Biological psychiatry. Cognitive neuroscience and neuroimaging最新文献

Background: Substance use disorders are associated with severe negative social and health-related outcomes. Evidence has accumulated that long-term substance use is associated with alterations in social interaction behavior, which likely contributes to the vicious cycle of substance use disorder. However, little is known about whether these social problems originate from contextual factors only or also from the substance use itself-in other words, if they are predisposed or substance induced.

Methods: We studied the causation behind behavioral alterations of substance users over a 9-year period (ages 11-20 years) in an urban age cohort (N = 1002) with a high prevalence of substance use at age 20. We identified common substance use patterns using toxicological hair analysis, examined behavioral alterations with incentivized games, and used teacher assessments across different ages to determine the causes and effects that underlie substance use-related impairments in social interaction.

Results: We found that opioid and stimulant users showed reduced prosocial behavior compared with nonusers, particularly in interpersonal trust and perspective taking (e.g., they were approximately 50% less likely to trust others). Our longitudinal analyses suggest a causal relationship between the nonmedical use of prescription opioids and impaired social behavior, whereas impairments among stimulant users seem to be partially predisposed. Moreover, women tended to be more severely affected by opioid use than men. However, no behavioral alterations were found among young adult cannabis or ecstasy users.

Conclusions: Highly addictive substances such as opioids can impair users' social behavior by undermining fundamental human interaction, thereby fueling a vicious cycle of substance use and social isolation.

Background: To progress adolescent mental health research beyond our present achievements - a complex account of brain and environmental risk factors without understanding neurobiological embedding in the environment - we need methods to unveil relationships between the developing brain and real-world environmental experiences.

Methods: We investigated associations among brain function, environments, and emotional and behavioral problems using participants from the Adolescent Brain and Cognitive Development Study (N=2,401 female). We applied manifold learning, a promising technique for uncovering latent structure from high-dimensional biomedical data like functional magnetic resonance imaging (fMRI). Specifically, we developed exogenous PHATE (E-PHATE) to model brain-environment interactions. We used E-PHATE embeddings of participants' brain activation during emotional and cognitive processing to predict individual differences in cognition and emotional and behavioral problems, both cross-sectionally and longitudinally.

Results: E-PHATE embeddings of participants' brain activation and environments at baseline show moderate-to-large associations with total, externalizing, and internalizing problems at baseline, across several subcortical regions and large-scale cortical networks, relative to the zero-to-small effects achieved by voxel or PHATE methods. E-PHATE embeddings of the brain and environment at baseline also relate to emotional and behavioral problems two years later. These longitudinal predictions show a consistent, moderate effect in the frontoparietal and attention networks.

Conclusions: Adolescent brain's embedding in the environment yields enriched insight into emotional and behavioral problems. Using E-PHATE, we demonstrate how the harmonization of cutting-edge computational methods with longstanding developmental theories advances detection and prediction of adolescent emotional and behavioral problems.

Background: Adolescents raised in families with different maternal and paternal parenting combinations exhibit variations in neurocognition and psychopathology; however, whether neural differences exist remains unexplored. This study used a longitudinal twin sample to delineate how different parenting combinations influence adolescent brain structure and to elucidate the genetic contribution.

Methods: A cohort of 216 twins participated in parenting assessments during early adolescence and underwent magnetic resonance imaging scanning during middle adolescence. We utilized latent profile analysis to distinguish between various maternal and paternal parenting profiles and subsequently investigated their influences on brain anatomy. Biometric analysis was applied to assess genetic influences on brain structure, and associations with internalizing symptoms were explored.

Results: In early adolescence, 4 parenting profiles emerged, which were characterized by levels of harshness and hostility in one or both parents. Compared with adolescents in "catparent" families (low harshness/hostility in both parents), those raised in "tigermom" families (harsh/hostile mother only) exhibited a smaller nucleus accumbens volume and larger temporal cortex surface area; those in "tigerdad" families demonstrated larger thalamus volumes; and those in "tigerparent" families displayed smaller volumes in the midanterior corpus callosum. Genetic risk factors contributed significantly to the observed brain structural heterogeneity and internalizing symptoms. However, the influences of parenting profiles and brain structure on internalizing symptoms were not significant.

Conclusions: The findings underscore distinct brain structural features linked to maternal and paternal parenting combinations, particularly in terms of subcortical volume and cortical surface area. This study suggests an interdependent role of maternal and paternal parenting in shaping adolescent neurodevelopment.

Background: Voice hearing (VH) is a transdiagnostic experience that is common in trauma-related disorders. However, the neural substrates that underlie trauma-related VH remain largely unexplored. While auditory perceptual dysfunction is among the abnormalities implicated in VH in schizophrenia, whether VH in trauma-related disorders also involves auditory perceptual alterations is unknown.

