Decoding Self-Regulation in Substance Use Disorders: Machine Learning and LORETA Neurofeedback at Precuneus
DOI:
https://doi.org/10.15540/nr.13.1.91Keywords:
EEG, neurofeedback, machine learning, Artificial intelligence, learning, substance use disordersAbstract
Substance use disorders (SUD) remain among the most treatment-resistant conditions, particularly in incarcerated populations. Despite decades of neuropsychological models, few approaches capture the dynamic, network-level self-regulation deficits observed in SUD. In this study, 63 incarcerated individuals completed 20 sessions of LORETA neurofeedback targeting alpha (8–13 Hz) at the left precuneus. Pre–post EEG current source density (CSD) and Personality Assessment Inventory (PAI) scores were analyzed. A Random Forest classifier was trained on spectral CSD features and behavioral deltas, with Shapley Additive Explanation (SHAP) values used to interpret model contributions. Results showed significant alpha increases at the trained ROI, accompanied by posterior-to-frontal energy redistribution and functional asymmetry. Notably, both alpha synchronization and desynchronization predicted behavioral improvement, with an overall PAI effect size of d = 0.85. Regression and PCA confirmed directional reorganization and subgroup differentiation. Cohen’s d analysis revealed frequency-specific effects in alpha and low beta bands. Machine learning (ML) revealed that changes in posterior and frontal regions of interest (ROI) were differentially predictive of treatment response, and Reliable Change Index (RCI) identified responders with physiological and behavioral concordance. These findings challenge static trait-based models of addiction and suggest that rhythmic neurofeedback and ML interpretation can uncover emergent regulatory subtypes. This work proposes a shift from amplitude-based training to network-informed modulation as a foundation for scalable, individualized SUD interventions.
References
Baldwin, D. R., Cannon, R., Fischer, S., & Kivisto, K. (2011). The inverse of psychopathology: A Loreta EEG and cortisol examination. Journal of Neurotherapy, 15(4), 374–388. https://doi.org/10.1080/10874208.2011.623095
Barry, R. J., Clarke, A. R., Johnstone, S. J., Magee, C. A., & Rushby, J. A. (2007). EEG differences between eyes-closed and eyes-open resting conditions. Clinical Neurophysiology, 118(12), 2765–2773. https://doi.org/10.1016/j.clinph.2007.07.028
Başar, E., Başar-Eroglu, C., Karakaş, S., & Schürmann, M. (2001). Gamma, alpha, delta, and theta oscillations govern cognitive processes. International Journal of Psychophysiology, 39(2–3), 241–248. https://doi.org/10.1016/s0167-8760(00)00145-8
Bassett, D. S., & Sporns, O. (2017). Network neuroscience. Nature Neuroscience, 20(3), 353–364. https://doi.org/10.1038/nn.4502
Bazanova, O. M., & Vernon, D. (2014). Interpreting EEG alpha activity. Neuroscience & Biobehavioral Reviews, 44, 94–110. https://doi.org/10.1016/j.neubiorev.2013.05.007
Belenko, S., & Peugh, J. (2005). Estimating drug treatment needs among state prison inmates. Drug and Alcohol Dependence, 77(3), 269–281. https://doi.org/10.1016/j.drugalcdep.2004.08.023
Bell, A. N., Moss, D., & Kallmeyer, R. J. (2019). Healing the neurophysiological roots of trauma: A controlled study examining LORETA z-score neurofeedback and HRV biofeedback for chronic PTSD. NeuroRegulation, 6(2), 54–70. https://doi.org/10.15540/nr.6.2.54
Breiman, L. (2001). Random forests. Machine Learning, 45(1), 5–32. https://doi.org/10.1023/A:1010933404324
