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IntroductionOutcomes of traumatic brain injury (TBI) are highly variable, with cognitive and psychiatric problems often present in survivors, including an increased dementia risk in the long term. Military personnel are at an increased occupational risk of TBI, with high rates of complex polytrauma including TBI characterising the UK campaign in Afghanistan. The ArmeD SerVices TrAuma and RehabilitatioN OutComE (ADVANCE)-TBI substudy will describe the patterns, associations and long-term outcomes of TBI in the established ADVANCE cohort.Methods and analysisThe ADVANCE cohort comprises 579 military personnel exposed to major battlefield trauma requiring medical evacuation, and 566 matched military personnel without major trauma. TBI exposure has been captured at baseline using a standardised interview and registry data, and will be refined at first follow-up visit with the Ohio State Method TBI interview (a National Institute of Neurological Disorders and Stroke TBI common data element). Participants will undergo blood sampling, MRI and detailed neuropsychological assessment longitudinally as part of their follow-up visits every 3–5 years over a 20-year period. Biomarkers of injury, neuroinflammation and degeneration will be quantified in blood, and polygenic risk scores calculated for neurodegeneration. Age-matched healthy volunteers will be recruited as controls for MRI analyses. We will describe TBI exposure across the cohort, and consider any relationship with advanced biomarkers of injury and clinical outcomes including cognitive performance, neuropsychiatric symptom burden and function. The influence of genotype will be assessed. This research will explore the relationship between military head injury exposure and long-term outcomes, providing insights into underlying disease mechanisms and informing prevention interventions.Ethics and disseminationThe ADVANCE-TBI substudy has received a favourable opinion from the Ministry of Defence Research Ethics Committee (ref: 2126/MODREC/22). Findings will be disseminated via publications in peer-reviewed journals and presentations at conferences.

The COVID-19 pandemic has dramatically altered the behaviour of most of the world's population, particularly affecting the elderly, including people living with dementia (PLwD). Here we use remote home monitoring technology deployed into 31 homes of PLwD living in the UK to investigate the effects of COVID-19 on behaviour within the home, including social isolation. The home activity was monitored continuously using unobtrusive sensors for 498 days from 1 December 2019 to 12 April 2021. This period included six distinct pandemic phases with differing public health measures, including three periods of home 'lockdown'. Linear mixed-effects modelling is used to examine changes in the home activity of PLwD who lived alone or with others. An algorithm is developed to quantify time spent outside the home. Increased home activity is observed from very early in the pandemic, with a significant decrease in the time spent outside produced by the first lockdown. The study demonstrates the effects of COVID-19 lockdown on home behaviours in PLwD and shows how unobtrusive home monitoring can be used to track behaviours relevant to social isolation.

Vestibular Agnosia - where peripheral vestibular activation triggers the usual reflex nystagmus response but with attenuated or no self-motion perception - is found in brain disease with disrupted cortical network functioning, e.g. traumatic brain injury (TBI) or neurodegeneration (Parkinson’s Disease). Patients with acute focal hemispheric lesions (e.g. stroke) do not manifest vestibular agnosia. Thus brain network mapping techniques, e.g. resting state functional MRI (rsfMRI), are needed to interrogate functional brain networks mediating vestibular agnosia. Whole-brain rsfMRI was acquired from 39 prospectively recruited acute TBI patients with preserved peripheral vestibular function, along with self-motion perceptual thresholds during passive yaw rotations in the dark. Following quality-control checks, 25 patient scans were analyzed. TBI patients were classified as having vestibular agnosia (n = 11) or not (n = 14) via laboratory testing of self-motion perception. Using independent component analysis, we found altered functional connectivity in the right superior longitudinal fasciculus and left rostral prefrontal cortex in vestibular agnosia. Moreover, regions of interest analyses showed both inter-hemispheric and intra-hemispheric network disruption in vestibular agnosia. In conclusion, our results show that vestibular agnosia is mediated by bilateral anterior and posterior network dysfunction and reveal the distributed brain mechanisms mediating vestibular self-motion perception.

We propose a parameter efficient Bayesian layer for hierarchical convolutional Gaussian Processes that incorporates Gaussian Processes operating in Wasserstein-2 space to reliably propagate uncertainty. This directly replaces convolving Gaussian Processes with a distance-preserving affine operator on distributions. Our experiments on brain tissue-segmentation show that the resulting architecture approaches the performance of well-established deterministic segmentation algorithms (U-Net), which has never been achieved with previous hierarchical Gaussian Processes. Moreover, by applying the same segmentation model to out-of-distribution data (i.e., images with pathology such as brain tumors), we show that our uncertainty estimates result in out-of-distribution detection that outperforms the capabilities of previous Bayesian networks and reconstruction-based approaches that learn normative distributions.

Background The optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts. Methods Differences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria. Results The prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05). There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker. Conclusion Different methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach., We have previously described a novel multivariate method (NMM) with theoretical statistical advantages over existing methods, which we assessed here in 3 cohorts of people living with HIV. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status.

Background Brain structural abnormalities have been reported in persons living with human immunodeficiency virus (HIV; PLWH) who are receiving suppressive combination antiretroviral therapy (cART), but their pathophysiology remains unclear. Methods We investigated factors associated with brain tissue volumes and white matter microstructure (fractional anisotropy) in 134 PLWH receiving suppressive cART and 79 comparable HIV-negative controls, aged ≥45 years, from the Comorbidity in Relation to AIDS cohort, using multimodal neuroimaging and cerebrospinal fluid biomarkers. Results Compared with controls, PLWH had lower gray matter volumes (−13.7 mL; 95% confidence interval, −25.1 to −2.2) and fractional anisotropy (−0.0073; 95% confidence interval, −.012 to −.0024), with the largest differences observed in those with prior clinical AIDS. Hypertension and the soluble CD14 concentration in cerebrospinal fluid were associated with lower fractional anisotropy. These associations were independent of HIV serostatus (Pinteraction = .32 and Pinteraction = .59, respectively) and did not explain the greater abnormalities in brain structure in relation to HIV infection. Conclusions The presence of lower gray matter volumes and more white matter microstructural abnormalities in well-treated PLWH partly reflect a combination of historical effects of AIDS, as well as the more general influence of systemic factors, such as hypertension and ongoing neuroinflammation. Additional mechanisms explaining the accentuation of brain structure abnormalities in treated HIV infection remain to be identified.

Age-associated disease and disability are placing a growing burden on society. However, ageing does not affect people uniformly. Hence, markers of the underlying biological ageing process are needed to help identify people at increased risk of age-associated physical and cognitive impairments and ultimately, death. Here, we present such a biomarker, 'brain-predicted age', derived using structural neuroimaging. Brain-predicted age was calculated using machine-learning analysis, trained on neuroimaging data from a large healthy reference sample (N=2001), then tested in the Lothian Birth Cohort 1936 (N=669), to determine relationships with age-associated functional measures and mortality. Having a brain-predicted age indicative of an older-appearing brain was associated with: weaker grip strength, poorer lung function, slower walking speed, lower fluid intelligence, higher allostatic load and increased mortality risk. Furthermore, while combining brain-predicted age with grey matter and cerebrospinal fluid volumes (themselves strong predictors) not did improve mortality risk prediction, the combination of brain-predicted age and DNA-methylation-predicted age did. This indicates that neuroimaging and epigenetics measures of ageing can provide complementary data regarding health outcomes. Our study introduces a clinically-relevant neuroimaging ageing biomarker and demonstrates that combining distinct measurements of biological ageing further helps to determine risk of age-related deterioration and death.Molecular Psychiatry advance online publication, 25 April 2017; doi:10.1038/mp.2017.62.

