Abnormalities in brain white matter structural networks associated with language function of post-stroke aphasia.

Previous neuroimaging studies revealed radiation-induced brain injury in patients with nasopharyngeal carcinoma (NPC) in the years after radiotherapy (RT). These injuries may be associated with structural and functional alterations. However, differences in the brain structural connectivity of NPC patients at different times after RT, especially in the early-delayed period, remain unclear. We acquired diffusion tensor imaging (DTI) data from three groups of NPC patients, 25 in the pre-RT (before RT) group, 22 in the early-delayed (1-6months) period (post-RT-ED) group, and 33 in the late-delayed (>6months) period (post-RT-LD) group. Then, we constructed brain white matter (WM) structural networks and used graph theory to compare their between-group differences. The NPC patients in the post-RT-ED group showed decreased global properties when compared with the pre-RT group. We also detected the nodes with between-group differences in nodal parameters. The nodes that differed between the post-RT-ED and pre-RT groups were mainly located in the default mode (DMN) and central executive networks (CEN); those that differed between the post-RT-LD and pre-RT groups were located in the limbic system; and those that differed between the post-RT-LD and post-RT-ED groups were mainly in the DMN. These findings may indicate that radiation-induced brain injury begins in the early-delayed period and that a reorganization strategy begins in the late-delayed period. Our findings may provide new insight into the pathogenesis of radiation-induced brain injury in normal-appearing brain tissue from the network perspective.

Neuroimaging studies suggested that drug addiction is linked to abnormal brain functional connectivity. However, little is known about the alteration of brain white matter (WM) connectivity in addictive drug users and nearly no study has been performed to examine the alterations of brain WM connectivity in heroin-dependent individuals (HDIs). Diffusion tensor imaging (DTI) offers a comprehensive technique to map the whole brain WM connectivity in vivo. In this study, we acquired DTI datasets from 20 HDIs and 18 healthy controls and constructed their brain WM structural networks using a deterministic fibre tracking approach. Using graph theoretical analysis, we explored the global and nodal topological parameters of brain network for both groups and adopted a network-based statistic (NBS) approach to assess between-group differences in inter-regional WM connections. Statistical analysis indicated the global efficiency and network strength were significantly increased, but the characteristic path length was significantly decreased in the HDIs compared with the controls. We also found that in the HDIs, the nodal efficiency was significantly increased in the left prefrontal cortex, bilateral orbital frontal cortices and left anterior cingulate gyrus. Moreover, the NBS analysis revealed that in the HDIs, the significant increased connections were located in the paralimbic, orbitofrontal, prefrontal and temporal regions. Our results may reflect the disruption of whole brain WM structural networks in the HDIs. Our findings suggest that mapping brain WM structural network may be helpful for better understanding the neuromechanism of heroin addiction.

This study aims to identify the topological abnormalities of the brain white matter structural network in adolescents with first episode, drug-naïve major depressive disorder (MDD), and to explore the relationship between these abnormalities and chronic childhood stress. T1-weighted images and diffusion tensor imaging (DTI) data were collected from 77 first-episode, drug-naïve MDD adolescents and 31 healthy controls (HCs). A whole-brain white matter structural network was constructed for each participant. Graph-theoretical analyses were employed to investigate the topological properties of white matter structural networks. Subsequently, we applied four machine learning methods-univariate linear regression, stepwise regression, LASSO regression, and random forest-to screen for relevant variables. The selected variables were then integrated into a final multivariate linear regression model to examine their correlations with Childhood Chronic Stress Questionnaire (CCSQ) scores. Compared with HCs, adolescents with MDD showed significantly larger network radius (t = -2.647, p = 0.009) and network diameter (t = -2.619, p = 0.010), as well as significantly lower small-worldness (t = 2.066, p = 0.041) and global efficiency (t = 2.083, p = 0.040) in brain white matter structural network. Local topological abnormalities were observed in multiple brain regions of adolescents with MDD, primarily involving paracentral lobular and mid cingulate cortex, MT+ complex, early auditory cortex, dorsolateral prefrontal cortex, orbital and polar frontal cortex, as well as anterior cingulate and medial prefrontal cortex. The final regression model showed that the weighted betweenness centrality in left area 1, left area 6mp, left frontal opercular area 4, left posterior OFC complex and left lateral belt complex, as well as the weighted local efficiency of the right ventral intraparietal complex and right orbital frontal complex (adjusted R2=0.270, Cohen's f2=0.630). We found that chronic childhood stress is associated with local topological abnormalities in multiple regions of the white matter structural networks of adolescents with MDD. These altered white matter network topological properties may be utilized in the future to aid in identifying depressive subtypes with high childhood stress exposure.

