Altered single-subject gray matter structural networks in drug-naïve attention deficit hyperactivity disorder children.

Altered topological organization of brain structural covariance networks has been observed in attention deficit hyperactivity disorder (ADHD). However, results have been inconsistent, potentially related to confounding medication effects. In addition, since structural networks are traditionally constructed at the group level, variabilities in individual structural features remain to be well characterized. Structural brain imaging with MRI was performed on 84 drug-naïve children with ADHD and 83 age-matched healthy controls. Single-subject gray matter (GM) networks were obtained based on areal similarities of GM, and network topological properties were analyzed using graph theory. Group differences in each topological metric were compared using nonparametric permutation testing. Compared with healthy subjects, GM networks in ADHD patients demonstrated significantly altered topological characteristics, including higher global and local efficiency and clustering coefficient, and shorter path length. In addition, ADHD patients exhibited abnormal centrality in corticostriatal circuitry including the superior frontal gyrus, orbitofrontal gyrus, medial superior frontal gyrus, precentral gyrus, middle temporal gyrus, and pallidum (all p < .05, false discovery rate [FDR] corrected). Altered global and nodal topological efficiencies were associated with the severity of hyperactivity symptoms and the performance on the Stroop and Wisconsin Card Sorting Test tests (all p < .05, FDR corrected). ADHD combined and inattention subtypes were differentiated by nodal attributes of amygdala (p < .05, FDR corrected). Alterations in GM network topologies were observed in drug-naïve ADHD patients, in particular in frontostriatal loops and amygdala. These alterations may contribute to impaired cognitive functioning and impulsive behavior in ADHD.

Disruption of gray matter morphological networks in patients with paroxysmal kinesigenic dyskinesia.

This study explores the topological properties of brain gray matter (GM) networks in patients with paroxysmal kinesigenic dyskinesia (PKD) and asks whether GM network features have potential diagnostic value. We used 3D T1-weighted magnetic resonance imaging and graph theoretical approaches to investigate the topological organization of GM morphological networks in 87 PKD patients and 115 age- and sex-matched healthy controls. We applied a support vector machine to GM morphological network matrices to classify PKD patients versus healthy controls. Compared with the HC group, the GM morphological networks of PKD patients showed significant abnormalities at the global level, including an increase in characteristic path length (Lp) and decreases in local efficiency (Eloc ), clustering coefficient (Cp), normalized clustering coefficient (γ), and small-worldness (σ). The decrease in Cp was significantly correlated with disease duration and age of onset. The GM morphological networks of PKD patients also showed significant changes in nodal topological characteristics, mainly in the basal ganglia-thalamus circuitry, default-mode network and central executive network. Finally, we used the GM morphological network matrices to classify individuals as PKD patients versus healthy controls, achieving 87.8% accuracy. Overall, this study demonstrated disruption of GM morphological networks in PKD, which might extend our understanding of the pathophysiology of PKD; further, GM morphological network matrices might have the potential to serve as network neuroimaging biomarkers for the diagnosis of PKD.

Functional connectivity of the thalamocortical circuit in patients with seizure relapse after antiseizure medication withdrawal.

OBJECTIVE: To characterize the features of thalamocortical functional connectivity during seizure recurrence at the time of antiseizure medication (ASM) withdrawal. METHODS: Patients with chronic epilepsy who attempted to discontinue medications were prospectively registered and followed up; 19 patients remained seizure-free (SF-group), 18 patients had seizure relapses (SR-group) after ASM withdrawal, and 28 healthy controls were recruited. Resting-state functional magnetic resonance imaging was performed before ASM withdrawal. Thalamus subdivisions were set as seeds to calculate voxelwise functional connectivity. Partial correlation analysis between functional connectivity and clinical variables was performed. A support vector machine was used to assess the predictive ability of the specific functional connectivity for seizure relapse. RESULTS: The within-group comparison indicated that the SR-group had more extensive functional connectivity than the SF-group; the left inferior pulvinar, left medial pulvinar, and right anterior pulvinar showed a significantly stronger functional connection with the precuneus in the SR-group than in the SF-group (Gaussian random field correction, voxel-level p < .001 and cluster-level p < .05). In the SR-group, a positive correlation was found between the left inferior pulvinar-precuneus connectivity and the active period (r = .46, p = .05), seizure-free period (r = .67, p = .002), and disease duration (r = .53, p = .02), and between the left medial pulvinar-precuneus connectivity and the seizure-free period (r = .58, p = .01). The combination of these thalamocortical connections showed a high predictive ability, with an area under the curve of .92 and accuracy of .90 (p = .01). SIGNIFICANCE: This study determined distinct features of thalamocortical functional connectivity at the time of ASM withdrawal in patients with and without seizure relapse, showing a potential for predicting seizure outcomes following ASM withdrawal.

