Connectivity profile of thalamic deep brain stimulation to effectively treat essential tremor

Abstract

Essential tremor is the most prevalent movement disorder and is often refractory to medical treatment. Deep brain stimulation offers a therapeutic approach that can efficiently control tremor symptoms. Several deep brain stimulation targets (ventral intermediate nucleus, zona incerta, posterior subthalamic area) have been discussed for tremor treatment. Effective deep brain stimulation therapy for tremor critically involves optimal targeting to modulate the tremor network. This could potentially become more robust and precise by using state-of-the-art brain connectivity measurements. In the current study, we utilized two normative brain connectomes (structural and functional) to show the pattern of effective deep brain stimulation electrode connectivity in 36 essential tremor patients. Our structural and functional connectivity models were significantly predictive of post-operative tremor improvement in out-of-sample data (p < 0.001 for both structural and functional leave-one-out cross-validation). Additionally, we segregated the somatotopic brain network based on head and hand tremor scores. These resulted in segregations that mapped onto the well-known somatotopic maps of both motor cortex and cerebellum. Crucially, this shows that slightly distinct networks need to be modulated to ameliorate head vs. hand tremor and that those networks could be identified based on somatotopic zones in motor cortex and cerebellum.Finally, we propose a multi-modal connectomic deep brain stimulation sweet spot that may serve as a reference to enhance clinical care, in the future. This spot resided in the posterior subthalamic area, encroaching on the inferior borders of ventral intermediate nucleus and sensory thalamus.Our results underscore the importance of integrating brain connectivity in optimizing deep brain stimulation targeting for essential tremor.

Network fingerprint of stimulation-induced speech impairment in essential tremor

“…This study demonstrates that SID in essential tremor patients is related to a modulation of the functional connectome of speech production by thalamic DBS. In spite of the Running head: Networks in DBS-induced dysarthria proximity of functional and structural connectivity patterns for tremor control, as identified by Al-Fatly et al (2019), and deterioration of speech, as identified in the present study, we were able to derive a fiber-based atlas structure, that could help to avoid SID in essential tremor patients. These findings might contribute to future lead placement and postoperative programming strategies.…”

“…This study demonstrates that SID in essential tremor patients is related to a modulation of the functional connectome of speech production by thalamic DBS. In spite of the Running head: Networks in DBS-induced dysarthria proximity of functional and structural connectivity patterns for tremor control, as identified by Al-Fatly et al (2019), and deterioration of speech, as identified in the present study, we were able to derive a fiber-based atlas structure, that could help to avoid SID in essential tremor patients. These findings might contribute to future lead placement and postoperative programming strategies.Keywords: thalamic deep brain stimulation, speech motor system, intelligibility, dysarthria, volume of tissue activated Abbreviations DBS = deep brain stimulation, DDK = diadochokinesis, SID = stimulation-induced dysarthria, PSA = posterior subthalamic area, STN = subthalamic nucleus, TRS = tremor rating scale, VIM = ventral intermediate nucleus, VTA = volume of tissue activated Running head: Networks in DBS-induced dysarthria…”

“…The functional connectivity difference image indicated stronger connectivity of VTAs causing SID (N = 51) to the precentral gyrus with a positive medio-lateral gradient, parts of the inferior and medial frontal gyrus, the supramarginal gyrus, the superior temporal gyrus, as well as the superior and the inferior cerebellar lobules, and the vermis. In the thalamic region, discriminative fibers for stimulation-induced worsening of intelligibility were located anterolaterally to fibers associated with tremor control as published by Al-Fatly et al (2019). The overlap of the respective clinical stimulation setting's VTAs with these fibers explained 33.2% of the variance of individual change in intelligibility compared to "OFF stimulation" in a leaveone-out design.…”

“…Besides exploring the origin of SID, there is an urgent need to establish strategies to avoid SID while maintaining effective tremor control. Several approaches aimed at optimizing Running head: Networks in DBS-induced dysarthria postoperative tremor control including probabilistic stimulation maps (Dembek et al, 2017), connectivity profiles associated with tremor control (Al-Fatly et al, 2019), or the identification and direct targeting of fiber tracts associated with beneficial outcomes, e.g. the dentatorubrothalamic tract (Coenen et al, 2014;.…”

Left prefrontal impact links subthalamic stimulation with depressive symptoms

“…Two studies have validated the pipeline using electrophysiological recordings 52,53 and others have demonstrated that results are capable of explaining clinical improvements across patients, DBS centers and cohorts 2,3,48,54,55 . Still, residual errors of electrode reconstructions cannot be excluded.…”