Functional and Structural Connectivity Patterns Associated with Clinical Outcomes in Deep Brain Stimulation of the Globus Pallidus Internus for Generalized Dystonia

Abstract

BACKGROUND AND PURPOSE: Deep brain stimulation is a well-established treatment for generalized dystonia, but outcomes remain variable. Establishment of an imaging marker to guide device targeting and programming could possibly impact the efficacy of deep brain stimulation in dystonia, particularly in the absence of acute clinical markers to indicate benefit. We hypothesize that the stimulation-based functional and structural connectivity using resting-state fMRI and DTI can predict therapeutic outcomes in patients with generalized dystonia and deep brain stimulation. MATERIALS AND METHODS:We performed a retrospective analysis of 39 patients with inherited or idiopathic-isolated generalized dystonia who underwent bilateral globus pallidus internus deep brain stimulation. After electrode localization, the volumes of tissue activated were modeled and used as seed regions for functional and structural connectivity measures using a normative data base. Resulting connectivity maps were correlated with postoperative improvement in the Unified Dystonia Rating Scale score.RESULTS: Structural connectivity between the volumes of tissue activated and the primary sensorimotor cortex was correlated with Unified Dystonia Rating Scale improvement, while more anterior prefrontal connectivity was inversely correlated with Unified Dystonia Rating Scale improvement. Functional connectivity between the volumes of tissue activated and primary sensorimotor regions, motor thalamus, and cerebellum was most correlated with Unified Dystonia Rating Scale improvement; however, an inverse correlation with Unified Dystonia Rating Scale improvement was seen in the supplemental motor area and premotor cortex.CONCLUSIONS: Functional and structural connectivity with multiple nodes of the motor network is associated with motor improvement in patients with generalized dystonia undergoing deep brain stimulation. Results from this study may serve as a basis for future development of clinical markers to guide deep brain stimulation targeting and programming in dystonia. ABBREVIATIONS: ACPC ¼ anterior/posterior commissure; DBS ¼ deep brain stimulation; GPi ¼ globus pallidus internus; MNI ¼ Montreal Neurological Institute; UDRS ¼ Unified Dystonia Rating Scale; VTA ¼ volume of tissue activated

Spatially coherent and topographically organized pathways of the human globus pallidus

“…v. coordinates of the stimulation site whose related volume of tissue activated (VTA) gathered the highest correlation with unified dystonia rating scale (UDRS) improvement in a cohort of 39 implanted patients suffering from idiopathic isolated generalized dystonia (Okromelidze et al, 2020);…”

“…In addition, we also considered other four optimal stimulation sites as provided in (Okromelidze et al, 2020;Reich et al, 2019;Schönecker et al, 2015;Starr, 2002). Similar results have been obtained for coordinates derived from (Starr, 2002) and (Schönecker et al, 2015) and derived sensorimotor MPMs (Figure 7 Our results suggest that the general topographical organization of connectivity parcels is highly consistent across the GPi and GPe, regardless of the bundle of interest, corroborating the hypothesis that different pathways, running parallel and in series to one other, may share the same spatial organization pattern ( Figure 5).…”

“…proposed and available optimal stimulation sites could be also interpreted in light of models of dystonia as a network-level disorder which ideally involves both the cortico-basal ganglia-thalamo-cortical and cerebello-thalamo-cortical loops (Corp et al, 2019;Okromelidze et al, 2020). In a lesion network mapping study investigating functional connectivity of lesions leading to secondary dystonia, a negative connectivity to somatosensory cortex and a positive connectivity to cerebellum (vermis, cerebellar cortex, and dentate nucleus) resulted to be specific for cervical dystonia (Corp et al, 2019).…”

“…In a lesion network mapping study investigating functional connectivity of lesions leading to secondary dystonia, a negative connectivity to somatosensory cortex and a positive connectivity to cerebellum (vermis, cerebellar cortex, and dentate nucleus) resulted to be specific for cervical dystonia (Corp et al, 2019). In particular, the negative functional connectivity of somatosensory cortex was interpreted as a possible expression of a "missing inhibition" of such area in patients with dystonia and it may be hypothesized that DBS within sensorimotor region of GPi could restore such altered equilibrium (Okromelidze et al, 2020). In line with the model proposed by Corp and colleagues, a recent study showed that functional connectivity between VTA and primary sensorimotor regions, motor thalamus and cerebellum was positively correlated to clinical improvements.…”

Microneurosurgical techniques and perioperative strategies utilized to optimize experimental supracollicular decerebration in rats

“…Neurosurgeons have extensively and variably utilized transcranial magnetic and deep brain stimulation of the motor cortex (Pagni et al, 2008), internal capsule (Franzini et al, 2008), thalamus (Yang et al, 2020), globus pallidus internus (Tan et al, 2016), subthalamic nucleus (Lin et al, 2020a;Tan et al, 2016;Vassal et al, 2019), pedunculopontine nucleus (Lin et al, 2020b), and cerebellum (Bologna and Beradrelli, 2018;Franҫa et al, 2018;Okromelidze et al, 2020;Rezaee et al, 2020) to ameliorate Parkinsonian tremor, rigidity, and bradykinesia (Lin et al, 2020a;Pagni et al, 2008;Tan et al, 2016;Vassal et al, 2019), essential tremor (Blaabjerg et al, 2020), and dystonia (Okromelidze et al, 2020;Pagni et al, 2008). Studies suggest, by extrapolative deduction, the putative efficacy of such techniques in relieving spasticity (Franzini et al, 2008;Pagni et al, 2008;Rezaee et al, 2020;Vassal et al, 2019).…”