Acute effects of MDMA (3,4-methylenedioxymethamphetamine) on EEG oscillations: alone and in combination with ethanol or THC (delta-9-tetrahydrocannabinol)

Item does not contain fulltextRATIONALE: Typical users of 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") are polydrug users, combining MDMA with alcohol or cannabis [most active compound: delta-9-tetrahydrocannabinol (THC)]. OBJECTIVES: The aim of the present study was to investigate whether co-administration of alcohol or THC with MDMA differentially affects ongoing electroencephalogram (EEG) oscillations compared to the administration of each drug alone. METHODS: In two separate experiments, 16 volunteers received four different drug conditions: (1) MDMA (100 mg); (2) alcohol clamp (blood alcohol concentration = 0.6 per thousand) or THC (inhalation of 4, 6 and 6 mg, interval of 1.5 h); (3) MDMA in combination with alcohol or THC; and (4) placebo. Before and after drug administration, electroencephalography was recorded during an eyes closed resting state. RESULTS: Theta and alpha power increased after alcohol intake compared to placebo and reduced after MDMA intake. No interaction between alcohol and MDMA was found. Significant MDMA x THC effects for theta and lower-1-alpha power indicated that the power attenuation after the combined intake of MDMA and THC was less than the sum of each drug alone. For the lower-2-alpha band, the intake of MDMA or THC alone did not significantly affect power, but the intake of combined MDMA and THC significantly decreased lower-2-alpha power. CONCLUSIONS: The present findings indicate that the combined intake of MDMA and THC, but not of MDMA and alcohol, affects ongoing EEG oscillations differently than the sum of either one drug alone. Changes in ongoing EEG oscillations may be related to the impaired task performance that has often been reported after drug intake

Impulsivity and conflict in the stroop task: an ERP study

It has been suggested that impulsive behavior can be attributed to weaker interference control. The present research used a Stroop task to test whether impulsivity within the normal population is associated with weaker interference control. Sixteen high- and 16 low-impulsive healthy volunteers performed a Stroop task, which varied in the proportion of incongruent trials to induce high conflict and provoke more impulsive behavior. Event-related brain potentials (ERP) were recorded to assess the brain correlates of Stroop interference (N/P450 and SP [sustained potential]), which have been suggested to reflect conflict processing and attentional control, respectively. Higher conflict resulted in more Stroop interference and enhanced N/P450 and SP. Source analyses indicated that the neural generators of the N/P450 and the SP may both be located near the anterior cingulate cortex (ACC), suggesting that both may reflect aspects of conflict processing. Differences in Stroop interference in terms of error rates, but not in terms of reaction time were found between high and low impulsives. This result may reflect enhanced sensitivity to the surprise value of unexpected stimulus categories, rather than enhanced interference. High impulsive participants did not differ from low impulsive participants with respect to the N/P450, but the SP seemed to originate from a more posterior and right-sided cortical network in high impulsive relative to low impulsive participants. In conclusion, high impulsiveness within the normal population as assessed by an impulsivity questionnaire is not associated with relatively early processes during response inhibition, but the present results may suggest an association between impulsiveness and further, more complex conflict processing

The medical food Souvenaid affects brain phospholipid metabolism in mild Alzheimer’s disease: results from a randomized controlled trial

Abstract Background Synaptic dysfunction contributes to cognitive impairment in Alzheimer’s disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients with Alzheimer’s disease. Methods Thirty-four drug-naive patients with mild Alzheimer’s disease (Mini Mental State Examination score ≥20) were enrolled in this exploratory, double-blind, randomized controlled study. Before and after 4-week intervention with Souvenaid or an isocaloric control product, phosphorus and proton magnetic resonance spectroscopy (MRS) was performed to assess surrogate measures of phospholipid synthesis and breakdown (phosphomonoesters [PME] and phosphodiesters [PDEs]), neural integrity (N-acetyl aspartate), gliosis (myo-inositol), and choline metabolism (choline-containing compounds [tCho]). The main outcome parameters were PME and PDE signal intensities and the PME/PDE ratio. Results MRS data from 33 patients (60–86 years old; 42% males; Souvenaid arm n = 16; control arm n = 17) were analyzed. PME/PDE and tCho were higher after 4 weeks of Souvenaid compared with control (PME/PDE least squares [LS] mean difference [95% CI] 0.18 [0.06–0.30], p = 0.005; tCho LS mean difference [95% CI] 0.01 [0.00–0.02], p = 0.019). No significant differences were observed in the other MRS outcome parameters. Conclusions MRS reveals that Souvenaid affects brain phospholipid metabolism in mild Alzheimer’s disease, in line with findings in preclinical studies. Trial registration Netherlands Trial Register, NTR3346 . Registered on 13 March 2012

Magnetoencephalography for the detection of intervention effects of a specific nutrient combination in patients with mild Alzheimer’s disease: Results from an exploratory double blind randomised controlled study

Synaptic loss is an early pathological finding in Alzheimer’s disease (AD) and correlates with memory impairment. Changes in macroscopic brain activity measured with electro- and magnetoencephalography (EEG and MEG) in AD indicate synaptic changes and may therefore serve as markers of intervention effects in clinical trials. EEG peak frequency and functional networks have shown, in addition to improved memory performance, to be sensitive to detect an intervention effect in mild AD patients of the medical food Souvenaid containing the specific nutrient combination Fortasyn® Connect, which is designed to enhance synapse formation and function. Here, we explore the value of MEG, with higher spatial resolution than EEG, in identifying intervention effects of the nutrient combination by comparing MEG spectral measures, functional connectivity and – networks between an intervention and a control group. Quantitative markers describing spectral properties, functional connectivity and graph theoretical aspects of MEG from the exploratory 24-week, double blind, randomized controlled Souvenir II MEG sub-study (NTR1975, http://www.trialregister.nl) in drug-naïve patients with mild AD were compared between a test group (n=27), receiving Souvenaid, and a control group (n=28), receiving an isocaloric control product. The groups were unbalanced at screening with respect to Mini-Mental State Examination (MMSE). Peak frequencies of MEG were compared to EEG peak frequencies, recorded in the same patients at similar time points, were compared with respect to sensitivity to intervention effects. No consistent statistically significant intervention effects were detected. In addition, we found no difference in sensitivity between MEG and EEG peak frequency. This exploratory study could not unequivocally establish the value of MEG in detecting interventional effects on brain activity, possibly due to small sample size and unbalanced study groups. We found no indication that the difference could be attributed to a lack of sensitivity of MEG compared to EEG. MEG in randomized controlled trials is feasible but its value to disclose intervention effects of Souvenaid in mild AD patients needs to be studied further

The Effect of Souvenaid on Functional Brain Network Organisation in Patients with Mild Alzheimer’s Disease: A Randomised Controlled Study

<div><p>Background</p><p>Synaptic loss is a major hallmark of Alzheimer’s disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials.</p><p>Objective</p><p>To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD.</p><p>Design</p><p>A 24-week randomised, controlled, double-blind, parallel-group, multi-country study.</p><p>Participants</p><p>179 drug-naïve mild AD patients who participated in the Souvenir II study.</p><p>Intervention</p><p>Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks.</p><p>Outcome</p><p>In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance.</p><p>Results</p><p>The network measures in the beta band were significantly different between groups: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance.</p><p>Conclusions</p><p>The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions.</p><p>Trial registration</p><p>Dutch Trial Register <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1975" target="_blank">NTR1975</a>.</p></div

Network models based on clustering coefficient C and path length L.

<p>Left: ordered model with high C and high L, middle: small-world model with high C and low L, right: random model with low C and low L. Adapted from Watts and Strogatz, Nature 1998.</p

Schematic representation of construction of graphs from EEG time series.

<p>EEG time series are measured from scalp electrodes. Phase Lag Index (PLI) as a measure of functional connectivity is calculated between all pairs of electrodes. From the PLI adjacency matrix, the functional brain network is reconstructed and network measures are computed.</p

Baseline demographics and characteristics of the subset of subjects for whom EEG data were available (intent-to-treat population).

<p><i>Note.</i> AD: Alzheimer’s disease; MMSE: Mini-Mental State Examination; Data are presented as mean (standard deviation) unless stated otherwise.</p