Abstract
Human immunodeficiency virus (HIV) and methamphetamine (METH) dependence are independently associated with neuronal dysfunction. The coupling between cerebral blood flow (CBF) and neuronal activity is the basis of many task-based functional neuroimaging techniques. We examined the interaction between HIV infection and a previous history of METH dependence on CBF within the lenticular nuclei (LN). Twenty-four HIV−/METH−, eight HIV−/METH+, 24 HIV+/METH−, and 15 HIV+/METH+ participants performed a finger tapping paradigm. A multiple regression analysis of covariance assessed associations and two-way interactions between CBF and HIV serostatus and/or previous history of METH dependence. HIV+ individuals had a trend towards a lower baseline CBF (−10%, p = 0.07) and greater CBF changes for the functional task (+32%, p = 0.01) than HIV− subjects. Individuals with a previous history of METH dependence had a lower baseline CBF (−16%, p = 0.007) and greater CBF changes for a functional task (+33%, p = 0.02). However, no interaction existed between HIV serostatus and previous history of METH dependence for either baseline CBF (p = 0.53) or CBF changes for a functional task (p = 0.10). In addition, CBF and volume in the LN were not correlated. A possible additive relationship could exist between HIV infection and a history of METH dependence on CBF with a previous history of METH dependence having a larger contribution. Abnormalities in CBF could serve as a surrogate measure for assessing the chronic effects of HIV and previous METH dependence on brain function.
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References
Allison JD, Meador KJ, Loring DW, Figueroa RE, Wright JC (2000) Functional MRI cerebral activation and deactivation during finger movement. Neurology 54:135–142
Ances BM, Ellis RJ (2007) Dementia and neurocognitive disorders due to HIV-1 infection. Semin Neurol 27:86–92
Ances BM, Roc AC, Wang J, Korczykowski M, Okawa J, Stern J, Kim J, Wolf R, Lawler K, Kolson DL, Detre JA (2006) Caudate blood flow and volume are reduced in HIV+ neurocognitively impaired patients. Neurology 66:862–866
Ances BM, Leontiev O, Perthen JE, Liang C, Lansing AE, Buxton RB (2008a) Regional differences in the coupling of cerebral blood flow and oxygen metabolism changes in response to activation: implications for BOLD-fMRI. Neuroimage 39:1510–1521
Ances BM, Roc AC, Korczykowski M, Wolf RL, Kolson DL (2008b) Combination antiretroviral therapy modulates the blood oxygen level-dependent amplitude in human immunodeficiency virus-seropositive patients. J Neurovirol 14:418–424
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 (2009) Resting cerebral blood flow: a potential biomarker of the effects of HIV in the brain. Neurology 73:702–708
Ances B, Vaida F, Ellis R, Buxton R (2010) Test-retest stability of calibrated BOLD-fMRI in HIV- and HIV+ subjects. Neuroimage 54:2156–2162
Bamford NS, Zhang H, Joyce JA, Scarlis CA, Hanan W, Wu NP, Andre VM, Cohen R, Cepeda C, Levine MS, Harleton E, Sulzer D (2008) Repeated exposure to methamphetamine causes long-lasting presynaptic corticostriatal depression that is renormalized with drug readministration. Neuron 58:89–103
Bokkers RP, van der Worp HB, Mali WP, Hendrikse J (2009) Noninvasive MR imaging of cerebral perfusion in patients with a carotid artery stenosis. Neurology 73:869–875
Boynton GM, Engel SA, Glover GH, Heeger DJ (1996) Linear systems analysis of functional magnetic resonance imaging in human V1. J Neurosci 16:4207–4221
Burock MA, Dale AM (2000) Estimation and detection of event-related fMRI signals with temporally correlated noise: a statistically efficient and unbiased approach. Hum Brain Mapp 11:249–260
Buxton RB (2010) Interpreting oxygenation-based neuroimaging signals: the importance and the challenge of understanding brain oxygen metabolism. Front Neuroenergetics 2:8
