The Influence of Regiochemistry on the Performance of Organic Mixed Ionic and Electronic Conductors.

Thiophenes functionalised in the 3-position are ubiquitous building blocks for the design and synthesis of organic semiconductors. Their non-centrosymmetric nature has long been used as a powerful synthetic design tool exemplified by the vastly different properties of regiorandom and regioregular poly(3-hexylthiophene) owing to the repulsive head-to-head interactions between neighbouring side chains in the regiorandom polymer. The renewed interest in highly electron-rich 3-alkoxythiophene based polymers for bioelectronic applications opens up new considerations around the regiochemistry of these systems as both the head-to-tail and head-to-head couplings adopt near-planar conformations due to attractive intramolecular S-O interactions. To understand how this increased flexibility in the molecular design can be used advantageously, we explore in detail the geometrical and electronic effects that influence the optical, electrochemical, structural, and electrical properties of a series of six polythiophene derivatives with varying regiochemistry and comonomer composition. We show how the interplay between conformational disorder, backbone coplanarity and polaron distribution affects the mixed ionic-electronic conduction. Ultimately, we use these findings to identify a new conformationally restricted polythiophene derivative for p-type accumulation-mode organic electrochemical transistor applications with performance on par with state-of-the-art mixed conductors evidenced by a µC* product of 267 F V-1 cm-1 s-1 .

Mobile assessment of decisions to drink in young adults: Examining the role of incentives and disincentives.

BACKGROUND: Research on decision-making (DM) biases in persons with alcohol use disorder have largely relied on behavioral economic DM tasks, which do not assess the dynamic multitude of factors associated with real-world decisions about drinking. The current study extends the literature on DM and alcohol use by using a mobile daily diary approach to investigate whether, and how, real-world incentives and disincentives are associated with actual drinking decisions in college students. METHODS: We assessed current drinking and lifetime alcohol problems in 104 young adults (61.5% female, 84.5% White) who, for 14 days, used a mobile daily diary to respond to questions about drinking decisions from the day prior. Mobile prompts assessed daily data on the timing of drinking decisions, alcohol quantity initially decided to drink, quantity actually decided to drink, and the incentives that influenced drinking decisions. RESULTS: Users of the app reported high usability, high compliance rates were observed, and incentive responses were reduced to three subtypes: alcohol, social/party, and mood. Daily mobile measures of drinking quantity were strongly correlated with self-reported drinking 2 weeks prior to the daily assessment. Lifetime alcohol problems were positively related to the average quantity decided to drink per event, drinking more than initially decided, and higher levels of self-reported drinking-decision incentives. "Alcohol" and "social/party" incentives were positively related to the quantity the participant decided to drink at drinking events. Mood incentives and disincentives showed little to no significant relationships with drinking decisions. CONCLUSIONS: The results suggest that mobile data collection can be useful for assessing aspects of real-world drinking decisions and the influence of multiple drinking decision incentives.

A New Perspective on "Drinking" Self: A Network Approach to Characterizing Drinking-Related Changes in Personality.

BACKGROUND: Previous research suggests that self-knowledge, particularly perceptions of oneself as a "drinker," may influence the development and progression of alcohol use and related problems, such as binge drinking. While existing studies have provided empirical evidence for the importance of assessing drinking self-perception within the five-factor model of personality framework, further examination with novel analytic methods, such as network analyses, could improve understanding of the drinker self-concept. Methods: Five factor traits of openness to experience, conscientiousness, extraversion, agreeableness, and emotional stability were assessed among a large sample of young adults (n = 423) across "general" and "drinking" contexts. Features of the personality networks were investigated, including topology, network centrality, stability of the network across "general" and "drinking" assessments, as well as differences in the network across the two assessments. Results: Individual personality items were more related to other items within the same trait than to other traits. There was no most central item in the networks, but item strength was uncorrelated to mean-level of the item. The network structure was stable across both assessments, although the overall strength of item relationships significantly increased in the drinking personality network. Conclusions: Examining drinking personality using a network analytic framework provided novel insights into drinker self-concept and the role drinking contexts might play in self-perception of personality in those contexts.Supplemental data for this article is available online at https://doi.org/10.1080/10826084.2022.2034874 .

The problems with delay discounting: a critical review of current practices and clinical applications.