Large-scale white matter network reorganization in posttraumatic stress disorder.

Recently, graph theoretical approaches applied to neuroimaging data have advanced understanding of the human brain connectome and its abnormalities in psychiatric disorders. However, little is known about the topological organization of brain white matter networks in posttraumatic stress disorder (PTSD). Seventy-six patients with PTSD and 76 age, gender, and years of education-matched trauma-exposed controls were studied after the 2008 Sichuan earthquake using diffusion tensor imaging and graph theoretical approaches. Topological properties of brain networks including global and nodal measurements and modularity were analyzed. At the global level, patients showed lower clustering coefficient (p = .016) and normalized characteristic path length (p = .035) compared with controls. At the nodal level, increased nodal centralities in left middle frontal gyrus, superior and inferior temporal gyrus and right inferior occipital gyrus were observed (p < .05, corrected for false-discovery rate). Modularity analysis revealed that PTSD patients had significantly increased inter-modular connections in the fronto-parietal module, fronto-striato-temporal module, and visual and default mode modules. These findings indicate a PTSD-related shift of white matter network topology toward randomization. This pattern was characterized by an increased global network integration, reflected by increased inter-modular connections with increased nodal centralities involving fronto-temporo-occipital regions. This study suggests that extremely stressful life experiences, when they lead to PTSD, are associated with large-scale brain white matter network topological reconfiguration at global, nodal, and modular levels.

Real-time effects of interictal spikes on hippocampus and amygdala functional connectivity in unilateral temporal lobe epilepsy: An EEG-fMRI study.

OBJECTIVE: To explore the real-time effects of interictal epileptiform discharges (IEDs) on hippocampus and amygdala functional connectivity (FC) in unilateral temporal lobe epilepsy (TLE). METHODS: Patients with unilateral TLE were recruited and underwent simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) scanning. Simultaneous EEG was used to define the prespike (10 s before spike) and postspike (10 s after spike) periods. Dynamic FC analysis was applied using the left/right hippocampus and amygdala separately as a seed region to map the network alterations after IED occurrence. RESULTS: A total of 261 IED events (133 left, 128 right) from 21 patients with unilateral TLE (10 left, 11 right) were analyzed. Left IEDs had a greater influence on the hippocampus-seeded networks, whereas right IEDs affected the amygdala-seeded networks more. Left IEDs disconnected the ipsilateral hippocampus and the default mode network, which might be related to cognitive impairment in TLE. The reward-emotion network (more of the prefrontal-limbic system) and visual network also showed FC changes after left IEDs. The reward-emotion network (more of the reward system) was coactivated after right IEDs, indicating a possible mechanism of forced normalization. SIGNIFICANCE: This study directly linked the disrupted functional networks in TLE to epileptic activities and offered a unique tool for future research to investigate mechanisms of comorbidities in TLE.

Reduced local segregation of single-subject gray matter networks in adult PTSD.

