Computational modelling of reinforcement learning and functional neuroimaging of probabilistic reversal for dissociating compulsive behaviours in gambling and cocaine use disorders.

BACKGROUND: Individuals with cocaine use disorder or gambling disorder demonstrate impairments in cognitive flexibility: the ability to adapt to changes in the environment. Flexibility is commonly assessed in a laboratory setting using probabilistic reversal learning, which involves reinforcement learning, the process by which feedback from the environment is used to adjust behavior. AIMS: It is poorly understood whether impairments in flexibility differ between individuals with cocaine use and gambling disorders, and how this is instantiated by the brain. We applied computational modelling methods to gain a deeper mechanistic explanation of the latent processes underlying cognitive flexibility across two disorders of compulsivity. METHOD: We present a re-analysis of probabilistic reversal data from individuals with either gambling disorder (n = 18) or cocaine use disorder (n = 20) and control participants (n = 18), using a hierarchical Bayesian approach. Furthermore, we relate behavioural findings to their underlying neural substrates through an analysis of task-based functional magnetic resonanceimaging (fMRI) data. RESULTS: We observed lower 'stimulus stickiness' in gambling disorder, and report differences in tracking expected values in individuals with gambling disorder compared to controls, with greater activity during reward expected value tracking in the cingulate gyrus and amygdala. In cocaine use disorder, we observed lower responses to positive punishment prediction errors and greater activity following negative punishment prediction errors in the superior frontal gyrus compared to controls. CONCLUSIONS: Using a computational approach, we show that individuals with gambling disorder and cocaine use disorder differed in their perseverative tendencies and in how they tracked value neurally, which has implications for psychiatric classification.

Exploring the role of autistic traits and eating disorder psychopathology on mentalising ability in the general population.

BACKGROUND: This study evaluated the role of overlapping traits and characteristics related to autism spectrum disorder (autism) and anorexia nervosa (AN) in the general population, and the impact of these traits on mentalising ability. METHODS: A sample of young adults (N = 306), aged 18-25 years, was recruited to complete an online study that consisted of 4 measures: the Autism-Spectrum Quotient, Eating Disorder Examination Questionnaire, the Mentalization Scale, and the Reading the Mind in the Eyes task. RESULTS: Higher levels of autistic traits, particularly difficulty with attention switching, were associated with increased eating disorder psychopathology. Overall, autistic traits and eating disorder psychopathology were related among females, but not males. Difficulty with attention switching, however, was related to eating disorder psychopathology among both females and males. Autistic traits also appear to have a greater role in mentalising ability than does eating disorder psychopathology. CONCLUSION: The role of attention switching in overlapping traits of autism and eating disorder psychopathology needs to be more comprehensively evaluated by future research, as does the role of biological sex. Expanded knowledge in this field will help to better understand and evaluate symptoms at presentation, leading to clearer diagnoses and potentially better treatment outcomes.

A systematic review of the neurobiological effects of theta-burst stimulation (TBS) as measured using functional magnetic resonance imaging (fMRI).

Theta burst stimulation (TBS) is associated with the modulation of a range of clinical, cognitive, and behavioural outcomes, but specific neurobiological effects remain somewhat unclear. This systematic literature review investigated resting-state and task-based functional magnetic resonance imaging (fMRI) outcomes post-TBS in healthy human adults. Fifty studies that applied either continuous-or intermittent-(c/i) TBS, and adopted a pretest-posttest or sham-controlled design, were included. For resting-state outcomes following stimulation applied to motor, temporal, parietal, occipital, or cerebellar regions, functional connectivity generally decreased in response to cTBS and increased in response to iTBS, though there were some exceptions to this pattern of response. These findings are mostly consistent with the assumed long-term depression (LTD)/long-term potentiation (LTP)-like plasticity effects of cTBS and iTBS, respectively. Task-related outcomes following TBS were more variable. TBS applied to the prefrontal cortex, irrespective of task or state, also produced more variable responses, with no consistent patterns emerging. Individual participant and methodological factors are likely to contribute to the variability in responses to TBS. Future studies assessing the effects of TBS via fMRI must account for factors known to affect the TBS outcomes, both at the level of individual participants and of research methodology.

An Investigation of Age-related Neuropathophysiology in Autism Spectrum Disorder Using Fixel-based Analysis of Corpus Callosum White Matter Micro- and Macrostructure.

