Biological psychiatry. Cognitive neuroscience and neuroimaging最新文献

Objective: Obsessive-compulsive disorder (OCD) is associated with impaired executive function and altered activity in associated neural circuits, contributing to reduced goal-directed behavior. To investigate neural activation during executive funtion, we conducted a mega-analysis in the ENIGMA-OCD consortium pooling individual participant data from 475 individuals with OCD and 345 healthy controls across 15 fMRI tasks collected worldwide.

Methods: Individual participant data was uniformly processed using HALFpipe to construct voxelwise statistical images of executive processing and task load contrasts. Parameter estimates extracted from regions of interest were entered into multilevel Bayesian models to examine regional and whole-brain effects of diagnosis, and, within OCD, the influence of medication status, symptom severity, and age of onset on task activation.

Results: We observed a robust task activation pattern across individuals with OCD and control participants in executive processing regions across tasks. Relative to controls, individuals with OCD showed moderate to very strong evidence of weaker activation of the dorsolateral prefrontal cortex, precuneus, frontal eye fields, and inferior parietal lobule during executive function (all positive posterior probabilities [P+]<0.1). Individuals with OCD also showed stronger activation in regions of the default mode network during executive function relative to controls. We found little evidence for differential activation during executive function in task-positive regions related to disease onset, severity and medication status.

Conclusion: In the first mega-analysis of fMRI studies of executive function in OCD, we found strong evidence of weaker frontoparietal activation during executive function tasks. Our findings also suggest a failure of default mode network regions to appropriately disengage during task performance in OCD.

Background: Although subtle differences in cortico-striato-thalamo-cortical (CTSC) circuit structure and function are critical to the current understanding of the neurocircuitry in obsessive-compulsive disorder (OCD), emerging evidence suggests that the cerebellum may also be involved. However, much of this evidence comes from studies with small samples and notable methodological heterogeneity.

Methods: We conducted a mega-analysis of individual participant data on cerebellar sub-regional volumes, comparing individuals with OCD and healthy controls (HC) from the ENIGMA-OCD Working Group. 3D T1-weighted volumetric structural brain magnetic resonance imaging (MRI) scans from 1,954 individuals with OCD and 2,091 HC across 22 sites (40 datasets) were processed using the ACAPULCO (Automatic Cerebellum Anatomical Parcellation using U-Net Locally Constrained Optimization) pipeline to extract cerebellar parcellations. We harmonized the volume measures across sites using the ComBat algorithm. Multiple linear regression models were fitted to estimate group differences separately within the pediatric (<12 years), adolescent (12-18 years), and adult (from 18 years) samples, adjusting for age, gender, and intracranial volume (ICV).

Results: In adults with OCD (versus HC), we found significantly smaller volumes of the corpus medullare (d=-0.093, p_fdr=0.036), left VIIb (d=-0.085, p_fdr=0.039) and right VIIb (d= -0.091, p_fdr= 0.036). None of the comparisons between children or adolescents with OCD versus HC remained statistically significant after FDR correction. In all three age groups, cerebellar (subregional) volumes were significantly moderated by medication status.

Conclusions: We report novel findings implicating specific cerebellar sub-regions across developmental stages of OCD, and the key impact of medication status. Further research on the functional significance of these findings may offer new translational leads.

Background: Adolescence is a sensitive period for the emergence and refinement of cortical rhythms, which are shaped by excitatory-inhibitory (E/I) neurotransmission. However, stress-related disruptions in E/I balance may contribute to major depressive disorder (MDD). The aperiodic components of neurophysiological signals-slope and offset-index E/I dynamics and broadband power, respectively. Although altered E/I balance has been implicated in MDD and neurodevelopment more broadly, the role of aperiodic activity in predicting recurrence among adolescents remains unclear.