Delay discounting paradigms have gained widespread popularity across clinical research. Given the prevalence in the field, researchers have set lofty expectations for the importance of delay discounting as a key transdiagnostic process and a 'core' process underlying specific domains of dysfunction (e.g. addiction). We believe delay discounting has been prematurely reified as, in and of itself, a core process underlying psychological dysfunction, despite significant concerns with the construct validity of discounting rates. Specifically, high delay discounting rates are only modestly related to measures of psychological dysfunction and therefore are not 'core' to these more complex behavioral problems. Furthermore, discounting rates do not appear to be specifically related to any disorder(s) or dimension(s) of psychopathology. This raises fundamental concerns about the utility of discounting, if the measure is only loosely associated with most forms of psychopathology. This stands in striking contrast to claims that discounting can serve as a 'marker' for specific disorders, despite never demonstrating adequate sensitivity or specificity for any disorder that we are aware of. Finally, empirical evidence does not support the generalizability of discounting rates to other decisions made either in the lab or in the real-world, and therefore discounting rates cannot and should not serve as a summary measure of an individual's decision-making patterns. We provide recommendations for improving future delay discounting research, but also strongly encourage researchers to consider whether the empirical evidence supports the field's hyper-focus on discounting.

The Influence of Harm Avoidance and Impulsivity on Delay Discounting Rates.

High rates of delay discounting are associated with a range of disorders characterized by behavioral disinhibition, such as substance abuse and childhood behavioral problems. The current study extends the research of the personality correlates of delay discounting by examining its association with two domains of disinhibited personality, impulsivity and low harm avoidance. Trait measures of impulsivity and harm avoidance as well as a delay discounting task were administered to 669 young adult subjects (350 male, 319 female). The primary hypothesis was that a combination of high impulsivity and low harm avoidance would be associated with the highest delay discounting rates. Delay discounting rates were significantly associated with high levels of impulsivity. Counterintuitively, the highest rates of delay discounting were associated with high rates of impulsivity and high rates of harm avoidance. Results suggest that those high in impulsivity and harm avoidance are more sensitive to immediate rewards. These results are novel and suggest more complex processes involved when considering a choice between an immediate and a delayed reward that may require longer waiting periods, which itself may be anxiety providing and perceived as potentially harmful.

Alterations in White Matter Microstructure and Connectivity in Young Adults with Alcohol Use Disorder.

BACKGROUND: Magnetic resonance imaging (MRI) studies have shown differences in volume and structure in the brains of individuals with alcohol use disorder (AUD). Most research has focused on neuropathological effects of alcohol that appear after years of chronic alcohol misuse. However, few studies have investigated white matter (WM) microstructure and diffusion MRI-based (DWI) connectivity during early stages of AUD. Therefore, the goal of this work was to investigate WM integrity and structural connectivity in emerging adulthood AUD subjects using both conventional DWI metrics and a novel connectomics approach. METHODS: Twenty-two AUD and 18 controls (CON) underwent anatomic and diffusion MRI. Outcome measures were scalar diffusion metrics and structural network connectomes. Tract-Based Spatial Statistics was used to investigate group differences in diffusion measures. Structural connectomes were used as input into a community structure procedure to obtain a coclassification index matrix (an indicator of community association strength) for each subject. Differences in coclassification and structural connectivity (indexed by streamline density) were assessed via the Network Based Statistics Toolbox. RESULTS: AUD had higher fractional anisotropy (FA) values throughout the major WM tracts, but also had lower FA values in WM tracts in the cerebellum and right insula (pTFCE  < 0.05). Mean diffusivity was generally lower in the AUD group (pTFCE  < 0.05). AUD had lower coclassification of nodes between ventral attention and default mode networks and higher coclassification between nodes of visual, default mode, and somatomotor networks. Additionally, AUD had higher fiber density between an adjacent pair of nodes within the default mode network. CONCLUSIONS: Our results indicate that emerging adulthood AUD subjects may have differential patterns of FA and distinct differences in structural connectomes compared with CON. These data suggest that such alterations in microstructure and structural connectivity may uniquely characterize early stages of AUD and/or a predisposition for development of AUD.

Sex Differences in Trait Anxiety's Association with Alcohol Problems in Emerging Adults: The Influence of Symptoms of Depression and Borderline Personality.