Fixel-based analysis was used to probe age-related changes in white matter micro- and macrostructure of the corpus callosum between participants with (N = 54) and without (N = 50) autism spectrum disorder (ASD). Data were obtained from the Autism Brain Imaging Data Exchange-II (ABIDE-II). Compared to age-matched controls, young adolescents with ASD (11.19 ± 7.54 years) showed reduced macroscopic fiber cross-section (logFC) and combined fiber-density and cross-section (FDC). Reduced fiber-density (FD) and FDC was noted in a marginally older (13.87 ± 3.15 years) ASD cohort. Among the oldest ASD cohort (17.07 ± 3.56 years), a non-significant trend indicative of reduced FD was noted. White matter aberration appears greatest and most widespread among younger ASD cohorts. This supports the suggestion that some early neuropathophysiological indicators in ASD may dissipate with age.

Brain networks alterations in cocaine use and gambling disorders during emotion regulation.

Background: Cocaine use disorder (CUD) and gambling disorder (GD) share clinical features and neural alterations, including emotion regulation deficits and dysfunctional activation in related networks. However, they also exhibit differential aspects, such as the neuroadaptive effects of long-term drug consumption in CUD as compared to GD. Neuroimaging research aimed at disentangling their shared and specific alterations can contribute to improve understanding of both disorders. Methods: We compared CUD (N = 15), GD (N = 16) and healthy comparison (HC; N = 17) groups using a network-based approach for studying temporally coherent functional networks during functional magnetic resonance imaging (fMRI) of an emotion regulation task. We focused our analysis in limbic, ventral frontostriatal, dorsal attentional (DAN) and executive networks (FPN), given their involvement in emotion regulation and their alteration in CUD and GD. Correlations with measures of emotional experience and impulsivity (UPPS-P) were also performed. Results: The limbic network was significantly decreased during emotional processing both for CUD and GD individuals compared to the HC group. Furthermore, GD participants compared to HC showed an increased activation in the ventral frontostriatal network during emotion regulation. Finally, networks' activation patterns were modulated by impulsivity traits. Conclusions: Functional network analyses revealed both overlapping and unique effects of stimulant and gambling addictions on neural networks underpinning emotion regulation.

Large-scale analysis of interindividual variability in single and paired-pulse TMS data.

OBJECTIVE: This study brought together over 60 transcranial magnetic stimulation (TMS) researchers to create the largest known sample of individual participant single and paired-pulse TMS data to date, enabling a more comprehensive evaluation of factors driving response variability. METHODS: Authors of previously published studies were contacted and asked to share deidentified individual TMS data. Mixed-effects regression investigated a range of individual and study level variables for their contribution to variability in response to single and paired-pulse TMS data. RESULTS: 687 healthy participant's data were pooled across 35 studies. Target muscle, pulse waveform, neuronavigation use, and TMS machine significantly predicted an individual's single-pulse TMS amplitude. Baseline motor evoked potential amplitude, motor cortex hemisphere, and motor threshold (MT) significantly predicted short-interval intracortical inhibition response. Baseline motor evoked potential amplitude, test stimulus intensity, interstimulus interval, and MT significantly predicted intracortical facilitation response. Age, hemisphere, and TMS machine significantly predicted MT. CONCLUSIONS: This large-scale analysis has identified a number of factors influencing participants' responses to single and paired-pulse TMS. We provide specific recommendations to minimise interindividual variability in single and paired-pulse TMS data. SIGNIFICANCE: This study has used large-scale analyses to give clarity to factors driving variance in TMS data. We hope that this ongoing collaborative approach will increase standardisation of methods and thus the utility of single and paired-pulse TMS.

Repetitive transcranial magnetic stimulation (rTMS) in autism spectrum disorder: protocol for a multicentre randomised controlled clinical trial.

