Self-regulation of brain oscillations as a treatment for aberrant brain connections in children with autism

Autism is a highly varied developmental disorder typically characterized by deficits in reciprocal social interaction, difficulties with verbal and nonverbal communication, and restricted interests and repetitive behaviors. Although a wide range of behavioral, pharmacological, and alternative medicine strategies have been reported to ameliorate specific symptoms for some individuals, there is at present no cure for the condition. Nonetheless, among the many incompatible observations about aspects of the development, anatomy, and functionality of the autistic brain, it is widely agreed that it is characterized by widespread aberrant connectivity. Such disordered connectivity, be it increased, decreased, or otherwise compromised, may complicate healthy synchronization and communication among and within different neural circuits, thereby producing abnormal processing of sensory inputs necessary for normal social life. It is widely accepted that the innate properties of brain electrical activity produce pacemaker elements and linked networks that oscillate synchronously or asynchronously, likely reflecting a type of functional connectivity. Using phase coherence in multiple frequency EEG bands as a measure of functional connectivity, studies have shown evidence for both global hypoconnectivity and local hyperconnectivity in individuals with ASD. However, the nature of the brain’s experience-dependent structural plasticity suggests that these abnormal patterns may be reversed with the proper type of treatment. Indeed, neurofeedback (NF) training, an intervention based on operant conditioning that results in self-regulation of brain electrical oscillations, has shown promise in addressing marked abnormalities in functional and structural connectivity. It is hypothesized that neurofeedback produces positive behavioral changes in ASD children by normalizing the aberrant connections within and between neural circuits. NF exploits the brain’s plasticity to normalize aberrant connectivity patterns apparent in the autistic brain. By grounding this training in known anatomical (e.g., mirror neuron system) and functional markers (e.g., mu rhythms) of autism, NF training holds promise to support current treatments for this complex disorder. The proposed hypothesis specifically states that neurofeedback-induced alpha mu (8–12 Hz) rhythm suppression or desynchronization, a marker of cortical activation, should induce neuroplastic changes and lead to normalization in relevant mirroring networks that have been associated with higher-order social cognition.     

Modeling the connections of brain regions in children with autism using cellular neural networks and electroencephalography analysis

The brain connections in the different regions demonstrate the characteristics of brain activities. In addition, in various conditions and with neuropsychological disorders, the brain has special patterns in different regions. This paper presents a model to show and compare the connection patterns in different brain regions of children with autism (53 boys and 36 girls) and control children (61 boys and 33 girls). The model is designed by cellular neural networks and it uses the proper features of electroencephalography. The results show that there are significant differences and abnormalities in the left hemisphere, (p < 0.05) at the electrodes AF3, F3, P7, T7, and O1 in the children with autism compared with the control group. Also, the evaluation of the obtained connections values between brain regions demonstrated that there are more abnormalities in the connectivity of frontal and parietal lobes and the relations of the neighboring regions in children with autism. It is observed that the proposed model is able to distinguish the autistic children from the control subjects with an accuracy rate of 95.1% based on the obtained values of CNN using the SVM method.     

A proposed mechanism for autism: an aberrant neuroimmune response manifested as a psychiatric disorder

