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What is ASD?

Autism spectrum disorder (ASD, includes autism and Asperger's syndrome) is a common neurodevelopmental disease that characterized by core deficits in 2 domains: social communication/interaction and restrictive, repetitive patterns of behavior.
Reasons for autism are still unknown, research supports genetic (prominent role) and environmental factors. ASD is 4 times as likely to occur in male than female individuals.
ASD prevalence worldwide has been estimated as ranging from 0.08 to 9.3%, and prevalence in the US has been estimated between 1.3 and 2.6% (more than 5 million Americans). Prevalence rates in US populations are like those of other industrialized countries. Lower rates are reported in resource-limited countries, where epidemiological data are more difficult to collect.

There are a lot of information that prevalence of children with ASD has increased over time. This increase may be attributable to several factors: changes in the diagnostic criteria with ongoing revisions of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV, increased public awareness of the disorder and its symptoms, recommendations for universal screening for ASD, increased availability of early intervention and school-based services for children with ASD.

The symptoms of autism are present from early childhood and affect daily functioning. Persistent deficits in social communication and social interaction and restricted, repetitive patterns of behavior, interests, or activities have a significant impact on patient's life. Features of autism are well known: children have troubles with social-emotional reciprocity (abnormal social approach and failure of normal back and-forth conversation; reduced sharing of interests, emotions, or affect; failure to initiate or respond to social interactions), nonverbal communicative behaviors used for social interaction (poorly integrated verbal and nonverbal communication; abnormalities in eye contact and body language or deficits in understanding and use of gestures; total lack of facial expressions and nonverbal communication), developing, maintaining, and understanding relationships (difficulties adjusting behavior to suit various social contexts; difficulties in sharing imaginative play or in making friends; absence of interest in peers).

Stereotyped or repetitive motor movements, use of objects, or speech (simple motor stereotypies, lining up toys or flipping objects, echolalia, idiosyncratic phrases), insistence on sameness, inflexible adherence to routines, or ritualized patterns or verbal nonverbal behavior (extreme distress at small changes, difficulties with transitions, rigid thinking patterns, greeting rituals, need to take same route or eat food every day), highly restricted, fixated interests that are abnormal in intensity or focus (strong attachment to or preoccupation with unusual objects, excessively circumscribed or perseverative interest), hyper- or hyporeactivity to sensory input or unusual interests in sensory aspects of the environment (apparent indifference to pain/temperature, adverse response to specific sounds or textures, excessive smelling or touching of objects, visual fascination with lights or movement) are also significant clinical features of autism.

The diagnosis of autism is based on identifying and reporting behaviorally defined clinical symptoms – by the Diagnostic and Statistical Manual of Mental Disorders (DSM)-V. Neither blood analyses nor instrumental methods сan reveal ASD. The average age of diagnosis is 5 years.

Co-occurring medical and behavioral conditions such as ADHD, anxiety, specific phobias, oppositional/conduct disorder, disorders of sleep and feeding, gastrointestinal tract symptoms, obesity, seizures affect the child's function and quality of life.

No current medication corrects core social and communication symptoms of autism. Children and youth with autism have service needs in behavioral, educational, health, leisure, family support, and other areas. Medication is used to help manage coexisting behavioral health disorders (eg, ADHD, mood disorders, or anxiety disorders) and associated problem behaviors or symptoms causing significant impairment and distress (aggression, self-injurious behavior, sleep disturbance, mood lability, anxiety, hyperactivity, impulsivity, inattention).

One or more psychotropic medications are prescribed:

- for 1% of children with autism younger than 3 years,

- for 10% - 11% of children aged 3 to 5 years,

- 38% - 46% of children aged 6 to 11 years,

- 64% - 67% of adolescents aged 12 to 17 years(!).