Non-invasive brain stimulation has been widely investigated for as a potential treatment for a range of neurological and psychiatric conditions, including brain injury. However, the behavioural effects of brain stimulation are very variable, for reasons that are poorly understood. This is a particular challenge for traumatic brain injury, where patterns of damage and their clinical effects are heterogenous. Here we test the hypothesis that the response to transcranial direct current stimulation following traumatic brain injury is dependent on white matter damage within the stimulated network. We used a novel simultaneous stimulation-MRI protocol applying anodal, cathodal and sham stimulation to 24 healthy and 35 moderate/severe traumatic brain injury patients. Stimulation was applied to the right inferior frontal gyrus/anterior insula node of the Salience Network, which was targeted because our previous work had shown its importance to executive function. Stimulation was applied during performance of the Stop Signal Task, which assesses response inhibition, a key component of executive function. Structural MRI was used to assess the extent of brain injury, including diffusion MRI assessment of post-traumatic axonal injury. Functional MRI, which was simultaneously acquired to delivery of stimulation, assessed the effects of stimulation on cognitive network function. Anodal stimulation improved response inhibition in control participants, an effect that was not observed in the patient group. The extent of traumatic axonal injury within the Salience Network strongly influenced the behavioural response to stimulation. Increasing damage to the tract connecting the stimulated right inferior frontal gyrus/anterior insula to the rest of the SN was associated with reduced beneficial effects of stimulation. In addition, anodal stimulation normalised Default Mode Network activation in patients with poor response inhibition, suggesting that stimulation modulates communication between the networks involved in supporting cognitive control. These results demonstrate an important principle: that white matter structure of the connections within a stimulated brain network influences the behavioural response to stimulation. This suggests that a personalised approach to non-invasive brain stimulation is likely to be necessary, with structural integrity of the targeted brain networks an important criteria for patient selection and an individualised approach to the selection of stimulation parameters.

Traumatic brain injury (TBI) affects millions of people worldwide with significant personal and social consequences. New materials and methods offer opportunities for improving designs of TBI prevention systems, such as helmets. We combined empirical impact tests and computational modelling to test the effectiveness of new viscoelastic add-on components in decreasing biomechanical forces within the brain during helmeted head impacts. Motorcycle helmets with and without the viscoelastic components were fitted on a head/neck assembly and were tested under oblique impact to replicate realistic accident conditions. Translational and rotational accelerations were measured during the tests. The inclusion of components reduced peak accelerations, with a significant effect for frontal impacts and a marginal effect for side and rear impacts. The head accelerations were then applied on a computational model of TBI to predict strain and strain-rate across the brain. The presence of viscoelastic components in the helmet decreased strain and strain-rate for frontal impacts at low impact speeds. The effect was less pronounced for front impact at high speeds and for side and rear impacts. This work shows the potential of the viscoelastic add-on components as lightweight and cost-effective solutions for enhancing helmet protection and decreasing strain and strain-rate across the brain during head impacts.

Background In neonatal encephalopathy (NE), the clinical manifestations of injury can only be reliably assessed several years after an intervention, complicating early prognostication and rendering trials of promising neuroprotectants slow and expensive. We aimed to determine the accuracy of thalamic proton magnetic resonance spectroscopy (1H MRS) biomarkers as early predictors of the neurodevelopmental abnormalities observed years after NE. Methods We conducted a prospective multi-centre cohort study across eight neonatal intensive care units, recruiting term neonates who received therapeutic hypothermia for NE. We obtained thalamic 1H MRS 4 to 14 days after birth, which were compared to clinical neurodevelopmental tests performed 18 to 24 months later. The primary endpoint was an abnormal outcome, defined as death, or moderate or severe disability. Receiver operating characteristic (ROC) curves were used to examine the strength of the relationship between selected biomarkers and this outcome. Findings We recruited 223 infants who all underwent MR imaging and spectroscopy at a median (IQR) age of 7 (5 to 10) days, with 190 (85%) followed up for neurological examination at a median (IQR) age of 23 (20 to 25) months. Of those followed up, 31 (16%) had moderate or severe disability, including one death. The thalamic concentration of Nacetylasparate, [NAA], had an area under the ROC curve (AUC) of 0·99 (95% CI 0·94 to 1·00, n=82), and lactate/NAA peak area ratio had an AUC of 0·94 (95% CI 0·89 to 0·97, n=160). From conventional MRI, abnormal signal in the posterior limb of the internal capsule (PLIC) gave an AUC of 0·82 (95% CI 0·76 to 0·87, n=190). Thalamic [NAA] was independently associated with neurodevelopmental outcome scores on multivariable analysis, and had higher prognostic accuracy than conventional MR imaging (98% versus 87%; p

