Cortical paired associative stimulation shows impaired plasticity of inhibition networks as a function of chronic alcohol use.

BACKGROUND: Response inhibition - or the ability to withhold a suboptimal response - relies on the efficacy of fronto-striatal networks, and is impaired in neuropsychiatric disorders including addiction. Cortical paired associative stimulation (cPAS) is a form of transcranial magnetic stimulation (TMS) which can strengthen neuronal connections via spike-timing-dependent plasticity mechanisms. Here, we used cPAS targeting the fronto-striatal inhibitory network to modulate performance on a response inhibition measure in chronic alcohol use. METHODS: Fifty-five participants (20 patients with a formal alcohol use disorder (AUD) diagnosis (26-74 years, 6[30%] females) and 20 matched healthy controls (HCs) (27-73 years, 6[30%] females) within a larger sample of 35 HCs (23-84 years, 11[31.4%] females) underwent two randomized sessions of cPAS 1-week apart: right inferior frontal cortex stimulation preceding right presupplementary motor area stimulation by either 4 ms (excitation condition) or 100 ms (control condition), and were subsequently administered the Stop Signal Task (SST) in both sessions. RESULTS: HCs showed decreased stop signal reaction time in the excitation condition (t(19) = -3.01, p = 0.007, [CIs]:-35.6 to -6.42); this facilitatory effect was not observed for AUD (F(1,31) = 9.57, p = 0.004, CIs: -68.64 to -14.11). Individually, rates of SST improvement were substantially higher for healthy (72%) relative to AUD (13.6%) groups (OR: 2.33, p = 0.006, CIs:-3.34 to -0.55). CONCLUSION: In line with previous findings, cPAS improved response inhibition in healthy adults by strengthening the fronto-striatal network through putative long-term potentiation-like plasticity mechanisms. Furthermore, we identified a possible marker of impaired cortical excitability, and, thus, diminished capacity for cPAS-induced neuroplasticity in AUD with direct implications to a disorder-relevant cognitive process.

Resilient functioning is associated with altered structural brain network topology in adolescents exposed to childhood adversity.

Childhood adversity is one of the strongest predictors of adolescent mental illness. Therefore, it is critical that the mechanisms that aid resilient functioning in individuals exposed to childhood adversity are better understood. Here, we examined whether resilient functioning was related to structural brain network topology. We quantified resilient functioning at the individual level as psychosocial functioning adjusted for the severity of childhood adversity in a large sample of adolescents (N = 2406, aged 14-24). Next, we examined nodal degree (the number of connections that brain regions have in a network) using brain-wide cortical thickness measures in a representative subset (N = 275) using a sliding window approach. We found that higher resilient functioning was associated with lower nodal degree of multiple regions including the dorsolateral prefrontal cortex, the medial prefrontal cortex, and the posterior superior temporal sulcus (z > 1.645). During adolescence, decreases in nodal degree are thought to reflect a normative developmental process that is part of the extensive remodeling of structural brain network topology. Prior findings in this sample showed that decreased nodal degree was associated with age, as such our findings of negative associations between nodal degree and resilient functioning may therefore potentially resemble a more mature structural network configuration in individuals with higher resilient functioning.

Impact and centrality of attention dysregulation on cognition, anxiety, and low mood in adolescents.

