The association of manganese overexposure and neurobehavioral function is moderated by arsenic: A metal mixture analysis of children living near coal ash storage sites.

Manganese is an essential element but can be neurotoxic if overexposed. Our previous study found that a higher level of manganese in nail biomarkers from children living near coal ash storage sites was associated with poorer neurobehavioral function. Children living near this type of pollution may be exposed to other metal neurotoxicants and a better understanding of manganese in the context of multiple exposures is needed. Mixture analyses were completed using nail samples from 251 children aged 6-14 years old. These biomarkers containing metals known to impact brain functioning were investigated to test our hypothesis that a mixture of metals including manganese impacts the development of children living near coal ash sites. Nails collected from children were analyzed using ICP-MS for manganese, arsenic, cadmium, lead, and zinc based on previous research on neurotoxicity. Bayesian kernel machine regression (BKMR) was used while adjusting for age, sex, and maternal education as potential covariates. Children also completed the Behavioral Assessment Research System (BARS) to provide neurobehavioral measures of attention and processing speed as outcomes for mixture analyses. Metal mixture analyses indicated that the relationship of manganese concentration and attention and processing speed was moderated by arsenic.,. When nail biomarkers for arsenic were highest (90th percentile), manganese was associated with poorer neurobehavioral performance on the BARS, measured by CPT hit latency. At low levels of arsenic (10th percentile), there was no evidence of harmful effects from overexposure to manganese on CPT hit latency based on BKMR analysis. Previously reported effects of manganese on neurobehavioral function may be moderated by arsenic exposure. Metal exposures and behavior outcomes can be studied with mixture analyses such as BKMR to evaluate effects of simultaneous exposures on children exposed to pollution.

Indoor coal ash and school and social competency among children aged 6-14 years.

BACKGROUND: A child's ability to succeed in social interactions and in a school setting are important for their development and growth. Exposure to environmental pollutants has been associated with poorer school performance and fewer social interaction in children. Fly ash, a waste product generated when burning coal for energy, is comprised of small glass spheres with neurotoxic heavy metal(loid)s found to be risk factors for learning and social problems in school. OBJECTIVE: The purpose of this novel study was to assess the association of fly ash in children's homes with school and social competency. METHODS: We recruited children aged 6-14 years old from communities located within 10 miles of two coal-burning power plants. In homes of the participants, fly ash was collected on polycarbonate filters using personal modular impactors. We measured school competency and social competency using the validated Child Behavioral Checklist. Using Tobit and linear regression we investigated the relationship of indoor fly ash with school and social competency. RESULTS: Forty-three percent of children in the study had fly ash in their homes. In covariate-adjusted Tobit models, children with fly ash in their homes scored on average 2.63 (95% CI: -4.98, -0.28) points lower on the school competency scale than peers without ash in their homes. We did not observe that fly ash in homes was related with lower social competency. SIGNIFICANCE: Results from this study suggest that children with fly ash in their homes had poorer performance in the school setting, compared to peers without fly ash in their homes. In the US, coal-fired power plants are being closed, however health concerns about pollution from coal ash storage facilities remains. Findings from this study can provide impetus for creating of public health policy and to highlight the need future research on children's exposure to fly ash. IMPACT: Children's growth and development are impacted by their social interactions and ability to perform in school settings. Environmental pollutants may impact these essential elements of development. Millions of children are exposed to fly ash which is a waste product generated from burning coal. Fly ash, an environmental health threat throughout the world, is comprised of small glass spheres with trace concentrations of neurotoxic metal(loid)s. Findings from this research show that children with fly ash in their homes are significantly more likely to have poorer school performance than children without fly ash in their homes.

Exposure to coal ash and depression in children aged 6-14 years old.

