Effects of ulotaront on brain circuits of reward, working memory, and emotion processing in healthy volunteers with high or low schizotypy.

Ulotaront, a trace amine-associated receptor 1 (TAAR1) and serotonin 5-HT1A receptor agonist without antagonist activity at dopamine D or the serotonin 5-HT2A receptors, has demonstrated efficacy in the treatment of schizophrenia. Here we report the phase 1 translational studies that profiled the effect of ulotaront on brain responses to reward, working memory, and resting state connectivity (RSC) in individuals with low or high schizotypy (LS or HS). Participants were randomized to placebo (n = 32), ulotaront (50 mg; n = 30), or the D receptor antagonist amisulpride (400 mg; n = 34) 2 h prior to functional magnetic resonance imaging (fMRI) of blood oxygen level-dependent (BOLD) responses to task performance.

Mapping the Homeostatic and Hedonic Brain Responses to Stevia Compared to Caloric Sweeteners and Water: A Double-Blind Randomised Controlled Crossover Trial in Healthy Adults.

Non-nutritive sweeteners have potential effects on brain function. We investigated neural correlates of responses to beverages differing in sweetness and calories. Healthy participants completed 4 randomised sessions: water vs.

The effects of disease activity, inflammation, depression and cognitive fatigue on resting state fMRI in systemic lupus erythematosus.

Objectives: Cognitive dysfunction (CD) and depression are interlinked comorbidities of SLE. They may be the result of altered brain mechanisms. This study aimed to examine SLE effects on functional connectivity (FC) within the default mode network (DMN) using resting state fMRI, and how depression may impact this.

The effects of disease activity on neuronal and behavioural cognitive processes in systemic lupus erythematosus.

Objectives: Factors common across many chronic diseases, such as fatigue and depression affect cognitive dysfunction (CD) but the effect of SLE disease activity on CD remains unclear. We aimed to explore the effects of disease activity in SLE on cognitive function whilst taking into consideration other potential mediators.

Methods: Two groups of SLE patients were recruited; stable/low disease activity (SLE-S, n = 36) and active disease (SLE-F, n = 26).

Changes in the neural correlates of self-blame following mindfulness-based cognitive therapy in remitted depressed participants.

Mindfulness-Based-Cognitive-Therapy (MBCT) reduces vulnerability for relapse into depression by helping individuals to counter tendencies to engage in maladaptive repetitive patterns of thinking and respond more compassionately to negative self-judgment. However, little is known about the neural correlates underlying these effects. To elucidate these correlates, we investigated fMRI brain activation during a task eliciting feelings of blaming oneself or others.

Stevia Beverage Consumption prior to Lunch Reduces Appetite and Total Energy Intake without Affecting Glycemia or Attentional Bias to Food Cues: A Double-Blind Randomized Controlled Trial in Healthy Adults.

Background: Stevia is a zero-calorie alternative to caloric sugars. Substituting caloric sweeteners with noncaloric sweeteners reduces available energy, but their effects on appetite, subsequent food intake, and neurocognitive responses are still unclear.

Objective: The aim was to examine whether sweetness with or without calories influences food intake, appetite, blood glucose concentrations, and attentional bias (AB) to food cues.

A Unique Brain Connectome Fingerprint Predates and Predicts Response to Antidepressants.

More than six decades have passed since the discovery of monoaminergic antidepressants. Yet, it remains a mystery why these drugs take weeks to months to achieve therapeutic effects, although their monoaminergic actions are present rapidly after treatment. In an attempt to solve this mystery, rather than studying the acute neurochemical effects of antidepressants, here we propose focusing on the early changes in the brain functional connectome using traditional statistics and machine learning approaches.

Evidence That Implementation Intentions Enhance Cognitive Training and Reduce Alcohol Consumption in Heavy Drinkers: A Randomized Trial.

Background: Current training tasks to improve the cognitive deficits thought to be involved in sustained heavy drinking need further investigation to optimize their effectiveness.

Purpose: The present study investigated whether combining implementation intention provision with a cognitive training task had a measurable effect on alcohol consumption in heavy drinkers and explored the neural mechanisms underpinning any reductions in subsequent alcohol consumption.

Methods: Thirty-two heavy-drinking participants completed approach-avoidance and visual probe training tasks preintervention and postintervention during functional Magnetic Resonance Imaging.

Increased activation of the pregenual anterior cingulate cortex to citalopram challenge in migraine: an fMRI study.

Background: The anterior cingulate cortex (ACC) is a key structure of the pain processing network. Several structural and functional alterations of this brain area have been found in migraine. In addition, altered serotonergic neurotransmission has been repeatedly implicated in the pathophysiology of migraine, although the exact mechanism is not known.

Spatiotemporal brain activation pattern following acute citalopram challenge is dose dependent and associated with neuroticism: A human phMRI study.

Background: The initial effects of selective serotonin reuptake inhibitors (SSRIs) in the human living brain are poorly understood. We carried out a 3T resting state fMRI study with pharmacological challenge to determine the brain activation changes over time following different dosages of citalopram.

Methods: During the study, 7.

Attentional bias to food varies as a function of metabolic state independent of weight status.

Eating behaviour requires that internal metabolic changes are recognized by the central nervous system which regulates brain responses to food cues. This function may be altered in obesity. The aim of this study was to examine potential differences in neurocognitive responses to visual food cues as a function of metabolic state and weight status.

Altered cognitive function in systemic lupus erythematosus and associations with inflammation and functional and structural brain changes.

Objectives: Cognitive dysfunction (CD) is common in systemic lupus erythematosus (SLE) but the cause remains unclear and treatment options are limited. We aimed to compare cognitive function in SLE and healthy controls (HCs) using both behavioural and neuroimaging techniques.

Methods: Patients with SLE with stable disease and HCs were recruited.

Regional default mode network connectivity in major depressive disorder: modulation by acute intravenous citalopram.

The relationship between altered default mode network (DMN) connectivity and abnormal serotonin function in major depressive disorder (MDD) has not been investigated. Using intravenous citalopram and resting-state fMRI, we investigated DMN intra-network connectivity and serotonin function in 77 healthy controls and patients with MDD. There were no significant main effects of MDD or citalopram on DMN intra-network connectivity; however, significant interactions indicated that group differences under saline were modified by citalopram.

Ketamine, but Not the NMDAR Antagonist Lanicemine, Increases Prefrontal Global Connectivity in Depressed Patients.

Background: Identifying the neural correlates of ketamine treatment may facilitate and expedite the development of novel, robust, and safe rapid-acting antidepressants. Prefrontal cortex (PFC) global brain connectivity with global signal regression (GBCr) was recently identified as a putative biomarker of major depressive disorder (MDD). Accumulating evidence have repeatedly shown reduced PFC GBCr in MDD, an abnormality which appears to normalize following ketamine treatment.

Time-dependent neuronal changes associated with craving in opioid dependence: an fMRI study.

Relapse after initially successful treatment is a significant problem facing the treatment of opioid dependence. Evidence suggests craving elicited by re-exposure to drug cues may precipitate relapse. Attempts to identify neural biomarkers of cue-elicited craving have yielded inconsistent findings.

Functional magnetic resonance imaging in dermatology: The skin, the brain and the invisible.

The skin and brain have a close bi-directional anatomical and functional connection. Historically, the skin-brain axis and the brain-skin axis have been well described. However, brain function in this context has only recently been demystified with the introduction of functional neuroimaging in dermatology.

Human brain responses to gastrointestinal nutrients and gut hormones.

Functional mapping of human brain activation has made it possible to understand how different nutrients in the gut impact on homeostatic and appetitive brain responses. Current data are limited, but nutrient-specific effects are observed, with differential responses to lipid and sugars. Responses are not a simple function of calorie intake.

Effects of acute tryptophan depletion on central processing of CT-targeted and discriminatory touch in humans.

C-tactile afferents (CTs) are slowly conducting nerve fibres, present only in hairy skin. They are optimally activated by slow, gentle stroking touch, such as those experienced during a caress. CT stimulation activates affective processing brain regions, alluding to their role in affective touch perception.

Comparing the actions of lanicemine and ketamine in depression: key role of the anterior cingulate.

Intravenous infusion of lanicemine (formerly AZD6765), a low trapping non-selective N-methyl-D-aspartate (NMDA) receptor antagonist, induces antidepressant effects with a similar time course to ketamine. We investigated whether a single dose lanicemine infusion would reproduce the previously reported decrease in subgenual anterior cingulate cortex (sgACC) activity evoked by ketamine, a potential mechanism of antidepressant efficacy. Sixty un-medicated adults meeting the criteria for major depressive disorder were randomly assigned to receive constant intravenous infusions of ketamine, lanicemine or saline during a 60min pharmacological magnetic resonance imaging (phMRI) scan.

Multivariate and repeated measures (MRM): A new toolbox for dependent and multimodal group-level neuroimaging data.

Repeated measurements and multimodal data are common in neuroimaging research. Despite this, conventional approaches to group level analysis ignore these repeated measurements in favour of multiple between-subject models using contrasts of interest. This approach has a number of drawbacks as certain designs and comparisons of interest are either not possible or complex to implement.

An investigation into aripiprazole's partial D₂ agonist effects within the dorsolateral prefrontal cortex during working memory in healthy volunteers.

Rationale: Working memory impairments in schizophrenia have been attributed to dysfunction of the dorsolateral prefrontal cortex (DLPFC) which in turn may be due to low DLPFC dopamine innervation. Conventional antipsychotic drugs block DLPFC D2 receptors, and this may lead to further dysfunction and working memory impairments. Aripiprazole is a D2 receptor partial agonist hypothesised to enhance PFC dopamine functioning, possibly improving working memory.

Subgenual Cingulate-Amygdala Functional Disconnection and Vulnerability to Melancholic Depression.

The syndromic heterogeneity of major depressive disorder (MDD) hinders understanding of the etiology of predisposing vulnerability traits and underscores the importance of identifying neurobiologically valid phenotypes. Distinctive fMRI biomarkers of vulnerability to MDD subtypes are currently lacking. This study investigated whether remitted melancholic MDD patients, who are at an elevated lifetime risk for depressive episodes, demonstrate distinctive patterns of resting-state connectivity with the subgenual cingulate cortex (SCC), known to be of core pathophysiological importance for severe and familial forms of MDD.

Ketamine and other potential glutamate antidepressants.

The need for rapid acting antidepressants is widely recognised. There has been much interest in glutamate mechanisms in major depressive disorder (MDD) as a promising target for the development of new antidepressants. A single intravenous infusion of ketamine, a N-methyl-d-aspartate (NMDA) receptor antagonist anaesthetic agent, can alleviate depressive symptoms in patients within hours of administration.

Resting state networks in major depressive disorder.

Resting state functional magnetic resonance imaging (fMRI) examines the spontaneous low frequency neural activity of the brain to reveal networks of correlated neural activity. A number of different methodologies, each with its own advantages and disadvantages, have been used to examine networks of neural activity that may be related to clinical presentation. Major depressive disorder (MDD) research has largely focused on the default mode network (DMN), which is most active at rest and may relate to negative rumination.