Subthalamic theta activity: a novel human subcortical biomarker for obsessive compulsive disorder

Pnina Rappel,Zvi Israel,David Arkadir,Idit Tamir,Atira S Bick,Odeya Marmor,Sara A Freedman,Renana Eitan,Eduard Linetsky,Moran Gilad,Hagai Bergman,Anna Castrioto,Tomer Mevorach

doi:10.1038/s41398-018-0165-z

Abstract

Obsessive-compulsive disorder (OCD) is a common and serious psychiatric disorder. Although subthalamic nucleus deep brain stimulation (DBS) has been studied as a treatment for OCD patients the underlying mechanism of this treatment and the optimal method of stimulation are unknown. To study the neural basis of subthalamic nucleus DBS in OCD patients we used a novel, implantable DBS system with long-term local field potential sensing capability. We focus our analysis on two patients with OCD who experienced severe treatment-resistant symptoms and were implanted with subthalamic nucleus DBS systems. We studied them for a year at rest and during provocation of OCD symptoms (46 recording sessions) and compared them to four Parkinson’s disease (PD) patients implanted with subthalamic nucleus DBS systems (69 recording sessions). We show that the dorsal (motor) area of the subthalamic nucleus in OCD patients displays a beta (25–35 Hz) oscillatory activity similar to PD patients whereas the ventral (limbic-cognitive) area of the subthalamic nucleus displays distinct theta (6.5–8 Hz) oscillatory activity only in OCD patients. The subthalamic nucleus theta oscillatory activity decreases with provocation of OCD symptoms and is inversely correlated with symptoms severity over time. We conclude that beta oscillations at the dorsal subthalamic nucleus in OCD patients challenge their pathophysiologic association with movement disorders. Furthermore, theta oscillations at the ventral subthalamic nucleus in OCD patients suggest a new physiological target for OCD therapy as well as a promising input signal for future emotional-cognitive closed-loop DBS.

Highlights

Obsessive compulsive disorder (OCD) is a debilitating psychiatric disorder characterized by obsessions and compulsions
Betaoscillatory activity was identified in the dorso-lateral region of the subthalamic nucleus (STN) in Parkinson’s patients and most interestingly in OCD patients (Fig. 1b–d)
Multiple macroelectrode local field potentials (LFPs) recordings during the first postoperative year clearly demonstrated that OCD patients had beta-oscillatory activity mainly at the dorso-lateral STN and theta-oscillatory activity mainly at the ventromedial STN (Fig. 2a, b)

Summary

Introduction

Obsessive compulsive disorder (OCD) is a debilitating psychiatric disorder characterized by obsessions and compulsions. The subthalamic nucleus (STN) has a central position within the CSTC circuits and through its sensorimotor, emotional and cognitive areas coordinates decision-making, actionselection and various high-order processes[3,4,5,6]. STN deep brain stimulation (DBS) has been studied as a treatment for severe resistant OCD patients[6,7,8,9,10,11,12,13]. Synchronized oscillatory activity is a feature of healthy brain that facilitates communication between nearby and distant neuronal networks[14]. In Parkinson’s disease, excessive synchronized low (12–25 Hz) and high (25–35 Hz) beta band activity in the dorsal STN has been identified as pathognomonic and thought to be responsible for some of the parkinsonian

Methods

Results

Conclusion