Nodal Level Research Articles

Structural and functional multilayer network analysis in restless legs syndrome patients.

The combination of brain structural and functional connectivity offers complementary insights into its organisation. Multilayer network analysis explores various relationships across different layers within a single system. We aimed to investigate changes in the structural and functional multilayer network in 69 patients with primary restless legs syndrome (RLS) compared with 50 healthy controls. Participants underwent diffusion tensor imaging (DTI) and resting state-functional magnetic resonance imaging (rs-fMRI) using a three-tesla MRI scanner. We constructed a structural connectivity matrix derived from DTI using a DSI program and made a functional connectivity matrix based on rs-fMRI using an SPM program and CONN toolbox. A multilayer network analysis, using BRAPH program, was then conducted to assess the connectivity patterns in both groups. At the global level, significant differences there were between the patients with RLS and healthy controls. The average multiplex participation was lower in patients with RLS than in healthy controls (0.804 vs. 0.821, p = 0.042). Additionally, several regions showed significant differences in the nodal level in multiplex participation between patients with RLS and healthy controls, particularly the frontal and temporal lobes. The regions affected included the inferior frontal gyrus, medial orbital gyrus, precentral gyrus, rectus gyrus, insula, superior and inferior temporal gyrus, medial and lateral occipitotemporal gyrus, and temporal pole. These results represent evidence of diversity in interactions between structural and functional connectivity in patients with RLS, providing a more comprehensive understanding of the brain network in RLS. This may contribute to a precise diagnosis of RLS, and aid the development of a biomarker to track treatment effectiveness.

Multilayer network changes in patients with migraine.

To investigate changes in the multilayer network in patients with migraine compared to healthy controls. This study enrolled 82 patients with newly diagnosed migraine without aura and 53 healthy controls. Brain magnetic resonance imaging (MRI) was conducted using a 3-tesla MRI scanner, including three-dimensional T1-weighted and diffusion tensor imaging (DTI). A gray matter layer matrix was created with a morphometric similarity network using T1-weighted imaging and the FreeSurfer program. A white matter layer matrix was also created with structural connectivity using the DTI studio (DSI) program. A multilayer network analysis was then performed by applying graph theory using the BRAPH program. Significant changes were observed in the multilayer network at the global level in patients with migraines compared to the healthy controls. The multilayer modularity (0.177vs. 0.160, p=.0005) and average multiplex participation (0.934vs. 0.924, p=.002) were higher in patients with migraines than in the healthy controls. In contrast, the average multilayer clustering coefficient (0.406vs. 0.461, p=.0005), average overlapping strength (56.061vs. 61.676, p=.0005), and average weighted multiplex participation (0.847vs. 0.878, p=.0005) were lower in patients with migraine than in the healthy controls. In addition, several regions showed significant changes in the multilayer network at the nodal level, including multiplex participation, multilayer clustering coefficients, overlapping strengths, and weighted multiplex participation. This study demonstrated significant changes in the multilayer network in patients with migraines compared to healthy controls. This could aid an understanding of the complex brain network in patients with migraine and may be associated with the pathophysiology of migraines. Patients with migraine show multilayer network changes in widespreading brain regions compared to healthy controls, and specific brain areas seem to play a hub role for pathophysiology of the migraine.

Preoperative predictors for recurrence sites associated with poor post-recurrence survival after surgery of non-small cell lung cancer: a multicenter study

