From Aberrant Brainwaves to Altered Plasticity: A Review of QEEG Biomarkers and Neurofeedback in the Neurobiological Landscape of ADHD
Abstract
1. Introduction
2. The Clinical Picture and Etiology of ADHD
2.1. Symptomatology and Developmental Course
2.2. The Multifactorial Etiology of ADHD
3. The Neurobiological Basis of ADHD
3.1. Genetic and Environmental Architecture
3.2. Dysregulation of Neurotransmitter Systems
3.2.1. Dopaminergic System
- The Mesocortical Pathway: This pathway projects to the prefrontal cortex. Its dysfunction is primarily associated with cognitive deficits, problems with attention, and impaired motor control;
3.2.2. Noradrenergic System
3.2.3. Other Systems
3.3. Structural and Functional Brain Alterations
3.3.1. Structural Findings
3.3.2. Functional Network Dysconnectivity
3.4. The Central Role of Impaired Neural Plasticity
4. QEEG in the Diagnosis of ADHD
4.1. The Methodology and Potential of QEEG
4.2. Characteristic Neurophysiological Patterns in ADHD
5. Potential QEEG Biomarkers for ADHD
5.1. The Theta-to-Beta Ratio (TBR): Promises and Controversies
5.2. Cross-Frequency Coupling (CFC): A Network Perspective
6. Differentiating ADHD Subtypes Based on QEEG
6.1. Classic Subtype Models
6.2. Newer Categorization Models
6.3. Synthesis of Subtype Models
7. The Application of QEEG in Neurofeedback Therapy
7.1. The Principle of Neurofeedback
- Measurement: The patient’s bioelectrical brain activity is continuously measured using EEG;
- Processing: Specialized software analyzes the incoming EEG signal in real-time and extracts key parameters, such as the amplitude of specific brainwaves in a particular area of the brain;
- Feedback: The processed information is then presented back to the patient in an accessible and engaging format, typically visual or auditory. This often takes the form of a video game, where progress and success depend on the patient’s ability to maintain the desired state of brain activity;
7.2. Brainwaves and Training Goals in ADHD Therapy
7.3. The Efficacy, Controversies, and Limitations of Neurofeedback in ADHD
7.4. A Review of Clinical Studies on the Efficacy of Neurofeedback
8. Discussion, Synthesis, and Future Directions
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
Abbreviations
ADHD | Attention-Deficit/Hyperactivity Disorder |
ASD | Autism Spectrum Disorders |
CFC | Cross-Frequency Coupling |
CNV | Copy Number Variant |
COMT | Catechol-O-Methyltransferase |
CT | Computed Tomography |
DAT1 | Dopamine Transporter 1 |
DMN | Default Mode Network |
DRD4 | Dopamine Receptor D4 |
DRD5 | Dopamine Receptor D5 |
DTI | Diffusion Tensor Imaging |
EEG | Electroencephalography |
fMRI | Functional Magnetic Resonance Imaging |
GABA | Gamma-Aminobutyric Acid |
GWAS | Genome-Wide Association Study |
HTR1B | Serotonin Receptor 1B |
IGD | Internet Gaming Disorder |
KLF | Kruppel-Like Factors |
LORETA | Low-Resolution Brain Electromagnetic Tomography |
MRI | Magnetic Resonance Imaging |
N/A | Not Applicable |
PET | Positron Emission Tomography |
QEEG | Quantitative Electroencephalography |
RCT | Randomized Controlled Trial |
SCL | Skin Conductance Level |
SN | Salience Network |
SMR | Sensorimotor Rhythm |
TBR | Theta/Beta Ratio |
TPN | Task-Positive Networks |
References
- Coelho, L.; Chaves, E.; Vasconcelos, S.; Fonteles, M.; De Sousa, F.; Viana, G. Transtorno Do Déficit de Atenção e Hiperatividade (TDAH) Na Criança: Aspectos Neurobiológicos, Diagnóstico e Conduta Terapêutica [Attention Deficit Hyperactivity Disorder (ADHD) in Children: Neurobiological Aspects, Diagnosis and Therapeutic Approach]. Acta Med. Port. 2010, 23, 689–696. [Google Scholar]
- Claussen, A.H.; Holbrook, J.R.; Hutchins, H.J.; Robinson, L.R.; Bloomfield, J.; Meng, L.; Bitsko, R.H.; O’Masta, B.; Cerles, A.; Maher, B.; et al. All in the Family? A Systematic Review and Meta-Analysis of Parenting and Family Environment as Risk Factors for Attention-Deficit/Hyperactivity Disorder (ADHD) in Children. Prev. Sci. 2024, 25, 249–271. [Google Scholar] [CrossRef] [PubMed]
- Luo, Y.; Weibman, D.; Halperin, J.M.; Li, X. A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD). Front. Hum. Neurosci. 2019, 13, 42. [Google Scholar] [CrossRef] [PubMed]
- Substance Abuse and Mental Health Services Administration (SAMHSA). DSM-5 Changes: Implications for Child Serious Emotional Disturbance; Substance Abuse and Mental Health Services Administration (SAMHSA): Rockville, MD, USA, 2016. [Google Scholar]
- Koutsoklenis, A.; Honkasilta, J. ADHD in the DSM-5-TR: What Has Changed and What Has Not. Front. Psychiatry 2023, 13, 1064141. [Google Scholar] [CrossRef]
- Kopańska, M.; Ochojska, D.; Trojniak, J.; Sarzyńska, I.; Szczygielski, J. The Role of Quantitative Electroencephalography in Diagnostic Workup of Mental Disorders. J. Physiol. Pharmacol. 2024, 75, 361–372. [Google Scholar] [CrossRef]
