Biology subjects

Reneman, L.

Publications and source records attributed to Reneman, L..

4 recordsLinked to original sources

bioRxiv2024

Concurrent assessment of neurometabolism and brain hemodynamics to comprehensively characterize the functional brain response to psychotropic drugs: an S-ketamine study

Neuroimaging techniques are crucial for understanding pharmacological treatment effects in neuropsychiatric disorders. Here, we present a novel approach that simultaneously assesses hemodynamic and neurometabolic brain responses to psychotropic drugs using interleaved pharmacological magnetic resonance imaging (phMRI) and magnetic resonance spectroscopy (phMRS). This method was tested using a double-dose, placebo-controlled, randomized, crossover design using S-ketamine, and acquiring 7 Tesla phMRI and phMRS data to evaluate time- and dose-dependent effects in 32 healthy controls. S-ketamine elicited robust phMRI responses in the dorsal-frontal, cingulate, and insular cortices, which correlated with glutamate and opioid receptor maps and subjective dissociation scores. These hemodynamic changes were paralleled by increases in glutamate and lactate, especially at higher doses. Furthermore, accuracy in predicting received S-ketamine dose increased when combining both techniques. Here, we show for the first time that concurrent phMRI and phMRS assessments provide important complementary insights into the functional brain response to pharmacological interventions.

neuroscience↗

bioRxiv2022

The functional circuits related to serotonin transporter and serotonin 1A receptor are differentially associated to serotonin transporter availability after an acute citalopram challenge

BackgroundSelective serotonin reuptake inhibitors (SSRIs) potentiate serotonergic neurotransmission by blocking the serotonin transporter (5-HTT), but the functional brain response to SSRIs involves neural circuits beyond regions with high 5-HTT expression. Currently, it is unclear whether and how changes in 5-HTT availability after SSRI administration modulate brain function of key serotoninergic circuits, including those characterized by high availability of serotonin 1A receptors (5-HT1AR). AimWe investigated the association between 5-HTT availability and 5-HTT- and 5-HT1AR-enriched functional connectivity (FC) after an acute citalopram challenge. MethodsWe analyzed multimodal data from a dose-response, placebo-controlled, double-blind study, in which 45 healthy women were randomized into three groups receiving placebo, a low (4 mg), or high (16 mg) oral dose of citalopram. Receptor-Enhanced Analysis of functional Connectivity by Targets was used to estimate 5-HTT- and 5-HT1AR-enriched FC from resting-state and task-based fMRI. 5-HTT availability was determined using [123I]FP-CIT single-photon emission computerized tomography. Results5-HTT availability was negatively correlated with resting-state 5-HTT-enriched FC, and with task-dependent 5-HT1AR-enriched FC. Our exploratory analyses revealed lower 5-HT1AR-enriched FC in the low dose group compared to the high dose group at rest and the placebo group during the task. ConclusionsTaken together, our findings provide evidence for differential links between 5-HTT availability and brain function within 5-HTT and 5-HT1AR pathways and in context- and dose-dependent manner. As such, they support a potential pivotal role of the 5-HT1AR in the effects of citalopram on the brain and add to its potential as a therapeutic avenue for mood and anxiety disturbances.

neuroscience↗

bioRxiv2021

Multimodal multilayer network centrality relates to executive functioning

Executive functioning is a higher-order cognitive process that is thought to depend on a brain network organization facilitating network integration across specialized subnetworks. The frontoparietal network (FPN), a subnetwork that has diverse connections to other brain modules, seems pivotal to this integration, and a more central role of regions in the FPN has been related to better executive functioning. Brain networks can be constructed using different modalities: diffusion MRI (dMRI) can be used to reconstruct structural networks, while resting-state fMRI (rsfMRI) and magnetoencephalography (MEG) yield functional networks. These networks are often studied in a unimodal way, which cannot capture potential complementary or synergistic modal information. The multilayer framework is a relatively new approach that allows for the integration of different modalities into one network of networks. It has already yielded promising results in the field of neuroscience, having been related to e.g. cognitive dysfunction in Alzheimers disease. Multilayer analyses thus have the potential to help us better understand the relation between brain network organization and executive functioning. Here, we hypothesized a positive association between centrality of the FPN and executive functioning, and we expected that multimodal multilayer centrality would supersede unilayer centrality in explaining executive functioning. We used dMRI, rsfMRI, MEG, and neuropsychological data obtained from 33 healthy adults (age range 22-70 years) to construct eight modality-specific unilayer networks (dMRI, fMRI, and six MEG frequency bands), as well as a multilayer network comprising all unilayer networks. Interlayer links in the multilayer network were present only between a nodes counterpart across layers. We then computed and averaged eigenvector centrality of the nodes within the FPN for every uni- and multilayer network and used multiple regression models to examine the relation between uni- or multilayer centrality and executive functioning. We found that higher multilayer FPN centrality, but not unilayer FPN centrality, was related to better executive functioning. To further validate multilayer FPN centrality as a relevant measure, we assessed its relation with age. Network organization has been shown to change across the life span, becoming increasingly efficient up to middle age and regressing to a more segregated topology at higher age. Indeed, the relation between age and multilayer centrality followed an inverted-U shape. These results show the importance of FPN integration for executive functioning as well as the value of a multilayer framework in network analyses of the brain. Multilayer network analysis may particularly advance our understanding of the interplay between different brain network aspects in clinical populations, where network alterations differ across modalities. HighlightsO_LIMultimodal neuroimaging and neurophysiology data were collected in healthy adults C_LIO_LIMultilayer frontoparietal centrality was positively associated with executive functioning C_LIO_LIUnilayer (unimodal) centralities were not associated with executive functioning C_LIO_LIThere was an inverted-U relationship between multilayer centrality and age C_LI

neuroscience↗

bioRxiv2019

ExploreASL: an image processing pipeline for multi-center ASL perfusion MRI studies

Arterial spin labeling (ASL) has undergone significant development since its inception, with a focus on improving standardization and reproducibility of its acquisition and quantification. In a community-wide effort towards robust and reproducible clinical ASL image processing, we developed the software package ExploreASL, allowing standardized analyses across centers and scanners. The procedures used in ExploreASL capitalize on published image processing advancements and address the challenges of multi-center datasets with scanner-specific processing and artifact reduction to limit patient exclusion. ExploreASL is self-contained, written in MATLAB and based on Statistical Parameter Mapping (SPM) and runs on multiple operating systems. The toolbox adheres to previously defined international standards for data structure, provenance, and best analysis practice. ExploreASL was iteratively refined and tested in the analysis of >10,000 ASL scans using different pulse-sequences in a variety of clinical populations, resulting in four processing modules: Import, Structural, ASL, and Population that perform tasks, respectively, for data curation, structural and ASL image processing and quality control, and finally preparing the results for statistical analyses on both single-subject and group level. We illustrate ExploreASL processing results from three cohorts: perinatally HIV-infected children, healthy adults, and elderly at risk for neurodegenerative disease. We show the reproducibility for each cohort when processed at different centers with different operating systems and MATLAB versions, and its effects on the quantification of gray matter cerebral blood flow. ExploreASL facilitates the standardization of image processing and quality control, allowing the pooling of cohorts to increase statistical power and discover between-group perfusion differences. Ultimately, this workflow may advance ASL for wider adoption in clinical studies, trials, and practice.

neuroscience↗