Oscillatory coupling of the subthalamic nucleus in obsessive compulsive disorder

Wojtecki, Lars; Hirschmann, Jan V.; Elben, Saskia; Boschheidgen, Matthias; Trenado, Carlos; Vesper, Jan; Schnitzler, Alfons

doi:10.1093/brain/awx164

Cited by 20 publications

(19 citation statements)

References 5 publications

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“…Alternatively, negative correlations such as between M1‐STN beta band synchrony and UPDRS‐III scores could merely reflect normal physiology, in which case one would expect healthy individuals to show stronger M1‐STN coherence than PD patients (Hirschmann, Ozkurt, et al, ). Obviously, it is not possible to perform invasive recordings of brain activity in controls to confirm this, but a case study in an obsessive–compulsive disorder patient, treated with STN‐DBS, confirmed the presence of a high STN‐motor cortical connectivity in the beta band (Wojtecki et al, ). Furthermore, advances in source reconstruction techniques, such as beamforming, increasingly allow the study of subcortical regions by means of MEG (Boon et al, ; Hillebrand, Nissen, et al, ; Jha et al, ).…”

Section: Discussionmentioning

confidence: 99%

A systematic review of MEG‐based studies in Parkinson's disease: The motor system and beyond

Boon

Geraedts

Hillebrand

et al. 2019

Human Brain Mapping

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Parkinson's disease (PD) is accompanied by functional changes throughout the brain, including changes in the electromagnetic activity recorded with magnetoencephalography (MEG). An integrated overview of these changes, its relationship with clinical symptoms, and the influence of treatment is currently missing. Therefore, we systematically reviewed the MEG studies that have examined oscillatory activity and functional connectivity in the PD‐affected brain. The available articles could be separated into motor network‐focused and whole‐brain focused studies. Motor network studies revealed PD‐related changes in beta band (13–30 Hz) neurophysiological activity within and between several of its components, although it remains elusive to what extent these changes underlie clinical motor symptoms. In whole‐brain studies PD‐related oscillatory slowing and decrease in functional connectivity correlated with cognitive decline and less strongly with other markers of disease progression. Both approaches offer a different perspective on PD‐specific disease mechanisms and could therefore complement each other. Combining the merits of both approaches will improve the setup and interpretation of future studies, which is essential for a better understanding of the disease process itself and the pathophysiological mechanisms underlying specific PD symptoms, as well as for the potential to use MEG in clinical care.

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Section: Discussionmentioning

confidence: 99%

A systematic review of MEG‐based studies in Parkinson's disease: The motor system and beyond

Boon

Geraedts

Hillebrand

et al. 2019

Human Brain Mapping

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“…Recordings from other DBS targets in OCD patients revealed high frequency discharge and variability of inter-spike intervals in the caudate nucleus ( n = 2) and lack of alpha-band (8–14 Hz) oscillatory activity in the bed nucleus of stria terminalis (in 5 OCD patients vs. 7 major depression patients) 33 , 34 . In a recent study using combined LFP and magnetoencephalography (MEG) recordings, theta-coupling was evident between the STN and the anterior cingulate cortex 23 .…”

Section: Discussionmentioning

confidence: 99%

“…Although many studies have investigated the sub-regions of the STN in PD patients, only two groups have reported acute STN recordings in OCD patients 19 – 23 . These invasive human recordings in a small group of patients have been recorded with intraoperative leads or temporarily externalized leads in the immediate post-operative period.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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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.

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“…The finding that a biomarker of concurrent parkinsonian motor sign severity can be recorded in real-time through the same electrodes that deliver the therapeutic stimulation has inspired the concept of a demand-dependent adaptive DBS paradigm [48], where the stimulation parameters are adapted directly according to the recorded electrophysiological parkinsonian symptom correlate, closing the loop from recording to stimulation [49,50]. Importantly, the presence of beta synchronization in the basal ganglia should not be mistaken as PD specific or pathological per se, as studies from other DBS patient groups, such as dystonia [51][52][53] and OCD [54][55][56], have reported peaks of beta activity in the basal ganglia. However, the relative higher amount of low beta (13-20 Hz) synchrony [29,57] and the correlation with motor sign severity [34,35] distinguish PD patients from other movement disorders.…”

Section: Pathophysiological Neural Activity In Dbs Patients With Parkmentioning

confidence: 99%

Toward Electrophysiology-Based Intelligent Adaptive Deep Brain Stimulation for Movement Disorders

et al. 2019

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Deep brain stimulation (DBS) represents one of the major clinical breakthroughs in the age of translational neuroscience. In 1987, Benabid and colleagues demonstrated that high-frequency stimulation can mimic the effects of ablative neurosurgery in Parkinson's disease (PD), while offering two key advantages to previous procedures: adjustability and reversibility. Deep brain stimulation is now an established therapeutic approach that robustly alleviates symptoms in patients with movement disorders, such as Parkinson's disease, essential tremor, and dystonia, who present with inadequate or adverse responses to medication. Currently, stimulation electrodes are implanted in specific target regions of the basal ganglia-thalamic circuit and stimulation pulses are delivered chronically. To achieve optimal therapeutic effect, stimulation frequency, amplitude, and pulse width must be adjusted on a patient-specific basis by a movement disorders specialist. The finding that pathological neural activity can be sampled directly from the target region using the DBS electrode has inspired a novel DBS paradigm: closed-loop adaptive DBS (aDBS). The goal of this strategy is to identify pathological and physiologically normal patterns of neuronal activity that can be used to adapt stimulation parameters to the concurrent therapeutic demand. This review will give detailed insight into potential biomarkers and discuss next-generation strategies, implementing advances in artificial intelligence, to further elevate the therapeutic potential of DBS by capitalizing on its modifiable nature. Development of intelligent aDBS, with an ability to deliver highly personalized treatment regimens and to create symptom-specific therapeutic strategies in real-time, could allow for significant further improvements in the quality of life for movement disorders patients with DBS that ultimately could outperform traditional drug treatment.

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Oscillatory coupling of the subthalamic nucleus in obsessive compulsive disorder

Cited by 20 publications

References 5 publications

A systematic review of MEG‐based studies in Parkinson's disease: The motor system and beyond

A systematic review of MEG‐based studies in Parkinson's disease: The motor system and beyond

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

Toward Electrophysiology-Based Intelligent Adaptive Deep Brain Stimulation for Movement Disorders

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