Brewer, J. A., Garrison, K. A., & Whitfield-Gabrieli, S. (2013). What about the “self” is processed in the posterior cingulate cortex? Frontiers in Human Neuroscience, 7, Article 647. https://doi.org/10.3389/fnhum.2013.00647
Buckner, R. L., Andrews-Hanna, J. R., & Schacter, D. L. (2008). The brain’s default network. Annals of the New York Academy of Sciences, 1124(1), 1–38. https://doi.org/10.1196/annals.1440.011
Cannon, R. L. (2009). Functional connectivity of EEG LORETA in cortical core components of the self and the default network (DNt) of the brain. [PhD dissertation, University of Tennessee]. https://trace.tennessee.edu/utk_graddiss/571
Cannon, R. L. (2014). Parietal foci for attention-deficit/hyperactivity disorder: Targets for LORETA neurofeedback with outcomes. Biofeedback, 42(2), 47–57. https://doi.org/10.5298/1081-5937-42.2.01
Cannon, R. L. (2025). Quantifying self-regulation: Neuroevolutionary insights from precuneus alpha modulation via LORETA neurofeedback. NeuroRegulation, 12(2), 65–81. https://doi.org/10.15540/nr.12.2.65
Cannon, R. L., Baldwin, D. R., Diloreto, D. J., Phillips, S. T., Shaw, T. L., & Levy, J. J. (2014). LORETA neurofeedback in the precuneus: Operant conditioning in basic mechanisms of self-regulation. Clinical EEG and Neuroscience, 45(4), 238–248. https://doi.org/10.1177/1550059413512796
Cannon, R. L., Baldwin, D. R., Shaw, T. L., Diloreto, D. J., Phillips, S. M., Scruggs, A. M., & Riechel, B. D. (2012). Reliability of quantitative EEG (qEEG) measures and LORETA current source density at 30 days. Neuroscience Letters, 518(1), 27–31. https://doi.org/10.1016/j.neulet.2012.04.035
Cannon, R., Lubar, J., & Baldwin, D. (2008). Self-perception and experiential schemata in the addicted brain. Applied and Psychophysiology Biofeedback, 33(4), 223–238. https://doi.org/10.1007/s10484-008-9067-9
Cannon, R., Lubar, J., Thornton, K., Wilson, S., & Congedo, M. (2004). Limbic beta activation and LORETA: Can hippocampal and related limbic activity be recorded and changes visualized using LORETA in an affective memory condition? Journal of Neurotherapy, 8(4), 5–24. https://doi.org/10.1300/J184v08n04_02
Cannon, R. L., Mills, C., Geroux, M., Zhart, L. A., Boluyt, K., Webber, R., & Cook, D. (2025). LORETA neurofeedback at precuneus: A standard approach for use in incarcerated populations with substance use problems. NeuroRegulation, 12(3), 213–233. https://doi.org/10.15540/nr.12.3.213
Cavanagh, J. F., & Frank, M. J. (2014). Frontal theta as a mechanism for cognitive control. Trends in Cognitive Sciences, 18(8), 414–421. https://doi.org/10.1016/j.tics.2014.04.012
Cavanna, A. E., & Trimble, M. R. (2006). The precuneus: A review of its functional anatomy and behavioural correlates. Brain, 129(3), 564–583. https://doi.org/10.1093/brain/awl004
Coan, J. A., & Allen, J. J. B. (2004). Frontal EEG asymmetry as a moderator and mediator of emotion. Biological Psychology, 67(1–2), 7–50. https://doi.org/10.1016/j.biopsycho.2004.03.002
Croen, L. A., Grether, J. K., Yoshida, C. K., Odouli, R., & Hendrick, V. (2011). Antidepressant use during pregnancy and childhood autism spectrum disorders. Archives of General Psychiatry, 68(11), 1104–1112. https://doi.org/10.1001/archgenpsychiatry.2011.73
Davidson, R. J. (2004). What does the prefrontal cortex “do” in affect: Perspectives on frontal EEG asymmetry research. Biological Psychology, 67(1–2), 219–233. https://doi.org/10.1016/j.biopsycho.2004.03.008
Drysdale, A. T., Grosenick, L., Downar, J., Dunlop, K., Mansouri, F., Meng, Y., Fetcho, R. N., Zebley, B., Oathes, D. J., Etkin, A., Schatzberg, A. F., Sudheimer, K., Keller, J., Mayberg, H. S., Gunning, F. M., Alexopoulos, G. S., Fox, M. D., Pascual-Leone, A., Voss, H. U. ... & Liston, C. (2017). Resting-state connectivity biomarkers define neurophysiological subtypes of depression. Nature Medicine, 23(1), 28–38. https://doi.org/10.1038/nm.4246
