Brain Sciences Special Issue “Modulatory Effects of Deep Brain Stimulation on Distributed Brain Networks”

I am editing a special issue in the #openaccess journal Brain Sciences about
In case you are working on topics that combine brain stimulation with connectomics, would like to write a review or short report in that domain, please consider submitting to this issue – deadline is july 2019.
Dear Colleagues,
The field of deep brain stimulation (DBS) is currently experiencing a paradigm-shift, from studying impacts on local brain tissue toward the analysis of modulatory effects on distributed brain networks. With the rise of modern non-invasive neuroimaging methods, this local-to-global shift bears promising potential to better-understand brain disorders, brain function, and to translate novel concepts into clinical practice. Already, network-based targets that may guide surgical planning and DBS programming are being introduced and prospectively validated with the potential to revolutionize the field.
In this Special Issue, we will discuss the indications, potentials, efficacy and validation of network-based brain stimulation concepts with a special focus on DBS. These include the combination of DBS imaging with resting-state functional magnetic resonance imaging, diffusion-weighted imaging based tractography and electrophysiological measures such as electroencephalography, magnetoencephalography and local field potential recordings.
Andreas Horn

Lesion Network Mapping for Parkinsonism and Tremor relief

In two articles published this month, Juho Joutsa and Michael D Fox have applied their lesion network mapping approach to symptoms that are highly relevant to the field of DBS.
The technique, which has been introduced by Aaron D Boes and Michael D Fox (Brain, 2015) uses a normative functional connectome off a large healthy cohort to create connectivity maps seeding from a lesion that caused a specific symptom. These maps are then thresholded and used to find a “common denominator”, i.e. a region to which all of the lesions are connected.
So far, the technique has been successfully applied to freezing of gait (Alfonso Fasano, AoN 2017), hemichorea/hemiballismus (Simon Laganiere, Neurology 2016), delusions/capgrass syndrome (Ryan Darby, Brain 2016), criminal behavior (Ryan Darby, PNAS 2017) and coma (David Fischer, Neurology 2016).
With the two most recent articles, Juho Joutsa has shown that the technique may add relevant new insight to the field of deep brain stimulation.
In the first article (AoN), Joutsa et al. showed that focal lesions that led to tremor relief were all functionally connected to the VIM of the thalamus. Not only does this show the potential of using brain lesions to define a DBS target, but it also gives a functional target in normative (MNI) space using functional MRI. Needless to say, in this example, the target (VIM) was already established. However, one could picture using this technique to find new treatment targets based on brain lesions that lead to different symptoms.
In the second article (Brain), Joutsa et al. showed that lesions that led to Parkinsonism were all functionally connected to a common brain network that involved multiple basal ganglia structures. In further analysis, the most specific and sensitive region that was highlighted was a part of the claustrum. At first glance, this finding may be surprising given the claustrum has not much been linked to Parkinsonism in the past. However, alpha-synuclein deposition was found in the claustrum in PD (Article Clinical correlates of pathology in the claustrum in Parkins…) and just recently, the group of Angelo Quartarone found decreased connectivity between the Claustrum and areas mainly involved in visuomotor and attentional systems in PD (Article Claustral structural connectivity and cognitive impairment i…).
Together with these studies, the article by Joutsa et al. may encourage for more research of the claustrum in Parkinsonism.
Joutsa articles about Tremor & Parkinsonism:
Boes article that introduced Lesion Network Mapping:
Other lesion network mapping articles published by the Fox group so far:

Lead-DBS updates in 2018

Three months into 2018, there have been several studies that used Lead-DBS to answer very interesting questions briefly summarized below.
1. Siobhan Ewert and Todd Herrington could recently show that automated segmentations of the STN and GPi performed with Lead-DBS are nearly as precise as manual expert segmentations of the same structures in both a high-definition MRI sample as well as a “typical clinical” quality sample. In total, they ran >11.000 nonlinear brain deformations and segmented 120 brains manually to evaluate i) which deformation algorithm & preset yields best results and ii) how much error is still obtained when using the best strategy. Their optimal normalization strategy has now become the default preset of Lead-DBS.
2. Roxanne Lofredi and Andrea A Kühn have demonstrated that movement velocity is encoded in subthalamic gamma bursts in a recent article that then applied the subcortical electrophysiology mapping (SEM) concept based on electrode localizations performed with Lead-DBS to localize the origin of this gamma activity.
3. Along the same lines: Xinyi Geng and Shouyan Wang have published a paper to put intraoperative LFP findings into an anatomical context following the same (SEM) concept. In their paper, they indirectly replicate main findings of two other recent studies
by Bernadette van Wijk and Vladimir Litvak (which had already extended the concept to PAC and High-frequency oscillations)
that used Lead-DBS to localize beta power within the STN. The work by Geng et al. further extends beyond these and for instance includes space-relationships for theta and gamma power.
Further info on the idea of “Subcortical Electrophysiology Mapping (SEM)” may be found in our blog post ( or knowledge-base article (
4. Franz Hell and Kai Bötzel published a very interesting study using drift-diffusion models, joint LFP- and EEG-recordings, as well as interventional DBS. Based on their findings, they propose that “motor and executive control networks with complementary oscillatory mechanisms are tonically active, react to stimuli and release inhibition at the response when uncertainty is resolved and return to their default state afterwards.” Lead-DBS was used to localize electrodes implanted to the sensorimotor functional zone of the STN.
5. Canan Peisker and Jens Kuhn published a study of NAc-DBS to treat substance use disorder. They used Lead-DBS to localize the electrodes implanted to the accumbens and investigated wether delay discounting would be modulated by NAc-DBS and concluded to the null-hypothesis.
6. Philip E Mosley and Alistair Perry published both a case report (persistence of mania after cessation of STN DBS) and a larger study that involved electrode localizations made with Lead-DBS. The latter represents a comprehensive study about the relationship between non-motor (side) effects of DBS and electrode placement.


New PNAS Study on Lesion induced criminal behavior

We just published a new study spearheaded by R. Ryan Darby that used the Lesion Network Mapping approach developed by Michael Fox to analyse lesion induced criminal behavior.

The study has been featured on multiple news outlets such as WSFA, Der Spiegel, The Independent and El País.

Findings show that lesions leading to criminal behavior are connected to a common brain network. This criminality-associated connectivity pattern was unique compared with lesions causing four other neuropsychiatric syndromes.

Explaining TMS treatment response in depression by means of functional connectivity

In a new BPS study (Prospective Validation That Subgenual Connectivity Predicts …) spearheaded by Anne Weigand and led by Michael D Fox, we were able to explain TMS treatment response by functional connectivity between the stimulation site in the left dorsolateral prefrontal cortex and the subgenual cingulate cortex. Specifically, strength of anticorrelations between DLPFC and subgenual were predictive of beneficial outcome. This relationship had been hypothesized by Michael D Fox and colleagues in 2012 (Efficacy of Transcranial Magnetic Stimulation Targets for De…) and was now prospectively validated in a sample of 25 patients treated at BIDMC with TMS.
Moreover, to exclude sham effects, a cohort of 16 patients treated by Stephan F Taylor in Michigan was retrospectively analyzed and showed the same relationship.

Electrophysiological Atlas of GPi Activity (Neumann 2017) included in Lead-DBS v2.0.0.6

Inside a new version of Lead-DBS (v2.0.0.6) released yesterday, we included the pallidal theta activity sweet spot defined in A localized pallidal physiomarker in cervical dystonia as well as optimal stimulation targets defined in Thomas Schönecker‘s Article Postoperative MRI localisation of electrodes and clinical ef… and Philip Starr’s Article Microelectrode-guided implantation of deep brain stimulators….

 Since all three spots fall into a very similar region of the GPi, this atlas gives some summarizing evidence for an optimal target inside the GPi. Of note, the target falls into the sensorimotor part of the GPi as defined in

We further included the CIT168 subcortical atlas defined in A High-Resolution Probabilistic In Vivo Atlas of Human Subco… that Wolfgang Pauli and colleagues from Caltech graciously shared for inclusion in Lead-DBS.

Furthermore, the new Schäfer parcellations defined in Local-Global Parcellation of the Human Cerebral Cortex from … that further subdivide the famous 7/17 rs-fMRI brain parcellation established by B.T. Thomas Yeo et al in The organization of the human cerebral cortex estimated by f…  have been added for DBS connectivity analyses.
Last but not least, we included‘s (PIs Stephen Coombes & David Villaincourt) HMAT
Three-dimensional locations and boundaries of motor and prem… and S-MATT A Template and Probabilistic Atlas of the Human Sensorimotor…  templates of the sensorimotor cortex and -tract as brain parcellations for connectivity analyses in Lead-DBS and Lead-Connectome (for more information on these very helpful templates see
For an updated list of subcortical atlases in Lead-DBS see, for a list of whole-brain / connectivity brain parcellations see

New SEM study out: “Relating pallidal theta activity to dystonic symptoms and anatomy of the GPi”

In a new study (A localized pallidal physiomarker in cervical dystonia) led by Wolf-Julian Neumann with Siobhan EwertJulius HueblChristof BrückeGerd-Helge Schneider and Andrea A Kühn, we were able to relate pallidal theta power to dystonic symptom severity for the first time.
Furthermore, using the “Subcortical Electrophysiology Mapping (SEM)” approach developed as part of Lead-DBS (implemented inside the “Lead Group” module), we were able to robustly localize theta activity to an anatomical subpart of the internal pallidum that most likely corresponds to its sensorimotor functional zone (based on an atlas developed by Siobhan Ewert et al. (Toward defining deep brain stimulation targets in MNI space:…).
The same approach had been used before to localize beta power in PD within the subthalamic nucleus (Toward an Electrophysiological ” Sweet Spot ” for Deep Brain…) and additionally high frequency oscillations in intraoperative LFP recordings (Localization of beta and high-frequency oscillations within …).
The approach is described in detail in a blog post ( and the Lead-DBS knowledge base ( on our website.
We hope that the technique may be applied to localize other LFP signatures to anatomy in the future – again using co-registered recordings of large patient cohorts.

VTA-model support for segmented Leads

Till Dembek created a segmented Lead Mesh that allows us to run our FEM-calculations (see Connectivity Predicts deep brain stimulation outcome in Park…; model implemented based on SimBio with great help from Johannes Vorwerk) to create VTAs for these electrodes.

Lead-DBS 2.0 out now

We are proud to release Lead-DBS 2.0 to the community – an open source tool to localize Deep Brain Stimulation (DBS) electrodes in the human brain.
A detailed description of all major new features is available here [], but in a nutshell they are:
  • DISTAL atlas: A detailed brain atlas of the human subcortex based on histology (graciously provided by M. Mallar Chakravarty and Louis Collins), MRI and structural connectivity. It is available in three different nomenclatures, thus serving as a rosetta stone for thalamic nomenclatures (See Siobhan Ewert‘s

    ; for a summary see here []).

  • FEM-based VTA model (beta): To model the physical effects of DBS in the brain, we teamed up with Johannes Vorwerk (SimBio/FieldTrip toolboxes) and Qianqian Fang (Iso2Mesh toolbox). Further help was provided by Ningfei Li (integration inside Lead-DBS), Robert Oostenveld (Initial counseling and help with FieldTrip-related code). This is the first open-source pipeline to model volumes of tissue activated (VTA) as a one-step solution (see Connectivity Predicts deep brain stimulation outcome in Park…and this page [] for details).
  • Human Motor Thalamus Atlas: Graciously provided by Igor & Kristy Ilinsky, the human motor thalamus settles controversies about motor projections in the human thalamus. It is based on specialized histological stains and was precisely co-registered to ICBM 2009b space. For more information about the dataset, see [].
  • PaCER: A fully automated method to precisely reconstruct DBS electrode localizations based on postoperative CT data will soon be published by Andreas Husch (Hertel group, Luxembourg) and was graciously provided to Lead-DBS. For more information about PaCER, see [].
  • MER-Mapping: Ari Kappel (Richardson lab, Pittsburgh) and Chadwick Boulay (Sachs lab, Ottawa) created an intuitive and precise tool to combine DBS reconstructions with microelectrode recordings within Lead-DBS.
  • Multiple novel atlases: In total, Lead-DBS now comes with 23 subcortical atlases [] and 14 whole-brain parcellations [] suited for connectomics.
  • Enhanced workflows: We re-designed large parts of the registration pipeline. For normalization strategies, all SPM routines, ANTs, FSL’s FNIRT and a MaGET-brain like procedure are available directly in Matlab (and without the need to install anything else).
We hope you like our new release – and please don’t hesitate to spread the word to colleagues in the DBS field. To download Lead-DBS now, see [].

DISTAL Atlas methods summary, data out soon

Summary of novel subcortical atlas that is “made for Lead-DBS”, based on multispectral high-resolution MNI template, histology and structural connectivity (Ewert et al., 2017) here:
Dataset out soon, original publication here: