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Lukas Goede @lukasgoede.bsky.social · Sep 4

What might the future of deep brain stimulation look like?

Not just continuous stimulation, but decoding symptoms in real time and directing stimulation to the right brain circuits.

Fascinating perspective article by @andreashorn.org & @julianneumann.bsky.social in @natrevneurol.nature.com:

Andreas Horn @andreashorn.org · Sep 3

In #DeepBrainStimulation

the two major developments across the last decade have been

1. Adaptive DBS and
2. Connectomic DBS

In a @natrevneurol.nature.com article with @julianneumann.bsky.social, we ask:

Could the two be united into a common framework?

www.nature.com/articles/s41...

A 🧵

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Reposted by Lukas Goede

Michael Fox @foxmdphd.bsky.social · May 24

Is there a shared brain circuit target for tremor that transcends diagnosis and DBS site? New work by @lukasgoede.bsky.social @andreashorn.org @braincircuits.bsky.social says YES

Lukas Goede @lukasgoede.bsky.social · May 22

Tremor is a common symptom across many neurological disorders.

But is there a shared tremor circuit across disorders - one that could guide treatment, regardless of diagnosis?

We think: yes.

Our study is out now in @natcomms.nature.com:

🔗 www.nature.com/articles/s41...

🧵 A thread.

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Lukas Goede @lukasgoede.bsky.social · May 22

And of course, institutions like Brigham and Women’s Hospital, Boston, and Charité - Universitätsmedizin Berlin, providing the environment that made this work possible.

Lukas Goede @lukasgoede.bsky.social · May 22

Projects like this are only possible thanks to strong research support.

Grateful for funding from the Thiemann Parkinson Foundation, @dfg.de, and many others who made this work possible - not just for the project, but personally for me as well.

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Lukas Goede @lukasgoede.bsky.social · May 22

Special thanks to @andreashorn.org and @foxmdphd.bsky.social for their mentorship at the @braincircuits.bsky.social, BWH.

This was a long-term project developed under @andreashorn.org's guidance, and I couldn’t be more grateful that it marks the conclusion of my time in Boston.

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Lukas Goede @lukasgoede.bsky.social · May 22

Thank you to patients, collaborators and coauthors who made this project possible!

To mention just a few colleagues who are here on BlueSky:
@patriciazvarova.bsky.social @bahnebahners.bsky.social @emiddlebrooksmd.bsky.social @jjoutsa.bsky.social @foxmdphd.bsky.social @andreashorn.org

@netstim.org

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Lukas Goede @lukasgoede.bsky.social · May 22

This was a huge team effort - combining datasets across disorders, continents, and methods.

We hope this work helps advance neuromodulation toward guided, symptom-specific treatment.

Full paper: www.nature.com/articles/s41...

Convergent mapping of a tremor treatment network - Nature Communications

Goede et al. combined multiple modalities to define a common tremor network across disorders. This finding may help optimize deep brain stimulation and guide future noninvasive therapies.

www.nature.com

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Lukas Goede @lukasgoede.bsky.social · May 22

We also provide a literature overview of a key structure consistently associated with tremor improvement:
👉 the dentato-rubro-thalamic tract (DRT).

The best DBS outcomes align closely with its trajectory - regardless of target or disorder.

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Lukas Goede @lukasgoede.bsky.social · May 22

We added extensive supplementary material, including a review on:
👉 What influences outcomes after DBS?

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Lukas Goede @lukasgoede.bsky.social · May 22

Of course, there are limitations.

We combined diverse datasets and methods - adding variability.
But this heterogeneity was deliberate, to build a more robust and generalizable network.

And while correlational analysis, the convergence of lesions, DBS, and EMG-fMRI supports causal insight.

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Lukas Goede @lukasgoede.bsky.social · May 22

So what do we take away from all this?

✅ Different forms of tremor share a common brain network
✅ DBS likely works by modulating this circuit
✅ STN, VIM, GPi may all be access points to the same network
✅ This opens the door to symptom-specific neuromodulation - both invasive and noninvasive

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Lukas Goede @lukasgoede.bsky.social · May 22

And yes - indeed.

Connectivity between GPi-DBS electrodes and the convergent tremor map explained significant variance in clinical outcomes.

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Lukas Goede @lukasgoede.bsky.social · May 22

We then integrated all maps - lesions, atrophy, fMRI, and DBS - into a multimodal tremor network map.

The key test:
Could this convergent map explain tremor outcomes in a new, independent cohort: Parkinson's disease patients with GPi-DBS?

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Lukas Goede @lukasgoede.bsky.social · May 22

To power these analyses, we created a new, high-resolution normative connectome:
🧠 Based on resting-state fMRI from 1,087 healthy subjects (HCP), 2 mm isotropic voxels

We also replicated results using a Parkinson’s disease-specific connectome from the PPMI cohort. Findings held up across datasets.

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Lukas Goede @lukasgoede.bsky.social · May 22

Building on these data, we analyzed two different DBS patient cohorts:

• Parkinson’s disease patients with subthalamic DBS
• Essential tremor patients with thalamic DBS

Outcome maps from each group could explain outcomes in the other.

Disorder-independent. Target-independent.

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Lukas Goede @lukasgoede.bsky.social · May 22

Another key step was to collaborate with Rick Helmich.

We incorporated a map from the well-known dimmer-switch model of tremor, based on EMG-fMRI:
🔗 academic.oup.com/brain/articl...

Once again, the same core regions emerged:
- Motor cortex
- Motor cerebellum

Three paths. One destination.

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Lukas Goede @lukasgoede.bsky.social · May 22

Next, we included an atrophy network map from essential tremor patients, based on a recent paper by Ellen Younger et al.:
🔗 doi.org/10.1212/WNL....

This atrophy-based network pointed to cerebellar regions, adding another independent layer of support.

Mapping Essential Tremor to a Common Brain Network Using Functional Connectivity Analysis | Neurology

Background and ObjectivesThe cerebello-thalamo-cortical circuit plays a critical role in essential tremor (ET). However, abnormalities have been reported in multiple brain regions outside this circuit...

doi.org

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Lukas Goede @lukasgoede.bsky.social · May 22

We found: the stronger the connection between a DBS site and this lesion-derived network, the better the tremor relief - even across different disorders.

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Lukas Goede @lukasgoede.bsky.social · May 22

First, we revisited stroke lesions that alleviated tremor.
As shown by @jjoutsa.bsky.social‬, these lesions mapped to a distinct functional network:

🔗 doi.org/10.1002/ana....

Identifying therapeutic targets from spontaneous beneficial brain lesions

Brain damage can occasionally result in paradoxical functional benefit, which could help identify therapeutic targets for neuromodulation. However, these beneficial lesions are rare and lesions in mu...

doi.org

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Lukas Goede @lukasgoede.bsky.social · May 22

We asked a simple question:

Does a shared tremor treatment network exist across diseases and deep brain stimulation (DBS) targets?

To find out, we combined four independent modalities:
🧠 Lesions
🧠 Atrophy
🧠 EMG-fMRI
🧠 DBS outcomes

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Lukas Goede @lukasgoede.bsky.social · May 22

Tremor is a common symptom across many neurological disorders.

But is there a shared tremor circuit across disorders - one that could guide treatment, regardless of diagnosis?

We think: yes.

Our study is out now in @natcomms.nature.com:

🔗 www.nature.com/articles/s41...

🧵 A thread.

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Lukas Goede @lukasgoede.bsky.social · May 19

Big thanks to @patriciazvarova.bsky.social and @bahnebahners.bsky.social for their wonderful contributions, and to @andreashorn.org for his mentorship on this project!

Read the full study here:

onlinelibrary.wiley.com/doi/10.1002/...

Patient Selection in Deep Brain Stimulation: A Role for Transcranial Direct Current Stimulation to Enhance the Levodopa Challenge?

Dopaminergic medication and deep brain stimulation (DBS) improve motor symptoms in Parkinson's disease (PD), but levodopa response alone may not predict DBS outcomes. We retrospectively analyzed 19 P....

onlinelibrary.wiley.com

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Lukas Goede @lukasgoede.bsky.social · May 19

Of course: this is a small sample and an exploratory analysis.

But this cohort is rare: patients who received all three interventions: tDCS, levodopa challenge, and DBS.

That makes these findings hypothesis-generating and worth building on.

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Lukas Goede @lukasgoede.bsky.social · May 19

Here’s the interesting part:

When we combined both tDCS and levodopa responses in a linear model, they jointly explained a significant amount of the variance in DBS outcomes.

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Lukas Goede @lukasgoede.bsky.social · May 19

So we asked, in our cohort:
(i) Does the levodopa response predict DBS outcome?
(ii) Does it correlate with the tDCS response?

The trends were there - but in this small sample (N = 10), neither reached significance on its own.

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