Abstract
Methadone as the most prevalent opioid substitution medication has been shown to influence the neurophysiological functions among heroin addicts. However, there is no firm conclusion on acute neuroelectrophysiological changes among methadone-treated subjects as well as the effectiveness of methadone in restoring brain electrical abnormalities among heroin addicts. This study aims to investigate the acute and short-term effects of methadone administration on the brain’s electrophysiological properties before and after daily methadone intake over 10 weeks of treatment among heroin addicts. EEG spectral analysis and single-trial event-related potential (ERP) measurements were used to investigate possible alterations in the brain’s electrical activities, as well as the cognitive attributes associated with MMN and P3. The results confirmed abnormal brain activities predominantly in the beta band and diminished information processing ability including lower amplitude and prolonged latency of cognitive responses among heroin addicts compared to healthy controls. In addition, the alteration of EEG activities in the frontal and central regions was found to be associated with the withdrawal symptoms of drug users. Certain brain regions were found to be influenced significantly by methadone intake; acute effects of methadone induction appeared to be associative to its dosage. The findings suggest that methadone administration affects cognitive performance and activates the cortical neuronal networks, resulting in cognitive responses enhancement which may be influential in reorganizing cognitive dysfunctions among heroin addicts. This study also supports the notion that the brain’s oscillation powers and ERPs can be utilized as neurophysiological indices for assessing the addiction treatment traits.
Similar content being viewed by others
References
Anokhin AP, Vedeniapin AB, Sirevaag EJ, Bauer LO, O'Connor SJ, Kuperman S, Porjesz B, Reich T, Begleiter H, Polich J, Rohrbaugh JW (2000) The P300 brain potential is reduced in smokers. Psychopharmacology 149:409–413. https://doi.org/10.1007/s002130000387
Ball JC, Ross A (1991) The effectiveness of methadone maintenance treatment: patients, programs, services, and outcome. Springer-Verlag Publishing
Başar E, Schürmann M (1994) Functional aspects of evoked alpha and theta responses in humans and cats. Biol Cybern 72:175–183
Bauer LO (2001) CNS recovery from cocaine, cocaine and alcohol, or opioid dependence: a P300 study. Clin Neurophysiol 112:1508–1515. https://doi.org/10.1016/s1388-2457(01)00583-1
Blankertz B, Lemm S, Treder M, Haufe S, Müller K-R (2011) Single-trial analysis and classification of ERP components — a tutorial. NeuroImage 56:814–825. https://doi.org/10.1016/j.neuroimage.2010.06.048
Bonnet MH, Arand DL (2001) Impact of activity and arousal upon spectral EEG parameters. Physiol Behav 74:291–298
Bostanov V, Kotchoubey B (2006) The t-CWT: a new ERP detection and quantification method based on the continuous wavelet transform and Student’s t-statistics. Clin Neurophysiol 117:2627–2644. https://doi.org/10.1016/j.clinph.2006.08.012
Brickman AM et al (2005) Category and letter verbal fluency across the adult lifespan: relationship to EEG theta power. Arch Clin Neuropsychol 20:561–573
Clarke JG, Stein MD, McGarry KA, Gogineni A (2001) Interest in smoking cessation among injection drug users. Am J Addict 10:159–166
Clemmey P, Brooner R, Chutuape MA, Kidorf M, Stitzer M (1997) Smoking habits and attitudes in a methadone maintenance treatment population. Drug Alcohol Depend 44:123–132
Costa L, Bauer L (1997) Quantitative electroencephalographic differences associated with alcohol, cocaine, heroin and dual-substance dependence. Drug Alcohol Depend 46:87–93
