Biological psychiatry. Cognitive neuroscience and neuroimaging最新文献

Background: Moral injury (MI) is a condition that may emerge following a violation of an individual's moral code. MI leads to significant functional impairment in many trauma-exposed civilians, with rumination proposed as a mechanism of action. Little is known about the neuropathophysiology of different MI dimensions, including MI related to transgressions caused by the self or others. We examined links between facets of MI, resting-state amplitude of low-frequency fluctuations (ALFF), and rumination in trauma-exposed civilians.

Methods: Sixty adults (ages 18-56 years; 51 female) completed measures of MI (Moral Injury Exposure and Symptom Scale for Civilians [MIESS-C]), rumination (Response Styles Questionnaire), and resting-state functional magnetic resonance imaging. Voxelwise linear regression on ALFF was performed with rumination and MIESS-C-derived self-, other-, and betrayal-related MI as regressors.

Results: Betrayal-related MI associated with higher ALFF in the bilateral precuneus and left medial prefrontal cortex (mPFC). Other-related MI was associated with lower ALFF in the left dorsolateral PFC and insula (voxelwise p < .001, cluster false discovery rate-corrected p < .05). Rumination severity was positively associated with betrayal-related ALFF clusters in the bilateral precuneus (r = 0.32, p = .012) and left mPFC (r = 0.31, p = .017).

Conclusions: Results revealed distinct neural signatures of MI, with betrayal-related MI associated with greater ALFF in default mode network regions and this activation related to rumination severity. Other-related MI was linked to diminished activation in cognitive control and interoceptive network regions, which may reflect physiological withdrawal. These signatures are attractive candidate neuromodulatory targets.

Background: Research has demonstrated a broad network of dysfunction across the brain in attention-deficit/hyperactivity disorder (ADHD), suggesting the potential role of white matter (WM) organization. In this study, we sought to estimate the developmental trajectories of brain WM myelination in children with ADHD.

Methods: Neuroimaging and clinical data were collected as part of a longitudinal community-based pediatric cohort (N_scans = 400; 195 with ADHD; age range = 9-14 years). Brain WM myelin was examined for 71 WM tracts across 3 time points using the T1-weighted (T1w)/T2-weighted (T2w) ratio. Tracts were defined via a deep learning-based automated tractography method, performed on participant diffusion-weighted images. Linear and nonlinear regression analyses were conducted to examine group differences in T1w/T2w ratio values. In addition to this, voxelwise analysis was undertaken at each time point.

Results: Brainwide, children with ADHD were found to exhibit the same developmental profile as children without ADHD for WM myelin. No group effects were seen at a cross-sectional or longitudinal level. Consistent with previous work, modeling suggests nonlinear developmental increases with age across most tracts. This nonlinear relationship was characterized by a positive parabolic or U-shaped developmental trajectory.

Conclusions: These findings indicate that there may not be distinct differences in the development of brain WM myelination between children with and without ADHD. However, this suggests that previously reported differences in ADHD brain WM development may be attributable to properties other than myelin, such as fiber architecture and axon diameter. This further informs the understanding of brain development and highlights the need for more multimodal longitudinal work.

Background: Large-scale brain network dysfunctions have been implicated in multiple neuropsychiatric disorders. Disrupted interactions between these networks may similarly underlie key symptoms in prolonged grief disorder (PGD).

Methods: In a cross-sectional functional magnetic resonance imaging study, resting-state functional connectivity (rsFC) between large-scale networks was compared in demographic- and time since loss-equated older adults with probable PGD (n = 42) and those with integrated grief (IG) (n = 45). Group independent component analysis revealed multiple networks, 8 of which (salience [SN], default mode [DMN], left and right executive control, ventral attention, dorsal attention, sensorimotor, and visual) were selected for further analyses, with rsFC strength between all network pairs computed. Networks with significant group differences were further assessed using fractional amplitude of low-frequency fluctuations (fALFF) to determine within-network differences. The relationships between connectivity measures and clinical symptoms were explored independently in the PGD and IG groups.

Results: Higher rsFC between SN and DMN was observed in the PGD group compared with the IG group (p_corrected = .014), which positively correlated with grief severity (p_corrected = .04) and grief-related avoidance (p_corrected = .04). In the PGD group, higher fALFF was observed in the DMN (p_uncorrected = .04), but not the SN. Principal component analysis revealed 4 symptom dimensions, with connectivity between multiple brain networks extending beyond the SN and DMN associated with an intrusive thoughts/yearning/avoidance component.

Conclusions: Aberrant connectivity between the SN and DMN appears to be a neurobiological correlate of grief severity and avoidance in PGD. Broader between-network connectivity disruptions correlate with intrusive thoughts, yearning, and avoidance, warranting further investigations into the mechanistic role of brain network dysfunction in PGD.

