Neurofeedback: An Alternative and Efficacious Treatment for Attention Deficit Hyperactivity Disorder

Current research has shown that neurofeedback, or EEG biofeedback as it is sometimes called, is a viable alternative treatment for Attention Deficit Hyperactivity Disorder (ADHD). The aim of this article is to illustrate current treatment modalities(s), compare them to neurofeedback, and present the benefits of utilizing this method of treatment to control and potentially alleviate the symptoms of ADHD. In addition, this article examines the prevalence rates and possible etiology of ADHD, the factors associated with ADHD and brain dysfunction, the current pharmacological treatments of ADHD, Ritalin, and the potential risks and side effects. Behavior modification and cognitive behavioral treatment for ADHD is discussed as well. Lastly, a brief history of the study of neurofeedback, treatment successes and clinical benefits, comparisons to medication, and limitations are presented.     

Electroencephalographic and Psychometric Differences Between Boys with and Without Attention-Deficit/Hyperactivity Disorder (ADHD): A Pilot Study

Attention-Deficit/Hyperactivity Disorder (ADHD) is reported to have an incidence of 3–5%, and is associated with a variety of interpersonal, academic, and social problem behaviors. There is controversy as to whether ADHD is a learned behavioral or brain dysfunction. Research has explored a variety of measures to assess behavioral and brain dysfunctions in this population, with no consistent and clearly diagnostic results. We investigated whether a new psychometric and a new electroencephalographic procedure would clearly differentiate ADHD. The psychometric was based on DSM-IV criteria and the EEG measure was based on the assumption that ADHD interferes with cognitive transition from one discrete task to another. Parents of four ADHD boys (ages 8–12) and four age- and interest-matched non-ADHD boys completed the ADHD Symptom Inventory, while their sons' EEG was monitored during viewing of a video and reading of a book. For the ADHD boys, this was repeated a second time, 3 months later, to assess test-retest reliability. Both the psychometric and the EEG measures clearly differentiated the two samples (p's < .01) with no overlap in scores, were reliable over 3 months (r = .87), and were significantly correlated with one another (r = .85). While a small sample size, these robust, related and reliable findings suggest that both the psychometric and the psychophysiological EEG measures deserve further replication and exploration.     

注意缺损多动障碍和儿茶酚-O-甲基转移酶基因无关联性

以往研究表明,儿茶酚胺系统可能参于注意缺损多动障碍（attention—deficit hyperactivityity disorder,ADHD）的发生,而儿茶酚胺-O-甲基转移酶（catechel—O—methyltransferase,COMT）是一种降解多巴胺和去甲肾上腺素系统的儿茶酚胺神经递质的酶。因此,采用两种以家系为基础的分析方法,即传递不平衡实验（transmission disequilibrium test,TDT）和单倍型为基础的单倍型相对风险率（haplotype—based haplotype relative risk,HHRR）去探讨COMT和中国人群中79个ADHD核心家系的关联性,ADHD诊断符合DSM—IV的诊断标准。TDT（X^2=1．03,df=1,P〉0．05）和HHRR（X^2=1．08,df=1,P〉0．05）两种方法的分析结果表明,COMT等位基因不能优先传递给ADHD儿童,提示在中国人群中ADHD与COMT基因无关联性。     

注意缺陷多动障碍儿童睡眠障碍与铁缺乏关系的临床研究

目的：探讨注意缺陷多动障碍（ADHD）患儿睡眠障碍与血清铁蛋白水平的关系。方法：符合美国精神疾病诊断与统计手册第4版（DSM-Ⅳ）中ADHD诊断标准的62例6．14岁ADHD患儿,由ADHD患儿的父母填写睡眠障碍量表（SDSC）,检测ADH-D患儿的血清铁蛋白水平。结果：与血清铁蛋白水平高于45／μg／L的ADHD患儿相比较,血清铁蛋白水平低于45／μg／L的ADHD患儿的SDSC“睡眠醒觉转换障碍”项评分和总分明显高于前者（P〈0．05）。2组间其他项评分比较无显著性差异（P〉0．05）。SDSC“睡眠醒觉转换障碍”项评分与血清铁蛋白水平成负相关（P〈0．05）。结论：血清铁蛋白水平低于451μg／LADHD患儿SDSC“睡眠醒觉转换障碍”（睡眠中的异常运动）的危险性显著增加。     

