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

View ORCID ProfileBassam Al-Fatly, Siobhan Ewert, Dorothee Kübler, Daniel Kroneberg, Andreas Horn, Andrea A. Kühn
doi: https://doi.org/10.1101/575209
Bassam Al-Fatly
1Department of Neurology with Experimental Neurology, Movement Disorders and Neuromodulation Unit, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
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  • ORCID record for Bassam Al-Fatly
  • For correspondence: bassam.al-fatly@charite.de
Siobhan Ewert
1Department of Neurology with Experimental Neurology, Movement Disorders and Neuromodulation Unit, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
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Dorothee Kübler
1Department of Neurology with Experimental Neurology, Movement Disorders and Neuromodulation Unit, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
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Daniel Kroneberg
1Department of Neurology with Experimental Neurology, Movement Disorders and Neuromodulation Unit, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
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Andreas Horn
1Department of Neurology with Experimental Neurology, Movement Disorders and Neuromodulation Unit, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
2Berlin Institute of Health
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Andrea A. Kühn
1Department of Neurology with Experimental Neurology, Movement Disorders and Neuromodulation Unit, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
3Exzellenzcluster NeuroCure, Charité – Universitätsmedizin Berlin
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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.

Footnotes

  • We added two major analyses: First, we analysed connectivity profiles associated with the emergence of side effects (dysarthria and ataxia). Crucially, largely distinct regions were involved in electrodes associated with side effects. In addition, we preoperatively scanned a novel patient with diffusion MRI to successfully predict his improvement using patient specific fibertracts. Albeit this analysis merely adds anecdotal evidence (and we present the results in supplementary material), it may line out that from a methodological standpoint, our pipeline could be used in clinical practice. Finally, we replicated our main findings using a different statistical method that works on the level of fibertracts directly (instead of voxels) and was recently introduced by our group (Baldermann et al., Biological Psychiatry). In doing so, we further confirm the validity of our results using a different method.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 09, 2019.
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Connectivity profile of thalamic deep brain stimulation to effectively treat essential tremor
Bassam Al-Fatly, Siobhan Ewert, Dorothee Kübler, Daniel Kroneberg, Andreas Horn, Andrea A. Kühn
bioRxiv 575209; doi: https://doi.org/10.1101/575209
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Connectivity profile of thalamic deep brain stimulation to effectively treat essential tremor
Bassam Al-Fatly, Siobhan Ewert, Dorothee Kübler, Daniel Kroneberg, Andreas Horn, Andrea A. Kühn
bioRxiv 575209; doi: https://doi.org/10.1101/575209

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