MIND II

MFB DBS IN DEPRESSION


Relevant for Research Area

A - Foundations

C - Applications


Summary

The MIND project aims to establish a chronic and concurrent voltammetry option in our validated animal models of depression. This in turn will lead to an increased understanding of the dynamics of spatial and temporal relationship of medial forebrain bundle (MFB) deep brain stimulation (DBS) within the neural networks associated with depression. To tackle this challenge a novel hybrid multi-modal DBS probe is proposed which facilitates electrical stimulation as well as the recording capability addressing both electrophysiological and neurochemical activities, i.e. dopaminergic fluctuations. To realize the sensory function, fast-scan cyclic voltammetry (FSCV) initially at carbon fiber microelectrode (CFM) is used to provide exquisite temporal and spatial resolution for monitoring the neurochemicals of interest. FSCV in rat models showed a clear increasing behavior after systemic injection of amphetamine which can be attributed to dopamine and considered as an evaluation on the developed platform. However, accounting for the fidelity and stability of the CFM in long-term applications, seeking for alternative sensing interfaces is inevitable.In parallel studies, more promising alternatives to CFM including diamond like carbon (DLC), novel laser induced carbon and PEDOT coatings are investigated and their electrochemical performance (in vitro) is evaluated. Compatibility of the proposed interfacing materials with thin-film electrodes makes it possible to integrate them and investigate their functionality on the multimodal hybrid probe which potentially paves our way towards clinical applications. Electrophysiological signatures (LFP) from the ventral tegmental area and the medial shell of the nucleus accumbens associated with the depressive phenotype are studied to investigate the impact of stimulation on neural transmission and behavior, and to use in future closed-loop stimulation paradigms.


Research Status

Role of midbrain dopamine (DA) following medial forebrain bundle deep brain stimulation (MFB DBS).The study implicates DA in the positive effects of human MFB-DBS in the experimental therapy of major depressive disorder MDD. The mechanisms need elucidation, but an experimentally evoked depressive phenotype through DA depletion in rodents can be rescued through MFB DBS. There are indications that non-DAergic pathways are also at play. Investigations concerning the network of depression using neuromodulation platforms in animal models will give insight into genesis and the DBS based treatment of major depression disorder. The biological sequelae of MFB stimulation using electric or optogenetic methods, the interplay between transmitter systems – in particularly the dopaminergic, serotonergic, GABAergic and glutaminergic – is the focus of current and future efforts.

Project Publications

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.