Autism Spectrum Disorder: Neuromodulation, Neurofeedback, and Sensory Integration Approaches to Research and Treatment

 

Preface

Manuel F. Casanova and Estate M. Sokhadze

University of South Carolina School of Medicine-Greenville, Greenville, SC

 

Luigi Galvani’s accidental discovery in 1780 that a dead animal’s muscles could twitch, if stimulated by an electrical spark, engendered the idea of “animal electricity”.  Nerves were more than tubes filled with fluid; they were conduits for electrical current.  Science stood in opposition to religion as it rapidly eroded the foundation of vitalism.  In a macabre leap of faith, Galvani’s nephew, Giovanni Aldini, progressed from frog legs to attempts at the reanimation of criminals. He would wait by the guillotine to collect the fresh specimens provided by decapitation and then pass a current through their mouth and ears so as to provoke facial grimacing. Reports of such efforts inspired Mary Shelley to write Frankenstein, the sapient creature whose vitality and life force originated from a burst of electricity; a force that presumably breached life and death.  The experiments sparked a debate as to the existence of an intrinsic source of animal electricity and whether the same was phenomenologically identical to other natural phenomena.  During this transformative time period, Benjamin Franklin (1752) showed that lightning was electrical in nature.  He also helped explain the behavior of the Leyden Jar, an early capacitor, as a storage device of electric charge.  Indeed, Benjamin Franklin introduce the term Leyden battery to describe the grouping together of a number of Leyden jars.  Shortly afterwards, Alessandro Volta combined zinc and copper discs in an acidic solution to provide a pile wherein the number of cells influenced the shock they produced. Contrary to the Leyden jar, the voltaic pile was able to deliver continuous electric current to a circuit.  Until the introduction of the dynamo in the 1870s, the electrical industry was powered by batteries.

The initial attempts at electrotherapy used electric baths and Oudin coils (an autotransformer) as means of delivering high voltages at low current levels to patients.  The availability of portable devices powered by batteries allowed for a more moderate and controlled intervention.  However, these improvised machines were soon adapted so that the low voltages produced by batteries were stepped up by transformers thus shocking those patients that held the electrodes in their hands or had them applied somewhere else on their bodies.  The machines looked impressive and complex enough to generate a placebo effect.  Electrotherapy was soon the object of wild theoretical assertions and a quack cure for a vast variety of conditions.  Among these, Radionics was the brainchild of Albert Abrams, a physician, who claimed to diagnose the ills of patients without meeting them in person. A sample derived from a patient (e.g., hair, blood, or handwritten note) was attached to a machine that allowed a measure of its “energy frequency”. It was Dr. Abrams belief that disease was caused by unhealthy frequencies and that they could be countered by healthy ones.  The American Medical Association went on to described Abrams as the “dean of gadget quacks” (Barrett, 2012).

One of the many imitators of Abrams was Royal Raymond Rife, an American inventor, who claimed to have visualized microbes with a specially designed optical microscope. He believed that these pathogens were the cause of cancer and themselves could be destroyed by applying a beam ray of destructive resonant frequencies.  Several deaths have resulted from the use of Rife’s devices and its fraudulent claims.

In the midst of these controversial claims, in the 1930’s, electroconvulsive therapy (ECT) was introduced to medical practice as a way of treating mental disorders. Drugs inducing convulsions had already been used in medical practice. The electric current passing through the brain induced a seizure lasting 30 to 60 seconds.  At the beginning, patients were not given anesthesia and high levels of current were used.  However, the technique was steadily modified and side effects were avoided.  It is presently used under anesthesia in patients with severe major depression, bipolar disorder or schizophrenia, that have not responded to other treatments.

By altering the action of nerve cells, ECT started the modern era of neuromodulation which now spans non-invasive (e.g., transcranial magnetic stimulation) and invasive techniques (e.g., deep brain stimulation).  Most of these techniques are thought to act by altering natural biological mechanisms and seem to find a place in multidisciplinary treatment settings when use of other interventions (e.g., drugs) may lead to the development of tolerance, addiction or adverse side effects.  Moreover, neuromodulation seems to be a promising treatment for some neurodevelopmental disorders.  Many of these conditions are recognized as complex or multifactorial disorders which are not tied to a single genetic cause.  Neurodevelopmental disorders are likely polygenic in origin and their expression dependent on lifestyle and environmental factors.  Indeed, the nature of multifactorial disorders makes them difficult to treat.  Drugs may target only one neurochemical system, when many different ones may be affected. Treatment is also compounded by the heterogeneity of clinical manifestations among affected patients.  Multifactorial conditions in this regard calls for individualized or precision interventions for homogenous subgroups within what otherwise may be described as a spectrum of disorders.

