Objective
Subthalamic nucleus deep brain stimulation (STN‐DBS) in Parkinson's disease (PD) not only stimulates focal target structures but also affects distributed brain networks. The impact this ...network modulation has on non‐motor DBS effects is not well‐characterized. By focusing on the affective domain, we systematically investigate the impact of electrode placement and associated structural connectivity on changes in depressive symptoms following STN‐DBS, which have been reported to improve, worsen, or remain unchanged.
Methods
Depressive symptoms before and after STN‐DBS surgery were documented in 116 patients with PD from 3 DBS centers (Berlin, Queensland, and Cologne). Based on individual electrode reconstructions, the volumes of tissue activated (VTAs) were estimated and combined with normative connectome data to identify structural connections passing through VTAs. Berlin and Queensland cohorts formed a training and cross‐validation dataset used to identify structural connectivity explaining change in depressive symptoms. The Cologne data served as the test‐set for which depressive symptom change was predicted.
Results
Structural connectivity was linked to depressive symptom change under STN‐DBS. An optimal connectivity map trained on the Berlin cohort could predict changes in depressive symptoms in Queensland patients and vice versa. Furthermore, the joint training‐set map predicted changes in depressive symptoms in the independent test‐set. Worsening of depressive symptoms was associated with left prefrontal connectivity.
Interpretation
Fibers connecting the electrode with left prefrontal areas were associated with worsening of depressive symptoms. Our results suggest that for the left STN‐DBS lead, placement impacting fibers to left prefrontal areas should be avoided to maximize improvement of depressive symptoms. ANN NEUROL 2020;87:962–975
Objective
This study was undertaken to gain insights into structural networks associated with stimulation‐induced dysarthria (SID) and to predict stimulation‐induced worsening of intelligibility in ...essential tremor patients with bilateral thalamic deep brain stimulation (DBS).
Methods
Monopolar reviews were conducted in 14 essential tremor patients. Testing included determination of SID thresholds, intelligibility ratings, and a fast syllable repetition task. Volumes of tissue activated (VTAs) were calculated to identify discriminative fibers for stimulation‐induced worsening of intelligibility in a structural connectome. The resulting fiber‐based atlas structure was then validated in a leave‐one‐out design.
Results
Fibers determined as discriminative for stimulation‐induced worsening of intelligibility were mainly connected to the ipsilateral precentral gyrus as well as to both cerebellar hemispheres and the ipsilateral brain stem. In the thalamic area, they ran laterally to the thalamus and posteromedially to the subthalamic nucleus, in close proximity, mainly anterolaterally, to fibers beneficial for tremor control as published by Al‐Fatly et al in 2019. The overlap of the respective clinical stimulation setting's VTAs with these fibers explained 62.4% (p < 0.001) of the variance of stimulation‐induced change in intelligibility in a leave‐one‐out analysis.
Interpretation
This study demonstrates that SID in essential tremor patients is associated with both motor cortex and cerebellar connectivity. Furthermore, the identified fiber‐based atlas structure might contribute to future postoperative programming strategies to achieve optimal tremor control without speech impairment in essential tremor patients with thalamic DBS. ANN NEUROL 2021;89:315–326
Open questions remain regarding the optimal target, or sweetspot, for deep brain stimulation (DBS) in, for example, Parkinson's disease. Previous studies introduced different methods of mapping DBS ...effects to determine sweetspots. While having a direct impact on surgical targeting and postoperative programming in DBS, these methods so far have not been compared.
This study investigated five previously published DBS mapping approaches regarding their potential to correctly identify a predefined target. Methods were investigated in silico in eight different use-case scenarios, which incorporated different types of clinical data, noise, and differences in underlying neuroanatomy. Dice coefficients were calculated to determine the overlap between identified sweetspots and the predefined target. Additionally, out-of-sample predictive capabilities were assessed using the amount of explained variance R2.
The five investigated methods resulted in highly variable sweetspots. Methods based on voxel-wise statistics against average outcomes showed the best performance overall. While predictive capabilities were high, even in the best of cases Dice coefficients remained limited to values around 0.5, highlighting the overall limitations of sweetspot identification.
This study highlights the strengths and limitations of current approaches to DBS sweetspot mapping. Those limitations need to be taken into account when considering the clinical implications. All future approaches should be investigated in silico before being applied to clinical data.
VPS13D: One Family, Same Mutations, Two Phenotypes Petry‐Schmelzer, Jan Niklas; Keller, Natalie; Karakaya, Mert ...
Movement disorders clinical practice (Hoboken, N.J.),
July 2021, Letnik:
8, Številka:
5
Journal Article
Clinical rating scales for tremors have significant limitations due to low resolution, high rater dependency, and lack of applicability in outpatient settings. Reliable, quantitative approaches for ...assessing tremor severity are warranted, especially evaluating treatment effects, e.g., of deep brain stimulation (DBS). We aimed to investigate how different accelerometry metrics can objectively classify tremor amplitude of Essential Tremor (ET) and tremor in Parkinson’s Disease (PD). We assessed 860 resting and postural tremor trials in 16 patients with ET and 25 patients with PD under different DBS settings. Clinical ratings were compared to different metrics, based on either spectral components in the tremorband or pure acceleration, derived from simultaneous triaxial accelerometry captured at the index finger and wrist. Nonlinear regression was applied to a training dataset to determine the relationship between accelerometry and clinical ratings, which was then evaluated in a holdout dataset. All of the investigated accelerometry metrics could predict clinical tremor ratings with a high concordance (>70%) and substantial interrater reliability (Cohen’s weighted Kappa > 0.7) in out-of-sample data. Finger-worn accelerometry performed slightly better than wrist-worn accelerometry. We conclude that triaxial accelerometry reliably quantifies resting and postural tremor amplitude in ET and PD patients. A full release of our dataset and software allows for implementation, development, training, and validation of novel methods.
•Proof that proximity to the dentatorubrothalamic tract (DRTT) is responsible for increased tremor suppression in deep brain stimulation (DBS) for essential tremor (ET).•High-quality prospective, ...randomized, double-blind clinical data from 13 ET subjects.•Population-based DRTTs using probabilistic tractography in state-of-the-art diffusion MRI data from the human connectome project with supplementary validation against clinical dMRI data from ET patients.•Implications for the future of direct DBS targeting in tremor patients.
To investigate the relation between deep brain stimulation (DBS) of the posterior-subthalamic-area (PSA) and the ventral-intermediate-nucleus (VIM) and the distance to the dentatorubrothalamic tract (DRTT) in essential tremor (ET).
Tremor rating scale (TRS) hemi-scores were analyzed in 13 ET patients, stimulated in both the VIM and the PSA in a randomized, crossover trial. Distances of PSA and VIM contacts to population-based DRTTs were calculated. The relationships between distance to DRTT and stimulation amplitude, as well as DBS efficiency (TRS improvement per amplitude) were investigated.
PSA contacts were closer to the DRTT (p = 0.019) and led to a greater improvement in TRS hemi-scores (p = 0.005) than VIM contacts. Proximity to the DRTT was related to lower amplitudes (p < 0.001) and higher DBS efficiency (p = 0.017).
Differences in tremor outcome and stimulation parameters between contacts in the PSA and the VIM can be explained by their different distance to the DRTT.
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