Biological psychiatry. Cognitive neuroscience and neuroimaging最新文献

Background: Adverse childhood experiences (ACEs) are key risk factors for adolescent mental health problems, including conduct problems (CPs). While ACEs may impact CPs through neurobiological pathways, it is unclear whether brain functional connectivity (FC) acts as the neurobiological link.

Methods: We included 11,868 children from the baseline sample of the Adolescent Brain Cognitive Development (ABCD) Study. First, the continuous association between ACEs and CP severity was analyzed using linear mixed-effects (LME) modeling. Next, connectome-based predictive modeling (CPM) was used to predict CP scores and identify the CP-related connections, which were validated in 174 Healthy Brain Network (HBN) clinical participants. Finally, mediation analyses assessed whether the strength of CP-related connections mediated the association between ACEs and CP scores collected at baseline, 2 years, and 4 years after the ACEs report in the ABCD sample.

Results: LME modeling showed total ACEs and all 10 ACE categories were associated with increased CP scores (d = 0.056-0.465, false discovery rate-corrected p < .01). CPM significantly predicted CP scores (ρ = 0.128, p < .001), validated in the HBN dataset (ρ = 0.148, p = .048). The identified CP-related connections are involved in sensorimotor processing, emotional cognition, and impulsivity. Mediation analysis revealed that the strength of CP-related connections partially mediated the association between ACEs and CP scores at baseline, 2-year follow-up, and 4-year follow-up (β = 0.0086-0.015, p < .01).

Conclusions: This is the first study to our knowledge to suggest that FC provides a biological link between ACEs and subsequent CPs. ACEs may impact the strength of CP-related connections, in turn increasing risk of CPs. These findings highlight the importance of early assessment of ACEs and suggest CP-related connections as potential biomarkers.

Background: Cerebello-thalamo-cortical (CTC) network dysfunctions are well documented in schizophrenia spectrum disorders (SSDs) and preclinical states. However, small samples and methodological heterogeneity often limit individual neuroimaging studies. To overcome these challenges, we conducted a coordinate-based meta-analysis to characterize CTC alterations across illness stages and examine associations with symptom dimensions.

Methods: Our meta-analysis was preregistered and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the recommendations of the Cochrane Handbook. A systematic search was conducted in 3 databases in September 2023. Included articles used seed-based resting-state functional magnetic resonance imaging in patients with SSDs, patients with first-episode psychosis, participants at clinical high risk for psychosis, and healthy control participants. Seeds were defined in the thalamus and the cerebellum. Two coordinate-based meta-analytic methods, activation likelihood estimation and seed-based d mapping, were used. Risk of bias was evaluated per the Organization for Human Brain Mapping recommendations.

Results: In SSDs thalamic hypoconnectivity was found in the prefrontal cortex, limbic lobe, thalamus, and cerebellum, whereas hyperconnectivity was observed in the somatomotor and visual association areas (29 studies, 2768 patients). Dysconnectivity was linked to disease progression and symptoms. Cerebellar analysis indicated hypoconnectivity in the prefrontal cortex, cerebellum, and thalamus, with hyperconnectivity in the motor cortex, somatosensory cortex, and orbitofrontal cortex (19 studies, 1159 patients). Cerebellar clusters did not survive multiple comparison correction.

Conclusions: Our findings provide robust meta-analytic evidence of CTC dysconnectivity in SSDs, suggesting that this network captures a core neurobiological feature of psychotic disorders. Consistent patterns of altered CTC connectivity underscore the importance of future clinical investigations of this network as a potential target for therapeutic interventions.

Background: Preterm (PT) birth is associated with important social vulnerabilities that can have long-term implications and may result in psychopathology (e.g., autism spectrum disorder). A recurring preterm behavioral phenotype has been described, although these difficulties may often be subtle and subclinical. As face processing is crucial for social interactions, and several studies have reported impaired face-processing performance in PT populations, we hypothesized that face-processing difficulties may contribute to or be a part of these social difficulties. Here, we investigated neural sensitivity to crucial sociocommunicative facial cues in school-age PT children.

Methods: Thirty-nine 8- to 12-year-old PT children born between 24 and 32 weeks of gestation and 38 term-born matched control children performed a series of innovative facial identity and expression discrimination frequency-tagging electroencephalography paradigms. More specifically, we evaluated the neural sensitivity to implicitly and automatically discriminate a different facial identity among a stream of identical faces, as well as an expressive face (fearful and happy, in separate sequences) among a stream of neutral faces.

Results: We found intact implicit facial identity and expression processing in both groups. Unexpectedly, PT participants showed a significantly greater neural sensitivity toward these subtle sociocommunicative facial cues. Correlations with neonatal measures such as gestational age and birth weight showed that this greater neural sensitivity was uniformly present among the PT group.

Conclusions: The evidence suggests that impaired neural sensitivity to facial cues may not be the primary cause of the behavioral face-processing and social difficulties often encountered in PT children.

Background: This study identified behavioral and neural indices of the specificity of emotion representations in adolescents' brains and assessed their association with resilience to childhood violence exposure.

Methods: Eighty 13- to 18-year-old adolescents with variable exposure to violence viewed emotion-eliciting videos and rated how angry, disgusted, sad, scared, and upset they felt. Sixty-nine participants viewed the same videos in the magnetic resonance imaging scanner, once while labeling their emotions and once while counting the number of people.

Results: Emotion labeling (vs. counting) led to greater blood oxygen level-dependent activation in the medial and ventrolateral prefrontal cortex. Based on representational similarity analysis, if 2 stimuli elicited more similar patterns of activation within those brain regions, those stimuli had more similar emotion ratings, suggesting that encoding of emotion categories within these brain regions is reflected in their activation patterns. Moreover, emotion differentiation measured behaviorally and the mean neural dissimilarity across all stimulus pairs for each participant each moderated the association between violence exposure and psychopathology such that the association between violence exposure and psychopathology was weaker in individuals with greater emotion differentiation and neural dissimilarity.

Conclusions: The granularity of emotions reflected in adolescents' brains and behavior contributes to resilience and therefore may serve as a target for preventive interventions.

Background: A key challenge in understanding the neurobehavioral mechanisms of psychotic disorders (PDs) is identifying the level and interactions of the affected brain regions. The early visual system, with its hierarchical structure, offers a model for studying such mechanisms. Specifically, variations in visual contrast are detected as early as in the retina, whereas binocular depth perception emerges at a higher level, in the visual cortex. Comparing these processes within individuals can provide insights into the mechanisms and progression of perceptual deficits in PDs.

Methods: Psychophysical sensitivity to stimulus contrast and binocular disparity were assessed in 53 participants with PDs and 58 demographically matched healthy control participants (HCs). Across the 2 tasks, the physical features of the stimuli were matched except for the primary variable of interest. Psychometric functions were fitted to the performance of each participant, and the normalized area under the psychometric curves quantified the average performance across stimulus strengths.

Results: The PD group showed significantly impaired performance in both visual contrast detection (p < .007) and binocular depth perception (p < .021) compared with the HC group. In the PD but not the HC group, the performance levels across the 2 tasks were correlated with each other. A direct comparison revealed a more pronounced deficit in depth perception than in contrast detection in the PD group. Differences in psychometric parameters (i.e., threshold, flatness, and lapse rate) revealed additional cognitive and attentional dysfunctions in the PD group.

Conclusions: These findings provide evidence for a progressive accumulation of deficits through the visual hierarchy in psychosis.

Background: The brain's responsiveness to rewarding stimuli is essential for adaptive functioning, while deficits in neural reward processing have been linked to the transdiagnostic symptom of anhedonia. Acute or prolonged stressors may negatively impact neural reward responses; however, few studies have examined whether real-world naturalistic stressors prospectively predict reductions in brain responses to rewards.

Methods: This preregistered analysis (https://osf.io/f6e8w) used data from the ARMOR (Advancing Research on Mechanisms of Resilience) study to assess whether exposure to basic combat training (BCT), which is a demanding and stress-inducing 10-week program, led to reductions in electrophysiological measures of reward response. One hundred fifteen military recruits completed a virtual gambling task while an electroencephalogram (EEG) was recorded before and after BCT. Mean EEG activity in the time window of the reward positivity (RewP; 175-325 ms post-feedback at FCz) was averaged separately for the gain and loss conditions.

Results: We found that neural response to both gain and loss feedback in the time window of the RewP significantly decreased from baseline following BCT (b = -0.67, p < .001), but the difference between conditions did not decrease (b = 0.28, p = .23). Greater reports of BCT-related stressors predicted decreased neural response to gain but not loss. Finally, baseline reward-related power in the delta-band frequency prospectively predicted less self-reported BCT-related stress.

Conclusions: These findings suggest that experiencing the stress of BCT is associated with reductions in neural processing of both reward and loss feedback. Furthermore, individuals with greater reward-related delta oscillatory activity may perceive less negative impact of real-world stressors.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a multifaceted neurodevelopmental disorder that affects cognitive control processes. While neurophysiological data (e.g., electroencephalography [EEG] data) have provided valuable insights into its underlying mechanisms, fully understanding the altered cognitive functions in ADHD requires advanced analytical approaches capable of capturing the highly dimensional nature of neurophysiological data more effectively.

Methods: We examined 59 individuals with ADHD and 63 neurotypical participants using a standard Go/NoGo task to assess response inhibition. We used EEG tensor decomposition to extract spectral, temporal, spatial, and trial-level features associated with inhibitory control deficits in ADHD. The trial-level features capture intraindividual variability, which is then used in a machine learning analysis to differentiate individuals with ADHD from neurotypical participants. We also applied a feature selection algorithm to identify the most important features for distinguishing the 2 groups in the classification process.

Results: We observed typical response inhibition deficits in ADHD. Contrary to common assumptions, frontocentral theta band activity did not seem to be the most distinguishing EEG feature between ADHD and neurotypical individuals. Instead, the most important distinguishing features were tensor components reflecting posterior alpha band activity during attentional selection time windows and posterior theta band activity during response selection and control time windows.

