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A recipe for accurate estimation of lifespan brain trajectories, distinguishing longitudinal and cohort effects
•Generalized additive mixed models (GAMMs) fit lifespan brain trajectories more accurately than traditional methods.•Optimal formulation of GAMMs for longitudinal data analysis is discussed, and compared in realistic simulation experiments and two application examples.•We discuss and contrast questions which can be answered with a single measurement per participant, and which questions require repeated measurements.•R code shows how GAMMs can be used in practice, with packages “gamm4” and “mgcv”.
We address the problem of estimating how different parts of the brain develop and change throughout the lifespan, and how these trajectories are affected by genetic and environmental factors. Estimation of these lifespan trajectories is statistically challenging, since their shapes are typically highly nonlinear, and although true change can only be quantified by longitudinal examinations, as follow-up intervals in neuroimaging studies typically cover less than 10% of the lifespan, use of cross-sectional information is necessary. Linear mixed models (LMMs) and structural equation models (SEMs) commonly used in longitudinal analysis rely on assumptions which are typically not met with lifespan data, in particular when the data consist of observations combined from multiple studies. While LMMs require a priori specification of a polynomial functional form, SEMs do not easily handle data with unstructured time intervals between measurements. Generalized additive mixed models (GAMMs) offer an attractive alternative, and in this paper we propose various ways of formulating GAMMs for estimation of lifespan trajectories of 12 brain regions, using a large longitudinal dataset and realistic simulation experiments. We show that GAMMs are able to more accurately fit lifespan trajectories, distinguish longitudinal and cross-sectional effects, and estimate effects of genetic and environmental exposures. Finally, we discuss and contrast questions related to lifespan research which strictly require repeated measures data and questions which can be answered with a single measurement per participant, and in the latter case, which simplifying assumptions that need to be made. The examples are accompanied with R code, providing a tutorial for researchers interested in using GAMMs.
Journal Article
European brain research area: The strategic level
Brain research in Europe is a rapidly evolving field, and increasingly at the forefront of science. Although considerable amounts of knowledge and innovative approaches have been generated, the translation into new health interventions is hindered by excessive fragmentation. Effective and efficient collaboration and cooperation among the various initiatives are often identified as a key success factor to achieve brain research full impact. EBRA fully responds to these needs by bringing together the various stakeholders and major brain research initiatives, at European level and beyond. EBRA creates the conditions for real and effective cross fertilisation, dialogue, building consensus and exploiting research potential. At the strategic level, EBRA acts by fostering alignment and better coordination of research strategies across European and global brain initiatives. Therefore, an overview of the scale and scope of brain research activities funded in the EU framework programme and the funding initiatives of JPND, NEURON and HBP has been created. The results of the mapping exercise then underpinned the development of a Shared European Brain Research Agenda (SEBRA). The SEBRA focuses on research opportunities and research gaps to be addressed in the field, and priorities for action in the short- and long-term. It integrates pre-existing documents as well as expert (i.e., researchers, neurologists/psychiatrists, patient representatives) input that has been collected through surveys and in a dedicated expert workshop. The SEBRA will be used to provide recommendations on future areas for excellent, innovative, and translational research comprising those for maximized cooperation, reduced overlap, and fragmentation.
Journal Article
We are our brains : a neurobiography of the brain, from the womb to alzheimer's
\"The culmination of renowned neuroscientist D.F. Swaab's life's work, We Are Our Brains unlocks the mysteries of the most complex organism in the human body, providing a fascinating overview of the brain's role in nearly every aspect of human existence. In short, engaging chapters, Swaab explains what is going on in our brains at every stage of life, including how a fetus's brain develops and the role that pregnancy plays in solidifying certain aspects of our identity; the radical neurological changes that occur during adolescence; what happens when we fall in love; and the neurological basis for a host of different disorders and personality traits\"-- Provided by publisher.
Book
Cognitive Motor Dissociation in Disorders of Consciousness
Among 241 persons with disorders of consciousness who had no observable response to commands, 25% had a verifiable response to commands on EEG or functional MRI, a condition known as cognitive motor dissociation.
Journal Article