Methods: Resting-state electroencephalography (EEG) and structured stress interviews were acquired from adolescents (N=148; ages 13-18-years-old) with current (n=42) or remitted MDD (n=106). Aperiodic slope and offset were parameterized across anterior, central, and posterior electrode clusters. In remitted youth, Cox proportional hazards models tested slope- and offset-by-stress interactions predicting MDD recurrence over the subsequent 12 months.

Results: Adolescents with current MDD exhibited significantly flatter aperiodic slopes across anterior, central, and posterior clusters (Range F=4.56-5.82, ps<.05) and lower offsets in anterior and central clusters (Range F=5.38-7.25, ps<.023) compared to remitted adolescents. Among remitted youth, significant slope-by-stress interactions predicted recurrence, wherein flatter slopes were protective against recurrence under low stress but conferred elevated risk under high stress. This effect was strongest in the anterior cluster (Hazard Ratio=2.13, p<.001). The aperiodic offset did not predict recurrence.

Conclusions: The aperiodic slope may function as a neurophysiological diathesis that amplifies stress-related risk for depression recurrence. Findings support a diathesis-stress model of adolescent MDD and highlight the aperiodic slope as a biomarker that may guide developmentally sensitive personalized prevention strategies.

Background: Major Depressive Disorder (MDD) and Bipolar Disorder (BD) are associated with persistent cognitive deficits, yet the biological mechanisms underlying these impairments remain unclear. Metabolic dysfunction, particularly insulin resistance (IR), may contribute to brain structural alterations and cognitive decline. However, diagnosis-specific metabolic effects on gray matter volumes (GMV) and cognition were not fully explored. Partial Least Squares Path Modeling was applied to examine associations among metabolic biomarkers, GMV, and cognitive performance in mood disorders, stratifying by diagnosis.

Methods: 81 BD (F=55, M=26) and 78 MDD (F=45, M=33) inpatients underwent neuropsychological evaluation with the Brief Assessment of Cognition in Schizophrenia. T1-weighted MRI images were processed to extract GMV. Blood samples were collected to assess metabolic markers.

Results: In the whole sample, the metabolism latent construct negatively predicted both GMV and cognition, with the GMV factor positively affecting cognition. A significant diagnostic difference emerged for the metabolism-to-cognition path (p = 0.0196). Stratified analyses showed that in BD, metabolism was significantly associated with both reduced GMV and poorer cognition, whereas in MDD no significant structural paths were identified. IR markers and leptin were the strongest positive contributors to the metabolism factor in both the full sample and BD group. Brain regions most affected encompassed areas central to cognitive and emotional regulation, characterized by a high density of insulin and leptin receptors.

Conclusion: These findings highlight the role of IR and leptin in shaping cognition in mood disorders and underscore the potential of insulin-related pathways as therapeutic targets, especially in BD with metabolic comorbidities.

Background: Ibogaine was recently found to result in significant functional improvements in treating the sequelae of traumatic brain injury (TBI) among Special Operations Forces veterans (SOVs). In the present article, we use multimodal neuroimaging to elucidate the neural correlates of ibogaine in 30 male SOVs who received ibogaine treatment.

Methods: Arterial spin labeling and blood oxygen level-dependent functional magnetic resonance imaging data were collected before, immediately after ibogaine treatment, and at 1-month follow-up. A whole-brain exploratory analysis was conducted to examine the effects of ibogaine on resting-state regional cerebral blood flow (rCBF) and functional connectivity.

Results: The results revealed gradual increases in rCBF in the cortical, limbic, and striatal subregions, and changes in functional connectivity across a wide range of functional networks. The magnitude of treatment-induced rCBF changes in the left insula and left anterior cingulate cortex correlated significantly with improvements in TBI-related disability symptoms.

Conclusion: Our results suggest that ibogaine may involve widespread reorganization of functional connections in the brain, and that persisting regional changes in metabolic activity after ibogaine treatment, particularly within paralimbic brain regions, might be related to the observed therapeutic effects of ibogaine. Our findings serve to generate future hypotheses for larger, controlled neuroimaging studies of ibogaine in humans, necessary to validate these initial findings.

