EEG Connectivity in ADHD Compared to a Normative Database: A Cohort Analysis of 120 Subjects from the ICAN Study.

This study explores how EEG connectivity measures in children with ADHD ages 7-10 (n = 140) differ from an age-matched nonclinical database. We differentiated connectivity in networks, Brodmann area pairs, and frequencies. Subjects were in the International Collaborative ADHD Neurofeedback study, which explored neurofeedback for ADHD. Inclusion criteria were mainly rigorously diagnosed ADHD and a theta/beta power ratio (TBR) ≤ 4.5. Using statistical and machine learning algorithms, connectivity values were extracted in coherence, phase, and lag coherence at all Brodmann, subcortical, and cerebellar areas within the main networks in all EEG frequencies and then compared with a normative database. There is a higher rate of dysregulation (more than ± 1.97SD), in some cases as much as 75%, of the Brodmann pairs observed in coherence and phase between BAs 7, 10, and 11 with secondary connections from these areas to BAs 21, 30, 35, 37, 39, and 40 in the ADHD children as compared to the normative database. Left and right Brodmann areas 10 and 11 are highly disconnected to each other. The most dysregulated Brodmann Areas in ADHD are 7, 10, and 11, relevant to ADHD executive-function deficits and provide important considerations when developing interventions for ADHD children.

Reversal of Acquired Prosopagnosia Using Quantitative Electroencephalography-Guided Laser Therapy.

Background: Currently treatment for prosopagnosia is limited. Methods: We report the reversal of acquired associative-type prosopagnosia (AAP) using quantitative electroencephalography (qEEG)-guided transcranial laser therapy (qGLT) in a subject with temporal lobe epilepsy (TLE) and mild cognitive impairment (MCI). Results: Objective and subjective measures of improvement in AAP, TLE, and MCI are presented. Additional improvement, measured through qEEG, was found 1-month post-treatment. Conclusions: There was no recurrence of AAP for 1 year. We conclude that further research into the utility of qGLT in the treatment of AAP is warranted.

Consensus on the reporting and experimental design of clinical and cognitive-behavioural neurofeedback studies (CRED-nf checklist).

Neurofeedback has begun to attract the attention and scrutiny of the scientific and medical mainstream. Here, neurofeedback researchers present a consensus-derived checklist that aims to improve the reporting and experimental design standards in the field.

Low-Resolution Electromagnetic Tomography (LORETA) of changed Brain Function Provoked by Pro-Dopamine Regulator (KB220z) in one Adult ADHD case.

Attention Deficit-Hyperactivity Disorder (ADHD) often continues into adulthood. Recent neuroimaging studies found lowered baseline dopamine tone in the brains of affected individuals that may place them at risk for Substance Use Disorder (SUD). This is an observational case study of the potential for novel management of Adult ADHD with a non-addictive glutaminergic-dopaminergic optimization complex KB200z. Low-resolution electromagnetic tomography (LORETA) was used to evaluate the effects of KB220z on a 72-year-old male with ADHD, at baseline and one hour following administration. The resultant z-scores, averaged across Eyes Closed, Eyes Open and Working Memory conditions, increased for each frequency band, in the anterior, dorsal and posterior cingulate regions, as well as the right dorsolateral prefrontal cortex during Working Memory, with KB220z. These scores are consistent with other human and animal neuroimaging studies that demonstrated increased connectivity volumes in reward circuitry and may offer a new approach to ADHD treatment. However, larger randomized trials to confirm these results are required.

Quantitative EEG and neurofeedback in children and adolescents: anxiety disorders, depressive disorders, comorbid addiction and attention-deficit/hyperactivity disorder, and brain injury.

This article explores the science surrounding neurofeedback. Both surface neurofeedback (using 2-4 electrodes) and newer interventions, such as real-time z-score neurofeedback (electroencephalogram [EEG] biofeedback) and low-resolution electromagnetic tomography neurofeedback, are reviewed. The limited literature on neurofeedback research in children and adolescents is discussed regarding treatment of anxiety, mood, addiction (with comorbid attention-deficit/hyperactivity disorder), and traumatic brain injury. Future potential applications, the use of quantitative EEG for determining which patients will be responsive to medications, the role of randomized controlled studies in neurofeedback research, and sensible clinical guidelines are considered.

