Focused Ultrasound Neuromodulation: Exploring a Novel Treatment for Severe Opioid Use Disorder.

Background: Opioid use disorder remains a critical healthcare challenge as current therapeutic strategies have limitations resulting in high recurrence and deaths. We evaluated safety and feasibility of focused ultrasound (FUS) neuromodulation to reduce substance cravings and use in severe opioid- and co-occurring substance use disorders.

Methods: This prospective, open-label, single-arm study enrolled 8 participants with severe, primary opioid use disorder with co-occurring substance use.

Perisylvian and Hippocampal Anomalies in Individuals With Pathogenic Variants.

Background And Objectives: Pathogenic variants in are associated with a spectrum of epilepsy-aphasia syndromes (EASs). Seizures as well as speech and language disorders occur frequently but vary widely in severity, both between individuals and across the life span. The link between this phenotypic spectrum and brain characteristics is unknown.

Stuttering associated with a pathogenic variant in the chaperone protein cyclophilin 40.

Stuttering is a common speech disorder that interrupts speech fluency and tends to cluster in families. Typically, stuttering is characterized by speech sounds, words or syllables which may be repeated or prolonged and speech that may be further interrupted by hesitations or 'blocks'. Rare variants in a small number of genes encoding lysosomal pathway proteins have been linked to stuttering.

Identifying biomarkers of drug use recurrence using wearable device technologies and phone applications.

Background: Identifying predictors of drug use recurrence (DUR) is critical to combat the addiction epidemic. Wearable devices and phone-based applications for obtaining self-reported assessments in the patient's natural environment (e.g.

Safety and feasibility clinical trial of nucleus accumbens deep brain stimulation for treatment-refractory opioid use disorder.

Objective: There were more than 107,000 drug overdose deaths in the US in 2021, the most ever recorded. Despite advances in behavioral and pharmacological treatments, over 50% of those receiving treatment for opioid use disorder (OUD) experience drug use recurrence (relapse). Given the prevalence of OUD and other substance use disorders (SUDs), the high rate of drug use recurrence, and the number of drug overdose deaths, novel treatment strategies are desperately needed.

In-depth characterisation of a cohort of individuals with missense and loss-of-function variants disrupting .

Background: Heterozygous disruptions of were the first identified molecular cause for severe speech disorder: childhood apraxia of speech (CAS), and yet few cases have been reported, limiting knowledge of the condition.

Methods: Here we phenotyped 28 individuals from 17 families with pathogenic -only variants (12 loss-of-function, five missense variants; 14 males; aged 2 to 62 years). Health and development (cognitive, motor, social domains) were examined, including speech and language outcomes with the first cross-linguistic analysis of English and German.

Atypical development of Broca's area in a large family with inherited stuttering.

Developmental stuttering is a condition of speech dysfluency, characterized by pauses, blocks, prolongations and sound or syllable repetitions. It affects around 1% of the population, with potential detrimental effects on mental health and long-term employment. Accumulating evidence points to a genetic aetiology, yet gene-brain associations remain poorly understood due to a lack of MRI studies in affected families.

Breath holding endurance: stability over time and relationship with self-assessed persistence.

Breath holding (BH) endurance has been suggested as a measure of the distress tolerance that could predict the outcome of attempts to implement behavior changes, such as stopping smoking or illicit substance use. It is not known however, to what degree BH endurance is a variable trait that may vary depending on situational context, or a stable state characteristic. We measured BH in two groups of participants at baseline and 22 and 89 days (N = 62 and N = 41) post-baseline and in a third group at multiple times points across a 5-week period (N = 44).

Treadmill exercise improves fitness and reduces craving and use of cocaine in individuals with concurrent cocaine and tobacco-use disorder.

Exercise may be a useful treatment for substance use disorders. Participants (N=24) included treatment-seeking individuals with concurrent cocaine and tobacco-use disorder (cigarette smokers). Participants were randomized to either running or walking (30min per session, 3 times per week) or sitting (control condition) for 4 consecutive weeks.

Cocaine-dependent adults and recreational cocaine users are more likely than controls to choose immediate unsafe sex over delayed safer sex.

Cocaine users have a higher incidence of risky sexual behavior and HIV infection than nonusers. Our aim was to measure whether safer sex discount rates-a measure of the likelihood of having immediate unprotected sex versus waiting to have safer sex-differed between controls and cocaine users of varying severity. Of the 162 individuals included in the primary data analyses, 69 met the Diagnostic and Statistical Manual of Mental Disorders (4th ed.

Doxazosin XL reduces symptoms of posttraumatic stress disorder in veterans with PTSD: a pilot clinical trial.

Background: Serotonin and norepinephrine reuptake inhibitors are effective first-line agents for the treatment of posttraumatic stress disorder (PTSD), but treatment is associated with a range of side effects that limit treatment adherence. Prazosin, an α1-noradrenergic antagonist with a half-life of roughly 2-3 hours, has shown promise in the treatment of sleep disturbance and nightmares. Doxazosin extended release (XL) is also an α1-noradrenergic antagonist but with a half-life of approximately 15-19 hours.

Anterior cingulum white matter is altered in tobacco smokers.

Background And Objectives: The anterior cingulate cortex (ACC) is hypothesized to be involved in decision making and emotion regulation. Previous observations of drug dependent individuals indicate that substance dependence may be associated with cingulum white matter abnormalities. The present study evaluated cingulum white matter in cigarette smokers.

Safety and Preliminary Efficacy of the Acetylcholinesterase Inhibitor Huperzine A as a Treatment for Cocaine Use Disorder.

