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jennifer O’Neill
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nichole L. Knott
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Howard S. Fox
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Susan Swindells
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tony W. Wilson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wilson, T.W., Heinrichs-Graham, E., Robertson, K.R. et al. Functional Brain Abnormalities During Finger-Tapping in HIV-Infected Older Adults: A Magnetoencephalography Study. J Neuroimmune Pharmacol 8, 965–974 (2013). https://doi.org/10.1007/s11481-013-9477-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11481-013-9477-1

Keywords

Search

Navigation