Does precrastination explain why some observers are suboptimal in a visual search task?

How do we decide where to search for a target? Optimal search relies on first considering the relative informational value of different locations and then executing eye movements to the best options. However, many participants consistently move their eyes to locations that can be easily ascertained to neither contain the target nor provide new information about the target's location. Here, we asked whether this suboptimal search behaviour represents a specific example of a general tendency towards precrastination: starting sub-goals of a task before they are needed, and in so doing, spending longer time on doing the task than is necessary. To test this hypothesis, we asked 200 participants to do two tasks: retrieve two heavy buckets (one close and one far) and search for a line segment. Precrastination is defined as consistently picking up the closer bucket first, versus the more efficient strategy of picking up the farther bucket first. Search efficiency is the proportion of fixations directed to more cluttered regions of the search array. Based on the pilot data, we predicted an association of precrastination with inefficient search strategies. Personality inventories were also administered to identify stable characteristics associated with these strategies. In the final dataset, there was no clear association between search strategy and precrastination, nor did these correlate strongly with any of the personality measures collected. This article received in-principle acceptance (IPA) at Royal Society Open Science on 29 January 2020. The accepted Stage 1 version of the manuscript, not including results and discussion, may be found at https://osf.io/p2sjx. This preregistration was performed prior to data collection and analysis.

An Overview of the Effects of Tenapanor on Visceral Hypersensitivity in the Treatment of Irritable Bowel Syndrome with Constipation.

Background: Patients with irritable bowel syndrome with constipation (IBS-C) experience persistent abdominal pain, a common symptom leading to greater healthcare utilization and reports of treatment non-response. Clinically significant improvements in abdominal pain were observed in clinical trials of tenapanor, a first-in-class inhibitor of sodium/hydrogen exchanger isoform 3 (NHE3), for the treatment of IBS-C in adults. Aim: This narrative review reports the current knowledge about visceral hypersensitivity as a mechanism for abdominal pain in patients with IBS-C and explores the published evidence for hypothesized mechanisms by which tenapanor may reduce visceral hypersensitivity leading to the observed clinical response of decreased abdominal pain. Findings: Abdominal pain is experienced through activation and signaling of nociceptive dorsal root ganglia that innervate the gut. These sensory afferent neurons may become hypersensitized through signaling of transient receptor potential cation channel subfamily V member 1 (TRPV1), resulting in reduced action potential thresholds. TRPV1 signaling is also a key component of the proinflammatory cascade involving mast cell responses to macromolecule exposure following permeation through the intestinal epithelium. Indirect evidence of this pathway is supported by observations of higher pain in association with increased intestinal permeability in patients with IBS. Tenapanor reduces intestinal sodium absorption, leading to increased water retention in the intestinal lumen, thereby improving gastrointestinal motility. In animal models of visceral hypersensitivity, tenapanor normalized visceromotor responses and normalized TRPV1-mediated nociceptive signaling. Conclusion: By improving gastrointestinal motility, decreasing intestinal permeability and inflammation, and normalizing nociception through decreased TRPV1 signaling, tenapanor may reduce visceral hypersensitivity, leading to less abdominal pain in patients with IBS-C. Therapies that have demonstrated effects on visceral hypersensitivity may be the future direction for meaningful abdominal pain relief for patients with IBS-C.

Trait-dependent effects of theta burst stimulation after psychosocial stress: a sham-controlled study in healthy individuals.

OBJECTIVE: Previous studies suggest that theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), applied to the left dorsolateral prefrontal cortex (DLPFC) might be a promising approach to modulate stress-reactive rumination and the associated psychophysiological stress response. Crucially, individuals showing higher levels of trait rumination might benefit more from prefrontal stimulation. METHODS: In this sham-controlled study, 127 healthy individuals, with varying ruminative tendencies, received a single-session of intermittent TBS (iTBS), continuous TBS (cTBS) or sham TBS (sTBS) over the left DLPFC before being confronted with a Trier Social Stress Test. RESULTS: Results showed significant TBS effects on salivary cortisol as a function of trait rumination. cTBS, as compared to sTBS and iTBS, resulted in an attenuated stress-induced cortisol response in high compared to low trait ruminators. Although independent of trait rumination levels, cTBS showed positive effects on stress-related changes in mood and, both cTBS and iTBS (versus sham) presented an enhanced heart rate recovery following the stressor. We found no evidence for (trait rumination-dependent) TBS effects on stress-reactive rumination, negative affect, subjective stress or heart rate variability. CONCLUSIONS: cTBS shows beneficial effects on certain measures of stress, especially in high trait ruminators. SIGNIFICANCE: These findings highlight the importance of accounting for individual differences when examining TBS effects.