BackgroundThe recurrence site that influences post-recurrence survival (PRS) in patients with non-small cell lung cancer (NSCLC) undergoing surgery and the preoperative predictors of recurrence remain unclear.MethodsCohorts 1 and 2 had 4520 (who underwent complete resection for p-stage 0-IIIA NSCLC) and 727 (who experienced recurrence after surgery) patients, respectively. The initial sites of recurrence were the lungs (309 cases), thoracic lymph nodes (225 cases), pleura (112 cases), bone (110 cases), central nervous system (86 cases), adrenal gland (25 cases), abdomen (60 cases), cervical and axillary lymph nodes (38 cases), chest wall (13 cases), skin (5 cases), and eye and tongue (3 cases). For cohort 2 analysis, the initial recurrence site that resulted in poor PRS was analyzed by multivariable analysis using a Cox proportional hazard model. For cohort 1 analysis, the preoperative predictors of recurrence patterns with poor PRS were analyzed by multivariable analysis using a logistic regression model.ResultsIn cohort 2 analysis, recurrence in the central nervous system (hazard ratio [HR], 1.70; p < 0.001), bone (HR, 1.75; p < 0.001), abdomen (HR, 2.39; p < 0.001), and pleura (HR, 1.69; p < 0.001) were independent poor prognostic recurrent sites for PRS and they were high-risk sites (HRS). Intrathoracic lymph nodes, cervical and axillary lymph nodes, lungs, chest wall, adrenal gland, eye and tongue, and skin were low-risk sites (LRS) that did not affect PRS. Patients with multiple LRS without HRS recurrence had a worse prognosis than those with a single LRS without HRS recurrence (5-year PRS 20.2% vs. 37.7%, p < 0.001) and were comparable to those with HRS recurrence (p = 1.000). In cohort 1 analysis, preoperative predictors for HRS and multiple LRS recurrences were positron emission tomography (PET) maximum standardized uptake value (maxSUV) ≥ 3.2 (HR, 5.09; p < 0.001), clinical nodal metastasis (HR, 2.00; p < 0.001), tumor size ≥ 2.4 cm (HR, 1.96; p < 0.001) and carcinoembryonic antigen (CEA) ≥ 5 ng/ml (HR, 1.41; p = 0.004). The cumulative incidence rates of HRS and multiple LRS recurrences within 5 years were 55.9%, 40.9%, 26.3%, 11.1%, and 3.5% (p < 0.001) in patients with 4, 3, 2, 1 and 0 of the above risks, respectively.ConclusionsHRS and multiple LRS were vital recurrences associated with poor PRS. Preoperative PET maxSUV, clinical nodal metastasis, tumor size, and CEA level predicted the incidence of vital recurrence.

Multilayer network analysis of dynamic network reconfiguration in patients with moderate-to-severe obstructive sleep apnea and its association with neurocognitive function

BackgroundBrain functional network disruption and neurocognitive dysfunction have been reported in obstructive sleep apnea (OSA) patients. Nevertheless, most research studies static networks, while brain evolution continues dynamically. PurposeTo investigate the characteristics of dynamical networks in moderate-to-severe OSA patients using multilayer network analysis of dynamic networks and compare their association with neurocognitive function. MethodsTwenty-seven moderate-to-severe OSA patients and twenty-five matched healthy controls (HCs) who completed the examination of the Epworth sleepiness scale (ESS), neurocognitive function, polysomnography, and functional magnetic resonance imaging (fMRI) were prospectively included. The dynamic variations of resting-state functional networks in both groups were described via network switching rate. Switching rates and their correlation with clinical parameters were analyzed. ResultsAt the global level, network switching rates were notably lower in the OSA group than in the HCs group (p = 0.002). More specifically, the differences include the default mode network (DMN), auditory network, and ventral attention network at the subnetwork level, and the right rolandic operculum, left middle temporal gyrus, and right precentral gyrus at the nodal level. Furthermore, these altered switching rates have a close correlation with ESS, sleep parameters, and neurocognitive function. ConclusionPatients with moderate-to-severe OSA showed lower network switching rates, especially in the DMN, auditory network, and ventral attention network. The disruption of dynamic functional networks may be a potentially crucial mechanism of neurocognitive dysfunction in moderate-to-severe OSA patients.

Occult Nodal Metastases in Individuals with Clinically Node-Negative Salivary Gland Malignancies.

Salivary gland malignancies comprise a heterogeneous group of pathologies, for which treatment of the clinically negative neck may vary depending on numerous factors. Herein we present data on occult nodal metastases (ONM) as well as survival and recurrence from a large series of cN0 salivary gland malignancies. Retrospective chart review was conducted on 532 patients, with 389 patients with major salivary gland cancers and 143 patients with minor salivary gland cancers. Demographic and treatment data were included and rates of ONM, overall survival, local recurrence, regional recurrence, and distant recurrence were analyzed. We found that the overall rate of ONM for parotid was 27% (63/235), for submandibular/sublingual was 35% (18/52), and for minor was 15% (4/26). Analysis of ONM rate at each nodal level was also performed, finding higher rates of level IV and V ONM than prior studies. Submandibular/sublingual and minor salivary gland malignancies showed a predominance of ONMs at levels I-III. Our survival and recurrence rates were similar to those found in previous studies. Our data also demonstrate a predominance of ONM in levels I-III for submandibular/sublingual and minor salivary gland cancers, suggesting elective dissection in these levels. 4 Laryngoscope, 134:1705-1715, 2024.