Background: Bipolar disorder (BD) has been associated with accelerated aging, but studies investigating Brain Age have yielded mixed results. This may reflect differences in methodology and model sensitivity.

Methods: We compared three publicly available Brain Age models (ENIGMA, PyBrainAge, Pyment) using T1-weighted MRI scans from 352 individuals with BD Type I and 327 controls across four sites. Predicted age difference (PAD) was calculated as Brain Age minus chronological age. We examined group differences, medication effects, and age-related patterns using linear mixed-effects models controlling for chronological age, sex, and scanner.

Results: PAD was higher in BD than controls across all models (PyBrainAge: +3.03 years; ENIGMA: +2.78 years; Pyment: +1.43 years; Cohen's d=0.26-0.36; all p<.001) with group differences more pronounced in participants ≥40 years. In region-based models, thalamic and ventricular volumes contributed most consistently to elevated PAD in BD. Across all models, lithium-treated BD participants showed no significant PAD elevation compared to controls (all p>.5), while non-lithium-treated participants exhibited significant elevation (+1.47-3.24 years all: p<.01). Within BD participants, mixed modeling of current any medication status, lithium treatment, and illness duration/severity measures showed current any medication status to be associated with increased PAD (+2.03-4.48 years; all: p<.05) whereas lithium use was associated with a 1.87-3.67-year reduction in PAD (all p<.05) and no associations were found with duration/severity metrics.

Conclusions: Our findings support the presence of elevated Brain Age in BD, lithium's suggested neuroprotective profile, and highlight the influence of the Brain Age model, MRI scanner, and other confounders on predictions.

Background: Magnetic resonance-guided focused ultrasound capsulotomy (MRgFUS-AC) is an experimental incisionless intervention for refractory obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). Although its clinical efficacy has been demonstrated, the longitudinal structural and microstructural brain changes it induces remain incompletely characterized.

Methods: A total of 33 patients with treatment-resistant obsessive-compulsive disorder (OCD, n = 14) or major depressive disorder (MDD, n = 19) underwent MRgFUS-AC targeting the ventral anterior limb of the internal capsule (ALIC). Diffusion and structural MRI were acquired preoperatively and at follow-up. White matter integrity was evaluated using probabilistic tractography, and cortical and subcortical volumes were quantified using the FreeSurfer longitudinal pipeline. Longitudinal changes were assessed with linear mixed-effects models.

Results: MRgFUS-AC produced small lesions (∼117 mm³) that regressed by over 80% within three months. Despite this, significant reductions in fractional anisotropy were observed along multiple cortico-thalamic and cortico-striatal tracts. Volume loss was detected in both cortical (medial orbitofrontal, inferior temporal, fusiform) and subcortical (bilateral caudate) regions, with more widespread effects in OCD. Smaller preoperative volume of the left pars triangularis predicted greater clinical improvement.

Conclusions: MRgFUS-AC induces measurable white matter and gray matter changes within fronto-striatal-thalamic circuits, even with small, regressing lesions. Structural effects were more pronounced in OCD than MDD. Preoperative imaging features may aid in stratifying response and optimizing individualized targeting strategies for psychiatric neurosurgery.

Background: Cognitive symptoms are among the core features of schizophrenia, but their underlying mechanisms remain unclear. Current hypotheses suggest that alterations in the frontal cortex cause network dysfunction, contributing to cognitive symptoms. Growing evidence links reactive astrocytes with cognitive function and the pathophysiology of schizophrenia. We aimed to investigate in vivo reactive astrocyte signals in the dysconnected networks underlying cognitive symptoms in patients with schizophrenia.

Methods: [¹⁸F]THK5351 positron emission tomography (PET) and resting-state functional MRI data were obtained from 32 patients with schizophrenia and 32 age- and sex-matched healthy controls. [¹⁸F]THK5351 PET was used to measure monoamine oxidase B, a marker of reactive astrocytes. We performed network analysis to identify dysconnected subnetworks related to cognitive symptoms and examined reactive astrocyte signals in these subnetwork regions.