注意缺陷多动障碍儿童睡眠障碍与铁缺乏关系 的临床研究

目的:探讨注意缺陷多动障碍(ADHD)患儿睡眠障碍与血清铁蛋白水平的关系。方法:符合美国精神疾病诊断与统计手册第4版(DSM-Ⅳ)中ADHD诊断标准的62例6-14岁ADHD患儿,由ADHD患儿的父母填写睡眠障碍量表(SDSC),检测ADHD患儿的血清铁蛋白水平。结果:与血清铁蛋白水平高于45μg/L的ADHD患儿相比较,血清铁蛋白水平低于45μg/L的ADHD患儿的SDSC"睡眠醒觉转换障碍"项评分和总分明显高于前者(P<0.05)。2组间其他项评分比较无显著性差异(P>0.05)。SDSC"睡眠醒觉转换障碍"项评分与血清铁蛋白水平成负相关(P<0.05)。结论:血清铁蛋白水平低于45μg/LADHD患儿SDSC"睡眠醒觉转换障碍"(睡眠中的异常运动)的危险性显著增加。     

A psychophysiological marker of attention deficit/hyperactivity disorder (ADHD)--defining the EEG consistency index

This study continues our research to further validate the idea that ADHD (Attention Deficit/Hyperactivity Disorder) interferes with transition from one task to another and this interference can be quantified by a Consistency Index (CI) derived from a specific mathematical representation of EEG data. We reanalyze 32 previously reported data sets present new data for 35 boys and girls, ages 7-12, ADHD or control. Each data set contains EEG, recorded and digitized while participants perform consecutive 10-min tasks: video, reading, and math. For boys, the CI in ADHD was four times lower than in controls, p < .005, for girls this difference was two times, p < .05. ADHD/control classification based on the CI coincided with the DSM-IV criteria for 88% of the boys and for 67% of the girls. Post hoc analysis indicated that the classification utility of the CI diminished with age. A CI below 40% could be a discriminating, reliable, and reproducible marker of ADHD in young boys.     

Salivary Melatonin Rhythm as a Marker of the Circadian System in Healthy Children and Those With Attention-Deficit/Hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood. Problems with sleep structure, efficiency, and timing have been reported in some, but not all, studies on ADHD children. As the sleep-wake cycle belongs to circadian rhythms, the timekeeping circadian system might be involved in ADHD. To assess whether the circadian system of ADHD children differs from that of controls, the rhythm of the pineal hormone melatonin was used as a reliable marker of the system. Saliva from 34 ADHD and 43 control 6- to 12-yr-old children was sampled at 2-h intervals throughout the entire 24-h cycle, and the melatonin profiles of the ADHD and control children were compared. The nocturnal melatonin peaks of the ADHD and control group did not differ significantly. The high nocturnal interindividual variability of the peaks seen in adulthood was present already in the studied children. The 24-h melatonin profiles of all the ADHD subjects did not differ significantly from those of the control subjects. Categorization of subjects according to age, into groups of 6- to 7-yr-old (9 ADHD, 5 control), 8- to 9-yr-old (16 ADHD, 26 control), and 10- to 12-yr-old (9 ADHD, 12 control) children, revealed significant differences between the ADHD and control group in the melatonin rhythm waveform, but not in nocturnal melatonin peaks; the peaks were about the same in both groups and did not change significantly with increasing age. In the oldest, but not in the younger, children, the melatonin signal duration in the ADHD group was shorter than in the control group. The difference might be due to the fact that whereas in the control group both the evening melatonin onset and the morning offset phase delayed in the oldest children relative to those in the youngest children, in the ADHD group only the onset, but not the offset, phase delayed with increasing age. The data may indicate subtle differences between the circadian system of ADHD and control children during development. (Author correspondence: sumova@biomed.cas.cz)     

Delayed Sleep Timing and Symptoms in Adults With Attention-Deficit/Hyperactivity Disorder: A Controlled Actigraphy Study