BACKGROUND: When coal is burned for energy, coal ash, a hazardous waste product, is generated. Throughout the world, over 1 billion tons of coal ash is produced yearly. In the United States, over 78 million tons of coal ash was produced in 2019. Fly ash, the main component of coal ash contains neurotoxic metal (loid)s that may affect children's neurodevelopment and mental health. The objective of this study was to investigate the association between fly ash and depressive problems in children aged 6-14 years old. METHODS: Children and their parents/guardians were recruited from 2015 to 2020. Tobit regression and logistic regression were used to assess the association between coal fly ash and depressive problems. To determine fly ash presence, Scanning Electron Microscopy was conducted on polycarbonate filters containing PM10 from the homes of the study participants. Depressive problems in children were measured using the Depressive Problems DSM and withdrawn/depressed syndromic problem scales of the Child Behavior Checklist. RESULTS: In covariate-adjusted Tobit regression models, children with fly ash on the filter had higher scores on the DSM Depressive Problems (3.13 points; 95% CI = 0.39, 5.88) compared with children who did not have fly ash on the filter. Logistic regression supported these findings. CONCLUSION: Coal ash is one of the largest waste streams in the U.S, but it is not classified as a hazardous waste by the Environmental Protection Agency. To our knowledge, no studies have assessed the impact of coal ash on children's mental health. This study highlights the need for further research into the effects of coal ash exposure on children's mental health, and improved regulations on release and storage of coal ash.

Proximity to coal-fired power plants and neurobehavioral symptoms in children.

BACKGROUND: Coal-fired power plants are a major source of air pollution that can impact children's health. Limited research has explored if proximity to coal-fired power plants contributes to children's neurobehavioral disorders. OBJECTIVE: This community-based study collected primary data to investigate the relationships of residential proximity to power plants and neurobehavioral problems in children. METHODS: 235 participants aged 6-14 years who lived within 10 miles of two power plants were recruited. Exposure to particulate matter ≤10 µm (PM10) was measured in children's homes using personal modular impactors. Neurobehavioral symptoms were assessed using the Child Behavior Checklist (CBCL). Multiple regression models were performed to test the hypothesized associations between proximity/exposure and neurobehavioral symptoms. Geospatial statistical methods were used to map the spatial patterns of exposure and neurobehavioral symptoms. RESULTS: A small proportion of the variations of neurobehavioral problems (social problems, affective problems, and anxiety problems) were explained by the regression models in which distance to power plants, traffic proximity, and neighborhood poverty was statistically associated with the neurobehavioral health outcomes. Statistically significant hot spots of participants who had elevated levels of attention deficit hyperactivity disorder, anxiety, and social problems were observed in the vicinity of the two power plants. SIGNIFICANCE: Results of this study suggest an adverse impact of proximity to power plants on children's neurobehavioral health. Although coal-fired power plants are being phased out in the US, health concern about exposure from coal ash storage facilities remains. Furthermore, other countries in the world are increasing coal use and generating millions of tons of pollutants and coal ash. Findings from this study can inform public health policies to reduce children's risk of neurobehavioral symptoms in relation to proximity to power plants.

Heavy Metal(loid) Body Burden in Environmentally Exposed Children With and Without Internalizing Behavior Problems.

The prevalence of internalizing behavior disorders in children is increasing. Reasons for increasing anxiety and depression include several factors with a less studied consideration being the potential neurotoxic effects of environmental exposures. One group at risk for environmental exposures is children living near coal-burning power plants with coal ash storage facilities. Multivariate logistic regression was used to assess the relationship between metal(loid) exposures and internalizing behaviors in children aged 6-14 years. Metal(loid)s in nail samples were determined by Proton-Induced X-ray Emission and internalizing behavior problems were obtained from the parent ratings on the Child Behavior Checklist. Results indicated that concentrations of metal(loid)s in nails differ between children with internalizing behaviors and without internalizing behaviors. Logistic regression models suggested that exposure to zinc and imputed zirconium were associated with internalizing behaviors in children. However, when a sex-metal(loid) interaction term was included, none of the metal(loid)s were associated with internalizing behaviors indicating a role of sex differences in neurotoxicity with zinc and copper showing effects only for males. In all models, greater exposure to traffic was associated with internalizing behaviors. Zinc has previously been shown to increase risk for mental health problems, while zirconium has received less attention. Out findings indicate that environmental exposures of zinc and zirconium deserve further attention in studies of childhood internalizing disorders.

Manganese body burden in children is associated with reduced visual motor and attention skills.