β-amyloid (Aβ) accumulation in the brain is one of two pathological hallmarks of Alzheimer's Disease (AD) and its spatial distribution has been studied extensively ex vivo. We apply mathematical modelling to Aβ in vivo PET imaging data in order to investigate competing theories of Aβ spread in AD. Our results provide evidence that Aβ accumulation starts in all brain regions simultaneously and that its spatiotemporal distribution is a result of heterogeneous regional carrying capacities (regional maximum possible concentration of Aβ) for the aggregated protein rather than longer term spreading from seed regions.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to head impacts. Its distinctive neuropathologic feature is deposition of tau proteins in sulcal depths and in perivascular regions. Previous work has investigated pathological and clinical features of CTE, and here the authors report recent work on exploring the link between strain and strain rate distribution within the brain and location of CTE pathology. The authors used a high fidelity finite element (FE) model of traumatic brain injury (TBI) to test the hypothesis that strain and strain rate produced by head impacts are greatest in sulci, where neuropathology is prominently seen in CTE. The authors also analyzed diffusion tensor imaging (DTI) data from a large cohort of TBI patients to provide converging evidence from empirical neuroimaging data for the model’s prediction.

OBJECTIVE: Traumatic brain injury (TBI) is a common disabling condition with limited treatment options. Diffusion tensor imaging (DTI) measures recovery of axonal injury in white matter (WM) tracts after TBI. Growth hormone deficiency (GHD) after TBI may impair axonal and neuropsychological recovery, and serum IGF-I may mediate this effect. We conducted a longitudinal study to determine the effects of baseline serum IGF-I concentrations on WM tract and neuropsychological recovery after TBI. METHODS: Thirty-nine adults after TBI (84.6% male; age median 30.5y; 87.2% moderate-severe; time since TBI median 16.3 months, n=4 with GHD) were scanned twice, 13.3 months (12.1-14.9) apart, and 35 healthy controls scanned once. Symptom and quality of life questionnaires and cognitive assessments were completed at both visits (n=33). Our main outcome measure was fractional anisotropy (FA), a measure of WM tract integrity, in a priori regions of interest: splenium of corpus callosum (SPCC), and posterior limb of internal capsule (PLIC). RESULTS: At baseline, FA was reduced in many WM tracts including SPCC and PLIC following TBI compared to controls, indicating axonal injury, with longitudinal increases indicating axonal recovery. There was a significantly greater increase in SPCC FA over time in patients with serum IGF-I above vs. below the median-for-age. Only the higher IGF-I group had significant improvements in immediate verbal memory recall over time. INTERPRETATION: WM recovery and memory improvements after TBI were greater in patients with higher serum IGF-I at baseline. These findings suggest that GH/IGF-I system may be a potential therapeutic target following TBI. This article is protected by copyright. All rights reserved.

Background: Long-term comorbidities such as cognitive impairment remain prevalent in otherwise effectively treated people-living-with-HIV. We investigate the relationship between cognitive impairment and brain structure in successfully treated patients using multi-modal neuroimaging from the Co-morBidity in Relation to AIDS (COBRA) cohort. Methods: Cognitive function, brain tissue volumes and white matter microstructure were assessed in 134 HIV-positive patients and 79 controls. All patients had suppressed plasma HIV RNA at cohort entry. In addition to comprehensive voxelwise analyses of volumetric and diffusion tensor imaging, we used an unsupervised machine learning approach to combine cognitive, diffusion and volumetric data, taking advantage of the complementary information they provide. Results: Compared to the highly comparable control group, cognitive function was impaired in four out of the six cognitive domains tested (median global T-scores: 50.8 vs. 54.2, p

