Exploration of electroencephalogram response to MPH treatment in ADHD patients.

Attention-deficit/hyperactivity disorder (ADHD) is known to be associated with several diagnostic resting-state electroencephalography (EEG) patterns, including the theta/beta ratio, but no objective predictive markers for each medication. In this study, we explored EEG markers with which the therapeutic efficacy of medications could be estimated at the 1st clinical visit. Thirty-two ADHD patients and thirty-one healthy subjects participated in this study. EEG was recorded during eyes-closed resting conditions, and ADHD symptoms were scored before and after the therapeutic intervention (8 ± 2 weeks). Although comparing EEG patterns between ADHD patients and healthy subjects showed significant differences, EEG dynamics, e.g., theta/beta ratio, in ADHD patients before and after MPH treatment were not significantly different despite improvements in ADHD symptoms. We demonstrated that MPH good responders and poor responders, defined by the efficacy of MPH, had significantly different theta band power in right temporal areas, alpha in left occipital and frontal areas, and beta in left frontal areas. Moreover, we showed that MPH good responders had significant improvements toward normalization in several coherence measures after MPH treatment. Our study implies the possibility of these EEG indices as predictive markers for ADHD therapeutic efficacy.

Histone Deacetylase 2 Knockdown Ameliorates Morphological Abnormalities of Dendritic Branches and Spines to Improve Synaptic Plasticity in an APP/PS1 Transgenic Mouse Model.

Disease-modifying therapies, such as neuroprotective and neurorestorative interventions, are strongly desired for Alzheimer's disease (AD) treatment. Several studies have suggested that histone deacetylase 2 (HDAC2) inhibition can exhibit disease-modifying effects in AD patients. However, whether HDAC2 inhibition shows neuroprotective and neurorestorative effects under neuropathic conditions, such as amyloid ß (Aß)-elevated states, remains poorly understood. Here, we performed HDAC2-specific knockdown in CA1 pyramidal cells and showed that HDAC2 knockdown increased the length of dendrites and the number of mushroom-like spines of CA1 basal dendrites in APP/PS1 transgenic mouse model. Furthermore, HDAC2 knockdown also ameliorated the deficits in hippocampal CA1 long-term potentiation and memory impairment in contextual fear conditioning tests. Taken together, our results support the notion that specific inhibition of HDAC2 has the potential to slow the disease progression of AD through ameliorating Aß-induced neuronal impairments.

Semi-Automated Biomarker Discovery from Pharmacodynamic Effects on EEG in ADHD Rodent Models.

We propose a novel semi-automatic approach to design biomarkers for capturing pharmacodynamic effects induced by pharmacological agents on the spectral power of electroencephalography (EEG) recordings. We apply this methodology to investigate the pharmacodynamic effects of methylphenidate (MPH) and atomoxetine (ATX) on attention deficit/hyperactivity disorder (ADHD), using rodent models. We inject the two agents into the spontaneously hypertensive rat (SHR) model of ADHD, the Wistar-Kyoto rat (WKY), and the Wistar rat (WIS), and record their EEG patterns. To assess individual EEG patterns quantitatively, we use an integrated methodological approach, which consists of calculating the mean, slope and intercept parameters of temporal records of EEG spectral power using a smoothing filter, outlier truncation, and linear regression. We apply Fisher discriminant analysis (FDA) to identify dominant discriminants to be heuristically consolidated into several new composite biomarkers. Results of the analysis of variance (ANOVA) and t-test show benefits in pharmacodynamic parameters, especially the slope parameter. Composite biomarker evaluation confirms their validity for genetic model stratification and the effects of the pharmacological agents used. The methodology proposed is of generic use as an approach to investigating thoroughly the dynamics of the EEG spectral power.

Combining behavior and EEG analysis for exploration of dynamic effects of ADHD treatment in animal models.

BACKGROUND: We analyze the dynamics of rodent EEG amplitude in an experiment accompanied by video recordings. Brain activity of animals is commonly acquired together with a video of behavior, but recordings are rarely combined in analysis. The data acquired is most commonly analyzed separately. To our knowledge, no study has used behavior to improve the analysis of EEG waveforms, specifically for artifact removal - other than through manual editing. COMPARISON WITH EXISTING METHOD(S): We explore two approaches: a traditional approach that relies on data preprocessing and artifact rejection by an expert; and an alternative approach that combines analysis of EEG with behavior extracted from video recordings. NEW METHOD: We use the level of activity extracted from the behavioral video as a measure of confidence in the acquired EEG waveform, and as a weighting factor in averaging and statistical comparisons. RESULTS: We find in analysis of the EEG that the two approaches lead to similar conclusions, but the analysis leveraging behavioral data achieves this while avoiding many subjective choices often required for artifact rejection and data preprocessing. CONCLUSIONS: The methods we describe allow for the inclusion of all recorded data in the analysis, thereby making statistical tests more friendly to interpretation, and making the data processing transparent and reproducible.

[Pharmacological profiles of benzodiazepinergic hypnotics and correlations with receptor subtypes].

We examined the behavioral pharmacological properties of six benzodiazepine (omega) receptor ligands including brotizoram, nitrazepam, quazepam, rilmazafone, zolpidem and zopiclone and the binding of these drugs with omega receptor subtypes. Behavioral tests were performed at the time of the maximal effects induced by each drug following its oral administration to mice. All of these drugs dose-dependently induced impairment of motor coordination as rotarod performance and potentiation of thiopental-induced anesthesia as hypnotic effect. The hypnotic effects of rilmazafone, whose major metabolites were bound to both omega1 and omega2 receptors with high affinity, and omega1 selective quazepam were about 20 times more effective than the induction of motor impairments when compared with ED50 values. However, there was no difference between the ED50 values of omega1 selective zolpidem alone in these two tests. An antianxiety efficacy of zolpidem was relatively weak unlike that of other drugs in the elevated plus-maze. It has been reported that omega2, but not omega1, receptors are associated with motor impairment and anxiolytic effect. The weak anxiolytic effect of zolpidem supports the previous hypothesis. However, the strong motor incoordination of zolpidem suggests that not only omega2 but also omega1 receptors are related to motor impairment unlike the previous hypothesis.