Patients with attention-deficit/hyperactivity disorder (ADHD) often exhibit disrupted sleep and circadian rhythms. Determination of whether sleep disturbance and/or circadian disruption are differentially associated with symptom severity is necessary to guide development of future treatment strategies. Therefore, we measured sleep and ADHD symptoms in participants aged 19–65 who met the DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) criteria for ADHD and insomnia without psychiatric comorbidities by monitoring actigraphy and daily sleep logs for 2 wks, as well as the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), the ADHD Rating Scale (ADHD-RS), and a clinic-designed sleep behavior questionnaire. Principal components analysis identified correlated circadian- and sleep-related variables in all participants with ADHD who completed the study (n?=?24). The identified components were entered into a backwards stepwise linear regression analysis, which indicated that delayed sleep timing and increased sleepiness (ESS) (but not sleep duration or sleep efficiency) significantly predicted greater severity of both hyperactive-impulsive and inattentive ADHD symptoms (p <?.05 for partial regression coefficients). In addition, combined subtypes had the most impaired age-adjusted sleep quality (PSQI scores; p?<?.05 compared with healthy controls; n?=?13), and 91.7% of them reported going to bed late due to being “not tired/too keyed up to sleep” compared with 57.2% and 50% of inattentive and symptom-controlled participants, respectively (p?<?.05). In conclusion, the results of this study suggest that ADHD symptom severity correlates with delayed sleep timing and daytime sleepiness, suggesting that treatment interventions aimed at advancing circadian phase may improve daytime sleepiness. In addition, ADHD adults with combined hyperactive-impulsive and inattentive symptoms have decreased sleep quality as well as the delayed sleep timing of predominately inattentive subtypes. (Author correspondence: rfargason@uab.edu)     

Calibration of ADHD Assessments Across Studies: A Meta-Analysis Tool

When analyzed separately, data from small studies provide only limited information with limited clinical generalizability, due to small sample size, differing assessments, and limited scope. In this methodological paper we outline a theoretical framework for performing meta-analysis of data obtained from disparate studies using disparate tests, based on calibration of the data from such studies and tests into a unified probability scale. We apply this method to combine the data from five studies examining the diagnostic abilities of different assessments of Attention Deficit/Hyperactivity Disorder (ADHD), including behavioral rating scales and EEG assessments. The studies enrolled a total of 111 subjects, 56 ADHD and 55 controls. Each individual study had a small sample focused on a specific age/gender group, for example 8 boys ages 6–10, and generally had insufficient power to detect statistically significant differences. No gender, or age comparisons were possible within any single study. However, when calibrated and combined, the data resulted in a clear separation between ADHD versus non-ADHD groups in males below the age of 16 (p < 0.001), males above the age of 16, (p = 0.015), females below the age of 16, (p = 0.0014), and females above the age of 16, (p = 0.0022).We conclude that if data from various studies using various tests are made comparable, the resulting combined sample size and the increased diversity of the combined sample lead to increased significance of the statistical tests and allow for cross-sectional comparisons, which are not possible within each individual study.     

注意缺损多动障碍关联于DXS7位点

用单细胞凝胶电泳法检测了稀土化合物氯化钇和氯化镨对人外周血淋巴细胞的DNA损伤效应。结果表明,与对照相比,3种不同浓度的氯化钇和氯化镨均可引起淋巴细胞DNA受损后DNA迁移率的显著升高,受损伤细胞的百分率与对照差异明显,提示氯化钇和氯化镨具有一定的遗传毒性。 Abstract:The effect of DNA damage in human lymphocytes induced by yttrium chloride and praseodymium chloride was detected using SCG assay.The results showed that a highly significant increase in DNA migration in DNA-damaged lymphocytes was induced by three different concentrations of yttrium and praseodymium compared with the control,The percentage of DNA-damaged have genetic toxicity.The relevant points to this study are discussed.     

Combined Psychophysiological Assessment of ADHD: A Pilot Study of Bayesian Probability Approach Illustrated by Appraisal of ADHD in Female College Students

Manifestations of ADHD are observed at both psychological and physiological levels and assessed via various psychometric, EEG, and imaging tests. However, no test is 100% accurate in its assessment of ADHD. This study introduces a stochastic assessment combining psychometric tests with previously reported (Consistency Index) and newly developed (Alpha Blockade Index) EEG-based physiological markers of ADHD. The assessment utilizes classical Bayesian inference to refine after each step the probability of ADHD of each individual. In a pilot study involving six college females with ADHD and six matched controls, the assessment achieved correct classification for all ADHD and non-ADHD participants. In comparison, the classification of ADHD versus non-ADHD participants was < 85% for any one of the tests separately. The procedure significantly improved the score separation between ADHD versus non-ADHD groups. The final average probabilities for ADHD were 76% for the ADHD group and 8% for the control group. These probabilities correlated (r = .87) with the Brown ADD scale and (r = .84) with the ADHD-Symptom Inventory used for the screening of the participants. We conclude that, although each separate test was not completely accurate, a combination of several tests classified correctly all ADHD and all non-ADHD participants. The application of the proposed assessment is not limited to the specific tests used in this study--the assessment represents a general paradigm capable of accommodating a variety of ADHD tests into a single diagnostic assessment.     