OBJECTIVE: The co-occurrence of alcohol use disorder (AUD) and internalizing psychopathology, such as anxiety and depression, has been well documented. However, most studies of the association between alcohol problems and anxiety, and do not simultaneously consider depression or borderline personality, which covary strongly with both anxiety symptoms and AUDs. The current study examined sex differences in the association between alcohol problems and anxiety, while accounting for depressive and borderline personality (BPD) symptoms. METHOD: A sample 810 (364 females) young adults aged 18-30 recruited from the community, who varied widely in lifetime alcohol problems, were administered diagnostic interviews and measures of a trait anxiety, depression, and BPD symptoms. RESULTS: Analyses revealed that trait anxiety, depression, and borderline symptoms were all significantly associated with higher lifetime alcohol problems in both males and females. However, the association between trait anxiety and alcohol problems was significantly stronger for males compared with females, even when controlling for depression and BPD symptoms. There were no significant sex differences in the association between alcohol problems and symptoms of either depression or BPD symptoms. CONCLUSION: This suggests specific sex differences in the mechanisms by which trait anxiety is associated with alcohol problems.

Predictors of Effective Working Memory Training in Individuals with Alcohol Use Disorders.

BACKGROUND: Low working memory (WM) capacity is associated with alcohol use disorders (AUDs). The importance of WM to adaptive functioning has led to a recent influx of studies attempting to improve individual WM capacity using various cognitive training methods. The present study aimed to examine the efficacy of complex WM training for improving WM capacity among individuals with AUD. METHODS: Individuals were randomized to complete either adaptive WM training or active control training. We applied a methodologically rigorous and structured approach, including a battery of near and moderate transfer measures in those with AUDs and a control group. Additionally, we examined cognitive factors (at baseline) and other predictors of adherence, training task improvement, and transfer. RESULTS: Results suggest improved WM in individuals with AUDs and controls, as evidenced by improved scores on several transfer measures, after adaptive WM training. However, individuals with AUDs showed poorer adherence and less improvement on the training tasks themselves. Neither IQ, WM, sex, nor condition predicted adherence. Level of training task performance, baseline WM, and IQ predicted transfer task improvement. CONCLUSIONS: This is the first study to rigorously examine both the efficacy of WM training in those with AUDs, and predictors of successful training program adherence and transfer in a large sample. Among study completers, results suggest that AUD status does not predict training improvement and transfer. However, AUD status did predict lower program adherence. WM training was more effective in those with higher cognitive ability at baseline. This study provides direct translation to the development of cognitive interventions for treating AUD.

Effects of Alcohol Cues on MRS Glutamate Levels in the Anterior Cingulate.

Growing evidence suggests that glutamate neurotransmission plays a critical role in alcohol addiction. Cue-induced change of glutamate has been observed in animal studies but never been investigated in humans. This work investigates cue-induced change in forebrain glutamate in individuals with alcohol use disorder (AUD). A total of 35 subjects (17 individuals with AUD and 18 healthy controls) participated in this study. The glutamate concentration was measured with single-voxel 1H-MR spectroscopy at the dorsal anterior cingulate. Two MRS sessions were performed in succession, the first to establish basal glutamate levels and the second to measure the change in response to alcohol cues. The changes in glutamate were quantified for both AUD subjects and controls. A mixed model ANOVA and t-tests were performed for statistical analysis. ANOVA revealed a main effect of cue-induced decrease of glutamate level in the anterior cingulate cortex (ACC). A significant interaction revealed that only AUD subjects showed significant decrease of glutamate in the ACC. There were no significant group differences in the level of basal glutamate. However, a negative correlation was found between the basal glutamate level and the number of drinking days in the past 2 weeks for the AUD subjects. Collectively, our results indicate that glutamate in key areas of the forebrain reward circuit is modulated by alcohol cues in early alcohol dependence.

Ethics and Phishing Experiments.

Phishing is a fraudulent form of email that solicits personal or financial information from the recipient, such as a password, username, or social security or bank account number. The scammer may use the illicitly obtained information to steal the victim's money or identity or sell the information to another party. The direct costs of phishing on consumers are exceptionally high and have risen substantially over the past 12 years. Phishing experiments that simulate real world conditions can provide cybersecurity experts with valuable knowledge they can use to develop effective countermeasures and prevent people from being duped by phishing emails. Although these experiments contravene widely accepted informed consent requirements and involve deception, we argue that they can be conducted ethically if risks are minimized, confidentiality and privacy are protected, potential participants have an opportunity to opt out of the research before it begins, and human subjects are debriefed after their participation ends.

Delay Discounting of Losses in Alcohol Use Disorders and Antisocial Psychopathology: Effects of a Working Memory Load.

