Search bioRxiv⌕ Search

Biology subjects

Angeles-Valdez, D.

Publications and source records attributed to Angeles-Valdez, D..

5 recordsLinked to original sources

Improved classification of alcohol intake groups in the Intermittent-Access Two-Bottle choice rat model using a latent class linear mixed model

Alcohol use disorder (AUD) is a major public health problem in which preclinical models allow the study of AUD development, comorbidities and possible new treatments. The intermittent access two-bottle choice (IA2BC) model is a validated preclinical model for studying alcohol intake patterns similar to those present in AUD in human clinical studies. Typically, the mean/median of overall alcohol intake or the last drinking sessions is used as a threshold to divide groups of animals into high or low alcohol consumers. However, it would be more statistically valuable to stratify the groups using the full consumption data from all drinking sessions. In this study, we aimed to evaluate the effectiveness of using the time series data of all drinking sessions to stratify the population into high or low alcohol consumption groups, using a latent class linear mixed model (LCLMM). We compared LCLMM to traditional classification methods: percentiles, k-means clustering, and hierarchical clustering, and used simulations to compare accuracy between methods. Our results demonstrated that LCLMM outperforms other approaches, achieving superior accuracy (0.94) in identifying consumption patterns. By considering the entire trajectory of alcohol intake, LCLMM provides a more robust and nuanced characterization of high and low alcohol consumers. We advocate for the adoption of longitudinal statistical models in substance use disorder research, both in human studies and preclinical investigations, as they hold promise for enhancing population stratification and refining treatment strategies.

neuroscience↗

Focal electrical stimulation on an alcohol disorder model using MRI-compatible chronic neural monopolar carbon fiber electrodes.

Neuromodulation interventions, such as Deep Brain Stimulation (DBS) and repeated transcranial magnetic stimulation (rTMS), are proposed as possible new complementary therapies to treat substance use disorders (SUD) such as alcohol use disorder (AUD). It is hypothesized that neuromodulation may induce neural plasticity in the reward and frontostriatal systems via electrical field induction, possibly reducing symptoms. Preclinical self-administration rodent models of AUD may help us gain insight into the effects of neuromodulation therapies on different pathology, as well as the neural mechanisms behind the positive effects. DBS, or any type of brain stimulation using intracranial electrodes in rodents, would benefit from the use of MRI to study the longitudinal effects and mechanisms of stimulation as well as novel targets, as it is a non-invasive technique that allows the analysis of structural and functional changes in the brain. To do this, there is a need for MRI-compatible electrodes that allow for MRI acquisition with minimal distortion of the magnetic field. In this protocol, we present a method for the construction and surgery of chronically implantable monopolar carbon electrodes for use in rats. Unlike conventional electrodes, carbon electrodes are resistant to high temperatures, flexible, and generate fewer artifacts in MRI compared to conventional ones. We validated its use by using a focal electrical stimulation high-frequency (20 Hz) protocol that lasted ~10 sessions. We propose that this technique can also be used for the research of the neurophysiological bases of the neuromodulatory treatment in other preclinical substance use disorders (SUD) models.

neuroscience↗

StandardRat: A multi-center consensus protocol to enhance functional connectivity specificity in the rat brain

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows comparison with invasive or terminal procedures. To date, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. We introduce StandardRat, a consensus rat functional MRI acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired in rats from 46 centers. We developed a reproducible pipeline for the analysis of rat data acquired with diverse protocols and determined experimental and processing parameters associated with a more robust functional connectivity detection. We show that the standardized protocol enhances biologically plausible functional connectivity patterns, relative to pre-existing acquisitions. The protocol and processing pipeline described here are openly shared with the neuroimaging community to promote interoperability and cooperation towards tackling the most important challenges in neuroscience.

neuroscience↗

Patterns of reduced cortical thickness and striatum pathological morphology in cocaine addiction.

Substance addiction is regarded as an important public health problem, perpetuated by fronto-striatal circuit pathology. A usual finding in neuroimaging human and murine studies is cortical thinning and lower volume when compared to healthy controls. In this study we wished to replicate cortical thinning findings and find if striatum morphology may explain the cortical pathology. For this we analyzed T1w neuroimaging data from an ongoing addiction Mexican dataset. This dataset includes cocaine addicts diagnosed by expert psychiatrists and healthy controls. For the analysis we used voxel-based morphometry, cortical thickness and volumetric analysis of the basal ganglia, and we correlated striatum volume with cortical thickness to find pathological patterns. Our group contrast showed cortical thinning and striatum volume differences in cocaine addicts correlated to their years of substance use, craving and age. Our correlation between striatum-cortex morphology showed higher significant correlations in healthy controls, not observed in cocaine addicts. The correlation between striatum volume and cortical thickness in healthy controls involved similar areas as those shown with less cortical thickness in cocaine addicts. We suggest that striatum morphological changes in addiction may explain the pattern of cortical thinning observed across several substances addiction studies.\n\nResearch Data Related to this SubmissionData set https://zenodo.org/record/1409808#.W5E3oCOZPIF Patterns of reduced cortical thickness and striatum pathological morphology in cocaine addiction\n\nThis dataset includes all the data and scripts needed to reproduce the analysis and results on the manuscript \"Patterns of reduced cortical thickness and striatum pathological morphology in cocaine addiction\" (link). The brain data is not raw, as T1w were not defaced. We will do so in the near future for version 2.0. Instead we include only the \"output/thickness\" files used in the final analysis. For the use of raw T1w images, please contact the main author EAGV.

neuroscience↗

Borderline personality disorder with cocaine dependence: impulsivity, emotional dysregulation and amygdala functional connectivity

Objective: Borderline personality disorder (BPD) is present in 19% of cocaine dependence (CD) cases; however, this dual pathology (DP) is poorly understood. We assessed impulsivity, emotional dysregulation (ED) and amygdala functional connectivity in this DP.\n\nMethods. We recruited 69 participants divided into 4 groups: DP (n = 20), CD without BPD (n = 19), BPD without CD (n = 10) and healthy controls (HC, n = 20). We used self-reported instruments to measure impulsivity and ED. We acquired resting state fMRI and performed seed-based analyses of functional connectivity (FC) of bilateral amygdalas.\n\nResults. BPD and CD factors had opposing effects in impulsivity and ED, as well as on FC between left amygdala and medial prefrontal cortex. For the FC between right amygdala and left insula, the effect of having both disorders was additive, reducing FC strength. Significant FC clusters were correlated with impulsivity and ED.\n\nConclusions. In this preliminary study, we found that clinical scores of DP patients were closer to those of BPD without CD than to those of CD without BPD, while amygdala to medial prefrontal cortex FC patterns in DP patients were closer to HC than expected.

neuroscience↗