Acute thalamic connectivity precedes chronic post-concussive symptoms in mild traumatic brain injury.

Chronic post-concussive symptoms are common after mild traumatic brain injury (mTBI) and are difficult to predict or treat. Thalamic functional integrity is particularly vulnerable in mTBI and may be related to long-term outcomes but requires further investigation. We compared structural MRI and resting state functional MRI in 108 patients with a Glasgow Coma Scale (GCS) of 13-15 and normal CT, and 76 controls. We examined whether acute changes in thalamic functional connectivity were early markers for persistent symptoms and explored neurochemical associations of our findings using PET data. Of the mTBI cohort, 47% showed incomplete recovery 6 months post-injury. Despite the absence of structural changes, we found acute thalamic hyperconnectivity in mTBI, with specific vulnerabilities of individual thalamic nuclei. Acute fMRI markers differentiated those with chronic post-concussive symptoms, with time- and outcome-dependent relationships in a sub-cohort followed longitudinally. Moreover, emotional and cognitive symptoms were associated with changes in thalamic functional connectivity to known serotonergic and noradrenergic targets, respectively. Our findings suggest that chronic symptoms can have a basis in early thalamic pathophysiology. This may aid identification of patients at risk of chronic post-concussive symptoms following mTBI, provide a basis for development of new therapies and facilitate precision medicine application of these therapies.

Structural disconnectivity in postoperative delirium: A perioperative two-center cohort study in older patients.

BACKGROUND: Structural disconnectivity was found to precede dementia. Global white matter abnormalities might also be associated with postoperative delirium (POD). METHODS: We recruited older patients (≥65 years) without dementia that were scheduled for major surgery. Diffusion kurtosis imaging metrics were obtained preoperatively, after 3 and 12 months postoperatively. We calculated fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), and free water (FW). A structured and validated delirium assessment was performed twice daily. RESULTS: Of 325 patients, 53 patients developed POD (16.3%). Preoperative global MD (standardized beta 0.27 [95% confidence interval [CI] 0.21-0.32] p < 0.001) was higher in patients with POD. Preoperative global MK (-0.07 [95% CI -0.11 to (-0.04)] p < 0.001) and FA (0.07 [95% CI -0.10 to (-0.04)] p < 0.001) were lower. When correcting for baseline diffusion, postoperative MD was lower after 3 months (0.05 [95% CI -0.08 to (-0.03)] p < 0.001; n = 183) and higher after 12 months (0.28 [95% CI 0.20-0.35] p < 0.001; n = 45) among patients with POD. DISCUSSION: Preoperative structural disconnectivity was associated with POD. POD might lead to white matter depletion 3 and 12 months after surgery.

Repeat traumatic brain injury exacerbates acute thalamic hyperconnectivity in humans.

Repeated mild traumatic brain injury is of growing interest regarding public and sporting safety and is thought to have greater adverse or cumulative neurological effects when compared with single injury. While epidemiological links between repeated traumatic brain injury and outcome have been investigated in humans, exploration of its mechanistic substrates has been largely undertaken in animal models. We compared acute neurological effects of repeat mild traumatic brain injury (n = 21) to that of single injury (n = 21) and healthy controls (n = 76) using resting-state functional MRI and quantified thalamic functional connectivity, given previous identification of its prognostic potential in human mild traumatic brain injury and rodent repeat mild traumatic brain injury. Acute thalamocortical functional connectivity showed a rank-based trend of increasing connectivity with number of injuries, at local and global scales of investigation. Thus, history of as few as two previous injuries can induce a vulnerable neural environment of exacerbated hyperconnectivity, in otherwise healthy individuals from non-specialist populations. These results further establish thalamocortical functional connectivity as a scalable marker of acute injury and long-term neural dysfunction following mild traumatic brain injury.

Outcomes and Mechanisms Associated With Selective Thalamic Neuronal Loss in Chronic Traumatic Brain Injury.

