The Effect of Uni- and Bilateral Thalamic Deep Brain Stimulation on Speech in Patients With Essential Tremor: Acoustics and Intelligibility

Becker, Johannes; Barbe, Michael T.; Hartinger, Mariam; Dembek, Till A.; Pochmann, Jil; Wirths, Jochen; Allert, Niels; Mücke, Doris; Hermes, Anne; Meister, Ingo G.; Visser‐Vandewalle, Veerle; Grice, Martine; Timmermann, Lars

doi:10.1111/ner.12546

Cited by 22 publications

(68 citation statements)

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“…Future studies may obtain even better VT control with unilateral stimulation of the most ventral and medial part of the “dominant” Vim nucleus [27, 42]. This is in contrast to stimulation-induced dysarthria which is caused by the electrodes placed more laterally and is more common following bilateral than unilateral stimulation [28, 49, 50]. Our results suggest that optimal voice outcomes following DBS are both target and side specific, in contrast to the improvement of limb tremor that can be achieved even with stimulation outside of the Vim nucleus [51-53].…”

Section: Discussionmentioning

confidence: 96%

“…These effects of stimulation were consistent between the perceptual evaluation and acoustic analysis of the recordings. Due to the exploratory nature of the analysis, we were interested in the effect of DBS on VT and did not analyze its overall effect on speech intelligibility, fluency, or articulation as has been demonstrated in previous studies [50]. Finally, limitations related with the imaging analysis including registration errors, distortion issues, and resolution issues which could have affected our assumptions in the anatomical location of the significant cluster and the tractography results.…”

Section: Discussionmentioning

confidence: 99%

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Unilateral Thalamic Deep Brain Stimulation for Voice Tremor

Avecillas-Chasín

Poologaindran

Morrison

et al. 2018

Stereotact Funct Neurosurg

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Background: Voice tremor (VT) is the involuntary and rhythmical phonatory instability of the voice. Recent findings suggest that unilateral deep brain stimulation of the ventral intermediate nucleus (Vim-DBS) can sometimes be effective for VT. In this exploratory analysis, we investigated the effect of Vim-DBS on VT and tested the hypothesis that unilateral thalamic stimulation is effective for patients with VT. Methods: Seven patients with VT and previously implanted bilateral Vim-DBS were enrolled in the study. Each patient was randomized and recorded performing sustained phonation during the following conditions: left thalamic stimulation, right thalamic stimulation, bilateral thalamic stimulation (Bil-ON), and no stimulation (Bil-OFF). Perceptual VT ratings and an acoustic analysis to find the rate of variation of the fundamental frequency measured by the standard deviation of the pitch (f0SD) were performed in a blinded manner. For the purposes of this study, a “dominant” side was defined as one with more than twice as much reduction in VT following Vim-DBS compared to the contralateral side. The Wilcoxon signed-rank test was performed to compare the effect of the dominant side stimulation in the reduction of VT scores and f0SD. The volume of activated tissue (VAT) of the dominant stimulation side was modelled against the degree of improvement in VT to correlate the significant stimulation cluster with thalamic anatomy. Finally, tractography analysis was performed to analyze the connectivity of the significant stimulation cluster. Results: Unilateral stimulation was beneficial in all 7 patients. Five patients clearly had a “dominant” side with either benefit only seen following stimulation of one side or more than twice as much benefit from one side compared to the other. Two patients had similar benefit with unilateral stimulation from either side. The Wilcoxon paired test showed significant differences between unilateral dominant and unilateral nondominant stimulation for VT scores (p = 0.04), between unilateral dominant and Bil-OFF (p = 0.04), and between Bil-ON and unilateral nondominant stimulation (p = 0.04). No significant differences were found between Bil-ON and unilateral dominant condition (p = 0.27), or between Bil-OFF and unilateral nondominant (p = 0.23). The dominant VAT showed that the significant voxels associated with the best VT control were located in the most ventral and medial part of the Vim nucleus and the ventralis caudalis anterior internus nucleus. The connectivity analysis showed significant connectivity with the cortical areas of the speech circuit. Conclusions: Unilateral dominant-side thalamic stimulation and bilateral thalamic stimulation were equally effective in reducing VT. Nondominant unilateral stimulation alone did not significantly improve VT.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Unilateral Thalamic Deep Brain Stimulation for Voice Tremor