INTRODUCTION: There are no well-established biomedical treatments for the core symptoms of autism spectrum disorder (ASD). A small number of studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, may improve clinical and cognitive outcomes in ASD. We describe here the protocol for a funded multicentre randomised controlled clinical trial to investigate whether a course of rTMS to the right temporoparietal junction (rTPJ), which has demonstrated abnormal brain activation in ASD, can improve social communication in adolescents and young adults with ASD. METHODS AND ANALYSIS: This study will evaluate the safety and efficacy of a 4-week course of intermittent theta burst stimulation (iTBS, a variant of rTMS) in ASD. Participants meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (n=150, aged 14-40 years) will receive 20 sessions of either active iTBS (600 pulses) or sham iTBS (in which a sham coil mimics the sensation of iTBS, but no active stimulation is delivered) to the rTPJ. Participants will undergo a range of clinical, cognitive, epi/genetic, and neurophysiological assessments before and at multiple time points up to 6 months after iTBS. Safety will be assessed via a structured questionnaire and adverse event reporting. The study will be conducted from November 2020 to October 2024. ETHICS AND DISSEMINATION: The study was approved by the Human Research Ethics Committee of Monash Health (Melbourne, Australia) under Australia's National Mutual Acceptance scheme. The trial will be conducted according to Good Clinical Practice, and findings will be written up for scholarly publication. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12620000890932).

Do comorbid personality disorders in cocaine dependence exacerbate neuroanatomical alterations? A structural neuroimaging study.

Cocaine dependence (CD) is highly comorbid with personality disorders, with implications for poorer treatment response. The neurobiological mechanisms of this comorbidity are unclear. We aimed to test the role of comorbid personality disorders in the neuroanatomy of CD. We examined 4 groups using high-resolution structural neuroimaging, psychological questionnaires and cognitive tests: CD (n = 19), CD and personality disorder type B (CD + B, n = 21), CD and personality disorder C (CD + C, n = 13) and 21 controls. We compared groups in neuroanatomy and hypothesised that (i) CD would show altered striatal areas ascribed to reward processing (i.e., accumbens, caudate and putamen), (ii) CD + B and CD + C would show altered areas supporting emotional regulation/social valuation and anxiety/avoidance (i.e., OFC and amygdala). The CD + B group had larger caudate volumes than CD (p = .01, d = 0.94) and reduced lateral OFC thickness than CD + C (p = .056, d = 0.71). Exploratory correlations showed that altered neural integrity of the OFC and of the caudate nucleus in these groups exacerbated with worse personality disorder severity and impulsivity scores. CD with and without comorbid personality disorders may have partially distinct underlying mechanisms and targets for treatment.

Inner Speech Moderates the Relationship Between Autism Spectrum Traits and Emotion Regulation.

Inner speech processes are thought to be associated with decreases in cognitive performance in autism spectrum disorder (ASD). Although verbal thinking is also a key component in emotional responses, no studies have investigated whether inner speech is linked to emotion regulation in ASD. The aim of this study was to investigate whether inner speech moderates the relationship between ASD traits and emotion regulation strategies. Our results indicate that only the evaluative/motivational form of inner speech moderates the relationship between ASD traits and cognitive reappraisal; inner speech processes did not moderate the association between ASD traits and expressive suppression. These findings are a first step to further investigate the role of inner speech in affective and self-regulatory processes in ASD.

Is the Putative Mirror Neuron System Associated with Empathy? A Systematic Review and Meta-Analysis.

Theoretical perspectives suggest that the mirror neuron system (MNS) is an important neurobiological contributor to empathy, yet empirical support is mixed. Here, we adopt a summary model for empathy, consisting of motor, emotional, and cognitive components of empathy. This review provides an overview of existing empirical studies investigating the relationship between putative MNS activity and empathy in healthy populations. 52 studies were identified that investigated the association between the MNS and at least one domain of empathy, representing data from 1044 participants. Our results suggest that emotional and cognitive empathy are moderately correlated with MNS activity, however, these domains were mixed and varied across techniques used to acquire MNS activity (TMS, EEG, and fMRI). Few studies investigated motor empathy, and of those, no significant relationships were revealed. Overall, results provide preliminary evidence for a relationship between MNS activity and empathy. However, our findings highlight methodological variability in study design as an important factor in understanding this relationship. We discuss limitations regarding these methodological variations and important implications for clinical and community translations, as well as suggestions for future research.

Impulsivity traits and neurocognitive mechanisms conferring vulnerability to substance use disorders.