- Kopańska, M.; Ochojska, D.; Sarzyńska, I.; Trojniak, J.; Banaś-Ząbczyk, A.; Szczygielski, J. The Use of Quantitative Electroencephalography (Eyes Closed) to Assess the Effectiveness of Neurofeedback in Therapy in Children with Mild Autism Spectrum Disorders That Reveal Attention Deficit Disorders. Acta Neuropsychol. 2025, 23, 27–46. [Google Scholar] [CrossRef]
- Michel, C.M.; Murray, M.M. Towards the Utilization of EEG as a Brain Imaging Tool. Neuroimage 2012, 61, 371–385. [Google Scholar] [CrossRef]
- Musullulu, H. Evaluating Attention Deficit and Hyperactivity Disorder (ADHD): A Review of Current Methods and Issues. Front. Psychol. 2025, 16, 1466088. [Google Scholar] [CrossRef]
- Salari, N.; Ghasemi, H.; Abdoli, N.; Rahmani, A.; Shiri, M.H.; Hashemian, A.H.; Akbari, H.; Mohammadi, M. The Global Prevalence of ADHD in Children and Adolescents: A Systematic Review and Meta-Analysis. Ital. J. Pediatr. 2023, 49, 48. [Google Scholar] [CrossRef]
- Gawrilow, C.; Kühnhausen, J.; Schmid, J.; Stadler, G. Hyperactivity and Motoric Activity in ADHD: Characterization, Assessment, and Intervention. Front. Psychiatry 2014, 5, 171. [Google Scholar] [CrossRef]
- Faraone, S.V.; Biederman, J.; Mick, E. The Age-Dependent Decline of Attention Deficit Hyperactivity Disorder: A Meta-Analysis of Follow-up Studies. Psychol. Med. 2006, 36, 159–165. [Google Scholar] [CrossRef]
- Merikangas, K.R.; He, J.P.; Burstein, M.; Swanson, S.A.; Avenevoli, S.; Cui, L.; Benjet, C.; Georgiades, K.; Swendsen, J. Lifetime Prevalence of Mental Disorders in U.S. Adolescents: Results from the National Comorbidity Survey Replication-Adolescent Supplement (NCS-A). J. Am. Acad. Child. Adolesc. Psychiatry 2010, 49, 980–989. [Google Scholar] [CrossRef]
- Faraone, S.V.; Larsson, H. Genetics of Attention Deficit Hyperactivity Disorder. Mol. Psychiatry 2019, 24, 562–575. [Google Scholar] [CrossRef]
- Faraone, S.V.; Perlis, R.H.; Doyle, A.E.; Smoller, J.W.; Goralnick, J.J.; Holmgren, M.A.; Sklar, P. Molecular Genetics of Attention-Deficit/Hyperactivity Disorder. Biol. Psychiatry 2005, 57, 1313–1323. [Google Scholar] [CrossRef]
- Neumann, A.; Walton, E.; Alemany, S.; Cecil, C.; González, J.R.; Jima, D.D.; Lahti, J.; Tuominen, S.T.; Barker, E.D.; Binder, E.; et al. Association between DNA Methylation and ADHD Symptoms from Birth to School Age: A Prospective Meta-Analysis. Transl. Psychiatry 2020, 10, 398. [Google Scholar] [CrossRef]
- Van Mil, N.H.; Steegers-Theunissen, R.P.M.; Bouwland-Both, M.I.; Verbiest, M.M.P.J.; Rijlaarsdam, J.; Hofman, A.; Steegers, E.A.P.; Heijmans, B.T.; Jaddoe, V.W.V.; Verhulst, F.C.; et al. DNA Methylation Profiles at Birth and Child ADHD Symptoms. J. Psychiatr. Res. 2014, 49, 51–59. [Google Scholar] [CrossRef]
- Vinci, M.; Greco, D.; Treccarichi, S.; Chiavetta, V.; Figura, M.G.; Musumeci, A.; Greco, V.; Federico, C.; Calì, F.; Saccone, S. Bioinformatic Evaluation of KLF13 Genetic Variant: Implications for Neurodevelopmental and Psychiatric Symptoms. Genes 2024, 15, 1056. [Google Scholar] [CrossRef]
- Caiazzo, M.; Colucci-D’Amato, L.; Volpicelli, F.; Speranza, L.; Petrone, C.; Pastore, L.; Stifani, S.; Ramirez, F.; Bellenchi, G.C.; di Porzio, U. Krüppel-like Factor 7 Is Required for Olfactory Bulb Dopaminergic Neuron Development. Exp. Cell Res. 2011, 317, 464–473. [Google Scholar] [CrossRef]
- Lindström, K.; Lindblad, F.; Hjern, A. Preterm Birth and Attention-Deficit/Hyperactivity Disorder in Schoolchildren. Pediatrics 2011, 127, 858–865. [Google Scholar] [CrossRef]
- Zhao, J.; Xia, L. Association between Hypertensive Disorders of Pregnancy and Risk of Attention-Deficit/Hyperactivity Disorder in the Offspring: A Systematic Review and Meta-Analysis. Hypertens. Pregnancy 2022, 41, 149–158. [Google Scholar] [CrossRef]
- Li, L.; Lagerberg, T.; Chang, Z.; Cortese, S.; Rosenqvist, M.A.; Almqvist, C.; D’Onofrio, B.M.; Hegvik, T.A.; Hartman, C.; Chen, Q.; et al. Maternal Pre-Pregnancy Overweight/Obesity and the Risk of Attention-Deficit/Hyperactivity Disorder in Offspring: A Systematic Review, Metaanalysis and Quasi-Experimental Family-Based Study. Int. J. Epidemiol. 2021, 49, 857–875. [Google Scholar] [CrossRef] [PubMed]
- He, Y.; Chen, J.; Zhu, L.H.; Hua, L.L.; Ke, F.F. Maternal Smoking During Pregnancy and ADHD: Results From a Systematic Review and Meta-Analysis of Prospective Cohort Studies. J. Atten. Disord. 2020, 24, 1637–1647. [Google Scholar] [CrossRef] [PubMed]
- Rattay, K.; Robinson, L.R. Identifying Risk Factors for Attention-Deficit/Hyperactivity Disorder (ADHD): A Public Health Concern and Opportunity. Prev. Sci. 2024, 25, 195–202. [Google Scholar] [CrossRef]
- Núñez-Jaramillo, L.; Herrera-Solís, A.; Herrera-Morales, W.V. ADHD: Reviewing the Causes and Evaluating Solutions. J. Pers. Med. 2021, 11, 166. [Google Scholar] [CrossRef]