Integration of XNAT/PACS, DICOM, and Research Software for Automated Multi-modal Image Analysis.

Traumatic brain injury (TBI) is an increasingly important public health concern. While there are several promising avenues of intervention, clinical assessments are relatively coarse and comparative quantitative analysis is an emerging field. Imaging data provide potentially useful information for evaluating TBI across functional, structural, and microstructural phenotypes. Integration and management of disparate data types are major obstacles. In a multi-institution collaboration, we are collecting electroencephalogy (EEG), structural MRI, diffusion tensor MRI (DTI), and single photon emission computed tomography (SPECT) from a large cohort of US Army service members exposed to mild or moderate TBI who are undergoing experimental treatment. We have constructed a robust informatics backbone for this project centered on the DICOM standard and eXtensible Neuroimaging Archive Toolkit (XNAT) server. Herein, we discuss (1) optimization of data transmission, validation and storage, (2) quality assurance and workflow management, and (3) integration of high performance computing with research software.

Generational association studies of dopaminergic genes in reward deficiency syndrome (RDS) subjects: selecting appropriate phenotypes for reward dependence behaviors.

UNLABELLED: Abnormal behaviors involving dopaminergic gene polymorphisms often reflect an insufficiency of usual feelings of satisfaction, or Reward Deficiency Syndrome (RDS). RDS results from a dysfunction in the "brain reward cascade," a complex interaction among neurotransmitters (primarily dopaminergic and opioidergic). Individuals with a family history of alcoholism or other addictions may be born with a deficiency in the ability to produce or use these neurotransmitters. Exposure to prolonged periods of stress and alcohol or other substances also can lead to a corruption of the brain reward cascade function. We evaluated the potential association of four variants of dopaminergic candidate genes in RDS (dopamine D1 receptor gene [DRD1]; dopamine D2 receptor gene [DRD2]; dopamine transporter gene [DAT1]; dopamine beta-hydroxylase gene [DBH]). METHODOLOGY: We genotyped an experimental group of 55 subjects derived from up to five generations of two independent multiple-affected families compared to rigorously screened control subjects (e.g., N = 30 super controls for DRD2 gene polymorphisms). Data related to RDS behaviors were collected on these subjects plus 13 deceased family members. RESULTS: Among the genotyped family members, the DRD2 Taq1 and the DAT1 10/10 alleles were significantly (at least p < 0.015) more often found in the RDS families vs. controls. The TaqA1 allele occurred in 100% of Family A individuals (N = 32) and 47.8% of Family B subjects (11 of 23). No significant differences were found between the experimental and control positive rates for the other variants. CONCLUSIONS: Although our sample size was limited, and linkage analysis is necessary, the results support the putative role of dopaminergic polymorphisms in RDS behaviors. This study shows the importance of a nonspecific RDS phenotype and informs an understanding of how evaluating single subset behaviors of RDS may lead to spurious results. Utilization of a nonspecific "reward" phenotype may be a paradigm shift in future association and linkage studies involving dopaminergic polymorphisms and other neurotransmitter gene candidates.

Overcoming qEEG abnormalities and reward gene deficits during protracted abstinence in male psychostimulant and polydrug abusers utilizing putative dopamine D2 agonist therapy: part 2.