Results: Patients showed impaired verbal learning (F = 18.97, p < 0.001) and memory (F = 24.31, p <0.001). In patients, reduced left medial orbitofrontal cortex (mOFC)-left dorsolateral prefrontal cortex and left mOFC-right dorsal anterior cingulate cortex connectivity predicted impaired verbal learning (β = 0.45, p = 0.011) and memory (β = 0.56, p = 0.001), respectively. The PET standardized uptake value ratio was greater in the left mOFC in patients than in controls (t = -2.61, p = 0.011).

Conclusions: We found evidence of increased reactive astrocyte activity in the key region of the dysconnected network underlying cognitive impairments in schizophrenia. These results suggest a potential link between reactive astrocytes in the mOFC and the pathophysiology underlying cognitive symptoms in schizophrenia.

Background: Effort-based decision making (EBDM) is a key component of motivation. Impairments in EBDM have been consistently linked to amotivation in individuals with schizophrenia (SZ). Similar deficits are seen in SZ and bipolar disorder (BD), despite striking differences in motivational profiles between the two disorders. Similar task behavior, but distinct motivational profiles, may arise from functional differences in brain regions supporting EBDM.

Methods: Twenty-eight veterans with SZ, 21 veterans with BD, and 30 healthy control participants completed a cognitive EBDM task during functional magnetic resonance imaging scanning. Participants chose between an easy and a more effortful working memory task. Reward values were manipulated to bias the participant toward choosing the more effortful task or the easier task or were relatively unbiased.

Results: Participants with SZ spent less time deliberating on unbiased trials and exhibited reduced task-related activation in the anterior cingulate cortex (ACC), anterior insula, and dorsolateral prefrontal cortex compared with participants in the healthy control and BD groups. Greater activation to hard-task biased trials relative to unbiased or biased toward easy task trials in the striatum, ventromedial prefrontal cortex, and posterior cingulate cortex was associated with motivation deficits in SZ but lower amotivation in BD.

Conclusions: Hypoactivation in response to the task in the ACC and other regions was found in the SZ group. Associations found between activation in several brain regions underlying EBDM and clinical amotivation suggest that distinct neurobehavioral processes contribute to motivational deficits in SZ and BD.

Background: Adverse Childhood Experiences (ACE) represent a strong influence on the developing brain, profoundly affect corticolimbic circuits, contributing to vulnerability for mental disorders. Individual differences in resilience-related behavior, such as physical activity, may mitigate these effects.

Methods: This retrospective study examined whether self-reported lifetime physical activity (LPA) modulates the relationship between ACE and resting-state functional connectivity (rs-FC) of key limbic regions among 75 adults (mean age = 31.8 years, 82.7% female). Interaction models (ACE × LPA) were constructed for seed-to-voxel analyses, using, the amygdala, hippocampus, and anterior cingulate cortex, as seeds. Significant clusters were extracted and subjected moderation analyses, and The Johnson-Neyman technique was used to determine sample-specific LPA ranges where the association between ACE and connectivity became statistically significant.

Results: Significant ACE × LPA interactions were observed across all three seed regions, with robust clusters located in subcortical-cerebellar, visual association, and motor networks. Across clusters, greater ACE exposure was associated with reduced connectivity at lower LPA levels, but increased connectivity at high levels, indicating a crossover moderation pattern. The Johnson-Neyman technique identified LPA ranges (∼150-390 min/week) where ACE effects on connectivity were statistically significant.

Conclusions: LPA moderated the association between ACE and rs-FC within emotion- and sensorimotor-related networks. Higher activity levels were linked to connectivity profiles consistent with potential neural resilience to early adversity. These findings highlight physical activity as a modifiable lifestyle factor associated with neurobiological adaptation following early adversity.