Darke S, Sims J, McDonald S, Wickes W (2000) Cognitive impairment among methadone maintenance patients. Addiction 95:687–695
Davydov DM, Polunina AG (2004) Heroin abusers’ performance on the Tower of London Test relates to the baseline EEG alpha2 mean frequency shifts. Prog Neuro-Psychopharmacol Biol Psychiatry 28:1143–1152. https://doi.org/10.1016/j.pnpbp.2004.06.006
Delorme A, Makeig S (2004) EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis. J Neurosci Methods 134:9–21
Delorme A, Sejnowski T, Makeig S (2007) Enhanced detection of artifacts in EEG data using higher-order statistics and independent component analysis. Neuroimage 34:1443–1449
Dien J, Spencer KM, Donchin E (2003) Localization of the event-related potential novelty response as defined by principal components analysis Cognitive Brain Research 17:637–650
Domino EF (2003) Effects of tobacco smoking on electroencephalographic, auditory evoked and event related potentials. Brain Cogn 53:66–74. https://doi.org/10.1016/s0278-2626(03)00204-5
Donchin E (1981) Surprise!… surprise? Psychophysiology 18:493–513
Donchin E, Coles MG (1988) Is the P300 component a manifestation of context updating? Behav Brain Sci 11:357–374
Doppelmayr M, Klimesch W, Schwaiger J, Auinger P, Winkler T (1998) Theta synchronization in the human EEG and episodic retrieval. Neurosci Lett 257:41–44
Duncan CC, Barry RJ, Connolly JF, Fischer C, Michie PT, Näätänen R, Polich J, Reinvang I, van Petten C (2009) Event-related potentials in clinical research: guidelines for eliciting, recording, and quantifying mismatch negativity, P300, and N400. Clin Neurophysiol 120:1883–1908
Dyer KR, White JM (1997) Patterns of symptom complaints in methadone maintenance patients. Addiction 92:1445–1455
Fingelkurts AA, Fingelkurts AA, Kivisaari R, Autti T, Borisov S, Puuskari V, Jokela O, Kähkönen S (2006) Increased local and decreased remote functional connectivity at EEG alpha and beta frequency bands in opioid-dependent patients. Psychopharmacology 188:42–52. https://doi.org/10.1007/s00213-006-0474-4
Fingelkurts AA, Fingelkurts AA, Kivisaari R, Autti T, Borisov S, Puuskari V, Jokela O, Kähkönen S (2007a) Opioid withdrawal results in an increased local and remote functional connectivity at EEG alpha and beta frequency bands. Neurosci Res 58:40–49. https://doi.org/10.1016/j.neures.2007.01.011
Fingelkurts AA, Kähkönen S, Fingelkurts AA, Kivisaari R, Borisov S, Puuskari V, Jokela O, Autti T (2007b) Composition of EEG oscillations and their temporal characteristics: methadone treatment. Int J Psychophysiol 64:130–140. https://doi.org/10.1016/j.ijpsycho.2007.01.001
Fingelkurts A, Kähkönen S, Fingelkurts AA, Kivisaari R, Borisov S, Puuskari V, Jokela O, Autti T (2008) Reorganization of the composition of brain oscillations and their temporal characteristics during opioid withdrawal. J Psychopharmacol 22:270–284. https://doi.org/10.1177/0269881108089810
Fingelkurts AA, Fingelkurts AA, Kivisaari R, Autti T, Borisov S, Puuskari V, Jokela O, Kähkönen S (2009) Methadone restores local and remote EEG functional connectivity in opioid-dependent patients. Int J Neurosci 119:1469–1493. https://doi.org/10.1080/00207450903007985
Fisher DJ, Daniels R, Jaworska N, Knobelsdorf A, Knott VJ (2012a) Effects of acute nicotine administration on behavioral and neural (EEG) correlates of working memory in non-smokers. Brain Res 1429:72–81. https://doi.org/10.1016/j.brainres.2011.10.029
Fisher DJ, Daniels R, Jaworska N, Knobelsdorf A, Knott VJ (2012b) Effects of acute nicotine administration on resting EEG in nonsmokers. Exp Clin Psychopharmacol 20:71–75. https://doi.org/10.1037/a0025221
