The Experts below are selected from a list of 2130 Experts worldwide ranked by ideXlab platform

Volker A Coenen - One of the best experts on this subject based on the ideXlab platform.

  • neuromodulation in psychiatric disorders experimental and clinical evidence for reward and motivation network deep brain stimulation focus on the Medial Forebrain Bundle
    European Journal of Neuroscience, 2021
    Co-Authors: Mate D Dobrossy, Chockalingam Ramanathan, Danesh Ashouri Vajari, Yixin Tong, Thomas E Schlaepfer, Volker A Coenen
    Abstract:

    Deep brain stimulation (DBS) in psychiatric illnesses has been clinically tested over the past 20 years. The clinical application of DBS to the superolateral branch of the Medial Forebrain Bundle in treatment-resistant depressed patients-one of several targets under investigation-has shown to be promising in a number of uncontrolled open label trials. However, there are remain numerous questions that need to be investigated to understand and optimize the clinical use of DBS in depression, including, for example, the relationship between the symptoms, the biological substrates/projections and the stimulation itself. In the context of precision and customized medicine, the current paper focuses on clinical and experimental research of Medial Forebrain Bundle DBS in depression or in animal models of depression, demonstrating how clinical and scientific progress can work in tandem to test the therapeutic value and investigate the mechanisms of this experimental treatment. As one of the hypotheses is that depression engenders changes in the reward and motivational networks, the review looks at how stimulation of the Medial Forebrain Bundle impacts the dopaminergic system.

  • Tractography-assisted deep brain stimulation of the superolateral branch of the Medial Forebrain Bundle (slMFB DBS) in major depression
    'Elsevier BV', 2018
    Co-Authors: Volker A Coenen, Thomas E Schlaepfer, Bastian Sajonz, Marco Reisert, Jan Bostroem, Bettina Bewernick, Horst Urbach, Carolin Jenkner, Peter C. Reinacher, Burkhard Madler
    Abstract:

    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: Surgical experience from bilateral implantation procedures in n = 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. Keywords: Deep brain stimulation, Depression, Diffusion tensor imaging, Fiber tracking, Medial Forebrain Bundle, OCD, slMFB, Stereotactic surgery, Tractograph

  • the anatomy of the human Medial Forebrain Bundle ventral tegmental area connections to reward associated subcortical and frontal lobe regions
    NeuroImage: Clinical, 2018
    Co-Authors: Volker A Coenen, Thomas E Schlaepfer, Horst Urbach, Peter C. Reinacher, Lena V Schumacher, Christoph P Kaller, Karl Egger, Marco Reisert
    Abstract:

    Abstract Introduction Despite their importance in reward, motivation, and learning there is only sparse anatomical knowledge about the human Medial Forebrain Bundle (MFB) and the connectivity of the ventral tegmental area (VTA). A thorough anatomical and microstructural description of the reward related PFC/OFC regions and their connection to the VTA - the superolateral branch of the MFB (slMFB) - is however mandatory to enable an interpretation of distinct therapeutic effects from different interventional treatment modalities in neuropsychiatric disorders (DBS, TMS etc.). This work aims at a normative description of the human MFB (and more detailed the slMFB) anatomy with respect to distant prefrontal connections and microstructural features. Methods and material Healthy subjects (n = 55; mean age ± SD, 40 ± 10 years; 32 females) underwent high resolution anatomical magnetic resonance imaging including diffusion tensor imaging. Connectivity of the VTA and the resulting slMFB were investigated on the group level using a global tractography approach. The Desikan/Killiany parceling (8 segments) of the prefrontal cortex was used to describe sub-segments of the MFB. A qualitative overlap with Brodmann areas was additionally described. Additionally, a pure visual analysis was performed comparing local and global tracking approaches for their ability to fully visualize the slMFB. Results The MFB could be robustly described both in the present sample as well as in additional control analyses in data from the human connectome project. Most VTA- connections reached the superior frontal gyrus, the middel frontal gyrus and the lateral orbitofrontal region corresponding to Brodmann areas 10, 9, 8, 11, and 11m. The projections to these regions comprised 97% (right) and 98% (left) of the total relative fiber counts of the slMFB. Discussion The anatomical description of the human MFB shows far reaching connectivity of VTA to reward-related subcortical and cortical prefrontal regions - but not to emotion-related regions on the Medial cortical surface - realized via the superolateral branch of the MFB. Local tractography approaches appear to be inferior in showing these far-reaching projections. Since these local approaches are typically used for surgical targeting of DBS procedures, the here established detailed map might - as a normative template - guide future efforts to target deep brain stimulation of the slMFB in depression and other disorders related to dysfunction of reward and reward-associated learning.

