Search

Das bei Bewegungsstorungen etablierte Verfahren der tiefen Hirnstimulation (THS) wird auch hinsichtlich seines Nutzens zur Behandlung psychiatrischer Indikationen untersucht. Ziel dieser Arbeit ist es, einen Uberblick uber die Datenlage zur Anwendung der THS beim Tourette-Syndrom zu geben. Die Ubersicht stutzt sich dabei auf eine selektive stichwortgebundene Literaturrecherche in Pubmed unter Berucksichtigung einschlagiger Referenzen und eigener Arbeiten. Es zeigt sich, dass zur Behandlung des Tourette-Syndroms mittels THS Ergebnisse aus mehreren Studien vorliegen, die zwar nur kleine Fallzahlen umfassen, dabei aber deutliche Besserungsquoten hinsichtlich der Tic-Symptomatik aufzeigen.

Item does not contain fulltext Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological changes of neurotransmission and is observed in Alzheimer’s disease. Here we report on six patients with mild to moderate Alzheimer’s disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer’s Disease Assessment Scale—cognitive subscale as the primary outcome measure. Electroencephalography and [18F]-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated. 8 p.

Die tiefe Hirnstimulation (THS) hat die Behandlungmoglichkeiten bei M. Parkinson nachhaltig erweitert. Auch fur andere neurodegenerative Erkrankungen wie Chorea Huntington wird die THS als Therapie-Option erprobt, vordergrundig mit dem Ziel die beeintrachtigenden Bewegungsstorungen zu reduzieren. Wir berichten uber den klinischen Verlauf einer Patientin mit fortgeschrittener Chorea Huntington Erkrankung unter THS des Globus pallidus internus. Dabei liesen sich positive Auswirkungen sowohl auf motorische Symptome als auch auf Kognition und Stimmung beobachten, die im Kontext der wenigen publizierten Daten zur THS bei Chorea Huntington diskutiert werden. Die Abnahme der kognitiven Leistungsfahigkeit, die im fortgeschrittenen Stadium neurodegenerativer Erkrankungen und insbesondere bei Chorea Huntington typisch ist, impliziert ein Problem hinsichtlich der Einwilligungsfahigkeit der Patienten zur tiefen Hirnstimulation. Die damit einhergehenden ethischen und rechtlichen Aspekte werden diskutiert und diesbezugliche Losungsansatze fur kognitiv eingeschrankte Patienten im Allgemeinen diskutiert.

Background: The spinothalamocortical tract (STC) is seen as a neural tract responsible for or involved in the generation or transmission of thalamic pain. Either the thalamus itself or the posterior limb of the internal capsule (PLIC) are targets for deep brain stimulation (DBS) in patients with thalamic pain, but due to its low contrast, conventional MRI cannot visualize the STC directly. Objectives: To show the feasibility of integrating diffusion tensor imaging-based tractography into the stereotactic treatment planning for identification of an object-oriented lead trajectory that allows STC-DBS with multiple electrode contacts. Methods: Diffusion tensor imaging was performed in 4 patients with thalamic pain. The STC was modeled and integrated into the stereotactic treatment planning for DBS. DBS-lead implantation was done according to trajectory planning along the modeled STC at the level of the PLIC. Results: After implantation, electrode stimulation was possible over a length of more than 20 mm with a tractography-based trajectory along the PLIC part of the STC. After a follow-up of 12 months, pain relief of more than 40% was achieved in 3 of 4 patients with rating on a visual analogue scale. In 1 patient, stimulation failed to reach any long-lasting positive effects. Conclusions: Integrating tractography data into stereotactic planning of DBS in thalamic pain is technically feasible. It can be used to identify a lead trajectory that allows for multiple contact stimulation along the STC at the level of the PLIC. Due to long-lasting positive stimulation effect, tractography-guided stimulation of sensory fibers seems to be beneficial for thalamic pain relief.

Deep brain stimulation (DBS) has successfully advanced our treatment options for putative therapy-resistant neuropsychiatric diseases. Building on this strong foundation, more and more mental disorders in the stadium of therapy-resistance are considered as possible indications for DBS. Especially, schizophrenia with its associated severe and difficult to treat symptoms is gaining attention. This attention demands critical questions regarding the assumed mechanisms of DBS and its possible influence on the supposed pathophysiology of schizophrenia. Here, we synoptically compare current approaches and theories of DBS and discuss the feasibility of DBS in schizophrenia as well as the transferability from other psychiatric disorders successfully treated with DBS. For this we consider recent advances in animal models of schizophrenic symptoms, results regarding the influence of DBS on dopaminergic transmission as well as data concerning neural oscillation and synchronisation. In conclusion, the use of DBS for some symptoms of schizophrenia seems to be a promising approach, but the lack of a comprehensive theory of the mechanisms of DBS as well as its impact on schizophrenia might hinder the use of DBS for schizophrenia at this point in time.

Following recent advances in neuromodulation therapy for mental disorders, we treated one patient with severe alcohol addiction with deep brain stimulation (DBS) of the nucleus accumbens (NAc). Before and one year following the surgery, we assessed the effects of DBS within the NAc on the addiction as well as on psychometric scores and electrophysiological measures of cognitive control. In our patient, DBS achieved normalization of addictive behavior and craving. An electrophysiological marker of error processing (the error-related negativity) linked to anterior mid-cingulate cortex (aMCC) functioning was altered through DBS, an effect that could be reversed by periods without stimulation. Thus, this case supports the hypothesis that DBS of the NAc could have a positive effect on addiction trough a normalization of craving associated with aMCC dysfunction.

Objective To investigate the effects of unilateral deep brain stimulation (DBS) in the right nucleus accumbens in patients with obsessive-compulsive disorder (OCD). Predominantly bilateral stimulation of the anterior limb of the internal capsule was utilized. Methods The study was designed as a double-blind sham-controlled crossover study. Patients received 3 months of deep brain stimulation followed by 3 months of sham stimulation, or vice versa. Subsequently, stimulation was continued unblinded for all patients. The primary outcome measure was the severity level of OCD, measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Secondary outcome measures were depressive symptoms, anxiety, psychological symptom severity, global functioning, quality of life, and cognitive function. Results The mean Y-BOCS scores decreased significantly from 32.2 (±4.0) at baseline to 25.4 (±6.7) after 12 months ( p =0.012). Five out of ten patients showed a decrease of more than 25%, indicating at least a partial response. One patient showed a decrease in Y-BOCS severity greater than 35%. Similarly, depression, global functioning and quality of life improved within one year. In contrast, anxiety, global symptom severity and cognitive function showed no significant changes. In general, DBS was well-tolerated. Conclusions DBS of the unilateral right nucleus accumbens showed encouraging results in patients with treatment-resistant OCD. Five out of ten patients reached at least a partial response after the first year.

