Resolving dyskinesias at sustained anti-OCD efficacy by steering of DBS away from the anteromedial STN to the mesencephalic ventral tegmentum - case report.

Here we describe therapeutic results in a female patient who underwent bilateral slMFB DBS for OCD. During a 35-month long course of stimulation, she suffered from stimulation-induced dyskinesia of her right leg which we interpreted as co-stimulation of the adjacent anteromedial subthalamic nucleus (amSTN). After reprogramming to steer the stimulation away from the amSTN medial into the direction of the mesencephalic ventral tegmentum (MVT which contains the ventral tegmental area, VTA), the dyskinesias disappeared.

"The Heart Asks Pleasure First"-Conceptualizing Psychiatric Diseases as Network Dysfunctions through Insights from slMFB DBS in Depression and Obsessive-Compulsive Disorder.

More than a decade ago, deep brain stimulation (DBS) of the superolateral medial forebrain bundle (slMFB), as part of the greater MFB system, had been proposed as a putative yet experimental treatment strategy for therapy refractory depression (TRD) and later for obsessive-compulsive disorders (OCD). Antidepressant and anti-OCD efficacy have been shown in open case series and smaller trials and were independently replicated. The MFB is anato-physiologically confluent with the SEEKING system promoting euphoric drive, reward anticipation and reward; functions realized through the mesocorticolimbic dopaminergic system.

Diverging prefrontal cortex fiber connection routes to the subthalamic nucleus and the mesencephalic ventral tegmentum investigated with long range (normative) and short range (ex-vivo high resolution) 7T DTI.

Uncertainties concerning anatomy and function of cortico-subcortical projections have arisen during the recent years. A clear distinction between cortico-subthalamic (hyperdirect) and cortico-tegmental projections (superolateral medial forebrain bundle, slMFB) so far is elusive. Deep Brain Stimulation (DBS) of the slMFB (for major depression, MD and obsessive compulsive disorders, OCD) has on the one hand been interpreted as actually involving limbic (prefrontal) hyperdirect pathways.

The psychological burden of a two-stage exchange of infected total hip and knee arthroplasties.

Infection is one of the most challenging complications after total joint arthroplasties affecting up to 30,000 patients in the US per year. This study investigates the psycho-social burden induced by the two-stage intervention in infected hip or knee replacements. All patients were treated with a two-stage exchange and were assessed at three different timepoints regarding their psychological conditions.

Johann Bernhard Aloys von Gudden: The Unrecognized Role of the Psychiatrist and Neuroanatomist in Modern Stereotactic Neurosurgery.

Bernhard von Gudden was the founder of the famous school of psychiatry and neuroanatomy in Munich, Germany. Beyond his association with the mysterious death of King Ludwig II of Bavaria, not much is known about Bernhard von Gudden's work in neuroanatomy. He pioneered fiber tract mapping by studying the effects of neurodegeneration following brain lesions.

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

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.

Effects of magnetic seizure therapy on anterograde and retrograde amnesia in treatment-resistant depression.

Background: Electroconvulsive therapy (ECT) is the gold standard for treatment-resistant depression (TRD). However, cognitive side effects, mainly anterograde and retrograde amnesia, frequently occur. Magnetic seizure therapy (MST) is tested using more focal seizure induction.

Frontal white matter architecture predicts efficacy of deep brain stimulation in major depression.

Major depression is a frequent and severe disorder, with a combination of psycho- and pharmacotherapy most patients can be treated. However, ~20% of all patients suffering from major depressive disorder remain treatment resistant; a subgroup might be treated with deep brain stimulation (DBS). We present two trials of DBS to the superolateral medial forebrain bundle (slMFB DBS; FORESEE I and II).

Machine learning-aided personalized DTI tractographic planning for deep brain stimulation of the superolateral medial forebrain bundle using HAMLET.

Background: Growing interest exists for superolateral medial forebrain bundle (slMFB) deep brain stimulation (DBS) in psychiatric disorders. The surgical approach warrants tractographic rendition. Commercial stereotactic planning systems use deterministic tractography which suffers from inherent limitations, is dependent on manual interaction (ROI definition), and has to be regarded as subjective.

Treatment resistance in major depression is correlated with increased plasma levels of neurofilament light protein reflecting axonal damage.

Treatment resistant major depression is accompanied with a sizable impact on quality of life with severe consequences for social integrity, individual health and socioeconomic state. In- and outpatient care of patients with treatment resistant major depression remains very challenging for both patients and the health system. One reason is the limited knowledge on the etiology of treatment resistance in major depression resulting difficulties developing efficient treatment strategies for this group of severe depressed patients.