  • the Medial Forebrain Bundle as a target for deep brain stimulation for obsessive compulsive disorder
    Cns Spectrums, 2017
    Co-Authors: Volker A Coenen, Thomas E Schlaepfer, Horst Urbach, Peter C. Reinacher, Peter Goll, Ulrich Voderholzer, Ludger Tebartz Van Elst, Tobias Freyer
    Abstract:

    Deep brain stimulation (DBS) is a promising putative modality for the treatment of refractory psychiatric disorders such as major depression and obsessive-compulsive disorder (OCD). Several targets have been posited; however, a clear consensus on differential efficacy and possible modes of action remain unclear. DBS to the supero-lateral branch of the Medial Forebrain Bundle (slMFB) has recently been introduced for major depression (MD). Due to our experience with slMFB stimulation for MD, and because OCD might be related to similar dysfunctions of the reward system, treatment with slMFB DBS seams meaningful. Here we describe our first 2 cases together with a hypothetical mode of action. We describe diffusion tensor imaging (DTI) fiber tractographically (FT)-assisted implantation of the bilateral DBS systems in 2 male patients. In a selected literature overview, we discuss the possible mode of action. Both patients were successfully implanted and stimulated. The follow-up time was 12 months. One patient showed a significant response (Yale-Brown Obsessive-Compulsive Scale [YBOCS] reduction by 35%); the other patient reached remission criteria 3 months after surgery (YBOCS<14) and showed mild OCD just above the remission criterion at 12 months follow-up. While the hypermetabolism theory for OCD involves the cortico-striato-thalamo-cortical (CSTC) network, we think that there is clinical evidence that the reward system plays a crucial role. Our findings suggest an important role of this network in mechanisms of disease development and recovery. In this uncontrolled case series, continuous bilateral DBS to the slMFB led to clinically significant improvements of ratings of OCD severity. Ongoing research focuses on the role of the reward system in OCD, and its yet-underestimated role in this underlying neurobiology of the disease.

  • deep brain stimulation to the Medial Forebrain Bundle for depression long term outcomes and a novel data analysis strategy
    Brain Stimulation, 2017
    Co-Authors: Bettina Bewernick, Volker A Coenen, Sarah Kayser, Sabrina M Gippert, Christina Switala, Thomas E Schlaepfer
    Abstract:

    Abstract Background Deep brain stimulation (DBS) of the supero-lateral branch of the Medial Forebrain Bundle (slMFB) in treatment-resistant depression (TRD) is associated with acute antidepressant effects. Objective Long-term clinical effects including changes in quality of life, side effects and cognition as well as long-term data covering four years are assessed. Methods Eight TRD patients were treated with DBS bilateral to the slMFB. Primary outcome measure was a 50% reduction in Montgomery-Asberg Depression Rating Scale (MADRS) (response) and remission (MADRS Results Six of eight patients (75%) were responders at 12 months, four patients reached remission. Long-term results revealed a stable effect up to four years. Antidepressant efficacy was also reflected in the global assessment of functioning. Main side effect was strabismus at higher stimulation currents. No change in cognition was identified. AUC analysis revealed a significant reduction in depression for 7/8 patients in most months. Conclusions Long-term results of slMFB-DBS suggest acute and sustained antidepressant effect; timeline analysis may be an alternative method reflecting patient's overall gain throughout the study. Being able to induce a rapid and robust antidepressant effect even in a small, sample of TRD patients without significant psychiatric comorbidity, render the slMFB an attractive target for future studies.