SummaryThe human brain is adept at anticipating upcoming events, but in a rapidly changing world, it is essential to detect and encode events that violate these expectancies. Unexpected events are more likely to be remembered than predictable events, but the underlying neural mechanisms for these effects remain unclear. We report intracranial EEG recordings from the hippocampus of epilepsy patients, and from the nucleus accumbens of depression patients. We found that unexpected stimuli enhance an early (187 ms) and a late (482 ms) hippocampal potential, and that the late potential is associated with successful memory encoding for these stimuli. Recordings from the nucleus accumbens revealed a late potential (peak at 475 ms), which increases in magnitude during unexpected items, but no subsequent memory effect and no early component. These results are consistent with the hypothesis that activity in a loop involving the hippocampus and the nucleus accumbens promotes encoding of unexpected events.

Background While most patients with depression respond to combinations of pharmacotherapy, psychotherapy, and electroconvulsive therapy (ECT), there are patients requiring other treatments. Deep brain stimulation (DBS) allows modulation of brain regions that are dysfunctional in depression. Since anhedonia is a feature of depression and there is evidence of dysfunction of the reward system, DBS to the nucleus accumbens (NAcc) might be promising. Methods Ten patients suffering from very resistant forms of depression (treatment-resistant depression [TRD]), not responding to pharmacotherapy, psychotherapy, or ECT, were implanted with bilateral DBS electrodes in the NAcc. The mean (±SD) length of the current episode was 10.8 (±7.5) years; the number of past treatment courses was 20.8 (±8.4); and the mean Hamilton Depression Rating Scale (HDRS) was 32.5 (±5.3). Results Twelve months following initiation of DBS treatment, five patients reached 50% reduction of the HDRS (responders, HDRS=15.4 [±2.8]). The number of hedonic activities increased significantly. Interestingly, ratings of anxiety (Hamilton Anxiety Scale) were reduced in the whole group but more pronounced in the responders. The [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography data revealed that NAcc-DBS decreased metabolism in the subgenual cingulate and in prefrontal regions including orbital prefrontal cortex. A volume of interest analysis comparing responders and nonresponders identified metabolic decreases in the amygdala. Conclusions We demonstrate antidepressant and antianhedonic effects of DBS to NAcc in patients suffering from TRD. In contrast to other DBS depression studies, there was also an antianxiety effect. These effects are correlated with localized metabolic changes.

The nucleus accumbens plays a key role in reinforcement-guided behaviors. Here, we report that electrophysiological oscillatory phase synchrony between the two nuclei accumbens may play a crucial role in using negative feedback to guide decision making. We recorded local field potentials from the human nucleus accumbens and the medial frontal cortex (via surface EEG) from patients who had deep brain stimulation electrodes implanted. Patients performed a reversal learning task in which they decided whether to alter their decision strategy following monetary losses. Strategy switches following losses were preceded by enhanced theta (4-8 Hz) phase synchrony between the nuclei accumbens, and a break-down of gamma (20-80 Hz)-alpha (8-12 Hz) coupling. Furthermore, the strength of the intersite phase synchrony predicted response time adjustments in the subsequent trial. These findings suggest that a neural network including the nucleus accumbens bilaterally becomes functionally connected via theta phase synchrony to signal the need to adjust behavior.

The use of intracranial recordings during the implantation of electrodes for deep brain stimulation offers the opportunity to detect the neural basics of the target structures’ cognitive functions with a high spatial and temporal resolution. Here we present the local field potentials from inside the nucleus accumbens (NAcc) of a patient suffering from OCD. We used an Eriksen-Flanker paradigm for investigating action monitoring processes related to the NAcc. A main aspect of action monitoring is the detection and correction of errors. By recording from two distinct sites during the surgery, one directly from inside the shell of the NAcc and the other 5 mm above, we were able to show a specific involvement of the NAcc in the processing of action errors. By using correlative procedures we could also show that this error-specific signal occurs first in the NAcc and then at the surface of the skull. This relationship is mainly caused by variations in the Θ band. Furthermore, during correct responses increases in the power of the β band occurred. These findings will be interpreted in terms of the reinforcement learning theory of action monitoring by Holroyd and Coles (2002).

Objective. Deep brain stimulation (DBS) increasingly attracts attention as a potential treatment of mental disorders. Beside depression and obsessive–compulsive disorders, DBS has already been shown to be beneficial for Tourette syndrome (TS). Clinical Presentation/Method. The authors report on the outcome of a patient with treatment-resistant TS who underwent bilateral DBS of the nucleus accumbens and the internal capsule. Results. Within the 10-month follow-up, a substantial reduction of tics has been observed. Yet, as a side-effect of DBS, the patient developed a transient manic-like episode when primarily stimulated by the most proximally contact in the internal capsule. Conclusions. This case supports the hypothesis that DBS of the nucleus accumbens and the internal capsule represents an effective therapeutic alternative for otherwise treatment-resistant TS. Yet, future controlled studies are needed to determine optimal stimulation parameters and to reduce negative side-effects such as transient hypomanic episodes.

Background The current notion that cortico-striato-thalamo-cortical circuits are involved in the pathophysiology of obsessive-compulsive disorder (OCD) has instigated the search for the most suitable target for deep brain stimulation (DBS). However, despite extensive research, uncertainty about the ideal target remains with many structures being underexplored. The aim of this report is to address a new target for DBS, the medial dorsal (MD) and the ventral anterior (VA) nucleus of the thalamus, which has thus far received little attention in the treatment of OCD. Methods In this retrospective trial, four patients (three female, one male) aged 31–48 years, suffering from therapy-refractory OCD underwent high-frequency DBS of the MD and VA. In two patients (de novo group) the thalamus was chosen as a primary target for DBS, whereas in two patients (rescue DBS group) lead implantation was performed in a rescue DBS attempt following unsuccessful primary stimulation. Results Continuous thalamic stimulation yielded no significant improvement in OCD symptom severity. Over the course of thalamic DBS symptoms improved in only one patient who showed “partial response” on the Yale-Brown Obsessive Compulsive (Y-BOCS) Scale. Beck Depression Inventory scores dropped by around 46% in the de novo group; anxiety symptoms improved by up to 34%. In the de novo DBS group no effect of DBS on anxiety and mood was observable. Conclusion MD/VA-DBS yielded no adequate alleviation of therapy-refractory OCD, the overall strategy in targeting MD/VA as described in this paper can thus not be recommended in DBS for OCD. The magnocellular portion of MD (MDMC), however, might prove a promising target in the treatment of mood related and anxiety disorders.

