Publications

Publication: NeuroImage

Buonincontri G, Biagi L, Retico A, Cecchi P, Cosottini M, Gallagher F, et al.

15 July 2019

Publication: Psychopharmacology

Robbins TW, Cardinal RN

4 April 2019

Psychopharmacology needs novel quantitative measures and theoretical approaches based on computational modelling that can be used to help translate behavioural findings from experimental animals to humans, including patients with neuropsychiatric disorders.

Here, researchers carried out a brief review which exemplifies this approach when applied to recent published studies of the effects of manipulating central dopaminergic and serotoninergic systems in rodents and marmoset monkeys, and possible comparisons with healthy human volunteers receiving systemic agents or patients with depression and schizophrenia.

Behavioural effects of central depletions of dopamine or serotonin in monkeys in probabilistic learning paradigms are characterised further by computational modelling methods and related to rodent and human data.

Several examples are provided of the power of computational modelling to derive new measures and reappraise conventional explanations of regional neurotransmitter depletion and other drug effects, whilst enhancing construct validation in patient groups. Specifically, effects are shown on such parameters as ‘stimulus stickiness’ and ‘side stickiness’, which occur over and above effects on standard parameters of reinforcement learning, reminiscent of some early innovations in data analysis in psychopharmacology.

Computational modelling provides a useful methodology for further detailed analysis of behavioural mechanisms that are affected by pharmacological manipulations across species and will aid the translation of experimental findings to understand the therapeutic effects of medications in neuropsychiatric disorders, as well as facilitating future drug discovery.

Publication: Journal of Neurology

Julie Wiggins, Claire J. Lansdall, Kate Dawson, Timothy Rittman & James B. Rowe

2 July 2019

In this study the researchers aimed to validate the use of the Test Your Memory (TYM) test in dementias other than Alzheimer’s disease, and to compare the TYM test to two other short cognitive tests.

Patients scored an average of 34.4/50 on the TYM test compared to 46.0/50 in age-matched controls. Using the threshold of 42/50, the TYM test detected 80% of non-Alzheimer dementias. The area under the ROC curve was 0.89 with a PPV of 0.80 and a NPV of 0.84. The TYM test performed better than the ACE-R (using the threshold of 83) which detected 69% of cases and the MMSE (using a threshold of 24) which detected only 27%.

The TYM test is a useful test in the detection of non-Alzheimer dementia. The TYM test performs much better than the MMSE at detecting non-Alzheimer dementias.

Publication: Journal of Experimental Medicine

Spencer S, Köstel Bal S, Egner W, Lango Allen H, Raza SI, Ma CA, Gürel M, Zhang Y, Sun G, Sabroe RA, Greene D, Rae W, Shahin T, Kania K, Ardy RC, Thian M, Staples E, Pecchia-Bekkum A, Worrall WPM, Stephens J, Brown M, Tuna S, York M, Shackley F, Kerrin D, Sargur R, Condliffe A, Tipu HN, Kuehn HS, Rosenzweig SD, Turro E, Tavaré S, Thrasher AJ, Jodrell DI, Smith KGC, Boztug K, Milner JD, Thaventhiran JED.

24 June 2019

Publication: Cerebral Cortex

The analysis of neural circuits can provide crucial insights into the mechanisms of neurodegeneration and dementias, and offer potential quantitative biological tools to assess novel therapeutics. Here the researchers used behavioral variant frontotemporal dementia (bvFTD) as a model disease.

They demonstrated that inversion of canonical microcircuit models to noninvasive human magnetoencephalography, using dynamic causal modeling, can identify the regional- and laminar-specificity of bvFTD pathophysiology, and their parameters can accurately differentiate patients from matched healthy controls.

The research team suggests that this approach provides an in vivo platform for testing mechanistic hypotheses about disease progression and pharmacotherapeutics.

Publication: Psychopharmacology

Alsiö J, Phillips BU, Sala Bayo J, Nilsson SRO, Calafat-Pla TC, Rizwand A, Plumbridge J, López-Cruz L, Dalley JW, Cardinal RN, Mar AC, Robbins TW

19 June 2019

Dopamine D2-like receptors (D2R) are important drug targets in schizophrenia and Parkinson’s disease, but D2R ligands also cause cognitive inflexibility such as poor reversal learning. The specific role of D2R in reversal learning remains unclear.

Here researchers tested the hypotheses that D2R agonism impairs reversal learning by blocking negative feedback and that antagonism of D1-like receptors (D1R) impairs learning from positive feedback.

Male Lister Hooded rats were trained on a novel visual reversal learning task. Performance on “probe trials”, during which the correct or incorrect stimulus was presented with a third, probabilistically rewarded (50% of trials) and therefore intermediate stimulus, revealed individual learning curves for the processes of positive and negative feedback.

The effects of D2R and D1R agonists and antagonists were evaluated. A separate cohort was tested on a spatial probabilistic reversal learning (PRL) task after D2R agonism.

Computational reinforcement learning modelling was applied to choice data from the PRL task to evaluate the contribution of latent factors.