- Zhu, T.; Gan, J.; Huang, J.; Li, Y.; Qu, Y.; Mu, D. Association between Perinatal Hypoxic-Ischemic Conditions and Attention-Deficit/Hyperactivity Disorder: A Meta-Analysis. J. Child. Neurol. 2016, 31, 1235–1244. [Google Scholar] [CrossRef]
- Da Silva, B.S.; Grevet, E.H.; Silva, L.C.F.; Ramos, J.K.N.; Rovaris, D.L.; Bau, C.H.D. An Overview on Neurobiology and Therapeutics of Attention-Deficit/Hyperactivity Disorder. Discov. Ment. Health 2023, 3, 2. [Google Scholar] [CrossRef]
- Purper-Ouakil, D.; Ramoz, N.; Lepagnol-Bestel, A.-M.; Gorwood, P.; Simonneau, M. Neurobiology of Attention Deficit/Hyperactivity Disorder. Pediatr. Res. 2011, 69, 69–76. [Google Scholar] [CrossRef]
- Thapar, A. Discoveries on the Genetics of ADHD in the 21st Century: New Findings and Their Implications. Am. J. Psychiatry 2018, 175, 943–950. [Google Scholar] [CrossRef]
- Kesebir, S.; Yosmaoğlu, A. QEEG in Affective Disorder: About to Be a Biomarker, Endophenotype and Predictor of Treatment Response. Heliyon 2018, 4, e00741. [Google Scholar] [CrossRef]
- Tenke, C.E.; Kayser, J. Reference-Free Quantification of EEG Spectra: Combining Current Source Density (CSD) and Frequency Principal Components Analysis (FPCA). Clin. Neurophysiol. 2005, 116, 2826–2846. [Google Scholar] [CrossRef]
- Madureira, D.Q.M.; de Carvalho, L.A.V.; Cheniaux, E. Modelagem Neurocomputacional Do Circuito Tálamo-Cortical: Implicações Para Compreensão Do Transtorno de Défi Cit de Atenção e Hiperatividade. Arq. Neuropsiquiatr. 2007, 65, 1043–1049. [Google Scholar] [CrossRef]
- Eme, R. The Neurobiology of Behavioral Impulsivity as Expressed in the Hyperactive-Impulsive and Combined Presentations of Attention-Deficit/ Hyperactivity Disorder. SOJ Neurol. 2017, 4, 1–3. [Google Scholar] [CrossRef]
- Cortese, S. The Neurobiology and Genetics of Attention-Deficit/Hyperactivity Disorder (ADHD): What Every Clinician Should Know. Eur. J. Paediatr. Neurol. 2012, 16, 422–433. [Google Scholar] [CrossRef]
- Ji, H.S.; Paik, K.C.; Park, W.S.; Lim, M.H. No Association between the Response to Methylphenidate and DRD4 Gene Polymorphism in Korean Attention Deficit Hyperactivity Disorder: A Case Control Study. Clin. Psychopharmacol. Neurosci. 2013, 11, 13–17. [Google Scholar] [CrossRef]
- Tahir, E.; Yazgan, Y.; Cirakoglu, B.; Ozbay, F.; Waldman, I.; Asherson, P.J. Association and Linkage of DRD4 and DRD5 with Attention Deficit Hyperactivity Disorder (ADHD) in a Sample of Turkish Children. Mol. Psychiatry 2000, 5, 396–404. [Google Scholar] [CrossRef] [PubMed]
- Kirley, A.; Hawi, Z.; Daly, G.; McCarron, M.; Mullins, C.; Millar, N.; Waldman, I.; Fitzgerald, M.; Gill, M. Dopaminergic System Genes in ADHD: Toward a Biological Hypothesis. Neuropsychopharmacology 2002, 27, 607–619. [Google Scholar] [CrossRef] [PubMed]
- Prasad, C.G.; Shivappa, M.; Jain, S.; Girimaji, S.C.; Purushottam, M. Attention Deficit Hyperactivity Disorder and Dopamine D4 Receptor (DRD4) Polymorphisms in South Indian Population. Ann. Natl. Acad. Med. Sci. 2024, 60, 157–163. [Google Scholar] [CrossRef]
- Effatpanah, H.; Effatpanah, M.; Mohammadi, M.J.; Geravandi, S.; Ghadami, M.; Ahmadkhaniha, H.; Djavid, G.E.; Arabgol, F. Determination of Association between the Polymorphism in Exon 3 of Dopamine Receptor Gene Type 4 with Attention Deficit-Hyperactivity Disorder. Clin. Epidemiol. Glob. Health 2020, 8, 290–294. [Google Scholar] [CrossRef]
- Faraone, S.V.; Mick, E. Molecular Genetics of Attention Deficit Hyperactivity Disorder. Psychiatr. Clin. N. Am. 2010, 33, 159–180. [Google Scholar] [CrossRef]
- Rubia, K.; Westwood, S.; Aggensteiner, P.M.; Brandeis, D. Neurotherapeutics for Attention Deficit/Hyperactivity Disorder (ADHD): A Review. Cells 2021, 10, 2156. [Google Scholar] [CrossRef]
- Garnock-Jones, K.P.; Keating, G.M. Atomoxetine: A Review of Its Use in Attention-Deficit Hyperactivity Disorder in Children and Adolescents. Pediatr. Drugs 2009, 11, 203–226. [Google Scholar] [CrossRef]
- Kuś, J.; Saramowicz, K.; Czerniawska, M.; Wiese, W.; Siwecka, N.; Rozpędek-Kamińska, W.; Kucharska-Lusina, A.; Strzelecki, D.; Majsterek, I. Molecular Mechanisms Underlying NMDARs Dysfunction and Their Role in ADHD Pathogenesis. Int. J. Mol. Sci. 2023, 24, 12983. [Google Scholar] [CrossRef]
- De La Fuente, A.; Xia, S.; Branch, C.; Li, X. A Review of Attention-Deficit/Hyperactivity Disorder from the Perspective of Brain Networks. Front. Hum. Neurosci. 2013, 15, 192. [Google Scholar] [CrossRef]
- Curatolo, P.; D’Agati, E.; Moavero, R. The Neurobiological Basis of ADHD. Ital. J. Pediatr. 2010, 36, 79. [Google Scholar] [CrossRef]
- Loriette, C.; Ziane, C.; Ben Hamed, S. Neurofeedback for Cognitive Enhancement and Intervention and Brain Plasticity. Rev. Neurol. 2021, 177, 1133–1144. [Google Scholar] [CrossRef]
- Forero, D.A.; Arboleda, G.H.; Vasquez, R.; Arboleda, H. Candidate Genes Involved in Neural Plasticity and the Risk for Attention-Deficit Hyperactivity Disorder: A Meta-Analysis of 8 Common Variants. J. Psychiatry Neurosci. 2009, 34, 361–366. [Google Scholar]
