Biological psychiatry. Cognitive neuroscience and neuroimaging最新文献

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.

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 (FC) 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 2 functional magnetic resonance imaging (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 FC 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 FC patterns observed during the MA and placebo conditions, identifying connections overlapping with networks related to arousal.

Conclusions: Together, these findings are consistent with previous work on other psychostimulants such as 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 used a dynamic systems approach to investigate patterns of simultaneous RSN activation-i.e., coactivation-in 867 participants, including 487 healthy control participants (HCs), 175 patients with current MDD (cMDD), and 205 patients with remitted MDD (rMDD) from the Marburg-Münster Affective Disorders Cohort Study. Using a pairwise maximum entropy model, we estimated RSN coactivation probabilities based on resting-state fMRI data of 7 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 coactivation.

Results: General linear models revealed elevated coactivation probabilities in cMDD, particularly for states involving the DMN, FPN, and VIS, with the coactivation state involving the DMN, VIS, DAN, FPN, and LAN showing the strongest association with MDD diagnosis, clinical status, and symptom severity. Furthermore, canonical correlation analysis (CCA) on the total sample identified 2 distinct network-symptom profiles: canonical variate (CV) 1 linked high DMN and DAN coactivation probabilities to cognitive, insomnia, and mood/anhedonia symptoms, while CV2 tied the 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 coactivation, pointing to altered dynamic network organization. Further, the results 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, but the 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 nonsystematic decision making) during both physical and cognitive ECDM in 5 diagnostic groups: healthy control (n = 90), schizophrenia spectrum disorder (SSD) (n = 67), current major depression (n = 70), remitted major depression (n = 52), and bipolar I disorder (n = 64). We examined the associations between ECDM phenotype, cognitive functioning, motivation, and diagnostic group.

Results: We found significant diagnostic group differences in the ECDM phenotype, such that individuals with an SSD, but not current or remitted major depression or bipolar disorder, were less likely to incorporate changing trialwise reward value information in cognitive effort exertion, with the same trend for physical effort. In all diagnostic groups, nonsystematic decision making was associated with lower cognitive functioning but not lower motivation. In addition, individuals with an SSD 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 with in mood disorders.

Background: Neuroimaging methods rely on models of neurovascular coupling that assume hemodynamic responses are canonical, evolving seconds after changes in neural activity. However, emerging evidence reveals noncanonical blood oxygen level-dependent (BOLD) responses that are delayed under stress and aberrant in neuropsychiatric conditions.

Methods: We simultaneously recorded electroencephalography (EEG) and functional magnetic resonance imaging data in people with schizophrenia (n = 57) and psychiatrically unaffected participants (n = 46) during a resting-state paradigm. We focused on alpha band power to examine correlations with voxelwise, time-lagged BOLD signals as a dynamic measure of EEG-BOLD coupling.

Results: We found pronounced diversity in the temporal profile of alpha-BOLD coupling across the brain. This included early coupling (0-2 seconds BOLD lag) for more posterior regions of the default mode network (DMN), thalamus, and brainstem. Anterior regions of the DMN showed coupling at more canonical lags (4-6 seconds), although some participants showed greater than expected lags associated with self-reported measures of stress and there were greater lag scores in participants with schizophrenia. Overall, noncanonical alpha-BOLD coupling is widespread across the DMN and other noncortical regions and is delayed in people with schizophrenia.

Conclusions: These findings suggest that hemodynamic signals are dynamically coupled to ongoing neural activity across distributed networks and that the hemoneural lag may be associated with subjective arousal or stress. Our work highlights the need for more studies of neurovascular coupling in psychiatric conditions.

Background: Major depressive disorder (MDD) with comorbid anxiety presents significant treatment challenges, with high relapse rates and suboptimal outcomes. Transcranial direct current stimulation (tDCS) offers a scalable, noninvasive intervention targeting neural dysfunction in the frontoparietal-amygdala circuitry implicated in anxious depression. In this study, we investigated the acute effects of tDCS on multilevel (neural, behavioral, and physiological) measures of threat sensitivity in individuals with anxious depression.

Methods: A double-blinded, parallel, randomized trial enrolled 141 participants (78% female, mean age 36.2 years) who met MDD criteria and had elevated anxiety (Overall Anxiety Severity and Impairment Scale ≥ 7). Participants received a 30-minute session of active (2 mA) or sham tDCS targeting the bilateral dorsolateral prefrontal cortex during functional magnetic resonance imaging. Neural responses to emotional face distractors were assessed using an attentional load paradigm. Fear-potentiated startle and anxiety-potentiated startle (APS) were measured via electromyography during the None, Predictable, Unpredictable threat task.

Results: Active tDCS increased activation in the bilateral inferior frontal gyrus and mid-cingulate and parietal cortex (η_p² = 0.44-0.78) under high attentional load and improved task accuracy (Cohen's d = 0.52) and reaction times (Cohen's d = 0.58). Unexpectedly, active tDCS heightened amygdala response under low attentional load (η² = 0.02), APS responses (partial η² = 0.07), and increased anxiety ratings (partial η_p² = 0.001).