Franken IH, Stam CJ, Hendriks VM, van den Brink W (2004) Electroencephalographic power and coherence analyses suggest altered brain function in abstinent male heroin-dependent patients. Neuropsychobiology 49:105–110
Gatt JM, Kuan SA, Dobson-Stone C, Paul RH, Joffe RT, Kemp AH, Gordon E, Schofield PR, Williams LM (2008) Association between BDNF Val66Met polymorphism and trait depression is mediated via resting EEG alpha band activity. Biol Psychol 79:275–284
Gorricho MD, Uson JRV (2008) QEEG mapping and methadone. Eur J Psychiatry 22:29–37
Greenwald MK, Roehrs TA (2005) Mu-opioid self-administration vs passive administration in heroin abusers produces differential EEG activation. Neuropsychopharmacology 30:212–221. https://doi.org/10.1038/sj.npp.1300596
Gritz ER, Shiffman SM, Jarvik ME, Haber J, Dymond AM, Coger R, Charuvastra V, Schlesinger J (1975) Physiological and psychological effects of methadone in man. Arch Gen Psychiatry 32:237–242
Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD (1987) Two new rating scales for opiate withdrawal. Am J Drug Alcohol Abuse 13:293–308
Handy TC (2005) Event-related potentials: a methods handbook. MIT press
Houlihan ME, Pritchard WS, Robinson JH (1996) Faster P300 latency after smoking in visual but not auditory oddball tasks. Psychopharmacology 123:231–238
Houlihan ME, Pritchard WS, Robinson JH (2001) Effects of smoking/nicotine on performance and event-related potentials during a short-term memory scanning task. Psychopharmacology 156:388–396. https://doi.org/10.1007/s002130100751
Jung T-P, Makeig S, Westerfield M, Townsend J, Courchesne E, Sejnowski TJ (2001) Analysis and visualization of single-trial event-related potentials Human Brain Mapping 14:166–185 https://doi.org/10.1002/hbm.1050
Kish SJ, Kalasinsky KS, Derkach P, Schmunk GA, Guttman M, Ang L, Adams V, Furukawa Y, Haycock JW (2001) Striatal dopaminergic and serotonergic markers in human heroin users. Neuropsychopharmacology 24:561–567
Kivisaari R, Lehtinen R, Autti T, Puuskari V, Jokela O, Ahveninen J, Rapeli P, Kähkönen S (2007) Impaired pre-attentive auditory processing in opioid dependence with and without benzodiazepine co-dependence revealed by combined magnetoencephalography and electroencephalography. Prog Neuro-Psychopharmacol Biol Psychiatry 31:1378–1386. https://doi.org/10.1016/j.pnpbp.2007.06.001
Klimesch W, Doppelmayr M, Russegger H, Pachinger T, Schwaiger J (1998) Induced alpha band power changes in the human EEG and attention. Neurosci Lett 244:73–76
Klimesch W, Doppelmayr M, Hea W, Schwaiger J, Röhm D, Gruber W, Hutzler F (2001) Theta band power changes in normal and dyslexic children. Clin Neurophysiol 112:1174–1185
Knott V, Bosman M, Mahoney C, Ilivitsky V, Quirt K (1999) Transdermal nicotine: single dose effects on mood, EEG, performance, and event-related potentials. Pharmacol Biochem Behav 63:253–261
Knyazeva M, Vil’davskii V (1986) Correspondence of spectral characteristics of EEG and regional blood circulation in 9-14 years old children. Physiologija Cheloveka (Human Physiology) 12:387–394
Kraus N, McGee T, Carrell TD, Sharma A (1995) Neurophysiologic bases of speech discrimination. Ear Hear 16:19–37. https://doi.org/10.1097/00003446-199502000-00003
Levin ED, McClernon FJ, Rezvani AH (2006) Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization. Psychopharmacology 184:523–539
Li Y, Ma Z, Lu W, Li Y (2006) Automatic removal of the eye blink artifact from EEG using an ICA-based template matching approach. Physiol Meas 27:425–436
Liddell BJ et al (2007) Rates of decline distinguish Alzheimer's disease and mild cognitive impairment relative to normal aging: integrating cognition and brain function. J Integr Neurosci 6:141–174