- Biasiucci, A.; Franceschiello, B.; Murray, M.M. Electroencephalography. Curr. Biol. 2019, 29, R80–R85. [Google Scholar] [CrossRef]
- Chumachenko, S.Y.; McVoy, M. A Narrative Review and Discussion of Concepts and Ongoing Data Regarding Quantitative EEG as a Childhood Mood Disorder Biomarker. Biomark. Neuropsychiatry 2023, 8, 100060. [Google Scholar] [CrossRef]
- McVoy, M.; Aebi, M.E.; Loparo, K.; Lytle, S.; Morris, A.; Woods, N.; Deyling, E.; Tatsuoka, C.; Kaffashi, F.; Lhatoo, S.; et al. Resting-State Quantitative Electroencephalography Demonstrates Differential Connectivity in Adolescents with Major Depressive Disorder. J. Child. Adolesc. Psychopharmacol. 2019, 29, 370–377. [Google Scholar] [CrossRef]
- Dattola, S.; Morabito, F.C.; Mammone, N.; La Foresta, F. Findings about LORETA Applied to High-Density EEG—A Review. Electronics 2020, 9, 660. [Google Scholar] [CrossRef]
- Duffy, F.H.; Als, H. A Stable Pattern of EEG Spectral Coherence Distinguishes Children with Autism from Neuro-Typical Controls—A Large Case Control Study. BMC Med. 2012, 10, 64. [Google Scholar] [CrossRef] [PubMed]
- Park, J.H.; Hong, J.S.; Han, D.H.; Min, K.J.; Lee, Y.S.; Kee, B.S.; Kim, S.M. Comparison of Qeeg Findings between Adolescents with Attention Deficit Hyperactivity Disorder (ADHD) without Comorbidity and Adhd Comorbid with Internet Gaming Disorder. J. Korean Med. Sci. 2017, 32, 514–521. [Google Scholar] [CrossRef]
- Barry, R.J.; Clarke, A.R.; Johnstone, S.J. A Review of Electrophysiology in Attention-Deficit/Hyperactivity Disorder: I. Qualitative and Quantitative Electroencephalography. Clin. Neurophysiol. 2003, 114, 171–183. [Google Scholar] [CrossRef]
- Kopańska, M.; Ochojska, D.; Dejnowicz-Velitchkov, A. Diagnosing ADHD Using QEEG and Planning EEG-Biofeedback (Neurofeedback) Therapy—Pilot Studies. Med. Ogólna Nauk. Zdrowiu 2021, 27, 205–212. [Google Scholar] [CrossRef]
- Alba, G.; Pereda, E.; Mañas, S.; Méndez, L.D.; González, A.; González, J.J. Electroencephalography Signatures of Attention-Deficit/Hyperactivity Disorder: Clinical Utility. Neuropsychiatr. Dis. Treat. 2015, 11, 2755–2769. [Google Scholar] [CrossRef]
- Barry, R.J.; Clarke, A.R.; McCarthy, R.; Selikowitz, M.; Rushby, J.A.; Ploskova, E. EEG Differences in Children as a Function of Resting-State Arousal Level. Clin. Neurophysiol. 2004, 115, 402–408. [Google Scholar] [CrossRef]
- Olejarczyk, E.; Marzetti, L.; Pizzella, V.; Zappasodi, F. Comparison of Connectivity Analyses for Resting State EEG Data. J. Neural Eng. 2017, 14, 036017. [Google Scholar] [CrossRef]
- Gu, D.; Lin, A.; Lin, G. Detection of Attention Deficit Hyperactivity Disorder in Children Using CEEMDAN-Based Cross Frequency Symbolic Convergent Cross Mapping. Expert. Syst. Appl. 2023, 226, 120105. [Google Scholar] [CrossRef]
- Bong, S.H.; Kim, J.W. The Role of Quantitative Electroencephalogram in the Diagnosis and Subgrouping of Attention-Deficit/Hyperactivity Disorder. J. Korean Acad. Child Adolesc. Psychiatry 2021, 32, 85–92. [Google Scholar] [CrossRef]
- Barry, R.J.; Clarke, A.R. Spontaneous EEG Oscillations in Children, Adolescents, and Adults: Typical Development, and Pathological Aspects in Relation to AD/HD. J. Psychophysiol. 2009, 23, 157–173. [Google Scholar] [CrossRef]
- Barry, R.J.; Clarke, A.R.; Johnstone, S.J.; McCarthy, R.; Selikowitz, M. Electroencephalogram θ/β Ratio and Arousal in Attention-Deficit/Hyperactivity Disorder: Evidence of Independent Processes. Biol. Psychiatry 2009, 66, 398–401. [Google Scholar] [CrossRef]
- Snyder, S.M.; Rugino, T.A.; Hornig, M.; Stein, M.A. Integration of an EEG Biomarker with a Clinician’s ADHD Evaluation. Brain Behav. 2015, 5, e00330. [Google Scholar] [CrossRef]
- Doesburg, S.M.; Vinette, S.A.; Cheung, M.J.; Pang, E.W. Theta-Modulated Gamma-Band Synchronization among Activated Regions during a Verb Generation Task. Front. Psychol. 2012, 3, 195. [Google Scholar] [CrossRef]
- Clarke, A.R.; Barry, R.J.; McCarthy, R.; Selikowitz, M. EEG-Defined Subtypes of Children with Attention-Deficit/Hyperactivity Disorder. Clin. Neurophysiol. 2001, 112, 2098–2105. [Google Scholar] [CrossRef]
- Bussalb, A.; Collin, S.; Barthélemy, Q.; Ojeda, D.; Bioulac, S.; Blasco-Fontecilla, H.; Brandeis, D.; Purper Ouakil, D.; Ros, T.; Mayaud, L. Is There a Cluster of High Theta-Beta Ratio Patients in Attention Deficit Hyperactivity Disorder? Clin. Neurophysiol. 2019, 130, 1387–1396. [Google Scholar] [CrossRef]
- Clarke, A.R.; Barry, R.J.; Dupuy, F.E.; Heckel, L.D.; McCarthy, R.; Selikowitz, M.; Johnstone, S.J. Behavioural Differences between EEG-Defined Subgroups of Children with Attention-Deficit/Hyperactivity Disorder. Clin. Neurophysiol. 2011, 122, 1333–1341. [Google Scholar] [CrossRef]
