Field Potential Oscillations in the Bed Nucleus of the Stria Terminalis Correlate with Compulsion in a Rat Model of Obsessive-Compulsive Disorder.
The bed nucleus of the stria terminalis (BNST) is implicated in anxiety and reward processing, both of which are associated with obsessive-compulsive disorder (OCD). Specific neuronal groups in the BNST related to anxiety and reward have been identified, but quantitative data about the information carried by local field potential (LFP) signals in this area during obsession/compulsion are lacking. Here we investigate the BNST LFP in the schedule-induced polydipsia, an animal model of OCD. We implanted electrodes bilaterally in the BNST and random control brain regions in 32 male Wistar rats, and recorded corresponding LFP during compulsive and noncompulsive behavior. We first applied high-frequency (100 Hz) electrical stimulation through the implanted electrodes and analyzed its effects on compulsive behavior. We then performed time-frequency analysis of LFPs and statistically compared the normalized power of δ (1-4 Hz), θ (4-8 Hz), α (8-12 Hz), β (12-30 Hz), and lower γ (30-45 Hz) bands between different groups. Our data showed that the normalized δ, β, and γ powers in the right BNST were specifically correlated with compulsive behaviors. δ and γ oscillations increased and decreased during the initiation phase of compulsion, respectively, whereas β increased after compulsion stopped. Moreover, the effect of BNST electrical stimulation, in terms of suppression of compulsion, was significantly correlated with the percentage change of these bands during compulsion. Our research reveals potential biomarkers and underlying neurophysiological mechanisms of compulsion and warrants further assessment of the use of LFP for closed-loop neuromodulation in OCD.



Although specific neuronal groups in the bed nucleus of the stria terminalis (BNST) related to anxiety and reward circuitries have been identified, psychopathological information carried by local field potentials in the BNST has not yet been described. We discovered that normalized powers of the right BNST δ, β, and γ oscillations were highly correlated with compulsion. Specifically, δ and γ oscillations increased and decreased during the initiation phase of compulsion, respectively, whereas β increased after compulsion stopped. Such correlations were not found in other parts of the brain during compulsion, or in the BNST during noncompulsive behavior. Current findings reveal real-time neurophysiological biomarkers of compulsion and warrant further assessment of the use of local field potentials for closed-loop neuromodulation for OCD.
Research Group Experimental Neurosurgery and Neuroanatomy, KU Leuven, 3000 Leuven, Belgium, hemmwu@stanford.edu.
Hemmings
H
Wu
Division of Animal and Human Health Engineering, Department of Biosystems, KU Leuven, 3000 Leuven, Belgium.
Tim
T
Tambuyzer
Division of Animal and Human Health Engineering, Department of Biosystems, KU Leuven, 3000 Leuven, Belgium.
Ioana
I
Nica
Research Group Experimental Neurosurgery and Neuroanatomy, KU Leuven, 3000 Leuven, Belgium.
Marjolijn
M
Deprez
Research Group Experimental Neurosurgery and Neuroanatomy, KU Leuven, 3000 Leuven, Belgium.
Kris
0000-0002-0028-6024
K
van Kuyck
Division of Animal and Human Health Engineering, Department of Biosystems, KU Leuven, 3000 Leuven, Belgium.
Jean-Marie
0000-0001-5548-9163
JM
Aerts
Department of Electrical Engineering, Division STADIUS, KU Leuven, 3000 Leuven, Belgium and iMINDs Medical IT, 3001 Leuven, Belgium, and.
Sabine
S
Van Huffel
Research Group Experimental Neurosurgery and Neuroanatomy, KU Leuven, 3000 Leuven, Belgium, Department of Neurosurgery, University Hospitals Leuven, 3000 Leuven, Belgium.
Bart
B
Nuttin
D000818:Animals; D001683:Biological Clocks; D001931:Brain Mapping / Q000379:methods*; D058256:Brain Waves; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D009771:Obsessive-Compulsive Disorder / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012686:Septal Nuclei / Q000503:physiopathology*; D013223:Statistics as Topic
bed nucleus of the stria terminalis; deep brain stimulation; local field potential; obsessive-compulsive disorder; schedule-induced polydipsia; time-frequency analysis
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