Objective To explore the changes of whole brain white matter (WM) structural network topological property in patients with schizophrenia (SP) and the associations between WM networks topological efficiency and clinical variables in patients. Methods Deterministic tractography was used to construct the WM networks of 59 patients with SP (patients group) and 41 age-, handedness-, and gender-matched healthy controls (HCs), and graph theoretical methods were applied to investigate abnormalities in the global and nodal properties of the WM network in these patients.Partial correlation analysis was used to analyze the relationship between global and nodal properties of the WM network and clinical variables in patients with SP. Results Both the patients with SP and HCs showed small-world organization of the WM networks.However, compared with HCs, the patients with SP exhibited significant abnormal global topology, including increased shortest path length (t=7.95, P=0.0001) and decreased global efficiency (30.83±16.08, 8.25±6.13, t=-9.81, P=0.002), clustering coefficiency (0.03±0.01, 0.02±0.01, t=-4.48, P=0.0003), the average clustering coefficiency (t=-8.28, P=0.002), the small-worldness (3.92±0.79, 2.79±0.56, t=-7.82, P=0.001) of their WM structural networks(all P<0.005, FDR corrected). Further, the patients with SP showed a reduction in nodal efficiency predominately in the cingulate gyrus (t=-4.11, P=0.000), superior occipital gyrus (t=-6.05, P=0.002), superior temporal gyrus (t=-10.46, P=0.001), middle temporal gyrus (t=-10.38, P=0.000), thalamus (t=-6.10, P=0.000) and putamen (t=-8.38, P=0.000) (P<0.005, FDR corrected). Partial correlation results showed that there was no significant correlation between global topological properties, node efficiency and clinical symptoms in patients group(Eglob: r=-0.14, P=0.279; Eloc: r=-0.06, P=0.628; Lp: r=0.28, P=0.031; Cp: r=0.27, P=0.043; λ: r=-0.18, P=0.166; γ: r=-0.29, P=0.026; σ: r=0.26, P=0.048; nEglob: r=0.36, P=0.005; nEloc: r=0.02, P=0.901). Conclusions The patients with SP exhibit the abnormal of whole brain WM structural network topological property and the node efficiencies of cortico-striato-thalamo circuitry are significantly reduced. Key words: Schizophrenia; White matter; Topological properties; Graph theoretical

BackgroundPrevious neuroimaging studies have described shared and distinct neurobiological mechanisms between autism spectrum disorders (ASDs) and attention-deficit/hyperactivity disorder (ADHD). However, little is known about the similarities and differences in topologically structural connectivity patterns between the two disorders.MethodsDiffusion tensor imaging (DTI) and deterministic tractography were used to construct the brain white matter (WM) structural networks of children and adolescents (age range, 6–16 years); 31 had ASD, 34 had ADHD, and 30 were age- and sex-matched typically developing (TD) individuals. Then, graph theoretical analysis was performed to investigate the alterations in the global and node-based properties of the WM structural networks in these groups. Next, measures of ASD traits [Social Responsiveness Scale (SRS)] and ADHD traits (Swanson, Nolan, and Pelham, version IV scale, SNAP-IV) were correlated with the alterations to determine the functional significance of such changes.ResultsFirst, there were no significant differences in the global network properties among the three groups; moreover, compared with that of the TD group, nodal degree (Ki) of the right amygdala (AMYG.R) and right parahippocampal gyrus (PHG.R) were found in both the ASD and ADHD groups. Also, the ASD and ADHD groups shared four additional hubs, including the left middle temporal gyrus (MTG.L), left superior temporal gyrus (STG.L), left postcentral gyrus (PoCG.L), and right middle frontal gyrus (MFG.R) compared with the TD group. Moreover, the ASD and ADHD groups exhibited no significant differences regarding regional connectivity characteristics. Second, the ADHD group showed significantly increased nodal betweenness centrality (Bi) of the left hippocampus (HIP.L) compared with the ASD group; also, compared with the ADHD group, the ASD group lacked the left anterior cingulate gyrus (ACG.L) as a hub. Last, decreased nodal efficiency (Enodal) of the AMYG.R, Ki of the AMYG.R, and Ki of the PHG.R were associated with higher SRS scores in the ASD group. Decreased Ki of the PHG.R was associated with higher SRS scores in the full sample, whereas decreased Bi of the PHG.R was associated with lower oppositional defiance subscale scores of the SNAP-IV in the ADHD group, and decreased Bi of the HIP.L was associated with lower inattention subscale scores of the SNAP-IV in the full sample.ConclusionFrom the perspective of the topological properties of brain WM structural networks, ADHD and ASD have both shared and distinct features. More interestingly, some shared and distinct topological properties of WM structures are related to the core symptoms of these disorders.

Previous neuroimaging studies have revealed cognitive dysfunction in patients with systemic lupus erythematosus (SLE) and suggested that it may be related to disrupted brain white matter (WM) connectivity. However, no study has examined the topological properties of brain WM structural networks in SLE patients, especially in patients with non-neuropsychiatric SLE (non-NPSLE). In this study, we acquired DTI datasets from 28 non-NPSLE patients and 24 healthy controls, constructed their brain WM structural networks by using a deterministic fiber tracking approach, estimated the topological parameters of their structural networks, and compared their group differences. We reached the following results: 1) At the global level, the non-NPSLE patients showed significantly increased characteristic path length, normalized clustering coefficient and small-worldness, but significantly decreased global efficiency and local efficiency compared to the controls; 2) At the nodal level, the non-NPSLE patients had significantly decreased nodal efficiency in regions related to movement control, executive control, and working memory (bilateral precentral gyri, bilateral middle frontal gyri, bilateral inferior parietal lobes, left median cingulate gyrus and paracingulate gyrus, and right middle temporal gyrus). In addition, to pinpointing the injured WM fiber tracts in the non-NPSLE patients, we reconstructed the major brain WM pathways connecting the abnormal regions at the nodal level with the corticospinal tract (CST), superior longitudinal fasciculus-parietal terminations (SLFP), and superior longitudinal fasciculus-temporal terminations (SLFT). By analyzing the diffusion parameters along these WM fiber pathways, we detected abnormal diffusion parameters in the bilateral CST and right SLFT in the non-NPSLE patients. These results seem to indicate that injured brain WM connectivity exists in SLE patients even in the absence of neuropsychiatric symptoms.

