ADHD and EEG-neurofeedback: a double-blind randomized placebo-controlled feasibility study.

Electroencephalography (EEG)-neurofeedback has been shown to offer therapeutic benefits to patients with attention-deficit/hyperactivity disorder (ADHD) in several, mostly uncontrolled studies. This pilot study is designed to test the feasibility and safety of using a double-blind placebo feedback-controlled design and to explore the initial efficacy of individualized EEG-neurofeedback training in children with ADHD. Fourteen children (8-15 years) with ADHD defined according to the DSM-IV-TR criteria were randomly allocated to 30 sessions of EEG-neurofeedback (n = 8) or placebo feedback (n = 6). Safety measures (adverse events and sleep problems), ADHD symptoms and global improvement were monitored. With respect to feasibility, all children completed the study and attended all study visits and training sessions. No significant adverse effects or sleep problems were reported. Regarding the expectancy, 75% of children and their parent(s) in the active neurofeedback group and 50% of children and their parent(s) in the placebo feedback group thought they received placebo feedback training. Analyses revealed significant improvements of ADHD symptoms over time, but changes were similar for both groups. This pilot study shows that it is feasible to conduct a rigorous placebo-controlled trial to investigate the efficacy of neurofeedback training in children with ADHD. However, a double-blind design may not be feasible since using automatic adjusted reward thresholds may not work as effective as manually adjusted reward thresholds. Additionally, implementation of active learning strategies may be an important factor for the efficacy of EEG-neurofeedback training. Based on the results of this pilot study, changes are made in the design of the ongoing study.

Developmental differences in behavioral and event-related brain responses associated with response preparation and inhibition in a go/nogo task.

The present study investigated developmental trends in response inhibition and preparation by studying behavior and event-related brain activity in a cued go/nogo task, administered to nine-year-old children and young adults. Hits, false alarms, inattention, and impulsivity scores and ERP measures of inhibition (fronto-central nogo-N2 and P3), target selection (parietal go-nogo P3 difference), and response preparation (contingent negative variation; CNV) were collected. Higher false alarm and impulsivity scores and the absence of the fronto-central nogo P3 all suggest a developmental lag in response inhibition in children. A developmental lag in sustained attention processes was suggested by worse target detection and larger parietal target/nontarget P3 effects in children. Cue orientation and response preparation processes were respectively measured by early and late CNV activity. Children displayed smaller early CNV amplitudes at fronto-central locations, but mature late CNV. The smaller early CNV activity might indicate inefficient cue-orientation processes caused by incomplete frontal lobe development.

Comparison of thermal threshold tests to assess small nerve fiber function: limits vs. levels.

OBJECTIVE: The method of limits (MLI) and the method of levels (MLE) are psychophysical stimulus procedures most commonly applied to quantify warm and cold sensation thresholds in humans. This paper evaluates basic methodological properties of both methods and investigates the correspondence between the method's results. METHODS: Warm sensation threshold was measured in 20 healthy participants using the psychophysical MLIs and MLEs. Two differently shaped kind of levels stimuli were used with triangular (TRIANG) and trapezoid (TRAP) temperature-time profile. RESULTS: A linear model of temperature response, based on threshold level-crossing, quantifies sensation threshold, independent of the MLI inherent 'reaction-time' artifact. It results from modeling MLI responses to warm stimuli with different rates of temperature change. The model also quantifies the reaction-time delay in the physiological system from thermal stimulus presentation until manual response. This study shows that using the reaction-time independent MLE, TRAP should preferably be used for optimal quantification of sensation threshold. CONCLUSIONS: Statistical testing shows that model-based MLI threshold equals MLE threshold provided MLE TRAP stimuli are used. Recommendations for optimal MLI and MLE stimulus configurations and properties are given in relation to application of quantitative sensory testing.

Monitoring the exposure of rats to 2-acetylaminofluorene by the estimation of mutagenic activity in excreta, sister-chromatid exchanges in peripheral blood cells and DNA adducts in peripheral blood, liver and spleen.

