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What is ADHD?

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder, that is among the most frequent diseases within child and adolescent psychiatry, with a prevalence of about 5-7% worldwide. Subthreshold ADHD is common in the population, with an estimated prevalence of approximately 10%.
ADHD is associated with lower quality of life, reducing or impair social, academic, or occupational functioning. Worse academic performance, lower rates of high school graduation, issues with interpersonal relationships, impulsive risk-seeking behaviors create a lot of problems for children with ADHD, their parents, and society.

ADHD is characterized by the heterogeneity of presentations, which may take opposite forms, such as

- predominantly inattentive (child fails to give close attention to details, makes careless mistakes; has trouble holding attention on tasks; doesn't seem to listen when spoken to directly; doesn't follow through on instructions and fails to finish the task; avoids, dislikes, or is reluctant to do tasks that require mental effort over a long period of time; often loses things; is easily distracted and forgetful in daily activities),

- predominantly hyperactive/impulsive (fidgets with or taps hands or feet or squirms in seat; leaves seat in situations when remaining seated is expected; unable to play or take part in leisure activities quietly; is often "on the go," acting as if "driven by a motor"; talks excessively; blurts out an answer before a question has been completed; often interrupts or intrudes on others (e.g., butts into conversations or games),

- combined presentation (both criteria fulfilled).

Behavioral symptoms are outside the limits of normal variation expected for the individual's age and level of intellectual functioning.

Neither blood analyses nor instrumental methods сan reveal ADHD. The Diagnostic and Statistical Manual of Mental Disorders, 5th edition and the International Classification of Diseases, edition 11 define ADHD according to behavioral criteria, based on observation and on informant reports.

ADHD is characterized by frequent comorbidity and overlap with other neurodevelopmental and mental disorders. The most frequent comorbidities are sleep disorders (up to 70%), learning and developmental coordination disorders (up to 50%), depression and anxiety disorders (up to 45%), Tourette's syndrome (20%), enuresis (17%), autism spectrum disorder (15%), obsessive compulsive disorder (5%), high risk of developing epilepsy (3x more frequent in ADHD than in typically developing children).

Nearly 60% of patients diagnosed in childhood continue to exhibit symptoms in adulthood. Universal ADHD prevalence in adults is estimated to lie at 2.8%, with higher rates in high-income (3.6%) than in low-income (1.4%) countries.

ADHD is associated with a variety of risks regarding daily functioning and social adaptation. Adolescents with ADHD show more school refusal and grade retention, earlier and more frequent use of marijuana, tobacco, and other drugs, earlier sexual engagement, and more frequent teenage pregnancy. In adults' occupational outcomes are also negatively affected by ADHD, with higher rates of unemployment, frequent job switching, and overall financial problems. The number of jobs in a given period is higher than in individuals without ADHD. There is an increased rate of separations and divorces. Individuals with ADHD show a higher prevalence of traffic accidents (speeding, driving after consumption of alcohol, or driving without a license) compared to individuals without ADHD. ADHD is associated with an increased risk for legal problems, convictions, and incarcerations. Criminal behavior starts earlier than in individuals without ADHD and the risk for recidivistic offending is increased.

Various treatment approaches aiming to reduce ADHD core symptoms have been evaluated: pharmacological treatments (psychostimulants and non-stimulants); cognitive behavioral and psychosocial treatments; noninvasive brain stimulation; neurofeedback.

Psychostimulants (including methylphenidate and amphetamine) have generally been recommended as first-line pharmacologic treatment and make children more attentive, less hyperactive, they have fewer problems at school and at home. Even though psychostimulants reduce symptoms in approximately 70% of patients, they are effective in controlling ADHD symptoms in the short term and benefits of medication are generally maintained only if medication is continued. In additional, normalization is rare. Moreover, stimulants have a high potential for abuse and dependence! By the way, such medications cause many side effects: the long-term therapeutic use can lead to severe sleep problems, decreased appetite and weight loss, increased blood pressure, headaches, dizziness, hallucinations, paranoia, rebound (irritability when the medication wears off), moodiness, irritability, and even neurological events (amphetamines may increase the risk of seizures).

In the United States, the prescription of methylphenidate peaked in 2012 and has since been slightly decreasing, while the use of amphetamines continues to rise. Obviously, the use of psychostimulants is not a solution, it's only the way to postpone the issue.

What is neurofeedback?

Neurofeedback (NF) is a safe, non-invasive approach for treating multiple brain-related conditions. It is a form of biofeedback, a training of self-regulation aiming to achieve control over brain activity patterns or to normalize them and thereby reduce/adjust the symptoms of ADHD: learning of self-regulation is thus a key mechanism.

Neurofeedback settings involve recording of neural activity, extraction of neural features of interest, a transformation of these features, and feeding the resulting signal back to the subject via one of the sensory modalities: visual and auditory (the program uses them to reorganize or retrain brain signals). During NF sessions, participants have electroencephalographic (EEG) electrodes attached to their scalp, and EEG-activity is expressed in the form of sounds or pictures projected on a computer screen and fed back to them automatically through different feedback games. In other words, neurofeedback training enables users to learn self-regulation of their cortical oscillations by receiving moment-to-moment feedback from their electroencephalogram. Patients learn to alter their brainwaves to achieve a goal, reinforcing the state of attention; patients learn to regulate and improve their brain function and alleviate symptoms of various neurological and mental health disorders.

How does it work? The signal of interest should represent the activity of a population of neurons involved in attentional networks, which is translated into visual or auditory cues. The sensory feedback constitutes the rewards mechanism, promoting learning using, for instance, operant conditioning protocols. Operant conditioning enables the brain's neural plasticity (ability to learn and change), thus supporting the child in the task repetition and reinforcement, which achieve results in long-lasting neuronal reorganization. NF can change brain's activity into producing more of one type of waveform pattern and less of another type. Due to immediate feedback, the brain begins to understand the direction of desired change and begins to more frequently create this wave pattern. Sometime later, these changes become the brain's new reality and the brain creates such patterns constantly.

NF has been applied to a variety of different clinical conditions including migraine, seizures, autism, anxiety, depression, and traumatic brain injury. NF has also been applied in healthy participants to enhance several aspects of cognitive functions.

Does neurofeedback work in ADHD?

Neurofeedback is a well-investigated treatment for ADHD. Although the clinical value of neurofeedback is still debated, with evaluations ranging from "efficacious and specific" to "not enough exposure", ADHD has been the primary clinical application of neurofeedback for over thirty years. A device using EEG to help clinicians more accurately diagnose ADHD was cleared by the Food and Drug Administration (FDA).

NF has gained encouraging empirical support in recent years: meta-analysis on the effects of NF on ADHD symptoms showed medium to large effects for all three core domains of ADHD symptoms.

A lot of people with ADHD show abnormal levels of theta and beta waves in central and frontal locations or decreasing sensorimotor rhythm power in the central area in the EEG. And current neurofeedback protocols focus predominantly on theta/beta ratio. Increased theta activity is related to lower vigilance and decreased beta activity is associated with reduced attention. Theta/beta ratio neurofeedback strives to bring these waves into balance that will provide improvement of the brain's functioning.

As patients with ADHD have insufficient communication among the neurons in the brain, via neurofeedback, children with ADHD are trained to regulate their neurophysiologic profile or to bring it closer to that of nonaffected children.

A major advantage of the neurofeedback approach is the potential for sustained, long-term benefits after successful completion of treatment: investigations indeed found positive effects on ADHD symptoms being stable 6 months after training and even increase in time. Positive changes on the behavioral, neurophysiologic, and neuropsychological levels have been reported after as few as 20 and as many as 40 sessions of neurofeedback (2 -4 sessions per week). Sometimes few booster sessions are required.

There are no known contraindications for standard neurofeedback protocols. In special cases, epilepsy may represent a contraindication for the typical neurofeedback-therapy.

No severe or permanent side effects of neurofeedback have been reported, and even mild adverse effects such as headache, fatigue systematically decrease over training as for placebo control with blinded assessment.

Based on current knowledge, neurofeedback is likely to be used as an element in the broader set of nonpharmacologic treatments for ADHD in multimodal therapy, may be used alone in patients who have significant side effects from stimulants or in "mild" form of ADHD.



Research:

1) "Our extended meta-analysis (k = 16 studies) confirmed the previously obtained results of effect sizes in favor of NF efficacy as being significant when clinical scales of ADHD are rated by parents. The Systematic Analysis of Biases performed on k = 33 trials identified three main factors that have an impact on NF efficacy: first, a more intensive treatment, but not treatment duration, is associated with higher efficacy; second, teachers report a lower improvement compared to parents; third, using high-quality EEG equipment improves the effectiveness of the NF treatment. The identification of biases relating to an appropriate technical implementation of NF certainly supports the efficacy of NF as an intervention.

In this work we provide additional elements in favor of the effectiveness of NF for the treatment of ADHD. First, we confirm that a subgroup of standard NF studies shows a statistically significant improvement. Second, we identify technical factors as positive contributors to clinical effectiveness, which strongly suggests that it is mediated by a real mechanism of action based on EEG conditioning. Equally, treatment intensity was also found to contribute, corroborating what is known from learning theory (memory consolidation); that is to say, a more intense treatment leads to an increased clinical efficacy"

Bussalb A., Congedo M., Barthélemy Q., Ojeda D., Acquaviva E., Delorme R., Mayaud L. (2019). Clinical and Experimental Factors Influencing the Efficacy of Neurofeedback in ADHD: A Meta-Analysis. Frontiers in Psychiatry, 10. doi:10.3389/fpsyt.2019.00035
Frontiers | Clinical and Experimental Factors Influencing the Efficacy of Neurofeedback in ADHD: A Meta-Analysis | Psychiatry (frontiersin.org)

2) "Recent randomized controlled trials suggest that 30 to 40 sessions of TBR neurofeedback were as effective as methylphenidate in reducing inattentive and hyperactivity symptoms and were even associated with superior post-treatment academic performance"

Enriquez-Geppert S., Smit D., Pimenta M. G., Arns M. (2019). Neurofeedback as a Treatment Intervention in ADHD:
Current Evidence and Practice. Current Psychiatry Reports, 21(6). doi:10.1007/s11920-019-1021-4

Sci-Hub | Neurofeedback as a Treatment Intervention in ADHD: Current Evidence and Practice. Current Psychiatry Reports, 21(6) | 10.1007/s11920-019-1021-4

3) "Using a stricter version of the American Psychological Association guidelines, that standard neurofeedback protocols in the treatment of ADHD can be considered as well-established and 'efficacious and specific', with medium to large effect sizes and 32–47% remission rates and sustained effects as assessed after 6–12 months.

Based on two independent and recent systematic reviews and meta-analyses, significant efficacy of standard neurofeedback protocols was confirmed for both parent and teacher rated symptoms (Cortese et al. 2016), with a small-medium between-group effect size. Between group analysis resulted in small-medium ES (Cortese et al. 2016; Van Doren et al. 2018), whereas within-group analysis resulted in large ES and effects were sustained at 6–12 months follow-up (Van Doren et al. 2018).

Three open-label neurofeedback studies demonstrate similar or better efficacy compared to the multicenter RCT's, demonstrating the effects of neurofeedback translate well into clinical practice.

No significant neurofeedback-specific side effects have been reported in any prior study"

Arns M., Clark C. R., Trullinger M., deBeus R., Mack M., Aniftos M. (2020).
Neurofeedback and Attention-Deficit/Hyperactivity-Disorder (ADHD) in Children: Rating the Evidence and Proposed Guidelines.
Applied Psychophysiology and Biofeedback. doi:10.1007/s10484-020-09455-2

Sci-Hub | Neurofeedback and Attention-Deficit/Hyperactivity-Disorder (ADHD) in Children: Rating the Evidence and Proposed Guidelines. Applied Psychophysiology and Biofeedback | 10.1007/s10484-020-09455-2

4) "Regarding the clinical effects after SCP-NF, our results are in line with a recent meta-analysis, which analyzed sustained effects after NF in comparison with active and non-active control groups. This meta-analysis showed that superior clinical effect at follow-up for NF was observed only when it was compared with the non-active control groups; NF follow-up effects were similar to those of the active control conditions"

Aggensteiner P.-M., Brandeis D., Millenet S., Hohmann S., Ruckes C., Beuth S., Holtmann M. (2019).
Slow cortical potentials neurofeedback in children with ADHD: comorbidity, self-regulation, and clinical outcomes 6 months
after treatment in a multicenter randomized controlled trial. European Child & Adolescent Psychiatry.
doi:10.1007/s00787-018-01271-8

Sci-Hub | Slow cortical potentials neurofeedback in children with ADHD: comorbidity, self-regulation and clinical outcomes 6 months after treatment in a multicenter randomized controlled trial. European Child & Adolescent Psychiatry | 10.1007/s00787-018-01271-8

5) "The current study expands and reinforces the previous conclusions that NF standard protocols can be considered as well-established and "efficacious and specific" with medium to large effect size and 32% to 47% remission rates, as well as sustained effects on follow up. Moreover, our analysis indicates that the remission rates of personalized NF treatment with standard NF (57%) are superior to methylphenidate in an open-label trial (31%) and equivalent to monotreatment with medication in a controlled research setting (56%). Effect size remained stable or increased over the long term thus indicating a strengthening of effects for NF over time, without any additional treatment"

Garcia Pimenta M, Brown T, Arns M, Enriquez-Geppert S. Treatment Efficacy and Clinical Effectiveness of EEG Neurofeedback as a Personalized and Multimodal Treatment in ADHD: A Critical Review. Neuropsychiatr Dis Treat. 2021 Feb 25;17:637-648. doi: 10.2147/NDT.S251547
Treatment Efficacy and Clinical Effectiveness of EEG Neurofeedback as a Personalized and Multimodal Treatment in ADHD: A Critical Review (nih.gov)

6) "This study supports NF as a promising alternative treatment for ADHD in children who do not respond or experience significant adverse effects to ADHD medications. NF improved all ADHD symptoms according to parental reports and inattentive symptoms according to teacher reports with moderate effect size. NF may be used alone in patients who have significant side effects from stimulants or patients whose family refuses to try medication or used in combination with ADHD medication"

Sudnawa K. K., Chirdkiatgumchai V., Ruangdaraganon N., Khongkhatithum C., Udomsubpayakul U., Jirayucharoensak S., Israsena P. (2018). Effectiveness of Neurofeedback Versus Medication in Treatment of ADHD. Pediatrics International. doi:10.1111/ped.13641
Sci-Hub | Effectiveness of Neurofeedback Versus Medication in Treatment of ADHD. Pediatrics International | 10.1111/ped.13641

7) "Meta-analytic results of NF treatment follow-up suggest that there are sustained symptom reductions over time in comparison with non-active control conditions. The improvements seen here are comparable to active treatments (including methylphenidate) at a short-term follow up of 2–12 months. As such, NF can be considered a non-pharmacological treatment option for ADHD with evidence of treatment effects that are sustained when treatment is completed and withdrawn. The significant improvement in symptoms at follow up for both inattention and hyperactivity–impulsivity in the neurofeedback conditions indicates that NF results in lasting effects for approximately 6 months and potentially up to 1 year"

Van Doren J., Arns M., Heinrich H., Vollebregt M. A., Strehl U., K. Loo S. (2018). Sustained effects of neurofeedback in ADHD: a systematic review and meta-analysis. European Child & Adolescent Psychiatry. doi:10.1007/s00787-018-1121-4
Sci-Hub | Sustained effects of neurofeedback in ADHD: a systematic review and meta-analysis. European Child & Adolescent Psychiatry | 10.1007/s00787-018-1121-4