Tenapanor as Therapy for Hyperphosphatemia in Maintenance Dialysis Patients: Results from the OPTIMIZE Study.

BACKGROUND: OPTIMIZE was a randomized, open-label study evaluating different tenapanor initiation methods. OPTIMIZE evaluated tenapanor alone and in combination with phosphate binders (PBs) to achieve target serum phosphate (P) ≤5.5 mg/dL. METHODS: Patients with inadequately controlled P receiving maintenance dialysis from 42 US locations who were taking PBs with baseline P >5.5 mg/dL and ≤10.0 mg/dL, or were PB-naive with baseline P >4.5 mg/dL and ≤10.0 mg/dL, were included in OPTIMIZE. Participants taking PBs at baseline were randomized to switch from PBs to tenapanor (Straight Switch; n = 151) or reduce PB dosage by ≥50% and add tenapanor (Binder Reduction; n = 152); PB-naive patients started tenapanor alone (Binder-Naive; n = 30). Participants received tenapanor 30 mg twice a day for 10 weeks (part A), followed by an elective, 16-week open-label extension (part B). Outcomes included changes from baseline in P, intact fibroblast growth factor 23 (iFGF23), parathyroid hormone (PTH), serum calcium, and medication burden; patient-reported outcomes; and safety. RESULTS: By part A endpoint, 34.4% (Straight Switch), 38.2% (Binder Reduction), and 63.3% (Binder-Naive) of patients achieved P ≤5.5 mg/dL. Mean P reduction and median pill burden reduction from baseline to part A endpoint were 0.91± 1.7 mg/dL and 4 pills/day for the Straight Switch and 0.99± 1.8 mg/dL and 1 pill/day for the Binder Reduction group. The mean P reduction for Binder-Naive patients was 0.87± 1.5 mg/dL. Among Straight Switch and Binder Reduction patients who completed patient experience questionnaires, 205 of 243 (84.4%) reported an improved phosphate-management routine. Diarrhea was the most common adverse event (133 of 333 [39.9%]). CONCLUSIONS: Tenapanor as monotherapy or in combination with PBs effectively lowered P toward the target range in patients who were PB naïve or who were not at goal despite PB use. FUNDING: Ardelyx, Inc. TRIAL REGISTRATION: NCT04549597.

NHE3 inhibitor tenapanor maintains intestinal barrier function, decreases visceral hypersensitivity, and attenuates TRPV1 signaling in colonic sensory neurons.

