MFB DBS IN DEPRESSION
Prof. Dr. Volker Coenen (Contact PI)
Main goals of project, milestones and results achieved.
The project looked at the biological and technical aspects of assessing the short and long- term effects of MFB DBS in models of depression (WP1), aimed to develop novel interfaces to enable multimodular stimulation and recording options (WP2), and to develop a prototype “Hybrid multimodal DBS probe” with clinical application (WP3).
Main results achieved:
WP1: We have established protocols to behaviorally characterizing the animal models, the surgical and stimulation parameters. MFB Stimulation can produce anti-depressant effects and that these effects are in part dopamine related as dopamine release was observed in the ventral striatum (FSCV). Optogenetic stimulation of the midbrain dopamine pathway confirms anti-depressant effects of the stimulation. The output from WP1 gave rise to 8 peer-reviewed papers (see 2.3.1).
WP2: Laser-induced graphitic technology and glassy carbon interfaces were fabricated and mechanically/electrochemically characterized. Glassy carbon was selected as the technology of choice for the further development of the hybrid DSB probe (WP3).
WP3: A hybrid multimodal DBS probe was designed in which, a combination of a polyimide based thin-film devices and a silicone rubber substrate was introduced. In addition to the basic modalities (i.e., electrical stimulation and local field potentials (LFP) recording), this probe offers the possibility of performing FSCV to monitor the relative changes of the in situ neurotransmitter levels. The hybrid probe was made using cleanroom fabrication technology and features glassy carbon interface to facilitate neurochemical sensing as well as the electrical stimulation/recording. The hybrid probe was made in compliance with the conventional implantation methods and common applications.
1. Furlanetti LL, Coenen VA, Aranda IA, Döbrössy MD. Chronic Deep brain stimulation of the Medial Forebrain Bundle reverses depressive-like behavior in a hemi-parkinsonian rodent model. Exp Brain Res, 2015; 233 (11): 3073-3085.
2. Furlanetti LL, Cordeiro JG, Cordeiro KK, García JA, Winkler C, Lepski GA, Coenen VA, Nikkhah G, Döbrössy MD. Continuous High-Frequency Stimulation of the Subthalamic Nucleus Improves Cell Survival and Functional Recovery Following Dopaminergic Cell Transplantation in Rodents. Neurorehab Neural Re, 2015; 29 (10): 1001-1012.
3. Furlanetti LL, Döbrössy MD, Aranda IA, Coenen VA. Feasibility and Safety of Continuous and Chronic Bilateral Deep Brain Stimulation of the Medial Forebrain Bundle in the Naïve Sprague-Dawley Rat. Behav Neurol, 2015.
4. Döbrössy MD, Furlanetti LL, Coenen VA. Electrical stimulation of the medial forebrain bundle in pre-clinical studies of psychiatric disorders. Neurosci Biobehav R, 2015; 49 (2): 32- 42.
5. Furlanetti LL, Coenen VA, Döbrössy MD. Ventral tegmental area dopaminergic lesion- induced depressive phenotype in the rat is reversed by deep brain stimulation of the medial forebrain bundle. Behav Brain Res, 2016; 299: 132-140.
6. Thiele S, Spehl TS, Frings L, Braun F, Ferch M, Meyer PT, Rezvani A, Furlanetti LL, Coenen VA, Döbrössy MD. Long-term characterization of the Flinders Sensitive Line rodent model of depression: Behavioral and PET evidence of a dysfunctional entorhinal cortex. Behav Brain Res, 2016; 300: 11-24.
7. Cook A, Pfeiffer LM, Thiele S, Coenen VA, Döbrössy MD. Olfactory discrimination and memory deficits in the Flinders Sensitive Line rodent model of depression. Behavioural Processes, 2017; 143: 25-29.
8. Ashouri Vajari D, Vomero M, Erhardt J, Sadr A, Ordonez J, Coenen V.A., Stieglitz T, Integrity Assessment of a Hybrid DBS Probe that Enables Neurotransmitter Detection Simultaneously to Electrical Stimulation and Recording; Journal of Micromachines, (Issue cover journal) Neural Microelectrodes: design and application;2018, 9(10), 510.
