Improved green and red GRAB sensors for monitoring dopaminergic activity in vivo.

Dopamine (DA) plays multiple roles in a wide range of physiological and pathological processes via a large network of dopaminergic projections. To dissect the spatiotemporal dynamics of DA release in both dense and sparsely innervated brain regions, we developed a series of green and red fluorescent G-protein-coupled receptor activation-based DA (GRABDA) sensors using a variety of DA receptor subtypes. These sensors have high sensitivity, selectivity and signal-to-noise ratio with subsecond response kinetics and the ability to detect a wide range of DA concentrations. We then used these sensors in mice to measure both optogenetically evoked and behaviorally relevant DA release while measuring neurochemical signaling in the nucleus accumbens, amygdala and cortex. Using these sensors, we also detected spatially resolved heterogeneous cortical DA release in mice performing various behaviors. These next-generation GRABDA sensors provide a robust set of tools for imaging dopaminergic activity under a variety of physiological and pathological conditions.

Improved dual-color GRAB sensors for monitoring dopaminergic activity in vivo.

Dopamine (DA) plays multiple roles in a wide range of physiological and pathological processes via a vast network of dopaminergic projections. To fully dissect the spatiotemporal dynamics of DA release in both dense and sparsely innervated brain regions, we developed a series of green and red fluorescent GPCR activation-based DA (GRABDA) sensors using a variety of DA receptor subtypes. These sensors have high sensitivity, selectivity, and signal-to-noise properties with subsecond response kinetics and the ability to detect a wide range of DA concentrations. We then used these sensors in freely moving mice to measure both optogenetically evoked and behaviorally relevant DA release while measuring neurochemical signaling in the nucleus accumbens, amygdala, and cortex. Using these sensors, we also detected spatially resolved heterogeneous cortical DA release in mice performing various behaviors. These next-generation GRABDA sensors provide a robust set of tools for imaging dopaminergic activity under a variety of physiological and pathological conditions.

Competitive integration of time and reward explains value-sensitive foraging decisions and frontal cortex ramping dynamics.

The ability to make advantageous decisions is critical for animals to ensure their survival. Patch foraging is a natural decision-making process in which animals decide when to leave a patch of depleting resources to search for a new one. To study the algorithmic and neural basis of patch foraging behavior in a controlled laboratory setting, we developed a virtual foraging task for head-fixed mice. Mouse behavior could be explained by ramp-to-threshold models integrating time and rewards antagonistically. Accurate behavioral modeling required inclusion of a slowly varying "patience" variable, which modulated sensitivity to time. To investigate the neural basis of this decision-making process, we performed dense electrophysiological recordings with Neuropixels probes broadly throughout frontal cortex and underlying subcortical areas. We found that decision variables from the reward integrator model were represented in neural activity, most robustly in frontal cortical areas. Regression modeling followed by unsupervised clustering identified a subset of neurons with ramping activity. These neurons' firing rates ramped up gradually in single trials over long time scales (up to tens of seconds), were inhibited by rewards, and were better described as being generated by a continuous ramp rather than a discrete stepping process. Together, these results identify reward integration via a continuous ramping process in frontal cortex as a likely candidate for the mechanism by which the mammalian brain solves patch foraging problems.

Change in the food environment and measured adiposity in adulthood in the Christchurch Health and development birth cohort, Aotearoa, New Zealand: A birth cohort study.

This study investigated associations between change in the food environment and change in measured body mass index (BMI) and waist circumference (WC) in the Christchurch Health and Development Study (CHDS) birth cohort. Our findings suggest that cohort members who experienced the greatest proportional change towards better access to fast food outlets had the slightly larger increases in BMI and WC. Contrastingly, cohort members who experienced the greatest proportional change towards shorter distance and better access to supermarkets had slightly smaller increases in BMI and WC. Our findings may help explain the changes in BMI and WC at a population level.

Modelling admission lengths within psychiatric intensive care units.

OBJECTIVES: To examine whether discharge destination is a useful predictor variable for the length of admission within psychiatric intensive care units (PICUs). METHODS: A clinician-led process separated PICU admissions by discharge destination into three types and suggested other possible variables associated with length of stay. Subsequently, a retrospective study gathered proposed predictor variable data from a total of 368 admissions from four PICUs. Bayesian models were developed and analysed. RESULTS: Clinical patient-type grouping by discharge destination displayed better intraclass correlation (0.37) than any other predictor variable (next highest was the specific PICU to which a patient was admitted (0.0585)). Patients who were transferred to further secure care had the longest PICU admission length. The best model included both patient type (discharge destination) and unit as well as an interaction between those variables. DISCUSSION: Patient typing based on clinical pathways shows better predictive ability of admission length than clinical diagnosis or a specific tool that was developed to identify patient needs. Modelling admission lengths in a Bayesian fashion could be expanded and be useful within service planning and monitoring for groups of patients. CONCLUSION: Variables previously proposed to be associated with patient need did not predict PICU admission length. Of the proposed predictor variables, grouping patients by discharge destination contributed the most to length of stay in four different PICUs.

Dissociation and its biological and clinical associations in functional neurological disorder: systematic review and meta-analysis.

BACKGROUND: Studies have reported elevated rates of dissociative symptoms and comorbid dissociative disorders in functional neurological disorder (FND); however, a comprehensive review is lacking. AIMS: To systematically review the severity of dissociative symptoms and prevalence of comorbid dissociative disorders in FND and summarise their biological and clinical associations. METHOD: We searched Embase, PsycInfo and MEDLINE up to June 2021, combining terms for FND and dissociation. Studies were eligible if reporting dissociative symptom scores or rates of comorbid dissociative disorder in FND samples. Risk of bias was appraised using modified Newcastle-Ottawa criteria. The findings were synthesised qualitatively and dissociative symptom scores were included in a meta-analysis (PROSPERO CRD42020173263). RESULTS: Seventy-five studies were eligible (FND n = 3940; control n = 3073), most commonly prospective case-control studies (k = 54). Dissociative disorders were frequently comorbid in FND. Psychoform dissociation was elevated in FND compared with healthy (g = 0.90, 95% CI 0.66-1.14, I2 = 70%) and neurological controls (g = 0.56, 95% CI 0.19-0.92, I2 = 67%). Greater psychoform dissociation was observed in FND samples with seizure symptoms versus healthy controls (g = 0.94, 95% CI 0.65-1.22, I2 = 42%) and FND samples with motor symptoms (g = 0.40, 95% CI -0.18 to 1.00, I2 = 54%). Somatoform dissociation was elevated in FND versus healthy controls (g = 1.80, 95% CI 1.25-2.34, I2 = 75%). Dissociation in FND was associated with more severe functional symptoms, worse quality of life and brain alterations. CONCLUSIONS: Our findings highlight the potential clinical utility of assessing patients with FND for dissociative symptomatology. However, fewer studies investigated FND samples with motor symptoms and heterogeneity between studies and risk of bias were high. Rigorous investigation of the prevalence, features and mechanistic relevance of dissociation in FND is needed.

Distance-tuned neurons drive specialized path integration calculations in medial entorhinal cortex.

During navigation, animals estimate their position using path integration and landmarks, engaging many brain areas. Whether these areas follow specialized or universal cue integration principles remains incompletely understood. We combine electrophysiology with virtual reality to quantify cue integration across thousands of neurons in three navigation-relevant areas: primary visual cortex (V1), retrosplenial cortex (RSC), and medial entorhinal cortex (MEC). Compared with V1 and RSC, path integration influences position estimates more in MEC, and conflicts between path integration and landmarks trigger remapping more readily. Whereas MEC codes position prospectively, V1 codes position retrospectively, and RSC is intermediate between the two. Lowered visual contrast increases the influence of path integration on position estimates only in MEC. These properties are most pronounced in a population of MEC neurons, overlapping with grid cells, tuned to distance run in darkness. These results demonstrate the specialized role that path integration plays in MEC compared with other navigation-relevant cortical areas.

Dynamic and reversible remapping of network representations in an unchanging environment.

