Vector trace cells in the subiculum of the hippocampal formation

Successfully navigating in physical or semantic space requires a neural representation of allocentric (map-based) vectors to boundaries, objects and goals. Cognitive processes such as path-planning and imagination entail the recall of vector representations, but evidence of neuron-level memory for allocentric vectors has been lacking. Here, we describe a novel neuron type, vector trace cell (VTC), whose firing generates a new vector field when a cue is encountered and a ‘trace’ version of that field for hours after cue removal. VTCs are concentrated in subiculum, distal to CA1. Compared to non-trace cells, VTCs fire at further distances from cues and exhibit earlier-going shifts in preferred theta phase in response to newly introduced cues, which demonstrates a theta-linked neural substrate for memory encoding. VTCs suggest a vector-based model of computing spatial relationships between an agent and multiple spatial objects, or between different objects, freed from the constraints of direct perception of those objects

The effects of using the PReDicT Test to guide the antidepressant treatment of depressed patients: study protocol for a randomised controlled trial

Background Antidepressant medication is commonly used to treat depression. However, many patients do not respond to the first medication prescribed and improvements in symptoms are generally only detectable by clinicians 4–6 weeks after the medication has been initiated. As a result, there is often a long delay between the decision to initiate an antidepressant medication and the identification of an effective treatment regimen. Previous work has demonstrated that antidepressant medications alter subtle measures of affective cognition in depressed patients, such as the appraisal of facial expression. Furthermore, these cognitive effects of antidepressants are apparent early in the course of treatment and can also predict later clinical response. This trial will assess whether an electronic test of affective cognition and symptoms (the Predicting Response to Depression Treatment Test; PReDicT Test) can be used to guide antidepressant treatment in depressed patients and, therefore, hasten treatment response compared to a control group of patients treated as usual. Methods/design The study is a randomised, two-arm, multi-centre, open-label, clinical investigation of a medical device, the PReDicT Test. It will be conducted in five European countries (UK, France, Spain, Germany and the Netherlands) in depressed patients who are commencing antidepressant medication. Patients will be randomised to treatment guided by the PReDicT Test (PReDicT arm) or to Treatment as Usual (TaU arm). Patients in the TaU arm will be treated as per current standard guidelines in their particular country. Patients in the PReDicT arm will complete the PReDicT Test after 1 (and if necessary, 2) weeks of treatment. If the test indicates non-response to the treatment, physicians will be advised to immediately alter the patient’s antidepressant therapy by dose escalation or switching to another compound. The primary outcome of the study is the proportion of patients showing a clinical response (defined as 50% or greater decrease in baseline scores of depression measured using the Quick Inventory of Depressive Symptoms – Self-Rated questionnaire) at week 8. Health economic and acceptability data will also be collected and analysed. Discussion This trial will test the clinical efficacy, cost-effectiveness and acceptability of using the novel PReDicT Test to guide antidepressant treatment selection in depressed patients

Methane transport in agricultural soil after injection of isotopically-enriched methane in the sub-surface

Small quantities of radioactive methane (14CH4) may be released over prolonged periods from geological disposal facilities for radioactive waste. The impact of this release depends on the capacity of soil to oxidise 14CH4 to 14CO2 during transport from the sub-surface to the atmosphere. We investigated this capacity by pulse-injecting isotopically-enriched methane 50 cm below the surface of an agricultural soil in central England. Three sequential injections were made during growth of a spring wheat crop. Samples of gas were taken from the pore space throughout the soil profile at predetermined time points after injection, accompanied by samples of the atmosphere above the soil collected in sampling chambers, deployed at scheduled intervals. Methane and CO2 were measured in soil and above-ground gas using gas chromatography; the isotopic composition of CH4 and CO2 was determined using gas chromatography with isotopic ratio mass spectrometry. Supporting measurements of environmental variables were made during the experiment. The data can be used to test mathematical models describing CH4 and CO2 transport and fate in temperate agricultural soils

Cognition in meningioma: effects of tumour location and tumour removal.