Dwyer, D. B., Falkai, P., & Koutsouleris, N. (2018). Machine learning approaches for clinical psychology and psychiatry. Annual Review of Clinical Psychology, 14, 91–118. https://doi.org/10.1146/annurev-clinpsy-032816-045037
Enriquez-Geppert, S., Huster, R. J., & Herrmann, C. S. (2017). EEG-neurofeedback as a tool to modulate cognition and behavior: A review tutorial. Frontiers in Human Neuroscience, 11, Article 51. https://doi.org/10.3389/fnhum.2017.00051
Elliott, M. L., Romer, A., Knodt, A. R., & Hariri, A. R. (2018). A connectome-wide functional signature of transdiagnostic risk for mental illness. Biological Psychiatry, 84(6), 452–459. https://doi.org/10.1016/j.biopsych.2018.03.012
Friston, K. (2010). The free-energy principle: A unified brain theory? Nature Reviews Neuroscience, 11(2), 127–138. https://doi.org/10.1038/nrn2787
Gentile, S. (2010). Neurodevelopmental effects of prenatal exposure to psychotropic medications. Depression and Anxiety, 27(7), 675–686. https://doi.org/10.1002/da.20706
Gibson, B. C., Vakhtin, A., Clark, V. P., Abbott, C. C., & Quinn, D. K. (2022). Revisiting hemispheric asymmetry in mood regulation: Implications for rTMS for major depressive disorder. Brain Sciences, 12(1), Article 112. https://doi.org/10.3390/brainsci12010112
Gigerenzer, G. (2004). Mindless statistics. The Journal of Socio-Economics, 33(5), 587–606. https://doi.org/10.1016/j.socec.2004.09.033
Grace, A. A. (1991). Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: A hypothesis for the etiology of schizophrenia. Neuroscience, 41(1), 1–24. https://doi.org/10.1016/0306-4522(91)90196-U
Gusnard, D. A., & Raichle, M. E. (2001). Searching for a baseline: Functional imaging and the resting human brain. Nature Reviews Neuroscience, 2(10), 685–694. https://doi.org/10.1038/35094500
Hammond, D. C. (2011). What is neurofeedback: An update. Journal of Neurotherapy, 15(4), 305–336. https://doi.org/10.1080/10874208.2011.623090
Haugg, A., Sladky, R., Skouras, S., McDonald, A., Craddock, C., Kirschner, M., Herdener, M., Koush, Y., Papoutsi, M., Keynan, J. N., Hendler, T., Cohen Kadosh, K., Zich, C., MacInnes, J., Adcock, R. A., Dickerson, K., Chen, N. K., Young, K., Bodurka, J., Yao, S., … Scharnowski, F. (2020). Can we predict real-time fMRI neurofeedback learning success from pretraining brain activity? Human Brain Mapping, 41(14), 3839–3854. https://doi.org/10.1002/hbm.25089
Huster, R. J., Enriquez-Geppert, S., Lavallee, C. F., Falkenstein, M., & Herrmann, C. S. (2013). Electroencephalography of response inhibition tasks: Functional networks and cognitive contributions. International Journal of Psychophysiology, 87(3), 217–233. https://doi.org/10.1016/j.ijpsycho.2012.08.001
Insel, T. R., Cuthbert, B. N., Garvey, M., Heinssen, R., Pine, D. S., Quinn, K., Sanislow, C., & Wang, P. (2010). Research domain criteria (RDoC): Toward a new classification framework for research on mental disorders. American Journal of Psychiatry, 167(7), 748–751. https://doi.org/10.1176/appi.ajp.2010.09091379
Ioannidis, J. P. A. (2018). The challenge of reforming nutritional epidemiologic research. JAMA, 320(10), 969–970. https://doi.org/10.1001/jama.2018.11025
Jacobson, N. S., & Truax, P. (1991). Clinical significance: A statistical approach to defining meaningful change in psychotherapy research. Journal of Consulting and Clinical Psychology, 59(1), 12–19. https://doi.org/10.1037/0022-006X.59.1.12
