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Volker A. Coenen

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10 papers

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YNICL Journal 2025 Journal Article

The rubral wing and its connectome

Volker A. Coenen
Alexander Rau
Horst Urbach
Bastian E.A. Sajonz
Marco Reisert

PURPOSE: Imaging developments optimizing stereotactic surgery for tremor have yielded white matter attenuating sequences (FGATIR/FLAWS) showing a targetable hypointensity in the subthalamic region (rubral wing, RW). RW has been reported to coincide with yet to be defined portions of the dentato-rubro-thalamic tract (DRT). Its discernibility on the single subject level might be hampered by low signal-to-noise ratio (SNR), potentially compromising with surgical outcomes. We here set out to investigate RW as a target structure for tremor surgery by further characterizing it volumetrically and with tractography. METHODS: We performed manual delineations of RW on FLAWS sequences (n = 77, 3 raters) and warped results into MNI 152. We performed tractographic analyses of DRT (human connectome project body, n = 1000), using the red nuclei and RW as waypoints. Further, we investigated fiber tightness peaks of crossed (DRTx) and uncrossed DRT portions (DRTu) along their z-axis. RESULTS: Identification of RW was possible in all subjects. DICE coefficient for volumetric comparison was rather low with 0.54. Euclidean distance of the RW centers of gravity (COG) was <2 mm. RW defines DRTx and optimally routes fibers to the precentral gyrus (PCG). A tightness peak for fibers descending from PCG (DRTx only) was found to coincide with RW. CONCLUSIONS: RW potentially represents a valid candidate target for tremor surgery and is part of the post-crossing portion of the DRTx. COG of RW can be determined with good accuracy, but full volumetric appreciation is difficult on the single subject level (SNR), potentially necessitating additional imaging for surgical targeting.

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YNICL Journal 2024 Journal Article

Disbalanced recruitment of crossed and uncrossed cerebello-thalamic pathways during deep brain stimulation is predictive of delayed therapy escape in essential tremor

Bastian E.A. Sajonz
Marvin L. Frommer
Marco Reisert
Ganna Blazhenets
Nils Schröter
Alexander Rau
Thomas Prokop
Peter C. Reinacher

BACKGROUND: Thalamic deep brain stimulation (DBS) is an efficacious treatment for drug-resistant essential tremor (ET) and the dentato-rubro-thalamic tract (DRT) constitutes an important target structure. However, up to 40% of patients habituate and lose treatment efficacy over time, frequently accompanied by a stimulation-induced cerebellar syndrome. The phenomenon termed delayed therapy escape (DTE) is insufficiently understood. Our previous work showed that DTE clinically is pronounced on the non-dominant side and suggested that differential involvement of crossed versus uncrossed DRT (DRTx/DRTu) might play a role in DTE development. METHODS: F]Fluorodeoxyglucose positron emission tomography were applied. RESULTS: = 0.2319, p < 0.01). Moreover, increasing VAT size on the right (non-dominant) side was associated at trend level with more asymmetric glucose metabolism shifting towards the right (dominant) dentate nucleus. CONCLUSION: Our results suggest that a disbalanced recruitment of DRTu in the non-dominant VAT induces detrimental stimulation effects on the dominant cerebellar outflow (together with contralateral stimulation) leading to DTE and thus hampering the overall treatment efficacy.

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YNICL Journal 2024 Journal Article

The connection of motor improvement after deep brain stimulation in Parkinson’s disease and microstructural integrity of the substantia nigra and subthalamic nucleus

Marco G. Hermann
Nils Schröter
Alexander Rau
Marco Reisert
Nadja Jarc
Michel Rijntjes
Jonas A. Hosp
Peter C. Reinacher

BACKGROUND: Nigrostriatal microstructural integrity has been suggested as a biomarker for levodopa response in Parkinson's disease (PD), which is a strong predictor for motor response to deep brain stimulation (DBS) of the subthalamic nucleus (STN). This study aimed to explore the impact of microstructural integrity of the substantia nigra (SN), STN, and putamen on motor response to STN-DBS using diffusion microstructure imaging. METHODS: and records of motor improvement available. RESULTS: The association between a poorer DBS-response and increased free interstitial fluid showed notable effect sizes (rho > |0.4|) in SN and STN, but not in putamen. However, this did not reach significance after Bonferroni correction and controlling for sex and age. CONCLUSION: Microstructural integrity of SN and STN are potential biomarkers for the prediction of therapy efficacy following STN-DBS, but further studies are required to confirm these associations.