To psychoradiologically investigate the topological organization of single-subject gray matter networks in patients with PTSD. Eighty-nine adult PTSD patients and 88 trauma-exposed controls (TEC) underwent a structural T1 magnetic resonance imaging scan. The single-subject brain structural networks were constructed based on gray matter similarity of 90 brain regions. The area under the curve (AUC) of each network metric was calculated and both global and nodal network properties were measured in graph theory analysis. We used nonparametric permutation tests to identify group differences in topological metrics. Relationships between brain network measures and clinical symptom severity were analyzed in the PTSD group. Compared with TEC, brain networks of PTSD patients were characterized by decreased clustering coefficient (Cp ) (p = .04) and local efficiency (Eloc ) (p = .04). Locally, patients with PTSD exhibited altered nodal centrality involving medial superior frontal (mSFG), inferior orbital frontal (iOFG), superior parietal (SPG), middle frontal (MFG), angular, and para-hippocampal gyri (p < .05, corrected). A negative correlation between the segregation (Cp ) of gray matter and functional networks was found in PTSD patients but not the TEC group. Analyses of topological brain gray matter networks indicate a more randomly organized brain network in PTSD. The reduced segregation in gray matter networks and its negative relation with increased segregation in the functional network indicate an inverse relation between gray matter and functional changes. The present psychoradiological findings may reflect a compensatory increase in functional network segregation following a loss of segregation in gray matter networks.

MRI-based radiomics to compare the survival benefit of induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy plus adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma: A multicenter study.

BACKGROUND AND PURPOSE: It remains uncertain whether induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) or CCRT plus adjuvant chemotherapy (AC) is more effective in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). This study aimed to develop and validate a joint radiomic and clinical signature (RCS) for the prognostic stratification of LA-NPCs and to identify patients who might benefit more from IC + CCRT or CCRT + AC. MATERIALS AND METHODS: Overall, 893 LA-NPC patients who received IC + CCRT or CCRT + AC were enrolled from four hospitals. RCS based on pretreatment magnetic resonance images and clinical data was constructed for predicting 5-year progression-free survival (PFS). The predictive ability of the RCS and TNM staging system for 5-year PFS, locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were compared by Harrell's concordance indices (C-indices). Patients were divided into high- and low-risk subgroups based on RCS scores. The survival benefit of IC + CCRT vs. CCRT + AC in different subgroups was compared by Kaplan-Meier survival curves. RESULTS: The RCS combining the radiomic signature, TNM stage and EBV DNA demonstrated significantly higher C-indices than TNM stage for predicting 5-year PFS, LRRFS, DMFS and OS in the training and validation cohorts. In the high-risk group (RCS score ≥ 0.25), CCRT + AC achieved significantly better PFS, LRRFS, DMFS and OS than IC + CCRT. In the low-risk group (RCS score < 0.25), IC + CCRT yielded significantly better outcomes than CCRT + AC. CONCLUSION: The RCS provides a noninvasive way to predict the outcomes of LA-NPC and helps identify patients who may benefit more from IC + CCRT vs. CCRT + AC.

Chemotherapy-induced grey matter abnormalities in cancer survivors: a voxel-wise neuroimaging meta-analysis.

BACKGROUND: Findings regarding chemotherapy-induced grey matter abnormalities are heterogeneous, and no meta-analysis has quantitatively assessed brain structural alterations in cancer survivors treated with chemotherapy. PURPOSE: To investigate the grey matter abnormalities in non-CNS (central nervous system) cancer survivors treated with chemotherapy using Anisotropic Effect Size Signed Differential Mapping (AES-SDM) software. METHOD: We identified studies published up to Sep 2018 that compared grey matter in non-CNS cancer survivors treated with chemotherapy (CT+, 10 data sets including 433 individuals) and cancer survivors not treated with chemotherapy (CT-, 7 data sets including 210 individuals) or healthy controls (HC, 3 data sets including 407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. RESULTS: Compared with both CT- and HC, the CT + groups exhibited a reduced grey matter volume (GMV), mainly in the prefrontal and anterior cingulate cortex (ACC) and right fusiform gyrus (FG). A smaller GMV in the FG and prefrontal cortex were found in the CT + compared with the CT-groups and in the CT + groups with impaired cognition. GMV in two areas was positively associated with the time since chemotherapy. CONCLUSIONS: The present results suggest that non-CNS cancer survivors treated with chemotherapy exhibit grey matter abnormalities in the brain, especially in the prefrontal and ACC cortex. Grey matter volume changes after chemotherapy may contribute to cognitive impairments in cancer survivors that can be observed after chemotherapy.