BACKGROUND: It is well established that in both food- and drug-addicted individuals there is "dopamine resistance" associated with the DRD2 gene A1 allele. Based on earlier studies, evidence is emerging wherein the potential of utilizing a natural, nonaddicting, safe, putative D2 agonist may play a significant role in the recovery of individuals with reward deficiency syndrome, including those addicted to psychoactive chemicals. FINDINGS: Positive outcomes demonstrated by quantitative electroencephalographic (qEEG) imaging in a randomized, triple-blind, placebo-controlled, crossover study involving oral Synaptose Complex KB220Z™ showed an increase of alpha waves and low beta wave activity in the parietal brain region. Using t statistics, significant differences observed between placebo and Synaptose Complex KB220Z™ consistently occurred in the frontal regions after week 1 and then again after week 2 of analyses (P = 0.03). This is the first report to demonstrate involvement of the prefrontal cortex in the qEEG response to a natural putative D2 agonist (Synaptose Complex KB220Z™), especially evident in dopamine D2 A1 allele subjects. Independently, we have further supported this finding with an additional study of 3 serious polydrug abusers undergoing protracted abstinence who carried the DRD2 A1 allele. Significant qEEG differences were found between those who received 1 dose of placebo compared with those who were administered Synaptose Complex KB220Z™. Synaptose Complex KB220Z™ induced positive regulation of the dysregulated electrical activity of the brain in these addicts. The results are indicative of a phase change from low amplitude or low power in the brain to a more regulated state by increasing an average of 6.169 mV(2) across the prefrontal cortical region. In the first experiment we found that while 50% of the subjects carried the DRD2 A1 allele, 100% carried ≥ 1 risk allele. Specifically, based on the proposed addiction risk score for these 14 subjects, 72% had moderate-to-severe addiction risk. Similar findings were obtained by repeating the experiment in 3 additional currently abstinent polydrug abusers carrying the DRD2 A1 allele. CONCLUSION: This seminal work will provide important information that may ultimately lead to significant improvement in the recovery of individuals with psychostimulant and polydrug abuse problems, specifically those with genetically induced dopamine deficiency. Based on this small sample size, we are proposing that with necessary large populations supporting these initial results, and possibly even additional candidate genes and single nucleotide polymorphisms, we may eventually have the clinical ability to classify severity according to genotype and possession of risk alleles, along with offering a safe, nonaddicting, natural dopaminergic receptor agonist that potentially upregulates instead of downregulates dopaminergic receptors, preferably the D2 subtype.

Differentiating a network of executive attention: LORETA neurofeedback in anterior cingulate and dorsolateral prefrontal cortices.

INTRODUCTION: This study examines the differential effects of space-specific neuro-operant learning, utilizing low-resolution electromagnetic tomographic (LORETA) neurofeedback in three regions of training (ROTs), namely, the anterior cingulate gyrus (AC) and right and left dorsolateral prefrontal cortices (RPFC and LPFC respectively). METHODS: This study was conducted with 14 nonclinical students with a mean age of 22. We utilized electrophysiological measurements and subtests of the WAIS-III for premeasures and postmeasures. RESULTS: The data indicate that the AC shares a significant association with the RPFC and LPFC; however, each of the ROTs exhibits different cortical effects in all frequencies when trained exclusively. DISCUSSION: LORETA neurofeedback (LNFB) appears to enhance the functioning and strengthening of networks of cortical units physiologically related to each ROT; moreover, significant changes are mapped for each frequency domain, showing the associations within this possible attentional network.

Self-perception and experiential schemata in the addicted brain.

This study investigated neurophysiological differences between recovering substance abusers (RSA) and controls while electroencephalogram (EEG) was continuously recorded during completion of a new assessment instrument. The participants consisted of 56 total subjects; 28 RSA and 28 non-clinical controls (C). The participants completed the self-perception and experiential schemata assessment (SPESA) and source localization was compared utilizing standardized low-resolution electromagnetic tomography (sLORETA). The data show significant differences between groups during both the assessment condition and baselines. A pattern of alpha activity as estimated by sLORETA was shown in the right amygdala, uncus, hippocampus, BA37, insular cortex and orbitofrontal regions during the SPESA condition. This activity possibly reflects a circuit related to negative perceptions of self formed in specific neural pathways. These pathways may be responsive to the alpha activity induced by many substances by bringing the brain into synchrony if only for a short time. In effect this may represent the euphoria described by substance abusers.

Attention-deficit-hyperactivity disorder and reward deficiency syndrome.

Molecular genetic studies have identified several genes that may mediate susceptibility to attention deficit hyperactivity disorder (ADHD). A consensus of the literature suggests that when there is a dysfunction in the "brain reward cascade," especially in the dopamine system, causing a low or hypo-dopaminergic trait, the brain may require dopamine for individuals to avoid unpleasant feelings. This high-risk genetic trait leads to multiple drug-seeking behaviors, because the drugs activate release of dopamine, which can diminish abnormal cravings. Moreover, this genetic trait is due in part to a form of a gene (DRD(2) A1 allele) that prevents the expression of the normal laying down of dopamine receptors in brain reward sites. This gene, and others involved in neurophysiological processing of specific neurotransmitters, have been associated with deficient functions and predispose individuals to have a high risk for addictive, impulsive, and compulsive behavioral propensities. It has been proposed that genetic variants of dopaminergic genes and other "reward genes" are important common determinants of reward deficiency syndrome (RDS), which we hypothesize includes ADHD as a behavioral subtype. We further hypothesize that early diagnosis through genetic polymorphic identification in combination with DNA-based customized nutraceutical administration to young children may attenuate behavioral symptoms associated with ADHD. Moreover, it is concluded that dopamine and serotonin releasers might be useful therapeutic adjuncts for the treatment of other RDS behavioral subtypes, including addictions.

EEG neurofeedback: a brief overview and an example of peak alpha frequency training for cognitive enhancement in the elderly.

Neurofeedback (NF) is an electroencephalographic (EEG) biofeedback technique for training individuals to alter their brain activity via operant conditioning. Research has shown that NF helps reduce symptoms of several neurological and psychiatric disorders, with ongoing research currently investigating applications to other disorders and to the enhancement of non-disordered cognition. The present article briefly reviews the fundamentals and current status of NF therapy and research and illustrates the basic approach with an interim report on a pilot study aimed at developing a new NF protocol for improving cognitive function in the elderly. EEG peak alpha frequency (PAF) has been shown to correlate positively with cognitive performance and to correlate negatively with age after childhood. The present pilot study used a double-blind controlled design to investigate whether training older individuals to increase PAF would result in improved cognitive performance. The results suggested that PAF NF improved cognitive processing speed and executive function, but that it had no clear effect on memory. In sum, the results suggest that the PAF NF protocol is a promising technique for improving selected cognitive functions.

The effects of neurofeedback training in the cognitive division of the anterior cingulate gyrus.

This study examines the efficacy of neurofeedback training in the cognitive division of the anterior cingulate gyrus and describes its relationship with cortical regions known to be involved in executive functions. This study was conducted with eight non-clinical students, four male and four female, with a mean age of twenty-two. Learning occurred in the ACcd at significant levels over sessions and in the anterior regions that receive projections from the AC. There appears to be a multidimensional executive circuit that increases in the same frequency in apparent synchrony with the AC and it may be possible to train this sub-cortical region using LNFB.

Electroencephalographic biofeedback in the treatment of attention-deficit/hyperactivity disorder.

Historically, pharmacological treatments for attention-deficit/hyperactivity disorder (ADHD) have been considered to be the only type of interventions effective for reducing the core symptoms of this condition. However, during the past three decades, a series of case and controlled group studies examining the effects of EEG biofeedback have reported improved attention and behavioral control, increased cortical activation on quantitative electroencephalographic examination, and gains on tests of intelligence and academic achievement in response to this type of treatment. This review paper critically examines the empirical evidence, applying the efficacy guidelines jointly established by the Association for Applied Psychophysiology and Biofeedback (AAPB) and the International Society for Neuronal Regulation (ISNR). On the basis of these scientific principles, EEG biofeedback was determined to be "probably efficacious" for the treatment of ADHD. Although significant clinical improvement was reported in approximately 75% of the patients in each of the published research studies, additional randomized, controlled group studies are needed in order to provide a better estimate of the percentage of patients with ADHD who will demonstrate such gains in clinical practice.

Low-resolution electromagnetic tomography neurofeedback.