Methods: We investigated auditory cortex (AC)-related functional connectivity (FC) in 65 women with trauma-related disorders stemming from childhood abuse with varying severities of VH. Using a novel, computationally driven and individual-specific method of functionally parcellating the brain, we calculated the FC of 2 distinct AC subregions-Heschl's gyrus (corresponding to the primary AC) and lateral superior temporal gyrus (in the nonprimary AC)-with both the cerebrum and cerebellum. Then, we measured the association between VH severity and FC using leave-one-out cross-validation in the cerebrum and voxelwise multiple regression analyses in the cerebellum.

Results: We found that VH severity was positively correlated with left lateral superior temporal gyrus-frontoparietal network FC, while it was negatively correlated with FC between the left lateral superior temporal gyrus and both cerebral and cerebellar representations of the default mode network. VH severity was not predicted by FC of the left Heschl's gyrus or right AC subregions.

Conclusions: Our findings point to altered interactions between auditory perceptual processing and higher-level processes related to self-reference and executive functioning. This is the first study to show alterations in auditory cortical connectivity in trauma-related VH. While VH in trauma-related disorders appears to be mediated by brain networks that are also implicated in VH in schizophrenia, the results suggest a unique mechanism that could distinguish VH in trauma-related disorders.

Background: As research on psychedelics (hallucinogenic serotonin receptor 2A agonists) progresses, it is important to delineate the reliability of supposedly unique effects across this drug class. One such effect is how psychedelics impair the formation (i.e., encoding) of hippocampal-dependent recollections (retrieval of specific details) while potentially enhancing the encoding of cortical-dependent familiarity (a feeling of knowing that a stimulus has been previously experienced).

Methods: In a double-blind, placebo-controlled, within-participants study (N = 20), we tested the acute effects of 2 distinct psychedelics, psilocybin and 2C-B, on the encoding of emotional episodic memories. During acute drug effects, participants viewed negative, neutral, and positive pictures. The following day (while sober), participants completed 2 separate memory tests for these pictures.

Results: Using computational models of memory confidence, we found trends for psilocybin and 2C-B at encoding to impair estimates of recollection that were supported by other measures/analyses. Surprisingly, psilocybin and 2C-B at encoding impaired estimates of familiarity, but these impairments were likely due to a misattribution of heightened familiarity, because both drugs at encoding selectively increased familiarity-based false alarms, especially for negative and positive stimuli. Psilocybin and 2C-B at encoding also tended to impair estimates of metamemory (understanding one's own memory) for negative and neutral memories but enhanced estimates of metamemory for positive memories, although these effects were less reliable in additional analyses.

Conclusions: Despite differences in their chemistry, pharmacology, and subjective effects, both psilocybin and 2C-B distorted episodic familiarity, suggesting a common neurocognitive mechanism across psychedelics that may drive other phenomena.

Background: The mechanisms that link neural and behavioral indices of reduced reward sensitivity in depression, particularly in children, remain unclear. Reward positivity (RewP), a neural index of reward processing, has been consistently associated with depression. Separately, recent studies using the drift-diffusion model on behavioral data have delineated computational indices of reward sensitivity. Therefore, in the current study, we examined whether RewP is a neural mediator of drift-diffusion model-based indices of reward processing in predicting pediatric depression across varying levels of symptom severity.

Methods: A community sample of 166 girls, ages 8 to 14 years, completed 2 tasks. The first was a reward guessing task from which RewP was computed using electroencephalography; the second was a probabilistic reward-based decision-making task. On this second task, drift-diffusion model analysis was applied to behavioral data to quantify the efficiency of accumulating reward-related evidence (drift rate) and potential baseline bias (starting point) toward the differently rewarded choices. Depression severity was measured using the self-report Children's Depression Inventory.

Results: RewP was correlated with drift rate, but not starting point bias, toward the more rewarded choice. Furthermore, RewP completely mediated the association between a slower drift rate toward the more rewarded option and higher depression symptom severity.

Conclusions: Our findings suggest that reduced neural sensitivity to reward feedback may be a neural mechanism that underlies behavioral insensitivity to reward in children and adolescents with higher depression symptom severity, offering novel insights into the relationship between neural and computational indices of reward processing in this context.

Background: Binge-eating disorder (BED) is thought of as a disorder of cognitive control, but evidence regarding its neurocognitive mechanisms is inconclusive. Key limitations of previous research include a lack of consistent separation between effects of BED and obesity and a disregard for self-report evidence suggesting that neurocognitive alterations may emerge primarily in loss- or harm-avoidance contexts.