Microstructural features of the cerebral cortex: Implications for predicting epilepsy relapse after drug withdrawal.

A considerable portion of patients with well-controlled seizures and visually normal brain structures experience seizure recurrence after anti-seizure medication is withdrawn. Microstructural abnormalities of the cortex may play an essential role in epilepsy relapse. Patients with idiopathic/cryptogenic epilepsy were registered. At the follow-up endpoint, 18 patients with relapse (PR+ group), 20 patients without relapse (PR- group), and 30 healthy controls were included. High-resolution T1-weighted images were obtained at the time of drug withdrawal. Microstructural features including cortical thickness, surface area, cortical volume and mean curvature in 68 cortical areas were calculated. A general linear model was applied to investigate intergroup differences, and then post hoc analysis was performed. Additionally, factor analysis was conducted to extract components from imaging measures showing a difference between PR- and PR+ groups, and independent associations between components and epilepsy relapse were assessed using a logistic regression model. Cortical thickness of the left paracentral lobule, left temporal pole and right superior frontal gyrus; surface area of the bilateral lingual gyrus and bilateral pericalcarine cortex; and cortical volume of the bilateral pericalcarine cortex had significant intergroup differences (false discovery rate correction, P < 0.05). All measures, except for cortical thickness of the left temporal pole, showed differences between PR- and PR+ groups. Two dominant components were extracted from these measures, and both were independently associated with epilepsy relapse. In conclusion, epilepsy patients with relapse presented distinct microstructural features of cortex at the time of drug withdrawal, which may serve as a potential biomarker for predicting seizure recurrence.

Aberrant Gray Matter Networks in Non-comorbid Medication-Naive Patients With Major Depressive Disorder and Those With Social Anxiety Disorder.

Major depressive disorder (MDD) and social anxiety disorder (SAD) are among the most prevalent and frequently co-occurring psychiatric disorders in adults and may have, at least in part, a common etiology. However, the unique and the shared neuroanatomical characteristics of the two disorders have not been fully identified. The aim of this study was to compare the topological organization of gray matter networks between non-comorbid medication-naive MDD patients and SAD patients. High-resolution T1-weighted images were acquired from 37 non-comorbid medication-naive MDD patients, 24 non-comorbid medication-naive SAD patients, and 41 healthy controls. Single-subject gray matter graphs were extracted from structural MRI scans, and whole-brain neuroanatomic organization was compared across the three groups. The relationships between brain network measures and clinical characteristics were analyzed. Relative to healthy controls, both the MDD and the SAD patients showed global decreases in clustering coefficient, normalized clustering coefficient, and small-worldness and locally decreased nodal centralities and morphological connections in the left insular, lingual, and calcarine cortices. Compared with healthy controls, the SAD patients exhibited increased nodal centralities and morphological connections mainly involving the prefrontal cortex and the sensorimotor network. Furthermore, compared to the SAD patients, the MDD patients showed increased characteristic path length, reduced global efficiency, and decreased nodal centralities and morphological connections in the right middle occipital gyrus and the right postcentral gyrus. Our findings provide new evidence for shared and specific similarity-based gray matter network alterations in MDD and SAD and emphasize that the psychopathological changes in the right middle occipital gyrus and the right postcentral gyrus might be different between the two disorders.

Machine learning for detecting mesial temporal lobe epilepsy by structural and functional neuroimaging.

Mesial temporal lobe epilepsy (mTLE), the most common type of focal epilepsy, is associated with functional and structural brain alterations. Machine learning (ML) techniques have been successfully used in discriminating mTLE from healthy controls. However, either functional or structural neuroimaging data are mostly used separately as input, and the opportunity to combine both has not been exploited yet. We conducted a multimodal ML study based on functional and structural neuroimaging measures. We enrolled 37 patients with left mTLE, 37 patients with right mTLE, and 74 healthy controls and trained a support vector ML model to distinguish them by using each measure and the combinations of the measures. For each single measure, we obtained a mean accuracy of 74% and 69% for discriminating left mTLE and right mTLE from controls, respectively, and 64% when all patients were combined. We achieved an accuracy of 78% by integrating functional data and 79% by integrating structural data for left mTLE, and the highest accuracy of 84% was obtained when all functional and structural measures were combined. These findings suggest that combining multimodal measures within a single model is a promising direction for improving the classification of individual patients with mTLE.