Carey CL, Woods SP, Rippeth JD, Gonzalez R, Heaton RK, Grant I (2006) Additive deleterious effects of methamphetamine dependence and immunosuppression on neuropsychological functioning in HIV infection. AIDS Behav 10:185–190
Chalela JA, Alsop DC, Gonzalez-Atavales JB, Maldjian JA, Kasner SE, Detre JA (2000) Magnetic resonance perfusion imaging in acute ischemic stroke using continuous arterial spin labeling. Stroke 31:680–687
Chana G, Everall IP, Crews L, Langford D, Adame A, Grant I, Cherner M, Lazzaretto D, Heaton R, Ellis R, Masliah E (2006) Cognitive deficits and degeneration of interneurons in HIV+ methamphetamine users. Neurology 67:1486–1489
Chang L, Ernst T, Leonido-Yee M, Speck O (2000) Perfusion MRI detects rCBF abnormalities in early stages of HIV-cognitive motor complex. Neurology 54:389–396
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
Chang L, Ernst T, Speck O, Patel H, DeSilva M, Leonido-Yee M, Miller EN (2002) Perfusion MRI and computerized cognitive test abnormalities in abstinent methamphetamine users. Psychiatry Res 114:65–79
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
Chang L, Ernst T, Speck O, Grob CS (2005) Additive effects of HIV and chronic methamphetamine use on brain metabolite abnormalities. Am J Psychiatry 162:361–369
Chang L, Alicata D, Ernst T, Volkow N (2007) Structural and metabolic brain changes in the striatum associated with methamphetamine abuse. Addiction 102(Suppl 1):16–32
Cherner M, Letendre S, Heaton RK, Durelle J, Marquie-Beck J, Gragg B, Grant I (2005) Hepatitis C augments cognitive deficits associated with HIV infection and methamphetamine. Neurology 64:1343–1347
Cherner M, Suarez P, Casey C, Deiss R, Letendre S, Marcotte T, Vaida F, Atkinson JH, Grant I, Heaton RK (2010) Methamphetamine use parameters do not predict neuropsychological impairment in currently abstinent dependent adults. Drug Alcohol Depend 106:154–163
Chiarelli PA, Bulte DP, Piechnik S, Jezzard P (2007) Sources of systematic bias in hypercapnia-calibrated functional MRI estimation of oxygen metabolism. Neuroimage 34:35–43
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
Cox RW (1996) AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput Biomed Res 29:162–173
Domino EF, Minoshima S, Guthrie S, Ohl L, Ni L, Koeppe RA, Zubieta JK (2000) Nicotine effects on regional cerebral blood flow in awake, resting tobacco smokers. Synapse 38:313–321
Ellis RJ, Moore DJ, Childers ME, Letendre S, McCutchan JA, Wolfson T, Spector SA, Hsia K, Heaton RK, Grant I (2002) Progression to neuropsychological impairment in human immunodeficiency virus infection predicted by elevated cerebrospinal fluid levels of human immunodeficiency virus RNA. Arch Neurol 59:923–928
Fama R, Rosenbloom MJ, Nichols BN, Pfefferbaum A, Sullivan EV (2009) Working and episodic memory in HIV infection, alcoholism, and their comorbidity: baseline and 1-year follow-up examinations. Alcohol Clin Exp Res 33:1815–1824
Flora G, Lee YW, Nath A, Hennig B, Maragos W, Toborek M (2003) Methamphetamine potentiates HIV-1 Tat protein-mediated activation of redox-sensitive pathways in discrete regions of the brain. Exp Neurol 179:60–70
Fujimura RK, Goodkin K, Petito CK, Douyon R, Feaster DJ, Concha M, Shapshak P (1997) HIV-1 proviral DNA load across neuroanatomic regions of individuals with evidence for HIV-1-associated dementia. J Acquir Immune Defic Syndr Hum Retrovirol 16:146–152
Jernigan TL, Gamst AC, Archibald SL, Fennema-Notestine C, Mindt MR, Marcotte TD, Heaton RK, Ellis RJ, Grant I (2005) Effects of methamphetamine dependence and HIV infection on cerebral morphology. Am J Psychiatry 162:1461–1472
Juengst SB, Aizenstein HJ, Figurski J, Lopez OL, Becker JT (2007) Alterations in the hemodynamic response function in cognitively impaired HIV/AIDS subjects. J Neurosci Methods 163:208–212
Kastrup A, Kruger G, Neumann-Haefelin T, Glover GH, Moseley ME (2002) Changes of cerebral blood flow, oxygenation, and oxidative metabolism during graded motor activation. Neuroimage 15:74–82