Meningiomas are the most common type of primary intracranial tumour, yet very few studies have assessed the effects of tumour removal. Here we report analysis of patients with meningiomas who underwent routine neuropsychological assessment and surgery at an NHS hospital in the North East of England over a six-year period. Surgical removal of tumours significantly improved both Phonemic and Semantic Verbal Fluency, and some measures of Working memory and Declarative memory. There were no signs of deleterious effects of surgery. Post-operative improvements in cognition did not appear to rely upon changes in anxiety and mood. In summary, we conclude that tumour removal in meningioma can be associated with some benefits in cognition

The clinical effectiveness of using a predictive algorithm to guide antidepressant treatment in primary care (PReDicT): an open-label, randomised controlled trial

Depressed patients often do not respond to the first antidepressant prescribed, resulting in sequential trials of different medications. Personalised medicine offers a means of reducing this delay; however, the clinical effectiveness of personalised approaches to antidepressant treatment has not previously been tested. We assessed the clinical effectiveness of using a predictive algorithm, based on behavioural tests of affective cognition and subjective symptoms, to guide antidepressant treatment. We conducted a multicentre, open-label, randomised controlled trial in 913 medication-free depressed patients. Patients were randomly assigned to have their antidepressant treatment guided by a predictive algorithm or treatment as usual (TaU). The primary outcome was the response of depression symptoms, defined as a 50% or greater reduction in baseline score of the QIDS-SR-16 scale, at week 8. Additional prespecified outcomes included symptoms of anxiety at week 8, and symptoms of depression and functional outcome at weeks 8, 24 and 48. The response rate of depressive symptoms at week 8 in the PReDicT (55.9%) and TaU (51.8%) arms did not differ significantly (odds ratio: 1.18 (95% CI: 0.89–1.56), P = 0.25). However, there was a significantly greater reduction of anxiety in week 8 and a greater improvement in functional outcome at week 24 in the PReDicT arm. Use of the PReDicT test did not increase the rate of response to antidepressant treatment estimated by depressive symptoms but did improve symptoms of anxiety at week 8 and functional outcome at week 24. Our findings indicate that personalisation of antidepressant treatment may improve outcomes in depressed patients

Unifying Subicular Function: A Predictive Map Approach.

The successor representation has emerged as a powerful model for understanding mammalian navigation and memory; explaining the spatial coding properties of hippocampal place cells and entorhinal grid cells. However, the diverse spatial responses of subicular neurons, the primary output of the hippocampus, have eluded a unified account. Here, we demonstrate that incorporating rodent behavioural biases into the successor representation successfully reproduces the heterogeneous activity patterns of subicular neurons. This framework accounts for the emergence of boundary and corner cells; neuronal types absent in upstream hippocampal regions. We provide evidence that subicular firing patterns are more accurately described by the successor representation than a purely spatial or boundary vector cell model of subiculum. Our work offers a unifying theory of subicular function that positions the subiculum, more than other hippocampal regions, as a predictive map of the environment

Exploring the sensitivity of episodic and spatial memory tests to healthy and pathological cognitive aging

Introduction: In an increasingly aging society, testing hippocampal-dependent cognition in a quick and low resource manner will be crucial in: assessing the potential benefits of lifestyle choices and interventions affecting cognitive ageing (such as those involving exercise, diet, and sleep); detecting pathological aging, such as in Alzheimer’s disease, where hippocampal degeneration occurs relatively early on.Methods: Over 300 participants aged 18-89 completed three cognitive tests, namely the Addenbrooke’s Cognitive Examination-III (ACE-III), The Four Mountains Task (4MT), and a new task introduced here, the Spaces and Sequences Episodic Video Task (SSEVT). Hippocampal tissue is particularly vulnerable to aging, and the 4MT and SSEVT were designed to be hippocampal-dependent. Accordingly, we tested the hypothesis that 4MT and SSEVT performance would be significantly compromised by aging. As an initial proof-of-concept exploration of these tests’ ability to detect pathological aging, such as in Alzheimer’s disease, we compared 10 patients with Mild Cognitive Impairment (MCI) with matched subsamples of the older group (Healthy ageing, HA).Results: Supporting the hippocampal-aging related hypothesis, 4MT and SSEVT scores showed appreciably stronger age-related declines than ACE-III scores. The middle-aged group (mean: ∼51 years) were significantly worse than the young group (mean: ∼21 years) on the 4MT (Cohen’s d = 0.724) and the SSEVT (Cohen’s d = 0.443); and the older group (mean: ∼71 years) were significantly worse than the middle-aged group on the SSEVT (Cohen’s d = 0.724). Neither pattern was seen for ACE-III. Suggestively, the MCI patients performed worse than the matched HA group on the 4MT (consistent with previous work), and on our novel SSEVT, but not on the ACE-III.Discussion: We conclude that the 4MT and SSEVT may be suitable for assessing lifestyle choices and interventions affecting cognitive ageing. We also propose that these findings provide an initial proof-of-concept for these tests’ ability to detect pathological aging in its early stages and support further exploration of this with larger clinical samples

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries