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Modulation of Resting-State Brain Complexity After Bilateral Cerebellar Anodal Transcranial Direct Current Stimulation in Children with Autism Spectrum Disorders: a Randomized Controlled Trial Study

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Abstract

Background

Autism spectrum disorders (ASD) are heterogeneous neurodevelopmental disorders characterized by aberrant neural networks. Cerebellum is best known for its role in controlling motor behaviors; however, recently, there have been significant reports showed that dysfunction in cerebellar-cerebral networks contributes significantly to many of the clinical features of ASD. Hereby, this is a randomized controlled trial (RCT) study examining the potential modulating effects of bilateral anodal tDCS stimulation over cerebellar hemispheres on the resting-state brain complexity in children with ASD.

Methods

Thirty-six children with ASD (aged 4–14) years old were divided equally and randomly into a tDCS treatment group, which underwent 10 sessions (20-min duration, five sessions/per week) of bilateral anodal tDCS stimulation applied over left and right cerebellar hemispheres, and control group underwent the same procedures, but with sham tDCS stimulation. Resting-state brain complexity was evaluated through recording and calculating the approximate entropy (ApxEnt) values of the resting-state electroencephalograph (EEG) data obtained from a 64-channel EEG system before and after the interventions.

Results

Repeated measures of ANOVA showed that tDCS had significant effects on the treatment group (Wilks’ Lambda = 0.29, F (15, 16) = 2.67, p = 0.03) compared with the control group. Analyzed data showed a significant increase in the averaged ApxEnt values in the right frontal cortical region (F (1, 16) = 10.46, p = 0.005) after the bilateral cerebellar anodal tDCS stimulation. Besides, the Cohen’s d effect size showed a large effect size (0.70–0.92) of bilateral cerebellar anodal tDCS on the ApxEnt values increases in the left and right frontal cortical regions, the right central cortical region, and left parietal cortical region. However, there were no any significant differences or increases in the brain complexity before and after the sham tDCS stimulation of the control group.

Conclusion

Bilateral cerebellar anodal tDCS modulated and increased the brain complexity in children with ASD with no any reported adverse effect. Hereby, cerebellum and cerebellar-cerebral circuitry would serve as a promising target for non-invasive brain stimulation and neuro-modulation as a therapeutic intervention.

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Data Availability

Data is available upon request.

References

  1. Johnson CP, Myers SM, D American Academy of Pediatrics Council on Children With. Identification and evaluation of children with autism spectrum disorders. Pediatrics. 2007;120(5):1183–215.

    Article  PubMed  Google Scholar 

  2. Webb SJ, et al. Guidelines and best practices for electrophysiological data collection, analysis and reporting in autism. J Autism Dev Disord. 2015;45(2):425–43.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Liu T, et al. Altered electroencephalogram complexity in autistic children shown by the multiscale entropy approach. NeuroReport. 2017;28(3):169–73.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Zhang L, Wang XH, Li L. Diagnosing autism spectrum disorder using brain entropy: A fast entropy method. Comput Methods Programs Biomed. 2020;190:105240.

    Article  PubMed  Google Scholar 

  5. Takahashi T. Complexity of spontaneous brain activity in mental disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2013;45:258–66.

    Article  PubMed  Google Scholar 

  6. Sokunbi MO, et al. Resting state fMRI entropy probes complexity of brain activity in adults with ADHD. Psychiatry Res. 2013;214(3):341–8.

    Article  PubMed  Google Scholar 

  7. Demirtas-Tatlidede A, Vahabzadeh-Hagh AM, Pascual-Leone A. Can noninvasive brain stimulation enhance cognition in neuropsychiatric disorders? Neuropharmacology. 2013;64:566–78.

    Article  PubMed  CAS  Google Scholar 

  8. Schneider HD, Hopp JP. The use of the bilingual aphasia test for assessment and transcranial direct current stimulation to modulate language acquisition in minimally verbal children with autism. Clin Linguist Phon. 2011;25(6–7):640–54.

    Article  PubMed  Google Scholar 

  9. Amatachaya A, et al. Effect of anodal transcranial direct current stimulation on autism: a randomized double-blind crossover trial. Behav Neurol. 2014;2014:173073.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Amatachaya A, et al. The short-term effects of transcranial direct current stimulation on electroencephalography in children with autism: a randomized crossover controlled trial. Behav Neurol. 2015;2015:928631.

    Article  PubMed  PubMed Central  Google Scholar 

  11. van Steenburgh JJ, et al. Balanced bifrontal transcranial direct current stimulation enhances working memory in adults with high-functioning autism: a sham-controlled crossover study. Mol Autism. 2017;8:40.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Hadoush H, et al. Therapeutic effects of bilateral anodal transcranial direct current stimulation on prefrontal and motor cortical areas in children with autism spectrum disorders: a pilot study. Autism Res. 2020;13(5):828–36.

    Article  PubMed  Google Scholar 

  13. Kang J, et al. Transcranial direct current stimulation (tDCS) can modulate EEG complexity of children with autism spectrum disorder. Front Neurosci. 2018;12:201.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Limperopoulos C, et al. Does cerebellar injury in premature infants contribute to the high prevalence of long-term cognitive, learning, and behavioral disability in survivors? Pediatrics. 2007;120(3):584–93.

    Article  PubMed  Google Scholar 

  15. Stoodley CJ, Limperopoulos C. Structure-function relationships in the developing cerebellum: evidence from early-life cerebellar injury and neurodevelopmental disorders. Semin Fetal Neonatal Med. 2016;21(5):356–64.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Buckner RL, et al. The organization of the human cerebellum estimated by intrinsic functional connectivity. J Neurophysiol. 2011;106(5):2322–45.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Van Overwalle F, et al. Consensus paper: cerebellum and social cognition. Cerebellum. 2020;19(6):833–68.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Ferrucci R, et al. Cerebellum and processing of negative facial emotions: cerebellar transcranial DC stimulation specifically enhances the emotional recognition of facial anger and sadness. Cogn Emot. 2012;26(5):786–99.

    Article  PubMed  Google Scholar 

  19. Treasure T, MacRae KD. Minimisation: the platinum standard for trials? Randomisation doesn’t guarantee similarity of groups; minimisation does. BMJ. 1998;317(7155):362–3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Grimaldi G, et al. Cerebellar transcranial direct current stimulation (ctDCS): a novel approach to understanding cerebellar function in health and disease. Neuroscientist. 2016;22(1):83–97.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Grimaldi G, et al. Non-invasive cerebellar stimulation–a consensus paper. Cerebellum. 2014;13(1):121–38.

    Article  PubMed  CAS  Google Scholar 

  22. Grimaldi G, et al. Marked reduction of cerebellar deficits in upper limbs following transcranial cerebello-cerebral DC stimulation: tremor reduction and re-programming of the timing of antagonist commands. Front Syst Neurosci. 2014;8:9.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Pincus SM. Approximate entropy as a measure of irregularity for psychiatric serial metrics. Bipolar Disord. 2006;8(5 Pt 1):430–40.

    Article  PubMed  Google Scholar 

  24. Richman JS, Moorman JR. Physiological time-series analysis using approximate entropy and sample entropy. Am J Physiol Heart Circ Physiol. 2000;278(6):H2039–49.

    Article  PubMed  CAS  Google Scholar 

  25. Pincus SM, Goldberger AL. Physiological time-series analysis: what does regularity quantify? Am J Physiol. 1994;266(4 Pt 2):H1643–56.

    PubMed  CAS  Google Scholar 

  26. Hadoush H, Alafeef M, Abdulhay E. Automated identification for autism severity level: EEG analysis using empirical mode decomposition and second order difference plot. Behav Brain Res. 2019;362:240–8.

    Article  PubMed  Google Scholar 

  27. Delgado-Bonal A, Marshak A. Approximate entropy and sample entropy: a comprehensive tutorial. Entropy. 2019;(6):541.

  28. Pincus SM, Keefe DL. Quantification of hormone pulsatility via an approximate entropy algorithm. Am J Physiol. 1992;262(5 Pt 1):E741–54.

    PubMed  CAS  Google Scholar 

  29. Pincus SM, Viscarello RR. Approximate entropy: a regularity measure for fetal heart rate analysis. Obstet Gynecol. 1992;79(2):249–55.

    PubMed  CAS  Google Scholar 

  30. Coben R, et al. EEG power and coherence in autistic spectrum disorder. Clin Neurophysiol. 2008;119(5):1002–9.

    Article  PubMed  Google Scholar 

  31. Bosl W, et al. EEG complexity as a biomarker for autism spectrum disorder risk. BMC Med. 2011;9:18.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Okazaki R, et al. Changes in EEG complexity with electroconvulsive therapy in a patient with autism spectrum disorders: a multiscale entropy approach. Front Hum Neurosci. 2015;9:106.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Hadoush H, Alafeef M, Abdulhay E. Brain complexity in children with mild and severe autism spectrum disorders: analysis of multiscale entropy in EEG. Brain Topogr. 2019;32(5):914–21.

    Article  PubMed  Google Scholar 

  34. Wang J, et al. Resting state EEG abnormalities in autism spectrum disorders. J Neurodev Disord. 2013;5(1):24.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Stoodley CJ. The cerebellum and neurodevelopmental disorders. Cerebellum. 2016;15(1):34–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Oldrati V, et al. How social is the cerebellum? Exploring the effects of cerebellar transcranial direct current stimulation on the prediction of social and physical events. Brain Struct Funct. 2021.

  37. Oldrati V, Schutter D. Targeting the human cerebellum with transcranial direct current stimulation to modulate behavior: a meta-analysis. Cerebellum. 2018;17(2):228–36.

    Article  PubMed  Google Scholar 

  38. Cardinale RC, et al. Pervasive rightward asymmetry shifts of functional networks in autism spectrum disorder. JAMA Psychiat. 2013;70(9):975–82.

    Article  Google Scholar 

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Funding

This work is supported by a grant from the Scientific Research Support Fund—Jordanian Ministry of Higher Education (MPH/1/20/2014) and the Deanship of Research at Jordan University of Science and Technology (275/2015).

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Authors and Affiliations

  1. Department of Rehabilitation Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, P.O. Box 3030, Irbid, 22110, Jordan

    Hikmat Hadoush

  2. Department of Mechanical Engineering, Faculty of Engineering and Technology, Palestine Technical University – Kadoorie, Tulkarm, Palestine

    Ashraf Hadoush

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  1. Hikmat Hadoush
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Correspondence to Hikmat Hadoush.

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Hadoush, H., Hadoush, A. Modulation of Resting-State Brain Complexity After Bilateral Cerebellar Anodal Transcranial Direct Current Stimulation in Children with Autism Spectrum Disorders: a Randomized Controlled Trial Study. Cerebellum 22, 1109–1117 (2023). https://doi.org/10.1007/s12311-022-01481-6

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