BACKGROUND: Alcohol use disorders (AUDs) are associated with increased discounting of delayed rewards and reduced executive working memory (eWM) capacity. This association is amplified when comorbid with antisocial psychopathology (AP). Furthermore, recent studies suggest that reduced WM capacity is associated with disinhibited decisions reflected by increased impulsive decision making on the delay discounting of rewards task. While discounting of delayed rewards is well studied, the discounting of delayed losses has received significantly less experimental attention. METHODS: The current study investigated (i) the rate of discounting of delayed losses in individuals with AUD only (n = 61), AUD with comorbid AP (n = 79) and healthy controls (n = 64); (ii) the relationship between eWM capacity and discounting of delayed losses; and (iii) the effect of a WM load on discounting of delayed losses. Discounting performance was assessed using a computerized discounting of delayed losses task. RESULTS: Results showed that the AUD-only and AUD-AP groups had higher rates of discounting of delayed losses and lower eWM capacity compared to the control groups. Lower individual eWM capacity was associated with increased discounting of delayed losses. However, WM load did not increase discounting rates overall. CONCLUSIONS: These results support the hypothesis that greater discounting of delayed losses is associated with AUD and comorbid AP problems and lower individual eWM capacity.

Decisions to Attend and Drink at Party Events: The Effects of Incentives and Disincentives and Lifetime Alcohol and Antisocial Problems.

BACKGROUND: Alcohol use disorders are associated with patterns of impulsive/risky decision making on behavioral economic decision tasks, but little is known about the factors affecting drinking-related decisions. METHODS: The effects of incentives and disincentives to attend and drink at hypothetical alcohol-related party events as a function of lifetime (LT) alcohol and antisocial problems were examined in a sample of 434 young adults who varied widely in LT alcohol and antisocial problems. RESULTS: Moderate and high disincentives substantially discouraged decisions to attend the party events and were associated with decisions to drink less at the party events. High versus low party incentives were associated with more attendance decisions. LT antisocial problems were associated with being less deterred from attending by moderate and high disincentives. LT alcohol problems were associated with greater attendance at high party incentive contexts. LT alcohol problems were associated with drinking more at the majority of events; however, the results indicate that young adults with high levels of alcohol problems moderate their drinking in response to moderate and high disincentives. Finally, attendance and drinking decisions on this hypothetical task were significantly related to actual drinking practices. CONCLUSIONS: The results suggest that antisocial symptoms are associated with a reduced sensitivity to the potential negative consequences of drinking, while alcohol problems are associated with a greater sensitivity to the rewarding aspects of partying. The results also underline the value of directly assessing drinking-related decisions in different hypothetical contexts as well as assessing decisions about attendance at risky drinking events in addition to drinking amount decisions.

The Impact of Gain- and Loss-Framed Messages on Young Adults' Sexual Decision Making: An Experimental Study.

Messages that frame a target behavior in terms of its benefits (gain frame) or costs (loss frame) have been widely and successfully used for health promotion and risk reduction. However, the impact of framed messages on decisions to have sex and sexual risk, as well as moderators of these effects, has remained largely unexplored. We used a computerized laboratory task to test the effects of framed messages about condom use on young adults' sexual decision making. Participants (N = 127) listened to both gain- and loss-framed messages and rated their intentions to have sex with partners who posed a high and low risk for sexually transmitted infections (STIs). The effects of message frame, partner risk, participant gender, ability to adopt the messages, and message presentation order on intentions to have sex were examined. Intentions to have sex with high-risk partners significantly decreased after the loss-framed message, but not after the gain-framed message, and intentions to have sex increased for participants who received the gain-framed message first. Yet, participants found it easier to adopt the gain-framed message. Results suggest that loss-framed messages may be particularly effective in reducing intentions to have sex with partners who might pose a higher risk for STIs, and that message presentation order may alter the relative effectiveness of gain- and loss-framed messages on sexual decision making. Future studies should examine the precise conditions under which gain- and loss-framed messages can promote healthy sexual behaviors and reduce sexual risk behaviors.

Mortality following a cardiovascular or renal event in patients with type 2 diabetes in the ALTITUDE trial.

AIMS: Patients with type 2 diabetes mellitus (T2DM) are at high risk of developing cardiovascular (CV) and renal disease. We examined the burden of, and risk of death following, CV and renal events in the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE), a randomized trial of alikiren vs. placebo. METHODS AND RESULTS: We followed 8561 patients with T2DM and evidence of chronic kidney disease, CV disease, or both in ALTITUDE until the first non-fatal CV or renal event of myocardial infarction (MI), stroke, heart failure (HF), and end-stage renal disease (ESRD; initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL) and then to death or censoring. Time-updated multivariable Cox models were used to estimate the relative risk of death following each event. In total 1008 patients (12%) experienced at least one first non-fatal CV or renal event (4.1% HF, 2.8% MI, 2.8% stroke, and 2.2% ESRD). Death occurred subsequently in 26.4% of those experiencing a first HF event, 29.7% of those experiencing an MI event, 23.7% of those experiencing a stroke, and 14.7% of those experiencing ESRD, and in 6.5% (488) of the 7553 patients (88%) who did not experience a non-fatal CV or renal event. Compared with patients who did not experience a non-fatal event, the adjusted hazard ratio for death was 5.9 (95% confidence interval 4.6-7.6) after HF, 9.7 (7.5-12.6) after MI, 7.1 (5.3-9.5) after stroke, and 5.8 (3.7-9.0) after ESRD. CONCLUSION: The majority of deaths occurred in patients who did not experience a non-fatal CV or renal event, although the risk of death was higher following an event. Our findings illustrate continuing opportunities to reduce morbidity and mortality in patients with type 2 diabetes.

Effect of the angiotensin-receptor-neprilysin inhibitor LCZ696 compared with enalapril on mode of death in heart failure patients.

AIMS: The angiotensin-receptor-neprilysin inhibitor (ARNI) LCZ696 reduced cardiovascular deaths and all-cause mortality compared with enalapril in patients with chronic heart failure in the prospective comparison of ARNI with an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. To more completely understand the components of this mortality benefit, we examined the effect of LCZ696 on mode of death. METHODS AND RESULTS: PARADIGM-HF was a prospective, double-blind, randomized trial in 8399 patients with chronic heart failure, New York Heart Association Class II-IV symptoms, and left ventricular ejection fraction ≤40% receiving guideline-recommended medical therapy and followed for a median of 27 months. Mode of death was adjudicated by a blinded clinical endpoints committee. The majority of deaths were cardiovascular (80.9%), and the risk of cardiovascular death was significantly reduced by treatment with LCZ (hazard ratio, HR 0.80, 95% CI 0.72-0.89, P < 0.001). Among cardiovascular deaths, both sudden cardiac death (HR 0.80, 95% CI 0.68-0.94, P = 0.008) and death due to worsening heart failure (HR 0.79, 95% CI 0.64-0.98, P = 0.034) were reduced by treatment with LCZ696 compared with enalapril. Deaths attributed to other cardiovascular causes, including myocardial infarction and stroke, were infrequent and distributed evenly between treatment groups, as were non-cardiovascular deaths. CONCLUSIONS: LCZ696 was superior to enalapril in reducing both sudden cardiac deaths and deaths from worsening heart failure, which accounted for the majority of cardiovascular deaths. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/, NCT01035255.

Cause of Death in Patients With Diabetic CKD Enrolled in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).

BACKGROUND: The cause of death in patients with chronic kidney disease (CKD) varies with CKD severity, but variation has not been quantified. STUDY DESIGN: Retrospective analysis of prospective randomized clinical trial. SETTING & PARTICIPANTS: We analyzed 4,038 individuals with anemia and diabetic CKD from TREAT, a randomized trial comparing darbepoetin alfa and placebo. PREDICTORS: Baseline estimated glomerular filtration rate (eGFR) and protein-creatinine ratio (PCR). OUTCOMES: Cause of death as adjudicated by a blinded committee. RESULTS: Median eGFR and PCR ranged from 20.6 mL/min/1.73 m(2) and 4.1 g/g in quartile 1 (Q1) to 47.0 mL/min/1.73 m(2) and 0.1 g/g in Q4 (P<0.01). Of 806 deaths, 441, 298, and 67 were due to cardiovascular (CV), non-CV, and unknown causes, respectively. Cumulative CV mortality at 3 years was higher with lower eGFR (Q1, 15.5%; Q2, 11.1%; Q3, 11.2%; Q4, 10.3%; P<0.001) or higher PCR (Q1, 15.2%; Q2, 12.3%; Q3, 11.7%; Q4, 9.0%; P<0.001). Similarly, non-CV mortality was higher with lower eGFR (Q1, 12.7%; Q2, 8.4%; Q3, 6.7%; Q4, 6.1%; P<0.001) or higher PCR (Q1, 10.3%; Q2, 7.9%; Q3, 9.4%; Q4, 6.4%; P=0.01). Sudden death was 1.7-fold higher with lower eGFR (P=0.04) and 2.1-fold higher with higher PCR (P<0.001). Infection-related mortality was 3.3-fold higher in the lowest eGFR quartile (P<0.001) and 2.8-fold higher in the highest PCR quartile (P<0.02). The overall proportion of CV and non-CV deaths was not significantly different across eGFR or PCR quartiles. LIMITATIONS: Results may not be generalizable to nondiabetic CKD or diabetic CKD in the absence of anemia. Measured GFR was not available. CONCLUSIONS: In diabetic CKD, both lower baseline GFR and higher PCR are associated with higher CV and non-CV mortality rates, particularly from sudden death and infection. Efforts to improve outcomes should focus on CV disease and early diagnosis and treatment of infection.

