September 2024
PhD position at the Institute of Neuroscience - Identification of VNS response
Vagus nerve stimulation is an add-on treatment for patients with refractory epilepsy. Despite its well-established use in clinical practice, mechanisms of action remain poorly understood and only one third of implanted patients respond to the treatment.
This project aims to improve VNS therapy by developing new neurophysiological tools to identify biomarkers of clinical response.
The vagus nerve projects to the nucleus of tractus solitarius, activating in the brainstem the locus coeruleus (LC), the main source of noradrenaline (NE) in the brain, which relays to thalamus, amygdala and hippocampus, and in turn projects to the cortex1,2.
Noradrenergic transmission has a key role in antiepileptogenesis3, and preclinical experiments indicate that activation of the LC-NE system is critical to the seizure suppressing effect of VNS4–7. This pathway may provide an explanation to the antidepressant8,9, attentional10, and wakefulness-promoting effects11,12 also reported with VNS. Although a direct measurement of LC activity in VNS-implanted human patients is still lacking, there exists indirect evidence of LC activation. Pupil size and P300 responses to event-related-potentials are commonly used to study the tonic and phasic influences of the LC-NE system on brain excitability13,14 .
In addition, EEG studies postulated neural desynchronization as a possible mechanism of VNS action15. Interestingly, LC-derived noradrenaline may have a direct role in modulating EEG synchronization3,7. This project will have as goal to study P300/pupil dilation and EEG synchronisation in VNS patients, to better understand its mechanisms of action and find biomarkers of response.
The PhD research will start 1/10/2024. Funding is available until 1/12/2025, thereafter the candidate will need to apply for FNRS/FRIA funding. The researcher will be based at the UCLouvain, located in Brussels (Belgium). Your promotor will be Pr. Riëm El Tahry, neurologist at Cliniques Universitaires Saint Luc and PI at the Institute of Neuroscience (IoNS), UCLouvain, NEUR division. Your co-promoter will be Pr. Antoine Nonclercq, PI at BEAMS department, ULB.
We are looking for a highly motivated engineer with specific interest in Neurosciences, prepared to integrate in a multidisciplinary team consisting of neurologists, neurophysiologists and engineers. Fluent English and BASIC FRENCH are required. Matlab knowledge is highly appreciated.
Application: Interested candidates are requested to send their application to Pr. Riëm El Tahry (riem.eltahry@saintluc.uclouvain.be), with a copy to Pr. Antoine Nonclercq (antoine.nonclercq@ulb.be), including a cover letter describing yourself and your interests, a resume, your ranking and at least 1 recommendation letter.
1. Groves DA, Bowman EM, Brown VJ. Recordings from the rat locus coeruleus during acute vagal nerve stimulation in the anaesthetised rat. Neurosci Lett. 2005; 379(3):174–9.
2. Sara SJ. The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci. 2009; 10(3):211–23.
3. Giorgi FS, Pizzanelli C, Biagioni F, et al. The role of norepinephrine in epilepsy: from the bench to the bedside. Neurosci Biobehav Rev. 2004; 28(5):507–24.
4. Krahl SE, Clark KB, Smith DC, et al. Locus coeruleus lesions suppress the seizure-attenuating effects of vagus nerve stimulation. Epilepsia. 1998; 39(7):709–14.
5. Roosevelt RW, Smith DC, Clough RW, et al. Increased extracellular concentrations of norepinephrine in cortex and hippocampus following vagus nerve stimulation in the rat. Brain Res. 2006; 1119(1):124–32.
6. Raedt R, Clinckers R, Mollet L, et al. Increased hippocampal noradrenaline is a biomarker for efficacy of vagus nerve stimulation in a limbic seizure model. J Neurochem. 2011; 117(3):461–9.
7. Fornai F, Ruffoli R, Giorgi FS, et al. The role of locus coeruleus in the antiepileptic activity induced by vagus nerve stimulation. Eur J Neurosci. 2011; 33(12):2169–78.
8. Elger G, Hoppe C, Falkai P, et al. Vagus nerve stimulation is associated with mood improvements in epilepsy patients. Epilepsy Res. 2000; 42(2–3):203–10.