9. Vomero M, Oliviera A, Ashouri Vajari D, Eickenscheidt M, Stieglitz T Graphitic Carbon Electrodes on Flexible Substrate for Neural Applications Entirely Fabricated Using Infrared Nanosecond Laser Technology, , Scientific Rep., SREP(2018) 8:14749.
10 Vomero M, Castagnola E, Ordonez JS, Carli S, Zucchini E, Maggiolini E, Gueli C, Goshi N, CiarpellaF,Cea C, Fadiga L, Ricci D, Kassegne S, Stieglitz T Electrocorticography Arrays: Incorporation of Silicon Carbide and Diamond-Like Carbon as Adhesion Promoters Improves In Vitro and In Vivo Stability of Thin-Film Glassy Carbon Electrocorticography Arrays, 2018 Advanced Biosystems, Band: 2, Nummer: 1.
11. Khan S, Ordonez J.S. and Thomas Stieglitz. Reliability of spring interconnects for high channel-count polyimide electrode arrays. 2018 J. Micromech. Microeng. 28 055007.
12. Thiele S, Furlanetti L, Pfeiffer LM, Coenen VA, Döbrössy MD. The effects of bilateral, continuous, and chronic Deep Brain Stimulation of the medial forebrain bundle in a rodent model of depression.Exp Neurol, 2018; 303: 153-161.
(Peer-Reviewed Conf. Proceeding) Ashouri Vajari D., Ordonez J. S., Furlanetti L., Döbrössy M., Coenen V., Stieglitz T (2015). Hybrid Multimodal Deep Brain probe (DBS array) for Advanced Brain Research. Proc. of the IEEE-EMBS, ISBN. 978-1-4673-6389-1, Apr 22th – Apr 24rd, 2015, Montpellier (France).
(invited talk) Stieglitz T, Cvancara P, Müller M, Liljemalm R, Erhardt J, Boehler C, Ashouri D, Vomero M, Oliveira A, Eickenscheidt M, Asplund M, Ordonez JS. Bioelektronische Medizin Versprechen und Herausforderungen. 2017. Heidelberger Kolloquium Medizinische Biometrie, Informatik und Epidemologie, Universitätsklinikum Heidelberg
(Poster) Stieglitz T, Oliveira A, Ashouri Vajari D, Vomero M, Eickenscheidt M Laser- induced carbon microelectrode arrays for chronic neural applications. 2017 the 47th annual meeting of the Society for Neuroscience (SfN 2017), Washington, D.C., USA, November 11- 15, 2017
(Poster) Vomero M, Zuchini E, Gueli C, Delfino E, Ashouri Vajari D, Carli S, Fadiga L, Stieglitz T. Performance Evaluation of Glassy Carbon Electrodes for Neural Applications Based on Different Diameters. 2018 Gordon Research Conference on Neuroelectronic Interfaces, 25.-30.03.2018, Galveston, TX, USA
(Peer-Reviewed Conf. Proceeding) Vomero M, Castagnola E, Ordonez JS, Carli S, Zucchini E, Maggiolini E, Gueli C, Goshi N, Fadiga L, Ricci D, Kassegne S, Stieglitz T. Improved long-term stability of thin-film glassy carbon electrodes through the use of silicon carbide and amorphous carbon- 2017 8th International IEEE/EMBS Conference on Neural Engineering (NER),15 August 2017 , Shanghai, ChinaIEEE.
Furlanetti LL, Aguirre I, Coenen VA, Döbrössy MD. (2015) High-Frequency Stimulation of the Medial Forebrain Bundle Reverses Depressive-Like Behavior in a Combined Rodent Model of Depression and Parkinson's Disease. Conference of the Society of Biological Psychiatry, Toronto, 2015. BIOLOGICAL PSYCHIATRY, 77: 9, 395S-395S, ELSEVIER SCIENCE INC.