Importance: The chronic neuronal burden of traumatic brain injury (TBI) is not fully characterized by routine imaging, limiting understanding of the role of neuronal substrates in adverse outcomes. Objective: To determine whether tissues that appear healthy on routine imaging can be investigated for selective neuronal loss using [11C]flumazenil (FMZ) positron emission tomography (PET) and to examine whether this neuronal loss is associated with long-term outcomes. Design, Setting, and Participants: In this cross-sectional study, data were collected prospectively from 2 centers (University of Cambridge in the UK and Weill Cornell Medicine in the US) between September 1, 2004, and May 31, 2021. Patients with TBI (>6 months postinjury) were compared with healthy control participants (all aged >18 years). Individuals with neurological disease, benzodiazepine use, or contraindication to magnetic resonance imaging were excluded. Data were retrospectively collated with nonconsecutive recruitment, owing to convenience and scanner or PET ligand availability. Data were analyzed between February 1 and September 30, 2023. Exposure: Flumazenil voxelwise binding potential relative to nondisplaceable binding potential (BPND). Main Outcomes and Measures: Selective neuronal loss identified with FMZ PET was compared between groups on voxelwise and regional scales, and its association with functional, cognitive, and psychological outcomes was examined using Glasgow Outcome Scale (GOS) scores, measures of sustained executive attention (animal and sustained fluency), and 36-Item Short Form Health Survey (SF-36) scores. Diffusion tensor imaging was used to assess structural connectivity of regions of cortical damage, and its association with thalamic selective neuronal loss. Results: In this study, 24 patients with chronic TBI (mean [SD] age, 39.2 [12.3] years; 18 men [75.0%]) and 33 healthy control participants (mean [SD] age, 47.6 [20.5] years; 23 men [69.7%]) underwent FMZ PET. Patients with TBI had a median time of 29 (range, 7-95) months from injury to scan. They displayed selective neuronal loss in thalamic nuclei, over and above gross volume loss in the left thalamus, and bilateral central, mediodorsal, ventral-lateral dorsal, anterior, and ventral anterior thalamic nuclei, across a wide range of injury severities. Neuronal loss was associated with worse functional outcome using GOS scores (left thalamus, left ventral anterior, and bilateral central, mediodorsal, and anterior nuclei), worse cognitive outcome on measures of sustained executive attention (left thalamus, bilateral central, and right mediodorsal nuclei), and worse emotional outcome using SF-36 scores (right central thalamic nucleus). Chronic thalamic neuronal loss partially mirrored the location of primary cortical contusions, which may indicate secondary injury mechanisms of transneuronal degeneration. Conclusions and Relevance: The findings of this study suggest that selective thalamic vulnerability may have chronic neuronal consequences with relevance to long-term outcome, suggesting the evolving and potentially lifelong thalamic neuronal consequences of TBI. FMZ PET is a more sensitive marker of the burden of neuronal injury than routine imaging; therefore, it could inform outcome prognostication and may lead to the development of individualized precision medicine approaches.

Land use change increases contaminant sequestration in blue carbon sediments.

Coastal blue carbon habitats perform many important environmental functions, including long-term carbon and anthropogenic contaminant storage. Here, we analysed twenty-five 210Pb-dated mangrove, saltmarsh, and seagrass sediment cores from six estuaries across a land-use gradient to determine metal, metalloid, and phosphorous sedimentary fluxes. Cadmium, arsenic, iron, and manganese had linear to exponential positive correlations between concentrations, sediment flux, geoaccumulation index, and catchment development. Increases in anthropogenic development (agricultural or urban land uses) from >30 % of the total catchment area enhanced mean concentrations of arsenic, copper, iron, manganese, and zinc between 1.5 and 4.3-fold. A ~ 30 % anthropogenic land-use was the threshold in which blue carbon sediment quality begins to be detrimentally impacted on an entire estuary scale. Fluxes of phosphorous, cadmium, lead, and aluminium responded similarly, increasing 1.2 to 2.5-fold when anthropogenic land-use increased by at least 5 %. Exponential increases in phosphorus flux to estuary sediments seem to precede eutrophication as observed in more developed estuaries. Overall, multiple lines of evidence revealed how catchment development drives blue carbon sediment quality across a regional scale.