Objective: To investigate the topological properties of the white matter network in the drug-naive first-episode children and adolescent with obsessive-compulsive disorder (OCD). Methods: This study was a case-control study. First-episode OCD childhren and adolescents(OCD group) who were treated in the outpatient or inpatient department of the Second Affiliated Hospital of Xinxiang Medical University from July 2018 to October 2023 were collected as the research subjects. Healthy controls (control group)matched by gender, age and education level were used as controls. Deterministic tractography technique was used to construct the whole brain white matter structural network, and graph theory analysis method was used to analyze the topological attributes of the whole brain white matter structure network in OCD children and adolescents. A network-based statistical method was used to examine the inter-group differences in the functional connectivity strength of the whole brain network. Results: Finally, 31 cases were included in the obsessive-compulsive disorder group, including 22 males and 9 females, with an age of (13.5±1.6) years; There were 34 cases in the control group, including 22 males and 12 females, with an age of (12.7±1.4) years. The global efficiency and local efficiency of the OCD group (0.62±0.03, 0.70±0.07) were significantly higher than those of the control group (0.50±0.06, 0.54±0.21) [both P<0.01, false discovery rate(FDR)correction]; while the characteristic path length (1.77±0.08) was significantly smaller than that of the control group (2.10±0.23) (P<0.01, FDR correction).The centrality comparison of nodal betweenness centrality showed that in the OCD group, the connections were enhanced in the left lateral orbitofrontal gyrus, right dorsal agranular insula, left dorsal granular insula, right granular insula, right posterior central gyrus main area of parietal lobe, left ventral granular insula, granular insula, left ventral granulosa, left granular insula, and left dorsal agranular insula [all P<0.001, family wise error (FWE) correction], while the connection of right thalamic was weakened (P<0.001, FWE correction), There were sub-networks characterized by significantly enhanced connection strength of relevant nodes in subcortical, visual network, and default mode network (P<0.05, permutation test 5 000 times). Conclusions: The topological properties of the brain's functional network in children and adolescents with OCD exhibit abnormalities, indicating an immature state of brain functional connectivity.

This study explored the topological characteristics of brain white matter structural networks in patients with Paroxysmal Kinesigenic Dyskinesia (PKD), and the potential influence of the brain network stability gene PRRT2 on the structural connectome in PKD. Thirty‐five PKD patients with PRRT2 mutations (PKD‐M), 43 PKD patients without PRRT2 mutations (PKD‐N), and 40 demographically‐matched healthy control (HC) subjects underwent diffusion tensor imaging. Graph theory and network‐based statistic (NBS) approaches were performed; the topological properties of the white matter structural connectome were compared across the groups, and their relationships with the clinical variables were assessed. Both disease groups PKD‐M and PKD‐N showed lower local efficiency (implying decreased segregation ability) compared to the HC group; PKD‐M had longer characteristic path length and lower global efficiency (implying decreased integration ability) compared to PKD‐N and HC, independently of the potential effects of medication. Both PKD‐M and PKD‐N had decreased nodal characteristics in the left thalamus and left inferior frontal gyrus, the alterations being more pronounced in PKD‐M patients, who also showed abnormalities in the left fusiform and bilateral middle temporal gyrus. In the connectivity characteristics assessed by NBS, the alterations were more pronounced in the PKD‐M group versus HC than in PKD‐N versus HC. As well as the white matter alterations in the basal ganglia‐thalamo‐cortical circuit related to PKD with or without PRRT2 mutations, findings in the PKD‐M group of weaker small‐worldness and more pronounced regional disturbance show the adverse effects of PRRT2 gene mutations on brain structural connectome.