- Byeon, J.; Choi, T.Y.; Won, G.H.; Lee, J.; Kim, J.W. A Novel Quantitative Electroencephalography Subtype with High Alpha Power in ADHD: ADHD or Misdiagnosed ADHD? PLoS ONE 2020, 15, e0242566. [Google Scholar] [CrossRef]
- Krain, A.L.; Castellanos, F.X. Brain Development and ADHD. Clin. Psychol. Rev. 2006, 26, 433–444. [Google Scholar] [CrossRef]
- Anderson, J.L.; Bolden, J. The Role of Executive Functions in Depression and Attention-Deficit/Hyperactivity Disorder (ADHD) Symptomatology. University of Tennessee Honors Thesis Projects, University of Tennessee, Knoxville, TN, USA, 2018; pp. 2–19. [Google Scholar]
- Ahire, N.; Awale, R.N.; Wagh, A. Comprehensive Review of EEG Data Classification Techniques for ADHD Detection Using Machine Learning and Deep Learning. Rom. J. Pediatr. 2023, 72, 57–66. [Google Scholar] [CrossRef]
- Ogrim, G.; Kropotov, J.D. Predicting Clinical Gains and Side Effects of Stimulant Medication in Pediatric Attention-Deficit/Hyperactivity Disorder by Combining Measures From QEEG and ERPs in a Cued GO/NOGO Task. Clin. EEG Neurosci. 2019, 50, 34–43. [Google Scholar] [CrossRef]
- Michelini, G.; Norman, L.J.; Shaw, P.; Loo, S.K. Treatment Biomarkers for ADHD: Taking Stock and Moving Forward. Transl. Psychiatry 2022, 12, 444. [Google Scholar] [CrossRef] [PubMed]
- Arns, M.; De Ridder, S.; Strehl, U.; Breteler, M.; Coenen, A. Efficacy of Neurofeedback Treatment in ADHD: The Effects on Inattention, Impulsivity and Hyperactivity: A Meta-Analysis. Clin. EEG Neurosci. 2009, 40, 180–189. [Google Scholar] [CrossRef] [PubMed]
- Fernández, B.; Barros, J.; Machado, E.; Maldonado, E.; Moreira, A.R.; Gomes, H.J. Neurofeedback treatment for attention-deficit/hyperactivity disorder in adults. Eur. Psychiatry 2024, 67, S621. [Google Scholar] [CrossRef]
- Gevensleben, H.; Moll, G.H.; Rothenberger, A.; Heinrich, H. The Usage of Neurofeedback in Children with ADHD: The Method and Its Evaluation. Prax. Kinderpsychol. Kinderpsychiatr. 2011, 60, 666–676. [Google Scholar] [CrossRef]
- Ros, T.; Baars, B.J.; Lanius, R.A.; Vuilleumier, P. Tuning Pathological Brain Oscillations with Neurofeedback: A Systems Neuroscience Framework. Front. Hum. Neurosci. 2014, 8, 1008. [Google Scholar] [CrossRef]
- Gaume, A.; Vialatte, A.; Mora-Sánchez, A.; Ramdani, C.; Vialatte, F.B. A Psychoengineering Paradigm for the Neurocognitive Mechanisms of Biofeedback and Neurofeedback. Neurosci. Biobehav. Rev. 2016, 68, 891–910. [Google Scholar] [CrossRef]
- Alegria, A.A.; Wulff, M.; Brinson, H.; Barker, G.J.; Norman, L.J.; Brandeis, D.; Stahl, D.; David, A.S.; Taylor, E.; Giampietro, V.; et al. Real-Time FMRI Neurofeedback in Adolescents with Attention Deficit Hyperactivity Disorder. Hum. Brain Mapp. 2017, 38, 3190–3209. [Google Scholar] [CrossRef]
- Marx, A.M.; Ehlis, A.C.; Furdea, A.; Holtmann, M.; Banaschewski, T.; Brandeis, D.; Rothenberger, A.; Gevensleben, H.; Freitag, C.M.; Fuchsenberger, Y.; et al. Near-Infrared Spectroscopy (NIRs) Neurofeedback as a Treatment for Children with Attention Deficit Hyperactivity Disorder (ADHD)—A Pilot Study. Front. Hum. Neurosci. 2015, 8, 1038. [Google Scholar] [CrossRef]
- Zuberer, A.; Minder, F.; Brandeis, D.; Drechsler, R. Mixed-Effects Modeling of Neurofeedback Self-Regulation Performance: Moderators for Learning in Children with ADHD. Neural Plast. 2018, 2018, 15. [Google Scholar] [CrossRef]
- Gong, A.; Nan, W.; Yin, E.; Jiang, C.; Fu, Y. Efficacy, Trainability, and Neuroplasticity of SMR vs. Alpha Rhythm Shooting Performance Neurofeedback Training. Front. Hum. Neurosci. 2020, 14, 94. [Google Scholar] [CrossRef]
- Meisel, V.; Servera, M.; Garcia-Banda, G.; Cardo, E.; Moreno, I. Neurofeedback and Standard Pharmacological Intervention in ADHD: A Randomized Controlled Trial with Six-Month Follow-Up. Biol. Psychol. 2013, 94, 12–21. [Google Scholar] [CrossRef]
- Tosti, B.; Corrado, S.; Mancone, S.; Di Libero, T.; Rodio, A.; Andrade, A.; Diotaiuti, P. Integrated use of biofeedback and neurofeedback techniques in treating pathological conditions and improving performance: A narrative review. Front. Neurosci. 2024, 18, 1358481. [Google Scholar] [CrossRef] [PubMed]
- Markiewicz, R. The Use of EEG Biofeedback/Neurofeedback in Psychiatric Rehabilitation|Zastosowanie EEG Biofeedback/Neurofeedback w Rehabilitacji Psychiatrycznej. Psychiatr. Pol. 2017, 51, 1095–1106. [Google Scholar] [CrossRef] [PubMed]
- Marcuse, L.V.; Fields, M.C.; Yoo, J. Podstawy EEG z Miniatlasem, 2nd ed.; Domitrz, I., Sobieszek, A., Eds.; Edra Urban & Partner: Wrocław, Poland, 2017. [Google Scholar]
- Yuan, H.; Young, K.D.; Phillips, R.; Zotev, V.; Misaki, M.; Bodurka, J. Resting-State Functional Connectivity Modulation and Sustained Changes after Real-Time Functional Magnetic Resonance Imaging Neurofeedback Training in Depression. Brain Connect. 2014, 4, 690–701. [Google Scholar] [CrossRef]
