Telling the truth from lie in individual subjects with fast event-related fMRI

Deception is a clinically important behavior with poorly understood neurobiological correlates. Published functional MRI (fMRI) data on the brain activity during deception indicates that, on a multisubject group level, lie is distinguished from truth by increased prefrontal and parietal activity. These findings are theoretically important; however, their applied value will be determined by the accuracy of the discrimination between single deceptive and truthful responses in individual subjects. This study presents the first quantitative estimate of the accuracy of fMRI in conjunction with a formal forced-choice paradigm in detecting deception in individual subjects. We used a paradigm balancing the salience of the target cues to elicit deceptive and truthful responses and determined the accuracy of this model in the classification of single lie and truth events. The relative salience of the task cues affected the net activation associated with lie in the superior medial and inferolateral prefrontal cortices. Lie was discriminated from truth on a single-event level with an accuracy of 78%, while the predictive ability expressed as the area under the curve (AUC) of the receiver operator characteristic curve (ROC) was 85%. Our findings confirm that fMRI, in conjunction with a carefully controlled query procedure, could be used to detect deception in individual subjects. Salience of the task cues is a potential confounding factor in the fMRI pattern attributed to deception in forced choice deception paradigms

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Mood state and recent cocaine use are not associated with levels of cocaine cue reactivity

Eighty-one cocaine-dependent outpatients were assessed for their reactions to cocaine-related cues in a laboratory setting. All subjects contributed a urine sample prior to the session. Compared with non-drug control cues, the cocaine stimuli produced increases in physiological arousal, self-reports of high, craving, and withdrawal, and self-reports of negative mood. Subjects who tested cocaine-positive on the day of testing differed only in skin resistance responding from those who tested cocaine-negative. Changes in cue-induced physiological and self-report measures were also not associated with between-subject variations in mood as measured by the Profile of Mood States (POMS) questionnaire administered prior to cue assessment. Thus, variations in baseline mood and recent cocaine use history do not introduce an additional source of variability in cue reactivity measurements. However, negative mood states at the start of a session were associated with higher levels of self-reported craving, high, and withdrawal both before and after cue exposure

Limbic activation during cue-induced cocaine craving

OBJECTIVE: Since signals for cocaine induce limbic brain activation in animals and cocaine craving in humans, the objective of this study was to test whether limbic activation occurs during cue-induced craving in humans. METHOD: Using positron emission tomography, the researchers measured relative regional cerebral blood flow (CBF) in limbic and comparison brain regions of 14 detoxified male cocaine users and six cocaine-naive comparison subjects during exposure to both non-drug-related and cocaine-related videos and during resting baseline conditions. RESULTS: During the cocaine video, the cocaine users experienced craving and showed a pattern of increases in limbic (amygdala and anterior cingulate) CBF and decreases in basal ganglia CBF relative to their responses to the non-drug video. This pattern did not occur in the cocaine-naive comparison subjects, and the two groups did not differ in their responses in the comparison regions (i.e., the dorsolateral prefrontal cortex, cerebellum, thalamus, and visual cortex). CONCLUSIONS: These findings indicate that limbic activation is one component of cue-induced cocaine craving. Limbic activation may be similarly involved in appetitive craving for other drugs and for natural rewards

Brain Entropy Mapping Using fMRI

<div><p>Entropy is an important trait for life as well as the human brain. Characterizing brain entropy (BEN) may provide an informative tool to assess brain states and brain functions. Yet little is known about the distribution and regional organization of BEN in normal brain. The purpose of this study was to examine the whole brain entropy patterns using a large cohort of normal subjects. A series of experiments were first performed to validate an approximate entropy measure regarding its sensitivity, specificity, and reliability using synthetic data and fMRI data. Resting state fMRI data from a large cohort of normal subjects (n = 1049) from multi-sites were then used to derive a 3-dimensional BEN map, showing a sharp low-high entropy contrast between the neocortex and the rest of brain. The spatial heterogeneity of resting BEN was further studied using a data-driven clustering method, and the entire brain was found to be organized into 7 hierarchical regional BEN networks that are consistent with known structural and functional brain parcellations. These findings suggest BEN mapping as a physiologically and functionally meaningful measure for studying brain functions.</p></div

Evaluations of entropy mapping using fMRI.

<p>A) image of a cylinder water phantom; B) entropy map of the phantom. The color bar indicates the display color window for the entropy map; C) visual and sensorimotor functional activation induced brain entropy decrease as compared to the resting state. Red and green represent the test (session 1) and retest (session 2) experiment, respectively. The color bars indicate the color window used to display the statistical comparison results (t maps of the paired student t-testing). The statistical threshold for identifying the entropy decreasing clusters is p<0.001 and cluster size>30 (uncorrected for multiple comparisons); D) the correlation coefficient (CC) map of 50 subjects' resting BEN maps. The color bar was used to map the CC value from 0.5 to 1.</p

Spatial distribution and regional organization of BEN.

<p>A) The statistically defined higher-than-average BEN network (hot color) and lower-than-average BEN network (cool color). The significance level used for thresholding the distribution map (the statistical parametric map of the student t-test) is p<0.01 (corrected for multiple comparison); B) The 8 BEN clusters identified by clustering: a) OFC, b) TPLS, c) WM, d) VIS, e) DMN, f) MC, g) PFC, h) peripheral artifact. The text above each axial slice in B, C, and D indicates the slice location (z and x mean the x and z coordinate in mm, respectively) in the MNI space. The left side of image corresponds to the left side of brain.</p