Dataset Information

Effects of morphine and alcohol on functional brain connectivity during "resting state": a placebo-controlled crossover study in healthy young men.

ABSTRACT: A major challenge in central nervous system (CNS) drug research is to develop a generally applicable methodology for repeated measurements of drug effects on the entire CNS, without task-related interactions and a priori models. For this reason, data-driven resting-state fMRI methods are promising for pharmacological research. This study aimed to investigate whether different psychoactive substances cause drug-specific effects in functional brain connectivity during resting-state. In this double blind placebo-controlled (double dummy) crossover study, seven resting-state fMRI scans were obtained in 12 healthy young men in three different drug sessions (placebo, morphine and alcohol; randomized). Drugs were administered intravenously based on validated pharmacokinetic protocols to minimize the inter- and intra-subject variance in plasma drug concentrations. Dual-regression was used to estimate whole-brain resting-state connectivity in relation to eight well-characterized resting-state networks, for each data set. A mixed effects analysis of drug by time interactions revealed dissociable changes in both pharmacodynamics and functional connectivity resulting from alcohol and morphine. Post hoc analysis of regions of interest revealed adaptive network interactions in relation to pharmacokinetic and pharmacodynamic curves. Our results illustrate the applicability of resting-state functional brain connectivity in CNS drug research.

SUBMITTER: Khalili-Mahani N

PROVIDER: S-EPMC6870105 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effects of morphine and alcohol on functional brain connectivity during "resting state": a placebo-controlled crossover study in healthy young men.

Khalili-Mahani Najmeh N Zoethout Remco M W RM Beckmann Christian F CF Baerends Evelinda E de Kam Marieke L ML Soeter Roelof P RP Dahan Albert A van Buchem Mark A MA van Gerven Joop M A JM Rombouts Serge A R B SA

Human brain mapping 20110309 5

A major challenge in central nervous system (CNS) drug research is to develop a generally applicable methodology for repeated measurements of drug effects on the entire CNS, without task-related interactions and a priori models. For this reason, data-driven resting-state fMRI methods are promising for pharmacological research. This study aimed to investigate whether different psychoactive substances cause drug-specific effects in functional brain connectivity during resting-state. In this double ...[more]

PMID: 21391283

Similar Datasets

Project description:BackgroundUsing balanced placebo designs, seminal alcohol administration research has shown individuals' beliefs about whether they have consumed alcohol, irrespective of the actual presence of alcohol, can determine level of alcohol consumption and impact social behavior. Despite the known effect of expecting alcohol on drinking behavior, few studies have used the placebo manipulation to directly investigate the neural underpinnings of the expectancy-related effects that occur following perceived alcohol consumption in humans. The present paper examined placebo responses in the laboratory to better understand the neural basis for the psychological phenomenon of expectancies.MethodsAs part of a larger within-subjects study design, healthy young adults (N = 22, agemean+SD=23 +1) completed resting state fMRI scans and measures of subjective response before and after consuming placebo beverages. Effect of placebo beverage consumption (pre- versus post-beverage consumption) on functional connectivity within prefrontal cortical networks was examined using the CONN Toolbox. Relations between perceived subjective response to alcohol with functional connectivity response following placebo beverage consumption were examined.ResultsCompared to pre-beverage scan, placebo beverage consumption was associated with increased positive functional connectivity between right nucleus accumbens - ventromedial prefrontal cortex and subcallosal cingulate cortex (pFDR<0.05). Subjective ratings of intoxication (i.e., feeling 'drunk') positively correlated with placebo beverage-related increases in nucleus accumbens - subcallosal cingulate cortex functional connectivity.ConclusionResults suggest placebo response to alcohol is associated with increased functional connectivity within a key reward network (nucleus accumbens - ventromedial prefrontal cortex and subcallosal cingulate cortex) and put forth a mechanism by which alcohol expectancies may contribute to the subjective experience of intoxication.