Aberrant functional brain network organization is associated with relapse during 1-year follow-up in alcohol-dependent patients.

Alcohol dependence (AD) is a debilitating disease associated with high relapse rates even after long periods of abstinence. Thus, elucidating neurobiological substrates of relapse risk is fundamental for the development of novel targeted interventions that could promote long-lasting abstinence. In the present study, we analysed resting-state functional magnetic resonance imaging (rsfMRI) data from a sample of recently detoxified patients with AD (n = 93) who were followed up for 12 months after rsfMRI assessment. Specifically, we employed graph theoretic analyses to compare functional brain network topology and functional connectivity between future relapsers (REL, n = 59), future abstainers (ABS, n = 28) and age- and gender-matched controls (CON, n = 83). Our results suggest increased whole-brain network segregation, decreased global network integration and overall blunted connectivity strength in REL compared with CON. Conversely, we found evidence for a comparable network architecture in ABS relative to CON. At the nodal level, REL exhibited decreased integration and decoupling between multiple brain systems compared with CON, encompassing regions associated with higher-order executive functions, sensory and reward processing. Among patients with AD, increased coupling between nodes implicated in reward valuation and salience attribution constitutes a particular risk factor for future relapse. Importantly, aberrant network organization in REL was consistently associated with shorter abstinence duration during follow-up, portending to a putative neural signature of relapse risk in AD. Future research should further evaluate the potential diagnostic value of the identified changes in network topology and functional connectivity for relapse prediction at the individual subject level.

Long-term Intensive Soccer Training Induced Dynamic Reconfiguration of Brain Network.

Long-term motor skill learning has been shown to impact the functional plasticity of the brain. Athletes, as a unique population, exhibit remarkable adaptive changes in the static properties of their brain networks. However, studying the differences between expert and novice athletes using a dynamic brain network framework can provide a fresh perspective on how motor skill learning affects the functional organization of the brain. In this study, we investigated the dynamic properties of brain networks in expert and novice soccer players at the whole-brain, network, and region-based levels. Our findings revealed that expert soccer players displayed reduced integration and increased segregation at the whole-brain level. As for network level, experts exhibited increased segregation and reduced flexibility in the visual network, enhanced integration between the visual and ventral attention networks, and decreased integration in the subcortical-sensorimotor and subcortical-cerebellar networks. Additionally, specific brain regions within the visual network exhibited greater recruitment in expert soccer players compared to novices at the nodal level. Furthermore, classification analyses demonstrated the critical role played by the visual network in the classification process. In conclusion, our study provides new insights into the dynamic properties of brain networks in expert and novice soccer players, and suggests that reduced integration and increased segregation in the visual network may be neuroimaging marker that distinguish expert soccer players from novices. Our findings may have implications for the training and development of athletes and advance our understanding of how motor skill learning affects brain functional organization.

Tailoring Radiation to the Contralateral Neck for Midline HPV-Mediated Oropharyngeal Squamous Cell Carcinoma (p16+ OPSCC)