The team found that D2R agonism with quinpirole dose-dependently impaired both visual reversal and PRL. Analysis of the probe trials on the visual task revealed a complete blockade of learning from negative feedback at the 0.25 mg/kg dose, while learning from positive feedback was intact. Estimated parameters from the model that best described the PRL choice data revealed a steep and selective decrease in learning rate from losses. D1R antagonism had a transient effect on the positive probe trials. They concluded that D2R stimulation impairs reversal learning by blocking the impact of negative feedback.

Publication: Advances in Nutrition

Aljuraiban G, Gibson R, Oude Griep L, Okuda N, Steffen L, Van Horn L et al.

18 June 2019

Healthy dietary habits are the cornerstone of cardiovascular disease (CVD) prevention.

Numerous researchers have developed diet quality indices to help evaluate and compare diet quality across and within various populations.

The availability of these new indices raises questions regarding the best selection relevant to a given population.

In this perspective, we critically evaluate a priori–defined dietary indices commonly applied in epidemiological studies of CVD risk and mortality.

A systematic literature search identified 59 observational studies that applied a priori–defined diet quality indices to CVD risk factors and/or CVD incidence and/or CVD mortality.

Among 31 different indices, these scores were categorized as follows: 1) those based on country-specific dietary patterns, 2) those adapted from distinct dietary guidelines, and 3) novel scores specific to key diet-related factors associated with CVD risk.

The strengths and limitations of these indices are described according to index components, calculation methods, and the application of these indices to different population groups. Also, the importance of identifying methodological challenges faced by researchers when applying an index are considered, such as selection and weighting of food groups within a score, since food groups are not necessarily equivalent in their associations with CVD.

The lack of absolute cutoff values, emphasis on increasing healthy food without limiting unhealthy food intake, and absence of validation of scores with biomarkers or other objective diet assessment methods further complicate decisions regarding the best indices to use.

Future research should address these limitations, consider cross-cultural and other differences between population groups, and identify translational challenges inherent in attempting to apply a relevant diet quality index for use in CVD prevention at a population level.

Publication: Nature Medicine

Felipe A. Vieira Braga, Gozde Kar, Marijn Berg, Orestes A. Carpaij, Krzysztof Polanski, Lukas M. Simon, Sharon Brouwer, Tomás Gomes, Laura Hesse, Jian Jiang, Eirini S. Fasouli, Mirjana Efremova, Roser Vento-Tormo, Carlos Talavera-López, Marnix R. Jonker, Karen Affleck, Subarna Palit, Paulina M. Strzelecka, Helen V. Firth, Krishnaa T. Mahbubani, Ana Cvejic, Kerstin B. Meyer, Kourosh Saeb-Parsy, Marjan Luinge, Corry-Anke Brandsma, Wim Timens, Ilias Angelidis, Maximilian Strunz, Gerard H. Koppelman, Antoon J. van Oosterhout, Herbert B. Schiller, Fabian J. Theis, Maarten van den Berge, Martijn C. Nawijn, Sarah A. Teichmann

17 June 2019

_________________________________________________________________

Summary:

This research carried out a survey of structural and immune cells in the airways of healthy and asthmatic lungs and identified a novel set of T cells resident in asmatic airways. There is altered communication between immune and structural cells in asthmatic airways and these changes underlie the inflammation in these airways.

Publication: Alzheimer's and Dementia Diagnosis, Assessment & Disease Monitoring

Laura E. Hughes, Richard N. Henson, Ernesto Pereda, Ricardo Bruña, David López‐Sanz, Andrew J. Quinn, Mark W. Woolrich, Anna C. Nobre, James B. Rowe, Fernando Maestú

14 June 2019

An increasing number of studies are using magnetoencephalography (MEG) to study dementia. Here the researchers defined a common methodological framework for MEG resting‐state acquisition and analysis to facilitate the pooling of data from different sites.

They found that the spectral analyses confirmed frequency‐specific differences in patients with MCI, both in power and connectivity patterns, with highest classification accuracy from connectivity. Critically, site acquisition differences did not dominate the results.

This work provides detailed protocols and analyses that are sensitive to cognitive impairment, and that will enable standardized data sharing to facilitate large‐scale collaborative projects.

Publication: The Journal of Endocrinology & Medicine

Martineau AR, Thummel KE, Wang Z, Jolliffe DA, Boucher BJ, Griffin SJ, et al.

14 June 2019

Vitamin D2 and vitamin D3 have been hypothesized to exert differential effects on vitamin D metabolism.

The objective of this study was to compare the influence of administering vitamin D2 vs vitamin D3 on metabolism of vitamin D3.

The researchers measured baseline and 4-month serum concentrations of vitamin D3, in 52 adults randomized to receive a total of four oral bolus doses of 2.5 mg vitamin D2 or vitamin D3 over four months. Metabolite-to-parent compound ratios were calculated to estimate hydroxylase activity. Pairwise before vs after comparisons were made to evaluate effects of vitamin D2 and vitamin D3 on metabolism of vitamin D. Mean postsupplementation metabolite-to-parent ratios were then compared between groups.