Conclusions: tDCS enhanced executive function and task engagement, as evidenced by improved accuracy, reaction times, and frontal activation. However, it failed to reduce threat sensitivity as hypothesized. Contextual interventions engaging target circuits during stimulation may optimize tDCS efficacy as an adjunctive treatment for anxious depression. Future studies should explore synergistic therapeutic approaches.

Background: In vivo neuroimaging studies documenting the relationship between dopamine and γ-aminobutyric acid (GABA) or glutamate in schizophrenia are scarce and frequently involve patients in chronic phases of the disorder, which complicates distinguishing medication effects from illness progression.

Methods: We examined the contrast ratio of neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a proxy of dopaminergic function, in the substantia nigra and ventral tegmental area (SN-VTA) and its association with striatal and medial prefrontal GABA and the sum of glutamate and glutamine (Glx), measured by proton magnetic resonance spectroscopy, in 23 never-medicated first-episode psychosis (FEP) patients and 22 age- and sex-matched healthy controls. All participants were recruited at the Instituto Nacional de Neurología y Neurocirugía in Mexico City. All imaging studies were performed on a 3T MRI scanner.

Results: Among participants, the SN-VTA NM-MRI contrast in the substantia nigra showed a positive correlation with Glx in the striatum; striatal GABA levels were not associated with NM-MRI contrast. In the medial prefrontal cortex, we failed to identify correlations between Glx or GABA with NM-MRI contrast.

Conclusions: The present study provides preliminary evidence of the association between striatal glutamate and a novel validated proxy for dopaminergic function in antipsychotic-naïve FEP individuals. Future research, using a longitudinal design, on these combined MRI biomarkers as predictors of treatment response is warranted.

Background: Following the collapse of the World Trade Center (WTC), many people experienced severe trauma and 23% of WTC responders developed post-traumatic stress disorder (PTSD). We hypothesized gray-white contrast (GWC) would be different between participants with PTSD when compared to demographically matched trauma-exposed controls with no history of PTSD.

Methods: T1-weighted structural images for 99 WTC responders collected on a 3T Siemen's magnetic resonance imaging were retrieved and segmented to measure global, regional, and voxel-wise GWC. Group-level analyses adjusted for the false discovery rate (FDR=0.05). Area under the receiver-operating curve was reported (AUC). To determine correlates of PTSD, we also measured PTSD symptom severity and several putative neuroimaging measures linked to PTSD including cortical fractal dimensions, cortical free water fraction, characteristic path length and cerebral/cerebellar cortical thickness.

Results: WTC responders with PTSD exhibited reduced cerebral GWC globally (D=0.47, SE = 0.20, P=0.022), while vertex-wise results showed focal differences lobes (FDR<0.05) in the frontal, temporal, and parietal lobes. Among participants with PTSD, analyses identified correlations that passed FDR correction linking GWC with overall PTSD symptom severity (ρ=-0.24) that were strongest when examining re-experiencing symptom severity (ρ=-0.28) and when examining GWC in the Pars Triangularis (ρ=-0.37). GWC was not associated with cortical fractal dimensions, cortical free water fraction, characteristic path length or cerebral/cerebellar cortical thickness.

Conclusions: Results support emerging research suggesting that PTSD is associated with changes to intracortical health. If replicated, changes in GWC might provide novel treatment targets and could help to support diagnosis in research studies.

Background: It is important to unveil factors that differentiate persistent and distressing psychosis-like experiences (PLEs) in youth from more normative transient, nondistressing PLEs, as the former have been associated with greater symptom, cognitive, and functional impairment and psychopathology risk, including risk for psychosis. In this study, we examined 1) whether certain baseline latent profiles can differentiate PLE groups (persistent/transient, distressing/nondistressing) and 2) whether baseline profile membership predicts psychopathology symptoms and academic/social functioning at follow-up.

Methods: Latent profile analyses were conducted on the ABCD (Adolescent Brain Cognitive Development) Study baseline sample (N = 11,724; mean age = 9.91; 47.8% female) using biological, cognitive, clinical, and sociodemographic indicators. Generalized mixed-effects models predicted PLE group, grades, several mental health symptoms, mental health treatment seeking, and social problems at follow-up.

Results: From the final 6-profile solution, 2 profiles emerged as potentially pertinent to the emergence of clinically relevant PLEs. Both profiles were characterized by higher externalizing symptoms, goal-motivated behavior, and likelihood of psychosis family history, but one profile had broader psychopathology elevations including affective dysregulation, while the other profile had low neurocognitive scores, brain patterns more like those found in schizophrenia, and greater socioeconomic disadvantage. At follow-up, both profiles were linked to more persistent distressing PLEs than the other profiles and showed shared and differential associations with outcomes.

Conclusions: The 2 profiles most predictive of persistent distressing PLEs may represent youth at risk for psychosis through different pathways, a neurodevelopmental pathway linked to cognitive and environmental vulnerability and an affective pathway associated with genetic risk, stress reactivity, and emotion dysregulation.