The sensitivity of various methods suitable for biomonitoring the exposure to genotoxicants was compared in an animal model. The results were related to the presence of genotoxic effects in the target organ. Groups of male Wistar rats were given one oral dose of 0, 0.1, 10 or 200 mg 2-acetylaminofluorene (2-AAF)/5 ml dimethyl sulphoxide/kg body weight. Peripheral blood cells, excreta, liver and spleen were collected at different time intervals after dosing. Mutagenicity in urine and extracts of faeces was determined using the Ames test with Salmonella typhimurium TA98 with and without S9 and with and without beta-glucuronidase. Genotoxic effects were studied by measuring DNA-adduct formation in lymphocytes, liver and spleen, and sister-chromatid exchanges (SCEs) in lymphocytes. DNA adducts were measured with immunochemical techniques and postlabelling methods. Mutagenicity in urine and faeces, collected during the first 24 h after treatment, was detected at 2-AAF doses of 1 mg/kg b.w. and higher. At these doses DNA adducts also became apparent in the liver, the main target organ for tumour induction by 2-AAF. The adduct detected appeared to be the N-(deoxyguanosin-8-yl)-2-AAF adduct. There was no evidence of the presence of any other types of DNA adducts. At doses of 1 and 10 mg/kg b.w. no mutagenicity was detected in excreta collected during the second and third day after dosing. The DNA-adduct level in liver cells of the 1 mg/kg b.w. group was maximal 24 h after dosing. At 200 mg/kg b.w. a delay in excretion of mutagenicity with urine and faeces was seen and at 10 and 200 mg/kg b.w. the amount of DNA adducts continued to increase with time after dosing. At 24 and 48 h after treatment with 10 mg, the adduct levels were of the same order of magnitude as those found after the 20-fold higher dose. This points to overloading of the metabolizing system which in combination with the enterohepatic circulation, may lead to an increased retention of 2-AAF in the body. A slightly increased incidence of SCEs of doubtful significance was seen in lymphocytes, but only at the very high dose of 200 mg/kg b.w. No DNA adducts could be detected in blood lymphocytes or spleen cells at any of the dose levels applied, either with the immunochemical or with the postlabelling method.(ABSTRACT TRUNCATED AT 400 WORDS)

Use of monoclonal and polyclonal antibodies against DNA adducts for the detection of DNA lesions in isolated DNA and in single cells.

Interaction of genotoxic chemicals with their intracellular target, i.e., DNA, may result in the formation of covalent adducts. Various methods have been developed to estimate exposure to genotoxic chemicals by means of molecular dosimetry of DNA adducts. Such experiments have generally been carried out with radiolabeled genotoxicants administered in vitro to cultured cells or in vivo to laboratory animals. Biomonitoring of human exposure to genotoxic chemicals requires methods to detect very small quantities of nonradioactive DNA adducts in limited amounts of sample. Attention has been devoted to the development of immunochemical techniques in which specific DNA adducts can be detected with antibodies. The level of sensitivity achieved in these experiments renders these methods applicable for human biomonitoring. When suitable antibodies are available, the immunochemical approach enables one to analyze various types of adducts separately, and to discriminate between irrelevant (e.g., quickly repairable) and relevant lesions (key lesions) with respect to biological end points such as mutation induction and cancer. Polyclonal and monoclonal antibodies were used for the detection of DNA adducts in animal and human tissue. Adducts were measured in DNA from various organs of rats treated with the liver carcinogen 2-AAF. Human exposure to genotoxic agents was studied by the measurement of DNA adducts in blood cells from patients treated with the genotoxic cytostatic cisplatin. Also, the development is described of a system to detect and quantitate DNA adducts at the single-cell level by means of immunofluorescence microscopy, which allows the analysis of small samples of human tissue with preservation of cell morphology.

The organ-specific induction of DNA adducts in 2-acetylaminofluorene-treated rats, studied by means of a sensitive immunochemical method.

Exposure of cells to chemical carcinogens and mutagens may result in the formation of DNA adducts, which can give rise to mutations in the genome and to cellular transformation. Methods to measure DNA-adduct formation may be useful for 'biomonitoring', to establish exposure of laboratory animals or humans to DNA-damaging agents. For such purposes, immunochemical methods appear to be suitable, because they allow sensitive detection and quantification of DNA adducts in small amounts of sample in a non-radiolabelled form. We have worked out optimal conditions for the detection of DNA adducts by means of competitive enzyme-linked immunosorbent assay (ELISA). This technique involves interaction of soluble antigen, immobilized antigen and antibody. It appeared that the sensitivity of the competitive assay can be improved by lowering the amount of immobilized antigen, adsorbed to the wall of the plastic reaction vessel. On the basis of these observations, suitable conditions were selected for a sensitive quantitative assay of adducts in DNA isolated from various organs of rats, treated (p.o.) with the liver carcinogen 2-acetylaminofluorene (2-AAF). Under the conditions of these experiments, the available rabbit antiserum recognizes the guanosine-AAF adduct with high specificity. A time- and dose-dependent induction of AAF adducts could be measured in liver DNA from exposed rats, whereas the amount of adducts in DNA from spleen and nucleated blood cells remained below the detection limit (1 adduct/10(8) nucleotides). The implications of these findings with respect to the relevance of blood cell biomonitoring for target cell exposure are discussed.