Autism spectrum disorder (ASD) is a multifactorial condition of unknown origin. A triple hit hypothesis postulates the necessity of the combined influences of a genetic risk factor, environmental exigencies and a vulnerable time period of brain development (Casanova, 2007).  Symptoms suggest that it is a gray matter disease of generalized spread throughout the cerebral cortex while the presence of seizures indicates an imbalance in its excitatory to inhibitory bias.  EEG and threshold studies of vibrotactile sensation elucidates this shift in the excitatory/inhibitory bias as a defect of lateral inhibition.  The suggested pathology can be targeted by neuromodulation techniques while simultaneously providing for putative severity dependent outcome measures.

Transcranial magnetic stimulation (TMS) was the first neuromodulation technique used in ASD that targeted core pathological processes (Sokhadze et al., 2009).  Until that moment in time, therapeutic attempts in autism had been symptomatic and, in the case of drugs, had severe side effects.  Several hundred patients have now been treated in this way with significant improvements in behavior.  Synergism has now been reported when combining this technique with neurofeedback (Sokhadze et al., 2014). Given the high comorbidity between autism and attention deficit/hyperactivity disorder (ADHD) it will be useful to explore whether any benefit accrued to neurofeedback is primarily evident in this subgroup of patients.

In this book several researchers report their results using rTMS in autism.  Gomez et al.expand on several of their clinical trials and summarize the status of the field while Casanova et al. review some of their rTMS work as related to gamma oscillations.  In complementary fashion, Ni and Huang review the use of patterned theta burst TMS application in autism and report clinical results of their own trial.  Given the preliminary success of neuromodulation in ASD, the reader may consider it wise to think about other techniques of bran activity entrainment and, indeed, Casanova et al. propose using sympathetic (passive) resonance as a potential method of altering brain waves and behavioral states in autism.

More recently, low constant current stimulation has been introduced as a way of altering the resting membrane potential of neurons.  The simplicity, accessibility, and low risk of using a battery powered device has procreated a vast amount of research.  Studies are now focusing on its putative effects in autism.  Preliminary results show improvements in both behavioral and cognitive symptoms. Parmar et al. review the application of transcranial direct current stimulation (tDCS) in their chapter. Future research will focus on standardizing protocols, defining the most appropriate outcome measures and how enduring are its effects.

Electroencephalographic (EEG) biofeedback (i.e., neurofeedback) has more than 60 years of history steaming from the studies of Kamiya, Hardt, Green, Tansey, Sterman and other pioneers in late 60s and early 70s. Neurofeedback (NFB) has been recognized as a suitable tool for detecting and modulating neural plasticity.  By operant conditioning of EEG, NFB provides an effective way to train electrophysiological activity of the targeted cortical topography. Neurofeedback training is considered as one of the most effective and salient treatments for children with attention deficit hyperactivity (ADHD). The clinical efficacy of using NFB for ADHD treatments was reviewed and discussed in several meta-analyses of randomized clinical trials (Arns et al., 2009, 2013, 2014; Hurt et al., 2014). Considering that NFB has gained significant support as an effective treatment for ADHD, some attempts have been made to transfer this ADHD neurotherapy technique to treat core symptoms of ASD. Still, the question remains unanswered as to whether present day protocols that have been shown efficacious in ADHD are also effective for ASD.