8) "When used in combination with medication, theta/beta NF may decrease medication dosage in children who already use medication to treat their ADHD symptoms and has additive treatment effects on top of stimulant medication. There seems to be an unidentified group of patients who may benefit from NF treatment, also after 6-month follow-up, possibly those without comorbid disorders, those with higher baseline theta, those with low response to stimulant medication and those who are more prone to experience side effects due to stimulants. Thus, based on the current state of the art, the current review concludes that the present role of theta/beta NF in treating children diagnosed with ADHD should be considered as complementary in a multimodal treatment approach, individualized to the needs of the child, and may be considered a viable alternative to stimulants for a specific group of patients"

Razoki B. (2018). Neurofeedback versus psychostimulants in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a systematic review. Neuropsychiatric Disease and Treatment, Volume 14, 2905–2913. doi:10.2147/ndt.s178839
Sci-Hub | Neurofeedback versus psychostimulants in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a systematic review. Neuropsychiatric Disease and Treatment, Volume 14, 2905–2913 | 10.2147/ndt.s178839

9) "QEEG-informed neurofeedback was effective in decreasing ADHD symptoms and, importantly, response rates and effect sizes surpassed those of meta-analyses where one protocol was applied to the whole population (response rate of 76% (≥50% symptom reduction)) and large effect sizes for inattention and hyperactivity were observed"

Arns M., Drinkenburg W., Leon Kenemans J., 2012. The effects of QEEG-informed neurofeedback in ADHD:
an open-label pilot study. Appl. Psychophysiol. Biofeedback 37 (3), 171–180

The Effects of QEEG-Informed Neurofeedback in ADHD: An Open-Label Pilot Study | SpringerLink

10) "This study investigated the effects of neurofeedback therapy on core symptoms of ADHD using a meta-analytic approach. Fifteen studies were found fulfilling our criteria, with a total of 1194 subjects and the majority of studies conducted in Germany (6 studies) and the USA (5 studies). From the controlled studies in the meta-analysis it was evident that neurofeedback had large effect size on inattention and impulsivity and a medium effect size for hyperactivity.

Post-hoc analyses did not reveal any differences between the different neurofeedback approaches used such as theta/beta, SMR theta and SCP neurofeedback nor a differential efficacy for the 3 domains"

Arns M., de Ridder S., Strehl U., Breteler M., Coenen A. (2009). Efficacy of Neurofeedback Treatment in ADHD:
The Effects on Inattention, Impulsivity and Hyperactivity: A Meta-Analysis.
Clinical EEG and Neuroscience, 40(3), 180–189. doi:10.1177/155005940904000311

Sci-Hub | Efficacy of Neurofeedback Treatment in ADHD: The Effects on Inattention, Impulsivity and Hyperactivity: A Meta-Analysis. Clinical EEG and Neuroscience, 40(3), 180–189 | 10.1177/155005940904000311

11) "The major findings of this updated meta-analysis are that: EEG-NF significantly improves the ADHD total score on a parent-assessment scale with a medium effect size of −0.49; EEG-NF significantly improves both the inattention and hyperactivity/impulsivity dimensions on a parent-assessment scale with medium effect sizes of −0.46 and −0.34, respectively; and EEG-NF significantly improves the inattention dimension on a teacher-assessment scale with a smaller effect size of −0.30"

Micoulaud-Franchi J.-A., Geoffroy P. A., Fond G., Lopez R., Bioulac S., Philip P. (2014). EEG neurofeedback treatments in children with ADHD: an updated meta-analysis of randomized controlled trials. Frontiers in Human Neuroscience, 8. doi:10.3389/fnhum.2014.00906
Sci-Hub | EEG neurofeedback treatments in children with ADHD: an updated meta-analysis of randomized controlled trials. Frontiers in Human Neuroscience, 8 | 10.3389/fnhum.2014.00906


Recourses:

1) Márquez-Caraveo M.E., Rodríguez-Valentín R., Pérez-Barrón V., Vázquez-Salas R.A., Sánchez-Ferrer J.C., De Castro F., Allen-Leigh B., Lazcano-Ponce E. (2021) Children and adolescents with neurodevelopmental disorders show cognitive heterogeneity and require a person-centered approach. Sci Rep.;11(1):18463. doi: 10.1038/s41598-021-97551-6.