Kumar AM, Fernandez J, Singer EJ, Commins D, Waldrop-Valverde D, Ownby RL, Kumar M (2009) Human immunodeficiency virus type 1 in the central nervous system leads to decreased dopamine in different regions of postmortem human brains. J Neurovirol 15:257–274
Langford D, Grigorian A, Hurford R, Adame A, Crews L, Masliah E (2004) The role of mitochondrial alterations in the combined toxic effects of human immunodeficiency virus Tat protein and methamphetamine on calbindin positive-neurons. J Neurovirol 10:327–337
Marshall JF, O’Dell SJ, Weihmuller FB (1993) Dopamine-glutamate interactions in methamphetamine-induced neurotoxicity. J Neural Transm Gen Sect 91:241–254
Mumford JA, Hernandez-Garcia L, Lee GR, Nichols TE (2006) Estimation efficiency and statistical power in arterial spin labeling fMRI. Neuroimage 33:103–114
Nath A, Maragos WF, Avison MJ, Schmitt FA, Berger JR (2001) Acceleration of HIV dementia with methamphetamine and cocaine. J Neurovirol 7:66–71
Navia BA, Cho ES, Petito CK, Price RW (1986) The AIDS dementia complex: II. Neuropathology. Ann Neurol 19:525–535
Osawa A, Maeshima S, Shimamoto Y, Maeshima E, Sekiguchi E, Kakishita K, Ozaki F, Moriwaki H (2004) Relationship between cognitive function and regional cerebral blood flow in different types of dementia. Disabil Rehabil 26:739–745
Perthen JE, Bydder M, Restom K, Liu TT (2008a) SNR and functional sensitivity of BOLD and perfusion-based fMRI using arterial spin labeling with spiral SENSE at 3 T. Magn Reson Imaging 26:513–522
Perthen JE, Lansing AE, Liau J, Liu TT, Buxton RB (2008b) Caffeine-induced uncoupling of cerebral blood flow and oxygen metabolism: a calibrated BOLD fMRI study. Neuroimage 40:237–247
Pohl P, Vogl G, Fill H, Rossler H, Zangerle R, Gerstenbrand F (1988) Single photon emission computed tomography in AIDS dementia complex. J Nucl Med 29:1382–1386
Ramirez SH, Potula R, Fan S, Eidem T, Papugani A, Reichenbach N, Dykstra H, Weksler BB, Romero IA, Couraud PO, Persidsky Y (2009) Methamphetamine disrupts blood-brain barrier function by induction of oxidative stress in brain endothelial cells. J Cereb Blood Flow Metab 29:1933–1945
Restom K, Perthen JE, Liu TT (2008) Calibrated fMRI in the medial temporal lobe during a memory-encoding task. Neuroimage 40:1495–1502
Rippeth JD, Heaton RK, Carey CL, Marcotte TD, Moore DJ, Gonzalez R, Wolfson T, Grant I (2004) Methamphetamine dependence increases risk of neuropsychological impairment in HIV infected persons. J Int Neuropsychol Soc 10:1–14
Robins LN, Wing J, Wittchen HU, Helzer JE, Babor TF, Burke J, Farmer A, Jablenski A, Pickens R, Regier DA et al (1988) The Composite International Diagnostic Interview. An epidemiologic Instrument suitable for use in conjunction with different diagnostic systems and in different cultures. Arch Gen Psychiatry 45:1069–1077
Rosenbloom MJ, Sullivan EV, Sassoon SA, O’Reilly A, Fama R, Kemper CA, Deresinski S, Pfefferbaum A (2007) Alcoholism, HIV infection, and their comorbidity: factors affecting self-rated health-related quality of life. J Stud Alcohol Drugs 68:115–125
Scott JC, Woods SP, Matt GE, Meyer RA, Heaton RK, Atkinson JH, Grant I (2007) Neurocognitive effects of methamphetamine: a critical review and meta-analysis. Neuropsychol Rev 17:275–297
Simon SL, Dean AC, Cordova X, Monterosso JR, London ED (2010) Methamphetamine dependence and neuropsychological functioning: evaluating change during early abstinence. J Stud Alcohol Drugs 71:335–344
Spitzer RL, Williams JB, Gibbon M, First MB (1992) The Structured Clinical Interview for DSM-III-R (SCID). I: history, rationale, and description. Arch Gen Psychiatry 49:624–629
Stephans SE, Yamamoto BK (1994) Methamphetamine-induced neurotoxicity: roles for glutamate and dopamine efflux. Synapse 17:203–209