Marco R Celio - One of the best experts on this subject based on the ideXlab platform.

  • the lateral hypothalamic parvalbumin immunoreactive pv1 nucleus in rodents
    The Journal of Comparative Neurology, 2012
    Co-Authors: Zoltan Meszar, Franck Girard, Clifford B Saper, Marco R Celio
    Abstract:

    In the lateral hypothalamus, groups of functionally related cells tend to be widely scattered rather than confined to discrete, anatomically distinct units. However, by using parvalbumin (PV)-specific antibodies, a solitary, compact cord of PV-immunoreactive cells (the PV1-nucleus) has been identified in the ventrolateral tuberal hypothalamus in various species. Here we describe the topography, the chemo-, cyto-, and myeloarchitectonics, and the ultrastructure of this PV1-nucleus in rodents. The PV1-nucleus is located within the ventrolateral division of the Medial Forebrain Bundle. In the horizontal plane, it has a length of 1 mm in mice and 2 mm in rats. PV-immunoreactive perikarya fall into two distinct size categories and number (~800 in rats and ~400 in mice). They are intermingled with PV-negative neurons and coarse axons of the Medial Forebrain Bundle, some of which are PV-positive. Symmetric and asymmetric synapses, as well as PV-positive and PV-negative fiber endings, terminate on the perikarya of both PV-positive and PV-negative neurons. PV-positive neurons of the PV1-nucleus express glutamate, not γ-aminobutyric acid (GABA), the neurotransmitter that is usually associated with PV-containing nerve cells. Although we could not find evidence that PV1 neurons express either catecholamines or known neuropeptides, they sometimes are interspersed with the fibers and terminals of such cells. From its analogous topographical situation, the PV1-nucleus could correspond to the lateral tuberal nucleus in humans. We anticipate that the presence of the marker protein PV in the PV1-nucleus of the rodent hypothalamus will facilitate future studies relating to the connectivity, transcriptomics, and function of this entity.

Michael B Pritz - One of the best experts on this subject based on the ideXlab platform.

  • thalamic reticular nucleus in caiman crocodilus immunohistochemical staining
    Brain Behavior and Evolution, 2018
    Co-Authors: Michael B Pritz
    Abstract:

    The thalamic reticular nucleus in reptiles, Caiman crocodilus, shares a number of morphological similarities with its counterpart in mammals. In view of the immunohistochemical properties of this nucleus in mammals and the more recently identified complexity of this neuronal aggregate in Caiman, this nucleus was investigated using a number of antibodies. These results were compared with findings described for other amniotes. The following antibodies gave consistent and reproducible results: polyclonal sheep anti-parvalbumin (PV), monoclonal mouse anti-PV, and polyclonal sheep anti-glutamic acid decarboxylase (GAD). In the transverse plane, this nucleus is divided into two. In each part, a compact group of cells sits on top of the fibers of the Forebrain Bundle with scattered cells among these fibers. In the lateral Forebrain Bundle, this neuronal aggregate is represented by the dorsal peduncular nucleus and the perireticular nucleus while, in the Medial Forebrain Bundle, these parts are the interstitial nucleus and the scattered cells in this fiber tract. The results of this study are the following. First, the thalamic reticular nucleus of Caiman contains GAD(+) and PV(+) neurons, which is similar to what has been described in other amniotes. Second, the morphology and distribution of many GAD(+) and PV(+) neurons in the dorsal peduncular and perireticular nuclei are similar and suggest that these neurons colocalize these markers. Third, neurons in the interstitial nucleus and in the Medial Forebrain Bundle are GAD(+) and PV(+). At the caudal pole of the thalamic reticular nucleus, PV immunoreactive cells predominated and avoided the central portion of this nucleus where GAD(+) cells were preferentially located. However, GAD(+) cells were sparse when compared with PV(+) cells. This immunohistochemically different area in the caudal pole is considered to be an area separate from the thalamic reticular nucleus.

