Connectivity Pathways Research Articles

Incidence, pathophysiology, and treatment of failing Fontan after the total cavopulmonary connection.

Failing Fontan poses a significant clinical challenge. This study aims to improve patients' outcomes by comprehensively understanding the incidence, pathophysiology, risk factors, and treatment of failing Fontan after total cavopulmonary connection. We performed a retrospective analysis of patients who underwent total cavopulmonary connection at the German Heart Center Munich between 1994 and 2022. The onset of failing Fontan was defined as: protein-losing enteropathy, plastic bronchitis, NYHA class IV, NYHA class III for > one year, unscheduled hospital admissions for heart failure symptoms, and evaluation for heart transplantation. Among 634 patients, 76 patients presented with failing Fontan, and the incidence was 1.48 per 100 patient-years. Manifestations included protein-losing enteropathy (n = 34), hospital readmission (n = 28), NYHA III (n = 18), plastic bronchitis (n = 16), evaluation for heart transplantation (n = 14), and NYHA IV (n = 4). Risk factors for the onset of failing Fontan were dominant right ventricle (p = 0.010) and higher pulmonary artery pressure before total cavopulmonary connection (p = 0.004). A total of 72 interventions were performed in 59 patients, including balloon dilatation/stent implantation in the total cavopulmonary connection pathway (n = 49) and embolization of collaterals (n = 24). Heart transplantation was performed in four patients. The survival after the onset of Fontan failure was 77% at 10 years. Patients with failing Fontan revealed significantly higher zlog-NT-proBNP levels after onset compared to those without (p = 0.021). The incidence of Fontan failure was 1.5 per 100 patient years. Dominant right ventricle and higher pulmonary artery pressure before total cavopulmonary connection were significant risks for the onset of failing Fontan. Zlog-NT-proBNP is only a late marker of Fontan failure.

Long-term outcomes of direct total cavopulmonary connection versus extracardiac conduit in Fontan circulation

ObjectiveThe long-term outcomes of direct total cavopulmonary connection in Fontan circulation have not been reported yet. This study aimed to compare the long-term outcomes of the direct total cavopulmonary connection procedure with the extracardiac conduit procedure in patients undergoing the Fontan. MethodsFrom October 2004 to August 2021, 297 patients undergoing the Fontan operation by extracardiac conduit (n = 268) or direct total cavopulmonary connection (n = 29) procedure at our institution were retrospectively reviewed. The propensity score–matching method was used to match the extracardiac conduit and direct total cavopulmonary connection groups in a 1:2 ratio, yielding 23 patients in the direct total cavopulmonary connection group and 40 patients in the extracardiac conduit group. ResultsThe in-hospital morbidity and mortality were similar between the 2 groups in both prematched and matched cohorts (P > .05). The estimated transplantation-free survival at 10 years in the matched direct total cavopulmonary connection group was 89.7% ± 7.0%, in contrast to 92.8% ± 5.0% in the matched extracardiac conduit group (P = .55). The estimated 10-year estimated freedom from Fontan failure in the matched direct total cavopulmonary connection group was 85.2% ± 8.0%, also similar to the 85.9% ± 6.7% in the matched extracardiac conduit group (P = .72). The direct total cavopulmonary connection pathways at the follow-up were significantly larger than those before Fontan surgery (P < .05). ConclusionsThe direct total cavopulmonary connection procedure is a feasible and effective strategy for highly selected Fontan candidates who have well-developed pulmonary arteries of adequate length and size. This approach not only allows for the potential growth of direct total cavopulmonary connection pathways but also demonstrates noninferior short-term and long-term outcomes in contrast to the extracardiac conduit strategy.

Tracking animal movements via collaborative acoustic telemetry networks: Multiscale habitat use, phenology, and management insights.

