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. 2015 Apr 21:4:9921.
doi: 10.1038/srep09921.

Conceptualization and validation of an open-source closed-loop deep brain stimulation system in rat

Hemmings Wu  1 , Hartwin Ghekiere  2 , Dorien Beeckmans  1 , Tim Tambuyzer  2 , Kris van Kuyck  1 , Jean-Marie Aerts  2 , Bart Nuttin  1   3
Affiliations

Conceptualization and validation of an open-source closed-loop deep brain stimulation system in rat

Hemmings Wu et al. Sci Rep. .

Erratum in

Abstract

Conventional deep brain stimulation (DBS) applies constant electrical stimulation to specific brain regions to treat neurological disorders. Closed-loop DBS with real-time feedback is gaining attention in recent years, after proved more effective than conventional DBS in terms of pathological symptom control clinically. Here we demonstrate the conceptualization and validation of a closed-loop DBS system using open-source hardware. We used hippocampal theta oscillations as system input, and electrical stimulation in the mesencephalic reticular formation (mRt) as controller output. It is well documented that hippocampal theta oscillations are highly related to locomotion, while electrical stimulation in the mRt induces freezing. We used an Arduino open-source microcontroller between input and output sources. This allowed us to use hippocampal local field potentials (LFPs) to steer electrical stimulation in the mRt. Our results showed that closed-loop DBS significantly suppressed locomotion compared to no stimulation, and required on average only 56% of the stimulation used in open-loop DBS to reach similar effects. The main advantages of open-source hardware include wide selection and availability, high customizability, and affordability. Our open-source closed-loop DBS system is effective, and warrants further research using open-source hardware for closed-loop neuromodulation.

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Conflict of interest statement

BN holds a chair ‘Neurosurgery for psychiatric disorders', a donation from Medtronic. BN received grants for travel, research and education from Medtronic. BN owns a patent on deep brain stimulation for obsessive-compulsive disorder. The other authors declare that they have no competing financial interests.

Figures

Figure 1
Figure 1. One bipolar and two monopolar electrodes were implanted in the right hippocampus (recording) and bilateral mesencephalic reticular formation (stimulation), respectively.
Drawing by Stephany Pei-Yen Hsiao.
Figure 2
Figure 2. Schematic illustration of the open source, closed-loop deep brain stimulation system in rats.
↓(blue) indicates hippocampal local field potentials, recorded through amplifier, filter and data acquisition device, and analyzed in the PC. Based on real-time theta power analysis, electrical stimulation (indicated by ↓(red)) sent to the rat brain (mesencephalic reticular formation) is controlled via the Arduino board. AMP: custom amplifier, ARD: Arduino Uno board, DAQ: data acquisition card, MOC: mechanism operated cell, Stim: stimulator. Drawing by Stephany Pei-Yen Hsiao.
Figure 3
Figure 3. Measured hippocampal LFPs and theta power during closed-loop stimulation.
3a and b: Rat hippocampal LFP and power spectrogram, showing a clear peak in theta band during locomotion. 3c and d: Hippocampal LFP and power spectrums when the rat was resting. No peak in theta range was observed. 3e: Real-time theta power during closed-loop stimulation. --- indicates the predetermined individual theta threshold. Each black dot represents real-time hippocampal theta power. If theta power exceeded the threshold (black dot above ---), bilateral stimulation in the mesencephalic reticular formation was switched on (until theta power dropped below threshold). LFP: local field potential.
Figure 4
Figure 4. Effects of OFF, OL, RANDOM, and CL stimulations on locomotion (mean ± S.E.M., scatter plot), and corresponding percentage of stimulation-on time (mean, red columns).
Repeated-measure analysis of variance showed that the main effect of different intervention on percentage of movement detected via automated video analysis was significant (p = 0.012). Post hoc pairwise comparisons (Bonferroni correction) indicated that the percentage of movement during CL was significantly lower than during OFF (p = 0.042). Percentages of stimulation-on time during RANDOM and CL were 43.86 ± 0.80% and 55.57 ± 4.56%, respectively. OFF: no stimulation, OL: open-loop stimulation, RANDOM: randomly-applied, CL: closed-loop. *: p<0.05.
Figure 5
Figure 5. Graphical illustrations of hippocampal-mRt closed-loop deep brain stimulation.
Locomotion (e.g. exploratory walking) in rat (5a) and corresponding hippocampal theta activity (5b, local field potential sample of 1 second), which triggers bipolar electrical stimulation in the mRt (5c), and induces freezing and suppresses locomotion (5d). Drawing by Stephany Pei-Yen Hsiao (5a, c, and d).
See this image and copyright information in PMC

References

    1. Little S. et al. Adaptive deep brain stimulation in advanced Parkinson disease. Ann. Neurol. 74, 449–57 (2013). - PMC - PubMed
    1. Rosin B. et al. Closed-loop deep brain stimulation is superior in ameliorating parkinsonism. Neuron. 72, 370–84 (2011). - PubMed
    1. Newman J. P. et al. Closed-Loop, Multichannel Experimentation Using the Open-Source NeuroRighter Electrophysiology Platform. Front Neural Circuits 6, 98 (2012). - PMC - PubMed
    1. Kramis R., Vanderwolf C. H. & Bland B. H. Two types of hippocampal rhythmical slow activity in both the rabbit and the rat: relations to behavior and effects of atropine, diethyl ether, urethane, and pentobarbital. Exp. Neurol. 49, 58–85 (1975). - PubMed
    1. Robinson T. E. Electrical stimulation of the brain stem in freely moving rats: I. Effects on behavior. Physiol. Behav. 21, 223–31 (1978). - PubMed

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