Modulation of Fibers to Motor Cortex during Thalamic DBS in Tourette Patients Correlates with Tic Reduction

Abstract

Probabilistic tractography in Tourette syndrome (TS) patients have shown an alteration in the connectivity of the primary motor cortex and supplementary motor area with the striatum and thalamus, suggesting an abnormal connectivity of the cortico-striatum-thalamocortical-pathways in TS. Deep brain stimulation (DBS) of the centromedian nucleus–nucleus ventrooralis internus (CM-Voi complex) in the thalamus is an effective treatment for refractory TS patients. We investigated the connectivity of activated fibers from CM-Voi to the motor cortex and its correlation between these projections and their clinical outcome. Seven patients with TS underwent CM-Voi-DBS surgery and were clinically evaluated preoperatively and six months postoperatively. We performed diffusion tensor imaging to display the activated fibers projecting from the CM-Voi to the different motor cortex regions of interest. These analyses showed that the extent of tic reduction during DBS is associated with the degree of stimulation-dependent connectivity between CM-Voi and the motor cortex, and in particular, an increased density of projections to the presupplementary motor area (preSMA). Non-responder patients displayed the largest amount of active fibers projecting into cortical areas other than motor cortex compared to responder patients. These findings support the notion that an abnormal connectivity of thalamocortical pathways underlies TS, and that modulation of these circuits through DBS could restore the function and reduce symptoms.

Neuroanatomical Considerations for Optimizing Thalamic Deep Brain Stimulation in Tourette Syndrome

“…3A, 4A). This finding is consistent with that reported by a recent study showing that the relationship of tic reduction with the fibres connecting the thalamus and the motor cortex [37]. On the contrary, it is well known that high electrical intensity is usually required for tic suppression [4], and therapeutic stimulation may also modulate the limbic systems sub-clinically inducing psychiatric side effects.…”

A functional network target for tic reduction during thalamic stimulation for Tourette Syndrome

“…The observed results are highly congruent to the studies based on structural connectivity [8,12] but reveal the importance of additional regions. The strongest association with tic reduction was found for connectivity with the bilateral insulae and the medial frontal cortex encompassing the cingulate cortex and supplementary motor area.…”

Connectivity Patterns of Deep Brain Stimulation Targets in Patients with Gilles de la Tourette Syndrome

“…Using the open-source software Lead-DBS ( , Charité University Hospital, Berlin, Germany), the VTAs were estimated for these patients. The procedure has been described in detail in our previous publication [ 21 ]. The sham VTAs were transferred to each patient’s T2 sequence using FLIRT from the FSL v6.0 program (FMRIB Software Library, ) for affine linear matching, followed by deformable registration by advanced normalization tools (ANTs, ) [ 30 ].…”

“…Based on scholarly literature, we defined the prefrontal cortex, the primary motor cortex (M1), the primary sensory cortex (S1), the supplementary motor area (SMA), the pre-SMA, the amygdala, and the hippocampus as our seed regions [ 7 , 21 , 31 ]. M1, S1, and the prefrontal cortex were defined manually in the MNI space.…”

“…Recent studies have reported a correlation between the connectivity patterns of different DBS targets and a reduction in the symptoms of GTS patients [ 20 , 21 , 22 ]. However, most studies have focused on a single DBS target, with only one study comparing pallidal and thalamic stimulation [ 22 ].…”