Manganese (Mn) is an essential element, however, children with moderate to high Mn exposure can exhibit neurobehavioral impairments. One way Mn appears to affect brain function is through altering dopaminergic systems involved with motor and cognitive control including frontal - striatal brain systems. Based on the risk for motor and attention problems, we evaluated neurobehavioral function in 255 children at risk for Mn exposure due to living in proximity to coal ash storage sites. Proton Induced X-ray Emissions (PIXE) analysis was conducted on finger and toenails samples. Multiple neuropsychological tests were completed with the children. Fifty-five children had Mn concentrations above the limit of detection (LOD) (median concentration = 3.95 ppm). Children with detectable Mn concentrations had reduced visual motor skills (ß = -5.62, CI: -9.11, -2.12, p = 0.008) and more problems with sustained attention, based on incorrect responses on a computerized attention test, (ß = 0.40, CI: 0.21, 0.59, p < 0.001) compared with children who had Mn concentrations below the LOD. Findings suggest that Mn exposure impacts attention and motor control possibly due to neurotoxicity involving basal ganglia and forebrain regions. Visual-motor and attention tests may provide a sensitive measure of Mn neurotoxicity, useful for evaluating the effects of exposure in children and leading to better treatment options.

Nail Samples of Children Living near Coal Ash Storage Facilities Suggest Fly Ash Exposure and Elevated Concentrations of Metal(loid)s.

Children who live near coal-fired power plants are exposed to coal fly ash, which is stored in landfills and surface impoundments near residential communities. Fly ash has the potential to be released as fugitive dust. Using data collected from 263 children living within 10 miles of coal ash storage facilities in Jefferson and Bullitt Counties, Kentucky, USA, we quantified the elements found in nail samples. Furthermore, using principal component analysis (PCA), we investigated whether metal(loid)s that are predominately found in fly ash loaded together to indicate potential exposure to fly ash. Concentrations of several neurotoxic metal(loid)s, such as chromium, manganese, and zinc, were higher than concentrations reported in other studies of both healthy and environmentally exposed children. From PCA, it was determined that iron, aluminum, and silicon in fly ash were found to load together in the nails of children living near coal ash storage facilities. These metal(loid)s were also highly correlated with each other. Last, results of geospatial analyses partially validated our hypothesis that children's proximity to power plants was associated with elevated levels of concentrations of fly ash metal(loid)s in nails. Taken together, nail samples may be a powerful tool in detecting exposure to fly ash.

Protocol for measuring indoor exposure to coal fly ash and heavy metals, and neurobehavioural symptoms in children aged 6 to 14 years old.

INTRODUCTION: Fly ash is a waste product generated from burning coal for electricity. It is comprised of spherical particles ranging in size from 0.1 µm to over 100 µm in diameter that contain trace levels of heavy metals. Large countries such as China and India generate over 100 million tons per year while smaller countries like Italy and France generate 2 to 3 million tons per year. The USA generates over 36 million tons of ash, making it one of the largest industrial waste streams in the nation. Fly ash is stored in landfills and surface impoundments exposing communities to fugitive dust and heavy metals that leach into the groundwater. Limited information exists on the health impact of exposure to fly ash. This protocol represents the first research to assess children's exposure to coal fly ash and neurobehavioural outcomes. METHODS: We measure indoor exposure to fly ash and heavy metals, and neurobehavioural symptoms in children aged 6 to 14 years old. Using air pollution samplers and lift tape samples, we collect particulate matter ≤10 µm that is analysed for fly ash and heavy metals. Toenails and fingernails are collected to assess body burden for 72 chemical elements. Using the Behavioural Assessment and Research System and the Child Behaviour Checklist, we collect information on neurobehavioural outcomes. Data collection began in September 2015 and will continue until February 2021. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Boards of the University of Louisville (#14.1069) and the University of Alabama at Birmingham (#300003807). We have collected data from 267 children who live within 10 miles of two power plants. Children are at a greater risk for environmental exposure which justifies the rationale for this study. Results of this study will be distributed at conferences, in peer-reviewed journals and to the participants of the study.

Associations of the Behavioral Assessment and Research System (BARS) neurobehavioral outcomes with attention problems in children living near coal ash storage sites.