Methods: To address these gaps, in this longitudinal study we investigated behavioral flexibility and its underlying neurocomputational processes in reward-seeking and loss-avoidance contexts. Obese participants with BED, obese participants without BED, and healthy normal-weight participants (n = 96) performed a probabilistic reversal learning task during functional imaging, with different blocks focused on obtaining wins or avoiding losses. They were reinvited for a 6-month follow-up assessment.

Results: Analyses informed by computational models of reinforcement learning showed that unlike obese participants with BED, obese participants without BED performed worse in the win than in the loss condition. Computationally, this was explained by differential learning sensitivities in the win versus loss conditions in the groups. In the brain, this was echoed in differential neural learning signals in the ventromedial prefrontal cortex per condition. The differences were subtle but scaled with BED symptoms, such that more severe BED symptoms were associated with increasing bias toward improved learning from wins versus losses. Across conditions, obese participants with BED switched more between choice options than healthy normal-weight participants. This was reflected in diminished representation of choice certainty in the ventromedial prefrontal cortex.

Conclusions: Our study highlights the importance of distinguishing between obesity with and without BED to identify unique neurocomputational alterations underlying different styles of maladaptive eating behavior.

Recent neuroimaging studies and publicly disseminated analytic tools suggest that regional morphometric analyses covary for global thickness. We empirically demonstrated that this statistical approach severely underestimates regional thickness dysmorphology in psychiatric disorders. Study 1 included 90 healthy control participants, 51 participants at clinical high risk for psychosis, and 78 participants with early-illness schizophrenia. Study 2 included 56 healthy control participants, 83 participants with nonaffective psychosis, and 30 participants with affective psychosis. We examined global and regional thickness correlations, global thickness group differences, and regional thickness group differences with and without global thickness covariation. Global and regional thickness were strongly correlated across groups. Global thickness was lower in the schizophrenia spectrum groups than the other groups. Regional thickness deficits in schizophrenia spectrum groups were attenuated or eliminated with global thickness covariation. Eliminating the variation that regional thickness shares with global thickness eliminated disease-related effects. This statistical approach results in erroneous conclusions that regional thickness is normal in disorders like schizophrenia or clinical high risk syndrome.

Background: Working memory is a fundamental cognitive process that is critically involved in planning, comprehension, reasoning, and problem solving. Acute stress has been shown to impair working memory. This stress-induced working memory deficit has profound implications for cognitive functioning in everyday life as well as for stress-related mental disorders. Here, we tested whether a cognitive training intervention would make working memory more resistant to disruptive effects of acute stress.

Methods: In a preregistered, fully crossed between-subjects design with the factors stress (vs. control) and cognitive training (vs. sham), 123 healthy men and women (ages 18-35 years) completed a daily cognitive training program targeting working memory-related processes or a sham training over a period of 6 weeks. After this 6-week training intervention, participants underwent a standardized stress or control manipulation shortly before their working memory performance was tested.

Results: As expected, the exposure to acute stress led to a significant working memory impairment in the sham training group. Critically, although the subjective, autonomic, and endocrine stress responses were comparable in the 2 training groups, this stress-induced working memory impairment was abolished in the intervention training group.

Conclusions: These results are the first to show that a cognitive training intervention directed at prefrontal and hippocampal functioning can prevent the detrimental effects of stressful events on working memory performance.

Background: Restricted scan path mode is hypothesized to explain abnormal scanning patterns in patients with schizophrenia. Here, we calculated entropy scores (drawing on gaze data to measure the statistical randomness of eye movements) to quantify how strategical and random participants were when processing image stimuli.

Methods: Eighty-six patients with first-episode schizophrenia (FES), 124 individuals at clinical high risk (CHR) for psychosis, and 115 healthy control participants (HCs) completed an eye-tracking examination while freely viewing 35 static images (each presented for 10 seconds) and cognitive assessments. We compared group differences in the overall entropy score, as well as entropy scores under various conditions. We also investigated the correlations between entropy scores and symptoms and cognitive function.

Results: Increased overall entropy scores were noted in the FES and CHR groups compared with the HC group, and these differences were already apparent within 0 to 2.5 seconds. In addition, the CHR group exhibited higher entropy than the HC group when viewing low-meaning images. Moreover, the entropy within 0 to 2.5 seconds showed significant correlations with negative symptoms in the FES group, attention/vigilance scores in the CHR group, and speed of processing and attention/vigilance scores across all 3 groups.

Conclusions: The results indicate that individuals with FES and those at CHR scanned pictures more randomly and less strategically than HCs. These patterns also correlated with clinical symptoms and neurocognition. The current study highlights the potential of the eye movement entropy measure as a neurophysiological marker for early psychosis.