Future health systems require the means to assess and track the neural and physiological function of a user over long periods of time, and in the community. Human body responses are manifested through multiple, interacting modalities – the mechanical, electrical and chemical; yet, current physiological monitors (e.g. actigraphy, heart rate) largely lack in cross-modal ability, are inconvenient and/or stigmatizing. We address these challenges through an inconspicuous earpiece, which benefits from the relatively stable position of the ear canal with respect to vital organs. Equipped with miniature multimodal sensors, it robustly measures the brain, cardiac and respiratory functions. Comprehensive experiments validate each modality within the proposed earpiece, while its potential in wearable health monitoring is illustrated through case studies spanning these three functions. We further demonstrate how combining data from multiple sensors within such an integrated wearable device improves both the accuracy of measurements and the ability to deal with artifacts in real-world scenarios.

Post-traumatic amnesia is very common immediately after traumatic brain injury. It is characterised by a confused, agitated state and a pronounced inability to encode new memories and sustain attention. Clinically, post-traumatic amnesia is an important predictor of functional outcome. However, despite its prevalence and functional importance, the pathophysiology of post-traumatic amnesia is not understood. Memory processing relies on limbic structures such as the hippocampus, parahippocampus and parts of the cingulate cortex. These structures are connected within an intrinsic connectivity network, the Default Mode Network. Interactions within the Default Mode Network can be assessed using resting state functional magnetic resonance imaging, which can be acquired in confused patients unable to perform tasks in the scanner. Here we used this approach to test the hypothesis that the mnemonic symptoms of post-traumatic amnesia are caused by functional disconnection within the Default Mode Network. We assessed whether the hippocampus and parahippocampus showed evidence of transient disconnection from cortical brain regions involved in memory processing. 19 traumatic brain injury patients were classified into post-traumatic amnesia and traumatic brain injury control groups, based on their performance on a paired associates learning task. Cognitive function was also assessed with a detailed neuropsychological test battery. Functional interactions between brain regions were investigated using resting-state functional magnetic resonance imaging. Together with impairments in associative memory patients in post-traumatic amnesia demonstrated impairments in information processing speed and spatial working memory. Patients in post-traumatic amnesia showed abnormal functional connectivity between the parahippocampal gyrus and posterior cingulate cortex. The strength of this functional connection correlated with both associative memory and information processing speed and normalised when these functions improved. We have previously shown abnormally high posterior cingulate cortex connectivity in the chronic phase after traumatic brain injury, and this abnormality was also observed in patients with post-traumatic amnesia. Patients in post-traumatic amnesia showed evidence of widespread traumatic axonal injury measured using diffusion magnetic resonance imaging. This change was more marked within the cingulum bundle, the tract connecting the parahippocampal gyrus to the posterior cingulate cortex. These findings provide novel insights into the pathophysiology of post-traumatic amnesia and evidence that memory impairment acutely after traumatic brain injury results from altered parahippocampal functional connectivity, perhaps secondary to the effects of axonal injury on white matter tracts connecting limbic structures involved in memory processing.