Environmental exposures have been linked to childhood problems with overactivity, attention, and impulse control, and an increased risk of attention deficit hyperactivity disorder (ADHD) diagnosis. Two approaches to identify these types of exposure-related neurobehavioral problems include the use of computerized tests, such as the Behavioral Assessment and Research System (BARS), as well as the use of behavior rating scales. To assess comparability of these two types of measures, we analyzed data from 281 children aged 6 to 14 years enrolled in a 5-year research study investigating coal ash exposure and neurobehavioral health. All children lived in proximity of coal ash storage sites. We administered six computer tests from the BARS and obtained behavior measures from the parent-completed Child Behavior Checklist (CBCL) ADHD DSM oriented scale. BARS test performance was associated with age indicating that the tests could be used to evaluate neurodevelopmental changes over time or across a wide age range. Tests within the BARS including Continuous Performance (CPT) false alarm (standardized estimate 1.57, 95% confidence interval (CI) (0.67, 2.48), adjusted p = 0.006), Selective Attention (SAT) wrong count (standardized estimate 2.8, 95% CI (1.17, 4.44), adjusted p = 0.006), and SAT proportion correct (standardized estimate -2.45, 95% CI (-4.01, -0.88), adjusted p = 0.01) were associated with attention and impulse control problems on the CBCL after adjustment for multiple comparisons. Findings support that the BARS can contribute to research on environmental exposures by assessing subclinical behaviors related to ADHD such as sustained attention, impulse control, response inhibition, associative learning, and short-term memory. Future research can examine relationships of these BARS measures with biomarkers of neurotoxic exposures related to living near coal ash storage sites to better identify the potential risk for ADHD-related behaviors among children living near coal ash storage sites.

Sex differences in the association between exposure to indoor particulate matter and cognitive control among children (age 6-14 years) living near coal-fired power plants.

Coal fly ash consists of inhalable particulate matter with varying concentrations of neurotoxic metals. Children living near coal-fired power plants with coal fly ash storage facilities may be exposed to coal fly ash when it escapes as fugitive dust emissions into surrounding communities. Previous research on outdoor particulate matter air pollution of similar aerodynamic diameter (PM10) suggests exposure may be associated with impaired cognitive control. The purpose of this research was to investigate sex-differences in the association between exposure to indoor PM10 and cognitive control among children (n = 221), ages 6-14 years, living near coal-fired power plants with fly ash storage facilities. In an ongoing community-based study, we measured indoor PM10 concentrations in participants' housing units and used performance measures from the BARS (Behavior Assessment and Research System) Continuous Performance Test (CPT) and Selective Attention Test (SAT) to assess neurotoxic effects on cognitive control. In adjusted negative binomial regression models, we found children living in housing units with higher indoor PM10 concentrations had a higher risk of commission errors on the CPT (incidence rate ratio (IRR) = 1.22 per interquartile range difference (IQR = 0.72 µg/m3) in natural log-transformed PM10 concentrations; 95% CI = 1.01, 1.46) and SAT (IRR = 1.14; 95% CI = 1.01, 1.28). Furthermore, child sex modified the association between PM10 concentration and CPT commission errors. Among females, higher PM10 concentration was associated with higher risk of CPT commission errors (IRR = 1.39; 95% CI = 1.06, 1.82), but we found no association among males (IRR = 1.01; 95% CI = 0.79, 1.30). We found no association between PM10 concentrations and CPT or SAT response latency. Our results suggest females living near coal-fired plants with coal fly ash storage facilities may be more susceptible to impaired cognitive control associated with particulate matter exposure. Children living near coal-fired power plants with coal fly ash storage facilities who are exposed to particulate matter may have an increased risk of impulse control problems.

Recruitment strategies and challenges: Lessons learned from a coal ash and children's health study.

The purpose of this paper is to describe the approaches and recruitment strategies of a study focused on the impact of coal fly ash on neurobehavioral performance among children living in proximity to coal-burning power plants. Challenges encountered with each recruitment approach are highlighted as well as solutions used to overcome those challenges and ultimately enroll children and one of their parents or guardians. To ensure participants were distributed throughout the study area, geographical information systems were used to guide recruitment and achieve the target sample size (N = 300). Several approaches were employed to recruit the number of needed participants, including "shoe leather" or door-to-door recruitment, placement of flyers and brochures in public spaces, mailings to targeted addresses, media announcements, and local government outreach. Since September 2015, 265 participants have been enrolled in the study using a combination of the described recruitment approaches. Even with a well-designed plan, it is important to re-examine strategies at every step to maximize recruitment efforts. Researcher flexibility in adapting to new strategies is vital in facilitating recruitment efforts, and the recruitment of participants in the study remains a dynamic and evolving process.