Several papers reviewed application of neurofeedback for ASD treatment and many of them provide evidence that some of the core symptoms of autism can be improved by using neurofeedback training (Coben, 2013; Jarusiewicz, 2002; Kouijzer et al., 2009, 2013 ; Linden & Gunkelman, 2013; Wang et al., 2016). Most of them used suppression of theta at fronto-central or central sites, enhancement of low beta (13-21 Hz, sometimes 13-18 Hz) sub-band, or enhancement of sensory-motor rhythm (SMR, 12-15 Hz) at the central sites (C3, Cz, C4). Another line of treatment based on neurofeedback focuses on mu-rhythm training (Pineda et al., 2014). Some protocols use quantitative EEG-guided and coherence measures (Coben, 2013; Linden & Gunkelman, 2013).  Our group’s approach included neurofeedback training at the prefrontal topography, specifically at the midline prefrontal site. This selection of cortical topography was determined by prior studies on gamma oscillations in children with autism showing alterations of evoked and induced gamma oscillations during attention tests demonstrating notable changes at frontal topographies (Sokhadze et al., 2009). In our pilot study (Wang et al., 2016) using 40 Hz gamma power upregulation we found that theta-to-beta ratio showed a significant linear decrease over 18 sessions of neurofeedback. The positive effects of neurofeedback training further was manifested by improvement in the aberrant behavior scores. In a pilot study presently underway we have compared outcomes of 18 vs. 24 vs. 36 sessions of neurofeedback using three different NFB training protocol in children with autism and 2 or 3 sessions per week. More data on application of neurofeedback in ASD treatment can be found in the chapter by Basterian et al.

We decided to include in this book sensory integration approaches because sensory abnormalities are typical of autism spectrum disorder. Sensory stimuli cause inappropriate responses with some ASD individuals exhibiting over-stimulation, others showing under-stimulation, and some exhibiting both conditions at various times. These sensory challenges may result in some forms of the unusual behaviors that are present in autism (O’Connor, 2012). Many treatments and interventions have focused on methods to reduce the abnormalities of sensory processing in autism.  Sensory integration intervention is the most commonly implemented therapy by occupational therapists for children with ASD and is one of the most commonly requested types of Occupational Therapy treatments in general (Goin-Kochel et al., 2007).  In a chapter by Schoen et al. the authors describe their approaches to sensory integration in children with ASD.

A variety of interventions directed at reducing sound sensitivity and related auditory problems are currently used by practitioners and parents, with positive results reported in many cases. The Berard method of auditory integration training (AIT) is of particular interest for several reasons. There are some research studies that do provide behavioral and some physiological data to document efficacy (Berard & Brockett, 2011; Rimland & Edelson, 1994). The Berard AIT program is based on a theory that the use of electronically modulated, and on occasion, selectively filtered music, retrains the ear and auditory system to work properly. More detailed insight about Berard AIT is described in the chapter by Brockett.

According to several recent theories sensory processing abnormalities may play an important role in impairments of perception, cognition, and behavior noted in individuals with autism. Among these sensory abnormalities visual distortion may force autistic individuals to rely on peripheral vision, develop strabismus, and manifestation “stereotypic behaviors”. In a chapter by Kaplan and Kotsamanidis–Burg the authors review visual processing abnormalities typical for autism and visuo-motor training and therapy based on wearing prism lenses and intensive visual therapy course. The chapter is followed by a pilot experimental study conducted by Sokhadze et al. using Kaplan’s method of behavioral visual therapy.

The book is concluded by a series of cases studies where rTMS, neurofeedback, and sensory integration therapies (AIT, prism lenses-based therapy) are used in combination. Despite increased awareness about autism and increased prevalence of autism in the USA and worldwide, there is relatively little information available about the basics of core clinical symptoms and behavioral features of autism spectrum disorder and standard methods of diagnostic and treatment standards. This is one of the main reasons why we decided to write this book with two chapters devoted to clinician’s perspective on diagnostic and treatment of ASD. One more chapter is devoted to some questions related to genetic risks of autism. Another chapter by Sokhadze et al. reviews the role of autonomic nervous system dysfunctions in autism.

The book was initially planned as a collection of studies devoted to neuromodulation methods application in autism research and treatment but ended up with a wider scope, as understanding of various aspects of autism spectrum disorder is not possible without addressing numerous important clinical and neurodevelopmental facets of the disorder.  Even though it was technically impossible to cover all past and current approaches to neuromodulation, neurofeedbak and sensory integration therapies in autism, we hope that this book will serve as a useful contribution to the literature on this topic.

Published by the Foundation for Neurofeedback and Neuromodulation Research (available for preorder, to be printed sometime during March 2019).  Softbound, 392 pages, $69.00 from Amazon.

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