History of Alcohol Consumption and HIV Status Related to Functional Connectivity Differences in the Brain During Working Memory Performance

Author(s): Vaughn E. Bryant*, Joseph M. Gullett, Eric C. Porges, Robert L. Cook, Kendall J. Bryant, Adam J. Woods, John Williamson, Nicole Ennis, Ronald A. Cohen

Journal Name: Current HIV Research

Volume 18 , Issue 3 , 2020

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Graphical Abstract:


Background: Poorer working memory function has previously been associated with alcohol misuse, Human Immunodeficiency Virus (HIV) positive status, and risky behavior. Poorer working memory performance relates to alterations in specific brain networks.

Objective: The current study examined if there was a relationship between brain networks involved in working memory and reported level of alcohol consumption during an individual’s period of heaviest use. Furthermore, we examined whether HIV status and the interaction between HIV and alcohol consumption was associated with differences in these brain networks.

Methods: Fifty adults, 26 of whom were HIV positive, engaged in an n-back working memory task (0-back and 2-back trials) administered in a magnetic resonance imaging (MRI) scanner. The Kreek- McHugh-Schluger-Kellogg (KMSK) scale of alcohol consumption was used to characterize an individual’s period of heaviest use and correlates well with their risk for alcohol dependence. Connectivity analyses were conducted using data collected during n-back task.

Results: Functional connectivity differences associated with greater alcohol consumption included negative connectivity, primarily from parietal attention networks to frontal networks. Greater alcohol consumption was also associated with positive connectivity from working memory nodes to the precuneus and paracingulate. HIV positive status was associated with more nodes of negative functional connectivity relative to alcohol consumption history alone, particularly in the frontoparietal networks. The HIV positive individuals with heavier drinking history related to negative fronto-parietal connectivity, along with positive connectivity from working memory nodes to mesolimbic regions.

Conclusion: Findings allow for a better understanding of brain networks affected by HIV and alcohol and may provide avenues for interventions.

Keywords: HIV, alcohol, imaging, functional, connectivity, working, memory, brain.

Braithwaite RS, Conigliaro J, Roberts MS, et al. Estimating the impact of alcohol consumption on survival for HIV+ individuals. AIDS Care 2007; 19(4): 459-66.
[http://dx.doi.org/10.1080/09540120601095734] [PMID: 17453583]
Conigliaro J, Gordon AJ, McGinnis KA, Rabeneck L, Justice AC. Veterans Aging Cohort 3-Site Study. How harmful is hazardous alcohol use and abuse in HIV infection: do health care providers know who is at risk? J Acquir Immune Defic Syndr 1999; 133(4): 521-5.
Stein M, Herman DS, Trisvan E, Pirraglia P, Engler P, Anderson BJ. Alcohol use and sexual risk behavior among human immunodeficiency virus-positive persons. Alcohol Clin Exp Res 2005; 29(5): 837-43.
[http://dx.doi.org/10.1097/01.ALC.0000164363.40533.E0] [PMID: 15897729]
Duko B, Ayalew M, Ayano G. The prevalence of alcohol use disorders among people living with HIV/AIDS: a systematic review and meta-analysis. Subst Abuse Treat Prev Policy 2019; 1414(1): 52.
Abaynew Y, Deribew A, Deribe K. Factors associated with late presentation to HIV/AIDS care in South Wollo ZoneEthiopia: a case-control study. AIDS Res Ther 2011; 8(1): 8.
[http://dx.doi.org/10.1186/1742-6405-8-8] [PMID: 21356115]
Zulliger R, Maulsby C, Barrington C, et al. Retention in HIV care among female sex workers in the Dominican Republic: implications for research, policy and programming. AIDS Behav 2015; 19(4): 715-22.
[http://dx.doi.org/10.1007/s10461-014-0979-5] [PMID: 25566761]
Kader R, Govender R, Seedat S, Koch JR, Parry C. Understanding the Impact of Hazardous and Harmful Use of Alcohol and/or Other Drugs on ARV Adherence and Disease Progression. PLoS One 2015; 10(5) e0125088
[http://dx.doi.org/10.1371/journal.pone.0125088] [PMID: 25933422]
Shuper PA, Joharchi N, Irving H, Rehm J. Alcohol as a correlate of unprotected sexual behavior among people living with HIV/AIDS: review and meta-analysis. AIDS Behav 2009; 13(6): 1021-36.
[http://dx.doi.org/10.1007/s10461-009-9589-z] [PMID: 19618261]
Kalichman SC, Grebler T, Amaral CM, et al. Assumed infectiousness, treatment adherence and sexual behaviours: applying the Swiss Statement on infectiousness to HIV-positive alcohol drinkers. HIV Med 2013; 14(5): 263-72.
[http://dx.doi.org/10.1111/j.1468-1293.2012.01062.x] [PMID: 23107801]
Malbergier A, Amaral RA, Cardoso LD. Alcohol dependence and CD4 cell count: is there a relationship? AIDS Care 2015; 27(1): 54-8.
[http://dx.doi.org/10.1080/09540121.2014.947235] [PMID: 25179410]
Braithwaite RS, Nucifora KA, Kessler J, Toohey C, Li L, Mentor SM, et al. How inexpensive does an alcohol intervention in Kenya need to be in order to deliver favorable value by reducing HIVrelated morbidity and mortality? J Acquir Immune Defic Syndr 1999 1999 Jun 166(2): e54-8.
Bechara A, Martin EM. Impaired decision making related to working memory deficits in individuals with substance addictions. Neuropsychology 2004; 18(1): 152-62.
[http://dx.doi.org/10.1037/0894-4105.18.1.152] [PMID: 14744198]
Chang L, Speck O, Miller EN, et al. Neural correlates of attention and working memory deficits in HIV patients. Neurology 2001; 57(6): 1001-7.
[http://dx.doi.org/10.1212/WNL.57.6.1001] [PMID: 11571324]
Law WA, Martin A, Mapou RL, et al. Working memory in individuals with HIV infection. J Clin Exp Neuropsychol 1994; 16(2): 173-82.
[http://dx.doi.org/10.1080/01688639408402628] [PMID: 8021304]
Khurana A, Romer D, Betancourt LM, Brodsky NL, Giannetta JM, Hurt H. Working memory ability predicts trajectories of early alcohol use in adolescents: the mediational role of impulsivity. Addiction 2013; 108(3): 506-15.
[http://dx.doi.org/10.1111/add.12001] [PMID: 23033972]
Saloner R, Paolillo EW, Kohli M, et al. Genetic variation in alcohol dehydrogenase is associated with neurocognition in men with HIV and history of alcohol use disorder: preliminary findings. J Neurovirol 2020. Epub ahead of print
[PMID: 31933193]
Cohen RA, Gullett JM, Porges EC, et al. Heavy Alcohol Use and Age Effects on HIV-Associated Neurocognitive Function. Alcohol Clin Exp Res 2019; 43(1): 147-57.
[PMID: 30371953]
Ripamonti E, Clerici M. The association of memory disorders and chronic HIV disease in the antiretroviral therapy era: a systematic literature review. HIV Med 2020; 21(1): 9-20.
[http://dx.doi.org/10.1111/hiv.12793] [PMID: 31603624]
Baddeley AD, Hitch GJ. Developments in the concept of working memory. Neuropsychology 1994; 8(4): 485-93.
Wagner AD. Working memory contributions to human learning and remembering. Neuron 1999; 22(1): 19-22.
[http://dx.doi.org/10.1016/S0896-6273(00)80674-1] [PMID: 10027285]
Smith EE, Jonides J. Storage and executive processes in the frontal lobes. Science 1999; 283(5408): 1657-61.
[http://dx.doi.org/10.1126/science.283.5408.1657] [PMID: 10073923]
Funahashi S. Working Memory in the Prefrontal Cortex. Brain Sci Internet 2017; 7(5) E49http://www.ncbi.nlm.nih.gov/pubmed/28448453
[http://dx.doi.org/10.3390/brainsci7050049] [PMID: 28448453]
Atkinson RC, Shiffrin RM. Human Memory: A Proposed System and its Control Processes1Psychology of Learning and Motivation Internet. Academic Press 1968; pp. 89-195. Available at:. http://www.sciencedirect.com/science/article/pii/S0079742108604223
Naqvi NH, Bechara A. The insula and drug addiction: an interoceptive view of pleasure, urges, and decision-making. Brain Struct Funct 2010; 214(5-6): 435-50.
[http://dx.doi.org/10.1007/s00429-010-0268-7] [PMID: 20512364]
Rupp CI, Kemmler G, Kurz M, Hinterhuber H, Fleischhacker WW. Cognitive remediation therapy during treatment for alcohol dependence. J Stud Alcohol Drugs 2012; 73(4): 625-34.
[http://dx.doi.org/10.15288/jsad.2012.73.625] [PMID: 22630801]
Charlet K, Beck A, Jorde A, et al. Increased neural activity during high working memory load predicts low relapse risk in alcohol dependence. Addict Biol 2014; 19(3): 402-14.
[http://dx.doi.org/10.1111/adb.12103] [PMID: 24147643]
Penick EC, Knop J, Nickel EJ, et al. Do premorbid predictors of alcohol dependence also predict the failure to recover from alcoholism? J Stud Alcohol Drugs 2010; 71(5): 685-94.
[http://dx.doi.org/10.15288/jsad.2010.71.685] [PMID: 20731973]
Patterson F, Jepson C, Loughead J, et al. Working memory deficits predict short-term smoking resumption following brief abstinence. Drug Alcohol Depend 2010; 106(1): 61-4.
[http://dx.doi.org/10.1016/j.drugalcdep.2009.07.020] [PMID: 19733449]
Duka T, Townshend JM. The priming effect of alcohol pre-load on attentional bias to alcohol-related stimuli. Psychopharmacology (Berl) 2004; 176(3-4): 353-61.
[http://dx.doi.org/10.1007/s00213-004-1906-7] [PMID: 15164158]
Guillot CR, Fanning JR, Bullock JS, McCloskey MS, Berman ME. Effects of alcohol on tests of executive functioning in men and women: a dose response examination. Exp Clin Psychopharmacol 2010; 18(5): 409-17.
[http://dx.doi.org/10.1037/a0021053] [PMID: 20939644]
Lechner WV, Day AM, Metrik J, Leventhal AM, Kahler CW. Effects of alcohol-induced working memory decline on alcohol consumption and adverse consequences of use. Psychopharmacology (Berl) 2016; 233(1): 83-8.
[http://dx.doi.org/10.1007/s00213-015-4090-z] [PMID: 26407604]
Sutherland MT, McHugh MJ, Pariyadath V, Stein EA. Resting state functional connectivity in addiction: Lessons learned and a road ahead. Neuroimage 2012; 62(4): 2281-95.