Estuaries support diverse fish and invertebrate communities, including resident species that rely on estuarine habitats year-round and transient migratory species. The unique movement patterns of these animals connect habitats within and far beyond the estuary and are integrally linked to fisheries management objectives. With a focus on Chesapeake Bay, this study leveraged data from collaborative acoustic telemetry networks in the northwest Atlantic to assess habitat use and phenology of movements for seven species of fish (cownose rays, dusky sharks, smooth dogfish, alewife, striped bass, common carp, and blue catfish) and one invertebrate (horseshoe crabs). A total of 288 acoustically tagged individuals were detected >3.2 million times (6,743 to 2,095,717 detections per species) on receivers across ~20.5 degrees of latitude spanning the North American Atlantic seaboard from Florida, USA, to New Brunswick, Canada. Common metrics of movement and phenology grouped these species as resident (common carp, blue catfish, horseshoe crabs), primarily resident in estuaries (juvenile striped bass), and coastal migrant (cownose rays, dusky sharks, smooth dogfish, alewife); maximum distance traveled varied by three orders of magnitude among these species. Further analysis of phenology for coastal migrants elucidated the timing and duration of these species' use of Chesapeake Bay. Collectively, movements linked habitats within Chesapeake Bay and connected the estuary to coastal ecosystems both to the north (e.g., alewife) and south (e.g., cownose rays), creating networks of fisheries management jurisdictions that varied in complexity and identified opportunities for enhancement to current management or co-management of some species. Our results elucidate the importance of estuaries to species with diverse movement behaviors, identify scales and pathways of habitat connectivity via animal movements, and highlight the utility of collaborative acoustic telemetry networks for quantifying movements relevant to both ecological research and fisheries management.

Unravelling the genetic landscape of cervical insufficiency: Insights into connective tissue dysfunction and hormonal pathways

Background The intricate molecular pathways and genetic factors that underlie the pathophysiology of cervical insufficiency (CI) remain largely unknown and understudied. Methods We sequenced exomes from 114 patients in Latvia and Lithuania, diagnosed with a short cervix, CI, or a history of CI in previous pregnancies. To probe the well-known link between CI and connective tissue dysfunction, we introduced a connective tissue dysfunction assessment questionnaire, incorporating Beighton and Brighton scores. The phenotypic data obtained from the questionnaire was correlated with the number of rare damaging variants identified in genes associated with connective tissue disorders (in silico NGS panel). SKAT, SKAT-O, and burden tests were performed to identify genes associated with CI without a priori hypotheses. Pathway enrichment analysis was conducted using both targeted and genome-wide approaches. Results No patient could be assigned monogenic connective tissue disorder neither genetically, neither clinically upon clinical geneticist evaluation. Expanding our exploration to a genome-wide perspective, pathway enrichment analysis replicated the significance of extracellular matrix-related pathways as important contributors to CI’s development. A genome-wide burden analysis unveiled a statistically significant prevalence of rare damaging variants in genes and pathways associated with steroids (p-adj = 5.37E-06). Rare damaging variants, absent in controls (internal database, n = 588), in the progesterone receptor (PGR) (six patients) and glucocorticoid receptor (NR3C1) (two patients) genes were identified within key functional domains, potentially disrupting the receptors’ affinity for DNA or ligands. Conclusion Cervical insufficiency in non-syndromic patients is not attributed to a single connective tissue gene variant in a Mendelian fashion but rather to the cumulative effect of multiple inherited gene variants highlighting the significance of the connective tissue pathway in the multifactorial nature of CI. PGR or NR3C1 variants may contribute to the pathophysiology of CI and/or preterm birth through the impaired progesterone action pathways, opening new perspectives for targeted interventions and enhanced clinical management strategies of this condition.

Elucidating the molecular symphony: unweaving the transcriptional & epigenetic pathways underlying neuroplasticity in opioid dependence and withdrawal.

The persistent use of opioids leads to profound changes in neuroplasticity of the brain, contributing to the emergence and persistence of addiction. However, chronic opioid use disrupts the delicate balance of the reward system in the brain, leading to neuroadaptations that underlie addiction. Chronic cocaine usage leads to synchronized alterations in gene expression, causing modifications in the Nucleus Accumbens (NAc), a vital part of the reward system of the brain. These modifications assist in the development of maladaptive behaviors that resemble addiction. Neuroplasticity in the context of addiction involves changes in synaptic connectivity, neuronal morphology, and molecular signaling pathways. Drug-evoked neuroplasticity in opioid addiction and withdrawal represents a complicated interaction between environmental, genetic, and epigenetic factors. Identifying specific transcriptional and epigenetic targets that can be modulated to restore normal neuroplasticity without disrupting essential physiological processes is a critical consideration. The discussion in this article focuses on the transcriptional aspects of drug-evoked neuroplasticity, emphasizing the role of key transcription factors, including cAMP response element-binding protein (CREB), ΔFosB, NF-kB, Myocyte-enhancing factor 2 (MEF2), Methyl-CpG binding protein 2 (MeCP2), E2F3a, and FOXO3a. These factors regulate gene expression and lead to the neuroadaptive changes observed in addiction and withdrawal. Epigenetic regulation, which involves modifying gene accessibility by controlling these structures, has been identified as a critical component of addiction development. By unraveling these complex molecular processes, this study provides valuable insights that may pave the way for future therapeutic interventions targeting the mechanisms underlying addiction and withdrawal.