Avecillas-Chasín

Poologaindran

Morrison

et al. 2018

Stereotact Funct Neurosurg

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“…Thalamic DBS led to an impairment of articulatory coordination patterns, probably due to a modulation of cerebellothalamic connections (Mücke et al, 2018). Moreover, we observed articulatory imprecision and slowness affecting the production of the entire syllable cycle, most likely related to a modulation of the internal capsule (Mücke et al, 2014;Becker et al, 2017;Hermes et al, 2019). However, the exact pathogenesis of SID remains elusive.…”

Section: Introductionmentioning

confidence: 88%

“…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;.…”

Section: Introductionmentioning

confidence: 99%

Network fingerprint of stimulation-induced speech impairment in essential tremor

Petry‐Schmelzer

Jergas

Thies

et al. 2020

Preprint

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Word count abstract: 384/400Word count introduction: 440 Word count discussion: 1769Word count text: 4769/6000 Abstract Thalamic deep brain stimulation (DBS) is an effective treatment for patients with medically refractory essential tremor. However, stimulation-induced side-effects, especially stimulationinduced dysarthria (SID), interfere severely with quality of life and postoperative tremor control. Here, we present a functional and structural network approach to SID to gain insights into the associated brain areas and to predict stimulation-induced worsening of intelligibility. Monopolar reviews were conducted in 14 essential tremor patients with bilateral thalamic DBS by increasing the stimulation amplitude contact-wise until (i) a maximum of 10mA, (ii) the occurrence of intolerable side effects, or (iii) the onset of SID. Speech assessments included intelligibility ratings when reading a German standard text and a fast syllable repetition task.To detect brain areas associated with SID, a functional connectivity difference image of volumes of tissue activated (VTAs) causing SID, and VTAs not causing SID was created employing a state-of-the-art functional connectome, Lead-DBS, as well as the SPM toolbox.Additionally, discriminative fibers for stimulation-induced worsening of intelligibility were identified in a structural connectome using linear mixed effect models and validated in a leaveone-out design. A total of 111 contact assessments were included for further analysis. 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. 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 = diadoc...

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“…In most cases, DBS of the ventral intermediate nucleus of the thalamus (VIM) is an effective treatment of tremor in ET, but some patients do not respond [40], and DBS is sometimes associated with certain deficits in gait and balance [41] or speech [42,43] and can become less effective over time [44,45]. Stimulator programming is typically performed by a neurologist to minimize tremor while avoiding side effects such as paresthesias, but it is not clear to what extent additional symptoms are also treated.…”

Section: Deep Brain Stimulation Can Be An Effective Treatment For Tremormentioning

confidence: 99%

Computational modeling to improve treatments for essential tremor

Lee

Asaad

Jones

2016

Drug Discovery Today: Disease Models

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Essential tremor (ET) is a neurological disorder of unknown etiology that is typically characterized by an involuntary periodic movement of the upper limbs. No longer considered monosymptomatic, ET patients often have additional motor and even cognitive impairments. Although there are several pharmacological treatments, no drugs have been developed specifically for ET [1], and 30–70% of patients are medication-refractory [2]. A subset of medication-refractory patients may benefit from electrical deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus (VIM), which receives cerebellar inputs. Abnormal cerebellar input to VIM is presumed to be a major contributor to tremor symptoms, which is alleviated by DBS. Computational modeling of the effects of DBS in VIM has been a powerful tool to design DBS protocols to reduce tremor activity. However, far less is known about how these therapies affect non-tremor symptoms, and more experimental and computational modeling work is required to address these growing considerations. Models capable of addressing multiple facets of ET will lead to novel, more efficient treatment.

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The Effect of Uni- and Bilateral Thalamic Deep Brain Stimulation on Speech in Patients With Essential Tremor: Acoustics and Intelligibility

Cited by 22 publications

References 46 publications

Unilateral Thalamic Deep Brain Stimulation for Voice Tremor

Unilateral Thalamic Deep Brain Stimulation for Voice Tremor

Network fingerprint of stimulation-induced speech impairment in essential tremor

Computational modeling to improve treatments for essential tremor

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