Background Traumatic brain injury (TBI) is the leading cause of disability and mortality in children and young adults worldwide. It remains unclear, however, how TBI in childhood and adolescence is associated with adult mortality, psychiatric morbidity, and social outcomes. Methods and Findings In a Swedish birth cohort between 1973 and 1985 of 1,143,470 individuals, we identified all those who had sustained at least one TBI (n= 104,290 or 9.1%) up to age 25 y and their unaffected siblings (n= 68,268) using patient registers. We subsequently assessed these individuals for the following outcomes using multiple national registries: disability pension, specialist diagnoses of psychiatric disorders and psychiatric inpatient hospitalisation, premature mortality (before age 41 y), low educational attainment (not having achieved secondary school qualifications), and receiving means-tested welfare benefits. We used logistic and Cox regression models to quantify the association between TBI and specified adverse outcomes on the individual level. We further estimated population attributable fractions (PAF) for each outcome measure. We also compared differentially exposed siblings to account for unobserved genetic and environmental confounding. In addition to relative risk estimates, we examined absolute risks by calculating prevalence and KaplanMeier estimates. In complementary analyses, we tested whether the findings were moderated by injury severity, recurrence, and age at first injury (ages 0–4, 5–9, 6–10, 15–19, and 20–24 y). TBI exposure was associated with elevated risks of impaired adult functioning across all outcome measures. After a median follow-up period of 8 y from age 26 y, we found that TBI contributed to absolute risks of over 10% for specialist diagnoses of psychiatric disorders and low educational attainment, approximately 5% for disability pension, and 2% for premature mortality. The highest relative risks, adjusted for sex, birth year, and birth order, were found for psychiatric inpatient hospitalisation (adjusted relative risk [aRR] = 2.0; 95% CI: 1.9–2.0; 6,632 versus 37,095 events), disability pension (aRR = 1.8; 95% CI: 1.7–1.8; 4,691 versus 29,778 events), and premature mortality (aRR = 1.7; 95% CI: 1.6–1.9; 799 versus 4,695 events). These risks were only marginally attenuated when the comparisons were made with their unaffected siblings, which implies that the effects of TBI were consistent with a causal inference. A dose-response relationship was observed with injury severity. Injury recurrence was also associated with higher risks—in particular, for disability pension we found that recurrent TBI was associated with a 3-fold risk increase (aRR = 2.6; 95% CI: 2.4–2.8) compared to a single-episode TBI. Higher risks for all outcomes were observed for those who had sustained their first injury at an older age (ages 20–24 y) with more than 25% increase in relative risk across all outcomes compared to the youngest age group (ages 0–4 y). On the population level, TBI explained between 2%–6% of the variance in the examined outcomes. Using hospital data underestimates milder forms of TBI, but such misclassification bias suggests that the reported estimates are likely conservative. The sibling-comparison design accounts for unmeasured familial confounders shared by siblings, including half of their genes. Thus, residual genetic confounding remains a possibility but will unlikely alter our main findings, as associations were only marginally attenuated within families. Conclusions Given our findings, which indicate potentially causal effects between TBI exposure in childhood and later impairments across a range of health and social outcomes, age-sensitive clinical guidelines should be considered and preventive strategies should be targeted at children and adolescents.

OBJECTIVES: The objective of this study was to assess whether HIV-infected patients on long-term successful combination antiretroviral therapy (cART) have more extensive white matter hyperintensities (WMH) of presumed vascular origin compared with uninfected controls and whether these intensities are associated with cognitive impairment. Furthermore, we explored potential determinants of increased WMH loadin long-term suppressed HIV infection. DESIGN: A cross-sectional comparison of WMH in an observational cohort. METHODS: Clinical, cognitive and magnetic resonance imagingdata were collected from 103middle-aged, aviremic HIV-infected menon cART and 70 HIV-uninfected, otherwise similar controls. In the MRI data, WMH load was quantified by automated approaches and qualitatively reviewed by an experienced neuroradiologist using the Fazekas scale. RESULTS: HIV-infected men hadan increased WMHload. Among HIV-infected patients, increased WMH load was independently associated witholder age, higher diastolic blood pressure and D-dimer levels,and longer time spent with a CD4 count below 500 cells/mm. HIV-associated cognitive deficits were associated with increased WMHload. CONCLUSIONS: WMHare more extensive and associated with cognitive deficitsin middle-aged,aviremic cART-treated HIV-infected men. The extent of WMH load wasassociated with both cardiovascular risk factors and past immune deficiency. Since cognitive impairment in these same patients is also associated with these risk factors, this may suggest that in the setting of HIV, WMH and cognitive deficits share a common etiology. This supports the importance of optimizing cardiovascular risk management, and early, effective treatment of HIVinfection.

