Biological psychiatry. Cognitive neuroscience and neuroimaging最新文献

Background: Differences in sensory processing are a defining characteristic of autism, affecting up to 87% of autistic individuals. These differences cause widespread perceptual changes that can negatively impact cognition, development, and daily functioning. Our research identified five sensory processing 'phenotypes' with varied behavioural presentations; however, their neural basis remains unclear. This study aims to ground these sensory phenotypes in unique patterns of functional connectivity.

Methods: We analyzed data from 146 autistic participants from the Province of Ontario Neurodevelopmental Network. We classified participants into five sensory phenotypes using k-means clustering of scores from the Short Sensory Profile. We then computed a connectivity matrix from 200 cortical and 32 subcortical regions and calculated graph-theoretic measures (betweenness centrality, strength, local efficiency, and clustering coefficient) to assess information exchange between these regions. We then trained machine learning models to use these measures to classify between all pairs of sensory phenotypes.

Results: Our sample was clustered into five sensory phenotypes. The machine learning models distinguished seven of the ten total pairs of sensory phenotypes using graph-theoretic measures (p < 0.005). Information exchange within and between the somatomotor network, orbitofrontal cortex, posterior parietal cortex, prefrontal cortex and subcortical areas was predictive of sensory phenotype.

Conclusions: Sensory phenotypes in autism correspond to differences in functional connectivity across cortical, subcortical, and network levels. These findings support the view that variability in sensory processing is reflected in measurable neural patterns and motivate continued work to refine models of sensory processing, with the goal of better understanding and capturing the heterogeneity implicit in autism.

Background: Major depressive disorder (MDD) is a highly prevalent psychiatric disorder marked by disrupted brain dynamics. However, the neural mechanisms underlying remission remain poorly understood, particularly regarding common neural markers across diverse therapeutic interventions. Emerging evidence suggests that temporal brain dynamics and their hierarchical organization, referred to as Metastates, serve as sensitive markers of individual variability across cognitive functions. This study evaluated whether Metastate dynamics derived from resting-state functional magnetic resonance imaging (fMRI) differ according to remission status across pharmacotherapy, psychotherapy, and neuromodulation.

Methods: This multicenter observational study included 370 participants: 229 individuals with depression and 141 healthy controls. The depression cohort comprised individuals undergoing cognitive behavioral therapy (n=92), pharmacotherapy (n=59), electroconvulsive therapy (n=50), and repetitive transcranial magnetic stimulation (n=28). Resting-state functional MRI data were analyzed to derive Metastate dynamics, and comparisons were made according to remission status across treatment modalities.

Results: Two distinct Metastates were identified: one associated with higher-order cognitive brain regions, and another linked to sensory and motor systems. Participants who achieved remission exhibited greater predictability in transitions between brain states within Metastates, supporting higher-order cognitive functions. This altered transition pattern was accompanied by alterations in the anti-correlation between the default mode and executive function networks, which may underlie the increased predictability.

Conclusions: Remission from MDD may involve a reorganization of hierarchical brain dynamics-particularly in systems supporting cognitive control-and offer a potential treatment-modality-independent biomarker of remission.

Background: Low socioeconomic status (SES) is associated with alterations in brain development and youth psychopathology risk. However, the mechanisms linking SES to neurodevelopment remain unclear. We tested whether pubertal timing and tempo mediate the association between SES and cortical thinning in adolescence, and whether these neurobiological processes predict socioeconomic disparities in internalizing symptoms.

Methods: Participants (N=2,949; 1,474 females) were drawn from the Adolescent Brain Cognitive Development study (ages 10 to 14). Latent growth models tested whether pubertal development mediated the relationship between SES (operationalized as household income-to-needs ratio) and cortical thickness development. A second model tested associations with internalizing symptoms at age 14. These pathways were investigated for males and females separately in both global and region-specific models.

Results: In females, low SES was associated with earlier pubertal timing and slower tempo (standardized β=-0.23 and β=0.30,p<.001), which predicted faster and slower cortical thinning, respectively. Overall, low SES was associated with faster cortical thinning (β=0.33,p=.012), partially mediated through earlier timing (β=0.20,p<.001) and slower tempo (β=-0.18,p=.001) of pubertal development. These opposing pathways were observed for both global and regional cortical measures, in areas associated with social cognition, emotion regulation, and self-referential processing. Earlier pubertal timing and faster cortical thinning partially mediated the link between SES and internalizing problems. In males, no significant indirect effects were observed globally, with few regional effects.

Conclusions: Findings suggest that pubertal development mediates the link between disadvantage and cortical development, in turn predicting adolescent psychopathology. These pathways may represent targets for early intervention in socioeconomically disadvantaged youth.

Background: Cognitive behavioral therapy (CBT) for pediatric anxiety targets heightened emotional sensitivity and impaired cognitive control over emotion, core neurocognitive features of anxiety. Exposure is considered the most active component of CBT, but its efficacy varies. Pretreatment function of substrates for emotion processing and cognitive control may predict response to exposure relative to other CBT subcomponents, like relaxation.

Methods: Clinically anxious youth (N = 118, 7-17 years) completed an fMRI task probing emotion processing and cognitive control, then were randomized to 12 sessions of exposure-focused CBT (EF-CBT) or relaxation management training (RMT). Voxelwise linear mixed-effects models tested how pretreatment whole-brain activation associated with symptom reduction over the course of treatment.

Results: EF-CBT led to greater symptom reduction than RMT. Better EF-CBT response was predicted by lower pretreatment activation in the left dorsolateral prefrontal cortex during emotion processing, and the bilateral dorsal anterior cingulate cortex and inferior parietal lobe during cognitive control of emotion. Conversely, these patterns associated with poorer outcomes of RMT. Direct comparisons revealed EF-CBT was more effective than RMT for youth with low and mean activation in all clusters, but not high activation.

Conclusion: EF-CBT outperformed RMT for youth with low-to-mean activation in regions supporting emotional appraisal, cognitive control, and threat attention, indicating these patterns may be biomarkers of exposure readiness. Conversely, high activation in these regions did not confer differential benefit, and may reflect hypervigilance or overcontrol that could interfere with exposure-based learning. These findings support the value of preparatory interventions to optimize treatment readiness and personalize delivery of exposure-based CBT.

Background: Bipolar disorder coincides with one of the highest rates of suicide out of all psychiatric conditions. Individual differences in stress reactivity may contribute to increased susceptibility to suicide-related thoughts and behaviors (STBs). Research examining stress response and relations with STBs in bipolar disorder is limited. The purpose of this study was to investigate associations between recent perceived stress and neurophysiological response to acute psychosocial stress in anterior-paralimbic system in young adults with bipolar disorder with and without suicide attempt history.

Methods: Seventy-two young adults (22 with bipolar disorder and history of suicide attempt(s) [BD-SA], 21 diagnostic controls without suicide attempt history [BD-noSA], 29 typically developing [TD]) were assessed for past-month perceived stress (PSS) and completed a fMRI stress math task. Stress-related functional changes in anterior-paralimbic regions of interest were examined in relation to PSS. Effects of lifetime alcohol/cannabis use disorder and nicotine use on stress reactivity were explored.

Results: In BD-SA young adults, recent perceived stress was associated with greater reactivity to psychosocial stress in the medial orbitofrontal cortex, anterior insula, amygdala, and anterior cingulate cortex (group-by-PSS interactions: p's<0.008). These patterns were not observed in the BD-noSA or TD groups. Lifetime CUD and recent nicotine use related to greater anterior-paralimbic responses to stress in bipolar disorder (p's<0.002).

Conclusions: Heightened anterior-paralimbic reactivity to cumulative stress may represent a risk factor for STBs. Cannabis and nicotine use may exacerbate stress-related anterior-paralimbic dysregulation. Future longitudinal research is needed to extend findings and investigate temporal relations between stress reactivity, cannabis/nicotine use, and STBs.

Background: Individual differences in reward learning and motivational processes are reflected in sign-tracking behavior. This phenotype, characterized by heightened attraction to reward-associated cues, is linked to increased impulsivity, addiction vulnerability, and externalizing psychiatric disorders.

Methods: To identify underlying neural differences, we tested whether high sign-tracking individuals exhibit an elevated mid-frontal theta/beta ratio, a resting EEG biomarker indicating reduced cortical control over subcortical motivational circuits. Sixty volunteers completed a 5-minute resting-state EEG session followed by a Pavlovian learning task. Participants were classified into high or low sign-tracking groups based on objective eye-gaze metrics.

Results: High sign-tracking participants demonstrated a significantly higher mid-frontal theta/beta ratio compared to the low sign-tracking group.

Conclusions: These findings identify the mid-frontal theta/beta ratio as a neural marker capable of distinguishing individual differences in reward cue reactivity. This suggests a pathway for targeted interventions aimed at the underlying cortical-subcortical dysregulation associated with sign-tracking and related vulnerabilities.

With a rapidly growing population of older adults worldwide, understanding how aging shapes mental and cognitive health is an urgent public health priority. Although older age has been considered protective against the development of posttraumatic stress disorder (PTSD), this pattern is far from universal. Emerging evidence indicates that older adults with a history of trauma may experience delayed-onset PTSD or a reemergence of symptoms after years of dormancy. In this review, we examine how age-related changes in the brain intersect with known PTSD mechanisms to influence trajectories of risk and resilience in later life. We focus on the canonical fear network-comprising the amygdala, hippocampus, and ventromedial prefrontal cortex-which is central to fear learning, memory, and emotion regulation. These regions are also highly vulnerable to aging and neurodegenerative processes, yet older adults remain underrepresented in both neurobiological and treatment studies of PTSD. We argue that the structural and functional aging of these systems may exacerbate difficulties with associative learning and emotional regulation, while also interacting with psychosocial stressors unique to aging. At the same time, age-related strengths (such as positivity bias) may promote resilience. These insights carry important implications for clinical care: existing empirically-supported psychotherapies may benefit from adaptations to account for age-related neural and cognitive shifts. A lifespan neuroscience framework is essential for identifying shared mechanisms between PTSD and aging, with the goal of informing tailored, mechanism-driven interventions that promote the mental and cognitive health of trauma-exposed older adults.