Autism, an incurable neurodevelopmental brain disorder, is a complex psychopathology in which the affected individual cannot effectively self-regulate their sensory inputs toward coherent and focused motor outputs. There have been many hypotheses as to the etiology of autism - genetics, neurotransmitter imbalances, early childhood immunizations, xenobiotic and teratogenic agents, and maternal infection; the disorder can perhaps be studied best under the field of "Psychoneuroimmunology", which analyzes systemic and psychopathologies from an integrated approach through the combined effects of the nervous, immune, and endocrine systems. Using principles of psychoneuroimmunology along with previously established but yet un-linked scientific principles and observations, this paper proposes a neuroimmune-based mechanistic hypothesis for the etiology of autism that connects elevated levels of maternal pro-inflammatory cytokines to autistic symptoms in her offspring through a logical sequence of events. While both researchers and clinicians often note correlations between pro-inflammatory cytokine levels and autistic symptoms in affected individuals, no specific mechanism has been documented that logically and directly connects the two. I propose that pro-inflammatory cytokines arising from maternal inflammation, infection, and, possibly, autoimmunity, pass through the placenta; enter the fetal circulation; cross the fetal blood-brain barrier (BBB); and cause aberrant neuronal growth and plasticity within the fetal brain via a "cytokine-storm". Microglia and astrocyte stimulation lead to a positive-feedback loop that also facilitates the development of a chronic inflammatory environment within the fetus, pre-disposing it to lifelong comorbid psychiatric and systemic pathologies. Such a mechanism could account for many of the observed symptoms and behaviors of autistic individuals such as hyper-sensitivity to environmental stimuli, object fixation, echolalia, repetitive physical behaviors, chronic enterocolitis, autoimmune disease, and, at the extreme, savantism. The thiazolidinedione pioglitazone (and possibly rosiglitazone), a non-steroidal anti-inflammatory drug (NSAID), which is commonly used to lower blood glucose levels and associated inflammatory markers in patients with diabetes, and histamine receptor blockers, as well as monitoring and limiting sucrose-containing foods, might prove to be effective preventative therapies for the development of autism in the fetus for pregnant women displaying either a cytokine-induced depression or other elevated systemic inflammatory state conditions.     

Sensory connection,interest/attention and gamma synchrony in autism or autism,brain connections and preoccupation

Does motivational interest increase gamma synchrony across neuronal networking to enable computation of related sensory inputs that might lead to greater social understanding in autism spectrum conditions (ASC)? Meaning, is it possible/likely that in autism because individuals process one aspect of sensory input at any one time (therefore missing the wider picture in general) when they are motivated/interested or attending to particular stimuli their attention window is widened due to increased gamma synchrony and they might be enabled to connect in ways that do not occur when they are not motivated? This is my current research question. If gamma synchrony is helping with the binding of information from collective sensory inputs, in ASC, when and only if the individual is motivated, then this has huge potential for how learning might be encouraged for individuals with an ASC.     

Individual behavioral profiles and predictors of treatment effectiveness for children with autism

Differential responsiveness to intervention programs suggests the inadequacy of a single treatment approach for all children with autism. One method for reducing outcome variability is to identify participant characteristics associated with different outcomes for a specific intervention. In this investigation, an analysis of archival data yielded 2 distinct behavioral profiles for responders and nonresponders to a widely used behavioral intervention, pivotal response training (PRT). In a prospective study, these profiles were used to select 6 children (3 predicted responders and 3 predicted nonresponders) who received PRT. Children with pretreatment responder profiles evidenced positive changes on a range of outcome variables. Children with pretreatment nonresponder profiles did not exhibit improvements. These results offer promise for the development of individualized treatment protocols for children with autism.     

Targeting neurotensin as a potential novel approach for the treatment of autism

The pathophysiology of autism remains obscure. Recently, serum neurotensin levels in children with autistic disorder have been found to be higher than those of normal children. Neurotensin is known to intensify neuronal NMDA-mediated glutamate signaling, which may cause apoptosis in autism. Further, an imbalance of glutamate/GABAergic system in autism has been described. These observations lead to a postulate that neurotensin may accentuate the hyperglutaminergic state in autism, leading to apoptosis. Targeting neurotensin might be a possible novel approach for the treatment of autism.     

Neurocognitive and electrophysiological evidence of altered face processing in parents of children with autism: implications for a model of abnormal development of social brain circuitry in autism

Neuroimaging and behavioral studies have shown that children and adults with autism have impaired face recognition. Individuals with autism also exhibit atypical event-related brain potentials to faces, characterized by a failure to show a negative component (N170) latency advantage to face compared to nonface stimuli and a bilateral, rather than right lateralized, pattern of N170 distribution. In this report, performance by 143 parents of children with autism on standardized verbal, visual-spatial, and face recognition tasks was examined. It was found that parents of children with autism exhibited a significant decrement in face recognition ability relative to their verbal and visual spatial abilities. Event-related brain potentials to face and nonface stimuli were examined in 21 parents of children with autism and 21 control adults. Parents of children with autism showed an atypical event-related potential response to faces, which mirrored the pattern shown by children and adults with autism. These results raise the possibility that face processing might be a functional trait marker of genetic susceptibility to autism. Discussion focuses on hypotheses regarding the neurodevelopmental and genetic basis of altered face processing in autism. A general model of the normal emergence of social brain circuitry in the first year of life is proposed, followed by a discussion of how the trajectory of normal development of social brain circuitry, including cortical specialization for face processing, is altered in individuals with autism. The hypothesis that genetic-mediated dysfunction of the dopamine reward system, especially its functioning in social contexts, might account for altered face processing in individuals with autism and their relatives is discussed.     