The Screen for Child Anxiety-Related Emotional Disorders Is Sensitive but Not Specific in Identifying Anxiety in Children with High-Functioning Autism Spectrum Disorder: A Pilot Comparison to the Achenbach System of Empirically Based Assessment Scales.

Validated brief screening instruments are needed to improve the detection of anxiety disorders in autism spectrum disorder (ASD). The Screen for Child Anxiety-Related Emotional Disorders (SCARED), a 41-item parent- and self-reported scale measuring anxiety, was compared to the Achenbach System of Empirically Based Assessment (ASEBA) scales. One hundred participants with a clinical diagnosis of high-functioning ASD, aged 8-18 years, and their parents completed the above scales. We hypothesized that the SCARED would be useful in screening for anxiety and its results for total scores of anxiety would converge with ASEBA syndrome scales for anxiety and internalizing disorders. Significant correlations were shown between the SCARED and the Child Behavior Checklist (CBCL) and Youth Self-Report (YSR) across a broad spectrum of scales. The CBCL syndrome scale for anxious/depressed showed the highest correlation and predicted anxiety scores on the SCARED. While many of the YSR scales significantly correlated with child ratings of anxiety, none of the scales predicted the SCARED child scores. Differences in self and parent reports suggest that parents interpret externalizing behaviors as signs of anxiety in ASD, whereas youth may describe internalized symptoms as anxiety. Females were more likely to self-report anxiety than males. Results support the use of the SCARED as a screening tool for anxiety in high-functioning ASD, but it should be supplemented with other tools to increase the specificity of its results.

Heart Rate Variability and Skin Conductance During Repetitive TMS Course in Children with Autism.

Autism spectrum disorder (ASD) is a developmental disorder marked by difficulty in social interactions and communication. ASD also often present symptoms of autonomic nervous system (ANS) functioning abnormalities. In individuals with autism the sympathetic branch of the ANS presents an over-activation on a background of the parasympathetic activity deficits, creating an autonomic imbalance, evidenced by a faster heart rate with little variation and increased tonic electrodermal activity. The objective of this study was to explore the effect of 12 sessions of 0.5 Hz repetitive transcranial magnetic stimulation (rTMS) over dorsolateral prefrontal cortex (DLPFC) on autonomic activity in children with ASD. Electrocardiogram and skin conductance level (SCL) were recorded and analyzed during each session of rTMS. The measures of interest were time domain (i.e., R-R intervals, standard deviation of cardiac intervals, NN50-cardio-intervals >50 ms different from preceding interval) and frequency domain heart rate variability (HRV) indices [i.e., power of high frequency (HF) and low frequency (LF) components of HRV spectrum, LF/HF ratio]. Based on our prior pilot studies it was proposed that the course of 12 weekly inhibitory low-frequency rTMS bilaterally applied to the DLPFC will improve autonomic balance probably through improved frontal inhibition of the ANS activity, and will be manifested in an increased length of cardiointervals and their variability, and in higher frequency-domain HRV in a form of increased HF power, decreased LF power, resulting in decreased LF/HF ratio, and in decreased SCL. Our post-12 TMS results showed significant increases in cardiac intervals variability measures and decrease of tonic SCL indicative of increased cardiac vagal control and reduced sympathetic arousal. Behavioral evaluations showed decreased irritability, hyperactivity, stereotype behavior and compulsive behavior ratings that correlated with several autonomic variables.

Relative Power of Specific EEG Bands and Their Ratios during Neurofeedback Training in Children with Autism Spectrum Disorder.