Project description:Background: The basic functional organization of the resting brain, assessed as resting-state functional connectivity (rsFC), can be affected by previous stress experience and it represents the basis on which subsequent stress experience develops. Notably, the rsFC between the amygdala and the cortical regions associated with emotion regulation and anxiety are affected during stress. The multicomponent drug Neurexan® (Nx4) has previously demonstrated a reduction in amygdala activation in an emotional face matching task and it ameliorated stress-related symptoms. We, thus, investigated the effect of Nx4 on rsFC of the amygdala before stress induction compared with baseline in mildly to moderately stressed participants. Methods: In a randomized, placebo-controlled, double-blind, crossover trial 39 participants received a single dose of placebo or Nx4. Resting-state functional magnetic resonance imaging scans were performed pre-dose and 40 to 60 min post-dose, before any stress induction. First, highly connected functional hubs were identified by global functional connectivity density (gFCD) analysis. Second, by using a seed-based approach, rsFC maps of the left centromedial amygdala (CeMA) were created. The effect of Nx4 on both was evaluated. Results: The medial prefrontal cortex was identified as a relevant functional hub affected by Nx4 in an explorative whole brain gFCD analysis. Using the seed-based approach, we then demonstrated that Nx4 significantly enhanced the negative connectivity between the left CeMA and two cortical regions: the dorsolateral and medial prefrontal cortices. Conclusions: In a resting-state condition, Nx4 reduced the prefrontal cortex gFCD and strengthened the functional coupling between the amygdala and the prefrontal cortex that is relevant for emotion regulation and the stress response. Further studies should elaborate whether this mechanism represents enhanced regulatory control of the amygdala at rest and, consequently, to a diminished susceptibility to stress. ClinicalTrials.gov ID: NCT02602275.

Project description:Aims Currently, there are only a few studies concerning brain functional alterations after acute alcohol exposure, and the majority of existing studies attach more importance to the spatial properties of brain function without considering the temporal properties. The current study adopted sliding window to investigate the resting-state brain networks in healthy volunteers after acute alcohol intake and to explore the dynamic changes in network connectivity. Materials and methods Twenty healthy volunteers were enrolled in this study. Blood-oxygen-level-dependent (BOLD) data prior to drinking were obtained as control, while that 0.5 and 1 h after drinking were obtained as the experimental group. Reoccurring functional connectivity patterns (states) were determined following group independent component analysis (ICA), sliding window analysis and k-means clustering. Between-group comparisons were performed with respect to the functional connectivity states fractional windows, mean dwell time, and the number of transitions. Results Three optimal functional connectivity states were identified. The fractional windows and mean dwell time of 0.5 h group and 1 h group increased in state 3, while the fraction window and mean dwell time of 1 h group decreased in state 1. State 1 is characterized by strong inter-network connections between basal ganglia network (BGN) and sensorimotor network (SMN), BGN and cognitive executive network (CEN), and default mode network (DMN) and visual network (VN). However, state 3 is distinguished by relatively weak intra-network connections in SMN, VN, CEN, and DMN. State 3 was thought to be a characteristic connectivity pattern of the drunk brain. State 1 was believed to represent the brain’s main connection pattern when awake. Such dynamic changes in brain network connectivity were consistent with participants’ subjective feelings after drinking. Conclusion The current study reveals the dynamic change in resting-state brain functional network connectivity before and after acute alcohol intake. It was discovered that there might be relatively independent characteristic functional network connection patterns under intoxication, and the corresponding patterns characterize the clinical manifestations of volunteers. As a valuable imaging biomarker, dynamic functional network connectivity (dFNC) offers a new approach and basis for further explorations on brain network alterations after alcohol consumption and the alcohol-related mechanisms for neurological damage.

Dataset Information

Effects of morphine and alcohol on functional brain connectivity during "resting state": a placebo-controlled crossover study in healthy young men.

Publications

Effects of morphine and alcohol on functional brain connectivity during "resting state": a placebo-controlled crossover study in healthy young men.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets