Motor dominance and movement-outcome congruency influence the electrophysiological correlates of sensory attenuation for self-induced visual stimuli.

This study explores the impact of movement-outcome congruency and motor dominance on the action-associated modulations of early visual event-related potentials (ERPs). Employing the contingent paradigm, participants with varying degrees of motor dominance were exposed to stimuli depicting left or right human hands in the corresponding visual hemifields. Stimuli were either passively observed or evoked by voluntary button-presses with the dominant or non-dominant hand, in a manner that was either congruent or incongruent with stimulus laterality and hemifield. Early occipital responses (C1 and P1 components) revealed modulations consistent with sensory attenuation (SA) for self-evoked stimuli. Our findings suggest that sensory attenuation during the initial stages of visual processing (C1 component) is a general phenomenon across all degrees of handedness and stimulus/movement combinations. However, the magnitude of C1 suppression was modulated by handedness and movement-stimulus congruency, reflecting stronger SA in right-handed participants for stimuli depicting the right hand, when elicited by actions of the corresponding hand, and measured above the contralateral occipital lobe. P1 modulation suggested concurrent but opposing influences of attention and sensory prediction, with more pronounced suppression following stimulus-congruent button-presses over the hemisphere contralateral to movement, especially in left-handed individuals. We suggest that effects of motor dominance on the degree of SA may stem from functional/anatomical asymmetries in the processing of body parts (C1) and attention networks (P1). Overall, our results demonstrate the modulating effect of hand dominance and movement-outcome congruency on SA, underscoring the need for deeper exploration of their interplay. Additional empirical evidence in this direction could substantiate a premotor account for action-associated modulation of early sensory processing in the visual domain.

[What is adult ADHD after all?]

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset mental disorder, demonstrates genetical effects, and is characterized by attention deficit, hyperactivity, and impulsivity. While ADHD was previously only considered a childhood disorder, longitudinal studies over the past decades have proven that in a significant number of cases, the symptoms of the disorder can also be detected in adulthood, and therefore affects 2-4% of the adult population. In Hungary, adult ADHD programs started about 20 years ago and has been able to provide help to many adults living with ADHD. However, this form of care needs further development in many aspects and suffers from capacity deficits at the national level. On July 4-6, 2023 we organized a CME course on adult ADHD at the Department of Psychiatry and Psychotherapy Semmelweis University. The objective of this course was to deepen the knowledge of participants and alleviate care difficulties in the long term through the sharing of information and good practices. As part of this, a narrative review was written, which touches on the current issues of diagnosing and treating ADHD in adults.

Inflammatory biotype of ADHD is linked to chronic stress: a data-driven analysis of the inflammatory proteome.

The association between Attention Deficit Hyperactivity Disorder (ADHD) and low-grade inflammation has been explored in children but rarely in adults. Inflammation is characteristic of some, but not all, patients with ADHD and might be influenced by ADHD medication but also lifestyle factors including nutrition, smoking, and stress. It is also still unclear if any specific symptoms are related to inflammation. Therefore, we assessed 96 inflammatory proteins in a deeply phenotyped cohort of 126 adult ADHD participants with a stable medication status using OLINK technology. A data-based, unsupervised hierarchical clustering method could identify two distinct biotypes within the 126 ADHD participants based on their inflammatory profile: a higher inflammatory potential (HIP) and a lower inflammatory protein potential (LIP) group. Biological processes that differed strongest between groups were related to the NF-κB pathway, chemokine signaling, IL-17 signaling, metabolic alterations, and chemokine attraction. A comparison of sample characteristics revealed that the HIP group was more likely to have higher levels of chronic stress (p < 0.001), a higher clinical global impression scale score (p = 0.030), and a higher risk for suicide (p = 0.032). Medication status did not influence protein levels significantly (p ≥ 0.074), but psychotropic co-medication (p ≤ 0.009) did. In conclusion, our data suggest the presence of two distinct biotypes in adults with ADHD. Higher levels of inflammatory proteins in ADHD are linked to higher levels of chronic perceived stress in a linear fashion. Further research on inflammation in adults with ADHD should take stress levels into account.

Differential neurocognitive profiles in adult attention-deficit/hyperactivity disorder subtypes revealed by the Cambridge Neuropsychological Test Automated Battery.

Adult attention-deficit/hyperactivity disorder (aADHD) represents a heterogeneous entity incorporating different subgroups in terms of symptomatology, course, and neurocognition. Although neurocognitive dysfunction is generally associated with aADHD, its severity, association with self-reported symptoms, and differences between subtypes remain unclear. We investigated 61 outpatients (65.6% male, mean age 31.5 ± 9.5) diagnosed using DSM-5 criteria together with age-, sex-, and education-matched healthy controls (HC) (n = 58, 63.8% male, mean age 32.3 ± 9.6). Neurocognitive alterations were assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and compared between groups using the generalized linear model (GLM) method. Multivariate effects were tested by principal component analysis combined with multivariate pattern analysis. Self-reported symptom severity was tested for correlations with neurocognitive performance. GLM analyses revealed nominally significant differences between the aADHD and HC groups in several domains, however, only the Rapid Visual Information Processing measures survived correction, indicating impaired sustained attention and response inhibition in the aADHD group. Comparison of the predominantly inattentive and the hyperactive-impulsive/combined subtypes yielded nominally significant differences with higher levels of dysfunction in the inattentive group. In the stepwise discriminant analysis aADHD and HC groups were best separated with 2 factors representing sustained attention and reaction time. We found only weak correlations between symptom severity and CANTAB factors. aADHD patients are neuropsychologically heterogeneous and subtypes show different neurocognitive profiles. Differences between the aADHD and HC groups were driven primarily by the inattentive subtype. Sustained attention and its factor derivative showed the most significant alterations in aADHD patients.