As a well and long-established approach in the treatment of selected movement disorders, deep brain stimulation (DBS) is also increasingly considered a potential treatment method in the case of mental disorders. Only recently, a number of highly promising case reports and case series have been published, in which impressive therapeutic outcomes under application of DBS in otherwise treatment-resistant psychiatric illnesses are reported. The current article aims to provide a detailed synopsis of the DBS approach and more specifically its application to mental disorders. By means of a systematic literature search, all relevant treatment studies published to date and focusing on obsessive compulsive disorder, Tourette syndrome, major depression, anxiety disorder and autism were incorporated and evaluated with respect to the scientific evidence presented.

Deep brain stimulation (DBS) to different sites allows interfering with dysfunctional network function implicated in major depression. Because a prominent clinical feature of depression is anhedonia--the inability to experience pleasure from previously pleasurable activities--and because there is clear evidence of dysfunctions of the reward system in depression, DBS to the nucleus accumbens might offer a new possibility to target depressive symptomatology in otherwise treatment-resistant depression. Three patients suffering from extremely resistant forms of depression, who did not respond to pharmacotherapy, psychotherapy, and electroconvulsive therapy, were implanted with bilateral DBS electrodes in the nucleus accumbens. Stimulation parameters were modified in a double-blind manner, and clinical ratings were assessed at each modification. Additionally, brain metabolism was assessed 1 week before and 1 week after stimulation onset. Clinical ratings improved in all three patients when the stimulator was on, and worsened in all three patients when the stimulator was turned off. Effects were observable immediately, and no side effects occurred in any of the patients. Using FDG-PET, significant changes in brain metabolism as a function of the stimulation in fronto-striatal networks were observed. No unwanted effects of DBS other than those directly related to the surgical procedure (eg pain at sites of implantation) were observed. Dysfunctions of the reward system--in which the nucleus accumbens is a key structure--are implicated in the neurobiology of major depression and might be responsible for impaired reward processing, as evidenced by the symptom of anhedonia. These preliminary findings suggest that DBS to the nucleus accumbens might be a hypothesis-guided approach for refractory major depression.

The progression of Alzheimer's disease (AD) is associated with impaired nutritional status. New methods, such as deep brain stimulation (DBS), are currently being tested to decrease the progression of AD. DBS is an approved method in the treatment of Parkinson's disease, and its suitability for the treatment of AD patients is currently under experimental investigation. To evaluate the advantages and disadvantages of this new treatment, it is important to assess potential side effects of DBS regarding the nucleus basalis of Meynert; this new treatment is thought to positively affect cognition and might counteract the deterioration of nutritional status and progressive weight loss observed in AD. This study aims to assess the nutritional status of patients with AD before receiving DBS of the nucleus basalis of Meynert and after 1 year, and to analyze potential associations between changes in cognition and nutritional status.A 1-year phase I proof-of-concept study.The Department of Psychiatry and Psychotherapy at the University of Cologne.We assessed a consecutive sample of patients with mild to moderate AD (n=6) who fulfilled the inclusion criteria and provided written informed consent.Bilateral low-frequency DBS of the nucleus basalis of Meynert.Nutritional status was assessed using a modified Mini Nutritional Assessment, bioelectrical impedance analysis, a completed 3-day food diary, and analysis of serum levels of vitamin B12 and folate.With a normal body mass index (BMI) at baseline (mean 23.75 kg/m²) and after 1 year (mean 24.59 kg/m²), all but one patient gained body weight during the period of the pilot study (mean 2.38 kg, 3.81% of body weight). This was reflected in a mainly stable or improved body composition, assessed by bioelectrical impedance analysis, in five of the six patients. Mean energy intake increased from 1534 kcal/day (min 1037, max 2370) at baseline to 1736 kcal/day (min 1010, max 2663) after 1 year, leading to the improved fulfillment of energy needs in four patients. The only nutritional factors that were associated with changes in cognition were vitamin B12 level at baseline (Spearman's rho = 0.943, p = 0.005) and changes in vitamin B12 level (Spearman's rho = -0.829, p = 0.042).Patients with AD that received DBS of the nucleus basalis of Meynert demonstrated a mainly stable nutritional status within a 1-year period. Whether DBS is causative regarding these observations must be investigated in additional studies.

Objective: To determine the surgery-related and hardware-related complications of deep-brain stimulation (DBS) at a single centre. Methods: 262 consecutive patients (472 electrodes) operated for DBS in our department from February 1996 to March 2003 were retrospectively analysed to document acute adverse events (30 days postoperatively). The data of 180 of these patients were additionally revised to assess long-term complications (352 electrodes, mean follow-up 36.3 (SD 20.8) months). Results: The frequency of minor intraoperative complications was 4.2% (11/262 patients). Transient (0.2%) or permanent (0.4%) neurological deficits, and in one case asymptomatic intracranial haemorrhage (0.2%), were registered as acute severe adverse events caused by surgery. Among minor acute complications were subcutaneous bleeding along the extension wire (1.2%) and haematoma at the pulse generator implantation site (1.2%). Skin infection caused by the implanted material was registered in 15 of 262 patients (5.7%). The infection rate during the first observation period was 1.5% (4/262 patients) and the late infection rate was 6.1% (11/180 patients). Partial or complete removal of the stimulation system was necessitated in 12 of 262 (4.6%) patients because of skin infection. During the long-term observation period, hardware-related problems were registered in 25 of 180 (13.9%) patients. Conclusions: Stereotactic implantation of electrodes for DBS, if performed with multiplanar three-dimensional imaging and advanced treatment planning software, is a safe procedure with no mortality and low morbidity. The main causes for the patients’ prolonged hospital stay and repeated surgery were wound infections and hardware-related complications.