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YNICL Journal 2022 Journal Article

Unravelling delayed therapy escape after thalamic deep brain stimulation for essential tremor? – Additional clinical and neuroimaging evidence

Bastian E.A. Sajonz
Marvin L. Frommer
Isabelle D. Walz
Marco Reisert
Christoph Maurer
Michel Rijntjes
Tobias Piroth
Nils Schröter

BACKGROUND: Delayed therapy escape after thalamic deep brain stimulation (DBS) for essential tremor is a serious yet frequent condition. It is often difficult to detect this process at onset due to its gradual evolution. OBJECTIVE: Here we aim to identify clinical and neuroimaging hallmarks of delayed therapy escape. METHODS: F]FDG PET of an age-matched control group was performed. Exploratory correlation analyses were conducted with operationalized and parametric clinical data. RESULTS: compared with the healthy controls. CONCLUSIONS: Rebound frequency of postural tremor seems to be a good diagnostic marker for delayed therapy escape. Regional glucose metabolism suggests that this phenomenon may be associated with increased metabolic activity in the thalamus and dentate nucleus possibly due to antidromic stimulation effects. We see reasons to interpret the delayed therapy escape phenomenon as being related to long term and chronic DBS.

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YNIMG Journal 2021 Journal Article

Robust intra-individual estimation of structural connectivity by Principal Component Analysis

Lidia Konopleva
Kamil A. Il’yasov
Shi Jia Teo
Volker A. Coenen
Christoph P. Kaller
Marco Reisert

Fiber tractography based on diffusion-weighted MRI provides a non-invasive characterization of the structural connectivity of the human brain at the macroscopic level. Quantification of structural connectivity strength is challenging and mainly reduced to "streamline counting" methods. These are however highly dependent on the topology of the connectome and the particular specifications for seeding and filtering, which limits their intra-subject reproducibility across repeated measurements and, in consequence, also confines their validity. Here we propose a novel method for increasing the intra-subject reproducibility of quantitative estimates of structural connectivity strength. To this end, the connectome is described by a large matrix in positional-orientational space and reduced by Principal Component Analysis to obtain the main connectivity "modes". It was found that the proposed method is quite robust to structural variability of the data.

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YNICL Journal 2020 Journal Article

Identifying controllable cortical neural markers with machine learning for adaptive deep brain stimulation in Parkinson’s disease

Sebastián Castaño-Candamil
Tobias Piroth
Peter Reinacher
Bastian Sajonz
Volker A. Coenen
Michael Tangermann

The identification of oscillatory neural markers of Parkinson's disease (PD) can contribute not only to the understanding of functional mechanisms of the disorder, but may also serve in adaptive deep brain stimulation (DBS) systems. These systems seek online adaptation of stimulation parameters in closed-loop as a function of neural markers, aiming at improving treatment's efficacy and reducing side effects. Typically, the identification of PD neural markers is based on group-level studies. Due to the heterogeneity of symptoms across patients, however, such group-level neural markers, like the beta band power of the subthalamic nucleus, are not present in every patient or not informative about every patient's motor state. Instead, individual neural markers may be preferable for providing a personalized solution for the adaptation of stimulation parameters. Fortunately, data-driven bottom-up approaches based on machine learning may be utilized. These approaches have been developed and applied successfully in the field of brain-computer interfaces with the goal of providing individuals with means of communication and control. In our contribution, we present results obtained with a novel supervised data-driven identification of neural markers of hand motor performance based on a supervised machine learning model. Data of 16 experimental sessions obtained from seven PD patients undergoing DBS therapy show that the supervised patient-specific neural markers provide improved decoding accuracy of hand motor performance, compared to group-level neural markers reported in the literature. We observed that the individual markers are sensitive to DBS therapy and thus, may represent controllable variables in an adaptive DBS system.

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YNIMG Journal 2020 Journal Article

Neuroimaging and electrophysiology meet invasive neurostimulation for causal interrogations and modulations of brain states

Gabriel Gonzalez-Escamilla
Muthuraman Muthuraman
Dumitru Ciolac
Volker A. Coenen
Alfons Schnitzler
Sergiu Groppa