- Scheinost, D.; Stoica, T.; Wasylink, S.; Gruner, P.; Saksa, J.; Pittenger, C.; Hampson, M. Resting State Functional Connectivity Predicts Neurofeedback Response. Front. Behav. Neurosci. 2014, 8, 338. [Google Scholar] [CrossRef]
- Trousselard, M.; Canini, F.; Claverie, D.; Cungi, C.; Putois, B.; Franck, N. Cardiac Coherence Training to Reduce Anxiety in Remitted Schizophrenia, a Pilot Study. Appl. Psychophysiol. Biofeedback 2016, 41, 61–69. [Google Scholar] [CrossRef]
- Giedzinska-Simons, A. On Integrating an Integrative: Implications for Implementing a Biofeedback Program into an Inpatient Rehabilitation Hospital. Biofeedback 2014, 42, 115–120. [Google Scholar] [CrossRef]
- Escolano, C.; Navarro-Gil, M.; Garcia-Campayo, J.; Congedo, M.; Minguez, J. The Effects of Individual Upper Alpha Neurofeedback in ADHD: An Open-Label Pilot Study. Appl. Psychophysiol. Biofeedback 2014, 39, 193–202. [Google Scholar] [CrossRef]
- Aru, J.; Axmacher, N.; Do Lam, A.T.A.; Fell, J.; Elger, C.E.; Singer, W.; Melloni, L. Local Category-Specific Gamma Band Responses in the Visual Cortex Do Not Reflect Conscious Perception. J. Neurosci. 2012, 32, 14909–14914. [Google Scholar] [CrossRef]
- Cortese, S.; Ferrin, M.; Brandeis, D.; Holtmann, M.; Aggensteiner, P.; Daley, D.; Santosh, P.; Simonoff, E.; Stevenson, J.; Stringaris, A.; et al. Neurofeedback for Attention-Deficit/Hyperactivity Disorder: Meta-Analysis of Clinical and Neuropsychological Outcomes From Randomized Controlled Trials. J. Am. Acad. Child. Adolesc. Psychiatry 2016, 55, 444–455. [Google Scholar] [CrossRef]
- Enriquez-Geppert, S.; Smit, D.; Pimenta, M.G.; Arns, M. Neurofeedback as a Treatment Intervention in ADHD: Current Evidence and Practice. Curr. Psychiatry Rep. 2019, 21, 46. [Google Scholar] [CrossRef] [PubMed]
- Saif, M.G.M.; Sushkova, L. Clinical Efficacy of Neurofeedback Protocols in Treatment of Attention Deficit/Hyperactivity Disorder (ADHD): A Systematic Review. Psychiatry Res. Neuroimaging 2023, 335, 111723. [Google Scholar] [CrossRef] [PubMed]
- Thibault, R.T.; MacPherson, A.; Lifshitz, M.; Roth, R.R.; Raz, A. Neurofeedback with FMRI: A Critical Systematic Review. Neuroimage 2018, 172, 786–807. [Google Scholar] [CrossRef]
- Alino, M.; Gadea, M.; Espert, R. A Critical View of Neurofeedback Experimental Designs: Sham and Control as Necessary Conditions. Int. J. Neurol. Neurother. 2016, 3, 041. [Google Scholar] [CrossRef]
- Flückiger, C.; Del, A.C.; Wampold, B.E.; Horvath, A.O. The Alliance in Adult Psychotherapy: A Meta-Analytic Synthesis. Psychotherapy 2018, 55, 316–340. [Google Scholar] [CrossRef]
- Van Dongen-Boomsma, M.; Vollebregt, M.A.; Slaats-Willemse, D.; Buitelaar, J.K. A Randomized Placebo-Controlled Trial of Electroencephalographic (EEG) Neurofeedback in Children with Attention-Deficit/Hyperactivity Disorder. J. Clin. Psychiatry 2013, 74, 821–827. [Google Scholar] [CrossRef]
- Hasslinger, J.; Jonsson, U.; Bölte, S. Immediate and Sustained Effects of Neurofeedback and Working Memory Training on Cognitive Functions in Children and Adolescents with ADHD: A Multi-Arm Pragmatic Randomized Controlled Trial. J. Atten. Disord. 2022, 26, 1492–1506. [Google Scholar] [CrossRef]
- Schönenberg, M.; Wiedemann, E.; Schneidt, A.; Scheeff, J.; Logemann, A.; Keune, P.M.; Hautzinger, M. Neurofeedback, Sham Neurofeedback, and Cognitive-Behavioural Group Therapy in Adults with Attention-Deficit Hyperactivity Disorder: A Triple-Blind, Randomised, Controlled Trial. Lancet Psychiatry 2017, 4, 673–684. [Google Scholar] [CrossRef]
- Arnold, L.E.; Arns, M.; Barterian, J.; Bergman, R.; Black, S.; Conners, C.K.; Connor, S.; Dasgupta, S.; deBeus, R.; Higgins, T.; et al. Double-Blind Placebo-Controlled Randomized Clinical Trial of Neurofeedback for Attention-Deficit/Hyperactivity Disorder With 13-Month Follow-Up. J. Am. Acad. Child. Adolesc. Psychiatry 2021, 60, 841–855. [Google Scholar] [CrossRef]
Category of Factors | Example Risk Factors | Source |
---|---|---|
Genetic Factors | Functional variants or combinations of multiple genes (no single “ADHD gene” exists) | [1,14] |
The dopamine transporter gene (DAT1) and the dopamine D4 receptor gene (DRD4) | [15] | |
Epigenetic Factors | Differences in DNA methylation profiles in DRD4 and DAT1, linked to childhood ADHD symptoms. | [16,17] |
DNA methylation in KLF13 | [18,19] | |
Epigenetic changes in the DRD4 and DRD5 genes | [16,17] | |
Prenatal and Perinatal Factors | Preterm birth | [20] |
Low or very low birth weight | ||
Preeclampsia during pregnancy | [10,21] | |
Maternal hypertension | ||
Maternal overweight or obesity | [22] | |
Maternal exposure to smoking and illicit drugs during pregnancy | [23,24] | |
Perinatal hypoxia | [25,26] | |
Postnatal inflammation in the infant | [25] | |
Environmental and Family Factors | Negative parental reactions and harsh disciplinary practices | [2] |