BACKGROUND. A prospective study was conducted to assess the efficacy and side effects of linear accelerator (LINAC)-based radiosurgery (RS) performed with a reduced dose of therapeutic radiation for patients with surgically inaccessible pituitary macroadenomas. METHODS. From August 1990 through January 2004, 175 patients with pituitary macroadenomas were treated with LINAC-RS according to a prospective protocol. To minimize the risk for radiation-induced damage of the pituitary function, the therapeutic dose to be applied was limited to 20 grays. RESULTS. Among 175 patients, 142 patients who had a minimum follow-up of 12 months (mean ± standard deviation, 81.9 ± 37.2 months) were included in the current study. The local tumor control rate was 96.5%, and the tumor response rate was 32.4%. The mean time (± standard deviation) from LINAC-RS to normalization of pathologic hormone secretion was 36.2 ± 24.0 months. The probability for normalization was 34.3% at 3 years and 51.1% at 5 years. The frequency of endocrine cure (defined as the normalization of hormone secretion without specific medication intake) was 35.2% (mean ± standard deviation time to cure, 42.1 ± 25.0 months). Patients with Cushing disease had a statistically significant greater chance of achieving a cure (P = .001). Side effects of LINAC-RS were deterioration of anterior pituitary function (12.3%), radiation-induced tissue damage (2.8%), and radiation-induced neuropathy (1.4%). CONCLUSIONS. LINAC-RS using a lower therapeutic radiation dose achieved local tumor control and normalization or cure of hormone secretion comparable to the results achieved with γ-knife RS. Compared with the latter, the time to normalization or endocrine cure was delayed, most probably as a result of dose reduction. However, the lower therapeutic radiation dose did not prevent radiation-induced damage of pituitary function completely. Cancer 2006. © 2006 American Cancer Society.

We considered clinical observations in patients with obsessive-compulsive and anxiety disorders who underwent bilateral anterior capsulotomy, as well as anatomical and pathophysiological findings. Based on these considerations, we chose the shell region of the right nucleus accumbens as the target for deep-brain stimulation in a pilot series of four patients with severe obsessive-compulsive and anxiety disorders. Significant reduction in severity of symptoms has been achieved in three of the four patients treated. Clinical results, as well as a 15O-H2O-PET study performed in one patient during stimulation, speak in favor of the following hypothesis: As a central relay structure between the amygdala, basal ganglia, mesolimbic dopaminergic areas, mediodorsal thalamus, and prefrontal cortex, the nucleus accumbens seems to play a modulatory role in the flow of information from the amygdaloid complex to the latter areas. If disturbed, an imbalanced information flow from the amygdaloid complex can yield obsessive-compulsive and anxiety disorders. These can be counteracted by blocking the information flow within the shell region of the nucleus accumbens by means of deep-brain stimulation (DBS).

Synchronization of neuronal firing is a hallmark of several neurological diseases. Recently, stimulation techniques have been developed which make it possible to desynchronize oscillatory neuronal activity in a mild and effective way, without suppressing the neurons' firing. As yet, these techniques are being used to establish demand-controlled deep brain stimulation (DBS) techniques for the therapy of movement disorders like severe Parkinson's disease or essential tremor. We here present a first conceptualization suggesting that the nucleus accumbens is a promising target for the standard, that is, permanent high-frequency, DBS in patients with severe and chronic obsessive-compulsive disorder (OCD). In addition, we explain how demand-controlled DBS techniques may be applied to the therapy of OCD in those cases that are refractory to behavioral therapies and pharmacological treatment.

Parkinson’s disease (PD) is characterized by nigral degeneration of dopaminergic neurons in the pars compacta of the substantia nigra. Rather than treating only the symptomatic aspects of Parkinson’s disease, one may also consider treatments designed to retard, arrest, or even reverse this degenerative process. Such strategies could include preventive or restorative treatments instead of purely palliative treatments. A recent hypothesis states that glutamate output from the subthalamic nucleus (STN) to the substantia nigra contributes to the neurotoxic process underlying dopaminergic cell death in Parkinson’s disease. Furthermore, high-frequency stimulation (HFS) of the STN inhibits neurons resulting in the suppression of their glutamate output. Experiments in both rats and monkeys provide preliminary data supporting this hypothesis. Kainic acid (KA) lesions of the STN prevent the loss of dopaminergic neurons in the substantia nigra after intrastriatal injection of 6-hydroxydopamine (6-OHDA) in rats, and after systemic administration of MPTP in monkeys. In PD patients, the background level of their disease is evaluated in the off medication/off stimulation state (UPDRS III score), over a period of 5 years. Thirty percent of the patients are stabilized and 18% have persistent improvement of their disease-related impairment. Further experiments are needed, including controlled clinical trials utilizing functional imaging of the dopamine transporters and post-synaptic receptors.

To investigate the ability of genetically modified astrocytes to integrate into adult rat brain, two spontaneously immortalized cell lines and the allogenic nontumorigenic glioma cell line F98 were transduced with a high-capacity adenoviral vector (HC-Adv) expressing the EGFP gene from the hCMV promoter. In organotypic slice cultures the transduced astrocytes were shown to integrate into the brain tissue. Following transplantation of the transduced astrocytes into the striatum of adult rats, the transplanted cells survived at least for 6 weeks, continuously expressed the EGFP transgene, in close neighborhood with cells of the recipient tissue executing their differentiation capacity along the glial lineage. Thus, HC-Adv transduced astrocytes are promising vehicles to locally deliver therapeutic proteins for the treatment of neurodegenerative diseases.

Addiction remains one of the most serious public health problems worldwide. The successful use of deep brain stimulation (DBS) for treating movement disorders has prompted researchers to consider whether DBS might be a promising treatment modality for addiction as well. Indeed, there is emerging evidence from preliminary case reports of patients suffering from alcohol and heroin addiction, respectively, that indicates abstinence after DBS within the nucleus accumbens (NAc). These findings are further supported by translational studies showing modulation of addictive behavior patterns in animals by stimulating the NAc and other structures related to the brain’s intrinsic reward system. Explanations for the positive effect of DBS on abstinence are modulative mechanisms on the dysfunctional reward system. Moreover, we intend to expand this by giving a more general view that also includes alternative neurostimulatory techniques different from classical DBS, such as transcranial magnet stimulation (TMS) and transcranial direct current stimulation (tDCS) for evaluating their possible virtues in treating different issues of addiction.