Pesticide occurrence in an agriculturally intensive and ecologically important coastal aquatic system in Australia.

Coastal agricultural practices are often located in catchments upstream of ecologically important aquatic systems. Here, we investigate the occurrence of pesticides in a coastal creek flowing into a habitat-protected area within the Solitary Islands Marine Park, Australia. Water samples were collected from six sites along a creek transect during three sampling periods. Samples were analysed for 171 pesticide analytes, including organochlorines, organophosphates, herbicides, and fungicides. Five insecticides, two herbicides, and two fungicides were detected. The neonicotinoid imidacloprid was detected at 5 out of 6 sites, with concentrations reaching 294 µg L-1, the highest yet detected in Australian waterways. The organophosphate insecticide dimethoate was detected at 4 sites, which occurred at the 2nd highest detected concentration in the study (12.8 µg L-1). The presence of these pesticides in the aquatic environment downstream of horticulture in this and other regions may have serious implications for stream biota and ecologically important marine ecosystems.

Anthropogenic nitrate attenuation versus nitrous oxide release from a woodchip bioreactor.

Nitrogen loss via overland flow from agricultural land use is a global threat to waterways. On-farm denitrifying woodchip bioreactors can mitigate NO3- exports by increasing denitrification capacity. However, denitrification in sub-optimal conditions releases the greenhouse gas nitrous oxide (N2O), swapping the pollution from aquatic to atmospheric reservoirs. Here, we assess NO3--N removal and N2O emissions from a new edge-of-field surface-flow bioreactor during ten rain events on intensive farming land. Nitrate removal rates (NRR) varied between 5.4 and 76.2 g NO3--N m-3 wetted woodchip d-1 with a mean of 30.3 ± 7.3 g NO3--N m-3. The nitrate removal efficiency (NRE) was ∼73% in ideal hydrological conditions and ∼18% in non-ideal conditions. The fraction of NO3--N converted to N2O (rN2O) in the bioreactor was ∼3.3 fold lower than the expected 0.75% IPCC emission factor. We update the global bioreactor estimated Q10 (NRR increase every 10 °C) from a recent meta-analysis with previously unavailable data to >20 °C, yielding a new global Q10 factor of 3.1. Mean N2O CO2-eq emissions (431.9 ± 125.4 g CO2-eq emissions day-1) indicate that the bioreactor was not significantly swapping aquatic NO3- for N2O pollution. Our estimated NO3--N removal from the bioreactor (9.9 kg NO3--N ha-1 yr-1) costs US$13.14 per kg NO3--N removed and represents ∼30% NO3--N removal when incorporating all flow and overflow events. Overall, edge-of-field surface-flow bioreactors seem to be a cost-effective solution to reduce NO3--N runoff with minor pollution swapping to N2O.

Cryptic night-time trace metal and metalloid contamination in an intensively cultivated coastal catchment.

Detailed, high resolution time-series observations were performed to investigate sources, diel cycling, natural attenuation, and loadings of dissolved trace metals/metalloids in a subtropical headwater stream draining intensive horticulture in Australia. A transect of ∼3 km away from the source (farms) showed >75% reduction in concentration and loads of most trace elements. Mercury and arsenic had elevated loads downstream relative to other elements. Hourly time-series sampling revealed elevated creek discharge at night, accompanied by elevated nickel, selenium, copper, and mercury loads. Inputs from groundwater or treated sewage used for irrigation within the catchment are likely sources. Groundwater bore and treated sewage samples were highly contaminated with either zinc, copper, or mercury. Comparisons of daily and hourly samples indicated common sampling strategies can underestimate horticultural contaminant loadings. Load estimates for mercury and copper derived from hourly samples were 1.6- to 7- fold greater than loads from daily sample data collected over 79 days with varying rainfall. These high contaminant concentrations and loads are of concern to food products receiving irrigation and protected waterbodies downstream.