Takaki M, Ujike H, Kodama M, Takehisa Y, Yamamoto A, Kuroda S (2001) Increased expression of synaptophysin and stathmin mRNAs after methamphetamine administration in rat brain. Neuroreport 12:1055–1060
Taylor MJ, Schweinsburg BC, Alhassoon OM, Gongvatana A, Brown GG, Young-Casey C, Letendre SL, Grant I (2007) Effects of human immunodeficiency virus and methamphetamine on cerebral metabolites measured with magnetic resonance spectroscopy. J Neurovirol 13:150–159
Vafaee MS, Gjedde A (2004) Spatially dissociated flow-metabolism coupling in brain activation. Neuroimage 21:507–515
Wang GJ, Chang L, Volkow ND, Telang F, Logan J, Ernst T, Fowler JS (2004) Decreased brain dopaminergic transporters in HIV-associated dementia patients. Brain 127:2452–2458
Wang J, Zhang Y, Wolf RL, Roc AC, Alsop DC, Detre JA (2005) Amplitude-modulated continuous arterial spin-labeling 3.0-T perfusion MR imaging with a single coil: feasibility study. Radiology 235:218–228
Westover AN, McBride S, Haley RW (2007) Stroke in young adults who abuse amphetamines or cocaine: a population-based study of hospitalized patients. Arch Gen Psychiatry 64:495–502
Zubieta JK, Heitzeg MM, Xu Y, Koeppe RA, Ni L, Guthrie S, Domino EF (2005) Regional cerebral blood flow responses to smoking in tobacco smokers after overnight abstinence. Am J Psychiatry 162:567–577
Acknowledgements
This work was supported by a Dana Foundation Brain Immuno Imaging Award (DF3857-41880; B.A.) and NIH grants 1K23MH081786 and 1R01NR012657 (B.A.), NS-36722 and NS-42069 (R.B., C.G., and C.L.), MH22005 and AI47033 (F.V.), P30 MH62512 (M.C., R.E., I.G., F,V., and HNRC Group), and P01 DA12065. The authors would like to thank the contributions of study participants and staff at the HNRC and Translational Methamphetamine AIDS Research Center (P50 DA26306), San Diego, CA, USA. The HNRC Group is affiliated with the University of California, San Diego, the Naval Hospital, San Diego, the Veterans Affairs San Diego Healthcare System and includes Director: Igor Grant, M.D.; Co-Directors: J. Hampton Atkinson, M.D., Ronald J. Ellis, M.D., Ph.D., and J. Allen McCutchan, M.D.; Center Manager: Thomas D. Marcotte, Ph.D.; Assistant Center Manager: Jennifer Marquie-Beck; Business Manager: Melanie Sherman; Naval Hospital San Diego: Braden R. Hale, M.D., M.P.H. (P.I.); Neuromedical Component: Ronald J. Ellis, M.D., Ph.D. (P.I.), J. Allen McCutchan, M.D., Scott Letendre, M.D., Edmund Capparelli, Pharm.D., Rachel Schrier, Ph.D., and Terry Alexander, R.N.; Neurobehavioral Component: Robert K. Heaton, Ph.D. (P.I.), Mariana Cherner, Ph.D., Steven Paul Woods, Psy.D., David J. Moore, Ph.D.; Matthew Dawson, and Donald Franklin; Neuroimaging Component: Terry Jernigan, Ph.D. (P.I.), Christine Fennema-Notestine, Ph.D., Sarah L. Archibald, M.A., Marc Jacobson, Ph.D., Jacopo Annese, Ph.D., and Michael J. Taylor, Ph.D.; Neurobiology Component: Eliezer Masliah, M.D. (P.I.), Ian Everall, FRCPsych., FRCPath., Ph.D., and Cristian Achim, M.D., Ph.D.; Neurovirology Component: Douglas Richman, M.D., (P.I.) and David M. Smith, M.D.; International Component: J. Allen McCutchan, M.D., (P.I.); Developmental Component: Cristian Achim, MD, Ph.D. (P.I.) and Stuart Lipton, M.D., Ph.D.; Clinical Trials Component: J. Allen McCutchan, M.D., J. Hampton Atkinson, M.D., Ronald J. Ellis, M.D., Ph.D., and Scott Letendre, M.D.; Participant Accrual and Retention Unit: J. Hampton Atkinson, M.D. (P.I.) and Rodney von Jaeger, M.P.H.; Data Management Unit: Anthony C. Gamst, Ph.D. (P.I.) and Clint Cushman (Data Systems Manager); Statistics Unit: Ian Abramson, Ph.D. (P.I.), Florin Vaida, Ph.D., Tanya Wolfson, MS, and Reena Deutsch, Ph.D.
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Ances, B.M., Vaida, F., Cherner, M. et al. HIV and Chronic Methamphetamine Dependence Affect Cerebral Blood Flow. J Neuroimmune Pharmacol 6, 409–419 (2011). https://doi.org/10.1007/s11481-011-9270-y
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DOI: https://doi.org/10.1007/s11481-011-9270-y