Bioactive glasses (BGs) bond with bone by forming hydroxy carbonate apatite (HCA) upon reaction in physiological fluid, a phenomenon known as bioactivity. BGs structural network connectivity determines their bioactivity. Sol-gel BGs are synthesized through the hydrolysis and condensation of metal alkoxide precursors in the presence of a catalyst, in aqueous environments. Several sol-gel synthesis parameters directly impact BG network connectivity: pH (i.e. acid or basic catalysis), water to alkoxide ratio (Rw), alkoxide type and presence of dopant ions. However, the relationship between bioactivity and these parameters remains surprisingly unexplored. This study highlights the relationship between synthesis pH, Rw, network connectivity and bioactivity in silica-based sol-gel BGs and BGs doped with titanium (Ti) ions (TiBGs), the latter selected for their known ability to enhance network connectivity. BGs and TiBGs are synthesized with various Rw values under acidic and basic conditions, and their bioactivity is assessed in simulated body fluid for 7 days. Increasing Rw decreases network connectivity and increases bioactivity of BGs with high network connectivity, as observed for base-catalyzed BGs and for both acid and base catalyzed TiBGs, but not in BGs with lower connectivity as evidenced in acid-catalyzed BGs. Basic catalysis of TiBGs prevents crystalline TiO2 domain formation, which was instead consistently observed in TiBGs synthesized under acidic catalysis. These findings help the design of BGs for applications where ion release needs to be enhanced even in the presence of dopants that slow down HCA formation, and of BGs with specific properties, e.g. TiO2-containing BGs with potential bactericidal activity. STATEMENT OF SIGNIFICANCE: Bioactive glasses (BGs) bond with bone by dissolving and forming hydroxycarbonate apatite (HCA) on their surface, offering applications in medicine and dentistry. BG\'s network connectivity influences its dissolution rate, and hence HCA formation. While solution-gelation (sol-gel) is commonly used for BG production, the effect of sol gel synthesis parameters on HCA formation remains unexplored. We studied the relationship between synthesis parameters (water-to-alkoxide ratio (Rw), catalyst, and dopant ions, particularly titanium), BG network connectivity, and HCA formation. We find that increasing Rw with any catalyst enhances HCA formation, particularly in glasses with high network connectivity. This understanding allows tailoring BG synthesis for different applications, e.g. those requiring doping with ions that increase network connectivity and fills a crucial gap in BG literature.

There is such a vast proliferation of scientific theories of consciousness that it is worrying some scholars. There are even competitions to test different theories, and the results are inconclusive. Consciousness research, far from converging toward a unifying framework, is becoming more discordant than ever, especially with respect to theoretical elements that do not have a clear neurobiological basis. Rather than dueling theories, an integration across theories is needed to facilitate a comprehensive view on consciousness and on how normal nervous system dynamics can develop into pathological states. In dealing with what is considered an extremely complex matter, we try to adopt a perspective from which the subject appears in relative simplicity. Grounded in experimental and theoretical observations, we advance an encompassing biophysical theory, MaxCon, which incorporates aspects of several of the main existing neuroscientific consciousness theories, finding convergence points in an attempt to simplify and to understand how cellular collective activity is organized to fulfill the dynamic requirements of the diverse theories our proposal comprises. Moreover, a computable index indicating consciousness level is presented. Derived from the level of description of the interactions among cell networks, our proposal highlights the association of consciousness with maximization of the number of configurations of neural network connections -constrained by neuroanatomy, biophysics and the environment- that is common to all consciousness theories.

