Biological psychiatry. Cognitive neuroscience and neuroimaging最新文献

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-Anxiety Working Group investigated differences in microstructure of 25 WM tracts between individuals with SAD and healthy controls in a mega-analysis.

Methods: We analyzed data from 487 individuals with SAD and 1,604 healthy controls (HC) (age 8 - 65) from twelve cohorts worldwide. Analyses and quality control were performed using standardized ENIGMA diffusion tensor imaging (DTI)-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 in the full 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 full sample, individuals with SAD showed lower FA in several tracts, including the corpus callosum and fornix, when compared to HC. Widespread sex-by-diagnosis interactions were observed, mostly driven by lower FA in SAD females. Adults with SAD showed lower FA in multiple tracts, while age-by-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, both in the full sample and in age-group specific sensitivity analyses.

Background: The structure and tissue composition of the cortex may be sensitive to loss of synapses. However, the relation between measurements of synaptic density, cortical thickness and microstructure remains unknown. These measures are reduced in schizophrenia spectrum disorders (SSD) and to a lesser degree in unaffected relatives. Here, we investigated if synaptic density and cortical (micro)structure are related in healthy subjects, and if these associations are altered in patients with SSD and unaffected siblings.

Methods: Brain uptake of the tracer [¹¹C]UCB-J, measured in-vivo with positron emission tomography (PET) was used as a proxy measure for synaptic density. Healthy subjects (n=25), patients with SSD (n=24) and unaffected siblings (n=25) underwent [¹¹C]UCB-J PET, T1-weighted MRI and diffusion weighted imaging scans.

Results: We found a positive relation between [¹¹C]UCB-J BP_ND and cortical thickness (β=0.61, p=.02) and showed a similar (yet non-significant) positive relation in unaffected siblings (β=0.41, p=.09). This relation was not present in patients with SSD (β=0.03, p=.90). Additionally, [¹¹C]UCB-J BP_ND had a negative relation with mean diffusivity (MD) in controls (β=-0.54, p=.01) and unaffected siblings (β=-0.47, p=.01). In patients with SSD, again, this relation was disrupted (β=0.07, p=.78).

Conclusion: We found a robust association between synaptic density and cortical (micro)structure in healthy individuals. The lost relation in patients suggest that SSD-related synapse loss is not proportional to the number and organization of grey matter constituents. Despite the shared genetic risk, unaffected siblings preserve this relation, suggesting absence of a second hit inducing excessive synaptic pruning.

Background: Between-subjects studies suggest that psychostimulants can shift whole-brain functional connectivity toward patterns linked to heightened sustained attention. In this study, we examined how a single dose of methamphetamine (MA, 20 mg) changes sustained attention and associated network-level functional organization in healthy adults.

Methods: We conducted a within-subject study in which 76 healthy participants completed two fMRI scanning sessions after taking MA or placebo. We tested whether MA selectively affects behavioral and fMRI connectivity signatures of sustained attention and arousal.

Results: Under MA, participants showed improved sustained attention task performance as well as functional connectivity signatures of higher sustained attention and arousal. These network changes emerged consistently across resting-state and task-based fMRI, indicating that MA influences attention- and arousal-related networks regardless of cognitive context. Furthermore, a support vector classifier distinguished functional connectivity patterns observed during the MA and placebo conditions, identifying connections overlapping with networks related to arousal.

Conclusions: Together, these findings align with prior work on other psychostimulants like methylphenidate, showing that MA modulates sustained attention and related large-scale brain networks. By revealing how MA modulates attention-relevant brain connectivity patterns, our results highlight the utility of psychostimulants as causal tools for probing the robustness, generalizability, and interpretability of brain-based biomarkers of behavior.

Background: Major depressive disorder (MDD) involves subtle, distributed alterations across multiple large-scale resting-state brain networks (RSNs), highlighting the need for integrative approaches to uncover synergistic network patterns driving clinical symptoms.

Methods: In this study, we employed a dynamical systems approach to investigate patterns of simultaneous RSN activation - i.e. co-activation - in 867 participants, including 487 healthy controls (HC), 175 patients with current MDD (cMDD), and 205 with remitted MDD (rMDD) from the Marburg-Münster Affective Disorders Cohort Study. Using a pairwise Maximum Entropy Model, we estimated RSN co-activation probabilities based on resting state fMRI data of seven RSNs-default mode network (DMN), frontoparietal network (FPN), sensorimotor network (SMN), visual network (VIS), salience network, dorsal attention network (DAN), and language network (LAN)-capturing 128 possible states of co-activation.

Results: General linear models revealed elevated co-activation probabilities in cMDD, particularly for states involving DMN, FPN, and VIS, with the co-activation state involving DMN, VIS, DAN, FPN, and LAN showing the strongest association with MDD diagnosis, clinical status, and symptom severity. Canonical Correlation Analysis (CCA) on the full sample further identified two distinct network-symptom profiles: Canonical variate (CV) 1 linked high DMN and DAN co-activation probabilities to cognitive, insomnia, and mood/anhedonia symptoms, while CV2 tied SMN and VIS to cognitive and somatic symptom domains.

Conclusions: These results demonstrate that MDD, especially during acute episodes, is marked by a dominance of DMN, FPN, and VIS co-activation, pointing to altered dynamic network organization. They highlight how changes in brain state dynamics are linked to MDD symptoms.

Background: Effort-cost decision-making (ECDM) is a core component of motivational deficits across diagnostic boundaries, yet mechanisms underlying ECDM deficits are not yet fully understood. Importantly, similar behavioral phenotypes during ECDM paradigms may be associated with distinct underlying cognitive and affective processes across individuals.

Methods: We used a person-centered modeling approach to examine individual decision-making phenotypes (systematic or non-systematic decision-making) during both physical and cognitive ECDM in 5 diagnostic groups: healthy control (N=90), schizophrenia-spectrum disorder (N=67), current major depression (N=70), remitted major depression (N=52), and bipolar I disorder (N=64). We examined the association between ECDM phenotype, cognitive functioning, motivation, and diagnostic group.

Results: We found significant diagnostic group differences in ECDM phenotype, such that individuals with a schizophrenia-spectrum disorder, but not current or remitted major depression or bipolar disorder, were less likely to incorporate changing trial-wise reward value information in cognitive effort exertion, with the same trend for physical. Across all diagnostic groups, non-systematic decision-making was associated with lower cognitive functioning, but not lower motivation. In addition, individuals with a schizophrenia-spectrum disorder showed steeper effort discounting during both physical and cognitive ECDM paradigms.

Conclusions: These findings point toward substantial individual differences in ECDM phenotypes both within and across diagnostic boundaries, suggesting that deficits in subjective value representation may be more prevalent in psychosis, compared to in mood disorders.