Superolateral medial forebrain bundle deep brain stimulation in major depression: a gateway trial.

Short- and long-term antidepressant effects of deep brain stimulation (DBS) in treatment-resistant depression (TRD) have been demonstrated for several brain targets in open-label studies. For two stimulation targets, pivotal randomized trials have been conducted; both failed a futility analysis. We assessed efficacy and safety of DBS of the supero-lateral branch of the medial forebrain bundle (slMFB) in a small Phase I clinical study with a randomized-controlled onset of stimulation in order to obtain data for the planning of a large RCT.

Deep brain stimulation: current challenges and future directions.

The clinical use of deep brain stimulation (DBS) is among the most important advances in the clinical neurosciences in the past two decades. As a surgical tool, DBS can directly measure pathological brain activity and can deliver adjustable stimulation for therapeutic effect in neurological and psychiatric disorders correlated with dysfunctional circuitry. The development of DBS has opened new opportunities to access and interrogate malfunctioning brain circuits and to test the therapeutic potential of regulating the output of these circuits in a broad range of disorders.

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

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.

The anatomy of the human medial forebrain bundle: Ventral tegmental area connections to reward-associated subcortical and frontal lobe regions.

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.).

Clinical Predictors of Response to Magnetic Seizure Therapy in Depression: A Preliminary Report.

Objectives: Magnetic seizure therapy (MST) is a novel convulsive brain stimulation method in clinical testing, which is used as an alternative for electroconvulsive therapy in patients with treatment-resistant depression (TRD). Preliminary studies have suggested that MST leads to fewer cognitive adverse effects than electroconvulsive therapy but has similar efficacy. However, the clinical predictors of response to MST have not been evaluated yet.

Deep brain stimulation of the supero-lateral branch of the medial forebrain bundle does not lead to changes in personality in patients suffering from severe depression.

Background: Reports of changes in patients' social behavior during deep brain stimulation (DBS) raised the question whether DBS induces changes in personality. This study explored if (1) DBS is associated with changes in personality in patients suffering from treatment-resistant depression (TRD), (2) how personality dimensions and depression are associated, and (3) if TRD patients' self-ratings of personality are valid.

Methods: TRD patients were assessed before DBS (n = 30), 6 months (t2, n = 21), 2 (t3, n = 17) and 5 years (t4, n = 11) after the initiation of DBS of the supero-lateral branch of the medial forebrain bundle (slMFB-DBS).

Autonomy in Depressive Patients Undergoing DBS-Treatment: Informed Consent, Freedom of Will and DBS' Potential to Restore It.

According to the World Health Organization, depression is one of the most common and most disabling psychiatric disorders, affecting at any given time approximately 325 million people worldwide. As there is strong evidence that depressive disorders are associated with a dynamic dysregulation of neural circuits involved in emotional processing, recently several attempts have been made to intervene directly in these circuits via deep brain stimulation (DBS) in patients with treatment-resistant major depressive disorder (MDD). Given the promising results of most of these studies, the rising medical interest in this new treatment correlates with a growing sensitivity to ethical questions.

Degree of Postictal Suppression Depends on Seizure Induction Time in Magnetic Seizure Therapy and Electroconvulsive Therapy.

Objectives: Anesthesia is required for both magnetic seizure therapy (MST) and electroconvulsive therapy (ECT), although it has anticonvulsant properties. In this case, bispectral index (BIS) monitoring, a specific electroencephalogram-derived monitoring, can be used to find the optimal seizure induction time during anesthesia to elicit adequate seizures. A measurement of seizure adequacy in electroencephalogram is the postictal suppression.

Deep brain stimulation to the medial forebrain bundle for depression- long-term outcomes and a novel data analysis strategy.

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.

Being open minded about neuromodulation trials: Finding success in our "failures".

As part of the efforts of a multi-disciplinary, international working group focused on ethical issues in neuromodulation for neuro-psychiatric disorders, we propose a novel; strategy for study design which iteratively applies new knowledge to on-going and future trials. Under current practice, device studies may be closed or categorized as "failures" before knowledge embedded in them can be fully mined. We propose the use of an iterative process to gain knowledge from subjects who have responded to those who have not.

Walking away from depression-motor activity increases ratings of mood and incentive drive in patients with major depression.

Reduced motor activity is associated with depression. Lewinsohn's cognitive behavioural model of depression assumes a lack of positive experience due to a reduced level of activity as a key aspect of depression. The acute relationship between motor activity and mood as well as between motor activity and incentive drive (the motivation to engage in activities) is unknown.