Potential hormonal mechanisms of Attention-Deficit/Hyperactivity Disorder and Major Depressive Disorder: A new perspective

Hormonal influences on the organization of behavior are apparent to neuroendocrinologists but under-examined in relation to childhood and adolescent mental disorders. A central mystery in the field of developmental psychopathology is the preferential male vulnerability to behavior disorders in childhood and female vulnerability to emotional disorders in adolescence. Relative neglect of a hormonal explanation may be due to lack of simple or unifying conceptual paradigms to guide studies. This paper seeks to stimulate research in this area by drawing upon clinical psychology and neuroscience literatures to offer a heuristic paradigm for clinical research. Two syndromes are selected here for illustration: Attention-Deficit/Hyperactivity Disorder (ADHD) and Major Depressive Disorder (MDD), because they have opposite gender risk profiles. Two guiding theories are evaluated. First, prenatal organizational effects of testosterone may modulate striatally-based dopaminergic circuits in such a way as to place boys at greater risk for early developing inattention and disruptive behavioral disorders. Second, activational effects of estradiol at puberty may modulate amygdalar and other circuitry, with particular effects on serotonergic pathways, in such a way as to place girls at greater risk for internalizing and mood disorders. Hypotheses from these theories are evaluated based on the current available literature, and limitations of, and future directions for, this literature are discussed.     

Neurofeedback treatment for attention-deficit/hyperactivity disorder in children: a comparison with methylphenidate

Clinical trials have suggested that neurofeedback may be efficient in treating attention-deficit/hyperactivity disorder (ADHD). We compared the effects of a 3-month electroencephalographic feedback program providing reinforcement contingent on the production of cortical sensorimotor rhythm (12–15 Hz) and beta1 activity (15–18 Hz) with stimulant medication. Participants were N = 34 children aged 8–12 years, 22 of which were assigned to the neurofeedback group and 12 to the methylphenidate group according to their parents' preference. Both neurofeedback and methylphenidate were associated with improvements on all subscales of the Test of Variables of Attention, and on the speed and accuracy measures of the d2 Attention Endurance Test. Furthermore, behaviors related to the disorder were rated as significantly reduced in both groups by both teachers and parents on the IOWA-Conners Behavior Rating Scale. These findings suggest that neurofeedback was efficient in improving some of the behavioral concomitants of ADHD in children whose parents favored a nonpharmacological treatment.     

Testing candidate genes for attention-deficit/hyperactivity disorder in fruit flies using a high throughput assay for complex behavior

Fruit flies are important model organisms for functional testing of candidate genes in multiple disciplines, including the study of human diseases. Here we use a high-throughput locomotor activity assay to test the response on activity behavior of gene disruption in Drosophila melanogaster. The aim was to investigate the impact of disruption of 14 candidate genes for human attention-deficit/hyperactivity disorder (ADHD) on fly behavior. By obtaining a range of correlated measures describing the space of variables for behavioral activity we show, that some mutants display similar phenotypic responses, and furthermore, that the genes disrupted in those mutants had common molecular functions; namely processes related to cGMP activity, cation channels and serotonin receptors. All but one of the candidate genes resulted in aberrant behavioral activity, suggesting involvement of these genes in behavioral activity in fruit flies. Results provide additional support for the investigated genes being risk candidate genes for ADHD in humans.     

脑电生物反馈训练对ADHD 儿童心理、行为的影响

目的：探讨脑电生物反馈治疗对ADHD儿童心理、行为的影响。方法：对45例ADHD儿童采用脑电生物反馈训练。20次为一个疗程。治疗前和治疗后20、40次分别用症状评定量表进行比较。结果：接受20次训练的ADHD儿童注意、情感、活动水平、异常行为、学业等方面的问题都有明显好转;接受40次训练的ADHD儿童注意、情感、活动水平、异常行为、学业等方面的问题改善十分明显。P值〈0.01差异显著。结论：脑电生物反馈训练能有效地改善儿童注意、情感、活动水平、异常行为、学业等方面的问题。     

注意缺陷多动障碍低觉醒模型的新证据

注意缺陷多动障碍（Attention Deficit Hyperactivity Disorder,ADHD）是儿童期常见的一种发展性的异常,其病因及发生机理至今未明。低觉醒模型是ADHD成因的一种假设。本文从睡眠障碍导致的低觉醒探讨ADHD发生机理。通过对ADHD儿童的睡眠障碍进行分析以及将ADHD外在表现与睡眠剥夺后的表现进行对比分析,得出ADHD儿童存在的低觉醒是由于外显的或内隐的睡眠障碍引起的,一方面间接证明了低觉醒模型,另一方面为ADHD的成因研究开拓了新的思路。     

miRNA profiling in the hippocampus of attention-deficit/hyperactivity disorder rats

Attention-deficit/hyperactivity disorder (ADHD) is characterized by attention deficit, hyperactivity, impulsivity, and learning and memory impairment. Although the pathogenesis of learning and memory impairment is still unknown, some studies have suggested an association with hippocampus dysfunction. We aimed to explore the role of miRNAs in the learning and memory impairments observed in ADHD. Differentially expressed hippocampal micro-ribonucleic acids (miRNAs) in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs) were detected on an Illumina HiSeq. 2000 genome analyzer. A total of 25 differentially expressed miRNAs (fold-change ≥ 2 and P-value < 0.05) were identified. The target genes of these differentially expressed miRNAs were predicted using online tools (TargetScan and miRDB). Gene ontology and pathway analysis of the predicted target genes were carried out to assess their putative biological functions. Meanwhile, quantitative real-time PCR was used to validate the HiSeq results, revealing that three miRNAs (miR-1-b, miR-741-3p, and miR-206-3p) were upregulated and four (miR-182, miR-471-5p, miR-183-5p, and miR-211-5p) were downregulated in the SHR group compared with the WKY group. In addition, we confirmed that Dyrk1a is regulated by miR-211-5p. These results help us understand the contribution of miRNAs in the hippocampus to ADHD and provide new insights into the pathogenesis of this condition.     

Discourse on the development of EEG diagnostics and biofeedback for attention-deficit/hyperactivity disorders

This article presents a review of work that my colleagues and I have been doing during the past 15 years developing a rationale for the diagnosis of attention-deficit/hyperactivity disorder (ADHD) and treatment of ADHD employing EEG biofeedback techniques. The article first briefly reviews the history of research and theory for understanding ADHD and then deals with the development of EEG and event-related potential (ERP) assessment paradigms and treatment protocols for this disorder, including our work and that of others who have replicated our results. Illustrative material from our current research and child case studies is included. Suggestions for future experimental and clinical work in this area are presented and theoretical issues involving the understanding of the neurophysiological and neurological basis of ADHD are discussed.Over the years, many people have been involved both in my laboratory and at Southeastern Biofeedback Institute working with me in developing this area; I wish to acknowledge some of them. They are specifically Dr. Margaret Shouse and Dr. Chris Mann, who have been involved in the initial and recent stages of my research; Ms. Jennifer Samples, who has worked with us in the Institute for many years and has helped us in training many of the children that have benefited from EEG biofeedback. I would especially wish to acknowledge the skill and dedication of Judith O. Lubar, of Southeastern Biofeedback Institute, who has worked with me clinically in terms of developing treatment protocols for ADHD biofeedback and who has trained many of the children who have successfully completed EEG Biofeedback. I would like to acknowledge the generous help of the Lexicor Corporation of Boulder, Colorado who have provided support and instrumentation for recent studies in this area. Mr. Rod Bunn and Mr. Robert Muenchen, who have provided computer support, programming, and statistical assistance in evaluating data in various studies, are gratefully acknowledged. Some of this research was supported by a grant under the ESEA Title IV-C Program for the handicapped. I also gratefully acknowledge Children's Hospital of Knoxville, TN, who have provided essential contract support for our laboratory at the University of Tennessee.     

脑源性神经营养因子基因多态性与注意缺陷多动障碍的关联性研究

目的：探讨脑源性神经营养因子（Brain-derivedneurotrophicfactor,BDNF）G196A、C270T及Val66Met3个单核苷酸多态性（SNP）位点与注意缺陷多动障碍（ADHD）的关系。方法：选取无亲缘关系的ADHD患者共114例,健康对照共96例。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测G196A、C270T和Val66Met3个多态性位点的多态性,采用HaploView4.0及SPSS13.0软件进行连锁不平衡分析并比较两组基因型分布和等位基因频率。结果：BDNF三个多态性位点基因型及等位基因频率分布均符合Hardy-Weinberg定律。ADHD组G196A和C270T多态性位点分布与正常对照组比较差异无统计学意义,而BDNF基因Val66Met位点的基因型及等位基因频率分布在ADHD组与对照组存在显著性差异（p〈0.05）,ADHD组Val66Met位点的等位基因G（Val）频率显著高于正常对照组。结论：BDNF基因Val66Met多态性可能与ADHD发病有关,携带有Val66Met多态性位点G等位基因的个体可能更容易产生ADHD。