Sleep problems in children with autism

Autism is a developmental disability characterized by severe deficits in social interaction and communication, and the presence of repetitive-ritualistic behaviors. Sleep problems are frequently reported by parents of children with autism with prevalence estimates of 44-83% for sleep disorders in this population. To better understand sleep in autism, we surveyed sleep problems in 210 children with autism using a Likert-based questionnaire for parent report. The most frequently reported sleep problems included difficulty in falling asleep, restless sleep, not falling asleep in own bed, and frequent wakenings. Least frequently reported sleep problems were sleep walking, morning headaches, crying during sleep, apnea, and nightmares. When surveys were divided into mental retardation (MR)/not MR categories, no significant differences were identified in frequencies of reported sleep problems except for waking at night which occurred much more frequently in the MR group. There was also no difference in sleep problems related to age of the child other than nocturnal enuresis. An association was noted between certain medical problems and sleep problems. Vision problems, upper respiratory problems, and runny nose were associated with decreased nighttime sleep. Vision problems, poor appetite, and poor growth were associated with increased nighttime waking. Poor appetite and poor growth were associated with decreased willingness to fall asleep. This study confirms a high prevalence of sleep problems reported by parents of children with autism and points to the need for more systematic research as an initial step in developing treatment strategies.     

Sensory gating in young children with autism: relation to age, IQ, and EEG gamma oscillations

Unusual reactions to auditory stimuli are often observed in autism and may relate to ineffective inhibitory modulation of sensory input (sensory gating). A previous study of P50 sensory gating did not reveal abnormalities in high-functioning school age children [C. Kemner, B. Oranje, M.N. Verbaten, H. van Engeland, Normal P50 gating in children with autism, J. Clin. Psychiatry 63 (2002) 214-217]. Sensory gating deficit may, however, characterize younger children with autism or be a feature of retarded children with autism, reflecting imbalance of neuronal excitation/inhibition in these cohorts. We applied a paired clicks paradigm to study P50 sensory gating, and its relation to IQ and EEG gamma spectral power (as a putative marker of cortical excitability), in young (3-8 years) children with autism (N=21) and age-matched typically developing children (N=21). P50 suppression in response to the second click was normal in high-functioning children with autism, but significantly (p<0.03) reduced in those with mental retardation. P50 gating improved with age in both typically developing children and those with autism. Higher ongoing EEG gamma power corresponded to lower P50 suppression in autism (p<0.02), but not in control group. The data suggest that ineffective inhibitory control of sensory processing is characteristic for retarded children with autism and may reflect excitation/inhibition imbalance in this clinical group.     

Exercise as a treatment for hypertension in low-socioeconomic-status black children

Low-socioeconomic-status (SES) Black children have a higher mean blood pressure than most other groups. The antihypertensive effects of a 12-week aerobic exercise program were examined on 11 low-SES Black children, ages 8-12, who had blood pressure above the 95th percentile. A multiple baseline across three groups of children with baseline and exercise conditions was conducted. After the introduction of the exercise program, there were significant decreases in diastolic and systolic blood pressure. Cardiovascular fitness improved concurrently. The results suggest that vigorous exercise can decrease the blood pressure of low-SES hypertensive Black children.     

