Network-based Molecular Constraints on Synaptic Density Alterations in Schizophrenia.

Converging neuroimaging, genetic, and post-mortem evidence show a fundamental role of synaptic deficits in schizophrenia pathogenesis. However, the underlying molecular and cellular mechanisms that drive the onset and progression of synaptic pathology remain to be established. Here, we used synaptic density positron emission tomography (PET) imaging using the [C]UCB-J radiotracer to reveal a prominent widespread pattern ( < 0.

The early-onset Alzheimer's disease MRI signature: a replication and extension analysis in early-stage AD.

Early-onset Alzheimer's disease (EOAD) is less investigated than the more common late-onset Alzheimer's disease (LOAD) despite its more aggressive course. A cortical signature of EOAD was recently proposed and may facilitate EOAD investigation. Here, we aimed to validate this proposed MRI biomarker of EOAD neurodegeneration in an Appalachian clinical cohort.

Deficits in prefrontal metabotropic glutamate receptor 5 are associated with functional alterations during emotional processing in bipolar disorder.

Background: Elucidating biological mechanisms contributing to bipolar disorder (BD) is key to improved diagnosis and treatment development. With converging evidence implicating the metabotropic glutamate receptor 5 (mGlu5) in the pathology of BD, here, we therefore test the hypothesis that recently identified deficits in mGlu5 are associated with functional brain differences during emotion processing in BD.

Methods: Positron emission tomography (PET) with [F]FPEB was used to measure mGlu5 receptor availability and functional imaging (fMRI) was performed while participants completed an emotion processing task.

Neural correlates of altered emotional responsivity to infant stimuli in mothers who use substances.

Mothers who use substances during pregnancy and postpartum may have altered maternal behavior towards their infants, which can have negative consequences on infant social-emotional development. Since maternal substance use has been associated with difficulties in recognizing and responding to infant emotional expressions, investigating mothers' subjective responses to emotional infant stimuli may provide insight into the neural and psychological processes underlying these differences in maternal behavior. In this study, 39 mothers who used substances during the perinatal period and 42 mothers who did not underwent functional magnetic resonance imaging while viewing infant faces and hearing infant cries.

Linking resting-state network fluctuations with systems of coherent synaptic density: A multimodal fMRI and C-UCB-J PET study.

Resting-state network (RSN) connectivity is a widely used measure of the brain's functional organization in health and disease; however, little is known regarding the underlying neurophysiology of RSNs. The aim of the current study was to investigate associations between RSN connectivity and synaptic density assessed using the synaptic vesicle glycoprotein 2A radioligand C-UCB-J PET. Independent component analyses (ICA) were performed on resting-state fMRI and PET data from 34 healthy adult participants (16F, mean age: 46 ± 15 years) to identify RSNs of interest (default-mode, right frontoparietal executive-control, salience, and sensorimotor networks) and select sources of C-UCB-J variability (medial prefrontal, striatal, and medial parietal).

Age, gender and body-mass-index relationships with in vivo CB receptor availability in healthy humans measured with [C]OMAR PET.

Brain cannabinoid 1 receptors (CB1Rs) contribute importantly to the regulation of autonomic tone, appetite, mood and cognition. Inconsistent results have been reported from positron emission tomography (PET) studies using different radioligands to examine relationships between age, gender and body mass index (BMI) and CB1R availability in healthy individuals. In this study, we examined these variables in 58 healthy individuals (age range: 18-55 years; 44 male; BMI=27.

Multimodal neuroimaging of metabotropic glutamate 5 receptors and functional connectivity in alcohol use disorder.

Background: People recovering from alcohol use disorder (AUD) show altered resting brain connectivity. The metabotropic glutamate 5 (mGlu5) receptor is an important regulator of synaptic plasticity potentially linked with synchronized brain activity and a target of interest in treating AUD. The goal of this work was to assess potential relationships of brain connectivity at rest with mGlu5 receptor availability in people with AUD at two time points early in abstinence.

Lower prefrontal cortical synaptic vesicle binding in cocaine use disorder: An exploratory C-UCB-J positron emission tomography study in humans.

Preclinical studies have revealed robust and long-lasting alterations in dendritic spines in the brain following cocaine exposure. Such alterations are hypothesized to underlie enduring maladaptive behaviours observed in cocaine use disorder (CUD). The current study explored whether synaptic density is altered in CUD.

Longitudinal changes in network engagement during cognitive control in cocaine use disorder.

Background: Cocaine use disorder (CUD) is characterized by poor cognitive control and has limited empirically supported treatment options. Furthermore, an understanding of brain mechanisms underlying CUD is at a relatively early stage. Thus, this study aimed to investigate longitudinal alterations in functional neural networks associated with cognitive control in cocaine use disorder (CUD).

Identifying brain networks in synaptic density PET (C-UCB-J) with independent component analysis.

Background: The human brain is inherently organized into distinct networks, as reported widely by resting-state functional magnetic resonance imaging (rs-fMRI), which are based on blood-oxygen-level-dependent (BOLD) signal fluctuations. C-UCB-J PET maps synaptic density via synaptic vesicle protein 2A, which is a more direct structural measure underlying brain networks than BOLD rs-fMRI.

Methods: The aim of this study was to identify maximally independent brain source networks, i.

Identification and Validation of Distinct Latent Neurodevelopmental Profiles in the Adolescent Brain and Cognitive Development Study.

Background: Regardless of the precise mechanism, all neurodevelopmental models of risk assume that, at the population level, there exist subgroups of individuals that share similar patterns of neural function and development-and that these subgroups somehow relate to psychiatric risk. However, the existence of multiple neurodevelopmental subgroups at the population level has not been assessed previously.

Methods: In the current study, cross-validated latent profile analysis was used to test for the presence of empirically derived, brain-based developmental subgroups using functional magnetic resonance imaging data from 6758 individuals (49.

Altered functional network activities for behavioral adjustments and Bayesian learning in young men with Internet gaming disorder.

Background And Aims: Deficits in cognitive control represent a core feature of addiction. Internet Gaming Disorder (IGD) offers an ideal model to study the mechanisms underlying cognitive control deficits in addiction, eliminating the confounding effects of substance use. Studies have reported behavioral and neural deficits in reactive control in IGD, but it remains unclear whether individuals with IGD are compromised in proactive control or behavioral adjustment by learning from the changing contexts.

Multimodal investigation of dopamine D/D receptors, default mode network suppression, and cognitive control in cocaine-use disorder.

Stimulant-use disorders have been associated with lower availability of dopamine type-2 receptors (D2R) and greater availability of type-3 receptors (D3R). Links between D2R levels, cognitive performance, and suppression of the default mode network (DMN) during executive functioning have been observed in healthy and addicted populations; however, there is limited evidence regarding a potential role of elevated D3R in influencing cognitive control processes in groups with and without addictions. Sixteen individuals with cocaine-use disorder (CUD) and 16 healthy comparison (HC) participants completed [C]-(+)-PHNO PET imaging of D2R and D3R availability and fMRI during a Stroop task of cognitive control.

Separating dopamine D and D receptor sources of [C]-(+)-PHNO binding potential: Independent component analysis of competitive binding.

Development of medications selective for dopamine D or D receptors is an active area of research in numerous neuropsychiatric disorders including addiction and Parkinson's disease. The positron emission tomography (PET) radiotracer [C]-(+)-PHNO, an agonist that binds with high affinity to both D and D receptors, has been used to estimate relative receptor subtype occupancy by drugs based on a priori knowledge of regional variation in the expression of D and D receptors. The objective of this work was to use a data-driven independent component analysis (ICA) of receptor blocking scans to separate D-and D-related signal in [C]-(+)-PHNO binding data in order to improve the precision of subtype specific measurements of binding and occupancy.

Gradient theories of brain activation: A novel application to studying the parental brain.

Purpose Of Review: Parental brain research primarily employs general-linear-model-based (GLM-based) analyses to assess blood-oxygenation-level-dependent responses to infant auditory and visual cues, reporting common responses in shared cortical and subcortical structures. However, this approach does not reveal intermixed neural substrates related to different sensory modalities. We consider this notion in studying the parental brain.