Background: Accumulating evidence points to the cerebellum's role in executive functioning (EF) and transdiagnostic psychopathology. A general psychopathology 'p-factor,' capturing shared variation across mental disorders, has been associated with EF deficits and structural alterations within the posterior cerebellum. One hypothesis is that the cerebellum contributes to general psychopathology because of its role in executive dysfunctions.

Methods: To test this hypothesis, we employed functional magnetic resonance imaging (fMRI) data from the UCLA Consortium for Neuropsychiatric Phenomics study including 257 adults (aged 21-50) who met diagnostic criteria for schizophrenia, bipolar, or attention deficit-hyperactivity disorders or were healthy controls. We examined relations between p-factor scores and cerebellar activation across participants during three fMRI tasks of working memory (Spatial Capacity), cognitive flexibility (Task-Switching), and response inhibition (StopSignal). Specificity analyses of cerebellar activation associated with internalizing, externalizing, and thought disorder factor scores also were conducted.

Results: Robust posterior cerebellar activation was identified during all three fMRI tasks. Higher p-factor scores were associated with poorer EF performance, greater activation of cerebellar Crus I/II and lobule VIIIA/B with increasing working memory difficulty, and greater activation of lobules VI and VIIIA/B during successful inhibition (R² range: 0.078-0.108). Associations between cerebellar activation and internalizing, externalizing, and thought disorder factor scores were largely overlapping with associations with the p-factor.

Conclusions: These novel results identify functional alterations within the posterior cerebellum during EF in individuals high in general psychopathology. Greater activation of the posterior cerebellum may be a transdiagnostic dysfunction reflecting inefficient information processing during EF present across disorder categories.

Background: Fear processing is multifaceted, involving dissociable neural and computational pathways that vary depending on its source and context. Yet, modality-specific fear processing, such as empathic versus subjective fear, remains poorly understood. Moreover, the role of these distinctions in clarifying the high comorbidity between generalized anxiety disorder (GAD) and major depressive disorder (MDD) has been understudied.

Methods: In the current study, we combined fMRI with multivariate pattern analysis to develop two neurofunctional models: one for empathic fear (FEFS, n = 81) and another for subjective fear (SSFS, n = 81) evoked by visual stimuli. After validating these models in the independent cohorts (dynamic stimuli: n = 28), we generalized them to distinguish GAD and MDD during facial emotional processing (n = 80) and pain empathy (n = 87) tasks.

Results: Our findings revealed that both models engaged distributed brain systems, including cortical regions (e.g., prefrontal, cingulate, insula and parietal cortices) and subcortical areas (e.g., thalamus and amygdala). Crucially, we identified distinct functional profiles: FEFS-predominant regions were linked to execution, whereas SSFS-predominant regions mapped onto emotion processing. Notably, compared to SSFS, FEFS consistently discriminated between GAD and MDD during both fearful expression and affective pain empathy processing.

Conclusions: These findings demonstrate modality-specific processing of subjective and empathic fear, revealing distinct empathy-related neural signatures that may serve as potential biomarkers for differentiating GAD and MDD, offering new insights into their neurobiological distinctions.

Background: Studies investigating social anxiety disorder (SAD) have reported inconsistent alterations in white matter (WM) microstructure. The ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis)-Anxiety Working Group investigated differences in the microstructure of 25 WM tracts between individuals with SAD and healthy control (HC) participants in a mega-analysis.

Methods: We analyzed data from 487 individuals with SAD and 1604 HC participants (ages 8-65 years) from 12 cohorts worldwide. Analyses and quality control were performed using standardized ENIGMA diffusion tensor imaging protocols. We primarily examined fractional anisotropy (FA) as the main parameter of WM microstructure. Linear mixed-effects analyses were conducted to compare individuals with SAD with HC participants in the total sample. Next, adult (age >21) and adolescent (age ≤21) samples were analyzed separately. In sensitivity analyses, additional effects of sex, medication, symptom severity, and comorbid psychiatric disorders were investigated.

Results: In the total sample, individuals with SAD showed lower FA in several tracts, including the corpus callosum and fornix, compared with HC participants. Widespread sex × diagnosis interactions were observed, mostly driven by lower FA in females with SAD. Adults with SAD showed lower FA in multiple tracts, while age × diagnosis interactions were observed in adolescents.

Conclusions: Using a mega-analytic approach, several differences in WM microstructure were found between individuals with SAD and HC participants, both in the full sample and in age group-specific sensitivity analyses. Some neurobiological changes in WM tracts in individuals with SAD may vary with age and sex, whereas others may relate to broader transdiagnostic neurobiological features underlying psychopathology. Further research should investigate these issues in more detail.