Neurofeedback is a mode of treatment that is potentially useful for improving self-regulation skills in persons with autism spectrum disorder. We proposed that operant conditioning of EEG in neurofeedback mode can be accompanied by changes in the relative power of EEG bands. However, the details on the change of the relative power of EEG bands during neurofeedback training course in autism are not yet well explored. In this study, we analyzed the EEG recordings of children diagnosed with autism and enrolled in a prefrontal neurofeedback treatment course. The protocol used in this training was aimed at increasing the ability to focus attention, and the procedure represented the wide band EEG amplitude suppression training along with upregulation of the relative power of gamma activity. Quantitative EEG analysis was completed for each session of neurofeedback using wavelet transform to determine the relative power of gamma and theta/beta ratio, and further to detect the statistical changes within and between sessions. We found a linear decrease of theta/beta ratio and a liner increase of relative power of gamma activity over 18 weekly sessions of neurofeedback in 18 high functioning children with autism. The study indicates that neurofeedback is an effective method for altering EEG characteristics associated with the autism spectrum disorder. Also, it provides information about specific changes of EEG activities and details the correlation between changes of EEG and neurofeedback indexes during the course of neurofeedback. This pilot study contributes to the development of more effective approaches to EEG data analysis during prefrontal neurofeedback training in autism.

Effects of weekly low-frequency rTMS on autonomic measures in children with autism spectrum disorder.

The term autism spectrum disorder (ASD) describes a range of conditions characterized by impairments in social interactions, communication, and by restricted and repetitive behaviors. Autism spectrum disorder may also present with symptoms suggestive of autonomic nervous system (ANS) dysfunction. The objective of this study was to determine the effect of 18 sessions of low frequency (LF) repetitive transcranial magnetic stimulation (rTMS) on autonomic function in children with ASD by recording electrocardiogram (ECG) and electrodermal activity (EDA) pre- post- and during each rTMS session. The autonomic measures of interest in this study were R-R cardiointervals in EKG (R-R), time and frequency domain measures of heart rate variability (HRV) and skin conductance level (SCL). Heart rate variability measures such as R-R intervals, standard deviation of cardiac intervals, pNN50 (percentage of cardiointervals >50 ms different from preceding interval), power of high frequency (HF) and LF components of HRV spectrum, LF/HF ratio, were then derived from the recorded EKG. We expected that the course of 18 weekly inhibitory LF rTMS applied to the dorsolateral prefrontal cortex (DLPFC) would enhance autonomic balance by facilitating frontal inhibition of limbic activity thus resulting in decreased overall heart rate (HR), increased HRV (in a form of increased HF power), decreased LF power (resulting in decreased LF/HF ratio), and decreased SCL. Behavioral evaluations post-18 TMS showed decreased irritability, hyperactivity, stereotype behavior and compulsive behavior ratings while autonomic measures indicated a significant increase in cardiac interval variability and a decrease of tonic SCL. The results suggest that 18 sessions of LF rTMS in ASD results in increased cardiac vagal control and reduced sympathetic arousal.

Neuromodulation integrating rTMS and neurofeedback for the treatment of autism spectrum disorder: an exploratory study.

Autism spectrum disorder (ASD) is a pervasive developmental disorder characterized by deficits in social interaction, language, stereotyped behaviors, and restricted range of interests. In previous studies low frequency repetitive transcranial magnetic stimulation (rTMS) has been used, with positive behavioral and electrophysiological results, for the experimental treatment in ASD. In this study we combined prefrontal rTMS sessions with electroencephalographic (EEG) neurofeedback (NFB) to prolong and reinforce TMS-induced EEG changes. The pilot trial recruited 42 children with ASD (~14.5 years). Outcome measures included behavioral evaluations and reaction time test with event-related potential (ERP) recording. For the main goal of this exploratory study we used rTMS-neurofeedback combination (TMS-NFB, N = 20) and waitlist (WTL, N = 22) groups to examine effects of 18 sessions of integrated rTMS-NFB treatment or wait period) on behavioral responses, stimulus and response-locked ERPs, and other functional and clinical outcomes. The underlying hypothesis was that combined TMS-NFB will improve executive functions in autistic patients as compared to the WTL group. Behavioral and ERP outcomes were collected in pre- and post-treatment tests in both groups. Results of the study supported our hypothesis by demonstration of positive effects of combined TMS-NFB neurotherapy in active treatment group as compared to control WTL group, as the TMS-NFB group showed significant improvements in behavioral and functional outcomes as compared to the WTL group.

rTMS neuromodulation improves electrocortical functional measures of information processing and behavioral responses in autism.

