Computational modeling of working memory decline in normal and pathological aging

Research project description

A PhD position is available at the Centre de Recerca Matemàtica (CRM) under the supervision of Klaus Wimmer (computational neuroscientist). The successful candidate will be enrolled in the Mathematics doctoral programme  at the Universitat Autònoma de Barcelona (UAB) in the framework of the TOUCH project. TOUCH (“Towards the next generatiOn of excellent yoUng doctoral researchers on mental health by developing an intersectoral & transdisciplinary approaCH”) is a new excellent doctoral programme co-funded by the Marie Skłodowska-Curie (MSCA) Actions of the European Commission and led by the UAB for the recruitment and training of 24 doctoral candidates in the field of mental health and wellbeing.

This PhD thesis will study the effects of aging and Alzheimer’s disease on brain networks that underlie working memory, using a combination of large-scale computational modeling and analysis of experimental data.

Behavioral studies generally show a cognitive decline across the adult life span in both human and non-human primates, particularly in working memory tasks. Working memory is the brain mechanism for temporarily storing information, making it a critical cognitive ability for the activities of daily living. The cognitive changes that occur during normal aging appear to result from a combination of structural and functional changes in specific brain areas, inter-area connections, and individual neurons (Luebke et al. 2010; Peters and Keper 2012). However, despite a wealth of experimental data, a coherent theoretical framework of how the various age-related changes to neurons and neural pathways interact and lead to declines in working memory in aging and Alzheimer’s disease is currently lacking.

The main objective of this project is to develop a large-scale computational neural network model to fill this gap and reveal the functional consequences of age-related neuronal and connectivity changes on cognitive function. We will use new targeted analyses of a large dataset of 40 rhesus monkeys (young, middle-aged and aged), gathered by our collaborators in Boston University, to constrain realistic large-scale computational models of normal and pathological brain aging. The driving scientific question of this project is to advance our understanding of how age-related changes in neuronal connectivity impact neuronal network dynamics of working memory circuits and ultimately lead to disruption of neuronal networks that mediate behavioral function. We expect the project will reveal mechanisms that may compensate for age-related changes to restore function at the cellular, circuit and, ultimately, cognitive level. It has thus broad implications for strategies to enhance brain function in normal aging.

Academic background / Skills

The candidates must fulfil the following eligibility criteria from the EC: Mobility rule: candidates must not have resided or carried out their main activity (work, studies, etc.) in Spain for more than 12 months in the 36 months immediately preceding the deadline for the programme call. Experience rule: researchers must be doctoral candidates at the date of recruitment, that is not already in possession of a doctoral degree at the deadline of the open calls. Researchers who have successfully defended their doctoral thesis but have not yet formally awarded the doctoral degree will not be considered eligible. Candidates must hold a degree that allows admission to the official doctoral programme at UAB.

We are looking for a graduate student motivated to pursue a PhD thesis in computational neuroscience. As outlined above, the idea is to study the effects of aging on brain networks that underlie working memory and decision making, using a combination of large-scale computational modeling and analysis of experimental data obtained by a collaborating experimental laboratory.

The ideal candidate has strong quantitative skills (mathematics, physics and related disciplines) and a keen interest in neurobiology.

We offer a rich scientific environment at the CRM and in the Barcelona computational and systems neuroscience community (www.barccsyn.org).

A research stay in the experimental lab at Boston University is possible (and encouraged).

Research group/s description

The computational neuroscience unit at the CRM was founded in 2012 and is made up of six Principal Investigators (Alex Roxin, Klaus Wimmer, Alex Hyafil, Toni Guillamon, Gemma Huguet and Adrian Ponce) and their groups.

The unit is an active member of a larger, Barcelona-wide Neuroscience community which includes theoretical, experimental, and clinical groups located in a variety of university departments and research centers (www.barccsyn.org).

Research in the computational neuroscience unit is largely focused on systems-level neuroscience. Broadly speaking, this involves investigating how large assemblies of interacting neurons give rise to animal and human behavior.

Our approach is generally to combine computational modeling with data analysis.