Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy

Abstract

Functional and connectivity changes in corticostriatal systems have been reported in the brains of patients with obsessive–compulsive disorder (OCD); however, the relationship between basal ganglia activity and OCD severity has never been adequately established. We recently showed that deep brain stimulation of the subthalamic nucleus (STN), a central basal ganglia nucleus, improves OCD. Here, single-unit subthalamic neuronal activity was analysed in 12 OCD patients, in relation to the severity of obsessions and compulsions and response to STN stimulation, and compared with that obtained in 12 patients with Parkinson's disease (PD). STN neurons in OCD patients had lower discharge frequency than those in PD patients, with a similar proportion of burst-type activity (69 vs 67%). Oscillatory activity was present in 46 and 68% of neurons in OCD and PD patients, respectively, predominantly in the low-frequency band (1–8 Hz). In OCD patients, the bursty and oscillatory subthalamic neuronal activity was mainly located in the associative–limbic part. Both OCD severity and clinical improvement following STN stimulation were related to the STN neuronal activity. In patients with the most severe OCD, STN neurons exhibited bursts with shorter duration and interburst interval, but higher intraburst frequency, and more oscillations in the low-frequency bands. In patients with best clinical outcome with STN stimulation, STN neurons displayed higher mean discharge, burst and intraburst frequencies, and lower interburst interval. These findings are consistent with the hypothesis of a dysfunction in the associative–limbic subdivision of the basal ganglia circuitry in OCD's pathophysiology.

Changes of oscillatory activity in the subthalamic nucleus during obsessive-compulsive disorder symptoms: Two case reports

“…Second, it should be noted the presence of decreased STN activity in the right hemisphere, as well as an c o r t e x 6 0 ( 2 0 1 4 ) 1 4 5 e1 5 0 asymmetry of the shape of STN spectrum between left and right hemisphere. This may support an asymmetry of the STN pathophysiology in OCD as already reported from spontaneous per-operatory single-unit recordings where more burst neurons (suspected to be a marker of neuronal network dysfunction) were reported on the left side Welter et al, 2011). Put together, these two cases suggest that acute OCD symptoms may be related to abnormally high oscillatory activity in the STN, particularly in the left hemisphere and in the delta-alpha (1e12 Hz) frequency range.…”

“…Furthermore, these results suggest first an extension of the role of alpha-beta (8e30 Hz) oscillations to its already "antikinetic" role hypothesized in previous studies performed in movement disorder patients (Jenkinson & Brown, 2011): abnormally alphaebeta oscillations may not only overstabilize the motor system, but they would also prevent cognitive flexibility (Engel & Fries, 2010). Another theoretical interpretation of the increased level of STN oscillations is that it could correspond to modulation of the bursting activity of STN neurons (Welter et al, 2011) and might reflect an abnormal excitation of the STN during OCD. In EEG research, slow rhythms have been proposed to reflect inhibition of thalamocortical loops for action selection (Jensen & Mazaheri, 2010;Schroeder & Lakatos, 2009).…”

“…In PD, increased corticosubthalamic oscillatory activity in the alpha-beta bands (8e30 Hz) correlates with akinesia (Hirschmann et al, 2013). In OCD, increased oscillatory activity has also been observed in the STN and was found to correlate with the severity of OCD (Welter et al, 2011). Furthermore, some subthalamic neurons specifically increased their firing rate when doubt occurred during a verification task (Burbaud et al, 2013).…”

“…Studies on PD patients highlighted the relationship between STN alpha activity (oscillations) and valence-related emotional information processing, but there are still insufficient data elucidating the involvement of STN in OCD symptomatology. While the baseline firing pattern of STN neurons was shown to differ from that of PD patients and to correlate with the severity of OCD symptoms (Welter et al, 2011), the modulation of STN activity during OCD symptoms is unknown. Here, we report two exceptional cases of OCD patients implanted for DBS therapy, from whom STN local field potentials (LFP) were recorded during unexpected OCD symptoms that occurred during a cognitive task performed at the patient's bedside, within a few days between the implantation of the DBS leads and of the stimulator.…”

Response inhibition rapidly increases single-neuron responses in the subthalamic nucleus of patients with Parkinson's disease

“…A first possibility might be related to the anatomical location of the recordings that are likely to differ between studies: in OCD patients, the clinical target is located in the associative and limbic territory whereas in PD patients, the clinical target is located in the sensorimotor STN (Chabardes et al, 2012), and previous anatomical reconstruction did demonstrate that STN neurons recorded in OCD are more anterior than in PD Welter et al, 2011). Therefore, we speculate that the absence of error-monitoring cells in PD might be related to a lower sampling of the STN subregions where these cells might be clustered.…”