Abdominal obesity (AO) in women exhibits clinical heterogeneity, yet its neural mechanisms remain unclear. Using diffusion tensor imaging (DTI), this study conducts the first systematic investigation of whole-brain white matter (WM) structural network topological properties and female-specific neural mechanisms in AO patients stratified by appetite subtypes (strong appetite, SA; moderate appetite, MA). This study enrolled 60 female AO patients (stratified into 30 SA and 30 MA) and 30 age-matched healthy controls (HCs). Whole-brain WM structural networks were constructed, with global and local topological properties analyzed through graph theoretical approaches. Statistical correlations between network metrics and clinical measures were assessed. Global network analysis demonstrated intact small-world properties (γ > 1, σ > 1) across all groups. At the nodal level, compared with HCs, SA patients showed reduced degree centrality (DC) in the right temporal pole: superior temporal gyrus (TPOsup. R) (p = 0.017) and lower nodal local efficiency (NLE) in the right amygdala (AMYG. R) (p = 0.007). Notably, TPOsup. R DC positively correlated with appetite scores (r = 0.408, p = 0.025). Additionally, the SA group exhibited reduced betweenness centrality (BC) in the right rectus gyrus (REC. R) compared to the MA group (p = 0.041), which negatively correlated with appetite scores (r = −0.439, p = 0.015). Conversely, MA patients showed increased NLE in the right medial orbital superior frontal gyrus (ORBsupmed. R) (p = 0.005). Whole-brain connectome analysis identified a hypo-connected subnetwork specific to MA involving 23 nodes and 24 edges, highlighting weakened right amygdala (AMYG. R)–right superior occipital gyrus (SOG. R) (r = 0.464, p = 0.01) and right lingual gyrus (LING. R)–right fusiform gyrus (FFG. R) (r = 0.365, p = 0.047) connections that showed positive correlation with waist circumference. In summary, this study provides the first evidence that female patients with abdominal obesity exhibiting different appetite phenotypes possess specific white matter structural network patterns. The SA subtype is characterized by aberrant nodal topological properties within prefrontal-limbic circuits, reflecting a localized disruption associated with heightened appetite. In contrast, the MA subtype is defined by widespread structural disconnectivity between occipital sensory areas and limbic regions, appearing as a neuroanatomical consequence linked to abdominal adiposity severity.

Polymorphisms of the apolipoprotein E (APOE) promoter rs405509 are related to Alzheimer's disease (AD). The T/T allele of rs405509 decreases the transcription of the APOE gene and leads to impairments in a specific brain structural network in aged individuals; thus, it is an important risk factor for AD. However, it remains unknown whether rs405509 affects white matter networks during aging. Here, we investigated the effect of the rs405509 genotype (T/T versus G-allele) on age-related brain white matter structural networks via construction of the graph theory-based structural connectome using diffusion MRI data in a large cohort. Network communication efficiency was quantified, along with the network's betweenness centrality (Bc), global efficiency, local efficiency, and shortest path length. Regarding cognition, TT carriers had significant negative correlations between age and memory performance and between age and executive functions. A network analysis showed that TT carriers had an accelerated age-related loss of Bc and that regional Bc decreased in the left inferior frontal gyrus pars opercularis, the left posterior cingulate cortex, the right inferior occipital gyrus (IOG.R), and the left angular gyrus (ANG.L). Additional brain-behavior relationship analyses showed that polymorphism of rs405509 and age have strong interaction effects on the association of nodal Bc and cognition, mainly in the IOG.R and ANG.L. These results demonstrate that the rs405509 T/T allele of APOE causes an age-related cognitive decline in non-demented elderly people, possibly by modulating brain network communication efficiency, which may be beneficial for understanding the neural mechanisms of rs405509-related cognitive aging and AD pathogenesis.

Variation in Brain Subcortical Network Topology Between Men With and Without PE: A Diffusion Tensor Imaging Study

Neuropsychiatric Significance of Subcortical Hyperintensity

Growth hormone deficiency (GHD) in children results from impairment of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis. Although GHD's effects on brain structure and function have been studied, its impact on large-scale white matter (WM) structural connectivity remains poorly understood. We aimed to investigate the topological organization of WM structural connectome in pediatric GHD using diffusion tensor imaging (DTI) and graph theoretical analysis. This cross-sectional study included 58 drug-naïve children with GHD and 30 typically developing (TD) controls matched for age and gender. DTI data were analyzed using deterministic tractography, and the structural connectivity between 90 cortical and subcortical regions was assessed. Graph theoretical analysis was applied to evaluate topological parameters of the resulting graphs. Between-group comparison of networks metrics was assessed. Finally, a partial correlation analysis was performed to explore the relationship between significant topologic metrics and clinical symptom severity. Compared to TD groups, the GHD patients showed altered global properties, including increased characteristic path length (P<0.001), and decreased global (P<0.001) and local efficiency (P<0.001). Regarding nodal parameters, GHD showed abnormal nodal parameters (nodal degree, efficiency, betweenness) primarily in regions associated with the default mode network (DMN), central executive network (CEN), visual network (VN), salience network (SN), sensorimotor network (SMN), basal ganglia, and left thalamus. Besides, the scores of Achenbach's Child Behavior Check List (CBCL) of GHD was positively correlated with the nodal efficiency in the left middle occipital gyrus (P=0.048, uncorrected), right inferior parietal lobe (P=0.035, uncorrected), and left middle temporal gyrus (r=0.295; P=0.034, uncorrected). Our findings reveal disrupted WM topological organization in children with GHD, which may potentially relate to abnormal GH/IGF-1 levels and associated with behavioral problems. These alterations in structural brain networks may underlie the behavioral challenges observed in GHD, providing new insights into the neurobiological basis of this condition.