Risk of autism spectrum disorder in children with a history of hospitalization for neonatal jaundice

Background/aim Limited research has focused explicitly on the association between neonatal jaundice and autism spectrum disorder (ASD), and inconclusive evidence exists in the literature within this framework. This study aimed specifically to investigate whether neonatal jaundice is a potential risk factor for ASD and whether there is a connection between the types of neonatal jaundice and the severity of ASD.Materials and methodThis study involved 119 children with ASD [90 males (75.6%), 29 females (24.4%), mean age: 45.39 ± 11.29 months] and 133 healthy controls [100 males (75.2%), 33 females (24.8%), mean age: 46.92 ± 11.42 months]. Psychiatric disorders were diagnosed through the Diagnostic and Statistical Manual of Mental Disorders criteria. Childhood Autism Rating Scale (CARS) was used to assess the screening and diagnosis of autism. A specially prepared personal information sheet was employed to investigate socio-demographic characteristics and birth and clinical histories.ResultsThe rate of the history of jaundice and pathological jaundice requiring hospitalization and phototherapy were significantly higher in the ASD group compared to the controls. CARS total score and the mean scores of nearly all items were statistically higher in children with a history of pathological jaundice than those with a history of physiological jaundice.Conclusion Neonatal jaundice, depends on its severity, seems to be one of the possible biological factors associated with subsequent development of and the severity of ASD. Establishing a causal relationship between neonatal jaundice and ASD by more comprehensive studies may contribute to alleviating of the severity of ASD for individuals at risk.     

Converging evidence for brain stem injury in autism

The hypothesis that brain stem injury plays a role in the autism spectrum disorders was suggested by evidence that exposure to thalidomide during the earliest stages of brain development increases the risk of autism spectrum disorders. The implications for the embryological origin of autism first led to studies of neuroanatomy in a human case and an animal model and then to examinations of minor craniofacial features in autism. But the general hypothesis had much broader implications. It has now generated studies of the behavioral and neurological symptoms of human patients, of human molecular genetics and population genetics, and of animal behavioral teratology and molecular pharmacology. The collection of this range of data was made possible by adding experts from many fields to the research team. They worked both independently and collaboratively to try to unravel the etiology of autism.     

Colonic aberrant crypts in children with familial adenomatous polyposis

Aberrant crypt foci of the colonic mucosa have been reported in adults. The alteration may be defined macroscopically or histologically and may or may not be combined with adenomatous changes. Aberrant crypt foci have been regarded as precancerous lesions and are more common in patients with familial adenomatous polyposis. The present report describes the presence of many histologically recognizable aberrant crypt foci without adenomatous changes in the colonic mucosa of 3 children with familial adenomatous polyposis. The openings of the aberrant crypt foci contained inspissated granulofilamentous mucus. Additionally, this report documents the presence of a peculiar serrated appearance of the mucosae surface outline of the nonadenomatous areas. This appears to result from elongation of the crypts and dilated openings/micropapillary arrangement of the uppermost part of the walls of the crypts, with a thin intervening stroma. Neither of these findings has been reported previously to occur in children. They may represent the earliest histologically identifiable changes ever recorded in the colon of patients with familial adenomatous polyposis.     

Memory for actions in children with autism: self versus other

In order to ask whether autism is associated with difficulty in self-monitoring we gave a group of children and adolescents with autism a task in which they themselves had to remember whether they or another person had performed certain actions. In our first experiment, three groups of participants had to recall whether placements of picture cards had been made by themselves or by the experimenter. The participants with autism performed at a much lower level than the two comparison groups and, unlike the comparison groups, were not better at recalling their own placements. A second experiment tested the prediction arising from the monitoring-deficit account that the children with autism would be unimpaired when the placement of the items did not alternate between self and other. This prediction was confirmed moderately well. Additionally, in contrast to that of the comparison groups, the performance of the participants with autism was unaffected by whether self or other displaced the items. This is consistent with the existence of a monitoring deficit.     

Source memory in children with autism spectrum disorders

The evidence to date regarding memory processes in children with autism spectrum disorders (ASD) remains equivocal. Although children with these neurodevelopmental disorders have been shown to display exceptional memories for fact-based information, they seem to be less able to attach meaning or context to their memories. Thus, this study investigated the specific role of source memory in autism. Children with ASD were compared to a chronological and mental age-matched comparison group of typically developing children. Although children with autism performed similarly to controls on a fact recognition measure, their performance on a source memory task was significantly lower. The findings indicated, however, that the nature of source memory confusion in children with autism does not appear to reflect a generalized deficit in attaching context to memories but rather is dependent on the specific to-be-remembered information that, in this study, involves social aspects of context.