Neurons in the medial entorhinal cortex alter their firing properties in response to environmental changes. This flexibility in neural coding is hypothesized to support navigation and memory by dividing sensory experience into unique episodes. However, it is unknown how the entorhinal circuit as a whole transitions between different representations when sensory information is not delineated into discrete contexts. Here we describe rapid and reversible transitions between multiple spatial maps of an unchanging task and environment. These remapping events were synchronized across hundreds of neurons, differentially affected navigational cell types, and correlated with changes in running speed. Despite widespread changes in spatial coding, remapping comprised a translation along a single dimension in population-level activity space, enabling simple decoding strategies. These findings provoke reconsideration of how the medial entorhinal cortex dynamically represents space and suggest a remarkable capacity of cortical circuits to rapidly and substantially reorganize their neural representations.

Strengthening community connection and personal well-being through volunteering in New Zealand.

Volunteering is a way for people to develop meaningful relationships within a social group and can lead to the building of social capital, from which both individuals and the wider group can benefit in the form of enhanced well-being. This study aimed to explore and describe the impact of volunteering on the volunteer coordinators and volunteers themselves in the eastern suburbs of Christchurch, New Zealand, an area particularly impacted by the devastating earthquakes in the period 2010/2011. Data were collected via semi-structured interviews with volunteer coordinators and volunteers (n = 35; 16 men, 19 women) from November 2018 to mid-January 2019. Thematic analysis of data highlighted a key theme of Creating and strengthening valued community connections, with subthemes of Personal growth, Community connections and Role of coordination. The key theme illustrated how formal volunteering created effort and opportunities towards the strengthening of personal and community connectedness. Our study demonstrates the importance of social connection for both individual and community well-being, emphasises the important role of "champions" in facilitating the building of bridging and bonding relationships between individuals and communities, and suggests a role for healthcare professionals to prescribe volunteering as a way to improve individual health and well-being outcomes.

The good, the bad, and the environment: developing an area-based measure of access to health-promoting and health-constraining environments in New Zealand.

BACKGROUND: Accounting for the co-occurrence of multiple environmental influences is a more accurate reflection of population exposure than considering isolated influences, aiding in understanding the complex interactions between environments, behaviour and health. This study examines how environmental 'goods' such as green spaces and environmental 'bads' such as alcohol outlets co-occur to develop a nationwide area-level healthy location index (HLI) for New Zealand. METHODS: Nationwide data were collected, processed, and geocoded on a comprehensive range of environmental exposures. Health-constraining 'bads' were represented by: (i) fast-food outlets, (ii) takeaway outlets, (iii) dairy outlets and convenience stores, (iv) alcohol outlets, (v) and gaming venues. Health-promoting 'goods' were represented by: (i) green spaces, (ii) blue spaces, (iii) physical activity facilities, (iv) fruit and vegetable outlets, and (v) supermarkets. The HLI was developed based on ranked access to environmental domains. The HLI was then used to investigate socio-spatial patterning by area-level deprivation and rural/urban classification. RESULTS: Results showed environmental 'goods' and 'bads' co-occurred together and were patterned by area-level deprivation. The novel HLI shows that the most deprived areas of New Zealand often have the most environmental 'bads' and less access to environmental 'goods'. CONCLUSIONS: The index, that is now publicly available, is able to capture both inter-regional and local variations in accessibility to health-promoting and health-constraining environments and their combination. Results in this study further reinforce the need to embrace the multidimensional nature of neighbourhood and place not only when designing health-promoting places, but also when studying the effect of existing built environments on population health.

Investigating the Association Between Child Television Viewing and Measured Child Adiposity Outcomes in a Large Nationally Representative Sample of New Zealanders: A Cross-Sectional Study.

BACKGROUND: This study investigates the association between television (TV) viewing and child adiposity and if parental education and child ethnicity moderate this association. METHOD: Cross-sectional, pooled (2013/2014-2016/2017) adult and child New Zealand Health Survey were matched resulting in 13,039 children (2-14 y) and parent dyads. Child TV viewing was estimated using self-reported time for each weekday and weekend. The height (in centimeters), weight (in kilograms), and waist circumference of parents and children were measured. Childhood body mass index and obesity were defined using the International Obesity Task Force cutoff values. Effect modification was assessed by interaction and then by stratifying regression analyses by parent education (low, moderate, and high) and child ethnicity (Asian, European/other, Maori, and Pacific). RESULTS: Overall, watching ≥2 hours TV on average per day in the past week, relative to <2 hours TV viewing, was associated with a higher odds of obesity (adjusted odds ratio = 1.291 [1.108-1.538]), higher body mass index z score (b = 0.123 [0.061-0.187]), and higher waist circumference (b = 0.546 [0.001-1.092]). Interactions considering this association by child ethnicity and parent education revealed little evidence of effect modification. CONCLUSION: While TV viewing was associated with child adiposity, the authors found little support for a moderating role of parental education and child ethnicity.

National movement patterns during the COVID-19 pandemic in New Zealand: the unexplored role of neighbourhood deprivation.

BACKGROUND: The COVID-19 pandemic has asked unprecedented questions of governments around the world. Policy responses have disrupted usual patterns of movement in society, locally and globally, with resultant impacts on national economies and human well-being. These interventions have primarily centred on enforcing lockdowns and introducing social distancing recommendations, leading to questions of trust and competency around the role of institutions and the administrative apparatus of state. This study demonstrates the unequal societal impacts in population movement during a national 'lockdown'. METHODS: We use nationwide mobile phone movement data to quantify the effect of an enforced lockdown on population mobility by neighbourhood deprivation using an ecological study design. We then derive a mobility index using anonymised aggregated population counts for each neighbourhood (2253 Census Statistical Areas; mean population n=2086) of national hourly mobile phone location data (7.45 million records, 1 March 2020-20 July 2020) for New Zealand (NZ). RESULTS: Curtailing movement has highlighted and exacerbated underlying social and spatial inequalities. Our analysis reveals the unequal movements during 'lockdown' by neighbourhood socioeconomic status in NZ. CONCLUSION: In understanding inequalities in neighbourhood movements, we are contributing critical new evidence to the policy debate about the impact(s) and efficacy of national, regional or local lockdowns which have sparked such controversy.

Spatial-temporal patterns of childhood immunization in New Zealand (2006-2017): an improving pattern but not for all?

BACKGROUND: Declining childhood immunization represents a serious public health problem globally and in New Zealand. To guide efforts to increase immunization coverage, this study monitors nationwide change in immunization coverage since the introduction of the National Immunisation Register (NIR) in 2005 and spatiotemporal patterns of immunization coverage from 2006 to 2017. METHODS: The study population consisted of 4 482 499 individual immunization records that were obtained from the NIR (2005-2017). Data on yearly and average immunization coverage in census area units (CAUs) in New Zealand were calculated by milestone age (6/8/12/18/24/60/144 months). Data for 2005 were excluded due to missing records in the introductory period of the NIR. We analyzed spatial and spatiotemporal patterns using Gi* and SaTScan methods. RESULTS: Immunization coverage improved since the introduction of the NIR in 2005, reaching a peak in 2014 and 2015 with a slight decrease in 2016 and 2017. Well and insufficiently immunized areas were identified with spatial autocorrelation analyses highlighting several hot- and cold-spots. Comparison of CAUs with neighbouring CAUs allowed for the identification of places where immunization coverage was significantly higher or lower than expected, over both time and space. CONCLUSION: We provide the first spatiotemporal analysis of childhood immunization in New Zealand that utilizes a large sample of over 4.4 million individual immunization records. Our spatial analyses enable policymakers to understand the development of childhood immunization coverage and make more effective prevention strategies in New Zealand.

Mouse entorhinal cortex encodes a diverse repertoire of self-motion signals.

Neural circuits generate representations of the external world from multiple information streams. The navigation system provides an exceptional lens through which we may gain insights about how such computations are implemented. Neural circuits in the medial temporal lobe construct a map-like representation of space that supports navigation. This computation integrates multiple sensory cues, and, in addition, is thought to require cues related to the individual's movement through the environment. Here, we identify multiple self-motion signals, related to the position and velocity of the head and eyes, encoded by neurons in a key node of the navigation circuitry of mice, the medial entorhinal cortex (MEC). The representation of these signals is highly integrated with other cues in individual neurons. Such information could be used to compute the allocentric location of landmarks from visual cues and to generate internal representations of space.