The central auditory system has greater plasticity when children are 2-4 years old, called the auditory sensitive period, during which cochlear implantation (CI) can give a good prognosis to children with congenital sensorineural hearing loss (CSNHL), but some will have a poor prognosis. This experiment aims to construct a structural brain network by using diffusion tensor imaging (DTI) and analyze alterations of the topological properties of structural brain networks by graph theory method, provide an imaging basis for the pathophysiological mechanism of white matter network changes with age in SNHL children. A total of 109 children with SNHL and 61 normal control groups were included. According to the auditory sensitivity period, children were divided into a group within the auditory sensitivity period (group A, 12-47 months) and a group beyond the auditory sensitivity period (group B, 48-120 months). DTI data were collected to construct the structural brain network for graph theory analysis, identify the network changes of the topological properties of the SNHL, as well as the differences before and after the auditory sensitivity period. Compared with the control group, both groups of SNHL had network topological changes. Group A showed a decrease in nodal parameters in higher-order cognitive-related brain regions but no difference in global topology parameters and network connection strength. However, group B showed a decrease in the nodal parameters of multiple contact cortical brain regions and the global efficiency (Eglob) of structural networks. Besides, subnetwork analysis showed weakened connection strength between key brain regions related to higher-order cognition. The structural brain network of SNHL children before the auditory sensitive period has not undergone extensive changes, and once the auditory sensitive period of development is exceeded, the formation of deaf brain features will be more obvious, with greater impact on higher-order cognitive regions. Before the auditory sensitivity period, hearing stimulation should be introduced to SNHL children as soon as possible to reduce extensive damage to the white matter network.

Post-stroke aphasia (PSA), which refers to the loss or impairment of language, is typically caused by left hemisphere lesions. Previous neuroimaging studies have indicated that the pathology of PSA may be related to abnormalities in functional integration. In this study, we used resting-state functional magnetic resonance imaging (rs-fMRI) to examine functional connectivity density (FCD) in PSA. We compared short- and long-range FCD between individuals with PSA (n = 17) and healthy controls (HC, n = 20). We then performed Pearson's correlation analysis on the FCD values from the affected brain regions and the speech scores in the PSA group. Compared with HCs, individuals with PSA showed increased short-range FCD in the contralesional temporal gyrus, the inferior frontal gyrus, the thalamus, the insula, and the mesial temporal gyrus [hippocampus/parahippocampus (HIP/ParaHIP)]. PSA demonstrated an increased long-range FCD in the contralesional mesial temporal gyrus (HIP/ParaHIP). PSA also displayed decreased short-range FCD in the ipsilesional part of the frontal gyrus, the caudate, the thalamus, the fusiform gyrus, and the mesial temporal gyrus (HIP/ParaHIP), and decreased long-range FCD in the ipsilesional superior temporal gyrus, the fusiform gyrus, and the mesial temporal gyrus (HIP/ParaHIP). The decreased long-range FCD in the left superior temporal gyrus in PSA subjects was positively correlated with the spontaneous speech score. The altered FCD observed due to disrupted functional connectivity after stroke may lead to language production, semantic processing, and cognitive impairments. Our findings expand previous functional studies on stroke and provide new evidence of the intraregional and interregional interactions at the voxel level in the pathophysiology of PSA.