  • thalamic reticular nucleus in caiman crocodilus relationship with the dorsal thalamus
    Neuroscience, 2016
    Co-Authors: Michael B Pritz
    Abstract:

    The thalamic reticular nucleus was investigated in one group of crocodilians, Caiman crocodilus. This neuronal aggregate is composed of two parts: a compact portion and a diffuse region made up of scattered cells within the Forebrain Bundles. In Caiman, both the lateral and Medial Forebrain Bundles project to the telencephalon and the thalamic reticular nucleus is associated with each fiber tract. In the lateral Forebrain Bundle, the compact area is termed the nucleus of the dorsal peduncle (dorsal peduncular nucleus) while the diffuse part is called the perireticular area. In the Medial Forebrain Bundle, the interstitial nucleus comprises one part of the compact area while another region without a specific neuronal label is also present. Similar to the perireticular cells of the lateral Forebrain Bundle, scattered cells are also present in the Medial Forebrain Bundle. Morphological features of the thalamic reticular nucleus are revealed with stains for the following: fibers; cells; succinic acid dehydrogenase; and acetylcholinesterase. Regardless of which dorsal thalamic nucleus was injected, a localized region of the thalamic reticular nucleus contained retrogradely labeled cells and anterogradely labeled axons and terminals. This grouping was termed clusters and was felt to represent the densest interconnection between the dorsal thalamus and the reticular nucleus. Using clusters as an index of interconnections, the reticular nucleus was divided into sectors, each of which was associated with a specific dorsal thalamic nucleus. An organization similar to that found in Caiman is present in other sauropsids as well as in mammals. These data suggest that a thalamic reticular nucleus is present in all amniotes and has morphological properties similar to those described in this analysis. Lastly, a hypothesis is presented to explain how the external shape of the reticular nucleus in Caiman might be transformed into the homologous area in a representative bird and mammal.

Burkhard Madler - One of the best experts on this subject based on the ideXlab platform.

  • Tractography-assisted deep brain stimulation of the superolateral branch of the Medial Forebrain Bundle (slMFB DBS) in major depression
    'Elsevier BV', 2018
    Co-Authors: Volker A Coenen, Thomas E Schlaepfer, Bastian Sajonz, Marco Reisert, Jan Bostroem, Bettina Bewernick, Horst Urbach, Carolin Jenkner, Peter C. Reinacher, Burkhard Madler
    Abstract:

    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: Surgical experience from bilateral implantation procedures in n = 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. Keywords: Deep brain stimulation, Depression, Diffusion tensor imaging, Fiber tracking, Medial Forebrain Bundle, OCD, slMFB, Stereotactic surgery, Tractograph

  • rapid effects of deep brain stimulation for treatment resistant major depression
    Biological Psychiatry, 2013
    Co-Authors: Thomas E Schlaepfer, Burkhard Madler, Bettina Bewernick, Sarah Kayser, Volker A Coenen
    Abstract:

    Background Treatment-resistant major depressive disorder is a prevalent and debilitating condition. Deep brain stimulation to different targets has been proposed as a putative treatment. Methods In this pilot study, we assessed safety and efficacy of deep brain stimulation to the supero-lateral branch of the Medial Forebrain Bundle in seven patients with highly refractory depression. Primary outcome criterion was severity of treatment-resistant major depressive disorder as assessed with the Montgomery-Asberg Depression Rating Scale. General psychopathologic parameters, social functioning, and tolerance were assessed with standardized scales, the Global Assessment of Functioning scale, quality of life (Short-Form Health Survey Questionnaire), and neuropsychological tests. Results All patients showed strikingly similar intraoperative effects of increased appetitive motivation. Six patients attained the response criterion; response was rapid—mean Montgomery-Asberg Depression Rating Scale of the whole sample was reduced by>50% at day 7 after onset of stimulation. At last observation (12–33 weeks), six patients were responders; among them, four were classified as remitters. Social functioning (Global Assessment of Functioning) improved in the sample as a whole from serious to mild impairment. Mean stimulation current was 2.86 mA; all side effects (strabismus at higher stimulation current, one small intracranial bleeding during surgery, infection at the implanted pulse generator site) could be resolved at short term. Conclusions These preliminary findings suggest that bilateral stimulation of the supero-lateral branch of the Medial Forebrain Bundle may significantly reduce symptoms in treatment-resistant major depressive disorder. Onset of antidepressant efficacy was rapid (days), and a higher proportion of the population responded at lower stimulation intensities than observed in previous studies.

  • human Medial Forebrain Bundle mfb and anterior thalamic radiation atr imaging of two major subcortical pathways and the dynamic balance of opposite affects in understanding depression
    Journal of Neuropsychiatry and Clinical Neurosciences, 2012
    Co-Authors: Volker A Coenen, Trevor A Hurwitz, Jaak Panksepp, H Urbach, Burkhard Madler
    Abstract:

    The Medial Forebrain Bundle (MFB), a key structure of reward-seeking circuitry, remains inadequately characterized in humans despite its vast importance for emotional processing and development of addictions and depression. Using Diffusion Tensor Imaging Fiber Tracking (DTI FT) the authors describe potential converging ascending and descending MFB and anterior thalamic radiation (ATR) that may mediate major brain reward-seeking and punishment functions. Authors highlight novel connectivity, such as supero-lateral-branch MFB and ATR convergence, caudally as well as rostrally, in the anterior limb of the internal capsule and Medial prefrontal cortex. These anatomical convergences may sustain a dynamic equilibrium between positive and negative affective states in human mood-regulation and its various disorders, especially evident in addictions and depression.

  • Medial Forebrain Bundle stimulation as a pathophysiological mechanism for hypomania in subthalamic nucleus deep brain stimulation for parkinson s disease
    Neurosurgery, 2009
    Co-Authors: Trevor A Hurwitz, Christopher R Honey, Volker A Coenen, Ahmed A Rahman, Jacqueline Mcmaster, Uli Burgel, Burkhard Madler
    Abstract:

    Objective Hypomania accounts for approximately 4% to 13% of psychotropic adverse events during subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease. Diffusion of current into the inferior and Medial "limbic" STN is often reported to be the cause. We suggest a different explanation, in which the coactivation of the Medial Forebrain Bundle (MFB), outside the STN, leads to hypomania during STN DBS. Methods Six patients with advanced Parkinson's disease (age, 54 +/- 11 years) underwent bilateral STN DBS surgery. Preoperative diffusion tensor imaging scans for fiber tracking of the MFB were conducted on a 3T magnetic resonance imaging scanner. After implantation, the electrode positions were determined with computed tomography and integrated in a diffusion tensor imaging software environment. Results The Medial STN was shown to send tributaries to the MFB using it as a pathway to connect to the reward circuitry. One patient, who had a transient, stimulation-induced acute hypomanic episode, showed a direct contact between 1 active electrode contact and these putative limbic STN tributaries to the MFB unilaterally on the left. In 5 asymptomatic patients, the active contacts were between 2.9 and 7.5 mm distant from the MFB or its limbic STN tributaries. Conclusion We hypothesize that STN DBS-induced reversible acute hypomania might be elicited by inadvertent and unilateral coactivation of putative limbic STN tributaries to the MFB. These findings may provide insight into the neural pathways of hypomania and may facilitate future investigations of the pathophysiology of mood disorders.

Thomas E Schlaepfer - One of the best experts on this subject based on the ideXlab platform.

  • neuromodulation in psychiatric disorders experimental and clinical evidence for reward and motivation network deep brain stimulation focus on the Medial Forebrain Bundle
    European Journal of Neuroscience, 2021
    Co-Authors: Mate D Dobrossy, Chockalingam Ramanathan, Danesh Ashouri Vajari, Yixin Tong, Thomas E Schlaepfer, Volker A Coenen
    Abstract:

    Deep brain stimulation (DBS) in psychiatric illnesses has been clinically tested over the past 20 years. The clinical application of DBS to the superolateral branch of the Medial Forebrain Bundle in treatment-resistant depressed patients-one of several targets under investigation-has shown to be promising in a number of uncontrolled open label trials. However, there are remain numerous questions that need to be investigated to understand and optimize the clinical use of DBS in depression, including, for example, the relationship between the symptoms, the biological substrates/projections and the stimulation itself. In the context of precision and customized medicine, the current paper focuses on clinical and experimental research of Medial Forebrain Bundle DBS in depression or in animal models of depression, demonstrating how clinical and scientific progress can work in tandem to test the therapeutic value and investigate the mechanisms of this experimental treatment. As one of the hypotheses is that depression engenders changes in the reward and motivational networks, the review looks at how stimulation of the Medial Forebrain Bundle impacts the dopaminergic system.

  • Tractography-assisted deep brain stimulation of the superolateral branch of the Medial Forebrain Bundle (slMFB DBS) in major depression
    'Elsevier BV', 2018
    Co-Authors: Volker A Coenen, Thomas E Schlaepfer, Bastian Sajonz, Marco Reisert, Jan Bostroem, Bettina Bewernick, Horst Urbach, Carolin Jenkner, Peter C. Reinacher, Burkhard Madler
    Abstract:

    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: Surgical experience from bilateral implantation procedures in n = 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. Keywords: Deep brain stimulation, Depression, Diffusion tensor imaging, Fiber tracking, Medial Forebrain Bundle, OCD, slMFB, Stereotactic surgery, Tractograph

  • the anatomy of the human Medial Forebrain Bundle ventral tegmental area connections to reward associated subcortical and frontal lobe regions
    NeuroImage: Clinical, 2018
    Co-Authors: Volker A Coenen, Thomas E Schlaepfer, Horst Urbach, Peter C. Reinacher, Lena V Schumacher, Christoph P Kaller, Karl Egger, Marco Reisert
    Abstract:

    Abstract Introduction Despite their importance in reward, motivation, and learning there is only sparse anatomical knowledge about the human Medial Forebrain Bundle (MFB) and the connectivity of the ventral tegmental area (VTA). A thorough anatomical and microstructural description of the reward related PFC/OFC regions and their connection to the VTA - the superolateral branch of the MFB (slMFB) - is however mandatory to enable an interpretation of distinct therapeutic effects from different interventional treatment modalities in neuropsychiatric disorders (DBS, TMS etc.). This work aims at a normative description of the human MFB (and more detailed the slMFB) anatomy with respect to distant prefrontal connections and microstructural features. Methods and material Healthy subjects (n = 55; mean age ± SD, 40 ± 10 years; 32 females) underwent high resolution anatomical magnetic resonance imaging including diffusion tensor imaging. Connectivity of the VTA and the resulting slMFB were investigated on the group level using a global tractography approach. The Desikan/Killiany parceling (8 segments) of the prefrontal cortex was used to describe sub-segments of the MFB. A qualitative overlap with Brodmann areas was additionally described. Additionally, a pure visual analysis was performed comparing local and global tracking approaches for their ability to fully visualize the slMFB. Results The MFB could be robustly described both in the present sample as well as in additional control analyses in data from the human connectome project. Most VTA- connections reached the superior frontal gyrus, the middel frontal gyrus and the lateral orbitofrontal region corresponding to Brodmann areas 10, 9, 8, 11, and 11m. The projections to these regions comprised 97% (right) and 98% (left) of the total relative fiber counts of the slMFB. Discussion The anatomical description of the human MFB shows far reaching connectivity of VTA to reward-related subcortical and cortical prefrontal regions - but not to emotion-related regions on the Medial cortical surface - realized via the superolateral branch of the MFB. Local tractography approaches appear to be inferior in showing these far-reaching projections. Since these local approaches are typically used for surgical targeting of DBS procedures, the here established detailed map might - as a normative template - guide future efforts to target deep brain stimulation of the slMFB in depression and other disorders related to dysfunction of reward and reward-associated learning.