Object. The aim of this investigation was to assess new information concerning the capacity of transplanted embryonic stem cell (ESC)-derived neuronal cells to migrate into host brain and to evaluate these cells as a possible source for cell replacement therapy in neurodegenerative disorders such as Parkinson's disease (PD).Methods. The authors investigated the ability of ESC-derived neural precursor cells to migrate and differentiate in a host striatum by using a D3-derived ESC clone that was transfected stably with a chicken β-actin cytomegalovirus enhancer—driven green fluorescent protein (GFP)-labeled construct. This procedure allowed easy monitoring of all transplanted cells because of the green fluorescent labeling of donor cells. This approach also afforded easy estimation of cell integration and simultaneous observation of the entire transplanted cell population in relation to immunocytochemically identified neuronal and glial differentiation. After selection of nestin-positive neural precursor cells in a synthetic medium, they were implanted into the striatum of male adult Wistar rats. Their integration was analyzed on morphological studies performed 3 days to 4 weeks posttransplantation.Conclusions. The investigators found that after transplantation, a subpopulation of GFP-labeled cells differentiated into various neural morphological types that were positive for the mouse-specific Thy-1 antigen, which is known be expressed on neurons, as well as being positive for the astroglial marker glial fibrillary acidic protein. Moreover, GFP-expressing cells that were negative for either of these markers remained close to the injection site, presumably representing other derivatives of the neural lineage. Together, these findings contribute to basic research regarding future transplantation strategies in neurodegenerative diseases such as PD.

The close association of neurofibromatosis type 1 (NF1) with gliomas raises the question of whether the NF1 gene may be involved in the pathogenesis of sporadic astrocytic brain tumors. However, no frequent mutations within NF1 have been described in these tumors. Recent data on a limited series of gliomas indicate that NF1 expression may even be increased, thereby questioning the role of NF1 as a tumor suppressor in astrocytomas. In the present study, we examined the expression of NF1 in a series of 96 tumors including astrocytomas, meningiomas and plexiform neurofibromas. NF1 RNA transcription levels were compared to those of the reference genes B2M, ACTB and GAPD. The expression of OMGP, which is interposed in the NF1 gene, served as an additional control. NF1 expression did not significantly diverge among different malignancy stages of astrocytomas. As expected, the plexiform neurofibromas showed only very low NF1 expression. A striking finding was the highly variable expression of those genes selected to serve as references. While B2M and ACTB exhibited comparable levels of expression within different grades of astrocytomas and meningiomas, GAPD showed an inverse pattern in these tumors. In conclusion, NF1 expression is strongly reduced in NF1-associated plexiform neurofibromas but not in astrocytic tumors. The significant differences between B2M, ACTB and GAPD transcript levels brings into question the common practice of defining gene expression as a ratio between the transcripts of interest and those of these reference genes.

Deep brain stimulation (DBS) has the unique characteristic to very precisely target brain structures being part of functional brain circuits in order to reversibly modulate their function. It is an established adjunctive treatment of advanced Parkinson's disease and has virtually replaced ablative techniques in this indication. Several cases have been published relating effectiveness in neuroleptics-induced tardive dyskinesia. It is also investigated as a potential treatment of mood disorders. We report on the case of a 62 years old female suffering from a treatment refractory major depressive episode with comorbid neuroleptic-induced tardive dyskinesia. She was implanted a deep brain stimulation treatment system bilaterally in the globus pallidus internus and stimulated for 18 months. As well the dyskinesia as also the symptoms of depression improved substantially as measured by the Hamilton Rating Scale of Depression (HRSD) score and the Burke-Fahn-Marsden-Dystonia-Rating-Scale (BFMDRS) score. Scores dropped for HRSD from 26 at baseline preoperatively to 13 after 18 months; and for BFMDRS from 27 to 17.5. This case illustrates the potential of deep brain stimulation as a technique to be investigated in the treatment of severe and disabling psychiatric and movement disorders. DBS at different intracerebral targets being actually investigated for major depression might have similar antidepressant properties because they interact with the same cortico-basal ganglia-thalamocortical network found to be dysfunctional in major depression.

N. Peters, R. Wellenreuther, B. Rollbrocker, Y. Hayashi, B. Meyer-Puttlitz, E-M. Duerr, D. Lenartz, D.J. Marsh, J. Schramm, O.D. Wiestler, R. Parsons, C. Eng & A. von Deimling (1998) Neuropathology and Applied Neurobiology24, 3–8 Analysis of the PTEN gene in human meningiomas Previous observations demonstrated that the neurofibromatosis type 2 gene (NF2) plays an important role in the pathogenesis of the transitional, fibroblastic and malignant variants of human meningiomas. No specific genes have been associated with the pathogenesis of meningothelial meningiomas and with the progression to anaplastic meningiomas. However, allelic losses on chromosomal arms 1p, 10q and 14q have been implicated in the process of malignant progression. Recently, PTEN (phosphatase and tensin homolog deleted on chromosome ten) also termed MMAC1 (mutated in multiple advanced cancers 1) or TEP1 (TGF—regulated and epithelial cell-enriched phosphatase), emerged as a candidate gene on chromosome 10q23.3. Initial studies revealed mutations of PTEN in limited series of glioblastomas, breast, kidney and prostate carcinomas mainly as cell lines. In order to evaluate the involvement of PTEN in the development of meningiomas, we have analysed the entire coding sequence of the gene in a series of 55 meningiomas (WHO grade I), 10 atypical meningiomas (WHO grade II) and 10 anaplastic meningiomas (WHO grade III). No PTEN mutations were seen in the WHO grade I meningiomas. However, one of the anaplastic meningiomas carried a somatic mutation. In addition, all tumours were examined for the presence of homozygous deletions of PTEN but these were not detected in any of the meningiomas. Our data suggest that mutations in PTEN are not involved in the formation of low grade meningiomas, but may contribute to malignant progression in a fraction of anaplastic meningiomas.