Impulsivity - the tendency to act without sufficient consideration of potential consequences in pursuit of short-term rewards - is a vulnerability marker for substance use disorders (SUD). Since impulsivity is a multifaceted construct, which encompasses trait-related characteristics and neurocognitive mechanisms, it is important to ascertain which of these aspects are significant contributors to SUD susceptibility. In this review, we discuss how different trait facets, cognitive processes and neuroimaging indices underpinning impulsivity contribute to the vulnerability to SUD. We reviewed studies that applied three different approaches that can shed light on the role of impulsivity as a precursor of substance use related problems (versus a consequence of drug effects): (1) longitudinal studies, (2) endophenotype studies including non-affected relatives of people with SUD, and (3) clinical reference groups-based comparisons, i.e., between substance use and behavioural addictive disorders. We found that, across different methodologies, the traits of non-planning impulsivity and affect-based impulsivity and the cognitive processes involved in reward-related valuation are consistent predictors of SUD vulnerability. These aspects are associated with the structure and function of the medial orbitofrontal-striatal system and hyperexcitability of dopamine receptors in this network. The field still needs more theory-driven, comprehensive studies that simultaneously assess the different aspects of impulsivity in relation to harmonised SUD-related outcomes. Furthermore, future studies should investigate the impact of impulsivity-related vulnerabilities on novel patterns of substance use such as new tobacco and cannabinoid products, and the moderating impact of changes in social norms and lifestyles on the link between impulsivity and SUD. This article is part of the special issue on 'Vulnerabilities to Substance Abuse'.

Meta-Analysis Reveals Gait Anomalies in Autism.

Gait abnormalities are frequently reported in autism. The empirical literature, however, is characterized by inconsistent findings concerning which aspects of gait are affected. We conducted a meta-analysis to summarize study findings that examined temporal and spatial (i.e., two-dimensional) gait parameters in pediatric and adult samples comprising individuals with autism and healthy controls. After searching electronic databases, a total of 18 studies were identified and included in this review. Results from the meta-analyses revealed autism is associated with a wider step width, slower walking speed, longer gait cycle, longer stance time and longer step time. Additionally, autism appears to be associated with greater intra-individual variability on measures of stride length, stride time and walking speed. Meta-regression analyses revealed cadence and gait cycle duration differences, between autism and control groups, become more pronounced with age. Overall, this review demonstrates that autism is associated with gait abnormalities. However, assessment of the methodological quality of the studies reveal, additional research is required to understand the extent that gait abnormalities are specifically linked to autism, or whether they may be secondary to other factors commonly found in this group, such as increased weight. LAY SUMMARY: It is often noted by clinicians that individuals with autism have an awkward or unusual walking style, which is also referred to as gait. In this report, we reviewed past studies that compared gait in individuals with and without autism. Our review indicates autism is associated with an abnormal gait. However, it is not yet clear whether gait abnormalities are caused by autism, or arise due to other factors such as heavier weight, which often co-occurs in this group.

The Effect of Visual Articulatory Information on the Neural Correlates of Non-native Speech Sound Discrimination.

Behavioral studies have shown that the ability to discriminate between non-native speech sounds improves after seeing how the sounds are articulated. This study examined the influence of visual articulatory information on the neural correlates of non-native speech sound discrimination. English speakers' discrimination of the Hindi dental and retroflex sounds was measured using the mismatch negativity (MMN) event-related potential, before and after they completed one of three 8-min training conditions. In an audio-visual speech training condition (n = 14), each sound was presented with its corresponding visual articulation. In one control condition (n = 14), both sounds were presented with the same visual articulation, resulting in one congruent and one incongruent audio-visual pairing. In another control condition (n = 14), both sounds were presented with the same image of a still face. The control conditions aimed to rule out the possibility that the MMN is influenced by non-specific audio-visual pairings, or by general exposure to the dental and retroflex sounds over the course of the study. The results showed that audio-visual speech training reduced the latency of the MMN but did not affect MMN amplitude. No change in MMN amplitude or latency was observed for the two control conditions. The pattern of results suggests that a relatively short audio-visual speech training session (i.e., 8 min) may increase the speed with which the brain processes non-native speech sound contrasts. The absence of a training effect on MMN amplitude suggests a single session of audio-visual speech training does not lead to the formation of more discrete memory traces for non-native speech sounds. Longer and/or multiple sessions might be needed to influence the MMN amplitude.

Unpacking common and distinct neuroanatomical alterations in cocaine dependent versus pathological gambling.

