Most mental disorders originate in childhood, and once symptoms present, a variety of psychosocial and cognitive maladjustments may arise. Although early childhood problems are generally associated with later mental health impairments and psychopathology, pluripotent transdiagnostic trajectories may manifest. Possible predictors range from behavioral and neurobiological mechanisms, genetic predispositions, environmental and social factors, and psychopathological comorbidity. They may manifest in altered neurodevelopmental trajectories and need to be validated capitalizing on large-scale multi-modal epidemiological longitudinal cohorts. Moreover, clinical and etiological variability between patients with the same disorders represents a major obstacle to develop effective treatments. Hence, in order to achieve stratification of patient samples opening the avenue of adapting and optimizing treatment for the individual, there is a need to integrate data from multi-dimensionally phenotyped clinical cohorts and cross-validate them with epidemiological cohort data. In the present review, we discuss these aspects in the context of externalizing and internalizing disorders summarizing the current state of knowledge, obstacles, and pitfalls. Although a large number of studies have already increased our understanding on neuropsychobiological mechanisms of mental disorders, it became also clear that this knowledge might only be the tip of the Eisberg and that a large proportion still remains unknown. We discuss prediction strategies and how the integration of different factors and methods may provide useful contributions to research and at the same time may inform prevention and intervention.
Although neural signals of reward anticipation have been studied extensively, the functional relationship between reward and attention has remained unclear: Neural signals implicated in reward processing could either reflect attentional biases towards motivationally salient stimuli, or proceed independently of attentional processes.Here, we sought to disentangle reward and attention-related neural processes by independently modulating reward value and attentional task demands in a functional magnetic resonance imaging study in healthy human participants.During presentation of a visual reward cue that indicated whether monetary reward could be obtained in a subsequent reaction time task, participants either attended to the reward cue or performed an unrelated attention-demanding task at two different levels of difficulty.In ventral striatum and ventral tegmental area, neural responses were modulated by reward anticipation irrespective of attentional demands, thus indicating attention-independent processing of reward cues.By contrast, additive effects of reward and attention were observed in visual cortex.Critically, reward-related activations in right anterior insula strongly depended on attention to the reward cue.Dynamic causal modelling revealed that the attentional modulation of reward processing in insular cortex was mediated by enhanced effective connectivity from ventral striatum to anterior insula.Our results provide evidence for distinct functional roles of the brain regions involved in the processing of reward-indicating information: While subcortical structures signal the motivational salience of reward cues even when attention is fully engaged elsewhere, reward-related responses in anterior insula depend on available attentional resources, likely reflecting the conscious evaluation of sensory information with respect to motivational value.
Abstract Re-directing attention to objects in working memory can enhance their representational fidelity. However, how this attentional enhancement of memory representations is implemented across distinct, sensory and cognitive-control brain network is unspecified. The present fMRI experiment leverages psychophysical modelling and multivariate auditory- pattern decoding as behavioral and neural proxies of mnemonic fidelity. Listeners performed an auditory syllable pitch-discrimination task and received retro-active cues to selectively attend to a to-be-probed syllable in memory. Accompanied by increased neural activation in fronto-parietal and cingulo-opercular networks, valid retro-cues yielded faster and more perceptually sensitive responses in recalling acoustic detail of memorized syllables. Information about the cued auditory object was decodable from hemodynamic response patterns in superior temporal sulcus (STS), fronto-parietal, and sensorimotor regions. However, among these regions retaining auditory memory objects, neural fidelity in the left STS and its enhancement through attention-to-memory best predicted individuals’ gain in auditory memory recall precision. Our results demonstrate how functionally discrete brain regions differentially contribute to the attentional enhancement of memory representations.
Alcohol consumption (AC) leads to death and disability worldwide. Ongoing discussions on potential negative effects of the COVID-19 pandemic on AC need to be informed by real-world evidence.To examine whether lockdown measures are associated with AC and consumption-related temporal and psychological within-person mechanisms.This quantitative, intensive, longitudinal cohort study recruited 1743 participants from 3 sites from February 20, 2020, to February 28, 2021. Data were provided before and within the second lockdown of the COVID-19 pandemic in Germany: before lockdown (October 2 to November 1, 2020); light lockdown (November 2 to December 15, 2020); and hard lockdown (December 16, 2020, to February 28, 2021).Daily ratings of AC (main outcome) captured during 3 lockdown phases (main variable) and temporal (weekends and holidays) and psychological (social isolation and drinking intention) correlates.Of the 1743 screened participants, 189 (119 [63.0%] male; median [IQR] age, 37 [27.5-52.0] years) with at least 2 alcohol use disorder (AUD) criteria according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) yet without the need for medically supervised alcohol withdrawal were included. These individuals provided 14 694 smartphone ratings from October 2020 through February 2021. Multilevel modeling revealed significantly higher AC (grams of alcohol per day) on weekend days vs weekdays (β = 11.39; 95% CI, 10.00-12.77; P < .001). Alcohol consumption was above the overall average on Christmas (β = 26.82; 95% CI, 21.87-31.77; P < .001) and New Year's Eve (β = 66.88; 95% CI, 59.22-74.54; P < .001). During the hard lockdown, perceived social isolation was significantly higher (β = 0.12; 95% CI, 0.06-0.15; P < .001), but AC was significantly lower (β = -5.45; 95% CI, -8.00 to -2.90; P = .001). Independent of lockdown, intention to drink less alcohol was associated with lower AC (β = -11.10; 95% CI, -13.63 to -8.58; P < .001). Notably, differences in AC between weekend and weekdays decreased both during the hard lockdown (β = -6.14; 95% CI, -9.96 to -2.31; P = .002) and in participants with severe AUD (β = -6.26; 95% CI, -10.18 to -2.34; P = .002).This 5-month cohort study found no immediate negative associations of lockdown measures with overall AC. Rather, weekend-weekday and holiday AC patterns exceeded lockdown effects. Differences in AC between weekend days and weekdays evinced that weekend drinking cycles decreased as a function of AUD severity and lockdown measures, indicating a potential mechanism of losing and regaining control. This finding suggests that temporal patterns and drinking intention constitute promising targets for prevention and intervention, even in high-risk individuals.