Network-oriented research has been increasingly popular in many scientific areas. In neuroscience research, imaging-based network connectivity measures have become the key for understanding brain organizations, potentially serving as individual neural fingerprints. There are major challenges in analyzing connectivity matrices, including the high dimensionality of brain networks, unknown latent sources underlying the observed connectivity, and the large number of brain connections leading to spurious findings. In this paper we propose a novel blind source separation method with low-rank structure and uniform sparsity (LOCUS) as a fully data-driven decomposition method for network measures. Compared with the existing method that vectorizes connectivity matrices ignoring brain network topology, LOCUS achieves more efficient and accurate source separation for connectivity matrices using low-rank structure. We propose a novel angle-based uniform sparsity regularization that demonstrates better performance than the existing sparsity controls for low-rank tensor methods. We propose a highly efficient iterative node-rotation algorithm that exploits the block multiconvexity of the objective function to solve the nonconvex optimization problem for learning LOCUS. We illustrate the advantage of LOCUS through extensive simulation studies. Application of LOCUS to Philadelphia Neurodevelopmental Cohort neuroimaging study reveals biologically insightful connectivity traits which are not found using the existing method.

OBJECTIVE: Our objective was to explore the patterns of resting-state network (RSN) connectivity alterations and investigate how the influences of individual-level network connections on cognition varied across clinical stages without assuming a constant relationship.
METHODS: 108 PD patients with continuum of cognitive decline (PD-NC = 46, PD-MCI = 43, PDD = 19) and 34 healthy controls (HCs) underwent resting-state functional MRI and neuropsychological tests. Independent component analysis (ICA) and graph theory analyses (GTA) were employed to explore RSN connection changes. Additionally, stage-dependent differential impact of network communication on cognitive performance were examined using sparse varying coefficient modeling.
RESULTS: Compared to HCs, the dorsal attention network (DAN) and dorsal sensorimotor network (dSMN) were central networks with decreased connections in PD-NC and PD-MCI stage, while the lateral visual network (LVN) emerged as a central network in patients with dementia. Additionally, connectivity of the cerebellum network (CBN) increased in the PD-NC and PD-MCI stages. GTA demonstrated decreased nodal metrics for DAN and dSMN, coupled with an increase for CBN. Moreover, the degree centrality (DC) values of DAN and dSMN exhibited a stage-dependent differential impact on cognitive performance across the continuum of cognitive decline.
CONCLUSIONS: Our findings suggest that across the progression of cognitive impairment, the LVN gradually transitions into a core node with reduced connectivity, while the enhancement of connections in CBN diminishes. Furthermore, the non-linear relationship between the DC values of RSNs and cognitive decline indicates the potential for tailored interventions targeting specific stages.

BACKGROUND: Stress-induced Exhaustion Disorder (ED) is associated with work absenteeism and adverse health outcomes. Currently, little is known regarding how the symptoms of ED are interrelated and whether the patterns of symptoms influence treatment outcomes. To this end, the current study applied network analyses on ED patients participating in a multimodal intervention.
METHODS: The first aim of the study was to explore the internal relationships between exhaustion symptoms and identify symptoms that were more closely related than others. A second aim was to examine whether the baseline symptom network of non-responders to treatment was more closely connected than the baseline symptom networks of responders, by comparing the sum of all absolute partial correlations in the respective groups\' symptom network. This comparison was made based on the hypothesis that a more closely connected symptom network before treatment could indicate poorer treatment outcomes. Network models were constructed based on self-rated ED symptoms in a large sample of patients (n = 915) participating in a 24-week multimodal treatment program with a 12-month follow-up.
RESULTS: The internal relations between self-rated exhaustion symptoms were stable over time despite markedly decreased symptom levels throughout participation in treatment. Symptoms of limited mental stamina and negative emotional reactions to demands were consistently found to be the most closely related to other ED symptoms. Meanwhile, sleep quality and irritability were weakly related to other exhaustion symptoms. The symptom network for the full sample became significantly more closely connected from baseline to the end of treatment and 12-month follow-up. The symptom network of non-responders to treatment was not found to be more closely connected than the symptom network of responders at baseline.
CONCLUSIONS: The results of the current study suggest symptoms of limited mental stamina and negative emotional reactions to demands are central ED symptoms throughout treatment, while symptoms of irritability and sleep quality seem to have a weak relation to other symptoms of ED. The implications of these findings are discussed in relation to the conceptualization, assessment, and treatment of ED.
BACKGROUND: The clinical trial was registered on Clinicaltrials.gov 2017-12-02 (Identifier: NCT03360136).