Excessive exposure to media and screen time | [2] |
Subtype Name | Key QEEG Characteristics | Clinical Interpretation |
---|---|---|
Maturational Lag Type | An excess of slow Theta waves and a deficit of fast Beta waves | This pattern is considered evidence of slower brain development and immaturity of the central nervous system compared to neurotypical peers |
Thalamocortical Dysrhythmia (“Hypoarousal”) Type | Elevated power in both Theta and Beta bands, which translates to an increased TBR | This pattern is sometimes linked to dysfunction in the thalamocortical loop and may also be present in other psychiatric disorders, making it non-specific to ADHD |
“Hyperarousal” Type | Characterized by over-activity and increased power of Beta waves | This profile may be clinically associated with a tendency toward aggressive outbursts, anger, and general irritability |
Excess Alpha Waves Subtype | Increased power of Alpha waves | This profile is strongly associated with the co-occurrence of internalizing disorders, such as anxiety, depression, or emotional dysregulation. It is thought to reflect the presence of a comorbid condition rather than “pure” ADHD |
Subtype Name | Key QEEG Characteristics | Clinical Interpretation |
---|---|---|
Group A | Elevated relative Delta power with lower Theta activity | Consistent with the maturational lag type; this has been corroborated by MRI studies indicating smaller cortico-striatal regions |
Group B | Elevated relative power of slow Alpha waves | Alpha waves are associated with arousal; their elevated power correlates with symptoms of depression and anxiety, which can mimic the symptoms of ADHD |
Group C | Elevated Theta power with insufficient Alpha power | Consistent with the classic “hypoarousal” type |
Group D | Increased absolute power of fast Alpha and Beta waves | This is likely a measurement artifact. An excessive or insufficient amount of electrode paste can distort the measurement of absolute power. The relative power in this group was within the normal range |
Wave | Range [Hz] | Function | ADHD Manifestation | Training Goal | Source |
---|---|---|---|---|---|
Alpha | 8–12 | The Alpha rhythm dominates in a state of relaxed wakefulness with eyes closed, but is also linked to focus and creativity. Increasing its amplitude can lower anxiety levels | Although a deficit of alpha waves is often observed, in subtypes with comorbid anxiety, its power may be elevated | Dependent on the patient’s profile; may involve reinforcing alpha to improve relaxation capabilities and reduce anxiety | [87,88,89] |
Theta | 4–8 | This rhythm is associated with memory processes and association, but also with states of dreaminess and reduced concentration | An excess of theta waves in the frontal lobes is a key correlate of problems with concentration and attention | The primary goal in many ADHD protocols is to inhibit (decrease) the amplitude of Theta waves | [90] |
Beta | >12 | Beta waves are linked to alertness, concentration, logical thinking, and the processing of external stimuli. A specific sub-band, the SMR rhythm, is associated with calm focus and motor control | A deficit of Beta waves is often observed, particularly in the SMR band | A fundamental element of therapy is to reinforce (increase) the amplitude of SMR and/or Beta1 (15–18 Hz) waves. This training aims to improve concentration and reduce hyperactivity and impulsivity | [83,84,85,91,92] |
SMR | 12–15 | ||||
Delta | 0.5–4 | Delta is the rhythm of deep, restorative sleep; its presence during wakefulness is indicative of pathology | N/A 1 | Not typically a direct training target in standard protocols | [84,85] |
Gamma | >30 Hz | Gamma is associated with higher cognitive processes and the integration of information | N/A |
NCT ID | Study Title | Enrollment | Interventions | Primary Outcome Measure(s) | Study Status | Age | Sex | Study URL |
---|---|---|---|---|---|---|---|---|
NCT00723684 | Efficacy of EEG Neurofeedback in the Treatment of Children with ADHD | 63 | Placebo EEG Neurofeedback; EEG-Neurofeedback | Change in ADHD-IV Rating Scale | Completed | 8 to 12 years | All | https://clinicaltrials.gov/study/NCT00723684, accessed on 16 June 2025 |
NCT00886483 | Neurofeedback Treatment for Children with ADHD | 39 | Active neurofeedback; Sham neurofeedback | Change in the ADHD Rating Scale (ADHD-RS) | Completed | 7 to 11 years | All | https://clinicaltrials.gov/study/NCT00886483, accessed on 16 June 2025 |
NCT01692548 | Neurofeedback Training in Children with ADHD | 36 | Neurofeedback | Improvement in inattention and hyperactivity/impulsivity symptoms as measured by the FBB-HKS questionnaire | Completed | 7 to 9 years | All | https://clinicaltrials.gov/study/NCT01692548, accessed on 16 June 2025 |