[Borderline personality disorder in the light of developmental psychopathology]. / A borderline személyiségzavar a fejlodéspszichopatológia tükrében.

The incidence of borderline personality disorder (BPD) in psychiatric care has shown growing tendencies. Despite its frequency, it is an underdiagnosed disease. Profound knowledge of etiological factors of BPD is essential for the proper diagnosis and treatment. The present study aims to provide a developmental psychopathological analysis of borderline personality disorder, which includes a thorough review of genetic and environmental etiological factors, an introduction to the functionalist approach of evolutionary perspective, and an overview of age specific characteristics of borderline symptoms. Recent research suggests that in addition to neurobiological and psychosocial factors, genetic vulnerability may be responsible for the development of BPD. Psychosocial background includes childhood trauma, maternal mental illness, maladaptive parenting styles and dysfunctional parent-child relationship, all of which are recognized as contributing factors to the development of insecure or disorganized attachment styles in the infant. Regarding the neurobiological background, changes in the hypothalamic-pituitary-adrenal axis, neurotransmission, endogenous opioid system, and neuroplasticity play a prominent role, the development of which is also affected by childhood traumatic events. Brain imaging studies reveal differences in the limbic system (hippocampus, amygdala) and frontal cortex, which are also involved in stress response, cognition, memory function, and emotion regulation. Early developmental processes may also play an important role in the development of the disorder, as depression during pregnancy or increased stress affects the quality of maternal care and may also affect gene expression through epigenetic mechanisms. With respect to the gene-environment interaction, the interaction of the child's impulsive traits and the invalidating family environment can be highlighted, which can lead to disruption of emotion regulation. The persistence of BPD symptoms is supported by the evolutionary approach concerning several aspects. Fear of abandonment can be explained by the anticipation of exclusion and maladaptive attempts to avoid it. Developmental psychopathological analysis contributes to the development of effective prevention and intervention tools through a better understanding of the background of borderline personality disorder. In terms of prognosis, as a result of effective treatments, symptoms can be reduced, so improvement can be achieved in a large proportion of patients.

Treating impulsivity with probiotics in adults (PROBIA): study protocol of a multicenter, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Impulsivity and compulsivity are related to emotional and social maladjustment and often underlie psychiatric disorders. Recently, alterations in microbiota composition have been shown to have implications for brain development and social behavior via the microbiota-gut-brain axis. However, the exact mechanisms are not fully identified. Recent evidence suggests the modulatory effect of synbiotics on gut microbiota and the contribution of these agents in ameliorating symptoms of many psychiatric diseases. To date, no randomized controlled trial has been performed to establish the feasibility and efficacy of this intervention targeting the reduction of impulsivity and compulsivity. We hypothesize that supplementation with synbiotics may be an effective treatment in adults with high levels of impulsivity and/or compulsivity. METHODS/DESIGN: This is a prospective, multicenter, double-blind, randomized controlled trial with two arms: treatment with a synbiotic formula versus placebo treatment. The primary outcome is the response rate at the end of the placebo-controlled phase (response defined as a Clinical Global Impression-Improvement Scale score of 1 or 2 = very much improved or much improved, plus a reduction in the Affective Reactivity Index total score of at least 30% compared with baseline). A total of 180 participants with highly impulsive behavior and a diagnosis of attention deficit/hyperactivity disorder (ADHD) and/or borderline personality disorder, aged 18-65 years old, will be screened at three study centers. Secondary outcome measures, including changes in general psychopathology, ADHD symptoms, neurocognitive function, somatic parameters, physical activity, nutritional intake, and health-related quality of life, will be explored at assessments before, during, and at the end of the intervention. The effect of the intervention on genetics, microbiota, and several blood biomarkers will also be assessed. Gastrointestinal symptoms and somatic complaints will additionally be explored at 1-week follow-up. DISCUSSION: This is the first randomized controlled trial to determine the effects of supplementation with synbiotics on reducing impulsive and compulsive behavior. This clinical trial can contribute to explaining the mechanisms involved in the crosstalk between the intestinal microbiome and the brain. If effects can be established by reducing impulsive and compulsive behavior, new cost-effective treatments might become available to these patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03495375. Registered on 26 February 2018.

A novel experimental paradigm with improved ecological validity reveals robust action-associated enhancement of the N1 visual event-related potential in healthy adults.

