Discussion:
Different studies have revealed approximate circuits of tics, OCD and also TS which are generally known as CSTC circuit [1-3]. CSTC components including thalamus, posterolateral GPi and anteromedial GPi are among the most used targets for DBS procedure in TS, while other targets including subthalamic nucleus (STN), globus pallidus Externus (GPe), anterior internal capsule (ALIC), and nucleus accumbens (NA) are also considered useful in some studies [2]. It has been shown that stimulation of each target would lead to an improvement in specific set of components of the disease (e.g. tics, OCD and etc.) while it varies in different cases [2]. Anteromedial GPi is mostly known as an effective target for improvement of tic component of TS, while some studies have stated its ineffectiveness [2, 3]. Stimulation of anteromedial GPi also has been shown to be an effective target in the treatment of the isolated OCD [4], whereas the studies with the purpose of TS treatment have mentioned no significant improvement in the OCD component of TS [2]. Consequently, there is no a consensus yet on how stimulation of anteromedial GPi affects different components of TS (either tics or OCD) although is it generally thought to be effective in TS treatment [3].
In the current case, fluctuations and variations in the therapeutic outcome of TS components have been observed, depended to the stimulation parameters. During sessions, the optimal setup was achieved based on alterations in symptoms and patient’s compliance. With this setup, stimulation of anteromedial GPi led to significant improvement in OCD, but the tics were still existed and got worse progressively. To the best of our knowledge, stimulation of GPi with similar therapeutic outcome has not yet been reported.
In spite of many studies on how CSTC circuit may play an important role in Tic, OCD and TS, our observation along with many others are still needed to be explained in terms of variations in therapeutic outcomes. Many neural pathways are connecting different and specific parts of cerebral cortex, striatum and thalamus together, making multiple parallel and integrated circuits [5-7]. As an example, some areas in GPi, projects neurons to specific parts of thalamus [5] and the same interconnections would exist between thalamus and cerebral cortex [7], GP and other part of striatum [5], GP and thalamus [5] and also in GP itself [5]. In this case, there exist multiple neural pathways between cerebral cortex, striatum and thalamus, involving specific part of each.
Among all these complicated circuits, some specific areas and pathways are related to either tic or OCD pathophysiology and some others are in common; while a portion of them remains unrelated to both. To be more detailed, anterior cingulate cortex, dorsal lateral prefrontal and lateral orbito-frontal areas are related to both OCD and tic disorders [1] which we intend to call them common areas; while, motor and oculomotor areas are mostly related to tic disorder [8] and ventromedial prefrontal cortex is mostly the characteristic of OCD [4]. Interestingly, common areas including lateral orbito-frontal area and anterior cingulate cortex are responsible for reward processing and fear expression, respectively, which are common features and underlying causes of both tics and OCD, whereas motor functions in tics may be subsequent to involvement of motor cortex and unwanted reoccurring thoughts in OCD may be due to the involvement of limbic system specifically [1, 4, 8].
Anteromedial GPi is related to associative, motor and limbic areas through pallidothalamic and thalamocortical pathways [5-7, 9]. These pathways and areas may include the pathways or areas that are involved in the pathophysiology of either tic or OCD, or both. Therefore, Anteromedial GPi might be related to both common and tic-/OCD-specified areas and pathways and neural impulses from anteromedial GPi would find their way through specific neural pathways of pallidothalamic and thalamocortical pathways toward tic-/OCD-specified or common pathways and areas. DBS studies have also demonstrated that anteromedial GPi is a beneficial target for both tic and OCD [10] which indicates its involvement in both tic and OCD generating pathways and areas .
Here, we have hypothesized that through DBS procedure on anteromedial GPi, the stimulation impulse would travel through all possible related pathways to anteromedial GPi, including common or tic-/OCD-specified pathways and make an impact on any of them (figure 1). This impact may end up with an appropriate therapeutic outcome in either tic or OCD, or both in respect to physiological conditions of the pathways. In other words, physiological conditions of these pathways determine the variations in the therapeutic outcome. Moreover, it is probable that all tic or OCD generating circuits do not possess similar physiological conditions which leads to different responsiveness to certain stimulus. It can be said that specific stimulation adjustment may cause resynchronization as a probable effect in set of pathways, but causing no effect in the others in respect to their physiological condition. In our case, firstly we observed fluctuations in symptoms and eventually at the best adjustment, OCD improved significantly while tic remained unchanged. We think that stimulation of anteromedial GPi spread out to both tic-/OCD-specified pathways; and these pathways respond to the stimulus differently based on their physiological condition which led to fluctuations in symptoms. In other words, with certain adjustments, OCD-specified pathways probably resynchronized and improved better than tic-specified pathways in response to the stimulus because of the former’s higher susceptibility to this event, leading to an improvement in OCD and not tic. In conclusion, we hypothesize that the anteromedial GPi can be described as a portal to the pathways involved in both tic and OCD and stimulation of this target would make an impact on all these pathways but with different extents. Hence, anteromedial GPi itself is not the determining factor in improvement of OCD or tic components of TS and the condition of involved pathways is playing an important role. This hypothesis would also explain variations in therapeutic outcomes of DBS for TS patients in other studies.