The researchers concluded that bolus-dose vitamin D2 is less effective than bolus-dose vitamin D3 in elevating total serum 25(OH)D concentration.

Publication: Journal of Neurology, Neurosurgery and Psychiatry

Stefano Gazzina, Mario Grassi, Enrico Premi, Maura Cosseddu, Antonella Alberici, Silvana Archetti, Roberto Gasparotti, John Van Swieten, Daniela Galimberti, Raquel Sanchez-Valle, Robert Jr Laforce, Fermin Moreno, Matthis Synofzik, Caroline Graff, Mario Masellis, Maria Carmela Tartaglia, James B Rowe, Rik Vandenberghe, Elizabeth Finger, Fabrizio Tagliavini, Alexandre de Mendonça, Isabel Santana, Christopher R Butler, Simon Ducharme, Alex Gerhard, Adrian Danek, Johannes Levin, Markus Otto, Giovanni Frisoni, Sandro Sorbi, Alessandro Padovani, Jonathan D Rohrer, Barbara Borroni

10 June 2019

Cognitively engaging lifestyles have been associated with reduced risk of conversion to dementia. Multiple mechanisms have been advocated, including increased brain volumes (ie, brain reserve) and reduced disease progression (ie, brain maintenance). In cross-sectional studies of presymptomatic frontotemporal dementia (FTD), higher education has been related to increased grey matter volume. Here, the researchers examined the effect of education on grey matter loss over time.

Highly educated at-risk subjects had better cognition and higher grey matter volume at baseline; moreover, higher educational attainment was associated with slower loss of grey matter over time in mutation carriers.

This longitudinal study demonstrates that even in presence of ongoing pathological processes, education may facilitate both brain reserve and brain maintenance in the presymptomatic phase of genetic FTD.

Publication: Pediatric Nephrology

Jack L. Martin, Anja V. Gruszczyk, Timothy E. Beach, Michael P. Murphy, Kourosh Saeb-Parsy 

2 June 2018

_______________________________________________________________________

Acute kidney injury (AKI) is a major problem in critically unwell children, including ischaemic reperfusion (IR) injury involving mitochondria. This research proposes a variety of novel therapeutic targets as potential treaments of AKI.

Publication: Clinical Radiology

Gilbert F, Le E, Hickman S, Wang Y, Huang Y.

May 2019

Publication: Neurobiology of Aging

Rittman T, Borchert R, Jones S, van Swieten J, Borroni B, Galimberti D, et al.

May 2019

Publication: European Respiratory Journal

Sofianopoulou E, Kaptoge S, Graf S, Hadinnapola C, Treacy CM, Church C, et al.

30 May 2019

Publication: Brain

David Howett, Andrea Castegnaro, Katarzyna Krzywicka, Johanna Hagman, Deepti Marchment, Richard Henson, Miguel Rio, John A King, Neil Burgess, Dennis Chan

May 19

Summary:

This research showed that a virtual reality test of spatial navigation was more effective at identifying patients with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) than gold standard tests of memory and thinking currently used in clinic and research studies. More here

Publication: Nutrients

Furse S, Koulman A.

20 May 2019

We tested the hypothesis that the lipid composition of infant formula is consistent between manufacturers, countries and target demographic. We developed techniques to profile the lipid and glyceride fraction of milk and formula in a high throughput fashion. Formula from principal brands in the UK (2017–2019; bovine-, caprine-, soya-based), the Netherlands (2018; bovine-based) and South Africa (2018; bovine-based) were profiled along with fresh British animal and soya milk and skimmed milk powder.

We found that the lipid and glyceride composition of infant formula differed by region, manufacturer and date of manufacture. The formulations within some brands, aimed at different target age ranges, differed considerably where others were similar across the range. Soya lecithin and milk lipids had characteristic phospholipid profiles. Particular sources of fat, such as coconut oil, were also easy to distinguish. Docosahexaenoic acid is typically found in triglycerides rather than phospholipids in formula.

The variety by region, manufacturer, date of manufacture and sub-type for target demographics lead to an array of lipid profiles in formula. This makes it impossible to predict its molecular profile. Without detailed profile of the formula fed to infants, it is difficult to characterise the relationship between infant nutrition and their growth and development.

Publication: The Lancet

Forouhi NG, Unwin N

11 May 2019

Few, if any, would contest that diet and nutrition have a crucial and substantial impact on human health. But the devil is in the details. Common questions include: is there such a thing as an optimal diet? What is suboptimal? Which dietary components matter most? And given the necessity to take action on climate change and planetary health, what should the world eat?

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) contributes towards answering these questions by estimating the burden of mortality and disability attributable to specific dietary risks, within a comparative risk assessment framework that currently considers 84 behavioural, environmental, occupational, and metabolic risks across 195 countries and territories.

Publication: Journal of Alzheimer's Disease

Raha-Chowdhury R, Henderson JW, Raha AA, Vuono R, Bickerton A, Jones E, Fincham R, Allinson K, Holland A, Zaman SH.

7 May 2019

Publication: World Psychiatry

Sahakian BJ, Savulich G.

6 May 2019