Nanfang Pan

Emerging evidence indicates that the neuropathology of attention-deficit/hyperactivity disorder (ADHD) extends beyond localized anomalies, and graph theoretical approaches provide interpretable indices for characterizing network-level organization. However, reported alterations of topological measures in ADHD remain inconsistent across studies, making it difficult to determine their overall direction and magnitude through individual studies. Here, we conducted a systematic search and identified 31 eligible MRI datasets, including 14 structural network studies (459 ADHD individuals; 460 controls) and 17 functional network studies (975 ADHD individuals; 1287 controls). A random-effects meta-analysis was performed to examine global topological patterns, and nodal signatures were explored using coordinate-based neuroimaging meta-analysis. Individuals with ADHD demonstrated significantly reduced global efficiency (Hedge’s g = -0.31; p = .010) in structural networks, whereas functional networks did not display significant global alterations. No nodal findings survived multiple-comparison correction; however, exploratory analyses at an uncorrected threshold suggested centrality alterations in key regions, including the caudate (Z = -3.60) and putamen (Z = -3.11) in structural networks, and the caudate (Z = 3.50), orbitofrontal cortex (Z = -3.41), and precuneus (Z = -3.58) in functional networks. In conclusion, reduced structural global efficiency suggests compromised capacity for brain-wide information integration in ADHD. Exploratory nodal analyses suggest that abnormalities in ADHD may extend beyond global network organization to specific regional topological features.

Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ) are severe psychiatric disorders with distinct and overlapping clinical and neurobiological features. Despite extensive evidence of brain structural abnormalities, the transdiagnostic neuropathological mechanisms remain poorly understood. A comprehensive literature search was performed for voxel-based morphometry (VBM) studies reporting altered gray matter volume (GMV) in MDD, BD or SZ. A transdiagnostic meta-analysis was conducted to identify common and disorder-specific GMV alterations using the Seed-based d Mapping toolbox. Disease epicenter and buffering mapping were further investigated using a normative functional connectome to understand the network-constrained GM atrophy patterns. A total of 221 studies (MDD: n = 66; BD: n = 59; SZ: n = 96) encompassing 10,485 patients and 12,128 healthy controls were included. Transdiagnostic GMV reductions were identified in the medial prefrontal cortex and superior temporal gyrus. Less atrophy in the limbic/paralimbic regions and temporoparietal junction were observed for MDD, whereas SZ patients exhibited more pronounced GMV reductions in these areas. The ventrolateral prefrontal cortex emerged as a shared disease epicenter and the precuneus as a common buffer across these affective and psychotic disorders. The visual and dorsal attention networks exhibited the most pronounced buffering effects, while epicenter effects were primarily concentrated within the limbic, frontoparietal, subcortical and default mode networks. These findings suggested that affective and psychotic disorders are characterized by both shared and unique network-constrained GM atrophy patterns, which might advance precision diagnostics and inform targeted therapeutic strategies in the future.

Attention-deficit/hyperactivity disorder (ADHD) is thought to result from aberrant neurodevelopmental wiring of connectome architecture, yet the precise mechanisms underpinning this miswiring remain unclear. Here, we used a generative mathematical model to understand how physical and geometric constraints on brain network development might be altered in the disorder. Leveraging multisite diffusion magnetic resonance imaging (dMRI) datasets comprising 713 ADHD children and 304 neurotypical controls (aged 6-18 years), we fitted the recently developed geometric eigenmode model (GEM) to individual data describing connectivity between each pair of cortical regions, as quantified using probabilistic tractography. Replicating past work, the GEM was able to recover both topological and topographical properties of the empirical connectomes, but reconstruction accuracy was lower in ADHD children, suggesting a relative untethering of connectome architecture from geometric constraints. This untethering was particularly salient for long-range connections, which were disproportionately affected in the ADHD cohort. Regional variations in the degree to which connectivity was untethered from geometry were correlated with spatial maps of cortical developmental expansion, myelination, and transcriptomic organization, consistent with a neurodevelopmental basis for geometric untethering that is spatially patterned along the cortical hierarchy. Together, these findings suggest that aberrant neurodevelopment in ADHD may untether connectome development from typical geometric and physical constraints, resulting in subtle disruptions of long-range inter-regional connectivity.

Emerging evidence indicates that the neuropathology of attention-deficit/hyperactivity disorder (ADHD) extends beyond localized anomalies, and graph theoretical approaches provide interpretable indices for characterizing network-level organization. However, reported alterations of topological measures in ADHD remain inconsistent across studies, underscoring the need for a quantitative synthesis. We conducted a systematic search and identified 31 eligible datasets, including 14 structural network studies (459 ADHD individuals; 460 controls) and 17 functional network studies (975 ADHD individuals; 1287 controls). A random-effects meta-analysis was performed to examine global topological patterns, and nodal signatures were explored using coordinate-based neuroimaging meta-analysis. Individuals with ADHD demonstrated significantly reduced global efficiency (Hedge’s g = -0.31; p = .010) in structural networks, whereas functional networks did not display significant global alterations. No nodal findings survived multiple-comparison correction; however, exploratory analyses at an uncorrected threshold suggested centrality alterations in key regions, including the caudate (Z = -3.60) and putamen (Z = -3.11) in structural networks, and the caudate (Z = 3.50), orbitofrontal cortex (Z = -3.41), and precuneus (Z = -3.58) in functional networks. Together, reduced structural global efficiency suggests compromised capacity for brain-wide information integration in ADHD, while these spatially convergent nodal patterns may reflect altered network centrality. This configuration aligns with atypical network development in ADHD, and points to the involvement of regions linked to cognitive control and internally oriented processing.

Background: Bipolar I disorder (BD) is associated with reduced white matter microstructural integrity in the uncinate fasciculus (UF), a primary fiber tract connecting frontolimbic systems. Although familial history for BD, attention‐deficit/hyperactivity disorder (ADHD), and psychostimulants are important risk factors implicated in BD pathoetiology, their impact on UF microstructure remains poorly understood. Methods: This diffusion tensor imaging study investigated UF microstructural integrity prior to and following 12 weeks of psychostimulant treatment in ADHD youth with (‘high‐risk’, HR) and without (‘low‐risk’, LR) a first‐degree relative with BD. Healthy controls were included for comparative purposes. LR youth received 12‐week open‐label mixed amphetamine salts‐extended release (MAS‐XR), and HR youth were randomized to either MAS‐XR or placebo (PLA). Bilateral UF fractional anisotropy (FA) and axial diffusivity (AD) were assessed using automated fiber quantification. Results: A total of 137 participants were included in the analyses. At baseline, there were no significant group differences in bilateral UF microstructural metrics. Following 12‐week MAS‐XR treatment, significant group‐by‐time interactions were found for left UF FA and AD between HR‐MAS and LR‐MAS, as well as for left UF FA between HR‐MAS and HR‐PLA. Specifically, left UF FA and UF AD decreased significantly in HR‐MAS but remained unchanged in LR‐MAS and HR‐PLA groups. At week 12, left UF FA was lower in HR‐MAS relative to HC but not in LR‐MAS or HR‐PLA. Segment‐wise analyses further revealed that UF microstructural changes in the HR‐MAS group were localized to the anterior segments. Conclusions: These results suggest that HR‐ADHD youth are uniquely vulnerable to reductions in left UF microstructural integrity following psychostimulant treatment, suggesting potential relevance to BD pathoprogression.

The COVID-19 pandemic has posed an unprecedented threat to global health. However, neural substrates underlying mental health vulnerabilities brought by the pandemic remain elusive. We conducted a systematic review relating structural and functional brain abnormalities to mental health issues associated with COVID-19 at brain regional and network levels. A literature search on neuroimaging studies of mental health problems derived by COVID-19 was conducted in the PubMed, Web of Science and MEDLINE databases. We identified 46 studies across various imaging techniques and found that COVID-19-related mental health problems were principally associated with brain structural and functional alterations in the prefrontal cortex, insula, cingulate, hippocampus, and amygdala, as well as the affective cortical network. This review may facilitate the targeted development of therapies tailored to the pandemic context and provide insights for proactive prevention against future collective stressors and traumas.

Background: Psychostimulants and nonstimulants have partially overlapping pharmacological targets on attention-deficit/hyperactivity disorder (ADHD), but whether their neuroimaging underpinnings differ is elusive. We aimed to identify overlapping and medication-specific brain functional mechanisms of psychostimulants and nonstimulants on ADHD.Methods: After a systematic literature search and database construction, the imputed maps of separate and pooled neuropharmacological mechanisms were meta-analyzed by Seed-based d Mapping toolbox, followed by large-scale network analysis to uncover potential coactivation patterns and meta-regression analysis to examine the modulatory effects of age and sex.Results: Twenty-eight whole-brain task-based functional MRI studies (396 cases in the medication group and 459 cases in the control group) were included. Possible normalization effects of stimulant and nonstimulant administration converged on increased activation patterns of the left supplementary motor area (Z = 1.21, p < 0.0001, central executive network). Stimulants, relative to nonstimulants, increased brain activations in the left amygdala (Z = 1.30, p = 0.0006), middle cingulate gyrus (Z = 1.22, p = 0.0008), and superior frontal gyrus (Z = 1.27, p = 0.0006), which are within the ventral attention network. Neurodevelopmental trajectories emerged in activation patterns of the right supplementary motor area and left amygdala, with the left amygdala also presenting a sex-related difference.Conclusions: Convergence in the left supplementary motor area may delineate novel therapeutic targets for effective interventions, and distinct neural substrates could account for different therapeutic responses to stimulants and nonstimulants.