Deep brain stimulation (DBS) has developed over the last twenty years into a highly effective evidenced-based treatment option for neuropsychiatric disorders. Moreover, it has become a fascinating tool to provide illustrative insights into the functioning of brain networks. New anatomical and pathophysiological models of DBS action have accelerated our understanding of neurological and psychiatric disorders and brain functioning. The description of the brain networks arose through the unique ability to illustrate long-range interactions between interconnected brain regions as derived from state-of-the-art neuroimaging (structural, diffusion, and functional MRI) and the opportunity to record local and large-scale brain activity at millisecond temporal resolution (microelectrode recordings, local field potential, electroencephalography, and magnetoencephalography). In the first part of this review, we describe how neuroimaging techniques have led to current understanding of DBS effects, by identifying and refining the DBS targets and illustrate the actual view on the relationships between electrode locations and clinical effects. One step further, we discuss how neuroimaging has shifted the view of localized DBS effects to a modulation of specific brain circuits, which has been possible from the combination of electrode location reconstructions with recently introduced network imaging methods. We highlight how these findings relate to clinical effects, thus postulating neuroimaging as a key factor to understand the mechanisms of DBS action on behavior and clinical effects. In the second part, we show how invasive electrophysiology techniques have been efficiently integrated into the DBS set-up to precisely localize the neuroanatomical targets of DBS based on distinct region-specific patterns of neural activity. Next, we show how multi-site electrophysiological recordings have granted a real-time window into the aberrant brain circuits within and beyond DBS targets to quantify and map the dynamic properties of rhythmic oscillations. We also discuss how DBS alters the transient synchrony states of oscillatory networks in temporal and spatial domains during resting, task-based and motion conditions, and how this modulation of brain states ultimately shapes the functional response. Finally, we show how a successful decoding and management of electrophysiological proxies (beta bursts, phase-amplitude coupling) of aberrant brain circuits was translated into adaptive DBS stimulation paradigms for a targeted and state-dependent invasive electrical neuromodulation.

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YNICL Journal 2020 Journal Article

Tractographic description of major subcortical projection pathways passing the anterior limb of the internal capsule. Corticopetal organization of networks relevant for psychiatric disorders

Volker A. Coenen
Thomas E. Schlaepfer
Bastian Sajonz
Máté Döbrössy
Christoph P. Kaller
Horst Urbach
Marco Reisert

BACKGROUND: Major depression (MD) and obsessive-compulsive disorder (OCD) are psychiatric diseases with a huge impact on individual well-being. Despite optimal treatment regiments a subgroup of patients remains treatment resistant and stereotactic surgery (stereotactic lesion surgery, SLS or Deep Brain Stimulation, DBS) might be an option. Recent research has described four networks related to MD and OCD (affect, reward, cognitive control, default network) but only on a cortical and the adjacent sub-cortical level. Despite the enormous impact of comparative neuroanatomy, animal science and stereotactic approaches a holistic theory of subcortical and cortical network interactions is elusive. Because of the dominant hierarchical rank of the neocortex, corticofugal approaches have been used to identify connections in subcortical anatomy without anatomical priors and in part confusing results. We here propose a different corticopetal approach by identifying subcortical networks and search for neocortical convergences thereby following the principle of phylogenetic and ontogenetic network development. MATERIAL AND METHODS: This work used a diffusion tensor imaging data from a normative cohort (Human Connectome Project, HCP; n = 200) to describe eight subcortical fiber projection pathways (PPs) from subthalamic nucleus (STN), substantia nigra (SNR), red nucleus (RN), ventral tegmental area (VTA), ventrolateral thalamus (VLT) and mediodorsal thalamus (MDT) in a normative space (MNI). Subcortical and cortical convergences were described including an assignment of the specific pathways to MD/OCD-related networks. Volumes of activated tissue for different stereotactic stimulation sites and procedures were simulated to understand the role of the distinct networks, with respect to symptoms and treatment of OCD and MD. RESULTS: The detailed course of eight subcortical PPs (stnPP, snrPP, rnPP, vlATR, vlATRc, mdATR, mdATRc, vtaPP/slMFB) were described together with their subcortical and cortical convergences. The anterior limb of the internal capsule can be subdivided with respect to network occurrences in ventral-dorsal and medio-lateral gradients. Simulation of stereotactic procedures for OCD and MD showed dominant involvement of mdATR/mdATRc (affect network) and vtaPP/slMFB (reward network). DISCUSSION: Corticofugal search strategies for the evaluation of stereotactic approaches without anatomical priors often lead to confusing results which do not allow for a clear assignment of a procedure to an involved network. According to our simulation of stereotactic procedures in the treatment of OCD and MD, most of the target regions directly involve the reward (and affect) networks, while side-effects can in part be explained with a co-modulation of the control network. CONCLUSION: The here proposed corticopetal approach of a hierarchical description of 8 subcortical PPs with subcortical and cortical convergences represents a new systematics of networks found in all different evolutionary and distinct parts of the human brain.