Pathological gambling and cocaine dependence are highly pervasive disorders. Functional neuroimaging evidence implicates aberrant activity of prefrontal striatal pathways in both disorders. It is unclear if the neuroanatomy of these areas is also affected. Participants with pathological gambling (n = 18), cocaine dependence (n = 19) and controls (n = 21) underwent high-resolution structural MRI scan and cognitive assessments. In line with emerging functional neuroimaging findings, we hypothesised (i) lower volumes of corticostriatal areas ascribed to decision-making/inhibitory control, craving and reward processing (i.e., orbitofrontal cortex, inferior frontal gyrus, amygdala, striatum, insula) in both pathological gamblers and cocaine dependent participants versus controls; (ii) selected dopaminergic/glutamatergic pathways directly taxed by cocaine (i.e., superior, dorsolateral and anterior cingulate cortices) would be altered in cocaine dependent versus control participants only. Analyses were conducted with a bonferroni correction. Our results showed that both pathological gambling and cocaine dependent participants, compared to controls, had larger volumes of the right inferior frontal gyrus (ps <.01, ds = 0.66 and 0.62). Cocaine dependent participants had lower nucleus accumbens and medial orbitofrontal cortex volumes than pathological gamblers (ps <.05, ds = 0.51 and 0.72), with the latter being predicted by higher negative urgency scores. Inferior frontal gyrus volume may reflect common alterations of cocaine and gambling addictions, whereas cocaine dependence may be uniquely associated with reduced volume in dorsolateral and middle frontal regions. Cocaine's supra-physiological effects on mesolimbic neurons may explain reduced accumbens-orbitofrontal structure compared to gambling.

The neural interface between negative emotion regulation and motivation for change in cocaine dependent individuals under treatment.

BACKGROUND: Emotion regulation is important for cocaine addiction treatment success, particularly during early abstinence. In addition, the neural underpinnings of emotion processing overlap with those of motivation and goal-directed behavior. We examined if the neural underpinnings of emotion maintenance and its regulation correlate with cocaine treatment motivation. METHODS: Forty-five cocaine dependent individuals (CDIs) starting outpatient treatment in a public specialized addiction treatment clinic in Granada (Spain) underwent fMRI scans while performing a Reappraisal task, and completed the University of Rhode Island Change Assessment Scale (URICA), to measure treatment motivation. We conducted correlation analyses to examine the association between emotion maintenance and regulation related brain activation and URICA's Readiness to Change scores. We also explored links between Emotional reports during the fMRI reappraisal task, duration of abstinence, and anxiety and depression symptoms. RESULTS: Readiness to Change scores were positively correlated with activations in the right dorsolateral prefrontal and right parietal cortices, the midbrain (p ≤ 0.001, cluster extents ≥109 voxels), and basolateral amygdala (PFWE-SVC<0.05), while negatively with emotion maintenance related activation in the same cortical areas and activations in the dorsomedial frontal cortex, the nucleus accumbens and the left fusiform gyrus. Emotional reactivity negatively correlated with right dorsolateral prefrontal cortex reappraisal related activation (r= -0.40, p = 0.007), and the Regulate score positively correlated with the left fusiform gyrus emotion maintenance related activation (r = 0.31, p = 0.04). CONCLUSIONS: Emotional related activation in frontoparietal, accumbens, fusiform, amygdala and midbrain regions engaged during emotion regulation and its maintenance correlate with early treatment motivation in CDIs.

Dysfunctional Personality Beliefs Linked to Emotion Recognition Deficits in Individuals With Cocaine Addiction and Personality Disorders.

Background: Facial emotion recognition is impaired in addiction and personality disorders. Dysfunctional personality beliefs reflect negative interpersonal schemas that may underpin emotion recognition deficits. We aimed to examine the association between personality beliefs and emotion recognition among participants with cocaine use disorder including those with comorbid personality disorders. Methods: We recruited 70 participants with cocaine use disorder aged between 19 and 52 who had used 14 g of cocaine over 4.8 years on average. Thirty-eight participants had an additional personality disorder (11 Borderline, 7 Histrionic, 5 Antisocial, 10 Avoidant, and 5 Obsessive-Compulsive). Dysfunctional beliefs were indicated with the Personality Belief Questionnaire, and facial emotion recognition was indicated with the Ekman's Test. We applied correlations/multiple regressions to test the relationship between beliefs and emotion recognition. Results: Personality beliefs reflecting paranoid, borderline, and antisocial schemas were negatively associated with emotion recognition. Antisocial beliefs were associated with poorer recognition of fear, and paranoid beliefs with poorer recognition of disgust. Antisocial beliefs were significantly associated with emotion recognition after adjusting for cocaine use. Conclusion: Dysfunctional personality beliefs are associated with poorer emotion recognition in cocaine addiction. Personality-related negative schemas about the self and others can impact social cognition and interaction during cocaine treatment.