A decision support tool for habitat connectivity in Australia

Context Species connectivity mapping is a technically challenging task for conservation practitioners and nongovernment organisations to undertake as it requires experience in geographic information systems and often some computer programming. Aims We developed a decision support tool to provide spatial information and data on potential habitat connectivity and optimum connectivity pathways for a selection of forest-dependent vertebrate fauna in eastern and south-western Australia. Methods We systematically searched spatial data repositories for Australian spatial datasets for modelling connectivity. A least cost paths and patch connectivity approach was used to map potential habitat connectivity for (1) a single species – the glossy black cockatoo (Calyptorhynchus lathami) of South East Queensland, and (2) four species guilds – rainforest pigeons, gliding possums, the black cockatoos of south-western Western Australia and a landscape level forest connectivity. Optimum connectivity pathways were assessed for protection status. Key results In total 71 spatial datasets useful for habitat connectivity mapping were identified. Species and guild modelling found that the protection status for optimum connectivity pathways varied between 24.7% and 53.3%. A decision support mapping tool was then created to enable users to interactively explore the connectivity data and download the spatial datasets for further analysis. Conclusions The development of a decision support tool for mapping habitat connectivity in eastern and south-western Australia represents a useful platform for conservation practitioners as it provides valuable spatial information on potential connectivity pathways for forest-dependent vertebrate fauna. Implications The tool can aid in the prioritisation of conservation actions aimed at enhancing habitat connectivity and mitigating the impacts of habitat fragmentation on biodiversity in the two regions.

A multistrategy differential evolution algorithm combined with Latin hypercube sampling applied to a brain–computer interface to improve the effect of node displacement

Injection molding is a common plastic processing technique that allows melted plastic to be injected into a mold through pressure to form differently shaped plastic parts. In injection molding, in-mold electronics (IME) can include various circuit components, such as sensors, amplifiers, and filters. These components can be injected into the mold to form a whole within the melted plastic and can therefore be very easily integrated into the molded part. The brain–computer interface (BCI) is a direct connection pathway between a human or animal brain and an external device. Through BCIs, individuals can use their own brain signals to control these components, enabling more natural and intuitive interactions. In addition, brain–computer interfaces can also be used to assist in medical treatments, such as controlling prosthetic limbs or helping paralyzed patients regain mobility. Brain–computer interfaces can be realized in two ways: invasively and noninvasively, and in this paper, we adopt a noninvasive approach. First, a helmet model is designed according to head shape, and second, a printed circuit film is made to receive EEG signals and an IME injection mold for the helmet plastic parts. In the electronic film, conductive ink is printed to connect each component. However, improper parameterization during the injection molding process can lead to node displacements and residual stress changes in the molded part, which can damage the circuits in the electronic film and affect its performance. Therefore, in this paper, the use of the BCI molding process to ensure that the node displacement reaches the optimal value is studied. Second, the multistrategy differential evolutionary algorithm is used to optimize the injection molding parameters in the process of brain–computer interface formation. The relationship between the injection molding parameters and the actual target value is investigated through Latin hypercubic sampling, and the optimized parameters are compared with the target parameters to obtain the optimal parameter combination. Under the optimal parameters, the node displacement can be optimized from 0.585 to 0.027 mm, and the optimization rate can reach 95.38%. Ultimately, by detecting whether the voltage difference between the output inputs is within the permissible range, the reliability of the brain–computer interface after node displacement optimization can be evaluated.

Neuronal Remodelling as a Predictor of Autism Spectrum Disorder Diagnosis

People with Autism Spectrum Disorder (ASD) are a neurodevelopmental symptom group characterized by significant deficits in information connectivity, mainly caused by specific genetic mutations affecting the fluency of the gamma-aminobutyric acid (GABAergic) system. This disruption, to a greater or lesser degree, hinders the interactive process of incoming stimuli with previously stored information, preventing working memory from fulfilling its role of facilitating access to information in permanent memory and later recovery. In addition to the genetic components, environmental processes occurring, above all, in early childhood, related to specific organic and severe psycho-emotional diseases can produce the same effects in the brain system as the genetic karyotypic component through the concept of neuronal remodelling. In this sense, this research aims to empirically show the influence of neuronal remodelling on the GABAergic pathway leading to the traits of autism spectrum behaviour. A total of 175 participants from the three levels of ASD intensity have participated in this study. Data have been analysed through Linear Logistic Regression, which shows that both components, the genetic process and the environmental process, significantly influence the neural connective pathway that relates information, unlike other operationalized covariates, such as gender or age of the participants. Likewise, as shown by the Chi-Square Test, the interactions between genetic and environmental variables showed no differences in their interaction regarding the connectivity level that would explain the different levels of disorder. However, when there is a combination of genetic mutations in the diagnostic karyotype, there are significant differences between the genetic group and the environmental process over the neural network.

Supporting Early Language by Supporting Systemic Solutions

A large body of research shows connections between infants’ and toddlers’ home language input and a wide range of receptive and expressive early language skills. Some facets of caretaker input and early language skills are associated with socioeconomic status (SES), though not all. Given the complexity of language learning, language use, and its many pathways of connection to SES, testing causal links between these dimensions is difficult at best. Interventions aimed at changing parent language use have seen mixed success, in part because “language infusions” generally fail to target underlying challenges facing underresourced families, and perhaps because parent language is the wrong target. System-level interventions such as paid parental leave and expansion and enrichment of childcare and early education options hold greater promise for improving families’ lives, with positive repercussions for a broad range of family and child outcomes, including linguistic ones.

Comparison of in situ black-lipped oyster spat collection and larval dispersal modelling results in semi-closed pearl-farming lagoons of the Tuamotu Archipelago

Spat collection of the pearl oyster Pinctada margaritifera in atoll lagoons of French Polynesia is the fundamental sustain of black pearl farming. Spat collection has always yielded variable results in space and time, but obvious signs of steady decreases, even collapses, have emerged in several lagoons. Spat collection materializes the ecological connectivity pathways between wild spawning populations and the location of artificial larval settlement substrates. To assess if oyster larval dispersal modelling could capture such pathways, we compared four six-week long spat collector deployment periods with dispersal simulations in two different lagoons. Spat collectors displayed wide spatial and temporal variations. Numerical modelling and field experiments were generally not in agreement. Although both methods have limitations, they can still approximate each other. But the accuracy of model simulations cannot be ascertained with spat collection data only. Using a SWOT (Strength-Weakness-Opportunities-Threats) analysis, we emphasize the complementarity of both approaches for management decisions.

Impact of Early- and High-Dose Caffeine on the Cerebellum Development in Newborn Rats

Introduction: Preterm newborns struggle with maintaining an adequate respiratory pattern; early caffeine administration is suggested to stimulate respiration and reduce bronchopulmonary dysplasia, however, its consequences on the immature cerebellum remains unknown. This study aimed to assess the impact of early caffeine administration, at standard and high doses, accompanied by supplemental oxygen on cerebellar development in an experimental model. Methods: Five groups of Wistar pups were formed (n = 8 offspring/group): (a) negative control: no intervention; (b) placebo: pups remaining from birth until the 7th day of life (DOL) exposed to fractional inspired oxygen (FiO2) 45%, resembling preterm infant condition and as a placebo, 0.2 mL oral 5% dextrose, from the first DOL until the 14th DOL; (c) caffeine group: oral caffeine, 1st DOL 20 mg/kg, and from 2nd to 14th DOL, 5 mg/kg (standard dose); (d) caffeine at the standard dose, plus O2: during the first 7 DOLs (FiO2: 45%); (e) caffeine: 40 mg/kg in the first DOL, 10 mg/kg the next 14 DOLs, plus O2 in the first 7 DOLs (FiO2: 45%). Subjects were sacrificed on their 15th DOL; measurements were taken from the cerebellum, specifically the external granular layer (EGL) and molecular layer (ML), with quantification of cell migration. Results: Caffeine administration in pups resulted in a delay in cerebellum development based on persistent transitional EGL cells; this finding was exacerbated in groups exposed to caffeine plus O2, as evident from the thicker EGL. The negative control group showed near-complete cell migration with a thicker ML and a significantly smaller EGL. Conclusions: Early caffeine administration in newborn rats disrupts cerebellar cortex cell processes and connectivity pathways, with exacerbated effects in groups receiving caffeine plus O2.