Jensen, O., & Mazaheri, A. (2010). Shaping functional architecture by oscillatory alpha activity: Gating by inhibition. Frontiers in Human Neuroscience, 4, Article 186. https://doi.org/10.3389/fnhum.2010.00186
Kapur, S., Phillips, A. G., & Insel, T. R. (2012). Why has it taken so long for biological psychiatry to develop clinical tests and what to do about it? Molecular Psychiatry, 17(12), 1174–1179. https://doi.org/10.1038/mp.2012.105
Kayser, J., & Tenke, C. E. (2015). Issues and considerations for using the scalp surface Laplacian in EEG/ERP research: A tutorial review. International Journal of Psychophysiology, 97(3), 189–209. https://doi.org/10.1016/j.ijpsycho.2015.04.012
Kelley, L., Strunk, W., Cannon, R., & Leighton, J. (2019). EEG source localization and attention differences between children exposed to drugs in utero and those with attention-deficit/hyperactivity disorder: A pilot study. NeuroRegulation, 6(1), 23–37. https://doi.org/10.15540/nr.6.1.23
Kendler, K. S., Jacobson, K. C., Prescott, C. A., & Neale, M. C. (2003). Specificity of genetic and environmental risk factors for use and abuse/dependence of cannabis, cocaine, hallucinogens, sedatives, stimulants, and opiates. American Journal of Psychiatry, 160(4), 687–695. https://doi.org/10.1176/appi.ajp.160.4.687
Koc, D., Tiemeier, H., Stricker, B. H., Muetzel, R. L., Hillegers, M., & El Marroun, H. (2023). Prenatal antidepressant exposure and offspring brain morphologic trajectory. JAMA Psychiatry, 80(12), 1208–1217. https://doi.org/10.1001/jamapsychiatry.2023.3161
Koponen, A. M., Nissinen, N.-M., Gissler, M., Autti-Rämö, I., Sarkola, T., & Kahila, H. (2020). Prenatal substance exposure, adverse childhood experiences and diagnosed mental and behavioral disorders – A longitudinal register-based matched cohort study in Finland. SSM - Population Health, 11, Article 100625. https://doi.org/10.1016/j.ssmph.2020.100625
Klimesch, W. (1999). EEG alpha and theta oscillations reflect cognitive and memory performance: A review and analysis. Brain Research Reviews, 29(2–3), 169–195. https://doi.org/10.1016/S0165-0173(98)00056-3
Knyazev, G. G. (2013). EEG correlates of self-referential processing. Frontiers in Human Neuroscience, 7, Article 264. https://doi.org/10.3389/fnhum.2013.00264
Leech, R., & Sharp, D. J. (2014). The role of the posterior cingulate cortex in cognition and disease. Brain, 137(1), 12–32. https://doi.org/10.1093/brain/awt162
Lundberg, S. M., & Lee, S.-I. (2017). A unified approach to interpreting model predictions. In Advances in neural information processing systems (Vol. 30). https://doi.org/10.48550/arXiv.1705.07874
Menon, V. (2011). Large-scale brain networks and psychopathology: A unifying triple network model. Trends in Cognitive Sciences, 15(10), 483–506. https://doi.org/10.1016/j.tics.2011.08.003
Mericle, A. A., Casaletto, K., Knoblach, D., Brooks, A. C., & Carise, D. (2010). Drug policy by popular sovereignty. Journal of Drug Issues, 40(4), 819–839. https://doi.org/10.1177/002204261004000404
Micoulaud-Franchi, J. A., & Fovet, T. (2016). Neurofeedback: Time needed for a promising non-pharmacological therapeutic method. The Lancet Psychiatry, 3(9), Article e16. https://doi.org/10.1016/S2215-0366(16)30189-4
Mitchell, D. J., McNaughton, N., Flanagan, D., & Kirk, I. J. (2008). Frontal-midline theta from the perspective of hippocampal “theta.” Progress in Neurobiology, 86(3), 156–185. https://doi.org/10.1016/j.pneurobio.2008.09.005
Morey, L. C. (1991). Personality Assessment Inventory: Professional manual. Psychological Assessment Resources.
Mumola, C. J., & Karberg, J. C. (2006). Drug use and dependence, state and federal prisoners, 2004 (NCJ 213530). U.S. Department of Justice, Bureau of Justice Statistics.
