A shared effect of paroxetine treatment on gray matter volume in depressive patients with and without childhood maltreatment: A voxel-based morphometry study.

AIMS: This study assessed whether antidepressant drug treatment has a common effect on gray matter (GM) volume in MDD patients with and without childhood maltreatment (CM). METHODS: T1-weighted structural magnetic resonance imaging data were collected from 168 participants, including 51 MDD patients with CM, 31 MDD patients without CM, 48 normal controls with CM, and 38 normal controls without CM. MDD patients received 6 months of treatment with paroxetine, and 24 patients with CM, and 16 patients without CM received a second MRI scan. A whole-brain voxel-based morphometry approach was used to estimate GM volume in each participant at two time points. Two-way analysis of variance (ANOVA) was used to determine the effects of MDD and CM on GM volume at baseline. Repeated measures two-way ANOVA was used to determine the treatment-by-CM interactive effect and main effect of treatment during paroxetine treatment. We further investigated the relationship between GM volume and clinical variables. RESULTS: At baseline, significant MDD-by-CM interactive effects on GM volume were mainly observed in the left parahippocampal gyrus, left entorhinal cortex, and left cuneus. GM volume was significantly lower mainly in the right middle temporal gyrus in patients with MDD than in normal controls. We did not find any significant treatment-by-CM interactive effects. However, a treatment-related increase in GM was found in the right middle temporal gyrus in both MDD groups. CONCLUSIONS: These results suggest that paroxetine treatment operates via a shared neurobiological mechanism in MDD patients with and without CM.

Test-retest reliability of graph metrics in high-resolution functional connectomics: a resting-state functional MRI study.

BACKGROUND: The combination of resting-state functional MRI (R-fMRI) technique and graph theoretical approaches has emerged as a promising tool for characterizing the topological organization of brain networks, that is, functional connectomics. In particular, the construction and analysis of high-resolution brain connectomics at a voxel scale are important because they do not require prior regional parcellations and provide finer spatial information about brain connectivity. However, the test-retest reliability of voxel-based functional connectomics remains largely unclear. AIMS: This study tended to investigate both short-term (∼20 min apart) and long-term (6 weeks apart) test-retest (TRT) reliability of graph metrics of voxel-based brain networks. METHODS: Based on graph theoretical approaches, we analyzed R-fMRI data from 53 young healthy adults who completed two scanning sessions (session 1 included two scans 20 min apart; session 2 included one scan that was performed after an interval of ∼6 weeks). RESULTS: The high-resolution networks exhibited prominent small-world and modular properties and included functional hubs mainly located at the default-mode, salience, and executive control systems. Further analysis revealed that test-retest reliabilities of network metrics were sensitive to the scanning orders and intervals, with fair to excellent long-term reliability between Scan 1 and Scan 3 and lower reliability involving Scan 2. In the long-term case (Scan 1 and Scan 3), most network metrics were generally test-retest reliable, with the highest reliability in global metrics in the clustering coefficient and in the nodal metrics in nodal degree and efficiency. CONCLUSION: We showed high test-retest reliability for graph properties in the high-resolution functional connectomics, which provides important guidance for choosing reliable network metrics and analysis strategies in future studies.

Topological organization of the human brain functional connectome across the lifespan.

Human brain function undergoes complex transformations across the lifespan. We employed resting-state functional MRI and graph-theory approaches to systematically chart the lifespan trajectory of the topological organization of human whole-brain functional networks in 126 healthy individuals ranging in age from 7 to 85 years. Brain networks were constructed by computing Pearson's correlations in blood-oxygenation-level-dependent temporal fluctuations among 1024 parcellation units followed by graph-based network analyses. We observed that the human brain functional connectome exhibited highly preserved non-random modular and rich club organization over the entire age range studied. Further quantitative analyses revealed linear decreases in modularity and inverted-U shaped trajectories of local efficiency and rich club architecture. Regionally heterogeneous age effects were mainly located in several hubs (e.g., default network, dorsal attention regions). Finally, we observed inverse trajectories of long- and short-distance functional connections, indicating that the reorganization of connectivity concentrates and distributes the brain's functional networks. Our results demonstrate topological changes in the whole-brain functional connectome across nearly the entire human lifespan, providing insights into the neural substrates underlying individual variations in behavior and cognition. These results have important implications for disease connectomics because they provide a baseline for evaluating network impairments in age-related neuropsychiatric disorders.