[http://dx.doi.org/10.1016/j.neuroimage.2012.01.117] [PMID: 22326834]
Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacology 2010; 35(1): 217-38.
[http://dx.doi.org/10.1038/npp.2009.110] [PMID: 19710631]
Reid AT, Headley DB, Mill RD, et al. Advancing functional connectivity research from association to causation. Nat Neurosci 2019; 22(11): 1751-60.
[http://dx.doi.org/10.1038/s41593-019-0510-4] [PMID: 31611705]
Forbes EE, Rodriguez EE, Musselman S, Narendran R. Prefrontal response and frontostriatal functional connectivity to monetary reward in abstinent alcohol-dependent young adults. PLoS One 2014; 9(5) e94640 Available from::. https://dx.doi.org/ 10.1371%2Fjournal.pone.0094640/
[PMID: 24804780]
Mayhugh RE, Moussa MN, Simpson SL, et al. Moderate-Heavy Alcohol Consumption Lifestyle in Older Adults Is Associated with Altered Central Executive Network Community Structure during Cognitive Task. PLoS One 2016; 11(8) e0160214
[http://dx.doi.org/10.1371/journal.pone.0160214] [PMID: 27494180]
Schweinsburg BC, Scott JC, Schweinsburg AD, et al. HIV Neurobehavioral Research Center (HNRC) Group. Altered prefronto-striato-parietal network response to mental rotation in HIV. J Neurovirol 2012; 18(1): 74-9.
[http://dx.doi.org/10.1007/s13365-011-0072-z] [PMID: 22271019]
Meade CS, Lowen SB, MacLean RR, Key MD, Lukas SE. fMRI brain activation during a delay discounting task in HIV-positive adults with and without cocaine dependence. Psychiatry Res 2011; 192(3): 167-75.
[http://dx.doi.org/10.1016/j.pscychresns.2010.12.011] [PMID: 21546221]
Thames AD, Sayegh P, Terashima K, Foley JM, Cho A, Arentoft A. Increased subcortical neural activity among HIV+ individuals during a lexical retrieval task. Neurobiol Dis 2016; 92(Pt B): 175-82.
Ipser JC, Brown GG, Bischoff-Grethe A, et al. Translational Methamphetamine AIDS Research Center (TMARC) Group. HIV infection is associated with attenuated frontostriatal intrinsic connectivity: a preliminary study. J Int Neuropsychol Soc 2015; 21(3): 203-13.
[http://dx.doi.org/10.1017/S1355617715000156] [PMID: 25824201]
Pfefferbaum A, Rosenbloom MJ, Rohlfing T, Kemper CA, Deresinski S, Sullivan EV. Frontostriatal fiber bundle compromise in HIV infection without dementia. AIDS 2009; 23(15): 1977-85.
[http://dx.doi.org/10.1097/QAD.0b013e32832e77fe] [PMID: 19730350]
du Plessis S, Vink M, Joska JA, et al. HIV Infection Is Associated with Impaired Striatal Function during Inhibition with Normal Cortical Functioning on Functional MRI. J Int Neuropsychol Soc 2015; 21(9): 722-31.
[http://dx.doi.org/10.1017/S1355617715000971] [PMID: 26435417]
Rubin LH, Meyer VJ, Conant RJ, et al. Prefrontal cortical volume loss is associated with stress-related deficits in verbal learning and memory in HIV-infected women. Neurobiol Dis 2016; 92(Pt B): 166-74.
Caldwell JZK, Gongvatana A, Navia BA, et al. Neural dysregulation during a working memory task in human immunodeficiency virus-seropositive and hepatitis C coinfected individuals. J Neurovirol 2014; 20(4): 398-411.
[http://dx.doi.org/10.1007/s13365-014-0257-3] [PMID: 24867610]
Gullett JM, Lamb DG, Porges E, et al. The Impact of Alcohol Use on Frontal White Matter in HIV. Alcohol Clin Exp Res 2018; 42(9): 1640-9.
[http://dx.doi.org/10.1111/acer.13823] [PMID: 29957870]
Cohen RA, Siegel S, Gullett JM, et al. Neural response to working memory demand predicts neurocognitive deficits in HIV. J Neurovirol 2018; 24(3): 291-304.
[http://dx.doi.org/10.1007/s13365-017-0607-z] [PMID: 29280107]
Hakkers CS, Arends JE, Barth RE, Du Plessis S, Hoepelman AIM, Vink M. Review of functional MRI in HIV: effects of aging and medication. J Neurovirol 2017; 23(1): 20-32.