2) Albajara Sáenz A., Septier M., Van Schuerbeek P., Baijot S., Deconinck N., Defresne P., Delvenne V., Passeri G., Raeymaekers H., Salvesen L., Victoor L., Villemonteix T., Willaye E., Peigneux P., Massat I. (2020) ADHD and ASD: distinct brain patterns of inhibition-related activation? Transl Psychiatry; 10(1):24. doi: 10.1038/s41398-020-0707-z.

3) Mekkawy L. (2021). Efficacy of neurofeedback as a treatment modality for children in the autistic spectrum. Bull Natl Res Cent 45, 45. https://doi.org/10.1186/s42269-021-00501-5.

4) Drechsler R., Brem S., Brandeis D., Grünblatt E., Berger G., Walitza S. (2020). ADHD: Current Concepts and Treatments in Children and Adolescents. Neuropediatrics. doi:10.1055/s-0040-1701658.

5) American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.

6) Posner J., Polanczyk G. V., Sonuga-Barke E. (2020). Attention-deficit hyperactivity disorder. The Lancet. doi:10.1016/s0140-6736(19)33004-1.

7) Retz W., Ginsberg Y., Turner D., Barra S., Retz-Junginger P., Larsson H., Asherson P. (2020). Attention-Deficit/Hyperactivity Disorder (ADHD), antisociality and delinquent behavior over the lifespan. Neuroscience & Biobehavioral Reviews. doi:10.1016/j.neubiorev.2020.11.

8) Antshel K. M., Russo N. (2019). Autism Spectrum Disorders and ADHD: Overlapping Phenomenology, Diagnostic Issues, and Treatment Considerations. Current Psychiatry Reports, 21(5). doi:10.1007/s11920-019-1020-5.

9) Enriquez-Geppert S., Smit D., Pimenta M. G., Arns M. (2019). Neurofeedback as a Treatment Intervention in ADHD: Current Evidence and Practice. Current Psychiatry Reports, 21(6). doi:10.1007/s11920-019-1021-4.

10) Holtmann M., Sonuga-Barke E., Cortese S., Brandeis D. (2014). Neurofeedback for ADHD. Child and Adolescent Psychiatric Clinics of North America, 23(4), 789–806. doi:10.1016/j.chc.2014.05.006.

11) Duric N. S., Assmus J., Gundersen D., Duric Golos A., Elgen I. B. (2017). Multimodal treatment in children and adolescents with attention-deficit/hyperactivity disorder: a 6-month follow-up. Nordic Journal of Psychiatry, 71(5), 386–394. doi:10.1080/08039488.2017.1305446.

12) Enriquez-Geppert S., Smit D., Pimenta M. G., Arns M. (2019). Neurofeedback as a Treatment Intervention in ADHD: Current Evidence and Practice. Current Psychiatry Reports, 21(6). doi:10.1007/s11920-019-1021-4.

13) Caye A., Swanson J. M., Coghil, D., Rohde L. A. (2018). Treatment strategies for ADHD: an evidence-based guide to select optimal treatment. Molecular Psychiatry. doi:10.1038/s41380-018-0116-3.

14) Bussalb A., Congedo M., Barthélemy Q., Ojeda D., Acquaviva E., Delorme R., Mayaud L. (2019). Clinical and Experimental Factors Influencing the Efficacy of Neurofeedback in ADHD: A Meta-Analysis. Frontiers in Psychiatry, 10. doi:10.3389/fpsyt.2019.00035.

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