Functional brain hubs and their test-retest reliability: a multiband resting-state functional MRI study.

Resting-state functional MRI (R-fMRI) has emerged as a promising neuroimaging technique used to identify global hubs of the human brain functional connectome. However, most R-fMRI studies on functional hubs mainly utilize traditional R-fMRI data with relatively low sampling rates (e.g., repetition time [TR]=2 s). R-fMRI data scanned with higher sampling rates are important for the characterization of reliable functional connectomes because they can provide temporally complementary information about functional integration among brain regions and simultaneously reduce the effects of high frequency physiological noise. Here, we employed a publicly available multiband R-fMRI dataset with a sub-second sampling rate (TR=645 ms) to identify global hubs in the human voxel-wise functional networks, and further examined their test-retest (TRT) reliability over scanning time. We showed that the functional hubs of human brain networks were mainly located at the default-mode regions (e.g., medial prefrontal and parietal cortex as well as the lateral parietal and temporal cortex) and the sensorimotor and visual cortex. These hub regions were highly anatomically distance-dependent, where short-range and long-range hubs were primarily located at the primary cortex and the multimodal association cortex, respectively. We found that most functional hubs exhibited fair to good TRT reliability using intraclass correlation coefficients. Interestingly, our analysis suggested that a 6-minute scan duration was able to reliably detect these functional hubs. Further comparison analysis revealed that these results were approximately consistent with those obtained using traditional R-fMRI scans of the same subjects with TR=2500 ms, but several regions (e.g., lateral frontal cortex, paracentral lobule and anterior temporal lobe) exhibited different TRT reliability. Finally, we showed that several regions (including the medial/lateral prefrontal cortex and lateral temporal cortex) were identified as brain hubs in a high frequency band (0.2-0.3 Hz), which is beyond the frequency scope of traditional R-fMRI scans. Our results demonstrated the validity of multiband R-fMRI data to reliably detect functional hubs in the voxel-wise whole-brain networks, which motivated the acquisition of high temporal resolution R-fMRI data for the studies of human brain functional connectomes in healthy and diseased conditions.

Probabilistic diffusion tractography and graph theory analysis reveal abnormal white matter structural connectivity networks in drug-naive boys with attention deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD), which is characterized by core symptoms of inattention and hyperactivity/impulsivity, is one of the most common neurodevelopmental disorders of childhood. Neuroimaging studies have suggested that these behavioral disturbances are associated with abnormal functional connectivity among brain regions. However, the alterations in the structural connections that underlie these behavioral and functional deficits remain poorly understood. Here, we used diffusion magnetic resonance imaging and probabilistic tractography method to examine whole-brain white matter (WM) structural connectivity in 30 drug-naive boys with ADHD and 30 healthy controls. The WM networks of the human brain were constructed by estimating inter-regional connectivity probability. The topological properties of the resultant networks (e.g., small-world and network efficiency) were then analyzed using graph theoretical approaches. Nonparametric permutation tests were applied for between-group comparisons of these graphic metrics. We found that both the ADHD and control groups showed an efficient small-world organization in the whole-brain WM networks, suggesting a balance between structurally segregated and integrated connectivity patterns. However, relative to controls, patients with ADHD exhibited decreased global efficiency and increased shortest path length, with the most pronounced efficiency decreases in the left parietal, frontal, and occipital cortices. Intriguingly, the ADHD group showed decreased structural connectivity in the prefrontal-dominant circuitry and increased connectivity in the orbitofrontal-striatal circuitry, and these changes significantly correlated with the inattention and hyperactivity/impulsivity symptoms, respectively. The present study shows disrupted topological organization of large-scale WM networks in ADHD, extending our understanding of how structural disruptions of neuronal circuits underlie behavioral disturbances in patients with ADHD.