Conclusions: We identified novel neurophysiological facets of response inhibition in ADHD, enabling the classification of ADHD and neurotypical individuals. Our findings suggest that ADHD-related deficits emerge early during attentional selection and persist through response control stages. The findings underscore the need to refine conceptions about neural peculiarities in ADHD and adapt clinical interventions targeting inhibitory control deficits accordingly.

Background: A core part of cognitive therapy for low mood is learning to identify and challenge negative beliefs. However, it is currently unclear whether improved ability to recognize such beliefs, and the biased interpretations of events that may maintain them, is a mechanism of symptom change during treatment.

Methods: We investigated the effects of completing a learning task (training to identify and select self-enhancing interpretations of events) and a brief cognitive restructuring intervention (how exploring alternative explanations of events may result in improved mood) on causal attribution tendencies. Studies were conducted online using randomized controlled experimental designs (N = 200 and N = 164), and data were analyzed using hierarchical Bayesian models.

Results: We found that both learning training and the restructuring intervention decreased tendencies to make unhelpful attributions and increased tendencies to make self-enhancing attributions. Across 2 studies, changes in attribution tendencies were associated with higher learning rates during learning training, an effect specific to learning about different kinds of event attributions. Contrary to expectation, we found no evidence that faster learning was associated specifically with changes in attribution tendencies following cognitive restructuring. Because participants with higher learning rate estimates also provided explicit ratings and free-text descriptions of event causes that were closer to the ground truth, we interpret this as representing a greater benefit of learning training in individuals who were better able to understand the task state space.

Conclusions: We suggest that personalized training, in conjunction with feedback based on interpretable computational model output, may provide a useful form of augmentation or learning support tool during therapy.

Background: The hippocampus is smaller and functionally disrupted in individuals with 22q11.2 deletion syndrome (22q11DS), but the cause remains unclear. During gestational weeks 20 to 30, an inversion in the dentate gyrus and cornu ammonis occurs. This process can go awry, resulting in incomplete hippocampal inversion (IHI). In the general population, IHI is more common in the left hemisphere than the right hemisphere; however, its prevalence, severity, and functional impact in 22q11DS remain unexplored. Investigating IHI in 22q11DS could uncover morphological hippocampal abnormalities linked to neuropsychiatric and neurocognitive symptoms.

Methods: Using 3T structural magnetic resonance imaging data, the presence and severity of IHI were assessed in individuals with 22q11DS (n = 108) and healthy comparison participants (HCs) (n = 633). Total and subregional hippocampal volumes, psychopathology, and hippocampal-based memory were evaluated.

Results: IHI prevalence was significantly higher in individuals with 22q11DS compared with HCs in both the left (63% vs. 30%, p < .001) and right (29% vs. 8%, p < .001) hemispheres. IHI severity was also greater in participants with 22q11DS (p < .001) bilaterally. IHI influenced hippocampal volume differences, with left IHI primarily affecting the head (p < .01) and tail (p < .001) and right IHI affecting only the tail (p < .001). In exploratory analyses within participants with 22q11DS, left IHI presence was linked to poorer face memory (p < .05) but not to psychopathology.

Conclusions: These findings highlight a high prevalence of hippocampal morphological alterations in 22q11DS, which are associated with memory performance. Earlier developmental and longitudinal studies are needed to clarify the role of IHI in 22q11DS sequelae.

Background: Cortical structure alterations in bipolar disorder (BD) have consistently been reported in association with suicide with high heritability. Currently, the multifaceted genetic landscape responsible for replicable neuroanatomical alterations with suicidal effects is poorly explored but could help develop personalized risk assessments in clinics.

Methods: Anatomically informed suicidal effects quantified with morphometric similarity network (MSN) upon structural magnetic resonance imaging were evaluated in 2 independent BD cohorts that consisted of patients with suicide attempt (SA) and without SA (NSA) (discovery: 63 BD-SAs and 72 BD-NSAs with 6 potential suicide-related single nucleotide polymorphisms [SNPs] examined in 46 BD-SAs and 55 BD-NSAs; replication: 23 BD-SAs and 23 BD-NSAs) and 119 healthy control participants. In the discovery study, transcriptomic and neurotransmitter correlates of suicide-relevant MSN deficits were examined by partial least squares regression using the Allen Human Brain Atlas and dominance analysis on 9 distinct neurotransmitter systems. Molecularly informed MSN deficits were orthogonally validated by estimating genetic risks from targeted SNP genotyping using a multilevel mediation analysis. A reproducible pattern of genetically decoding suicide-relevant MSN changes was validated in the replication study.

Results: The μ opioid receptor was consistently suggested to be responsible for reproducible suicide-relevant MSN alterations identified in entorhinal and left lateral occipital cortices. MSN deficits of the entorhinal cortex positively mediated the effects of genetic risks of OPRM1 on SA (portion mediated = 61.3%; β = 6.99 × 10^-2; p = .02; 95% CI, 3.34 × 10^-2 to 0.11).

Conclusions: Abnormal cytoarchitecture communities, especially maladaptive changes in neuronal communication between the entorhinal cortex and the reward circuit regulated by opioid receptors and reflected by enhanced morphometric similarities could mediate the effect on increased suicidal tendencies involved in OPRM1 gene variants in BD.