Rafael Rodriguez-Rojas

Zolpidem induces paradoxical metabolic and vascular changes in a patient with PVS

Abstract Introduction: Zolpidem is a non-benzodiazepine drug used for the therapy of insomnia, which has selectivity for stimulating the effect of GABA-A receptors. Recently, a paradoxical arousing effect of zolpidem in patients with severe brain damage has been repeatedly reported. Methods: A placebo-controlled magnetic resonance study was conducted to evaluate its effect on BOLD and metabolites spectral signals in a patient with severe brain injuries and an age-matched healthy volunteer. A multi-modal analysis was used to assess aspects in the pharmacologically-induced changes in the resting-state brain metabolism. Results: A significantly increased BOLD signal was transiently localized in the left frontal cortices, bilateral anterior cingulated areas, left thalamus and right head of the caudate nucleus. The healthy subject showed a deactivation of the frontal, parietal and temporal cortices. BOLD signal changes were found to significantly correlate with concentrations of extravascular metabolites in the left frontal cortex. It is discussed that, when zolpidem attaches to modified GABA receptors of neurodormant brain cells, brain activation is induced. This might explain the significant correlations of BOLD signal changes and proton-MRS metabolites in this patient after zolpidem. Conclusion: It was concluded that proton-MRS and BOLD signal assessment could be used to study zolpidem-induced metabolic modulation in a resting state.

Neuroimages in Autism

This chapter summarizes findings of the morphological and functional brain changes in autistic spectrum disorders (ASD), demonstrated by a growing body of researches that employs diverse neuroimaging methods. We discuss major anatomical findings from studies in ASD utilizing structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). We also explore findings from functional MRI (fMRI) studies, including task-related activation studies and functional connectivity. Regional changes in brain metabolism are examined using magnetic resonance spectroscopy (MRS) and nuclear medicine techniques, including positron emission tomography (PET) and single-photon emission tomography (SPECT). Finally, we highlight directions for continued research in neuroimaging of ASD at a network level using graph theoretical approaches.

Neural activity changes in the Supplementary Motor Area induced by dopaminergic treatment in parkinsonian patients

In this research, we study the neural activity changes in supplementary motor area (SMA) in patients with Parkinsons disease using functional magnetic resonance imaging (fMRI) and the effect of DOPA medication on neural activity. The correlation between the observed changes and motor improvement was also tested. Statistical parametric mapping was used to detect differences in the cortical activity when the pattern of parkinsons disease (PD) patients is compared with both the normal pattern and after DOPA supply. Patients show abnormal activation intensities in rostral and caudal supplementary motor area (SMA), which is normalized after dopaminergic pathways (DOPA) medication. The improvement in the clinical outcome correlated with an increase in fMRI signal, particularly with improvement of hypokinesia. The study indicates that cardinal symptoms in PD are associated with inappropriate underactivity in SMA.

Zolpidem efficacy and safety in disorders of consciousness

ABSTRACT Sutton and Clauss presented a detailed review about the effectiveness of zolpidem, discussing recoveries from brain damage due to strokes, trauma and hypoxia. A significant finding has been the unexpected and paradoxical increment of brain activity in vegetative state/unresponsive wakefulness syndrome (VS/UWS). On the contrary, zolpidem is considered one of the best sleep inducers in normal subjects. We have studied series of VS/UWS cases after zolpidem intake. We have demonstrated EEG activation, increment of BOLD signal in different brain regions, and an autonomic influence, mainly characterized by a vagolytic chronotropic effect without a significant increment of the vasomotor sympathetic tone. As this autonomic imbalance might induce cardio- circulatory complications, which we didn’t find in any of our patients, we suggest developing future trials under control of physiological indices by bedside monitoring. However, considering that the paradoxical arousing zolpidem effect might be certainly related to brain function improvement, we agree with Sutton and Clauss that future multicentre and multinational clinical trials should be developed, but under control of physiological indices

Using Graph Theory to Identify Aberrant Hierarchical Patterns in Parkinsonian Brain Networks

The topology of complex brain networks allows efficient dynamic interactions between spatially distinct regions. Neuroimaging studies have provided consistent evidence of dysfunctional connectivity among the cortical circuitry in Parkinson’s disease; however, little is known about the topological properties of brain networks underlying these alterations. This paper introduces a methodology to explore aberrant changes in hierarchical patterns of nodal centrality through cortical networks, combining graph theoretical analysis and morphometric connectivity. The edges in graph were estimated by correlation analysis and thresholding between 148 nodes defined by cortical regions. Our findings demonstrated that the networks organization was disrupted in the patients with PD. We found a reconfiguration in hierarchical weighting of high degree hubs in structural networks associated with levels of cognitive decline, probably related to a system-wide compensatory mechanism. Simulated targeted attack on the network’s nodes as measures of network resilience showed greater effects on information flow in advanced stages of disease.

Exploring sparse connectivity in the motor system using multivariate autoregression analysis

Background Multivariate autoregressive (MAR) models can be used in the identification of causal relations from functional MRI time series. Connectivity information is extracted from large neural networks combining graphical modeling methods and Granger causality. The aim of this paper is to demonstrate the feasibility of working with the MAR models to identify functional circuits in the human motor system, and demonstrates their application to data of motor performance in patients with Parkinsons disease (PD).