Drinking and responses to antidrinking messages among young adults: An fMRI study.

Young adults consume most of their alcohol by binge drinking, and more than one-third report binge drinking in the past month. Some will transition out of excessive drinking, while others will maintain or increase alcohol use into adulthood. Public health campaigns depicting negative consequences of drinking have shown some efficacy at reducing this behavior.

Is monetary reward processing altered in drug-naïve youth with a behavioral addiction? Findings from internet gaming disorder.

Current models of addiction biology highlight altered neural responses to non-drug rewards as a central feature of addiction. However, given that drugs of abuse can directly impact reward-related dopamine circuitry, it is difficult to determine the extent to which reward processing alterations are a trait feature of individuals with addictions, or primarily a consequence of exogenous drug exposure. Examining individuals with behavioral addictions is one promising approach for disentangling neural features of addiction from the direct effects of substance exposure.

Neurofunctional Differences Related to Methamphetamine and Sexual Cues in Men With Shorter and Longer Term Abstinence Methamphetamine Dependence.

Background: Stimulant use and sexual behaviors have been linked in behavioral and epidemiological studies. Although methamphetamine-related neurofunctional differences have been investigated, few studies have examined neural responses to drug and sexual cues with respect to shorter or longer term methamphetamine abstinence in individuals with methamphetamine dependence.

Methods: Forty-nine men with shorter term methamphetamine abstinence, 50 men with longer term methamphetamine abstinence, and 47 non-drug-using healthy comparison men completed a functional magnetic resonance imaging cue-reactivity task consisting of methamphetamine, sexual, and neutral visual cues.

Spiritual experiences are related to engagement of a ventral frontotemporal functional brain network: Implications for prevention and treatment of behavioral and substance addictions.

Background And Aims: Spirituality is an important component of 12-step programs for behavioral and substance addictions and has been linked to recovery processes. Understanding the neural correlates of spiritual experiences may help to promote efforts to enhance recovery processes in behavioral addictions. We recently used general linear model (GLM) analyses of functional magnetic resonance imaging data to examine neural correlates of spiritual experiences, with findings implicating cortical and subcortical brain regions.

Differential responses to infant faces in relation to maternal substance use: An exploratory study.

Background: Maternal substance use and addiction has been associated with negative consequences for parenting and may increase addiction vulnerability in the developing child. Neuroimaging research suggests that substance use may decrease the reward of caring for infants and heighten stress reactivity to affective infant cues.

Methods: Thirty-two substance-using mothers and twenty-two non-substance-using mothers were presented with emotional face and cry stimuli generated from their own and a demographically matched unknown infant during fMRI scanning.

Relationships between drinking quantity and frequency and behavioral and hippocampal BOLD responses during working memory performance involving allocentric spatial navigation in college students.

Background: Quantity and frequency of drinking may be used to effectively quantify the severity of alcohol-use. Drinking-severity has been related to neurocognitive impairments in such domains as spatial working memory (SWM). Youth drinking has been associated with altered neurofunctional underpinnings of SWM.

Alterations in functional networks during cue-reactivity in Internet gaming disorder.

Background: Cue-induced brain reactivity has been suggested to be a fundamental and important mechanism explaining the development, maintenance, and relapse of addiction, including Internet gaming disorder (IGD). Altered activity in addiction-related brain regions has been found during cue-reactivity in IGD using functional magnetic resonance imaging (fMRI), but less is known regarding the alterations of coordinated whole brain activity patterns in IGD.

Methods: To investigate the activity of temporally coherent, large-scale functional brain networks (FNs) during cue-reactivity in IGD, independent component analysis was applied to fMRI data from 29 male subjects with IGD and 23 matched healthy controls (HC) performing a cue-reactivity task involving Internet gaming stimuli (i.

Can neuroimaging help combat the opioid epidemic? A systematic review of clinical and pharmacological challenge fMRI studies with recommendations for future research.

The current opioid epidemic is an urgent public health problem, with enormous individual, societal, and healthcare costs. Despite effective, evidence-based treatments, there is significant individual variability in treatment responses and relapse rates are high. In addition, the neurobiology of opioid-use disorder (OUD) and its treatment is not well understood.