Traumatic brain injury (TBI) causes long-term structural and functional alterations to the brain. Some of these changes are thought to be progressive in nature,1,2 and potentially underlie the increased risk for early cognitive decline3 and dementia4 observed in TBI patients. Similar behavioral and anatomical changes are also associated with normal ageing,5,6 raising the possibility that the chronic consequences of TBI may contribute to the premature development of age-associated changes to the brain.2 Normal ageing can be considered as the progression along a temporal trajectory, where individuals gradually accumulate pathologies associated with physical decline, cognitive impairment, and brain volume loss.7,8 Insults, such as TBI, may trigger a sequence of neurobiological events that alter that trajectory, prematurely causing brain atrophy, and potentially manifesting as an early onset of neurodegeneration.9 As illustrated in Figure 1, an environmental insult like TBI might cause a one-off increase in apparent "brain age," or could result in an ongoing interaction between injury and ageing-related or other neurodegenerative processes that cause progressive brain atrophy.2 In the latter case, as more time passes since the TBI occurred, the greater the discrepancy between chronological age and estimated brain age will be. This possibility is consistent with the progressive decline associated with TBI, even years after injury, as demonstrated by neuropsychological,10 neuroimaging,11–14 and animal1 research. Figure 1 Model of premature brain ageing in traumatic brain injury. Illustration of the conceptual framework for the investigation of brain age in traumatic brain injury (TBI). The short-dashed line represents the trajectory of healthy ageing as age (x-axis) increases, ... Using neuroimaging, it is possible to predict age in healthy individuals,15 allowing the discrepancy between chronological age and predicted brain age to be calculated. In clinical samples, this discrepancy can be considered as an index of the deviation from a normal ageing trajectory. Estimates of brain age, derived using machine learning, have previously been used in a number of contexts. These include measuring normal brain maturation during development,16,17 predicting conversion from mild cognitive impairment to Alzheimer disease,18 and in neurodevelopmental disorders such as schizophrenia and borderline personality disorder, where patients were shown to have apparently "older" brains.19 The deviation from normal ageing may reflect important neurological changes relating to clinical features such as cognitive impairment. Characteristic changes to cognition seen during normal ageing affect the domains of executive function, memory, and information processing speed.20 TBI patients show a similar pattern of cognitive deficits,10 further suggesting links between TBI and ageing of the brain. Here we developed and tested a predictive model of brain age. Machine learning techniques were used to define a model that accurately predicted chronological age in healthy individuals. The model was then applied to brain images from TBI patients, allowing a prediction of their brains' ages to be made. It was expected that TBI patients' brains would be older than their chronological age and that this discrepancy would increase with longer time since injury (TSI), reflecting a progressive atrophy of brain tissue. Furthermore, we hypothesized that the discrepancy between chronological age and predicted brain age would be reflected in cognitive changes that would be consistent with age-related cognitive impairment normally seen in older individuals.

Functional neuroimaging reveals both increases (task-positive) and decreases (task-negative) in neural activation with many tasks. Many studies show a temporal relationship between task positive and task negative networks that is important for efficient cognitive functioning. Here we provide evidence for a spatial relationship between task positive and negative networks. There are strong spatial similarities between many reported task negative brain networks, termed the default mode network, which is typically assumed to be a spatially fixed network. However, this is not the case. The spatial structure of the DMN varies depending on what specific task is being performed. We test whether there is a fundamental spatial relationship between task positive and negative networks. Specifically, we hypothesize that the distance between task positive and negative voxels is consistent despite different spatial patterns of activation and deactivation evoked by different cognitive tasks. We show significantly reduced variability in the distance between within-condition task positive and task negative voxels than across-condition distances for four different sensory, motor and cognitive tasks - implying that deactivation patterns are spatially dependent on activation patterns (and vice versa), and that both are modulated by specific task demands. We also show a similar relationship between positively and negatively correlated networks from a third ‘rest’ dataset, in the absence of a specific task. We propose that this spatial relationship may be the macroscopic analogue of microscopic neuronal organization reported in sensory cortical systems, and that this organization may reflect homeostatic plasticity necessary for efficient brain function.

Objective: Traumatic brain injury (TBI) often results in traumatic axonal injury (TAI). This can be difficult to identify using conventional imaging. Diffusion tensor imaging (DTI) offers a method of assessing axonal damage in vivo, but has previously mainly been used to investigate groups of patients. Machine learning techniques are increasingly used to improve diagnosis based on complex imaging measures. We investigated whether machine learning applied to DTI data can be used to diagnose white matter damage after TBI and to predict neuropsychological outcome in individual patients. Methods: We trained pattern classifiers to predict the presence of white matter damage in 25 TBI patients with microbleed evidence of TAI compared to neurologically healthy age-matched controls. We then applied these classifiers to 35 additional patients with no conventional imaging evidence of TAI. Finally, we used regression analyses to predict indices of neuropsychological outcome for information processing speed, executive function, and associative memory in a group of 70 heterogeneous patients. Results The classifiers discriminated between patients with microbleeds and age-matched controls with a high degree of accuracy, and outperformed other methods. When the trained classifiers were applied to patients without microbleeds, patients having likely TAI showed evidence of greater cognitive impairment in information processing speed and executive function. The classifiers were also able to predict the extent of impairments in information processing speed and executive function. Interpretation: The work provides a proof of principle that multivariate techniques can be used with DTI to provide diagnostic information about clinically significant TAI. © 2013 American Neurological Association.

Following its acquisition of North Ltd in 2000, Rio Tinto acquired 114 ha of coastal land at Punakaiki on New Zealand’s South Island. Westland Ilmenite Ltd (WIL) had carried out pilot-scale mining and processing in the early 1990s but had concluded that mining would not be viable. The site had been in care and maintenance from 1994, and the plant and buildings were still present, but in poor condition. Though much of the land has been cleared for pasture, the area is of high conservation value. The site is located between the Paparoa National Park in the hills to the east and the coastal dunes, and it contains remnant coastal forest and wetlands and is adjacent to Nikau Scenic Reserve. The Paparoa National Park contains the only known breeding colonies of the vulnerable Westland Black Petrel, classified as Vulnerable in the IUCN Red List of Threatened Species. Consultations with community groups, local and regional government as well as the New Zealand Department of Conservation Te Papa Atawhai (DOC) found strong support for rehabilitating the land as a conservation area. A vision emerged from these consultations to restore the ecological corridor from the mountains to the sea, to provide a scenic gateway just south of the popular Pancake Rocks at Punakaiki. This vision led to the creation of Punakaiki Coastal Restoration Project (PCRP), a partnership between Rio Tinto, DOC and Conservation Volunteers New Zealand (CVNZ). The WIL land was gifted to DOC and became the Te Ara Taiko Nature Reserve in 2010, which forms a contiguous conservation area, including Paparoa National Park and two other reserves. The PCRP is managed by Conservation Volunteers on behalf of the partners, who oversee the project via a management committee. This structure reflects Rio Tinto’s existing 15 years relationship with Conservation Volunteers in Australia. The PCRP partnership has enabled Conservation Volunteers to establish in New Zealand and develop additional projects with the Department of Conservation, other government agencies and the corporate sector. Conservation Volunteers use the refurbished office and workshop buildings as the project administration centre and plan to use the site as a hub for its west coast activities. A plant nursery has been established, and more than 12,500 seedlings have been collected and raised to augment commercial supply. Over 5,000 volunteer days have been devoted to removing gorse and other weeds and to propagating and planting over 100,000 native forest species seedlings on 12 ha of the former pasture. Students from a local school and polytechnic are regular visitors and participate in activities that complement their studies. Visual monitoring transects have been established to monitor restoration progress, and a research collaboration has been established with Lincoln University to develop methods to monitor the restoration over the long term.