Possible pharmacogenetic factors in clozapine treatment failure: a case report.

There is still much to learn about the predictors of therapeutic response in psychiatry, but progress is gradually being made and precision psychiatry is an exciting and emerging subspeciality in this field. This is critically important in the treatment of refractory psychotic disorders, where clozapine is the only evidence-based treatment but only about half the patients experience an adequate response. In this case report, we explore the possible biological mechanisms underlying treatment failure and discuss possible ways of improving clinical outcomes. Further work is required to fully understand why some patients fail to respond to the most effective treatment in refractory schizophrenia. Therapeutic drug monitoring together with early pharmacogenetic testing may offer a path for some patients with refractory psychotic symptoms unresponsive to clozapine treatment.

Transport changes and COVID-19: From present impacts to future possibilities.

Changes in people's movement and travel behaviour have been apparent in many places during the COVID-19 pandemic, with differences seen at a range of spatial scales. These changes, occurring as a result of the COVID-19 'natural experiment', have afforded us an opportunity to reimagine how we might move in our day-to-day travels, offering a hopeful glimpse of possibilities for future policy and planning around transport. The nature and scale of changes in movement and transport resulting from the pandemic have shown we can shift travel behaviour with strong policy responses, which is especially important in the concurrent climate change crisis.

A geospatial analysis of Type 2 Diabetes Mellitus and the food environment in urban New Zealand.

The aim of this research is to analyse the spatial epidemiology of Type 2 Diabetes Mellitus (T2DM) and investigate associations with the built environment in urban New Zealand. Data on T2DM was sourced from the New Zealand Virtual Diabetes Register (2016), and data on environmental variables sourced from the Ministry for Primary Industries and Territorial Authorities (2013-2016). Novel measures of the built environment using an enhanced two-step floating catchment area model were established using data on fast food outlets, takeaways, dairy/convenience stores, supermarkets and fruit/vegetable stores. Rates of T2DM per 1000 population and standardised morbidity ratios were computed and visualised for all urban areas. Getis Ord was used to assess spatial clustering, and Bayesian modelling was used to understand associations between T2DM and environmental variables. Results indicate that T2DM is influenced by demographic factors, spatially clustered and associated with accessibility to environmental exposures. Health-promoting resources, such as fruit/vegetable stores, were shown to have a consistently protective effect on T2DM while those considered detrimental to health showed varying, and largely insignificant, associations. This is the first study in New Zealand to spatially quantify the effects of multiple environmental exposures on population level T2DM for all urban areas using a geospatial approach. It has implications for both policy and future research efforts as a deeper knowledge of local environments forms a basis on which to better understand spatial associations between the built environment and health, as well as formulate policy directed toward environmental influences on chronic health conditions.

Investigating spatial variation and change (2006-2017) in childhood immunisation coverage in New Zealand.

BACKGROUND: Immunisation is a safe and effective way of protecting children and adults against harmful diseases. However, immunisation coverage of children is declining in some parts of New Zealand. AIM: Use a nationwide sample to first, examine the socioeconomic and demographic determinants of immunisation coverage and spatial variation in these determinants. Second, it investigates change in immunisation coverage in New Zealand over time. METHODS: Individual immunisation records were obtained from the National Immunisation Register (NIR) (2005-2017; 4,482,499 events). We calculated the average immunisation coverage by year and milestone age for census area units (CAU) and then examined the immunisation coverage by selected socioeconomic and demographic determinants. Finally, local variations in the association between immunisation coverage and selected determinants were investigated using geographically weighted regression. RESULTS: Findings showed a decrease of immunisation rates in recent years in CAUs with high immunisation coverage in the least deprived areas and increasing immunisation rates in more deprived areas. Nearly all explanatory variables exhibited a spatial variation in their association with immunisation coverage. For instance, the strongest negative effect of area-level deprivation is observed in the northern part of the South Island, the central-southern part of the North Island, around Auckland, and in Northland. CONCLUSION: Our findings show that childhood immunisation coverage varies by socioeconomic and demographic factors across CAUs. We also identify important spatial variation and changes over time in recent years. This evidence can be used to improve immunisation related policy in New Zealand.