Logemann HNA, Bocker KBE, Deschamps PKH, Kemner C, Kenemans JL (2014a) The effect of enhancing cholinergic neurotransmission by nicotine on EEG indices of inhibition in the human brain. Pharmacol Biochem Behav 122:89–96. https://doi.org/10.1016/j.pbb.2014.03.019
Logemann HNA, Bocker KBE, Deschamps PKH, Kemner C, Kenemans JL (2014b) The effect of the augmentation of cholinergic neurotransmission by nicotine on EEG indices of visuospatial attention. Behav Brain Res 260:67–73. https://doi.org/10.1016/j.bbr.2013.11.044
Lopes da Silva FH, Vos J, Mooibroek J, Van Rotterdam A (1980) Relative contributions of intracortical and thalamo-cortical processes in the generation of alpha rhythms, revealed by partial coherence analysis. Electroencephalogr Clin Neurophysiol 50:449–456
Lubman DI, Allen NB, Peters LA, Deakin JFW (2007) Electrophysiological evidence of the motivational salience of drug cues in opiate addiction. Psychol Med 37:1203–1209. https://doi.org/10.1017/s0033291707009932
Lubman DI, Yucel M, Kettle JWL, Scaffidi A, MacKenzie T, Simmons JG, Allen NB (2009) Responsiveness to drug cues and natural rewards in opiate addiction associations with later heroin use. Arch Gen Psychiatry 66:205–213
Marques-Teixeira JE, Barbosa MFS (2005) Emotional states and informational brain processing in drug addicts free of drugs: an ERPs study. Int J Psychiatry Clin Pract 9:213–220. https://doi.org/10.1080/13651500510029101
McEvoy LK, Pellouchoud E, Smith ME, Gevins A (2001) Neurophysiological signals of working memory in normal aging. Cogn Brain Res 11:363–376
Mintzer MZ, Stitzer ML (2002) Cognitive impairment in methadone maintenance patients. Drug Alcohol Depend 67:41–51
Morie KP, Garavan H, Bell RP, De Sanctis P, Krakowski MI, Foxe JJ (2014) Intact inhibitory control processes in abstinent drug abusers (II): a high-density electrical mapping study in former cocaine and heroin addicts. Neuropharmacology 82:151–160. https://doi.org/10.1016/j.neuropharm.2013.02.023
Motlagh F, Tang S, Motlagh O (2012) Combination of continuous and discrete wavelet coefficients in single-trial P300 detection. IEEE EMBS Conference on Biomedical Engineering and Sciences (IECBES), 2012 IEEE:954–959
Motlagh F, Tang S, Motlagh O (2013) Optimal accuracy and runtime trade-off in wavelet based single-trial P300 detection. IEEE International Conference on Signal and Image Processing Applications (ICSIPA), 2013 IEEE:343–348
Motlagh F, Ibrahim F, Menke JM, Rashid R, Seghatoleslam T, Habil H (2016) Neuroelectrophysiological approaches in heroin addiction research: a review of literatures. J Neurosci Res 94:297–309
Neuhaus A, Bajbouj M, Kienast T, Kalus P, von Haebler D, Winterer G, Gallinat J (2006) Persistent dysfunctional frontal lobe activation in former smokers. Psychopharmacology 186:191–200. https://doi.org/10.1007/s00213-006-0366-7
O'Donnell BF, Faux SF, McCarley R, Kimble MO, Salisbury DF, Nestor PG, Kikinis R, Jolesz FA, Shenton ME (1995) Increased rate of P300 latency prolongation with age in schizophrenia: electrophysiological evidence for a neurodegenerative process. Arch Gen Psychiatry 52:544–549
Pangman VC, Sloan J, Guse L (2000) An examination of psychometric properties of the mini-mental state examination and the standardized mini-mental state examination: implications for clinical practice. Appl Nurs Res 13:209–213
Papageorgiou C, Liappas I, Asvestas P, Vasios C, Matsopoulos GK, Nikolaou C, Nikita KS, Uzunoglu N, Rabavilas A (2001) Abnormal P600 in heroin addicts with prolonged abstinence elicited during a working memory test. Neuroreport 12:1773–1778. https://doi.org/10.1097/00001756-200106130-00051