De-intensification strategies for locally advanced p16+ OPSCC are under active investigation, including omission of contralateral neck radiation (RT) for well-lateralized T1-2N0-2a. This study evaluates the outcomes of omitting contralateral neck nodal levels for p16+ OPSCC that are not well-lateralized. A retrospective review was done of 134 consecutive patients with non-metastatic p16+ OPSCC that were not well-lateralized (< 1 cm from midline or ≥ 1 cm extension to soft palate or base of tongue) who were treated with definitive chemoradiation from 2013 to 2019. IMRT to an EQD2 6364-6735 cGy (200-220 cGy per fraction) was used to treat the primary tumor and ipsilateral or bilateral neck, with tailored nodal level coverage and dose, and with concurrent paclitaxel and carboplatin. Contralateral neck RT was tailored in 121 patients: omitted in 11, limited to level II in 9, and limited to level II and III in 101 (contralateral lower neck omitted); the remaining 13 had bilateral level II-IV neck RT. Local and regional recurrences were evaluated. Median follow up was 45.34 months. Local and/or regional recurrence was noted in 9/134 (6.7%). 3 (2%) recurred in the contralateral neck in unirradiated tissue (out-of-field). All three were salvaged. The remaining 6 recurrences (4%) were in-field; one was at the primary site and 5 were nodal (all ipsilateral). 4 of the 5 regional recurrences were in a location that was treated to EQD2 7000 cGy (all had PET avid nodal disease upfront that was included in the high dose level); the other region of recurrence was treated to an EQD2 6353 cGy (the only recurrence in a never smoker). 4 of the 5 neck recurrences underwent neck dissection; one further underwent adjuvant RT to 5940 cGy in 33 fractions and remains disease-free. 2 of those who underwent salvage neck dissection alone subsequently developed distant metastases. The majority of first recurrences were distant, 19.4% (26/134). 3-year progression free survival (PFS) was 74.41% (95% CI, 65.63-81.26). Taken together, regional recurrence rate in the contralateral, unirradiated neck was 2.5% (3/121) and ultimate locoregional control was 99% (132/134). Our tailored approach demonstrates a contralateral neck local control of 97.5% (118/121) regardless of tumor lateralization; those who recurred in unirradiated cervical lymph nodes were successfully salvaged. Limiting this analysis is moderate sample size and retrospective nature, but it raises important alternative de-escalation strategies (RT volume reduction) for p16+ OPSCC aside from dose reduction, which is under active investigation in phase II/III trials. Improved systemic therapies are needed to combat distant metastases. Prospective randomized clinical trials are needed for further evaluation of nodal omission for definitive chemoradiation of non-well-lateralized p16+ OPSCC.

Lymph node level ratio as a predictor of survival in oral cavity squamous cell carcinoma

ObjectiveTo evaluate whether nodal yields and ratios based on level serves as prognostic indicators in patients with oral cavity squamous cell carcinoma undergoing neck dissection. Materials and MethodsA retrospective analysis of 342 patients with oral cavity squamous cell carcinoma treated surgically between 1998 and 2017 were included.Demographics and clinicopathologic data were collated. Disease specific survival and overall survival were analyzed via Kaplan-Meier method and log-rank test as well as univariable and multivariable Cox models. ResultsTotal nodal yield is associated with improved overall and disease specific survival (p < 0.01). Total positive nodal yield (p < 0.01), positive nodal ratio per level (p < 0.001), and identification of <4 lymph nodes/level (p < 0.001) are associated with worse disease specific survival and overall survival. A ratio of at least 4 lymph nodes/level dissected yields the maximal hazard ratio on for both disease specific and overall survival optimizes the Kaplan-Meier split between survival groups. After controlling for sex, age, margin status, disease stage, extranodal extension, perineural invasion, and lymphovascular invasion as fixed covariates in the Cox models, a nodal level ratio of 4 lymph nodes/level provides hazard ratio (95% CI) of 3.59 (1.69, 7.60); p < 0.0006) for disease free survival and 2.90 (1.54, 5.46; p < 0.001) for overall survival. ConclusionNodal level ratio of < 4 lymph nodes/level is associated with worse disease specific and overall survival in oral cavity squamous cell carcinoma. This level-specific metric may prove useful qualitatively and in predicting survival in oral cavity cancer with broader utility to address variations in levels of neck dissection performed.

Brain network analysis reveals convergent and divergent aberrations between mild stroke patients with cortical and subcortical infarcts during cognitive task performing.