Nixon, S. J., & Lewis, B. (2020). Brain structure and function in recovery. Alcohol Research: Current Reviews, 40(3), Article 04. https://doi.org/10.35946/arcr.v40.3.04
Northoff, G., Heinzel, A., de Greck, M., Bermpohl, F., Dobrowolny, H., & Panksepp, J. (2006). Self-referential processing in our brain—A meta-analysis of imaging studies on the self. NeuroImage, 31(1), 440–457. https://doi.org/10.1016/j.neuroimage.2005.12.002
Oberlander, T. F., Reebye, P., Misri, S., Papsdorf, M., Kim, J., & Grunau, R. E. (2007). Externalizing and attentional behaviors in children of depressed mothers treated with a selective serotonin reuptake inhibitor antidepressant during pregnancy. Archives of Pediatrics & Adolescent Medicine, 161(1), 22–29. https://doi.org/10.1001/archpedi.161.1.22
Open Science Collaboration. (2015). Estimating the reproducibility of psychological science. Science, 349(6251), Article aac4716. https://doi.org/10.1126/science.aac4716
Pascual-Marqui, R. D., Michel, C. M., & Lehmann, D. (1994). Low resolution electromagnetic tomography: A new method for localizing electrical activity in the brain. International Journal of Psychophysiology, 18(1), 49–65. https://doi.org/10.1016/0167-8760(84)90014-x
Pascual-Marqui, R. D. (2002). Standardized low-resolution brain electromagnetic tomography (sLORETA): Technical details. Methods and Findings in Experimental and Clinical Pharmacology, 24(Suppl D), 5–12.
Pascual-Marqui, R. D., Esslen, M., Kochi, K., & Lehmann, D. (2002). Functional imaging with low-resolution brain electromagnetic tomography (LORETA): A review. Methods and Findings in Experimental and Clinical Pharmacology, 24 (Suppl C), 91–95.
Peniston, E. G., & Kulkosky, P. J. (1989). Alpha–theta brainwave training and beta-endorphin levels in alcoholics. Alcoholism: Clinical and Experimental Research, 13(2), 271–279. https://doi.org/10.1111/j.1530-0277.1989.tb00325.x
Riha, C. (2021). Developing individual neurofeedback: Latent class modeling of responder trajectories in alpha-band training [Doctoral dissertation]. University of Zurich.
Ros, T., Enriquez-Geppert, S., Zotev, V., Young, K. D., Wood, G., Whitfield-Gabrieli, S., Wan, F., Vuilleumier, P., Vialatte, F., Van De Ville, D., Todder, D., Surmeli, T., Sulzer, J. S., Strehl, U., Sterman, M. B., Steiner, N. J., Sorger, B., Soekadar, S. R., Sitaram, R., … Thibault, R. T. (2020). Consensus on the reporting and experimental design of clinical and cognitive-behavioural neurofeedback studies (CRED-nf checklist). Brain, 143(6), 1674–1685. https://doi.org/10.1093/brain/awaa009
Scheeringa, R., Petersson, K. M., Oostenveld, R., Norris, D. G., Hagoort, P., & Bastiaansen, M. C. M. (2008). Trial-by-trial coupling between EEG and BOLD identifies networks related to alpha and theta EEG power increases during working memory maintenance. NeuroImage, 44(3), 1224–1238. https://doi.org/10.1016/j.neuroimage.2008.08.041
Sitaram, R., Ros, T., Stoeckel, L., Haller, S., Scharnowski, F., Lewis-Peacock, J., Weiskopf, N., Blefari, M. L., Rana, M., Oblak, E., Birbaumer, N., & Sulzer, J. (2017). Closed-loop brain training: The science of neurofeedback. Nature Reviews Neuroscience, 18(2), 86–100. https://doi.org/10.1038/nrn.2016.164
Zhang, L., Qin, K., Pan, N., Xu, H., & Gong, Q. (2025). Shared and distinct patterns of default mode network in major depressive disorder and bipolar disorder: A comparative meta-analysis. Journal of Affective Disorders, 368, 23–32. https://doi.org/10.1016/j.jad.2024.09.021
Zhou, Y., Dougherty, J. H. Jr., Hubner, K. F., Bai, B., Cannon, R. L., & Hutson, R. K. (2008). Abnormal connectivity in the posterior cingulate and hippocampus in early Alzheimer’s disease and mild cognitive impairment. Alzheimer’s & Dementia, 4(4), 265–270. https://doi.org/10.1016/j.jalz.2008.04.006
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