Background: Cholinergic transmission is altered by drugs of abuse and contributes to psychostimulant reinforcement. In particular, acetylcholinesterase inhibitors, like huperzine A, may be effective as treatments for cocaine use disorder.

Methods: The current report describes results from a double-blind, placebo-controlled study in which participants (n=14-17/group) were randomized to huperzine A (0.

Genetic variation of the dopamine transporter (DAT1) influences the acute subjective responses to cocaine in volunteers with cocaine use disorders.

Objective: The aim of this study was to identify gene variants of DAT1 (SLC6A3) that modulate subjective responses to acute cocaine exposure.

Methods: Non-treatment-seeking volunteers (n=66) with cocaine use disorders received a single bolus infusion of saline and cocaine (40 mg, intravenous) in a randomized order. Subjective effects were assessed with visual analog scales administered before (-15 min) and up to 20 min after infusion.

Alterations in interhemispheric functional and anatomical connectivity are associated with tobacco smoking in humans.

Abnormal interhemispheric functional connectivity correlates with several neurologic and psychiatric conditions, including depression, obsessive-compulsive disorder, schizophrenia, and stroke. Abnormal interhemispheric functional connectivity also correlates with abuse of cannabis and cocaine. In the current report, we evaluated whether tobacco abuse (i.

Withdrawal Symptoms and Nicotine Dependence Severity Predict Virtual Reality Craving in Cigarette-Deprived Smokers.

Introduction: Virtual reality (VR) has been shown to be effective in eliciting responses to nicotine cues in cigarette smokers. The primary aim of this study was to investigate whether cigarette-deprived smokers would exhibit increased craving and changes in heart rate when viewing cigarette related cues as compared to non-smoking cues in a VR environment, and the secondary aim was to assess the extent to which self-assessed measures of withdrawal and dependence correlated with VR craving.

Methods: Nicotine-dependent cigarette smokers were recruited for a 2 day study.

Characterizing white matter changes in cigarette smokers via diffusion tensor imaging.

Background: Tobacco use remains the most preventable cause of death; however, its effects on the brain, and particularly white matter, remain elusive. Previous diffusion tensor imaging (DTI) studies have failed to yield consistent findings, with some reporting elevated measures of fractional anisotropy (FA) and others reporting lowered FA.

Methods: In our study, we sought to elucidate the effects of tobacco on white matter by using enhanced imaging acquisition parameters and multiple analysis methods, including tract-based spatial statistics (TBSS) with crossing fiber measures and probabilistic tractography.

A comparison of impulsivity, depressive symptoms, lifetime stress and sensation seeking in healthy controls versus participants with cocaine or methamphetamine use disorders.

Previous research has focused on developing theories of addiction that may explain behavior in cocaine- and methamphetamine-dependent individuals. The primary goal of this report was to compare and contrast the prevalence of self-reported measures of impulsivity, depression, lifetime stress and sensation-seeking in healthy controls versus individuals with cocaine or methamphetamine use disorders. Twenty-nine individuals with cocaine use disorders and 31 individuals with methamphetamine use disorders were matched with 31 healthy control participants on several demographic variables.

Perceptions about e-cigarette safety may lead to e-smoking during pregnancy.

Electronic cigarettes (e-cigarettes) are nicotine-delivery devices that are increasingly used, especially by young people. Because e-cigarettes lack many of the substances found in regular tobacco, they are often perceived as a safer smoking alternative, especially in high-risk situations such as pregnancy. However, studies suggest that it is exposure to nicotine that is most detrimental to prenatal development.

Choosing Money over Drugs: The Neural Underpinnings of Difficult Choice in Chronic Cocaine Users.

Addiction is considered a disorder that drives individuals to choose drugs at the expense of healthier alternatives. However, chronic cocaine users (CCUs) who meet addiction criteria retain the ability to choose money in the presence of the opportunity to choose cocaine. The neural mechanisms that differentiate CCUs from non-cocaine using controls (Controls) while executing these preferred choices remain unknown.

Treatment with modafinil and escitalopram, alone and in combination, on cocaine-induced effects: a randomized, double blind, placebo-controlled human laboratory study.

Background: Concurrent administration of dopamine and serotonin reuptake inhibitors reduces cocaine self-administration in monkeys. Consonant with this, clinical trials assessing modafinil and selective serotonin reuptake inhibitors alone show some efficacy as potential pharmacotherapies for cocaine dependence. We hypothesized that combining modafinil with escitalopram would attenuate the euphoric effects of cocaine to a greater degree than modafinil alone.

Safety and efficacy of varenicline to reduce positive subjective effects produced by methamphetamine in methamphetamine-dependent volunteers.

Methamphetamine use is increasing in the US. Although there are no Food and Drug Administration (FDA)-approved medications for methamphetamine dependence, preclinical and clinical studies suggest that methamphetamine users may benefit from treatments that enhance cholinergic neurotransmission. Consequently, we determined the safety and the efficacy of varenicline treatment, a partial agonist at α4β2 and a full agonist at α7 nicotinic acetylcholine receptors, to reduce positive subjective effects produced by smoked methamphetamine.

The aesthetic appeal of auditory-visual synaesthetic perceptions in people without synaesthesia.

The term 'visual music' refers to works of art in which both hearing and vision are directly or indirectly stimulated. Our ability to create, perceive, and appreciate visual music is hypothesised to rely on the same multisensory processes that support auditory visual (AV) integration in other contexts. Whilst these mechanisms have been extensively studied, there has been little research on how these processes affect aesthetic judgments (of liking or preference).