TRIAC Treatment Improves Impaired Brain Network Function and White Matter Loss in Thyroid Hormone Transporter Mct8/Oatp1c1 Deficient Mice.

Dysfunctions of the thyroid hormone (TH) transporting monocarboxylate transporter MCT8 lead to a complex X-linked syndrome with abnormal serum TH concentrations and prominent neuropsychiatric symptoms (Allan-Herndon-Dudley syndrome, AHDS). The key features of AHDS are replicated in double knockout mice lacking MCT8 and organic anion transporting protein OATP1C1 ( DKO). In this study, we characterize impairments of brain structure and function in DKO mice using multimodal magnetic resonance imaging (MRI) and assess the potential of the TH analogue 3,3',5-triiodothyroacetic acid (TRIAC) to rescue this phenotype.

Transfer learning for medical image classification: a literature review.

Background: Transfer learning (TL) with convolutional neural networks aims to improve performances on a new task by leveraging the knowledge of similar tasks learned in advance. It has made a major contribution to medical image analysis as it overcomes the data scarcity problem as well as it saves time and hardware resources. However, transfer learning has been arbitrarily configured in the majority of studies.

Cocaine addicted rats show reduced neural activity as revealed by manganese-enhanced MRI.

Cocaine addiction develops as a continuum from recreational to habitual and ultimately compulsive drug use. Cocaine addicts show reduced brain activity. However, it is not clear if this condition results from individual predisposing traits or is the result of chronic cocaine intake.

Chronic alcohol consumption alters extracellular space geometry and transmitter diffusion in the brain.

Already moderate alcohol consumption has detrimental long-term effects on brain function. However, how alcohol produces its potent addictive effects despite being a weak reinforcer is a poorly understood conundrum that likely hampers the development of successful interventions to limit heavy drinking. In this translational study, we demonstrate widespread increased mean diffusivity in the brain gray matter of chronically drinking humans and rats.

The influence of ketamine's repeated treatment on brain topology does not suggest an antidepressant efficacy.

As ketamine is increasingly used as an effective antidepressant with rapid action, sustaining its short-lived efficacy over a longer period of time using a schedule of repeated injections appears as an option. An open question is whether repeated and single administrations would affect convergent neurocircuits. We used a combination of one of the most robust animal models of depression with high-field neuroimaging to perform a whole-brain delineation of functional mechanisms underlying ketamine's effects.

Differences between ketamine's short-term and long-term effects on brain circuitry in depression.

Ketamine acts as a rapid clinical antidepressant at 25 min after injection with effects sustained for 7 days. As dissociative effects emerging acutely after injection are not entirely discernible from therapeutic action, we aimed to dissect the differences between short-term and long-term response to ketamine to elucidate potential imaging biomarkers of ketamine's antidepressant effect. We used a genetical model of depression, in which we bred depressed negative cognitive state (NC) and non-depressed positive cognitive state (PC) rat strains.

Microstructural White Matter Alterations in Men With Alcohol Use Disorder and Rats With Excessive Alcohol Consumption During Early Abstinence.

Importance: Although the detrimental effects of alcohol on the brain are widely acknowledged, observed structural changes are highly heterogeneous, and diagnostic markers for characterizing alcohol-induced brain damage, especially in early abstinence, are lacking. This heterogeneity, likely contributed to by comorbidity factors in patients with alcohol use disorder (AUD), challenges a direct link of brain alterations to the pathophysiology of alcohol misuse. Translational studies in animal models may help bridge this causal gap.

Lateral habenula perturbation reduces default-mode network connectivity in a rat model of depression.

Hyperconnectivity of the default-mode network (DMN) is one of the most widely replicated neuroimaging findings in major depressive disorder (MDD). Further, there is growing evidence for a central role of the lateral habenula (LHb) in the pathophysiology of MDD. There is preliminary neuroimaging evidence linking LHb and the DMN, but no causal relationship has been shown to date.

Neural Mechanisms of Early-Life Social Stress as a Developmental Risk Factor for Severe Psychiatric Disorders.

Background: To explore the domain-general risk factor of early-life social stress in mental illness, rearing rodents in persistent postweaning social isolation has been established as a widely used animal model with translational relevance for neurodevelopmental psychiatric disorders such as schizophrenia. Although changes in resting-state brain connectivity are a transdiagnostic key finding in neurodevelopmental diseases, a characterization of imaging correlates elicited by early-life social stress is lacking.

Methods: We performed resting-state functional magnetic resonance imaging of postweaning social isolation rats (N = 23) 9 weeks after isolation.

Antagonism at the NR2B subunit of NMDA receptors induces increased connectivity of the prefrontal and subcortical regions regulating reward behavior.

Rationale: Evidence indicates that ketamine's rapid antidepressant efficacy likely results from its antagonism of NR2B-subunit-containing NMDA receptors (NMDAR). Since ketamine equally blocks NR2A- and NR2B-containing NMDAR, and has affinity to other receptors, NR2B-selective drugs might have improved therapeutic efficiency and side effect profile.

Objectives: We aimed to compare the effects of (S)-ketamine and two different types of NR2B-selective antagonists on functional brain networks in rats, in order to find common circuits, where their effects intersect, and that might explain their antidepressant action.

[18F]-Fluorodeoxyglucose-Positron Emission Tomography in Rats with Prolonged Cocaine Self-Administration Suggests Potential Brain Biomarkers for Addictive Behavior.

The DSM5-based dimensional diagnostic approach defines substance use disorders on a continuum from recreational drug use to habitual and ultimately addicted behavior. Biomarkers that are indicative of recreational drug use and addicted behavior are lacking. We performed a translational [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) study in the multi-dimensional 0/3crit model of cocaine addiction.

Dynamical state transitions into addictive behaviour and their early-warning signals.

The theory of critical transitions in complex systems (ecosystems, climate, etc.), and especially its ability to predict abrupt changes by early-warning signals based on analysis of fluctuations close to tipping points, is seen as a promising avenue to study disease dynamics. However, the biomedical field still lacks a clear demonstration of this concept.

A multiscale cerebral neurochemical connectome of the rat brain.

Understanding the rat neurochemical connectome is fundamental for exploring neuronal information processing. By using advanced data mining, supervised machine learning, and network analysis, this study integrates over 5 decades of neuroanatomical investigations into a multiscale, multilayer neurochemical connectome of the rat brain. This neurochemical connectivity database (ChemNetDB) is supported by comprehensive systematically-determined receptor distribution maps.

In vivo structural imaging in rats reveals neuroanatomical correlates of behavioral sub-dimensions of cocaine addiction.

Cocaine addiction is a multi-dimensional behavioral disorder characterized by a loss of control over cocaine taking despite of detrimental consequences. Structural MRI studies have revealed association between cocaine consumption and gray matter volume (GMV) in cocaine-addicted patients. However, the behavioral correlates of GMV in cocaine addiction are poorly understood.

Largely overlapping neuronal substrates of reactivity to drug, gambling, food and sexual cues: A comprehensive meta-analysis.

Cue reactivity to natural and social rewards is essential for motivational behavior. However, cue reactivity to drug rewards can also elicit craving in addicted subjects. The degree to which drug and natural rewards share neural substrates is not known.