9. Grimonprez A, Raedt R, Portelli J, et al. The antidepressant-like effect of vagus nerve stimulation is mediated through the locus coeruleus. J Psychiatr Res. 2015; 68:1–7.
10. Sun L, Perakyla J, Holm K, et al. Vagus nerve stimulation improves working memory performance. J Clin Exp Neuropsychol. 2017; 39(10):954–64.
11. Rizzo P, Beelke M, De Carli F, et al. Chronic vagus nerve stimulation improves alertness and reduces rapid eye movement sleep in patients affected by refractory epilepsy. Sleep. 2003; 26(5):607–11.
12. Martinez-Vargas D, Valdes-Cruz A, Magdaleno-Madrigal VM, et al. Effect of Electrical Stimulation of the Nucleus of the Solitary Tract on Electroencephalographic Spectral Power and the Sleep-Wake Cycle in Freely Moving Cats. Brain Stimul. 2017; 10(1):116–25.
13. Murphy PR, Robertson IH, Balsters JH, et al. Pupillometry and P3 index the locus coeruleus-noradrenergic arousal function in humans. Psychophysiology. 2011; 48(11):1532–43.
14. Nieuwenhuis S, De Geus EJ, Aston-Jones G. The anatomical and functional relationship between the P3 and autonomic components of the orienting response. Psychophysiology. 2011; 48(2):162–75.
15. ZANCHETTI A, WANG SC, MORUZZI G. The effect of vagal afferent stimulation on the EEG pattern of the cat. Electroencephalogr Clin Neurophysiol. 1952; 4(3):357–61.
June 2024
PhD or Postdoc Position on Computational and Systems Neuroscience
Project Title:
Quantitative models of human motor control in healthy and clinical populations
Project Description:
The laboratory recruits highly motivated people to work in a dynamic environment on motor control and systems neuroscience. This research project aims to build models of human sensorimotor coordination based on current theories of motor control, and extend them to explore new hypotheses on how these models can integrate contextual factors linked to adaptation, memory, perception, and decision-making. The project will also investigate how these models can explain abnormal movements in clinical populations. The project will draw on a broad range of motor systems, including locomotion, reaching control, object manipulation and eye movements. We will combine theoretical models, behavioral experiments in healthy and clinical populations and electrophysiological recordings. Applications for a doctoral program (4 years, fully funded) or postdoctoral training (2 years) are encouraged. In both cases, opportunities to attract individual funding will be explored.
Host Institution and Supervision
The successful candidate will be appointed with the Institute of Information and Communication Technologies Electronics and Applied Mathematics (ICTEAM, division of Applied Mathematics, https://uclouvain.be/en/research-institutes/icteam ) and corss-appointed with the Institute of Neuroscience (IoNS, division Systems and Cognition https://uclouvain.be/en/research-institutes/ions ). The research will be supervised by F. Crevecoeur (https://scholar.google.com/citations?hl=fr&user=-EEfvcEAAAAJ&view_op=list_works )
Requirements
For applications to a PhD position:
- Master’s degree in engineering (closer fields include but are not limited to: applied mathematics, biomedical, data science, computer science, mechanical, electrical), neuroscience, physics, or equivalent.
For an application to a postdoc position:
- PhD in neuroscience with a component in computational modeling of behavioural and neural data.
For both:
- Ability to work in a laboratory environment with strong technical skills or willingness to learn (use of equipment, preparation of experiments, data collection)
- Oral and written communication skills, proficiency in English is an asset
- Critical thinking, leadership and ability to work sometimes independently, sometimes within a team
- Coding skills in Python and R for data analysis, processing and simulations are an asset, or will be part of the training program
- Curiosity, willingness to learn new topics, and creativity
Applications
Applications should be sent to F. Crevecoeur: frederic.crevecoeur@uclouvain.be as a single PDF document with a letter of motivation, a CV and one (doctoral) or two (postdoctoral) letters of recommendation. The tentative application deadline is July 17 with an anticipated start in fall 2024, please send any requests for additional information to: frederic.crevecoeur@uclouvain.be.