The histogenesis of oligoastrocytomas remains controversial, with some data arguing similarity of oligoastrocytomas to astrocytic tumors, and other data suggesting closer relationships with oligodendroglial neoplasms. Since the molecular genetic changes in astrocytomas differ from those of oligodendrogliomas, we characterized 120 astrocytic and oligodendroglial tumors, including 38 oligoastrocytomas, for genetic alterations that occur disproportionately between astrocytomas and oligodendrogliomas, i.e. TP53 gene mutations and allelic loss of chromosomes 1p, 17p and 19q. As previously reported, TP53 mutations were common in astrocytic gliomas, occurring in approximately half of WHO grade II and III astrocytomas, but in only 5% of WHO grades II and III oligodendrogliomas. Allelic losses of chromosomes 1p and 19q, however, were common in oligodendrogliomas (41% and 63%), but less frequent in astrocytomas (9% and 35%). Oligoastrocytomas showed TP53 mutations in 12/38 (32%) cases and allelic losses of chromosomes 1p and 19q in 52% and 70%, respectively. Most importantly, TP53 mutations and allelic losses on chromosomes 1p and 19q were inversely correlated in oligoastrocytomas (p < 0.011 and p < 0.019). These data suggest the existence of two genetic subsets of oligoastrocytomas, one genetically related to astrocytomas and the other genetically related to oligodendrogliomas. Histologically, those oligoastrocytomas with TP53 mutations were more often astrocytoma-predominant, while those with chromosome 19q loss were more often oligodendro-glioma-predominant.

Deep brain stimulation (DBS) is an established, in selected cases therapeutically effective, non-lesional treatment method delivering current rectangular pulses into dysfunctional brain structures via chronically implanted stimulation electrodes. DBS is a recognized method applied in movement disorders and is increasingly evaluated as a possible therapeutic option for psychiatric diseases such as refractory obsessive-compulsive disorders, Gilles de la Tourette syndrome, major depression and substance-related addiction. Latest research indicates that DBS may be a method for improving cognitive functions in Alzheimer’s dementia (AD). Translational data in healthy and AD animals appear to support this notion. Nevertheless, many aspects remain unclear, particularly with regard to the optimal target structure. The objective of this review is to present a systematic overview regarding published research on DBS and cognitive functioning in animal and human studies as well as to provide a systematic overview of the feasibility and efficacy of the treatment. We describe three studies investigating the effects of DBS in patients with dementia, using either the fornix or the nucleus basalis of Meynert as a target. In total, we identified 25 animal studies with 10 brain structures being targeted: fornix, nucleus basalis of Meynert, anterior caudate nucleus, dorsal striatum, anterior thalamic nucleus, midline thalamic nuclei, central thalamic nuclei, lateral hypothalamus, hippocampus (entorhinal cortex, perforant path) and amygdala. Considering the wide and diverse spectrum of targets, we add to this review a supposition about possible underlying mechanisms of operation and recommendations for further research.

Background Since its first application in 1999, the potential benefit of deep brain stimulation (DBS) in reducing symptoms of otherwise treatment-refractory Tourette syndrome (TS) has been documented in several publications. However, uncertainty regarding the ideal neural targets remains, and the eventuality of so far undocumented but possible negative long-term effects on personality fuels the debate about the ethical implications of DBS. Methods In this prospective open-label trial, eight patients (three female, five male) 19–56 years old with severe and medically intractable TS were treated with high-frequency DBS of the ventral anterior and ventrolateral motor part of the thalamus. To assess the course of TS, its clinical comorbidities, personality parameters, and self-perceived quality of life, patients underwent repeated psychiatric assessments at baseline and 6 and 12 months after DBS onset. Results Analysis indicated a strongly significant and beneficial effect of DBS on TS symptoms, trait anxiety, quality of life, and global functioning with an apparently low side-effect profile. In addition, presurgical compulsivity, anxiety, emotional dysregulation, and inhibition appeared to be significant predictors of surgery outcome. Conclusions Trading off motor effects and desirable side effects against surgery-related risks and negative implications, stimulation of the ventral anterior and ventrolateral motor part of the thalamus seems to be a valuable option when considering DBS for TS.

Addiction is one of the most challenging health problems. It is associated with enormous individual distress and tremendous socioeconomic consequences. Unfortunately, its underlying mechanisms are not fully understood, and pharmacological, psychological, or social interventions often fail to achieve long-lasting remission. Next to genetic, social, and contextual factors, a substance-induced dysfunction of the brain's reward system is considered a decisive factor for the establishment and maintenance of addiction. Due to its successful application and approval for several neurological disorders, deep brain stimulation (DBS) is known as a powerful tool for modulating dysregulated networks and has also been considered for substance addiction. Initial promising case reports of DBS in alcohol and heroin addiction in humans have recently been published. Likewise, results from animal studies mimicking different kinds of substance addiction point in a similar direction. The objective of this review is to provide an overview of the published results on DBS in addiction, and to discuss whether these preliminary results justify further research, given the novelty of this treatment approach.

Meningiomas are among the most frequent intracranial tumors. The secretory variant of meningioma is characterized by glandular differentiation, formation of intracellular lumina and pseudopsammoma bodies, expression of a distinct pattern of cytokeratins and clinically by pronounced perifocal brain edema. Here we describe whole-exome sequencing analysis of DNA from 16 secretory meningiomas and corresponding constitutional tissues. All secretory meningiomas invariably harbored a mutation in both KLF4 and TRAF7. Validation in an independent cohort of 14 secretory meningiomas by Sanger sequencing or derived cleaved amplified polymorphic sequence (dCAPS) assay detected the same pattern, with KLF4 mutations observed in a total of 30/30 and TRAF7 mutations in 29/30 of these tumors. All KLF4 mutations were identical, affected codon 409 and resulted in a lysine to glutamine exchange (K409Q). KLF4 mutations were not found in 89 non-secretory meningiomas, 267 other intracranial tumors including gliomas, glioneuronal tumors, pituitary adenomas and metastases, 59 peripheral nerve sheath tumors and 52 pancreatic tumors. TRAF7 mutations were restricted to the WD40 domains. While KLF4 mutations were exclusively seen in secretory meningiomas, TRAF7 mutations were also observed in 7/89 (8 %) of non-secretory meningiomas. KLF4 and TRAF7 mutations were mutually exclusive with NF2 mutations. In conclusion, our findings suggest an essential contribution of combined KLF4 K409Q and TRAF7 mutations in the genesis of secretory meningioma and demonstrate a role for TRAF7 alterations in other non-NF2 meningiomas.