Although consistent evidence has revealed that cognitive impairment is a common sequela in patients with mild stroke, few studies have focused on it, nor the impact of lesion location on cognitive function. Evidence on the neural mechanisms underlying the effects of mild stroke and lesion location on cognitive function is limited. This prompted us to conduct a comprehensive and quantitative study of functional brain network properties in mild stroke patients with different lesion locations. Specifically, an empirical approach was introduced in the present work to explore the impact of mild stroke-induced cognitive alterations on functional brain network reorganization during cognitive tasks (i.e., visual and auditory oddball). Electroencephalogram functional connectivity was estimated from three groups (i.e., 40 patients with cortical infarctions, 48 patients with subcortical infarctions, and 50 healthy controls). Using graph theoretical analysis, we quantitatively investigated the topological reorganization of functional brain networks at both global and nodal levels. Results showed that both patient groups had significantly worse behavioral performance on both tasks, with significantly longer reaction times and reduced response accuracy. Furthermore, decreased global and local efficiency were found in both patient groups, indicating a mild stroke-related disruption in information processing efficiency that is independent of lesion location. Regarding the nodal level, both divergent and convergent node strength distribution patterns were revealed between both patient groups, implying that mild stroke with different lesion locations would lead to complex regional alterations during visual and auditory information processing, while certain robust cognitive processes were independent of lesion location. These findings provide some of the first quantitative insights into the complex neural mechanisms of mild stroke-induced cognitive impairment and extend our understanding of underlying alterations in cognition-related brain networks induced by different lesion locations, which may help to promote post-stroke management and rehabilitation.

Effects of phase encoding direction on test-retest reliability of human functional connectome

The majority of human connectome studies in the literature based on functional magnetic resonance imaging (fMRI) data use either an anterior-to-posterior (AP) or a posterior-to-anterior (PA) phase encoding direction (PED). However, whether and how PED would affect test-retest reliability of functional connectome is unclear. Here, in a sample of healthy subjects with two sessions of fMRI scans separated by 12 weeks (two runs per session, one with AP, the other with PA), we tested the influence of PED on global, nodal, and edge connectivity in the constructed brain networks. All data underwent the state-of-the-art Human Connectome Project (HCP) pipeline to correct for phase-encoding-related distortions before entering analysis. We found that at the global level, the PA scans showed significantly higher intraclass correlation coefficients (ICCs) for global connectivity compared with AP scans, which was particularly prominent when using the Seitzman-300 atlas (versus the CAB-NP-718 atlas). At the nodal level, regions most strongly affected by PED were consistently mapped to the cingulate cortex, temporal lobe, sensorimotor areas, and visual areas, with significantly higher ICCs during PA scans compared with AP scans, regardless of atlas. Better ICCs were also observed during PA scans at the edge level, in particular when global signal regression (GSR) was not performed. Further, we demonstrated that the observed reliability differences between PEDs may relate to a similar effect on the reliability of temporal signal-to-noise ratio (tSNR) in the same regions (that PA scans were associated with higher reliability of tSNR than AP scans). Averaging the connectivity outcome from the AP and PA scans could increase median ICCs, especially at the nodal and edge levels. Similar results at the global and nodal levels were replicated in an independent, public dataset from the HCP-Early Psychosis (HCP-EP) study with a similar design but a much shorter scan session interval. Our findings suggest that PED has significant effects on the reliability of connectomic estimates in fMRI studies. We urge that these effects need to be carefully considered in future neuroimaging designs, especially in longitudinal studies such as those related to neurodevelopment or clinical intervention.

Role of MMP1 and MMP10 in local invasion and distant metastasis in different levels of oral squamous cell carcinoma - A immunohistochemical comparative study.

Matrix metalloproteinases (MMPs) are basically a part of a large family of proteolytic enzymes. They play an important role in degrading extracellular matrix and basement membrane, which is a basic mechanism in local invasion and tumour metastasis. The aim of this study was to evaluate immunohistochemically the expression of MMP1 and MMP10 in tumour invasion locally and at distant levels, including lymph nodes at different levels in oral squamous cell carcinoma (OSCC). A total of 50 tissue samples with clinically confirmed OSCC and 15 normal oral mucosal tissues will be included in the study. Immunohistochemical staining will be performed for the demonstration of MMP1 and MMP10 in lesional tissue, perilesional tissue, and lymph nodes of different levels that were evaluated with respect to microscopic features. All OSCC cases had MMP1 and MMP10 expression levels. The expression increased as the nodal level increased from level I to level V. This difference was statistically significant at P < 0.001 Both MMPs were not expressed in normal epithelial cells. There was no significant correlation between MMP1 and MMP10 expression. This study showed that MMP1 and MMP10 are expressed in the tissues of OSCC and may serve as prognostic indicators for the disease.

Aberrant modular segregation of brain networks in female patients with bulimia nervosa.