Cost of Being Online for Brain: Changing Working Memory Attributes, Associated Metacognitive Knowledge and Long-Term Memory Processing

Converging evidence from neuroscience and psychological sciences demonstrates that continuous sensory stimulation within the intensive internet use affects brain functioning on a broad scale. This includes essential memory, and metacognitive functions extend to the healthiness and disorders which are critical for the adaptive behavior and learning processes. This study aims to show the relation between intensive internet use and the responds of the brain in neural and behavioral levels through some working memory attributes and associated metacognitive functions and long-term memory processing. Accordingly, functional magnetic resonance imaging (fMRI) studies suggest that being online intensively has an impact on activation levels in Anterior Cingulate Cortex, Dorsolateral Prefrontal Cortex, Orbitofrontal Cortex, Medial and Medial frontal Gyrus, ventral striatum, and the dynamic connectivity pathways including frontal, medial and parietal networks such as Default Mode Network and Task Network which are important for memory and metacognitive functions. Moreover, intensive internet use habits affect some cognitive skills such as the selection of information cues, manipulation and retention of the information and attentional control; evaluation of one’s present knowledge, and regulation of the learning processes for; encoding, consolidation and retrieval of information for long-term memory processes are the effected features. As a conclusion, intensive internet use has a critical impact on neural processes in modular and whole brain level and could play a strong role for the alteration of memory and metacognitive processes.

Additive effects of depression and obesity on neural correlates of inhibitory control

BackgroundDepression and obesity are associated with impaired inhibitory control. Behavioral evidence indicates an exacerbating additive effect when both conditions co-occur. However, the underlying neural mechanisms remain unclear. Moreover, systemic inflammation affects neurocognitive performance in both individuals with depression and obesity. Here, we investigate additive effects of depression and obesity on neural correlates of inhibitory control, and examine inflammation as a connecting pathway. MethodsWe assessed inhibitory control processing in 64 individuals with obesity and varying degrees of depressed mood by probing neural activation and connectivity during an fMRI Stroop task. Additionally, we explored associations of altered neural responses with individual differences in systemic inflammation. Data were collected as part of the BARICO (Bariatric surgery Rijnstate and Radboudumc neuroimaging and Cognition in Obesity) study. ResultsConcurrent depression and obesity were linked to increased functional connectivity between the supplementary motor area and precuneus and between the inferior occipital and inferior parietal gyrus. Exploratory analysis revealed that circulating inflammation markers, including plasma leptin, IL-6, IL-8, and CCL-3 correlated with the additive effect of depression and obesity on altered functional connectivity. LimitationsThe observational design limits causal inferences. Future research employing longitudinal or intervention designs is required to validate these findings and elucidate causal pathways. ConclusionThese findings suggest increased neural crosstalk underlying impaired inhibitory control in individuals with concurrent obesity and depressed mood. Our results support a model of an additive detrimental effect of concurrent depression and obesity on neurocognitive functioning, with a possible role of inflammation.

Finding the Words: How Does the Aging Brain Process Language? A Focused Review of Brain Connectivity and Compensatory Pathways.

As people age, there is a natural decline in cognitive functioning and brain structure. However, the relationship between brain function and cognition in older adults is neither straightforward nor uniform. Instead, it is complex, influenced by multiple factors, and can vary considerably from one person to another. Reserve, compensation, and maintenance mechanisms may help explain why some older adults can maintain high levels of performance while others struggle. These mechanisms are often studied concerning memory and executive functions that are particularly sensitive to the effects of aging. However, language abilities can also be affected by age, with changes in production fluency. The impact of brain changes on language abilities needs to be further investigated to understand the dynamics and patterns of aging, especially successful aging. We previously modeled several compensatory profiles of language production and lexical access/retrieval in aging within the Lexical Access and Retrieval in Aging (LARA) model. In the present paper, we propose an extended version of the LARA model, called LARA-Connectivity (LARA-C), incorporating recent evidence on brain connectivity. Finally, we discuss factors that may influence the strategies implemented with aging. The LARA-C model can serve as a framework to understand individual performance and open avenues for possible personalized interventions.