BACKGROUND: The combination of apolipoprotein E ε4 (ApoE ε4) status, odor identification, and odor familiarity predicts conversion to mild cognitive impairment (MCI) and Alzheimer\'s disease (AD).
METHODS: To further understand olfactory disturbances and AD risk, ApoE ε4 carrier (mean age 76.38 ± 5.21) and ε4 non-carrier (mean age 76.8 ± 3.35) adults were given odor familiarity and identification tests and performed an odor identification task during fMRI scanning. Five task-related functional networks were detected using independent components analysis. Main and interaction effects of mean odor familiarity ratings, odor identification scores, and ε4 status on network activation and task-modulation of network functional connectivity (FC) during correct and incorrect odor identification (hits and misses), controlling for age and sex, were explored using multiple linear regression.
RESULTS: Findings suggested that sensory-olfactory network activation was positively associated with odor identification scores in ε4 carriers with intact odor familiarity. The FC of sensory-olfactory, multisensory-semantic integration, and occipitoparietal networks was altered in ε4 carriers with poorer odor familiarity and identification. In ε4 carriers with poorer familiarity, connectivity between superior frontal areas and the sensory-olfactory network was negatively associated with odor identification scores.
CONCLUSIONS: The results contribute to the clarification of the neurocognitive structure of odor identification processing and suggest that poorer odor familiarity and identification in ε4 carriers may signal multi-network dysfunction. Odor familiarity and identification assessment in ε4 carriers may contribute to the predictive value of risk for MCI and AD due to the breakdown of sensory-cognitive network integration. Additional research on olfactory processing in those at risk for AD is warranted.

Motor abnormalities have been identified as one common symptom in patients with generalized tonic-clonic seizures (GTCS) inspiring us to explore the disease in a motor execution condition, which might provide novel insight into the pathomechanism.
Resting-state and motor-task fMRI data were collected from 50 patients with GTCS, including 18 patients newly diagnosed without antiepileptic drugs (ND_GTCS) and 32 patients receiving antiepileptic drugs (AEDs_GTCS). Motor activation and its association with head motion and cerebral gradients were assessed. Whole-brain network connectivity across resting and motor states was further calculated and compared between groups.
All patients showed over-activation in the postcentral gyrus and the ND_GTCS showed decreased activation in putamen. Specifically, activation maps of ND_GTCS showed an abnormal correlation with head motion and cerebral gradient. Moreover, we detected altered functional network connectivity in patients within states and across resting and motor states by using repeated-measures analysis of variance. Patients did not show abnormal connectivity in the resting state, while distributed abnormal connectivity in the motor-task state. Decreased across-state network connectivity was also found in all patients.
Convergent findings suggested the over-response of activation and connection of the brain to motor execution in GTCS, providing new clues to uncover motor susceptibility underlying the disease.

Soil phoD-harboring microorganisms can facilitate phosphorus (P) transformation and increase the available P (AP) in P-limited soils; however, the mechanism by which these microorganisms enhance AP throughout the vegetation recovery process of karst ecosystems is poorly understood. Accordingly, this study investigates the effect of vegetation recovery on soil AP and the community composition and network connectivity of phoD-harboring microorganisms to elucidate the mechanism by which phoD-harboring microorganisms enhance soil AP in the four vegetation recovery stages (i.e., grassland, shrubland, shrub-arbor forest, and arbor forest) in a karst ecosystem. Results show that soil total P, AP, and microbial biomass P concentrations, as well as alkaline phosphatase activities, litter and soil nutrients, and plant diversity indices (Shannon-Wiener and Pielou) increase with advancing vegetation recovery. Moreover, the diversity indices (Shannon-Wiener and Simpson) and network complexity of the phoD-harboring microorganisms also increase with advancing vegetation recovery, leading to distinct communities among the four recovery stages. Rhizobiales, Pseudomonadales, and Burkholderiales comprise the dominant phoD-harboring microorganism orders. The relative abundances of Pseudomonadales and Burkholderiales increase with advancing vegetation recovery; Rhizobiales is the highest in shrubland and the lowest in grassland. The structural equation model results show that advanced vegetation recovery is associated with increased plant diversity, litter nutrients, and soil nutrients. The network connectivity is enhanced with advancing vegetation recovery accompanied by increasing soil phosphatase activity and P availability. These results suggest that regulating the phoD-harboring microorganism composition and network connectivity is essential to alleviate plant P limitation in karst ecosystems.