[http://dx.doi.org/10.1007/s13365-016-0483-y] [PMID: 27718211]
Plessis SD, Vink M, Joska JA, Koutsilieri E, Stein DJ, Emsley R. HIV infection and the fronto-striatal system: a systematic review and meta-analysis of fMRI studies. AIDS 2014; 28(6): 803-11.
[http://dx.doi.org/10.1097/QAD.0000000000000151] [PMID: 24300546]
Thomas JB, Brier MR, Snyder AZ, Vaida FF, Ances BM. Pathways to neurodegeneration: effects of HIV and aging on resting-state functional connectivity. Neurology 2013; 80(13): 1186-93.
[http://dx.doi.org/10.1212/WNL.0b013e318288792b] [PMID: 23446675]
Ortega M, Brier MR, Ances BM. Effects of HIV and combination antiretroviral therapy on cortico-striatal functional connectivity. AIDS 2015; 29(6): 703-12.
[http://dx.doi.org/10.1097/QAD.0000000000000611] [PMID: 25849834]
Meyerhoff DJ. Effects of alcohol and HIV infection on the central nervous system. Alcohol Res Health 2001; 25(4): 288-98.
[PMID: 11910707]
Haley AP, Sweet LH, Gunstad J, et al. Verbal working memory and atherosclerosis in patients with cardiovascular disease: an fMRI study. J Neuroimaging 2007; 17(3): 227-33.
[http://dx.doi.org/10.1111/j.1552-6569.2007.00110.x] [PMID: 17608908]
Irani F, Sweet LH, Haley AP, et al. A fMRI Study of Verbal Working Memory, Cardiac Output, and Ejection Fraction in Elderly Patients with Cardiovascular Disease. Brain Imaging Behav 2009; 3(4): 350-7.
[http://dx.doi.org/10.1007/s11682-009-9077-0] [PMID: 23227137]
Owen AM, McMillan KM, Laird AR, Bullmore E. N-back working memory paradigm: a meta-analysis of normative functional neuroimaging studies. Hum Brain Mapp 2005; 25(1): 46-59.
[http://dx.doi.org/10.1002/hbm.20131] [PMID: 15846822]
Kellogg SH, McHugh PF, Bell K, et al. The Kreek-McHugh-Schluger-Kellogg scale: a new, rapid method for quantifying substance abuse and its possible applications. Drug Alcohol Depend 2003; 69(2): 137-50.
[http://dx.doi.org/10.1016/S0376-8716(02)00308-3] [PMID: 12609695]
DeWitt SJ, Ketcherside A, McQueeny TM, Dunlop JP, Filbey FM. The hyper-sentient addict: an exteroception model of addiction. Am J Drug Alcohol Abuse 2015; 41(5): 374-81.
[http://dx.doi.org/10.3109/00952990.2015.1049701] [PMID: 26154169]
Schacht JP, Anton RF, Myrick H. Functional neuroimaging studies of alcohol cue reactivity: a quantitative meta-analysis and systematic review. Addict Biol 2013; 18(1): 121-33.
[http://dx.doi.org/10.1111/j.1369-1600.2012.00464.x] [PMID: 22574861]
Claus ED, Ewing SWF, Filbey FM, Sabbineni A, Hutchison KE. Identifying neurobiological phenotypes associated with alcohol use disorder severity. Neuropsychopharmacology 2011; 36(10): 2086-96.
[http://dx.doi.org/10.1038/npp.2011.99] [PMID: 21677649]
Cavanna AE, Trimble MR. The precuneus: a review of its functional anatomy and behavioural correlates. Brain 2006; 129(Pt 3): 564-83.
[http://dx.doi.org/10.1093/brain/awl004] [PMID: 16399806]
Buckner RL, Carroll DC. Self-projection and the brain. Trends Cogn Sci (Regul Ed) 2007; 11(2): 49-57.
[http://dx.doi.org/10.1016/j.tics.2006.11.004] [PMID: 17188554]
Goldstein RZ, Volkow ND. Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am J Psychiatry 2002; 159(10): 1642-52.
[http://dx.doi.org/10.1176/appi.ajp.159.10.1642] [PMID: 12359667]
Chen G, Cuzon Carlson VC, Wang J, et al. Striatal involvement in human alcoholism and alcohol consumption, and withdrawal in animal models. Alcohol Clin Exp Res 2011; 35(10): 1739-48.
[http://dx.doi.org/10.1111/j.1530-0277.2011.01520.x] [PMID: 21615425]
Antinori A, Arendt G, Becker JT, et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology 2007; 69(18): 1789-99.
[http://dx.doi.org/10.1212/01.WNL.0000287431.88658.8b] [PMID: 17914061]
Chang C, Glover GH. Time-frequency dynamics of resting-state brain connectivity measured with fMRI. Neuroimage 2010; 50(1): 81-98.
[http://dx.doi.org/10.1016/j.neuroimage.2009.12.011] [PMID: 20006716]
Andrews SC, Hoy KE, Enticott PG, Daskalakis ZJ, Fitzgerald PB. Improving working memory: the effect of combining cognitive activity and anodal transcranial direct current stimulation to the left dorsolateral prefrontal cortex. Brain Stimul 2011; 4(2): 84-9.
[http://dx.doi.org/10.1016/j.brs.2010.06.004] [PMID: 21511208]
Zaehle T, Sandmann P, Thorne JD, Jäncke L, Herrmann CS. Transcranial direct current stimulation of the prefrontal cortex modulates working memory performance: combined behavioural and electrophysiological evidence. BMC Neurosci 2011; 12: 2.
[http://dx.doi.org/10.1186/1471-2202-12-2] [PMID: 21211016]
Nissim NR, O’Shea A, Indahlastari A, et al. Effects of in-Scanner Bilateral Frontal tDCS on Functional Connectivity of the Working Memory Network in Older Adults. Front Aging Neurosci 2019; 11: 51.
[http://dx.doi.org/10.3389/fnagi.2019.00051] [PMID: 30930766]
Jansen JM, Daams JG, Koeter MWJ, Veltman DJ, van den Brink W, Goudriaan AE. Effects of non-invasive neurostimulation on craving: a meta-analysis. Neurosci Biobehav Rev 2013; 37(10 Pt 2): 2472-80.
[http://dx.doi.org/10.1016/j.neubiorev.2013.07.009] [PMID: 23916527]
Trojak B, Soudry-Faure A, Abello N, et al. Efficacy of transcranial direct current stimulation (tDCS) in reducing consumption in patients with alcohol use disorders: study protocol for a randomized controlled trial. Trials 2016; 17(1): 250.
[http://dx.doi.org/10.1186/s13063-016-1363-8] [PMID: 27188795]
Emch M, Ripp I, Wu Q, Yakushev I, Koch K. Neural and Behavioral Effects of an Adaptive Online Verbal Working Memory Training in Healthy Middle-Aged Adults. Front Aging Neurosci 2019; 11: 300.
[http://dx.doi.org/10.3389/fnagi.2019.00300] [PMID: 31736741]
Fraser S, Cockcroft K. Working with memory: Computerized, adaptive working memory training for adolescents living with HIV. Child Neuropsychol J Norm Abnorm Dev Child Adolesc 2019; 9: 1-23.
Teixeira-Santos AC, Moreira CS, Magalhães R, et al. Reviewing working memory training gains in healthy older adults: A meta-analytic review of transfer for cognitive outcomes. Neurosci Biobehav Rev 2019; 103: 163-77.
[http://dx.doi.org/10.1016/j.neubiorev.2019.05.009] [PMID: 31100297]
Brito VV, Manhães AG, França AI, Marins M. Evaluation of the Working Memory Training Program for the Elderly. CoDAS 2019; 31(3) e20180089
[http://dx.doi.org/10.1590/2317-1782/20182018089] [PMID: 31188906]
Brum PS, Borella E, Carretti B, Sanches Yassuda M. Verbal working memory training in older adults: an investigation of dose response. Aging Ment Health 2020; 24(1): 81-91.
[http://dx.doi.org/10.1080/13607863.2018.1531372] [PMID: 30596450]
Khemiri L, Brynte C, Stunkel A, Klingberg T, Jayaram-Lindström N. Working Memory Training in Alcohol Use Disorder: A Randomized Controlled Trial. Alcohol Clin Exp Res 2019; 43(1): 135-46.
[http://dx.doi.org/10.1111/acer.13910] [PMID: 30462837]
Hendershot CS, Wardell JD, Vandervoort J, McPhee MD, Keough MT, Quilty LC. Randomized trial of working memory training as an adjunct to inpatient substance use disorder treatment. Psychol Addict Behav 2018; 32(8): 861-72.
[http://dx.doi.org/10.1037/adb0000415] [PMID: 30475014]

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Year: 2020
Published on: 11 June, 2020
Page: [181 - 193]
Pages: 13
DOI: 10.2174/1570162X18666200217100123
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