The pathogenesis of irritable bowel syndrome (IBS) is multifactorial, characterized in part by increased intestinal permeability, and visceral hypersensitivity. Increased permeability is associated with IBS severity and abdominal pain. Tenapanor is FDA-approved for the treatment of IBS with constipation (IBS-C) and has demonstrated improvements in bowel motility and a reduction in IBS-related pain; however, the mechanism by which tenapanor mediates these functions remains unclear. Here, the effects of tenapanor on colonic pain signaling and intestinal permeability were assessed through behavioral, electrophysiological, and cell culture experiments. Intestinal motility studies in rats and humans demonstrated that tenapanor increased luminal sodium and water retention and gastrointestinal transit versus placebo. A significantly reduced visceral motor reflex (VMR) to colonic distension was observed with tenapanor treatment versus vehicle in two rat models of visceral hypersensitivity (neonatal acetic acid sensitization and partial restraint stress; both P < 0.05), returning VMR responses to that of nonsensitized controls. Whole cell voltage patch-clamp recordings of retrogradely labeled colonic dorsal root ganglia (DRG) neurons from sensitized rats found that tenapanor significantly reduced DRG neuron hyperexcitability to capsaicin versus vehicle (P < 0.05), an effect not mediated by epithelial cell secretions. Tenapanor also attenuated increases in intestinal permeability in human colon monolayer cultures caused by incubation with proinflammatory cytokines (P < 0.001) or fecal supernatants from patients with IBS-C (P < 0.005). These results support a model in which tenapanor reduces IBS-related pain by strengthening the intestinal barrier, thereby decreasing permeability to macromolecules and antigens and reducing DRG-mediated pain signaling.NEW & NOTEWORTHY A series of nonclinical experiments support the theory that tenapanor inhibits IBS-C-related pain by strengthening the intestinal barrier. Tenapanor treatment reduced visceral motor responses to nonsensitized levels in two rat models of hypersensitivity and reduced responses to capsaicin in sensitized colonic nociceptive dorsal root ganglia neurons. Intestinal permeability experiments in human colon monolayer cultures found that tenapanor attenuates increases in permeability induced by either inflammatory cytokines or fecal supernatants from patients with IBS-C.

Abdominal Symptom Improvement During Clinical Trials of Tenapanor in Patients With Irritable Bowel Syndrome With Constipation: A Post Hoc Analysis.

INTRODUCTION: This post hoc analysis evaluated the efficacy of tenapanor on abdominal symptoms in patients with irritable bowel syndrome with constipation. Abdominal symptoms assessed included pain, discomfort, bloating, cramping, and fullness. METHODS: The abdominal symptom data were pooled from 3 randomized controlled trials (NCT01923428, T3MPO-1 [NCT02621892], and T3MPO-2 [NCT02686138]). Weekly scores were calculated for each abdominal symptom, and the Abdominal Score (AS) was derived as the average of weekly scores for abdominal pain, discomfort, and bloating. The overall change from baseline during the 12 weeks was assessed for each symptom weekly score and the AS. The AS 6/12-week and 9/12-week response rates (AS improvement of ≥2 points for ≥6/12- or ≥9/12-week) were also evaluated. The association of weekly AS response status (reduction of ≥30%) with weekly complete spontaneous bowel movement (CSBM) status (=0 and >0) was assessed. RESULTS: Among 1,372 patients (684 tenapanor [50 mg twice a day] and 688 placebo), the least squares mean change from baseline in AS was -2.66 for tenapanor vs -2.09 for placebo ( P < 0.0001). The 6/12-week AS response rate was 44.4% for tenapanor vs 32.4% for placebo ( P < 0.0001), and for 9/12-week AS, 30.6% for tenapanor vs 20.5% for placebo ( P < 0.0001). A significant association between weekly CSBM status and weekly AS response status was observed each week ( P < 0.0001), with a greater proportion achieving an AS reduction in patients with >0 CSBMs in a week. DISCUSSION: Tenapanor significantly reduced abdominal symptoms in patients with irritable bowel syndrome with constipation, particularly pain, discomfort, and bloating measured by AS, compared with placebo.

Thinking on your feet: Anticipatory foot placements in repeated bimanual object displacements.

Effective handling of objects requires proper use of the hands. If the object handling is done while standing or walking, it also requires proper use of the feet. We asked how people position their feet to meet future and ongoing object-handling demands. In previous research on this topic, participants walked to a table and picked up an object for a single displacement from one place to another. These studies shed light on sensitivity to kinematics but, strictly speaking, may not have revealed anything about sensitivity to dynamics. In the present study, we asked participants to walk to a table to move an object back and forth over different distances and at different rates. Prior to walking to the table, participants had full knowledge of what the task would be. By using a rhythmic rather than discrete object placement task, we could analyze participants' sensitivity to dynamics as well as kinematics. Consistent with our expectation that participants would tune their foot separations to demands related to dynamics, we found that stance width was wider for long than for short object displacements and was more pronounced for high displacement rates than for low displacement rates. Also consistent with our expectations about planning, these effects were evident as soon as participants reached the table. Our results add to the limited research on coordinated action of the hands and feet in purposeful object manipulation.