Primary intracranial leiomyosarcoma in an immunocompetent patient: Case report with emphasis on imaging features.

RATIONALE: Primary intracranial leiomyosarcoma (LMS) is an extremely rare tumor in the central nervous system (CNS), and usually seen in immunocompromised individuals. Only a few cases of primary intracranial LMS have been documented in the literature and no study focused on their MRI findings. We reported a case of primary intracranial leiomyosarcoma in a immunocompetent patient and review its imaging features. PATIENT CONCERNS: A 20-year-old female was admitted to our hospital, complaining with nausea, weight loss and progressive headache in recent 2 years. DIAGNOSIS: The magnetic resonance imaging scan of the brain revealed a large well-defined extra-cerebral mass adherent to left temporal meninges. The mass was iso-intense on T1-weighted images (T1WI), lightly iso to hypointense on T2-weighted images (T2WI) and enhanced uniformly with contrast medium. The preoperative diagnosis is meningioma. INTERVENTIONS: A left craniotomy was performed for the complete resection of the mass. OUTCOMES: The lesion was diagnosed via surgical histopathology and immunochemistry as leiomyosarcoma. No evidence of recurrence and complications were found in the following 13 months. LESSIONS: Primary intracranial leiomyosarcoma which has some special MR imaging features should be considered in the differential diagnosis of intracranial tumor.

Different patterns of white matter changes after successful surgery of mesial temporal lobe epilepsy.

OBJECTIVES: To explore the dynamic changes of white matters following anterior temporal lobectomy (ATL) in mesial temporal lobe epilepsy (MTLE) patients who achieved seizure-free at two-year follow-up. METHODS: Diffusion tensor imaging (DTI) was obtained in ten MTLE patients at five serial time points: before surgery, three months, six months, 12 months and 24 months after surgery, as well as in 11 age- and sex-matched healthy controls at one time point. Regions with significant postoperative fractional anisotropy (FA) changes and their dynamic changes were confirmed by comparing all preoperative and postoperative data using Tract-Based Spatial Statistics (TBSS). RESULTS: After successful ATL, significant FA changes were found in widespread ipsilateral and contralateral white matter regions (P <.05, FWE correction). Ipsilateral external capsule, cingulum, superior corona radiate, body of corpus callosum, inferior longitudinal fasciculus, optic radiation and contralateral inferior cerebellar peduncle, inferior longitudinal fasciculus showed significant FA decrease at three months after surgery, without further changes. Ipsilateral superior cerebellar peduncle and contralateral corpus callosum, anterior corona radiate, external capsule, optic radiation showed significant FA decrease at three months follow up but increase later. Ipsilateral cerebral peduncle and contralateral middle cerebellar peduncle showed significant FA decrease at three months follow up, with further decrease after that. While ipsilateral posterior limb of internal capsule, retrolenticular part of internal capsule and contralateral posterior corona radiate showed significant FA increase after surgery. CONCLUSIONS: FA changes after successful ATL presented as four distinct patterns, reflecting different structural adaptions following epilepsy surgery. Some FA increases indicated the reversibility of preoperative diffusion abnormalities and the possibility of structural reorganization, especially in the contralateral hemisphere.

Integrity of the corpus callosum in patients with periventricular nodular heterotopia related epilepsy by FLNA mutation.