OBJECTIVES: Reports in autism spectrum disorders (ASD) of a minicolumnopathy with consequent deficits of lateral inhibition help explain observed behavioral and executive dysfunctions. We propose that neuromodulation based on low frequency repetitive Transcranial Magnetic Stimulation (rTMS) will enhance lateral inhibition through activation of inhibitory double bouquet interneurons and will be accompanied by improvements in the prefrontal executive functions. In addition we proposed that rTMS will improve cortical excitation/inhibition ratio and result in changes manifested in event-related potential (ERP) recorded during cognitive tests. MATERIALS AND METHODS: Along with traditional clinical behavioral evaluations the current study used ERPs in a visual oddball task with illusory figures. We compared clinical, behavioral and electrocortical outcomes in two groups of children with autism (TMS, wait-list group). We predicted that 18 session long course in autistic patients will have better behavioral and ERP outcomes as compared to age- and IQ-matched WTL group. We used 18 sessions of 1 Hz rTMS applied over the dorso-lateral prefrontal cortex in 27 individuals with ASD diagnosis. The WTL group was comprised of 27 age-matched subjects with ASD tested twice. Both TMS and WTL groups were assessed at the baseline and after completion of 18 weekly sessions of rTMS (or wait period) using clinical behavioral questionnaires and during performance on visual oddball task with Kanizsa illusory figures. RESULTS: Post-TMS evaluations showed decreased irritability and hyperactivity on the Aberrant Behavior Checklist (ABC), and decreased stereotypic behaviors on the Repetitive Behavior Scale (RBS-R). Following rTMS course we found decreased amplitude and prolonged latency in the frontal and fronto-central N100, N200 and P300 (P3a) ERPs to non-targets in active TMS treatment group. TMS resulted in increase of P2d (P2a to targets minus P2a to non-targets) amplitude. These ERP changes along with increased centro-parietal P100 and P300 (P3b) to targets are indicative of more efficient processing of information post-TMS treatment. Another important finding was decrease of the latency and increase of negativity of error-related negativity (ERN) during commission errors that may reflect improvement in error monitoring and correction function. Enhanced information processing was also manifested in lower error rate. In addition we calculated normative post-error treaction time (RT) slowing response in both groups and found that rTMS treatment was accompanied by post-error RT slowing and higher accuracy of responses, whereas the WTL group kept on showing typical for ASD post-error RT speeding and higher commission and omission error rates. CONCLUSION: RESULTS from our study indicate that rTMS improves executive functioning in ASD as evidenced by normalization of ERP responses and behavioral reactions (RT, accuracy) during executive function test, and also by improvements in clinical evaluations.

Neurofeedback training aimed to improve focused attention and alertness in children with ADHD: a study of relative power of EEG rhythms using custom-made software application.

Neurofeedback is a nonpharmacological treatment for attention-deficit hyperactivity disorder (ADHD). We propose that operant conditioning of electroencephalogram (EEG) in neurofeedback training aimed to mitigate inattention and low arousal in ADHD, will be accompanied by changes in EEG bands' relative power. Patients were 18 children diagnosed with ADHD. The neurofeedback protocol ("Focus/Alertness" by Peak Achievement Trainer) has a focused attention and alertness training mode. The neurofeedback protocol provides one for Focus and one for Alertness. This does not allow for collecting information regarding changes in specific EEG bands (delta, theta, alpha, low and high beta, and gamma) power within the 2 to 45 Hz range. Quantitative EEG analysis was completed on each of twelve 25-minute-long sessions using a custom-made MatLab application to determine the relative power of each of the aforementioned EEG bands throughout each session, and from the first session to the last session. Additional statistical analysis determined significant changes in relative power within sessions (from minute 1 to minute 25) and between sessions (from session 1 to session 12). Analysis was of relative power of theta, alpha, low and high beta, theta/alpha, theta/beta, and theta/low beta and theta/high beta ratios. Additional secondary measures of patients' post-neurofeedback outcomes were assessed, using an audiovisual selective attention test (IVA + Plus) and behavioral evaluation scores from the Aberrant Behavior Checklist. Analysis of data computed in the MatLab application, determined that theta/low beta and theta/alpha ratios decreased significantly from session 1 to session 12, and from minute 1 to minute 25 within sessions. The findings regarding EEG changes resulting from brain wave self-regulation training, along with behavioral evaluations, will help elucidate neural mechanisms of neurofeedback aimed to improve focused attention and alertness in ADHD.