Neural mechanisms of high-risk decisions-to-drink in alcohol-dependent women.

A hallmark of alcohol dependence (AD) is continually drinking despite the risk of negative consequences. Currently, it is not known if the pattern of disordered activation in AD is more compatible with an over-sensitive reward system, a deficit in control systems or a combination of both to produce the high risk-taking behavior observed in alcohol dependents (ADs). Here, alcohol cues were used in an ecological decisions-to-drink task that involved high- and low-risk scenarios where the chance of serious negative imagined consequences was varied. Non-alcohol cues were included as control stimuli. Functional magnetic resonance imaging (fMRI) was used to measure blood oxygen level-dependent (BOLD) signal change in 15 alcohol-dependent and 16 control women. This design allowed us to address two major questions concerning AD: first, is there a specific pattern of disordered activation that drives the heightened endorsement of high-risk decisions-to-drink in ADs? And, second, is that pattern specific to decisions-to-drink or does it generalize to other appetitive and/or neutral cues? The results showed that, during high-risk decisions-to-drink, alcohol-dependent women activated reward circuits, cognitive control circuits and regions of the default-mode network (DMN), while control women deactivated approach circuits and showed enhanced activation in regions of the DMN. Group differences were found only for decisions-to-drink, suggesting that they are specific to alcohol cues. Simultaneous activation of reward networks, cognitive control networks and the DMN in alcohol-dependent women suggests that over-endorsement of high-risk drinking decisions by alcohol-dependent women may be due to a problem with switching between different neural networks.

Applying a dual process model of self-regulation: The association between executive working memory capacity, negative urgency, and negative mood induction on pre-potent response inhibition.

This study tested a dual-process model of self-control where the combination of high impulsivity (negative urgency - NU), weak reflective / control processes (low executive working memory capacity - E-WMC), and a cognitive load is associated with increased failures to inhibit pre-potent responses on a cued go/no-go task. Using a within-subjects design, a cognitive load with and without negative emotional load was implemented to consider situational factors. Results suggested that: (1) high NU was associated with low E-WMC; (2) low E-WMC significantly predicted more inhibitory control failures across tasks; and (3) there was a significant interaction of E-WMC and NU, revealing those with low E-WMC and high NU had the highest rates of inhibitory control failures on all conditions of the task. In conclusion, results suggest that while E-WMC is a strong independent predictor of inhibitory control, NU provides additional information for vulnerability to problems associated with self-regulation.

Temporal interference electrical neurostimulation at 20 Hz beat frequency leads to increased fMRI BOLD activation in orbitofrontal cortex in humans.

Temporal interference electrical neurostimulation (TI) is a relatively new method of non-invasive neurostimulation that may be able to stimulate deep brain regions without stimulating the overlying superficial regions. Although some recent studies have demonstrated the success of TI in modulating task-induced BOLD activity in humans, there is limited information on intended and off-target effects of TI during resting-state. We simultaneously performed TI stimulation with the set-up optimized for maximum focality in the left caudate and collected resting-state fMRI data to investigate the effects of TI on human BOLD signals. We found increased BOLD activation in a part of the mid-orbitofrontal cortex (OFC) and parahippocampal gyrus. Results indicate that TI can induce increased BOLD activation in the region that receives the highest magnitude of TI amplitude modulation in humans, with good safety and tolerability profiles. We also show the limits of spatial precision and explore the nature and causes of additional off-target effects. TI may be a promising approach for addressing questions about the causal role of deep brain structures in human cognition and may also afford new clinical treatments.