  • the Medial Forebrain Bundle as a target for deep brain stimulation for obsessive compulsive disorder
    Cns Spectrums, 2017
    Co-Authors: Volker A Coenen, Thomas E Schlaepfer, Horst Urbach, Peter C. Reinacher, Peter Goll, Ulrich Voderholzer, Ludger Tebartz Van Elst, Tobias Freyer
    Abstract:

    Deep brain stimulation (DBS) is a promising putative modality for the treatment of refractory psychiatric disorders such as major depression and obsessive-compulsive disorder (OCD). Several targets have been posited; however, a clear consensus on differential efficacy and possible modes of action remain unclear. DBS to the supero-lateral branch of the Medial Forebrain Bundle (slMFB) has recently been introduced for major depression (MD). Due to our experience with slMFB stimulation for MD, and because OCD might be related to similar dysfunctions of the reward system, treatment with slMFB DBS seams meaningful. Here we describe our first 2 cases together with a hypothetical mode of action. We describe diffusion tensor imaging (DTI) fiber tractographically (FT)-assisted implantation of the bilateral DBS systems in 2 male patients. In a selected literature overview, we discuss the possible mode of action. Both patients were successfully implanted and stimulated. The follow-up time was 12 months. One patient showed a significant response (Yale-Brown Obsessive-Compulsive Scale [YBOCS] reduction by 35%); the other patient reached remission criteria 3 months after surgery (YBOCS<14) and showed mild OCD just above the remission criterion at 12 months follow-up. While the hypermetabolism theory for OCD involves the cortico-striato-thalamo-cortical (CSTC) network, we think that there is clinical evidence that the reward system plays a crucial role. Our findings suggest an important role of this network in mechanisms of disease development and recovery. In this uncontrolled case series, continuous bilateral DBS to the slMFB led to clinically significant improvements of ratings of OCD severity. Ongoing research focuses on the role of the reward system in OCD, and its yet-underestimated role in this underlying neurobiology of the disease.

  • deep brain stimulation to the Medial Forebrain Bundle for depression long term outcomes and a novel data analysis strategy
    Brain Stimulation, 2017
    Co-Authors: Bettina Bewernick, Volker A Coenen, Sarah Kayser, Sabrina M Gippert, Christina Switala, Thomas E Schlaepfer
    Abstract:

    Abstract Background Deep brain stimulation (DBS) of the supero-lateral branch of the Medial Forebrain Bundle (slMFB) in treatment-resistant depression (TRD) is associated with acute antidepressant effects. Objective Long-term clinical effects including changes in quality of life, side effects and cognition as well as long-term data covering four years are assessed. Methods Eight TRD patients were treated with DBS bilateral to the slMFB. Primary outcome measure was a 50% reduction in Montgomery-Asberg Depression Rating Scale (MADRS) (response) and remission (MADRS Results Six of eight patients (75%) were responders at 12 months, four patients reached remission. Long-term results revealed a stable effect up to four years. Antidepressant efficacy was also reflected in the global assessment of functioning. Main side effect was strabismus at higher stimulation currents. No change in cognition was identified. AUC analysis revealed a significant reduction in depression for 7/8 patients in most months. Conclusions Long-term results of slMFB-DBS suggest acute and sustained antidepressant effect; timeline analysis may be an alternative method reflecting patient's overall gain throughout the study. Being able to induce a rapid and robust antidepressant effect even in a small, sample of TRD patients without significant psychiatric comorbidity, render the slMFB an attractive target for future studies.