Biological psychiatry. Cognitive neuroscience and neuroimaging最新文献

Background: Familial high risk (FHR) is the strongest predictor of developing schizophrenia (SZ) and bipolar disorder (BP). Children at FHR uniquely allow for the identification of early brain markers of vulnerability. Previous studies have often spanned wide age ranges and neglected sex differences, despite evidence of distinct sex-specific brain developmental trajectories. We investigated sex-specific group differences in brain morphometry among 11- to 12-year-old children at FHR-SZ or FHR-BP.

Methods: This study included 278 children from VIA 11 (the Danish High Risk and Resilience Study): 101 FHR-SZ (51 boys), 64 FHR-BP (32 boys), and 113 population-based control (PBC) (57 boys) children. Structural magnetic resonance imaging scans were acquired on 3T scanners at 2 sites. Brain volume, cortical volume, surface area, and cortical thickness were extracted using FreeSurfer.

Results: Significant group-by-sex interactions were observed for brain, cortical, and intracranial volume and surface area (η² = 0.030-0.038, p = .006-.016). Boys at FHR-SZ exhibited smaller brain, cortical, and intracranial volume and surface area than PBC boys (Cohen's d = -0.677 to -0.489, p = .001-.015). Girls at FHR-BP had larger brain and cortical volumes than PBC girls (Cohen's d = 0.525 to 0.537, p = .017-.020). No significant differences were observed for cortical thickness (p > .210).

Conclusions: Children at FHR-SZ and FHR-BP exhibited sex-specific morphometric differences, potentially reflecting sex-specific endophenotypic markers of risk. Given the smaller size of the FHR-BP group, these findings should be interpreted cautiously. Nevertheless, our findings underscore the importance of considering sex as a factor in neurodevelopmental psychiatric research. Longitudinal studies are needed to track how these neuroanatomical differences evolve over time and to evaluate their predictive value for transition to SZ or BP.

Background: This preregistered functional magnetic resonance imaging study aimed to test and possibly extend the triple network hypothesis of psychosocial stress processing, positing that responses in the salience network (SN) and the default mode network (DMN) dominate at the expense of the central executive network (CEN). Furthermore, we tested the hypothesis that stress-related responses in SN and DMN structures are associated with hormonal, cardiovascular, and affective stress responses, while CEN and DMN structures are associated with task performance. We also examined sex-specific associations between neural and stress-induced cortisol, heart rate, and negative affect responses as well as task performance.

Methods: We reviewed all psychosocial stress studies and conducted a mega-analysis of ScanSTRESS datasets (n = 459; 222 female) with harmonized preprocessing.

Results: Our findings advanced the original hypothesis, revealing activations and deactivations across all 3 networks, related in a complex way to cortisol, heart rate, negative affect, and performance parameters. Additionally, we identified a novel age effect of increasing DMN activation with age, replicated an exposure-time effect of decreasing activation with duration, showed sex-specific patterns, and confirmed the involvement of all networks by task-based connectivity analyses.

Conclusions: Based on our findings we suggest a new, differentiated triple network hypothesis of psychosocial stress processing. Reactivity in SN and DMN structures is associated with hormonal, cardiovascular, and affective stress responses, whereas CEN and DMN structures process the stress-eliciting tasks. Moreover, the age effect may indicate that the ability to downregulate the DMN is reduced with age. Finally, we suggest that the exposure-time effect (decreasing signal within ScanSTRESS) may be a promising resilience biomarker.

Background: Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are associated with alterations in the functional connectome, specifically in canonical resting-state networks including the default mode network (DMN), central executive network (CEN), and salience network (SN). Comorbid PTSD+TBI is linked to worse functional outcomes, but little is known about effects on the functional connectome.

Methods: We investigated brain phenotypes from resting-state functional magnetic resonance imaging associated with PTSD (n = 326), mTBI (n = 448), and comorbid PTSD+mTBI (n = 289) in military veterans and civilians (N = 1526) from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis)-TBI and ENIGMA-PTSD studies. We examined static functional connectivity (FC) and dynamic functional connectivity (DFC), which we quantified both as variability in FC (VFC) over time and as dwell time in recurring FC states identified through clustering. Analysis of covariance was followed by post hoc linear regression analysis to test main and interaction effects of diagnosis on FC metrics.

Results: We found a significant (false discovery rate-corrected p < .05) interaction of diagnosis × age on VFC. Older participants with comorbid PTSD+mTBI had greater VFC within the SN, between the SN and CEN, and between the SN and DMN than older control participants. Compared with control participants, comorbid participants had significantly greater dwell time in an externally focused state. Participants in the comorbid and mTBI groups had greater dwell time in a moderate-connectivity transition state than control participants.

Conclusions: DFC related to the SN revealed distinct brain network patterns across diagnostic groups, with participants with comorbid PTSD+mTBI showing age- and anxiety-related effects. Older comorbid participants had heightened hypervigilance and reduced network segregation. PTSD and anxiety may synergistically worsen network instability, while mTBI reflects more rigid, disconnected states, highlighting DFC as a sensitive marker of neuropsychiatric comorbidity.

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: 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: 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.