Papageorgiou C, Rabavilas A, Liappasa L, Stefanis C (2003) Do obsessive-compulsive patients and abstinent heroin addicts share a common psychophysiological mechanism? Neuropsychobiology 47:1–11. https://doi.org/10.1159/000068868
Papageorgiou CC, Liappas IA, Ventouras EM, Nikolaou CC, Kitsonas EN, Uzunoglu NK, Rabavilas AD (2004) Long-term abstinence syndrome in heroin addicts: indices of P300 alterations associated with a short memory task. Prog Neuro-Psychopharmacol Biol Psychiatry 28:1109–1115. https://doi.org/10.1016/j.pnpbp.2004.05.049
Pernet CR, Sajda P, Rousselet GA (2011) Single-trial analyses: why bother? Front Psychol 2:322
Pfurtscheller G, Klimesch W (1990) Topographical display and interpretation of event-related desynchronization during a visual-verbal task. Brain Topogr 3:85–93
Polich J (1998) P300 clinical utility and control of variability. J Clin Neurophysiol 15:14–33
Polunina AG, Davydov DM (2004) EEG spectral power and mean frequencies in early heroin abstinence. Prog Neuro-Psychopharmacol Biol Psychiatry 28:73–82. https://doi.org/10.1016/j.pnpbp.2003.09.022
Polunina AG, Davydov DM (2006) EEG correlates of Wechsler adult intelligence scale. Int J Neurosci 116:1231–1248. https://doi.org/10.1080/00207450600550287
Polunina AG, Davydov DM, Kozlov AA (2007) Brain disintegration in heroin addicts: the natural course of the disease and the effects of methadone treatment Heroin Addiction and Related Clinical Problems 17
Porjesz B, Almasy L, Edenberg HJ, Wang K, Chorlian DB, Foroud T, Goate A, Rice JP, O'Connor SJ, Rohrbaugh J, Kuperman S, Bauer LO, Crowe RR, Schuckit MA, Hesselbrock V, Conneally PM, Tischfield JA, Li TK, Reich T, Begleiter H (2002) Linkage disequilibrium between the beta frequency of the human EEG and a GABAA receptor gene locus. Proc Natl Acad Sci 99:3729–3733
Prosser J, Cohen LJ, Steinfeld M, Eisenberg D, London ED, Galynker II (2006) Neuropsychological functioning in opiate-dependent subjects receiving and following methadone maintenance treatment. Drug Alcohol Depend 84:240–247
Quiroga RQ, Garcia H (2003) Single-trial event-related potentials with wavelet denoising. Clin Neurophysiol 114:376–390
Rapeli P, Kivisaari R, Autti T, Kahkonen S, Puuskari V, Jokela O, Kalska H (2006) Cognitive function during early abstinence from opioid dependence: a comparison to age, gender, and verbal intelligence matched controls. Bmc Psychiatry 6. https://doi.org/10.1186/1471-244x-6-9
Roemer RA, Cornwell A, Dewart D, Jackson P, Ercegovac DV (1995) Quantitative electroencephalographic analyses in cocaine-preferring polysubstance abusers during abstinence. Psychiatry Res 58:247–257
Rousselet GA, Foxe JJ, Bolam JP (2016) A few simple steps to improve the description of group results in neuroscience. Eur J Neurosci 44:2647–2651. https://doi.org/10.1111/ejn.13400
Roth A, Roesch-Ely D, Bender S, Weisbrod M, Kaiser S (2007) Increased event-related potential latency and amplitude variability in schizophrenia detected through wavelet-based single trial analysis International Journal of Psychophysiology 66:244–254 https://doi.org/10.1016/j.ijpsycho.2007.08.005
Samar VJ, Bopardikar A, Rao R, Swartz K (1999) Wavelet Analysis of Neuroelectric Waveforms: A Conceptual Tutorial Brain and Language 66:7–60 https://doi.org/10.1006/brln.1998.2024
Schlögl A, Keinrath C, Zimmermann D, Scherer R, Leeb R, Pfurtscheller G (2007) A fully automated correction method of EOG artifacts in EEG recordings. Clin Neurophysiol 118:98–104
Shah D, Impey D, Chique-Alfonzo M, Fisher D, Lorenzo-Lopez L, Knott V (2011) Neural effects of acute nicotinic treatment on visual spatial attention in non-smokers. Pharmacol Biochem Behav 100:228–236. https://doi.org/10.1016/j.pbb.2011.08.018