Spatial and temporal change of hydrological connectivity in the Wusuli River Basin

Study regionThe study region of this paper is the Wusuli River basin, which is comprised of nine sub-basins. The basin is located on the border between China and Russia. Study focusWe investigated the hydrological connectivity of the Wusuli River basin, an international boundary river that has received little attention. The spatial and temporal evolution of hydrological connectivity over the last 38 years was characterized using a geostatistical connectivity function combined with the remote sensing technique. In particular, some key sub-basins were identified to help strengthen China-Russian cooperation on ecological protection of the basin. New hydrological insights for the regionThe results show that the hydrological connectivity in the northwestern region of the Wusuli River basin was unstable with several surges from 1984 to 2021. Analyzed from a temporal perspective, the effective range of hydrological connectivity is expanding and connectivity is showing an overall upward trend due to increased fluctuations in rainfall. Analyzed from a spatial perspective, the connectivity of the right bank of the Wusuli River is better than that of the left bank due to the influence of topography. Stable connectivity pathways are a must for efficient hydrological connectivity within a watershed. Another finding is that the capacity of the Wusuli River basin to resist extreme rainfall is weakening.

Water management and mass transport of a fractal metal foam flow-field based polymer electrolyte fuel cell using operando neutron imaging

Metal foam flow-fields (MFFs) exhibit immense potential for enhancing the performance of polymer electrolyte fuel cells (PEFCs) owing to their advantageous pore connectivity and abundant gas pathways. Nevertheless, challenges remain with the conventional MFF concerning reactant homogeneity and water management. To address these concerns, this study incorporates a fractal manifold into the MFF design. By employing operando neutron imaging, device-level testing, and electrochemical impedance spectroscopy (EIS), a comprehensive understanding of mass transfer and water management characteristics across the fractal manifold MFF is obtained. This novel design delivers better cell performance and lower mass transport resistance compared to the conventional MFF under all experimental conditions investigated. Notably, neutron imaging reveals that the fractal manifold MFF consistently exhibits a reduced liquid water content and more uniformly distributed liquid water compared to the conventional MFF. These superior characteristics of the design contribute to a substantial ∼15% increase in maximum power density compared to the conventional MFF-based PEFC. The results indicate the potential for further performance improvement by optimizing manifold parameters.

Parkinsonism originates in a discrete secondary and dystonia in a primary motor cortical-basal ganglia subcircuit.

Although manifesting contrasting phenotypes, Parkinson's disease and dystonia, the two most common movement disorders, can originate from similar pathophysiology. Previously, we demonstrated that lesioning (silencing) of a discrete dorsal region in the globus pallidus (rodent equivalent to globus pallidus externa) in rats and produced parkinsonism, while lesioning a nearby ventral hotspot-induced dystonia. Presently, we injected fluorescent-tagged multi-synaptic tracers into these pallidal hotspots (n = 36 Long Evans rats) and permitted 4 days for the viruses to travel along restricted connecting pathways and reach the motor cortex before sacrificing the animals. Viral injections in the Parkinson's hotspot fluorescent labeled a circumscribed region in the secondary motor cortex, while injections in the dystonia hotspot labeled within the primary motor cortex. Custom probability mapping and N200 staining affirmed the segregation of the cortical territories for Parkinsonism and dystonia to the secondary and primary motor cortices. Intracortical microstimulation localized territories specifically to their respective rostral and caudal microexcitable zones. Parkinsonian features are thus explained by pathological signaling within a secondary motor subcircuit normally responsible for initiation and scaling of movement, while dystonia is explained by abnormal (and excessive) basal ganglia signaling directed at primary motor corticospinal transmission.

Edge-wise analysis reveals white matter connectivity associated with focal to bilateral tonic-clonic seizures.

