Our Projects

Thesis Topic : Miniaturized head-mounted fluorescence microscopes for in vivo calcium imaging in mice

Description: In this thesis, the student will design, fabricate, and characterize miniaturized head-mounted fluorescence microscopes for in vivo calcium imaging. 1-photon imaging microscopes relying on fiber bundles and computational imaging techniques for volumetric imaging will be developed. Extensions to include neural probes with nanophotonic waveguides for patterned light delivery will be investigated. 2-photon miniaturized microscopes will also be developed with emphasis on advanced functionality, such as electrically tunable focusing for selecting depth planes and dual wavelength operation for simultaneous imaging and photostimulation.
In collaboration with neuroscientists, the functionality of the microscopes will be validated in vivo in freely behaving mice and for studies of epilepsy and seizure suppression. The student will work closely with scientists and postdocs at the MPI for optical design and for investigation of integration with nanophotonic neural probes. This is a highly challenging and multidisciplinary effort that will require excellent theoretical and practical experience in electromagnetics, electronics, semiconductors, computational analysis, and neuroscience. Excellent organizational and communication skills are also required due to the large number of collaborators involved. An openness to learn new skills and new disciplines is a must!

Thesis Topic : Neurocomputational models of escape and avoidance for suicide prevention.

Description: Suicide is the second leading cause of death among young adults. Decades of research have sought to identify risk factors and treatment targets, but success has been elusive, with the pathophysiological brain mechanisms associated with suicidal thoughts and behaviours remaining unknown. In this project, we will use advanced functional magnetic resonance imaging (fMRI) to perform cognitive network modelling aimed at examining the brain mechanisms eliciting aberrant beliefs associated with increased suicide risk. We will employ cognitive tasks targeting active escape and avoidance, computational modelling of behaviour, fMRI and dynamic causal modelling of the effective brain connectivity underlying the observed fMRI activations; and will focus on the roles of serotonergic and noradrenergic systems in mediating the effects of controllability and stress reactivity, respectively. This is a highly interdisciplinary project at the intersection of medical biophysics, mathematics, and psychiatry. While this study aims to validate the proposed cognitive network models in healthy adults, it will deliver an advanced fMRI and neurocomputational modelling protocol for future prospective studies in major depression (which is a prime route to suicidality). By testing concrete hypotheses about the involvement of specific neuromodulators, this project will hopefully open a path towards individualized therapies for suicidality in treatment-resistant depression.

Thesis Topic: Oculomotor representations in human medial temporal lobe.

Description: Eye movements allow us to explore the world by shifting the visual field, yet it remains elusive how oculomotion interacts with visual perception as well as higher-level cognition like memory. Focusing on the medial temporal lobe (MTL) which was recently shown to respond to oculomotion (presumably mediated by a corollary discharge), this project aims at examining the perceptual and cognitive functions that arise from the structure during oculomotion. We view oculomotor signals as potential navigational signals for the “cognitive map” within the MTL, which generate strong hypotheses about predictive visual processing and memory. We plan to combine eye tracking, state-of-the-art single neuron recording, and electrical stimulation to investigate this topic in epilepsy patients when they perform a variety of cognitive tasks. Moreover, dynamic circuit models will be used to describe as well as predict neural data. The student will work in the labs of Prof. Taufik Valiante at the University of Toronto and Lucia Melloni at the Max Planck Institute for Empirical Aesthetics to approach the topic with multidisciplinary skill sets (e.g., eye tracking, psychophysics, systems and computational neuroscience). This collaborative project aims at opening new doors for research on sensorimotor integration and action-cognition interaction.

Thesis Topic: Neural mechanisms of use-dependent working memory distortion.

Description: Visual working memory (VWM) allows us to accurately hold in mind a limited amount of visual information so that it can be compared with new visual inputs. As such, VWM supports a wide range of goal-directed behaviors (e.g., identifying a suspect in a line-up). Dr. Rademaker identified that the human brain maintains multiple copies of a VWM representation in distinct coding formats across visual and parietal brain regions. This multiplexity ensures both flexibility and robustness of VWM representations as they are used in goal-directed behaviors. Nevertheless, VWM is susceptible to systematic distortions when making comparisons to new visual inputs, as demonstrated by Dr. Fukuda. Such memory distortions can result in grave consequences in real life (e.g., wrongful conviction due to inaccurate line-up identification). The current proposal aims to elucidate the neural mechanisms underlying VWM robustness and distortion. The supervisors’ shared expertise on computational techniques, and their independent expertise with neuroimaging techniques (fMRI for Dr. Rademaker; EEG for Dr. Fukuda) will enable the PhD student to investigate how VWM representations change over time across multiple brain regions as they are compared to visual inputs. This will allow us to predict and identify neural mechanisms responsible for memory distortions of practical importance.