Functional impairments in cognition are frequently thought to be a feature of individuals with depression or anxiety. However, documented impairments are both broad and inconsistent, with little known about when they emerge, whether they are causes or effects of affective symptoms, or whether specific cognitive systems are implicated. Here, we show, in the adolescent ABCD cohort (N = 11,876), that attention dysregulation is a robust factor underlying wide-ranging cognitive task impairments seen in adolescents with moderate to severe anxiety or low mood. We stratified individuals high in DSM-oriented depression or anxiety symptomology, and low in attention deficit hyperactivity disorder (ADHD), as well as vice versa - demonstrating that those high in depression or anxiety dimensions but low in ADHD symptoms not only exhibited normal task performance across several commonly studied cognitive paradigms, but out-performed controls in several domains, as well as in those low in both dimensions. Similarly, we showed that there were no associations between psychopathological dimensions and performance on an extensive cognitive battery after controlling for attention dysregulation. Further, corroborating previous research, the co-occurrence of attention dysregulation was associated with a wide range of other adverse outcomes, psychopathological features, and executive functioning (EF) impairments. To assess how attention dysregulation relates to and generates diverse psychopathology, we performed confirmatory and exploratory network analysis with different analytic approaches using Gaussian Graphical Models and Directed Acyclic Graphs to examine interactions between ADHD, anxiety, low mood, oppositional defiant disorder (ODD), social relationships, and cognition. Confirmatory centrality analysis indicated that features of attention dysregulation were indeed central and robustly connected to a wide range of psychopathological traits across different categories, scales, and time points. Exploratory network analysis indicated potentially important bridging traits and socioenvironmental influences in the relationships between ADHD symptoms and mood/anxiety disorders. Trait perfectionism was uniquely associated with both better cognitive performance and broad psychopathological dimensions. This work suggests that attentional dysregulation may moderate the breadth of EF, fluid, and crystalized cognitive task outcomes seen in adolescents with anxiety and low mood, and may be central to disparate pathological features, and thus a target for attenuating wide-ranging negative developmental outcomes.

Assessing online gaming and pornography consumption patterns during COVID-19 isolation using an online survey: Highlighting distinct avenues of problematic internet behavior.

BACKGROUND AND AIM: The Coronavirus (COVID-19) pandemic has required drastic safety precautions to contain virus spread, involving a protracted self-isolation period. Those with greater perceived or actual life stress are vulnerable to develop problematic internet behaviors. Thus, we assessed how COVID-19 social isolation affected online gaming (OG) and pornography viewing (PV) in the general population. METHODS: We developed an online cross-sectional survey, Habit Tracker (HabiT), completed by 1,344 adults (≥18 years). HabiT was released internationally with individuals from 80 countries participating; a majority residing in the United States and United Kingdom. We measured changes in OG (IGDS9-SF) and PV (CYPAT) behaviors before and during the COVID-19 quarantine period. We also assessed psychiatric factors such as anxiety, depression (HADS), and impulsivity (SUPPS-P). The primary outcome measures were change in amount of, and current OG and PV severity during quarantine. These measures were related to ten COVID-19-related stress factors. RESULTS: Overall, we observed a large increase in OG and a minor increase in PV. Those who increased OG (63%) and PV (43%) during quarantine were younger individuals, males, those who left the quarantine household infrequently, those who reported low frequency or poor quality social interactions, and those with higher depression, anxiety, and urgency impulsivity. DISCUSSION: Our findings highlight similarities between forms of problematic internet behaviors driven by stress, depression, anxiety; while highlighting distinct avenues which these behaviors can manifest. CONCLUSION: We emphasize the relevance of identifying those in need of emotional regulation interventions, to mitigate problematic internet behaviors in the context of COVID-19 isolation.

RAISE study protocol: a cross-sectional, multilevel, neurobiological study of resilience after individual stress exposure.

INTRODUCTION: This paper describes the protocol for an ongoing project funded by the Royal Society, the Resilience After Individual Stress Exposure (RAISE) study; which aims to examine the factors and mechanisms that facilitate resilient functioning after childhood adversity (CA). METHODS AND ANALYSIS: We aim to recruit up to 200 participants. We will use dimension reduction techniques (principal component analysis) on standard-normally transformed individual parameters of mental health, social functioning and CA to calculate a composite measure of adaptive (ie, 'resilient') psychosocial functioning. To examine the neuroimmune responses to stress and their relationship with the brain and social environment, we will use a well validated functional MRI task; the Montreal imaging stress task and venepuncture. We will run group or dimensional comparisons in multiple levels of biological and psychological outcomes, as well as mediation and moderation analyses to study how key biological systems (ie, the hypothalamic-pituitary-adrenal axis and the immune system) interrelate and interact with brain function and social influences in order to facilitate resilient functioning after CA. We hypothesise that resilient functioning will be facilitated by reduced morning cortisol and cytokine levels before and after the stressor and improved neural responses to such stress, as well as increased gray matter volume in the hippocampus and prefrontal cortex, enhanced inhibitory control and emotion regulation, and more friendship and family support. ETHICS AND DISSEMINATION: This study has been reviewed and given favourable opinion by the National Research Ethics Service, NRES Committee East of England-Cambridge Central and external reviewers from the Royal Society (RGF\R1\180064 and RGF\EA\180029). The results of the RAISE study will be disseminated through (1) publications in scientific peer reviewed journals, (2) presentations on relevant scientific conferences and meetings, (3) publications and presentations for the general public and (4) through social media.

Assessing international alcohol consumption patterns during isolation from the COVID-19 pandemic using an online survey: highlighting negative emotionality mechanisms.

OBJECTIVES: The COVID-19 pandemic has required drastic safety measures to control virus spread, including an extended self-isolation period. Stressful situations increase alcohol craving and consumption in alcohol use disorder (AUD) and non-AUD drinkers. Thus, we assessed how COVID-19 related stress may have affected drinking behaviours in the general population. DESIGN: We developed an online cross-sectional survey, Habit Tracker (HabiT), which measured changes in drinking behaviours before and during COVID-19 quarantine. We also assessed psychiatric factors such as anxiety, depression (Hospital Anxiety and Depression Scale) and impulsivity (Short-Impulsive Behavior Scale). Lastly, we related drinking behaviours to COVID-19 specific stress factors. SETTING: HabiT was released internationally, with individuals from 83 countries participating. PARTICIPANTS: Participants were included if they were 18 years of age or older and confirmed they were proficient in English. The survey was completed by 2873 adults with 1346 usable data (46.9% accurately completed). PRIMARY OUTCOME MEASURES: Primary outcome measures were change in amount and severity of drinking behaviours before and during quarantine, and current drinking severity during quarantine. RESULTS: Although drinking behaviours decreased overall during quarantine, 36% reported an increase in alcohol use. Those who increased alcohol use during quarantine were older individuals (95% CI 0.04 to 0.1, p<0.0001), essential workers (95% CI -0.58 to -0.1, p=0.01), individuals with children (95% CI -12.46 to 0.0, p=0.003), those with a personal relationship with someone severely ill from COVID-19 (95% CI -2 to -0.38, p=0.01) and those with higher depression (95% CI 0.67 to 1.45, p<0.0001), anxiety (95% CI 0.61 to 1.5, p=0.0002), and positive urgency impulsivity (95% CI 0.16 to 0.72, p=0.009). Furthermore, country-level subsample analyses indicated that drinking amount (95% CI 9.36 to 13.13, p=0.003) increased in the UK during quarantine. CONCLUSIONS: Our findings highlight a role for identifying those vulnerable for alcohol misuse during periods of self-isolation and underscore the theoretical mechanism of negative emotionality underlying drinking behaviours driven by stress. Limitations include a large degree of study dropout (n=1515). Future studies should assess the long-term effects of isolation on drinking behaviours.

Anterior Cingulate Cortex in Addiction: New Insights for Neuromodulation.

OBJECTIVES: Substance use disorder (SUD) is characterized by compulsive use of addictive substances with considerable impact on both the medical system and society as a whole. The craving of substances leads to relapse in the majority of patients within one year of traditional treatments. In recent decades, neuromodulation approaches have emerged as potential novel treatments of SUD, but the ideal neural target remains contentious. MATERIALS AND METHODS: In this review, we discuss new insights on the anterior cingulate cortex (ACC) as a neuromodulation target for SUD. RESULTS AND CONCLUSION: First, we illustrate that the ACC serves as a central "hub" in addiction-related neural networks of cognitive functions, including, but not limited to, decision-making, cognitive inhibition, emotion, and motivation. Then, we summarize the literature targeting the ACC to treat SUDs via available neuromodulation approaches. Finally, we propose potential directions to improve the effect of stimulating the ACC in SUD treatment. We emphasize that the ACC can be divided into at least four sub-regions, which have distinctive functions and connections. Studies focusing on these sub-regions may help to develop more precise and effective ACC stimulation according to patients' symptom profiles and cognitive deficits.