Bulimia nervosa (BN) is an eating disorder associated with the dysfunction of intrinsic brain networks. However, whether the network disruptions in BN patients manifest as dysconnectivity or imbalances of network modular segregation remains unclear. We collected data from 41 women with BN and 41 matched healthy control (HC) women. We performed graph theory analysis based on resting-state functional magnetic resonance imaging (RS-fMRI) data; then, we computed the participation coefficient (PC) among brain modules to characterize the modular segregation for the BN and HC groups. The number of intra- and inter-modular connections was calculated to explain the PC changes. Additionally, we examined the potential associations of the measures mentioned above with clinical variables within the BN group. Compared with the HC group, the BN group showed significantly decreased PC in the fronto-parietal network (FPN), cingulo-opercular network (CON), and cerebellum (Cere). Additionally, the number of intra-modular connections of the default mode network (DMN) and the number of the inter-modular connections between the DMN and CON, FPN and Cere, and CON and Cere in the BN group were lower than those in the HC group. The nodal level analysis showed that the BN group had a decreased PC of the anterior prefrontal cortex (aPFC), dorsal frontal cortex (dFC), inferior parietal lobule (IPL), thalamus, and angular gyrus. Further, these metrics were significantly correlated with clinical variables in the BN group. These findings may provide novel insights to capture atypical topologies associated with pathophysiology mechanisms and clinical symptoms underlying BN.

Functional brain network alterations in the co-occurrence of autism spectrum disorder and attention deficit hyperactivity disorder.

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are two highly prevalent and commonly co-occurring neurodevelopmental disorders. The neural mechanisms underpinning the comorbidity of ASD and ADHD (ASD + ADHD) remain unclear. We focused on the topological organization and functional connectivity of brain networks in ASD + ADHD patients versus ASD patients without ADHD (ASD-only). Resting-state functional magnetic resonance imaging (rs-fMRI) data from 114 ASD and 161 typically developing (TD) individuals were obtained from the Autism Brain Imaging Data Exchange II. The ASD patients comprised 40 ASD + ADHD and 74 ASD-only individuals. We constructed functional brain networks for each group and performed graph-theory and network-based statistic (NBS) analyses. Group differences between ASD + ADHD and ASD-only were analyzed at three levels: nodal, global, and connectivity. At the nodal level, ASD + ADHD exhibited topological disorganization in the temporal and occipital regions, compared with ASD-only. At the global level, ASD + ADHD and ASD-only displayed no significant differences. At the connectivity level, the NBS analysis revealed that ASD + ADHD showed enhanced functional connectivity between the prefrontal and frontoparietal regions, as well as between the orbitofrontal and occipital regions, compared with ASD-only. The hippocampus was the shared region in aberrant functional connectivity patterns in ASD + ADHD and ASD-only compared with TD. These findings suggests that ASD + ADHD displays altered topology and functional connectivity in the brain regions that undertake social cognition, language processing, and sensory processing.

Altered White Matter Network Topology in Panic Disorder

Panic disorder (PD) is an anxiety disorder that impairs life quality and social function and is associated with distributed brain regions. However, the alteration of the structural network remains unclear in PD patients. This study explored the specific characteristics of the structural brain network in patients with PD by graph theory analysis of diffusion tensor images (DTI). A total of 81 PD patients and 48 matched healthy controls were recruited for this study. The structural networks were constructed, and the network topological properties for individuals were estimated. At the global level, the network efficiency was higher, while the shortest path length and clustering coefficient were lower in the PD group compared to the healthy control (HC) group. At the nodal level, the PD group showed a widespread higher nodal efficiency and lower average shortest path length in the prefrontal, sensorimotor, limbic, insula, and cerebellum regions. Overall, the current results showed that the alteration of information processing in the fear network might play a role in the pathophysiology of PD.