Background: For most people, gambling is a type of entertainment that engages pleasure, risk, and reward drives. However, some individuals develop gambling disorder (GD), a behavioral addiction that involves continued gambling despite negative consequences. Disturbances in reward neurocircuitry have been implicated in GD but are not well characterized, including how neural alterations relate to the clinical symptomatology of GD and commonly co-occurring presentations such as depression.

Methods: Electroencephalography (EEG) was recorded while participants with GD (n = 26) and healthy control participants (HCs) (n = 54) completed a slot machine task. Event-related potential (ERP) components reflecting reward anticipation (stimulus preceding negativity [SPN]) and reward outcome evaluation (reward positivity [RewP], late positive potential [LPP]) were assessed. Within GD, we examined associations between reward ERPs and a clinical summary score that reflected greater problem gambling and depressive symptoms and lower global functioning.

Results: Compared with HCs, participants with GD had larger (more negative) SPN amplitudes to possible wins versus total-miss losses (t₇₈ = 2.45, p = .017), equivalent RewP amplitudes, and higher LPP amplitudes (F_1,78 = 9.08, p = .003) to both wins (t₇₈ = 2.90, p = .004) and near-miss losses (t₇₈ = 2.69, p = .004). More severe clinical symptomatology covaried with more negative SPN amplitudes (Spearman's rho = -0.523, p = .021, false discovery rate corrected) but not with RewP or LPP.

Conclusions: Individuals with GD showed larger neural responses during reward anticipation (SPN) and late-stage processing of reward outcomes (LPP). Exaggerated neural responses during reward anticipation were most pronounced among individuals with more severe clinical symptomatology. These findings suggest that excessive reward anticipation as well as heightened salience to outcomes, regardless of valence, are potential mechanisms underlying GD.

Background: Anxiety disorders may partly stem from altered neurodevelopment of attention-related networks. Neonatal alterations in resting-state functional connectivity (rsFC) among the dorsal attention network (DAN), frontoparietal network (FPN), salience network (SN), and default mode network (DMN) relate to fearful temperament, a risk marker for anxiety. Nevertheless, few studies have examined the development of these networks beyond the first months of life, particularly in fearful infants. In this study, we examined how changes in these networks during the first 2 years of life relate to fearful temperament.

Methods: Using data from the Baby Connectome Project (from 180 infants across 396 sessions), we conducted independent component analysis to extract rsFC among the DMN, SN, DAN, and FPN. Longitudinal modeling characterized 1) age-related changes (slope) in rsFC through age 2 years, 2) the relationship between rsFC change (slope) and fearfulness at age 2 years, and 3) the relationship between rsFC and fearfulness trajectories (slope and intercept) during the first 2 years of life.

Results: Age-related decreases occurred in DAN-FPN and DMN-SN rsFCs. Smaller decreases in DAN-FPN rsFC over time related to greater fear at age 2 and to increases in fearfulness over time. High initial DAN-FPN rsFC and low initial DAN-SN rsFC also related to increasing fearfulness over time.

Conclusions: This study provides the first evidence that changes in attention-related brain networks are related to early-life fearfulness, a robust early-life risk marker of anxiety.

Background: Humans prefer to make choices freely, even when doing so does not maximize future outcomes, which suggests that free choice is intrinsically rewarding. While value-based decision impairments are well documented in Parkinson's disease (PD), the mechanisms that underlie intrinsically motivated behavior remain unclear. In this study, we investigated how the dopaminergic (DAergic) and basal ganglia systems contribute to intrinsic reward in PD.

Methods: We designed a decision-making task to dissociate the intrinsic value of free choice from extrinsic reward. Twenty PD patients with subthalamic nucleus deep brain stimulation (STN-DBS) and 25 on DA therapy completed the task both while ON and OFF treatment. Performance was compared with 20 age-matched healthy control participants. We analyzed DBS electrode contacts, modeled activated tissue volumes, and examined cortico-subthalamic connectivity using high-resolution diffusion magnetic resonance imaging.

Results: PD patients OFF STN-DBS showed reduced preference for free choice, which increased when STN-DBS was ON. This effect was associated with recruitment of the right medial prefrontal cortex (mPFC). Acute ON/OFF DA therapy did not alter free-choice preference. However, patients with lower chronic DA doses-comparable to those in the DBS group-exhibited reduced free-choice preference compared with patients with higher chronic intake.

Conclusions: STN-DBS enhances free-choice preference by modulating the right mPFC-STN network, suggesting that this hyperdirect pathway influences intrinsic valuation of choice. These results indicate that STN-DBS promotes self-determined behavior even in risky contexts. Furthermore, chronic DAergic therapy may influence sensitivity to intrinsic reward.

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.