The goals of treatment of children with autism are to minimize core deficits (social communication and interaction and restricted or repetitive behaviors and interests) and co-occurring associated impairments; maximize functional independence by facilitating learning and acquisition of adaptive skills; eliminate, minimize, or prevent problem behaviors that may interfere with functional skills.

Many young adults with autism do not receive any healthcare for years after they stop seeing a pediatrician.

By Leigh and al., direct and indirect costs of caring for children and adults with ASD in the United States in 2015 were estimated to be $268 billion, more than the cost of stroke and hypertension combined and would rise to $461 billion by 2025 in the absence of more-effective interventions and support across the life span. On average, medical expenditures for children and adolescents with ASD were 4.1 to 6.2 times greater than for those without autism.

Social aspects of autism:

  • More than half of young adults with autism remain unemployed and unenrolled in higher education in the two years after high school. This is a lower rate than that of young adults in other disability categories, including learning disabilities, intellectual disability or speech-language impairment.
  • Of the nearly 18,000 people with autism who used state-funded vocational rehabilitation programs in 2014, only 60 percent left the program with a job. Of these, 80 percent worked part-time at a median weekly rate of $160, putting them well below the poverty level.
  • Nearly half of 25-year-olds with autism have never held a paying job.
Research demonstrates that job activities that encourage independence reduce autism symptoms and increase daily living skills (resource: US Centers for disease control and prevention).

What is neurofeedback?

Neurofeedback (NF) is a safe, noninvasive 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 and ASD: learning of self-regulation is thus a key mechanism.

Neurofeedback settings involve recording of neural activity, extraction of neural features of interest, transformation of these features, and feeding the resulting signal back to the subject via one of sensory modalities: visual and auditory (the program uses them to reorganize or retrain brain signals). During NF session, 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 brain's neural plasticity (ability to learn and change), thus supporting the child in the task repetition and reinforcement, which achieve to result 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 ASD?

A variety of studies demonstrate that NFT shows remarkable improvements in children's cognitive abilities, emotion regulation, and behavior:

1) "The current study investigated the effects of slow cortical potentials (SCP) training on core symptomatology in adolescents with ASD. The analysis revealed a substantial improvement in the core symptomatology of ASD in the experimental group, which was slightly superior to that observed in the control group. Besides a reduction in the general severity of ASD symptomatology indicated by a decrease in SRS Total score (i.e., a general improvement of social responsivity), the subscales Social Cognition and Autistic Mannerism were those that differentiated the most between the experimental and the control group. Although random differences between the SRS scores of the groups, present at the beginning of the interventions, may limit straightforward interpretations of the treatment improvements, numerous previous SCP studies support our findings of disorder-specific improvements related to SCP neurofeedback training.

Changes in SLP manifested themselves as different trajectories depending on the different feedback conditions and tasks. Further, the model of PSD revealed a continuous decrease in delta power, parallel to an increase in alpha power. Our analyses suggest that behavioral and neural processes of change related to neurofeedback training are complex and non-linear"

Konicar L., Radev S., Prillinger K., Klöbl M., Diehm R., Birbaumer N., Poustka L. (2021). Volitional modification of brain activity in adolescents with Autism Spectrum Disorder: A Bayesian analysis of Slow Cortical Potential neurofeedback. NeuroImage: Clinical, 29, 102557. doi:10.1016/j.nicl.2021.102557
Sci-Hub | Volitional modification of brain activity in adolescents with Autism Spectrum Disorder: A Bayesian analysis of Slow Cortical Potential neurofeedback. NeuroImage: Clinical, 29, 102557 | 10.1016/j.nicl.2021.102557

2) "The study is one of the approaches aiming at understanding the correlation between EEG brain waves activity and NFB training in ASD population. In addition to the practical evaluation of NFB as a modality tool of treatment for ASD, the current study aimed to understand the cognitive and neural processes that underlie NFB improvements in the core of ASD.
The present study assisted in the evaluation of using NFB training protocol (using theta/beta ratio as a prognostic tool) as a treatment modality for autistic children. It was hypothesized that reduction of theta power improves children's cognitive capacities/functions. Consonant with the study's prediction, children included in this study managed to improve their performance over a range of variable cognitive processes after NFB training. Furthermore, these findings provided evidence supporting that NFB may be considered as a valuable treatment modality for children with ASD: at a neurophysiological level, NFB training was able to increase low beta power (12–15 Hz) and reduce theta power (4–7 Hz) in all autistic participants. Teta/beta ratios showed marked regression over 40 sessions of NFB, changes in EEG amplitude following NFB training mainly affected 3 main areas in the brain, regressive changes were mostly seen in FZ, F4 (areas of socialization and communication) followed by CZ (area of activity) and lastly the temporal areas T3, T4 (areas of emotions). In addition, t-score showed that the ratios decreased statistically throughout the whole course of treatment.
According to the results of the current study, statistical significant improvement in TBR was found throughout the whole treatment course.

At the intellectual level, NFB treatment was theorized to enhance the cognitive functions of children with ASD. Results indicated significant improvement in attentional span, cognitive flexibility in addition to social interaction for children in the studied group where their parents reported improvement on the CBCL questionnaire subscales.
However, only five patients did not show any improvement; those five patients were males in gender with mean age (10.7) and mean IQ level (74.8).
To conclude, applying a NFB treatment protocol to a group of ASD children proved to be reasonably successful. NFB therapy showed remarkable improvements in children's cognitive abilities. These findings advocate a correlation between amplified TBR training in these children and hypo-activation of the anterior cingulate cortex as a possible neural core problem for this impairment"

Mekkawy L. (2021). Efficacy of neurofeedback as a treatment modality for children in the autistic spectrum. Bulletin of the National Research Centre, 45(1). doi:10.1186/s42269-021-00501-5
Sci-Hub | Efficacy of neurofeedback as a treatment modality for children in the autistic spectrum. Bulletin of the National Research Centre, 45(1) | 10.1186/s42269-021-00501-5

3) "The current study indicated the effectiveness of prefrontal neurofeedback aimed at modulating the disordered EEG activities associated with ASD.
Theta/beta ratios (both theta/low beta and theta/high beta) showed the significant decrease over 18 sessions of neurofeedback, and in addition t-test showed that the ratios decreased statistically from the first to the last NFB training sessions. Theta/beta ratio is one of the classical indices for characterizing the ability to focus attention and to concentrate. The current study showed that both prefrontal theta/beta ratio and power of gamma activity could be modulated positively by operant conditioning during the NFB training in high functioning children with ASD. It is well-known that most ASD subjects have difficulties with switching focused attention. The "Focus/40 Hz Gamma" protocol used in the study provided a successful way for positively modulating both gamma activity and focused concentration abilities in ASD.
The positive effects of the neurofeedback training further can be manifested by the improvement in the behavioral scores measured by the ABC. Our results show a significant reduction in the Lethargy/Social Withdrawal subscale of the ABC and a negative correlation with the theta/beta ratio. The Hyperactivity scores of ABC also showed a decrease but the same did not correlate with any EEG or NFB indices used in this study. The improvement of behavioral changes assessed by ABC before and after the 18 sessions of NFB treatments was in accordance to the functional outcomes seen in the EEG profile changes. Our study showed that compared to previous protocols that required more sessions per subject (> 30) and a more frequent training rate (e.g., twice per week), the statistical significant improvement either in EEG or in behavioral measures can also be achieved within a shorter number of sessions (i.e., 18 NFB sessions in ASD, or even 12 sessions in ADHD) and weekly visits. Probably more than 18 sessions might contribute to better consolidation of results of operant conditioning using neurofeedback, and currently we have studies in progress that will compare outcomes of 12 vs. 18 vs. 24 sessions of neurofeedback using the same protocol in children with autism"

Wang Y., Sokhadze E. M., El-Baz A. S., Li X., Sears L., Casanova M. F., Tasman A. (2016). Relative Power of Specific EEG Bands and Their Ratios during Neurofeedback Training in Children with Autism Spectrum Disorder. Frontiers in Human Neuroscience, 9. doi:10.3389/fnhum.2015.00723
Sci-Hub | Relative Power of Specific EEG Bands and Their Ratios during Neurofeedback Training in Children with Autism Spectrum Disorder. Frontiers in Human Neuroscience, 9 | 10.3389/fnhum.2015.00723

4) "The present study investigated the effects of sensorimotor mu-based neurofeedback training (NFT) on imitation-related brain activation. It assessed social behaviors in a group of high functioning children and adolescents with ASD, compared to a matched group of typically developed children.

Our findings suggest that in children and adolescents with ASD, sensorimotor muNFT has significant positive effects on social behaviors, as well as on the neurofunctional substrates of those behaviors, potentially centered on mirror neuron networks. While similar NFT protocols have previously been shown to positively influence electrophysiological signatures of mirror neuron networks in autism, this is the first study using fMRI to directly localize effects of mu-NFT on brain regions involved in action observation and imitation. The finding of strong correlations between behavioral improvements and activation changes specifically in these brain regions supports the use of mu-NFT to improve clinical outcomes for individuals on the autism spectrum.
Furthermore, we report for the first time that these benefits are accompanied by – and in fact correlated with – neurophysiological changes in imitation-related brain areas following the training"

Datko M., Pineda J. A., Müller R.-A. (2017). Positive effects of neurofeedback on autism symptoms correlate with brain activation during imitation and observation. European Journal of Neuroscience, 47(6), 579–591. doi:10.1111/ejn.13551
Sci-Hub | Positive effects of neurofeedback on autism symptoms correlate with brain activation during imitation and observation. European Journal of Neuroscience, 47(6), 579–591 | 10.1111/ejn.13551

5) "Thirteen children with ASD completed pre-/post-assessments and 16 NFT-sessions. The NFT was based on a game that encouraged social interactions and provided feedback based on imitation and emotional responsiveness. Bidirectional training of EEG mu suppression and enhancement (8–12 Hz over somatosensory cortex) was compared to the standard method of enhancing mu. Children learned to control mu rhythm with both methods and showed improvements in (1) electrophysiology: increased mu suppression, (2) emotional responsiveness: improved emotion recognition and spontaneous imitation, and (3) behavior: significantly better behavior in every-day life. Electrophysiologically, there was more mu suppression in the post- than in the pre-test indicating activation of the MNS. In terms of emotional responsiveness, children displayed significantly more correct responses in the emotion recognition task and exhibited more appropriate spontaneous imitation behavior to emotional stimuli in the post- than in the pre-test. Behaviorally, parents indicated in every-day life situations a significant reduction of ASD symptoms, significantly better social responsiveness, and better behavioral adaptation, respectively, in the post- than in the pre-test.
As positive feedback during NFT was inhibited by exceeding theta and beta frequency bands as well as EMG of the hand, it gave greater assurance that children with ASD did gain control of the mu rhythm itself rather than via blinks or muscle movements.
The results provide the most substantial argument to date that mu-based NFT can be an effective tool for improving aspects of behavior necessary for successful social interactions in children with ASD.

In the pre- and posttests, participants showed significantly enhanced mu suppression in executed movement compared to movement observation, greater correct responses in the gender than in the emotion imitation task and more muscle activation at the zygomaticus major while watching positive and more at the corrugator supercilii while watching negative faces. These results indicate that the children understood the tasks, followed the instructions and that the data are indeed valid and can be considered reliable indicators of improvement.

Thus, these NFT paradigms improve aspects of behavior necessary for successful social interactions"

Friedrich E.V.C., Sivanathan A., Lim T. et al. (2015) An Effective Neurofeedback Intervention to Improve Social Interactions in Children with Autism Spectrum Disorder. J Autism Dev Disord 45, 4084–4100.
https://doi.org/10.1007/s10803-015-2523-5
An Effective Neurofeedback Intervention to Improve Social Interactions in Children with Autism Spectrum Disorder (escholarship.org)

6) "The present study investigated the effects of sensorimotor mu-based neurofeedback training on imitation-related brain activation. It assessed social behaviors in a group of high functioning children and adolescents with ASD, compared to a matched group of typically developed children. The results show learning during NFT and support the hypothesis that mu-NFT has positive behavioral effects (reduced symptom severity on the ATEC and SRS) in children with ASD. Furthermore, we report for the first time that these benefits are accompanied by – and in fact correlated with – neurophysiological changes in imitation-related brain areas following the training.

Our findings suggest that in children and adolescents with ASD, sensorimotor muNFT has significant positive effects on social behaviors, as well as on the neurofunctional substrates of those behaviors, potentially centered on mirror neuron networks. While similar NFT protocols have previously been shown to positively influence electrophysiological signatures of mirror neuron networks in autism, this is the first study using fMRI to directly localize effects of mu-NFT on brain regions involved in action observation and imitation. The finding of strong correlations between behavioral improvements and activation changes specifically in these brain regions supports the use of mu-NFT to improve clinical outcomes for individuals on the autism spectrum"

Datko M., Pineda J. A., Müller R.-A. (2017). Positive effects of neurofeedback on autism symptoms correlate with brain activation during imitation and observation. European Journal of Neuroscience, 47(6), 579–591. doi:10.1111/ejn.13551
Sci-Hub | Positive effects of neurofeedback on autism symptoms correlate with brain activation during imitation and observation. European Journal of Neuroscience, 47(6), 579–591 | 10.1111/ejn.13551

7) "The aim of the present study was to examine the effect of neurofeedback training (NFT) and speech therapy on learning and speech ability in patients with a diagnosis of autism spectrum. According to the results, significant difference was found in brain wave power after neurotherapy in the studied case. At a neurophysiological level, neurofeedback training successfully increased power of theta (4–7 Hz) and beta3 (15–18 Hz) bands in this case. At a cognitive level, neurofeedback training was hypothesized to improve the executive functions of children with ASD. Significant improvement in attention control, cognitive flexibility and goal setting were noted for this case according to mother's and teacher's report. Results of the present study indicated that autistic subject was able to increase slow wave brain activity and that neurofeedback caused changes in qEEG and improvement in set-shifting, reciprocal social interactions, and communication skills"

Karimi, M., Haghshenas, S., & Rostami, R. (2011). Neurofeedback and autism spectrum: A case study. Procedia - Social and Behavioral Sciences, 30, 1472–1475. doi:10.1016/j.sbspro.2011.10.285
Sci-Hub | Neurofeedback and autism spectrum: A case study. Procedia - Social and Behavioral Sciences, 30, 1472–1475 | 10.1016/j.sbspro.2011.10.285


Resources:

1) Kodak T., Bergmann S. (2020). Autism Spectrum Disorder. Pediatric Clinics of North America. doi:10.1016/j.pcl.2020.02.007

2) Lord C., Brugha T. S., Charman T., Cusack J., Dumas G., Frazier T., Veenstra-VanderWeele J. (2020). Autism spectrum disorder. Nature Reviews Disease Primers, 6(1). doi:10.1038/s41572-019-0138-4

3) Hyman S. L., Levy S. E., Myers S. M. (2019). Identification, Evaluation, and Management of Children With Autism Spectrum Disorder. Pediatrics, 145(1), e20193447. doi:10.1542/peds.2019-3447

4) Leigh JP, Du J. (2015) Brief report: forecasting the economic burden of autism in 2015 and 2025 in the United States. J Autism Dev Disord., 45(12): 4135–4139

5) 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.

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

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.

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