OBJECTIVE: To investigate the quantitative diffusion properties of the corpus callosum (CC) in a large group of patients with periventricular nodular heterotopia (PNH) related epilepsy and to further investigate the effect of Filamin A (FLNA) mutation on these properties. METHODS: Patients with PNH (n = 34), subdivided into FLNA-mutated (n = 11) and FLNA-nonmutated patients (n = 23) and healthy controls (n = 34), underwent 3.0 T structural MRI and diffusion imaging scan (64 direction). Fractional anisotropy (FA) and mean diffusivity (MD) were measured in the three major subdivisions of the CC (genu, body and splenium). Correlations between DTI metric changes and clinical parameters were also evaluated. Furthermore, the effect of FLNA mutation on structural integrity of the corpus callosum was examined. RESULTS: Patients with PNH and epilepsy had significant reductions in FA for the genu and splenium of the CC, accompanied by increases in MD for the splenium, as compared to healthy controls. There were no correlations between clinical parameters of epilepsy and MD. The FA value in the splenium negatively correlated with epilepsy duration. Interestingly, FLNA-mutated patients showed significantly decreased FA for all three major subdivisions of the CC, and increased MD for the genu and splenium, as compared to HCs and FLNA-nonmutated patients. CONCLUSIONS: These findings support the conclusion that patients with epilepsy secondary to PNH present widespread microstructural changes found in the corpus callosum that extend beyond the macroscopic MRI-visible lesions. This study also indicates that FLNA may affect white matter integrity in this disorder.

Disrupted grey matter network morphology in pediatric posttraumatic stress disorder.

Introduction: Disrupted topological organization of brain functional networks has been widely observed in posttraumatic stress disorder (PTSD). However, the topological organization of the brain grey matter (GM) network has not yet been investigated in pediatric PTSD who was more vulnerable to develop PTSD when exposed to stress. Materials and methods: Twenty two pediatric PTSD patients and 22 matched trauma-exposed controls who survived a massive earthquake (8.0 magnitude on Richter scale) in Sichuan Province of western China in 2008 underwent structural brain imaging with MRI 8-15 months after the earthquake. Brain networks were constructed based on the morphological similarity of GM across regions, and analyzed using graph theory approaches. Nonparametric permutation testing was performed to assess group differences in each topological metric. Results: Compared with controls, brain networks of PTSD patients were characterized by decreased characteristic path length (P = 0.0060) and increased clustering coefficient (P = 0.0227), global efficiency (P = 0.0085) and local efficiency (P = 0.0024). Locally, patients with PTSD exhibited increased centrality in nodes of the default-mode (DMN), central executive (CEN) and salience networks (SN), involving medial prefrontal (mPFC), parietal, anterior cingulate (ACC), occipital and olfactory cortex and hippocampus. Conclusions: Our analyses of topological brain networks in children with PTSD indicate a significantly more segregated and integrated organization. The associations and disassociations between these grey matter findings and white matter (WM) and functional changes previously reported in this sample may be important for diagnostic purposes and understanding the brain maturational effects of pediatric PTSD.

Region-specific connectivity in patients with periventricular nodular heterotopia and epilepsy: A study combining diffusion tensor imaging and functional MRI.

OBJECTIVES: Periventricular nodular heterotopia (PNH) is an important cause of chronic epilepsy. The purpose of this study was to evaluate region-specific connectivity in PNH patients with epilepsy and assess correlation between connectivity strength and clinical factors including duration and prognosis. METHODS: Diffusion tensor imaging (DTI) and resting state functional MRI (fMRI) were performed in 28 subjects (mean age 27.4years; range 9-56years). The structural connectivity of fiber bundles passing through the manually-selected segmented nodules and other brain regions were analyzed by tractography. Cortical lobes showing functional correlations to nodules were also determined. RESULTS: For all heterotopic gray matter nodules, including at least one in each subject, the most frequent segments to which nodular heterotopia showed structural (132/151) and functional (146/151) connectivity were discrete regions of the ipsilateral overlying cortex. Agreement between diffusion tensor tractography and functional connectivity analyses was conserved in 81% of all nodules (122/151). In patients with longer duration or refractory epilepsy, the connectivity was significantly stronger, particularly to the frontal and temporal lobes (P<0.05). CONCLUSIONS: Nodules in PNH were structurally and functionally connected to the cortex. The extent is stronger in patients with longstanding or intractable epilepsy. These findings suggest the region-specific interactions may help better evaluate prognosis and seek medical or surgical interventions of PNH-related epilepsy.