Background. A dysfunctional differentiation between self-relevant and irrelevant information may affect the perception of environmental stimuli as abnormally salient. The aberrant salience hypothesis assumes that positive symptoms arise from an attribution of salience to irrelevant stimuli accompanied by the feeling of self-relevance. Self-referential processing relies on the activation of cortical midline structures which was demonstrated to be impaired in psychosis. We investigated the neural correlates of self-referential processing, aberrant salience attribution, and the relationship between these 2 measures across the psychosis continuum. Methods. Twenty-nine schizophrenia patients, 24 healthy individuals with subclinical delusional ideation, and 50 healthy individuals participated in this study. Aberrant salience was assessed behaviorally in terms of reaction times to task irrelevant cues. Participants performed a self-reference task during fMRI in which they had to apply neutral trait words to them or to a public figure. The correlation between self-referential processing and aberrant salience attribution was tested. Results. Schizophrenia patients displayed increased aberrant salience attribution compared with healthy controls and individuals with subclinical delusional ideation, while the latter exhibited intermediate aberrant salience scores. In the self-reference task, schizophrenia patients showed reduced activation in the ventromedial prefrontal cortex (vmPFC), but individuals with subclinical delusional ideation did not differ from healthy controls. In schizophrenia patients, vmPFC activation correlated negatively with implicit aberrant salience attribution. Conclusions. Higher aberrant salience attribution in schizophrenia patients is related to reduced vmPFC activation during self-referential judgments suggesting that aberrant relevance coding is reflected in decreased neural self-referential processing as well as in aberrant salience attribution.
Everyday life requires an adaptive balance between distraction-resistant maintenance of information and the flexibility to update this information when needed. These opposing mechanisms are proposed to be balanced through a working memory gating mechanism. Prior research indicates that obesity may elevate the risk of working memory deficits, yet the underlying mechanisms remain elusive. Dopaminergic abnormalities have emerged as a potential mediator. However, current models suggest these abnormalities should only shift the balance in working memory tasks, not produce overall deficits. The empirical support for this notion is currently lacking, however. To address this gap, we pooled data from three studies (N = 320) where participants performed a working memory gating task. Higher BMI was associated with overall poorer working memory, irrespective of whether there was a need to maintain or update information. However, when participants, in addition to BMI level, were categorized based on certain putative dopamine-signaling characteristics (Single Nucleotide Polymorphisms; specifically, Taq1A and DARPP), distinct working memory gating effects emerged. These SNPs, primarily associated with striatal dopamine transmission, specifically influenced updating in high-BMI individuals. Moreover, blood amino acid ratio, which indicates central dopamine synthesis capacity, combined with BMI, shifted the balance between distractor-resistant maintenance and updating. These findings suggest that both dopamine-dependent and dopamine-independent cognitive effects exist in obesity. Understanding these effects is crucial if we aim to modify maladaptive cognitive profiles in individuals with obesity.
Alcohol dependence is one of the most fatal mental diseases amongst men in western industrialized nations and is the major risk factor for the development of more than 60 chronic illnesses. With no further intervention, relapse rates in detoxified alcoholics are high and usually exceed 85% of all detoxified patients. It has been suggested that stress and exposure to priming doses of alcohol and to alcohol-associated stimuli (cues) contribute to the relapse risk after detoxification. In the last decades there has been substantial progress in scientific research of the neurobiological principles of alcohol-related disorders. Recent studies using multi modal imaging techniques like functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) observed dysfunctions of the mesolimbic dopaminergic brain reward system (ventral striatum including the nucleus accumbens): Functional brain activation is increased during the processing of alcohol-associated cues and decreased during the confrontation with other non-alcoholic reward-indicating stimuli. This alcohol-associated “hijacking” of the reward system is associated with craving and the prospective relapse risk. Moreover, the reward-associated learning seems to be disturbed in alcohol-dependent patients, so that addicted persons have problems to integrate informations about positive and negative consequences of their actions and to adapt their behavior accordingly. Personality traits like impulsiveness seem to be relevant in this context as well. These findings about the different neurobiological mechanisms of addiction and relapse raise hope for new psychotherapeutic and pharmacological treatment approaches of alcohol dependence that is adapted to individual relapse mechanisms and needs.