Exploring the neural basis and modulating factors of implicit altercentric spatial perspective-taking with fNIRS.

Humans spontaneously take the perspective of others when encoding spatial information in a scene, especially with agentive action cues present. This functional near-infrared spectroscopy (fNIRS) study explored how action observation influences implicit spatial perspective-taking (SPT) by adapting a left-right spatial judgment task to investigate whether transformation strategies underlying altercentric SPT can be predicted on the basis of cortical activation. Strategies associated with two opposing neurocognitive accounts (embodied versus disembodied) and their proposed neural correlates (human mirror neuron system; hMNS versus cognitive control network; CCN) are hypothesized. Exploratory analyses with 117 subjects uncover an interplay between perspective-taking and post-hoc factor, consistency of selection, in regions alluding to involvement of the CCN. Descriptively, inconsistent altercentric SPT elicited greater activation than consistent altercentric SPT and/or inconsistent egocentric SPT in the left inferior frontal gyrus (IFG), left dorsolateral prefrontal cortex (DLPFC) and left motor cortex (MC), but not the inferior parietal lobules (IPL). Despite the presence of grasping cues, spontaneous embodied strategies were not evident during implicit altercentric SPT. Instead, neural trends in the inconsistent subgroups (22 subjects; 13 altercentric; 9 egocentric) suggest that inconsistency in selection modulates the decision-making process and plausibly taps on deliberate and effortful disembodied strategies driven by the CCN. Implications for future research are discussed.

In situ fNIRS measurements during cognitive behavioral emotion regulation training in rumination-focused therapy: A randomized-controlled trial.

Repetitive negative thinking (RNT), including rumination, plays a key role in various psychopathologies. Although several psychotherapeutic treatments have been developed to reduce RNT, the neural correlates of those specific treatments and of psychotherapy in general are largely unknown. Functional near-infrared spectroscopy (fNIRS) offers the potential to investigate the neural correlates of psychotherapeutic techniques in situ. Therefore, in this study we investigated the efficacy and neural correlates of a fNIRS adapted Mindfulness-based Emotion Regulation Training (MBERT) for the treatment of depressive rumination in 42 subjects with major depressive disorder (MDD) in a cross-over designed randomized controlled trial. Using psychometric measures, subjective ratings and fNIRS, we analyzed in situ changes in depressive symptom severity, ruminative thoughts and cortical activity in the Cognitive Control Network (CCN). Our results show that MBERT is effective in treating depressive symptoms and rumination. On a neural level, we found consistently higher cortical activation during emotion regulation training compared to control trials in the bilateral inferior frontal gyrus (IFG) and dorsolateral prefrontal cortex (DLPFC). Furthermore, cortical oxygenation decreased from session to session in the bilateral DLPFC. The relevance of the results for the psychotherapeutic treatment of MDD as well as further necessary investigations are discussed.

Long-term safety of tenapanor in patients with irritable bowel syndrome with constipation in the T3MPO-3 study.

BACKGROUND: Tenapanor, a first-in-class, minimally systemic inhibitor of intestinal sodium/hydrogen exchanger isoform 3 (NHE3), is approved for the treatment of irritable bowel syndrome with constipation (IBS-C) in adults based on two randomized, placebo-controlled, phase III studies (T3MPO-1 [NCT02621892], T3MPO-2 [NCT02686138]). The open-label T3MPO-3 extension study (NCT02727751) enrolled patients who completed these studies to investigate long-term safety and tolerability of tenapanor. METHODS: Patients who completed T3MPO-1 (16 weeks) or T3MPO-2 (26 weeks) were eligible for enrollment in T3MPO-3. Patients in T3MPO-3 received open-label tenapanor 50 mg twice a day for up to an additional 39 (T3MPO-1) or 26 (T3MPO-2) weeks. Treatment-emergent adverse events (TEAEs) were evaluated in the entire T3MPO-3 safety population and in patients who received a total of ≥52 weeks of tenapanor. KEY RESULTS: A total of 312 patients were enrolled in T3MPO-3; 90 received ≥52 weeks of tenapanor. TEAEs were reported in 117 (37.5%) patients in the safety population and in 52 (57.8%) patients who received ≥52 weeks of tenapanor. Diarrhea was the most common TEAE, occurring in 10.6% of the safety population and in 11.1% of patients who received ≥52 weeks of tenapanor. Most cases were mild or moderate in severity, with only two severe cases reported in the safety population. No deaths occurred during the T3MPO-3 study. CONCLUSIONS: Tenapanor was tolerable over ≥52 weeks of treatment and showed similar safety to that seen in shorter studies. Combined results of the T3MPO studies indicate that tenapanor is a valuable new treatment option for patients with IBS-C.

Prefrontal hypoactivation induced via social stress is more strongly associated with state rumination than depressive symptomatology.

Previous studies have consistently shown a pattern of prefrontal hypoactivation in depressed patients (DP); however, it remains unclear whether this neural correlate is a consequence or concomitant feature of depression and/or whether ruminative thinking might be underlying. Using a sample comprising 65 healthy controls (HC) and 77 DP, we investigated the behavioral and neural correlates in response to stress and their association with depressive symptomatology, trait and state rumination. Fitting repeated-measurement MANOVAs including 21 fNIRS-channels covering the bilateral Inferior Frontal Gyrus (IFG), Dorsolateral Prefrontal Cortex (DLPFC) and Somatosensory Association Cortex (SAC), we investigated the predictive value of diagnostic group (HC vs. DP) and state rumination. In DP, we observed significantly lower increases in cortical oxygenation under stress in channels of the right IFG and bilateral DLPFC. Participants reporting lower state rumination and no increases in state rumination under stress showed higher increases in cortical oxygenation compared to the other groups and in more channels compared to the analysis on diagnostic group. Re-running our fNIRS-analysis while correcting for performance resulted in time-dependent changes dependent on group (DP vs. HC) no longer yielding significance, however for the differentiation of state rumination groups.

Evaluation of a Web-Based Self-Help Intervention for Patients With Generalized Anxiety Disorder: Protocol for a Randomized Controlled Trial.

BACKGROUND: Generalized anxiety disorder (GAD) is a highly prevalent and severely distressing condition that can lead to functional impairments and is considered one of the most difficult anxiety disorders to treat. Following new technological developments, a highly structured cognitive behavioral therapy (CBT) approach that has already shown success in face-to-face psychotherapy can be implemented: internet-delivered CBT (iCBT). There is now evidence for the efficacy of both guided and unguided iCBT interventions for GAD regarding symptom reduction. OBJECTIVE: To establish the usefulness of such interventions, we plan to evaluate the efficacy of a web-based self-help program (Selfapy) for GAD in a relatively large sample. We aim to assess effects beyond symptom reduction, including effects on well-being, functioning, and mental health literacy, as well as the effect on health care burden, while testing the intervention in conditions comparable to routine care. METHODS: Patients (n=156) who have been diagnosed with GAD, are aged between 18 and 65 years, have internet access, and have sufficient German language skills will be recruited for this study. The intervention group (n=78) will receive access to the 12-week self-help web-based program Selfapy. The waitlist control group (n=78) will receive no intervention in the context of the study. However, both groups will be allowed to access further health care services (eg, psychotherapy, medication), reflecting current routine care in Germany. Outcome measures will be assessed at baseline (T1) and 6 weeks (T2) and 12 weeks (T3) after the start of the intervention. The primary outcome will be generalized anxiety symptoms and quality of life at T3. Additional outcomes include depression, work capacity, therapy-related expenses and burdens, health literacy, and negative effects. RESULTS: By May 2023, all participants had finished the trial and the report was being prepared for publication. CONCLUSIONS: Web-based interventions may be an important addition to the German health care system to reduce barriers to treatment access. Further, they may prove cost-effective for the treatment of GAD. TRIAL REGISTRATION: Deutsches Register Klinischer Studien DRKS00023799; https://tinyurl.com/22bds38x. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41440.

New insights into the function and pathophysiology of the ectodomain sheddase A Disintegrin And Metalloproteinase 10 (ADAM10).

The 'A Disintegrin And Metalloproteinase 10' (ADAM10) has gained considerable attention due to its discovery as an 'α-secretase' involved in the nonamyloidogenic processing of the amyloid precursor protein, thereby possibly preventing the excessive generation of the amyloid beta peptide, which is associated with the pathogenesis of Alzheimer's disease. ADAM10 was found to exert many additional functions, cleaving about 100 different membrane proteins. ADAM10 is involved in many pathophysiological conditions, ranging from cancer and autoimmune disorders to neurodegeneration and inflammation. ADAM10 cleaves its substrates close to the plasma membrane, a process referred to as ectodomain shedding. This is a central step in the modulation of the functions of cell adhesion proteins and cell surface receptors. ADAM10 activity is controlled by transcriptional and post-translational events. The interaction of ADAM10 with tetraspanins and the way they functionally and structurally depend on each other is another topic of interest. In this review, we will summarize findings on how ADAM10 is regulated and what is known about the biology of the protease. We will focus on novel aspects of the molecular biology and pathophysiology of ADAM10 that were previously poorly covered, such as the role of ADAM10 on extracellular vesicles, its contribution to virus entry, and its involvement in cardiac disease, cancer, inflammation, and immune regulation. ADAM10 has emerged as a regulator controlling cell surface proteins during development and in adult life. Its involvement in disease states suggests that ADAM10 may be exploited as a therapeutic target to treat conditions associated with a dysfunctional proteolytic activity.

Carrying groceries: More items in early trips than in later trips or the reverse? Implications for pre-crastination.

Returning home from the grocery store with a car full of groceries requires decisions about how many bags to carry when. If the decisions exemplify procrastination, people should carry more bags per trip in late trips than in early trips (putting the hard work off until later), but if the decisions exemplify the recently discovered phenomenon of pre-crastination (Rosenbaum et al. in Psychol Sci 25: 1487-1496, 2014), people should carry more bags per trip in early trips than in late trips (doing the hard work early). To distinguish between these possibilities, we asked university students to carry 5 or 11 dodgeballs from one bin to another 4, 8, 12, or 16 feet away in as many trips as they wished. A random half of the subjects did the tasks with an additional requirement to memorize and then recall 7 digits after carrying all the balls from the home to the target bin. Consistent with pre-crastination, participants carried the most balls per trip in early trips, and consistent with the hypothesis that pre-crastination relates to memory load, the number of balls carried per trip was affected by the presence of a memory load. The results add to the growing evidence for the generality of pre-crastination.

Comparing two psychosocial stress paradigms for imaging environments - ScanSTRESS and fNIRS-TSST: Correlation structures between stress responses.

The present post-hoc analysis of two independent studies conducted in different laboratories aimed at comparing reactions of stress activation systems in response to two different psychosocial stress induction paradigms. Both paradigms are based on the Trier Social Stress Test (TSST) and suited for neuroimaging environments. In an in-depth analysis, data from 67 participants (36 men, 31 women) from a functional magnetic resonance imaging study implementing ScanSTRESS were compared with data from a functional near-infrared spectroscopy (fNIRS) study implementing the so-called 'fNIRS-TSST' including 45 participants (8 men, 37 women). We tested the equivalence of correlation patterns between the stress response measures cortisol, heart rate, affect, and neural responses in the two samples. Moreover, direct comparisons of affective and neural responses were made. Similar correlation structures were identified for all stress activation systems, except for neural contrasts of paradigm conditions (stress vs. control) showing significant differences in association with cortisol, heart rate, and affective variables between the two samples. Furthermore, both stress paradigms elicited comparable affective and cortical stress responses. Apart from methodological differences (e.g., procedure, timing of the paradigms) the present analysis suggests that both paradigms are capable of inducing moderate acute psychosocial stress to a comparable extent with regard to affective and cortical stress responses. Moreover, similar association structures between different stress response systems were found in both studies. Thus, depending on the study objective and the respective advantages of each imaging approach, both paradigms have demonstrated their usefulness for future studies.

Do People Work Hard to Maintain Social Distance?

How far away from each other people sit or stand reveals much about their social proximity, but merely sitting or standing may not test the limits of social boundaries as much as collaborating on tasks requiring physical coordination. In this study, we asked university students to walk two abreast while carrying a long pipe from one end of a workspace to another. Hurdles in the workspace forced the dyads to decide whether to walk close together without stepping over the hurdles or walk farther apart, stepping over the hurdles. The subjects often chose the latter option, stepping over 18-inch high hurdles rather than walking on level ground.

Visual Alcohol Cue-Reactivity and Cognitive Control in Non-Dependent Heavy Alcohol Drinkers Assessed by Simultaneous fNIRS-EEG.

OBJECTIVE: Addictive behavior is characterized by fast automatic responses to drug-related cues (termed cue reactivity) and deficient cognitive control. The ability to detect errors is a prerequisite for an adaptive increase of cognitive control to prevent further errors. In the current study, cue-reactivity effects on cognitive control were assessed via hemodynamic activity within the dorsolateral prefrontal cortex (dlPFC) using functional near-infrared spectroscopy (fNIRS) and simultaneous electroencephalography (EEG), assessing error monitoring (error-related negativity/error negativity, ERN/Ne) and error adaption in subsequent trials (N2). Nondependent social drinkers were the focus in this multimodal approach. METHOD: Effects of alcohol consumption patterns and the personality trait of impulsivity were assessed in n = 55 social drinkers. Hemodynamic activity within the dlPFC (cognitive control), error monitoring (ERN/Ne), post-error conflict monitoring (N2), error rates, and post-error slowing (PES) were measured during a modified Eriksen flanker task cued by beverage pictures. RESULTS: ERN/Ne amplitudes were reduced during alcohol-cued trials. Post-error adaption was reflected in increased dlPFC activity after errors, whereas N2 amplitudes were reduced. There was a correlation of impulsivity and alcohol-cued ERN/Ne amplitude that was mediated by alcohol consumption pattern. CONCLUSIONS: Impulsivity-related decreases in error monitoring during cue reactivity were mediated by alcohol consumption pattern. However, cognitive control was not affected by cue reactivity, suggesting more complex interactions than previously assumed.

Induced feelings of external influence during instructed imaginations in healthy subjects.

The psychopathological phenomenon of delusions of influence comprises variable disturbances of the self-environment-border leading to the feeling of external influence on thoughts, feelings, impulses or behaviors. Delusions of influence are a hallmark in psychotic illness, but nevertheless, attenuated forms can also appear in healthy individuals. Here we present a newly developed paradigm to induce and assess feelings of external influence during instructed imaginations in healthy individuals. In the current study, we asked 60 healthy individuals to visually imagine different objects. To induce feelings of external influence, we applied one of three different physical setups (low-amplitude transcranial direct current stimulation, eye contact, or skin-to-skin hand touch), and informed the participants whether or not an external influence was attempted during the respective trial. The physical setup (setup vs. no setup, Z = -3.847, p < 0.001, r = 0.497) as well as the information given to the participants (confirmation vs. negation, Z = -5.218, p < 0.001, r = 0.674) alone were able to modulate the feeling of external influence in all three interventions. The impact of information (whether influence was attempted or not attempted) significantly exceeded the impact of the physical setup on the ratings of experienced external influence (Z = -2.394, p = 0.016, r = 0.310). Moreover, the response latency correlated with the estimated feeling of external influence (r S = 0.392, p = 0.002). Additional analyses addressed the influence of the emotional content of imagined objects and examined the intensity and emotional valence of the imaginations. Further supplemental analyses correlated external influence estimation of the participants with other psychopathological measures (trait markers for supernatural beliefs, proneness to hallucinations, and delusions and attributional style). In conclusion, this study endorses a quantitative model of psychopathological characteristics, in this case feelings of external influence that can be induced by external cues.