We treated a thirteen year old boy for life-threatening self-injurious behavior (SIB) and severe Kanner’s autism with Deep Brain Stimulation (DBS) in the amygdaloid complex as well as in the supra-amygdaloid projection system. Two DBS-electrodes were placed in both structures of each hemisphere. The stimulation contacts targeted the paralaminar, the basolateral, the central amygdala as well as the supra-amygdaloid projection system. DBS was applied to each of these structures, but only stimulation of the baso-lateral part proved effective in improving SIB and core symptoms of the autism spectrum in the emotional, social and even cognitive domains over a follow up of now 24 months. These results, which have been gained for the first time in a patient, support hypotheses, according to which the amygdala may be pivotal in the pathogeneses of autism and point to the special relevance of the baso-lateral part.

Addiction is one of the most challenging health problems. It is associated with enormous individual distress and tremendous socioeconomic consequences. Unfortunately, its underlying mechanisms are not fully understood, and pharmacological, psychological, or social interventions often fail to achieve long-lasting remission. Next to genetic, social, and contextual factors, a substance-induced dysfunction of the brain's reward system is considered a decisive factor for the establishment and maintenance of addiction. Due to its successful application and approval for several neurological disorders, deep brain stimulation (DBS) is known as a powerful tool for modulating dysregulated networks and has also been considered for substance addiction. Initial promising case reports of DBS in alcohol and heroin addiction in humans have recently been published. Likewise, results from animal studies mimicking different kinds of substance addiction point in a similar direction. The objective of this review is to provide an overview of the published results on DBS in addiction, and to discuss whether these preliminary results justify further research, given the novelty of this treatment approach.

Meningiomas are among the most common human brain tumors. Occasionally patients develop multiple meningiomas. While it has been surmised that these are multiple primary meningiomas, it is possible that they represent spread of a single primary tumor. Recently, the neurofibromatosis type 2 (NF2) tumor suppressor gene has been shown to carry mutations in meningiomas. In the present study we have analyzed multiple meningiomas from two patients for point mutations in the NF2 gene by SSCP analysis and direct sequencing. We detected point mutations in the meningiomas from both patients. The first patient from which six tumors were available had a three base pair deletion in the splice donor region of exon 7. All tumors showed the identical mutation. The second patient with two independent meningiomas had a nonsense mutation in exon 8 which was the same in both tumors. Analysis of constitutional DNA revealed a wildtype DNA sequence in both cases. There was no family history of neurofibromatosis type 2 in either patient. These data provide strong evidence for a monoclonal origin of multiple meningiomas. Early subarachnoid spread is the most likely mechanism for the formation of these tumors.

Objective Deep brain stimulation (DBS) is a therapeutically effective neurosurgical method originally applied in movement disorders. Over time, the application of DBS has increasingly been considered as a therapeutic option for several neuropsychiatric disorders, including Gilles de la Tourette syndrome, obsessive compulsive disorder, major depression and addiction. Latest research suggests beneficial effects of DBS in Alzheimer dementia (AD). Because of the high prevalence and the considerable burden of the disease, we endeavored to discuss and reveal the challenges of DBS in AD. Methods Recent literature on the pathophysiology of AD, including translational data and human studies, has been studied to generate a fundamental hypothesis regarding the effects of electrical stimulation on cognition and to facilitate our ongoing pilot study regarding DBS of the nucleus basalis Meynert (NBM) in patients with AD. Results It is hypothesized that DBS in the nucleus basalis Meynert could probably improve or at least stabilize memory and cognitive functioning in patients with AD by facilitating neural oscillations and by enhancing the synthesis of nerve growth factors. Conclusions Considering the large number of patients suffering from AD, there is a great need for novel and effective treatment methods. Our research provides insights into the theoretical background of DBS in AD. Providing that our hypothesis will be validated by our ongoing pilot study, DBS could be an opportunity in the treatment of AD.

Deep brain stimulation (DBS) has successfully advanced treatment options of putative therapy-resistant neuropsychiatric diseases. Building on this strong foundation more and more mental disorders in the stadium of therapy-resistance are considered as possible indications for DBS. Especially schizophrenia with its associated severe and difficult to treat symptoms is gaining attention. This attention demands critical questions regarding the assumed mechanisms of DBS and its possible influence on the supposed pathophysiology of schizophrenia. Here we synoptically compare current approaches and theories of DBS and discuss the feasibility of DBS in schizophrenia as well as the transferability from other psychiatric disorders successfully treated with DBS. For this we consider recent advances in animal models of schizophrenic symptoms, results regarding the influence of DBS on dopaminergic transmission as well as data concerning neural oscillation and synchronization. In conclusion the use of DBS for some symptoms of schizophrenia seems to be a promising approach, but the lack of a comprehensive theory of the mechanisms of DBS as well as its impact on schizophrenia might void the use of DBS in schizophrenia at this point. Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Normalni tabulka"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

Following recent advances in neuromodulation therapy for mental disorders, we treated one patient with severe alcohol addiction with deep brain stimulation (DBS) of the nucleus accumbens (NAc). Before and one year following the surgery, we assessed the effects of DBS within the NAc on the addiction as well as on psychometric scores and electrophysiological measures of cognitive control. In our patient, DBS achieved normalization of addictive behavior and craving. An electrophysiological marker of error processing (the error-related negativity) linked to anterior mid-cingulate cortex (aMCC) functioning was altered through DBS, an effect that could be reversed by periods without stimulation. Thus, this case supports the hypothesis that DBS of the NAc could have a positive effect on addiction trough a normalization of craving associated with aMCC dysfunction.

Platinum drugs are playing an increasingly major role in cancer treatment, but systemic administration of these agents has resulted in significant toxicity. To examine the effects of cisplatin and two newer agents, iproplatin and carboplatin, we injected the agents directly into the cerebrospinal fluid of rats and found that neurotoxic reactions resulted from doses of cisplatin (10 nmol) much lower than those of iproplatin (40 nmol) or carboplatin (80 nmol). Moreover, central nervous system tissue appeared to be less adversely affected by direct exposure to carboplatin since chronic toxicity was not observed in any of the animals receiving carboplatin until a lethal dose was reached. Furthermore, only the animals receiving cisplatin showed histologic damage in their spinal cords, and ultrastructural studies confirmed that while significant abnormalities were observed in the spinal cords of rats receiving 40 nmol cisplatin, no architectural changes were detected in the spinal cords of animals receiving 240 nmol carboplatin. We conclude that platinum drugs can be delivered intrathecally to achieve a much greater concentration of active drug than can be achieved by intravenous administration and that carboplatin appears to be the most suitable platinum-based drug for use in systems delivering drugs directly to the brain and spinal cord.