Sheehan DV et al (1998) The mini-international neuropsychiatric interview (MINI): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59:22–33
Simpson DD, Sells SB (1982) Effectiveness of treatment for drug abuse: an overview of the DARP research program. Adv Alcohol Subst Abuse 2:7–29
Singh SM, Basu D, Kohli A, Prabhakar S (2009) Auditory P300 event-related potentials and neurocognitive functions in opioid dependent men and their brothers. Am J Addict 18:198–205. https://doi.org/10.1080/10550490902786975
Sommer W, Matt J (1990) Awareness of P300-related cognitive processes: a signal detection approach. Psychophysiology 27:575–585. https://doi.org/10.1111/j.1469-8986.1990.tb01980.x
Specka M, Finkbeiner T, Lodemann E, Leifert K, Kluwig J, Gastpar M (2000) Cognitive-motor performance of methadone-maintained patients. Eur Addict Res 6:8–19
Stam C (2000) Brain dynamics in theta and alpha frequency bands and working memory performance in humans. Neurosci Lett 286:115–118
Stefanics G, Kremláček J, Czigler I (2014) Visual mismatch negativity: a predictive coding view. Front Hum Neurosci 8
Tomberg C, Desmedt JE (1998) Human perceptual processing: inhibition of transient prefrontal-parietal 40 Hz binding at P300 onset documented in non-averaged cognitive brain potentials. Neurosci Lett 255:163–166. https://doi.org/10.1016/S0304-3940(98)00740-X
Wang GY, Wouldes TA, Kydd R, Jensen M, Russell BR (2014) Neuropsychological performance of methadone-maintained opiate users. J Psychopharmacol 0269881114538541
Wang GY, Kydd R, Wouldes TA, Jensen M, Russell BR (2015) Changes in resting EEG following methadone treatment in opiate addicts. Clin Neurophysiol 126:943–950
Whitford TJ, Rennie CJ, Grieve SM, Clark CR, Gordon E, Williams LM (2007) Brain maturation in adolescence: concurrent changes in neuroanatomy and neurophysiology. Hum Brain Mapp 28:228–237
Xu N, Gao X, Hong B, Miao X, Gao S, Yang F (2004) BCI competition 2003-data set IIb: enhancing P 300 wave detection using ICA-based subspace projections for BCI applications. IEEE Trans Biomed Eng 51:1067–1072
Yang B, Yang SY, Zhao L, Yin LH, Liu X, An SS (2009) Event-related potentials in a Go/Nogo task of abnormal response inhibition in heroin addicts. Sci China C Life Sci 52:780–788. https://doi.org/10.1007/s11427-009-0106-4
Acknowledgments
We would like to acknowledge and thank the University of Malaya and Ministry of Higher Education for providing High Impact Research Grant, account codes E000007-20001 to fund this project. This research was also supported by the Special Prime Minister’s project (Project No. 66-02-03-0061/oracle 8150061).
Author information
Authors and Affiliations
Contributions
All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: FM, FI, RR, and HH. Acquisition of data: FM, RR. Analysis and interpretation of data: FEM and FI. Drafting of the manuscript: FEM, FI, TS. Critical revision of the manuscript for important intellectual content: NS, TS. Obtained funding: HH. Study supervision: FI, HH.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no competing interests.
Additional information
Highlights
• Acute effects of methadone administration on the brain’s electrophysiological properties
• EEG spectral analysis and single-trial ERP measurements were utilized in this study
• Methadone enhances the cognitive responses and alternates the brain spectral oscillations
Rights and permissions
About this article
Cite this article
Motlagh, F., Ibrahim, F., Rashid, R. et al. Acute effects of methadone on EEG power spectrum and event-related potentials among heroin dependents. Psychopharmacology 235, 3273–3288 (2018). https://doi.org/10.1007/s00213-018-5035-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-018-5035-0