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YNIMG Journal 2018 Journal Article

The dynamics of error processing in the human brain as reflected by high-gamma activity in noninvasive and intracranial EEG

Martin Völker
Lukas D.J. Fiederer
Sofie Berberich
Jiří Hammer
Joos Behncke
Pavel Kršek
Martin Tomášek
Petr Marusič

Error detection in motor behavior is a fundamental cognitive function heavily relying on local cortical information processing. Neural activity in the high-gamma frequency band (HGB) closely reflects such local cortical processing, but little is known about its role in error processing, particularly in the healthy human brain. Here we characterize the error-related response of the human brain based on data obtained with noninvasive EEG optimized for HGB mapping in 31 healthy subjects (15 females, 16 males), and additional intracranial EEG data from 9 epilepsy patients (4 females, 5 males). Our findings reveal a multiscale picture of the global and local dynamics of error-related HGB activity in the human brain. On the global level as reflected in the noninvasive EEG, the error-related response started with an early component dominated by anterior brain regions, followed by a shift to parietal regions, and a subsequent phase characterized by sustained parietal HGB activity. This phase lasted for more than 1 s after the error onset. On the local level reflected in the intracranial EEG, a cascade of both transient and sustained error-related responses involved an even more extended network, spanning beyond frontal and parietal regions to the insula and the hippocampus. HGB mapping appeared especially well suited to investigate late, sustained components of the error response, possibly linked to downstream functional stages such as error-related learning and behavioral adaptation. Our findings establish the basic spatio-temporal properties of HGB activity as a neural correlate of error processing, complementing traditional error-related potential studies.

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YNICL Journal 2018 Journal Article

Tractography-assisted deep brain stimulation of the superolateral branch of the medial forebrain bundle (slMFB DBS) in major depression

Volker A. Coenen
Bastian Sajonz
Marco Reisert
Jan Bostroem
Bettina Bewernick
Horst Urbach
Carolin Jenkner
Peter C. Reinacher

Background: Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (slMFB) emerges as a - yet experimental - treatment for major depressive disorder (MDD) and other treatment refractory psychiatric diseases. First experiences have been reported from two open label pilot trials in major depression (MDD) and long-term effectiveness for MDD (50 months) has been reported. Objective: To give a detailed description of the surgical technique for DBS of the superolateral branch of the medial forebrain bundle (slMFB) in MDD. Methods: = 24 patients with MDD is reported. The detailed procedure of tractography-assisted targeting together with detailed electrophysiology in 144 trajectories in the target region (recording and stimulation) is described. Achieved electrode positions were evaluated based on postoperative helical CT and fused to preoperative high resolution anatomical magnetic resonance imaging (MRI; Philips Medical Systems, Best, Netherlands), including the pre-operative diffusion tensor imaging (DTI) tractographic information (StealthViz DTI, Medtronic, USA; Framelink 5.0, Medtronic, USA). Midcommissural point (MCP) coordinates of effective contact (EC) location, together with angles of entry into the target region were evaluated. To investigate incidental stimulation of surrounding nuclei (subthalamic nucleus, STN; substantia nigra, SNr; and red nucleus, RN) as a possible mechanism, a therapeutic triangle (TT) was defined, located between these structures (based on MRI criteria in T2) and evaluated with respect to EC locations. Results: Bilateral slMFB DBS was performed in all patients. We identified an electrophysiological environment (defined by autonomic reaction, passive microelectrode recording, acute effects and oculomotor effects) that helps to identify the proper target site on the operation table. Postoperative MCP-evaluation of effective contacts (EC) shows a significant variability with respect to localization. Evaluation of the TT shows that responders will typically have their active contacts inside the triangle and that surrounding nuclei (STN, SNr, RN) are not directly hit by EC, indicating a predominant white matter stimulation. The individual EC position within the triangle cannot be predicted and is based on individual slMFB (tractography) geometry. There was one intracranial bleeding (FORESEE I study) during a first implantation attempt in a patient who later received full bilateral implantation. Typical oculomotor side effects are idiosyncratic for the target region and at inferior contacts. Conclusion: The detailed surgical procedure of slMFB DBS implantation has not been described before. The slMFB emerges as an interesting region for the treatment of major depression (and other psychiatric diseases) with DBS. So far it has only been successfully researched in open label clinical case series and in 15 patients published. Stimulation probably achieves its effect through direct white-matter modulation of slMFB fibers. The surgical implantation comprises a standardized protocol combining tractographic imaging based on DTI, targeting and electrophysiological evaluation of the target region. To this end, slMFB DBS surgery is in technical aspects comparable to typical movement disorder surgery. In our view, slMFB DBS should only be performed under tractographic assistance.

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