The thalamocortical system plays an important role in consciousness. How anesthesia modulates the thalamocortical interactions is not completely known.  We simultaneously recorded local field potentials(LFPs) in thalamic reticular nucleus(TRN) and ventroposteromedial thalamic nucleus(VPM), and electrocorticographic(ECoG) activities in frontal and occipital cortices in freely moving rats (n = 11). We analyzed the changes in thalamic and cortical local spectral power and connectivities, which were measured with phase-amplitude coupling (PAC), coherence and multivariate Granger causality, at the states of baseline, intravenous infusion of propofol 20, 40, 80 mg/kg/h and after recovery of righting reflex. We found that propofol-induced burst-suppression results in a synchronous decrease of spectral power in thalamus and cortex (p < 0.001 for all frequency bands). The cross-frequency PAC increased by propofol, characterized by gradually stronger \'trough-max\' pattern in TRN and stronger \'peak-max\' pattern in cortex. The cross-region PAC increased in the phase of TRN modulating the amplitude of cortex. The functional connectivity (FC) between TRN and cortex for α/β bands also significantly increased (p < 0.040), with increased directional connectivity from TRN to cortex under propofol anesthesia. In contrast, the corticocortical FC significantly decreased (p < 0.047), with decreased directional connectivity from frontal cortex to occipital cortex. However, the thalamothalamic functional and directional connectivities remained largely unchanged by propofol anesthesia.  The spectral powers and connectivities are differentially modulated with the changes of propofol doses, suggesting the changes in neural dynamics in thalamocortical system could be used for distinguishing different vigilance levels caused by propofol.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s11571-022-09912-0.

OBJECTIVE: The purpose of this study was to assess the differences of topological characteristic and rich club organization between temporal lobe epilepsy (TLE) patients with focal seizure (FS) only and those with focal to bilateral tonic-clonic seizures (FBTCS).
METHODS: We recruited 130 unilateral TLE patients, of which 57 patients with FS only and 73 patients with both FS and FBTCS, and 68 age- and gender-matched healthy controls (HC). Whole-brain networks were constructed based on diffusion weighted imaging data. Graph theory was applied to quantify the topological network metrics and rich club organization. Network-based statistic (NBS) analysis was administered to investigate the difference in edge-wise connectivity strength. The non-parametric permutation test was applied to evaluate the differences between groups. Benjamini-Hochberg FDR at the alpha of 5% was carried out for multiple comparations.
RESULTS: In comparison with HC, both the FS and FBTCS group displayed a significant reduction in whole-brain connectivity strength and global efficiency. The FBTCS group showed lower connectivity strength both in the rich club and feeder connections compared to HC. The FS group had lower connectivity strength in the feeder and local connections compared to HC. NBS analysis revealed a wider range of decreased connectivity strength in the FBTCS group, involving 90% of the rich club regions, mainly affecting temporal-subcortical, frontal-parietal, and frontal-temporal lobe, the majority decreasing connections were between temporal lobe and stratum. While the decreased connectivity strength in the FS group were relatively local, involving 50% of rich club regions, mainly concentrated on the temporal-subcortical lobe.
CONCLUSIONS: Network integration was reduced in TLE. TLE with FBTCS selectively disrupted the rich club regions, while TLE with FS only were more likely to affect the non-rich club regions, emphasizing the contribution of rich club organization to seizure generalization.