Impaired structural and reserved functional topological organizations of brain networks in Parkinson’s disease with freezing of gait

Freezing of gait (FOG) is a common disabling motor disturbance in Parkinson's disease (PD). Our study aimed to probe the topological organizations of structural and functional brain networks and their coupling in FOG. In this cross-sectional retrospective study, a total of 30 PD patients with FOG (PD-FOG), 40 patients without FOG, and 25 healthy controls (HCs) underwent clinical assessments and magnetic resonance imaging (MRI) scanning. Large-scale structural and functional brain networks were constructed. Subsequently, global and nodal graph theoretical properties and functional-structural coupling were investigated. Finally, correlations between the altered brain topological properties and freezing severity were analyzed in PD-FOG. For structural networks, at the global level, PD-FOG exhibited increased normalized characteristic path length (P=0.040, Bonferroni-corrected) and decreased global efficiency (P=0.005, Bonferroni-corrected) compared with controls, and showed reduced global (P=0.001, Bonferroni-corrected) and local (P=0.032, Bonferroni-corrected) efficiency relative to patients without FOG. At the nodal level, nodal efficiency of structural networks was reduced in PD-FOG compared with PD patients without FOG, located in the left supplementary motor area (SMA), gyrus rectus, and middle cingulate cortex (MCC) (all P<0.05, Bonferroni-corrected). Notably, altered global and nodal properties of structural networks were significantly correlated with Freezing of Gait Questionnaire scores [all P<0.05, false discovery rate (FDR)-corrected]. However, only an increase in local efficiency (P=0.003, Bonferroni-corrected) of functional networks was identified in PD-FOG compared with those without FOG. No significant structural-functional coupling was detected among the 3 groups. This study demonstrates the extensively impaired structural and relatively reserved functional network topological organizations in PD-FOG. Our results also provide evidence that the pathogenesis of PD-FOG is primarily attributable to network vulnerability established by crucial structural damage, especially in the left SMA, gyrus rectus, and MCC.

Directed Functional Brain Connectivity is Altered in Sub-threshold Amyloid-β Accumulation in Cognitively Normal Individuals.

Several studies have shown that amyloid-β (Aβ) deposition below the clinically relevant cut-off levels is associated with subtle changes in cognitive function and increases the risk of developing future Alzheimer's disease (AD). Although functional MRI is sensitive to early alterations occurring during AD, sub-threshold changes in Aβ levels have not been linked to functional connectivity measures. This study aimed to apply directed functional connectivity to identify early changes in network function in cognitively unimpaired participants who, at baseline, exhibit Aβ accumulation below the clinically relevant threshold. To this end, we analyzed baseline functional MRI data from 113 cognitively unimpaired participants of the Alzheimer's Disease Neuroimaging Initiative cohort who underwent at least one 18F-florbetapir-PET after the baseline scan. Using the longitudinal PET data, we classified these participants as Aβ negative (Aβ-) non-accumulators (n = 46) and Aβ- accumulators (n = 31). We also included 36 individuals who were amyloid-positive (Aβ+) at baseline and continued to accumulate Aβ (Aβ+ accumulators). For each participant, we calculated whole-brain directed functional connectivity networks using our own anti-symmetric correlation method and evaluated their global and nodal properties using measures of network segregation (clustering coefficient) and integration (global efficiency). When compared to Aβ- non-accumulators, the Aβ- accumulators showed lower global clustering coefficient. Moreover, the Aβ+ accumulator group exhibited reduced global efficiency and clustering coefficient, which at the nodal level mainly affected the superior frontal gyrus, anterior cingulate cortex, and caudate nucleus. In Aβ- accumulators, global measures were associated with lower baseline regional PET uptake values, as well as higher scores on the Modified Preclinical Alzheimer Cognitive Composite. Our findings indicate that directed connectivity network properties are sensitive to subtle changes occurring in individuals who have not yet reached the threshold for Aβ positivity, which makes them a potentially viable marker to detect negative downstream effects of very early Aβ pathology.

Mapping white matter structural and network alterations in betel quid-dependent chewers using high angular resolution diffusion imaging.

To evaluate brain white matter diffusion characteristics and anatomical network alterations in betel quid dependence (BQD) chewers using high angular resolution diffusion imaging (HARDI). The current study recruited 53 BQD chewers and 37 healthy controls (HC) in two groups. We explored regional diffusion metrics alternations in the BQD group compared with the HC group using automated fiber quantification (AFQ). We further employed the white matter (WM) anatomical network of HARDI to explore connectivity alterations in BQD chewers using graph theory. BQD chewers presented significantly lower FA values in the left and right cingulum cingulate, the left and right thalamic radiation, and the right uncinate. The BQD has a significantly higher RD value in the right uncinate fasciculus than the HC group. At the global WM anatomical network level, global network efficiency (p = 0.008) was poorer and Lp (p = 0.016) was greater in the BQD group. At the nodal WM anatomical network level, nodal efficiency (p < 0.05) was lower in the BQD group. Our findings provide novel morphometric evidence that brain structural changes in BQD are characterized by white matter diffusivity and anatomical network connectivity among regions of the brain, potentially leading to the enhanced reward system and impaired inhibitory control.