Through continuous feedback of the electroencephalogram (EEG) humans can learn how to shape their brain electrical activity in a desired direction. The technique is known as EEG biofeedback, or neurofeedback, and has been used since the late 1960s in research and clinical applications. A major limitation of neurofeedback relates to the limited information provided by a single or small number of electrodes placed on the scalp. We establish a method for extracting and feeding back intracranial current density and we carry out an experimental study to ascertain the ability of the participants to drive their own EEG power in a desired direction. To derive current density within the brain volume, we used the low-resolution electromagnetic tomography (LORETA). Six undergraduate students (three males, three females) underwent tomographic neurofeedback (based on 19 electrodes placed according to the 10-20 system) to enhance the current density power ratio between the frequency bands beta (16-20 Hz) and alpha (8-10 Hz). According to LORETA modeling, the region of interest corresponded to the Anterior Cingulate (cognitive division). The protocol was designed to improve the performance of the subjects on the dimension of sustained attention. Two hypotheses were tested: 1) that the beta/alpha current density power ratio increased over sessions and 2) that by the end of the training subjects acquired the ability of increasing that ratio at will. Both hypotheses received substantial experimental support in this study. This is the first application of an EEG inverse solution to neurofeedback. Possible applications of the technique include the treatment of epileptic foci, the rehabilitation of specific brain regions damaged as a consequence of traumatic brain injury and, in general, the training of any spatial specific cortical electrical activity. These findings may also have relevant consequences for the development of brain-computer interfaces.

Electroencephalographic peak alpha frequency correlates of cognitive traits.

EEG peak alpha frequency (PAF) has been shown to differentiate groups of adults with higher memory performance from those of lower performance, groups of children with advanced reading ability from matched controls, and to predict state-dependent working memory. The present study attempted to explore PAF as a predicting variable for verbal and attentional cognitive trait abilities in young adults. Nineteen undergraduate students had their EEG recorded during initial rest, reading, and post-reading rest, and at a different day were evaluated on reading, vocabulary, and attentional performance. Results showed significant correlations of reading vocabulary and response control with PAF during reading and post-reading recordings, but not during initial rest. PAF may reflect some general cognitive ability that is not necessarily memory or reading, possibly response control or the ability to acquire vocabulary. It is suggested that cognitive ability traits may reflect the ability to induce cognitive states.

Peak alpha frequency: an electroencephalographic measure of cognitive preparedness.

OBJECTIVE: Electroencephalographic (EEG) peak alpha frequency (PAF) (measured in Hz) has been correlated to cognitive performance between healthy and clinical individuals, and among healthy individuals. PAF also varies within individuals across developmental stages, among different cognitive tasks, and among physiological states induced by administration of various substances. The present study suggests that, among other things, PAF reflects a trait or state of cognitive preparedness. METHODS: Experiment 1 involved 19-channel EEG recordings from 10 individuals with traumatic brain injury (TBI) and 12 healthy matched controls, before, during, and after tasks of visual and auditory attention. Experiment 2 involved EEG recordings from 19 healthy young adults before and after a working memory task (WAIS-R Digit Span), repeated on 2 different days to measure within-individual differences. RESULTS: Experiment 1 showed significantly lower PAF in individuals with TBI, mostly during post-task rest. Experiment 2 showed PAF during pre-task baseline to be significantly correlated with Digit Span performance of the same day but not with Digit Span performance of another day. Moreover, PAF was significantly increased after Digit Span for those participants whose PAF was lower than the sample median before the task, but not for those who had it higher. Finally, both PAF and Digit Span performance were increased during the second day. CONCLUSIONS: PAF was shown to detect both trait and state differences in cognitive preparedness, as well as to be affected by cognitive tasks. Traits are better reflected during post-task rest, whereas states are better reflected during initial resting baseline recordings.

Low-resolution electromagnetic tomography (LORETA) of cerebral activity in chronic depressive disorder.

In this study we compared the current density power and power asymmetry in 15 right-handed, medication-free chronically depressed females (of the unipolar type) and age-matched non-clinical female controls. We used frequency domain LORETA (Low-Resolution Electromagnetic Tomography). In the interhemispheric asymmetry analysis, compared with the control group, the depression group exhibited a left-to-right Alpha2 (10-12 Hz) current density dominance in the left postcentral gyrus. The pattern of left-to-right dominance included frontal (especially medial and middle frontal gyri) and temporal locations. The between groups comparison of spectral power revealed decreased activity in the right middle temporal gyrus in the depressed group. The decrease emerged in the whole frequency spectrum analyzed (2-32 Hz), although it reached significance in the Delta (2-3.5 Hz) band only. These findings are discussed in terms of the existing literature on affect using EEG, PET and SPECT.