INDUCED EEG GAMMA OSCILLATION ALIGNMENT IMPROVES DIFFERENTIATION BETWEEN AUTISM AND ADHD GROUP RESPONSES IN A FACIAL CATEGORIZATION TASK.

INTRODUCTION: Children diagnosed with an autism spectrum disorder (ASD) often lack the ability to recognize and properly respond to emotional stimuli. Emotional deficits also characterize children with attention deficit/hyperactivity disorder (ADHD), in addition to exhibiting limited attention span. These abnormalities may effect a difference in the induced EEG gamma wave burst (35-45 Hz) peaked approximately 300-400 milliseconds following an emotional stimulus. Because induced gamma oscillations are not fixed at a definite point in time post-stimulus, analysis of averaged EEG data with traditional methods may result in an attenuated gamma burst power. METHODS: We used a data alignment technique to improve the averaged data, making it a better representation of the individual induced EEG gamma oscillations. A study was designed to test the response of a subject to emotional stimuli, presented in the form of emotional facial expression images. In a four part experiment, the subjects were instructed to identify gender in the first two blocks of the test, followed by differentiating between basic emotions in the final two blocks (i.e. anger vs. disgust). EEG data was collected from ASD (n=10), ADHD (n=9), and control (n=11) subjects via a 128 channel EGI system, and processed through a continuous wavelet transform and bandpass filter to isolate the gamma frequencies. A custom MATLAB code was used to align the data from individual trials between 200-600 ms post-stimulus, EEG site, and condition by maximizing the Pearson product-moment correlation coefficient between trials. The gamma power for the 400 ms window of maximum induced gamma burst was then calculated and compared between subject groups. RESULTS AND CONCLUSION: Condition (anger/disgust recognition, gender recognition) × Alignment × Group (ADHD, ASD, Controls) interaction was significant at most of parietal topographies (e.g., P3-P4, P7-P8). These interactions were better manifested in the aligned data set. Our results show that alignment of the induced gamma oscillations improves sensitivity of this measure in differentiation of EEG responses to emotional facial stimuli in ADHD and ASD.

Prefrontal neuromodulation using rTMS improves error monitoring and correction function in autism.

One important executive function known to be compromised in autism spectrum disorder (ASD) is related to response error monitoring and post-error response correction. Several reports indicate that children with ASD show reduced error processing and deficient behavioral correction after an error is committed. Error sensitivity can be readily examined by measuring event-related potentials (ERP) associated with responses to errors, the fronto-central error-related negativity (ERN), and the error-related positivity (Pe). The goal of our study was to investigate whether reaction time (RT), error rate, post-error RT change, ERN, and Pe will show positive changes following 12-week long slow frequency repetitive TMS (rTMS) over dorsolateral prefrontal cortex (DLPFC) in high functioning children with ASD. We hypothesized that 12 sessions of 1 Hz rTMS bilaterally applied over the DLPFC will result in improvements reflected in both behavioral and ERP measures. Participants were randomly assigned to either active rTMS treatment or wait-list (WTL) groups. Baseline and post-TMS/or WTL EEG was collected using 128 channel EEG system. The task involved the recognition of a specific illusory shape, in this case a square or triangle, created by three or four inducer disks. ERN in TMS treatment group became significantly more negative. The number of omission errors decreased post-TMS. The RT did not change, but post-error RT became slower. There were no changes in RT, error rate, post-error RT slowing, nor in ERN/Pe measures in the wait-list group. Our results show significant post-TMS differences in the response-locked ERP such as ERN, as well as behavioral response monitoring measures indicative of improved error monitoring and correction function. The ERN and Pe, along with behavioral performance measures, can be used as functional outcome measures to assess the effectiveness of neuromodulation (e.g., rTMS) in children with autism and thus may have important practical implications.