NCT01841151 | Neurofeedback in the Treatment of ADHD in Children and Adolescents | 202 | SCP training; Live Z-score training; WM training | Change in the parent-rated ADHD symptoms scale (FBB-ADHD) | Completed | 7 to 13 years | All | https://clinicaltrials.gov/study/NCT01841151, accessed on 16 June 2025 |
NCT01879644 | Combined Treatment (Neurofeedback and Stimulants) in ADHD | 120 | Neurofeedback; Methylphenidate; Parent Education; Standard Treatment | Change in teacher ratings of ADHD symptoms | Active, Not Recruiting | 7 to 10 years | All | https://clinicaltrials.gov/study/NCT01879644, accessed on 16 June 2025 |
NCT01883765 | Neurofeedback and Metacognitive Training in Adults with ADHD | 118 | Active neurofeedback; Sham neurofeedback; Metacognitive Training | Change in Conners’ Adult ADHD Rating Scale (CAARS-O) | Completed | 18 to 50 years | All | https://clinicaltrials.gov/study/NCT01883765, accessed on 16 June 2025 |
NCT02251743 | A Randomized Controlled Trial of Neurofeedback for ADHD | 144 | Neurofeedback treatment | Change in the ADHD Rating Scale—Parent Version | Completed | 7 to 10 years | All | https://clinicaltrials.gov/study/NCT02251743, accessed on 16 June 2025 |
NCT02358941 | A Comparison of Neurofeedback and Computerized Cognitive Training | 102 | Neurofeedback training; Computerized cognitive training | Change in the Swanson, Nolan, and Pelham (SNAP-IV) scale | Completed | 7 to 12 years | All | https://clinicaltrials.gov/study/NCT02358941, accessed on 16 June 2025 |
NCT02572180 | Combined Biofeedback and Neurofeedback Training in ADHD | 90 | EMG-based biofeedback training; NIRS-based neurofeedback training | Change in ADHD Rating Scale IV (ADHD-RS-IV) | Unknown | 7 to 15 years | All | https://clinicaltrials.gov/study/NCT02572180, accessed on 16 June 2025 |
NCT02754336 | Comparison of Working Memory Training with Neurofeedback in Children with ADHD | 6 | Cogmed Robomemo, working memory training; Othmer, neurofeedback | Change in working memory test scores | Unknown | 8 to 12 years | All | https://clinicaltrials.gov/study/NCT02754336, accessed on 16 June 2025 |
NCT02778360 | Neurofeedback as an Adjunctive Treatment for ADHD | 179 | Neurofeedback NFT; Methylphenidate MPH | Change in ADHD-RS-IV (Parent Version) | Recruiting | 6 to 12 years | All | https://clinicaltrials.gov/study/NCT02778360, accessed on 16 June 2025 |
NCT04112082 | Efficacy of a Mobile Neurofeedback System in Adults with ADHD | 70 | Mobile neurofeedback; Treatment as usual | Change in the Adult ADHD Self-Report Scale (ASRS-SK) | Recruiting | 18 to 60 years | All | https://clinicaltrials.gov/study/NCT04112082, accessed on 16 June 2025 |
NCT04408521 | Efficacy of EEG Neurofeedback for the Treatment of Adult ADHD | 5 | NEUROFEEDBACK; CONTROL | Change in clinician rating of ADHD symptoms | Unknown | 18 to 50 years | All | https://clinicaltrials.gov/study/NCT04408521, accessed on 16 June 2025 |
NCT04469335 | Mobile Neurofeedback in Children with ADHD (m-NFB-ADHD) | 165 | Mobile neurofeedback; Sham mobile neurofeedback; Medication + mobile neurofeedback; Medication + sham mobile neurofeedback | Change in the parent-rated ADHD scale (FBB-HKS) | Unknown | 7 to 12 years | All | https://clinicaltrials.gov/study/NCT04469335, accessed on 16 June 2025 |
NCT05635318 | Quantitative EEG Neurofeedback as an Add-on Therapy for ADHD | 102 | FDA-approved medications for ADHD plus Quantitative EEG Neurofeedback; FDA-approved medications for ADHD | Change in the ADHD-RS-V rating scale | Unknown | 6 to 12 years | All | https://clinicaltrials.gov/study/NCT05635318, accessed on 16 June 2025 |
NCT06142786 | Individualized Alpha Frequency-based Neurofeedback in ADHD | 60 | Enhancement of individualized upper alpha band and suppression of lower alpha band; Sham neurofeedback | Change in the Swanson, Nolan and Pelham (SNAP) scale | Unknown | 8 to 12 years | All | https://clinicaltrials.gov/study/NCT06142786, accessed on 16 June 2025 |
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Kopańska, M.; Trojniak, J. From Aberrant Brainwaves to Altered Plasticity: A Review of QEEG Biomarkers and Neurofeedback in the Neurobiological Landscape of ADHD. Cells 2025, 14, 1339. https://doi.org/10.3390/cells14171339
Kopańska M, Trojniak J. From Aberrant Brainwaves to Altered Plasticity: A Review of QEEG Biomarkers and Neurofeedback in the Neurobiological Landscape of ADHD. Cells. 2025; 14(17):1339. https://doi.org/10.3390/cells14171339
Chicago/Turabian StyleKopańska, Marta, and Julia Trojniak. 2025. "From Aberrant Brainwaves to Altered Plasticity: A Review of QEEG Biomarkers and Neurofeedback in the Neurobiological Landscape of ADHD" Cells 14, no. 17: 1339. https://doi.org/10.3390/cells14171339
APA StyleKopańska, M., & Trojniak, J. (2025). From Aberrant Brainwaves to Altered Plasticity: A Review of QEEG Biomarkers and Neurofeedback in the Neurobiological Landscape of ADHD. Cells, 14(17), 1339. https://doi.org/10.3390/cells14171339