Focal to bilateral tonic-clonic seizures (FBTCS) represent a challenging subtype of focal temporal lobe epilepsy (TLE) in terms of both severity and treatment response. Most studies have focused on regional brain analysis that is agnostic to the distribution of white matter (WM) pathways associated with a node. We implemented a more selective, edge-wise approach that allowed for identification of the individual connections unique to FBTCS. T1-weighted and diffusion-weighted images were obtained from 22 patients with solely focal seizures (FS), 43 FBTCS patients, and 65 age/sex-matched healthy participants (HPs), yielding streamline (STR) connectome matrices. We used diffusion tensor-derived STRs in an edge-wise approach to determine specific structural connectivity changes associated with seizure generalization in FBTCS compared to matched FS and HPs. Graph theory metrics were computed on both node- and edge-based connectivity matrices. Edge-wise analyses demonstrated that all significantly abnormal cross-hemispheric connections belonged to the FBTCS group. Abnormal connections associated with FBTCS were mostly housed in the contralateral hemisphere, with graph metric values generally decreased compared to HPs. In FBTCS, the contralateral amygdala showed selective decreases in the structural connection pathways to the contralateral frontal lobe. Abnormal connections in TLE involved the amygdala, with the ipsilateral side showing increases and the contralateral decreases. All the FS findings indicated higher graph metrics for connections involving the ipsilateral amygdala. Data also showed that some FBTCS connectivity effects are moderated by aging, recent seizure frequency, and longer illness duration. Data showed that not all STR pathways are equally affected by the seizure propagation of FBTCS. We demonstrated two key biases, one indicating a large role for the amygdala in the propagation of seizures, the other pointing to the prominent role of cross-hemispheric and contralateral hemisphere connections in FBTCS. We demonstrated topographic reorganization in FBTCS, pointing to the specific WM tracts involved.

Interviews With Lay Caregivers About Their Experiences Supporting Patients Throughout Kidney Transplantation.

Introduction: Lay caregivers provide essential support to patients throughout the kidney transplant process, pretransplant through discharge. Sparse data exists about kidney transplant caregiver experience and facilitators of caregiver engagement. The aim of this study was to explore and describe lay caregivers' accounts of supporting a patient before and early after kidney transplantation. Methods: Caregivers of recent kidney transplant recipients were individually interviewed about their experiences, coping strategies, and perspectives of center-specific support approaches for patients and caregivers in a single transplant center. Results: Inductive content analysis of transcribed interviews with 23 caregivers revealed 6 domain areas: visit preparation, initial evaluation, caregiver role discussion, exposure to support resources, transplant preparedness, and coping styles. Caregivers used and appreciated information offered by the transplant center, including materials directed to the patient. They recommended repeating information, online access, and adding video to complement print resources. They valued and requested information directed to them, both within passive materials and communication with providers. Social network interactions were helpful for practical, emotional, and informational support. Support group reminders and connection pathways to peers were suggested for both patients and caregivers. Conclusion: Findings highlight steps that can be taken by transplant centers and may stimulate caregiver engagement. Featuring caregiver-focused information and communication more prominently may support caregivers to improve patient progress in navigating kidney transplantation.

Corticostriatal causality analysis in children and adolescents with attention-deficit/hyperactivity disorder.

The effective connectivity between the striatum and cerebral cortex has not been fully investigated in attention-deficit/hyperactivity disorder (ADHD). Our objective was to explore the interaction effects between diagnosis and age on disrupted corticostriatal effective connectivity and to represent the modulation function of altered connectivity pathways in children and adolescents with ADHD. We performed Granger causality analysis on 300 participants from a publicly available Attention-Deficit/Hyperactivity Disorder-200 dataset. By computing the correlation coefficients between causal connections between striatal subregions and other cortical regions, we estimated the striatal inflow and outflow connection to represent intermodulation mechanisms in corticostriatal pathways. Interactions between diagnosis and age were detected in the superior occipital gyrus within the visual network, medial prefrontal cortex, posterior cingulate gyrus, and inferior parietal lobule within the default mode network, which is positively correlated with hyperactivity/impulsivity severity in ADHD. Main effect of diagnosis exhibited a general higher cortico-striatal causal connectivity involving default mode network, frontoparietal network and somatomotor network in ADHD compared with comparisons. Results from high-order effective connectivity exhibited a disrupted information pathway involving the default mode-striatum-somatomotor-striatum-frontoparietal networks in ADHD. The interactions detected in the visual-striatum-default mode networks pathway appears to be related to the potential distraction caused by long-term abnormal information input from the retina in ADHD. Higher causal connectivity and weakened intermodulation may indicate the pathophysiological process that distractions lead to the impairment of motion planning function and the inhibition/control of this unplanned motion signals in ADHD.