Structural covariance network of the hippocampus-amygdala complex in medication-naïve patients with first-episode major depressive disorder.

The hippocampus and amygdala are densely interconnected structures that work together in multiple affective and cognitive processes that are important to the etiology of major depressive disorder (MDD). Each of these structures consists of several heterogeneous subfields. We aim to explore the topologic properties of the volume-based intrinsic network within the hippocampus-amygdala complex in medication-naïve patients with first-episode MDD. High-resolution T1-weighted magnetic resonance imaging scans were acquired from 123 first-episode, medication-naïve, and noncomorbid MDD patients and 81 age-, sex-, and education level-matched healthy control participants (HCs). The structural covariance network (SCN) was constructed for each group using the volumes of the hippocampal subfields and amygdala subregions; the weights of the edges were defined by the partial correlation coefficients between each pair of subfields/subregions, controlled for age, sex, education level, and intracranial volume. The global and nodal graph metrics were calculated and compared between groups. Compared with HCs, the SCN within the hippocampus-amygdala complex in patients with MDD showed a shortened mean characteristic path length, reduced modularity, and reduced small-worldness index. At the nodal level, the left hippocampal tail showed increased measures of centrality, segregation, and integration, while nodes in the left amygdala showed decreased measures of centrality, segregation, and integration in patients with MDD compared with HCs. Our results provide the first evidence of atypical topologic characteristics within the hippocampus-amygdala complex in patients with MDD using structure network analysis. It provides more delineate mechanism of those two structures that underlying neuropathologic process in MDD.

Frequency of Skip Metastasis to the Cervical Lymph Nodes in Oral Squamous Cell Carcinoma

Background: Oral Squamous Cell Carcinoma (OSCC) commonly spreads across regional lymph nodes. Presence or lack of metastasis to the cervical lymph nodes is an essential prognostic factor. The regional metastatic pattern to the cervical lymph nodes is defined as the orderly involvement of the successive anatomical lymph node levels. When the sequential order of involvement is lost and metastases are found at a lower level without involving the first echelon nodes or groups of intermediate nodes, then it is called skip metastases. Knowledge of Skip metastases will allow patients to prevent from receiving under and overt therapy. Current treatment of oral squamous cell carcinoma is primary resection followed by elective/therapeutic neck dissection. Regarding neck dissection, there is a dilemma that up to which level should be performed. Some prefer up to level III and some prefer up to level IV based on evidence of skip metastasis to level IV. This study conducted to find out the frequency of skip metastasis and its pattern according to the site, size and grading of primary oral squamous cell carcinoma.&#x0D; Materials and methods: This was a cross sectional study performed in between August 2018 to September 2019 among 58 patients having histologically proven oral squamous cell carcinoma of tongue, buccal mucosa and retro molar trigone undergoing elective and therapeutic neck dissection. Cervical lymph nodes along with fibro-fatty tissue from patients underwent neck dissection except super selective neck dissection were fixed with 10% formalin in separate containers. The containers were marked with nodal level and sent to pathology department for histopathological examination.&#x0D; Results: Out of 58 patients, 32 (55.2%) had cervical nodal metastasis on postoperative histopathology report, 26 (44.8%) patients had no nodal metastasis and 7 (12.1%) developed skip metastasis. Oral squamous cell carcinoma of tongue was found to be the most frequent site to develop skip metastasis to the cervical lymph node. Also, skip metastases were relatively higher in greater tumour grading and T-stages.&#x0D; Conclusion: Chances of skip metastasis should be considered during treatment planning, especially for oral squamous cell carcinoma of the tongue. For the majority of cases with N0 neck, elective neck dissection up to level III should be performed. In case of carcinoma of Tongue, high-grade tumour and advanced T-stages, elective neck dissection should be performed up to level IV.&#x0D; IAHS Medical Journal Vol 4(2), December 2021; 36-40