Global network modulation during thalamic stimulation for Tourette syndrome

Abstract

Background and objectivesDeep brain stimulation (DBS) of the thalamus is a promising therapeutic alternative for treating medically refractory Tourette syndrome (TS). However, few human studies have examined its mechanism of action. Therefore, the networks that mediate the therapeutic effects of thalamic DBS remain poorly understood.MethodsFive participants diagnosed with severe medically refractory TS underwent bilateral thalamic DBS stereotactic surgery. Intraoperative fMRI characterized the blood oxygen level-dependent (BOLD) response evoked by thalamic DBS and determined whether the therapeutic effectiveness of thalamic DBS, as assessed using the Modified Rush Video Rating Scale test, would correlate with evoked BOLD responses in motor and limbic cortical and subcortical regions.ResultsOur results reveal that thalamic stimulation in TS participants has wide-ranging effects that impact the frontostriatal, limbic, and motor networks. Thalamic stimulation induced suppression of motor and insula networks correlated with motor tic reduction, while suppression of frontal and parietal networks correlated with vocal tic reduction. These regions mapped closely to major regions of interest (ROI) identified in a nonhuman primate model of TS.ConclusionsOverall, these findings suggest that a critical factor in TS treatment should involve modulation of both frontostriatal and motor networks, rather than be treated as a focal disorder of the brain. Using the novel combination of DBS-evoked tic reduction and fMRI in human subjects, we provide new insights into the basal ganglia-cerebellar-thalamo-cortical network-level mechanisms that influence the effects of thalamic DBS. Future translational research should identify whether these network changes are cause or effect of TS symptoms.

Distinctive tics suppression network in Gilles de la Tourette syndrome distinguished from suppression of natural urges using multimodal imaging

“…To summarize our findings, the tic suppression networks appear to be mainly limbic and associative. This is in line a recent study investigating the effect of thalamic deep brain stimulation in GTS ( Jo et al, 2018 ). Ultimately, GTS might be best considered as a social decision-making network disorder, instead of a BG disorder, as was recently proposed because patients can choose to alter or inhibit tics in social contexts( Albin, 2018 ).…”

“…A recent study of intraoperative functional MRI demonstrated that thalamic stimulation in GTS patients has widespread effects on the frontostriatal, limbic, and motor networks. Motor tic reduction was correlated with suppression of motor and insula networks due to thalamic stimulation, while suppression of frontal and parietal networks correlated with vocal tic reduction ( Jo et al, 2018 ). In contrast, our study primarily found a limbic suppression strategy in GTS patients suppressing ocular tics.…”

Neurovascular coupling during deep brain stimulation

“…We applied constant current (700 mA) biphasic chargedbalanced rectangular pulses, pulse width 100 or 200 ms (100 ms in animal 1, 2 and 4 while 200 ms in animals 3, 5e7), to the VL thalamus using an isolated pulse stimulator (Model 2100, A-M Systems, Carlsborg, WA). Based on our previous study [59] identifying the time course and saturation of stimulation at 50 Hz, here stimulation was applied for 3 s at 7 different frequencies (10,20,30,40,60,80 and 100 Hz). In all experiments, charge density was kept below the level which causes tissue damage [61].…”

A Comprehensive Review of Brain Connectomics and Imaging to Improve Deep Brain Stimulation Outcomes

“…TS is also associated with neuropsychiatric comorbidities and has critical dysfunction of frontal, limbic, and motor networks . Jo and colleagues investigated the functional global connectivity of 5 TS patients in response to bilateral thalamic DBS of the centromedian and parafasicularis complex (CMPf) . The CMPf is a unique target in that its location allows connectivity into the sensory, motor, and limbic circuitries .…”