In the late 1980s a team of researchers in Grenoble, led by the neurosurgeon A. L. Benabit, introduced the technique of chronic stimulation of subcortical regions of the brain to treat movement disorders (e1, e2). This procedure, known as deep brain stimulation (DBS), involves stereotactic implantation of electrodes that then continuously emit short high-frequency electrical impulses in order to modulate functional neuronal circuits (Figure 1; eSupplement 1). The tip of each electrode contains at least four poles. Postoperatively, this permits a wide range of modes of stimulation from outside the brain. Each electrode is connected via a lead to the impulse generator, which is usually implanted under the collarbone (eSupplement 2). Figure 1 Target areas for deep brain stimulation in psychiatric diseases: Th, Thalamus; STh, subthalamic nucleus; Ac, nucleus accumbens; Cg25, subgenual area of cingulum, Figure: Jurgen Stoffels, Medizin Foto Koln Supplement 1: Effect of High-Frequency Stimulation on Brain Structures The mechanisms of action of deep brain stimulation (DBS) are not yet fully understood. Reversible functional inhibition of the stimulated target structures by depolarization blockade of the neurons around the electrode, or of the voltage-dependent ion channels on the cell membrane, constitutes one explanation (e50). The inhibition of the physiological activity of stimulated cells, which persists for about 5 minutes after the end of stimulation, correlates with the almost immediate and reversible effect of DBS on Parkinson-plus symptoms and tremor, depending on the functional status of the impulse generator (on/off). Synaptically mediated neuronal inhibition by antidromic excitation of inhibitory GABAergic afferents has also been discussed (e51). A third feasible mechanism is synaptic depression by orthodromic stimulation of efferent axons and consecutive inhibition of transmission by exhaustion of the neurotransmitter pool (e52). In dystonia and in psychiatric disorders the positive effect of DBS – like that of psychopharmaceuticals when first prescribed – often kicks in only after a number of weeks. This phenomenon cannot be wholly explained by a directly inhibiting mechanism; rather, the system evidently behaves in a plastic manner. Functional adaptation via complex and long-term modulation of neuronal systems seems to enable the effect. Functional magnetic resonance imaging, positron emission tomography (PET), and animal studies show, partially and in certain modalities, an elevation of the hemodynamic response and glucose metabolism of stimulated deep brain structures and their efferent projection areas—a sign of additional excitatory mechanisms of action (e53– e55). It can be assumed that the action of DBS rests on a large number of effects and interferences, which—depending on stimulation site, stimulation parameters, and the underlying disease—vary in importance and modulate the pathophysiological processes in various ways (e56– e58). Summarized very simply, DBS influences disordered neuronal networks and circuits by altering the distribution of excitation in the area of the target structure. The aim of DBS is to modulate and ideally eliminate the pathological signal transmission. Reconfiguration of the neuronal activity has a positive impact on the patient’s disease. Supplement 2: DBS Procedure (Planning and Operation) in the Cologne Study Group The procedure for deep brain stimulation (DBS) in patients with psychiatric disorders is analogous to that in movement disorders. Shortly before surgery the patient undergoes cranial magnetic resonance imaging with various weightings and particular modalities—the so-called planning MRI. Furthermore, after application of the stereotactic frame using sedation and local anesthesia, intraoperative computed tomography (CT) is performed. On the basis of the data obtained, and after consulting stereotactic atlases, the target is selected and the electrode pathways visualized in three dimensions. Following borehole trepanation the electrodes are implanted. Quadripolar (or multipolar) electrodes are used; by selection of the actively stimulating pole, these permit postoperative adjustment and modification of the stimulation site. A previous microdischarge, routine in DBS for movement disorders and serving to check correct positioning of the electrodes, is often performed in psychiatric diseases but is not regularly described. The localization of the electrodes can be checked by postoperative X-ray or cranial CT (and under certain circumstances also MRI). MRI is often not possible after implantation of electrodes because of the potential adverse effects. The initial parameter settings are mostly decided on the basis of empirical experience. The stimulation parameters can vary as follows: amplitude of current from 1 to 6 V, pulse duration from 60 to 200 µs, and stimulation frequency from 120 to 180 Hz. Surgery is completed in a second session with the infraclavicular implantation of the impulse generator. In DBS for the treatment of movement disorders the operation is usually performed without symptom-specific medication in order to be able to tell whether the desired effects are achieved with the intraoperative test stimulation. As yet there is no consensus whether medication should be continued or discontinued for DBS of psychiatric diseases, partly because the desired effects of DBS mostly appear only after a considerable interval. If intraoperative exposure and test stimulation are planned, however, it is advisable to reduce the dosage of specific medication as much as possible or interrupt it entirely. In Parkinson’s disease and essential tremor, DBS has proved so effective that it has been licensed as a treatment option (e3). Furthermore, there have been promising case studies on DBS treatment of certain subtypes of refractory epilepsy (e4, e5), dystonia (e6, e7), and chronic cluster headache (e8, e9). The DBS technique that has been in use for more than 20 years has become well known, and despite its invasive nature is associated with only minor adverse effects. The idea of extending DBS to the treatment of psychiatric disorders is based on the following considerations: In various cases, psychiatric adverse effects (induction of depressivity and hypomanic states) were observed in DBS-treated Parkinson’s disease patients. This gave rise to the proposal to employ DBS for primary modulation of psychopathological states (e10, e11). In recent years knowledge of the mechanisms of origin of psychiatric diseases has grown, largely due to modern imaging procedures. The underlying pathophysiological processes and disordered neuronal networks have to some extent been determined and localized. It is thus now possible to identify potential stimulation sites for DBS. The lesional procedures employed in the past as a last resort in cases of refractory psychiatric disease—anterior capsulotomy, cingulotomy, limbic leukotomy, etc.—achieved positive results (e12, e13). They do not come into question, however, because of the irreversible brain damage and their severe adverse-effect profile. The DBS technique, which is much less invasive, potentially reversible, and capable of modulation, can be applied to similar anatomic structures and may enable adjustment of the profile of action in the direction of the desired effects.