Thesis Topic: The role of the substantia nigra in reward processing, impulsivity and apathy in Parkinson’s disease.

Description:  Processing and learning about rewards is essential to operate in, and adapt successfully to, the environment. Impairments in these functions can contribute to cognitive and psychological disorders such as apathy, impulsivity and depression, e.g., in patients with Parkinson’s disease (PD). A key structure in reward processing and learning is the substantia nigra (SN), which is involved in the neuropathology of PD. Dopaminergic SN pars compacta neurons encode temporally-sophisticated reward prediction error signals in non-human primates and humans. Their phasic activity contributes to the learning of actions based on reward; their tonic activity has been suggested as providing motivational force by reporting the average reward rate. Such conclusions are consistent with the effects of SN manipulations in animals and in humans using deep brain stimulation.

Thesis Topic: Wireless Magnetopiezoelectic Micro/Nanomaterials-based Deep Brain Stimulation.

Description: The project aims to conduct Deep Brain Stimulation wirelessly using magnetopiezoelectric nanoparticles and other micro/nanomaterials.  Deep Brain Stimulation can be used to treat movement disorders associated with Parkinson’s disease, essential tremor, dystopia and other neurological conditions. The novelty of the project lies within piezoelectric part of electrodes, which could create electric charge wirelessly locally when external alternating and constant magnetic fields are applied on the magnetostrictive part of materials.  Core-shell magnetopiezoelectric nanoparticles have shown initial promise on such wireless Deep Brain Stimulations.  However, design,  fabrication,  precise control, and implementation of this technology require further investigation. By developing magnetopiezoelectric nanoparticles, the project could improve the health of people suffering from movement disorders.

Thesis Topic: Towards restoration of E:I balance in Parkinson’s disease and dystonia.

Description:

Many brain circuits operate in a dynamic state governed by the balance between excitation and inhibition (E:I balance). Fluctuations in E:I balance underlie various physiological functions, while aberrant shifts have been implicated in neurological and psychiatric disorders. Recent computational work has estimated E:I changes from the power law exponent of electrophysiological power spectra, as validated by extracellular neural data in rats and macaques. However, these methods have not yet been validated at the single-unit level, nor have consequences on circuit communication been studied in humans. We propose to leverage this exciting methodology to study the implications of E:I balance in movement disorders. In particular, opposing shifts in E:I balance have been postulated to give rise to the hypo- and hyperkinetic symptoms in Parkinson’s disease and dystonia, respectively. We propose to leverage intracranial recordings (single-neuron, local-field-potential, electrocorticography, magnetoencephalography) from the human basal-ganglia-thalamo-cortical network (BGTCN) to validate such hypotheses, and to explore the possibility for therapeutic restoration of E:I balance by manipulation of BGTCN circuitry using deep brain stimulation. Furthermore, we will seek a deeper understanding of these processes by mechanistic modelling of the BGTCN network using neural mass models, linking E:I balance to behavioral consequences, electrophysiological activity, and brain stimulation.

Thesis Topic: Spatially Resolved and Single-Cell Proteomics to Assess Physiological Microglia States.

Description:

We will develop a cutting-edge methodology - ex vivo digital microfluidic isolation of single cells for Omics (evDISCO) - to study transcriptomic and proteomic profiles of microglia in defined physiological states, focusing on functional consequences of neuronal inputs to microglia. Beyond their role in brain pathophysiology, microglia appear to also act as physiological regulators of brain function, by receiving specific input from surrounding neurons and feeding back regulatory information via chemical messengers and cell-cell contacts. We plan to explore the underlying biology by using evDISCO in microglia reporter mouse lines, focusing on the effects of neuronal signaling on microglia transcriptomes and proteomes in defined brain regions and single cells. To this end, our PhD student will comparatively profile microglia (i) from transmitter-secretion-deficient brains (organotypic Unc13 KO brain slices) to determine how overall circuit activity affects microglia states, and (ii) from multiple brain regions (e.g. frontal cortex, visual cortex, hippocampus, striatum, a.o.) to systematically assess how the specific neuronal environment defines specific microglia states. As the evDISCO approach circumvents the requirement of complex additional reporter lines (e.g. RiboTag or BioID), we expect that the planned PhD-project will rapidly provide deep insights into how microglia interact with neurons to co-define circuit function.