The association between an action and its sensory consequence has been linked to our sense of agency (SoA). While ecological validity is crucial in investigating such a complex phenomenon, previous paradigms focusing on the cortical analysis of movement-related images used simplified experimental protocols. Here, we examined the influence of action-associated predictive processes on visual event-related potentials (ERPs) in a paradigm that models everyday actions more precisely, using a commercial gesture control device, ecological stimuli depicting a human hand and a behavioural training to reinforce the sense of control over action outcomes. We assessed whether a more natural setup would result in robust ERP modifications following self-initiated movements relative to passive viewing of the same images. We found no compelling evidence for amplitude modulation for the early occipital C1 and P1 components. Crucially, we observed strong action-associated amplitude enhancement for the posterior N1, an effect that was not present in our previous study that relied on conventional button-presses. We propose that the N1 effect in our ecologically more valid paradigm can either reflect stronger attentional amplification of domain-specific visual processes following self-initiated actions, or indicate that sensory predictions in the visual N1 latency range manifest in larger (rather than reduced) ERPs. Overall, our novel approach utilizing a gesture-control device can be a potent tool for investigating the behavioural and neural manifestations of SoA in the visual modality.

Mild Effect of Nalmefene on Alcoholic Cue-Induced Response Invigoration in Alcohol Use Disorder Without Accompanying Changes in Electrophysiological Signatures of Early Visual Processing and Executive Control.

Nalmefene is approved for as-needed pharmacological treatment in alcohol use disorder (AUD) by the European Medicines Agency. While the cellular effects of nalmefene have been thoroughly investigated, data are very limited on how this agent influences neural signals associated with inhibitory control and the visual analysis of environmental cues. This double-blind crossover study assessed the behavioral and neural effects of acute nalmefene administration in patients diagnosed with AUD. In experiment 1, we validated our experimental paradigm (electroencephalography combined with a modified Go/NoGo task using images of alcoholic and nonalcoholic drinks as prime stimuli) in 20 healthy adults to ensure that our protocol is suitable for assessing the behavioral and neural aspects of executive control. In experiment 2, we recruited 19 patients with AUD, and in a double-blind crossover design, we investigated the effects of nalmefene versus placebo on task performance (response accuracy, the sensitivity index, and reaction times), visual responses to appetitive cues (occipital P1, N1, and P2 components), and electrophysiological markers of conflict detection and response inhibition (frontal N2 and P3 waveforms). Under placebo, patients produced faster reaction times to alcohol-primed Go stimuli, an effect that was weak despite being statistically significant. However, the effect of alcoholic cues on the speed of response initiation disappeared after receiving nalmefene. We found no placebo versus nalmefene difference regarding our patients' ability to accurately inhibit responses to NoGo stimuli or for occipital and frontal event-related potentials. Our results suggest that nalmefene might be potent in reducing the vigor to act upon alcoholic cues in AUD patients, but this effect is most probably mediated via subcortical (rather than cortical) neural circuits.

Action-associated modulation of visual event-related potentials evoked by abstract and ecological stimuli.

This study investigated the influence of action-associated predictive processes on visual ERPs. In two experiments, we sought evidence for sensory attenuation (SA) indexed by ERP amplitude reductions for self-induced stimuli when compared to passive viewing of the same images. We assessed if SA is (a) present for both ecological and abstract stimuli (pictures depicting hands or checkerboards), (b) modulated by the degree of stimulus predictability (certain or uncertain action-effect contingencies), and (c) sensitive to laterality of hand movements (dominant or subdominant hand actions). We found reduced occipital responses in the early 77-90 ms time interval (C1 component), irrespective of stimulus type, predictability, or the laterality of hand movements. However, the subsequent P1 component was increased (rather than reduced) for all action-associated stimuli. In addition, this P1 effect was influenced by the degree of stimulus predictability for ecological stimuli only. Finally, the posterior N1 component was not modulated by self-initiated actions. Overall, our findings indicate that movement-related predictive processes attenuate early visual responses. Moreover, we propose that amplitude modulations in the P1 time range reflect the interaction between expectation-based SA and attention-associated amplitude enhancements. These results can have implications for assessing the influence of action-associated predictions on visual processing in psychiatric disorders characterized by aberrant sensory predictions and alterations in hemispheric asymmetry, such as schizophrenia.

The first independent study on the complex trial protocol version of the P300-based concealed information test: Corroboration of previous findings and highlights on vulnerabilities.

More than a dozen studies of the Complex Trial Protocol (CTP) version of the P300-based Concealed Information Test have been published since its introduction (Rosenfeld et al., 2008), and it has been fairly consistently proven to provide high accuracy and strong resistance to countermeasures (Rosenfeld et al., 2013). However, no independent authors have verified these findings until now. In the present, first independent study, we corroborate the accuracy and countermeasure-resistance of the CTP, when the probe item (critical presented information, e.g., crime detail; P) vs. all irrelevant items (Iall) comparison is used for classifying participants as guilty or innocent, but we also show that the CTP is severely vulnerable to countermeasures, when the P vs. the irrelevant item with the largest P300 responses (Imax) comparison is used. This latter measure can be defeated by creating "oddball" items among the irrelevant items (through targeting them with covert responses), and thereby making their P300 responses statistically indistinguishable from those of the probe item. Practical implications are discussed.