DÄ internationalArchive7/2010Deep Brain Stimulation for Psychiatric Disorders

Review article

Deep Brain Stimulation for Psychiatric Disorders

Dtsch Arztebl Int 2010; 107(7): 105-13. DOI: 10.3238/arztebl.2010.0105

Kuhn, J; Gründler, T O J; Lenartz, D; Sturm, V; Klosterkötter, J; Huff, W

Background: Deep brain stimulation (DBS), an established treatment for some movement disorders, is now being used experimentally to treat psychiatric disorders as well. In a number of recently published case series, DBS yielded an impressive therapeutic benefit in patients with medically intractable psychiatric diseases.
Methods: This review of the use of DBS to treat psychiatric disorders is based on literature retrieved from a selective Pubmed search for relevant keywords, reference works on the topic, and the authors’ own research.
Results: Studies have been performed on the use of DBS to treat medically intractable obsessive-compulsive disorder, depressive disorders, and Tourette syndrome. The case numbers in the cited publications were small, yet at least some of them involved a methodologically sound investigation. Thus, in some studies, the strength of the effect was controlled with a double-blinded interval in which the stimulation was turned off. In general, the primary symptoms were found to improve markedly, by 35% to 70%, although not all patients responded to the treatment. Adverse effects of DBS were very rare in most studies and could usually be reversed by changing the stimulation parameters.
Conclusions: The results of DBS for psychiatric disorders that have been published to date are encouraging. They open up a new perspective in the treatment of otherwise intractable disorders. Nonetheless, the efficacy, mechanism of action, and adverse effects of DBS for this indication still need to be further studied in methodologically adequate trials that meet the highest ethical standard.
LNSLNS 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 gif ppt; eSupplement 1 pdf). 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 pdf).

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.

Methods
The study presented here was based on data retrieved from a search of the Pubmed database for relevant publications in the period from 1980 to January 2009. The search terms were “obsessive compulsive disorder”, “Tourette syndrome”, “depression”, “psychiatric disorder,” “mental disorder,” and “substance abuse” in combination with “deep brain stimulation” (DBS). By using various combinations of these search terms, all Pubmed-listed studies on DBS in psychiatric disease were identified and the reference lists of the relevant publications were screened.

In a further step the search results were limited to studies that explicitly reported the outcome of DBS treatment of primary psychiatric disease in at least three patients. These treatment studies are all discussed below.

Application of DBS in psychiatric disease
Obsessive-compulsive disorders
Obsessive-compulsive disorder is a relatively common psychiatric disease with a lifetime prevalence of around 2% (e14). It manifests clinically in the form of obsessive thoughts and actions with onset between childhood and early adulthood. There is high comorbidity with depression, but also with anxiety and personality disorders (e15). Pathophysiologically, patients with -obsessive-compulsive disorder are thought to have a dysequilibrium of the cortico-striato-thalamocortical conduction pathways with a resultant absence of inhibition. With regard to the neurochemistry, the current theory postulates dysregulation of the serotoninergic and dopaminergic systems. These assumptions are based on the known positive effect of the selective serotonin reuptake inhibitors (SSRI), the primarily serotoninergically aligned clomipramine, and some neuroleptics.

Apart from these pharmacological treatment approaches, high rates of success can be achieved with cognitive behavioral therapy, particularly with Exposure and Response Prevention (ERP) (e16).

While 70% to 80% of patients with obsessive-compulsive disorder respond well to cognitive behavioral therapy and pharmacotherapy, most of the remainder display a severe, chronic disease course. These patients were previously candidates for neurosurgical procedures. Among these techniques, all of which involve infliction of irreversible lesions, patients profited most from bilateral anterior capsulotomy, which had the highest success rate at over 60% (e17, e18). These data were obtained in prospective longitudinal studies, some of them over several years, but under non-controlled conditions (e13, e19).

Reports of DBS in the treatment of patients with refractory obsessive-compulsive disorder have been published continuously since 1999. Many of the publications are case reports. We identified five groups of authors who each reported more than three patients whose obsessive-compulsive disorder was treated with DBS (Table 1 gif ppt). In the groups led by Nuttin (1, 49), Abelson (2), and Mallet (3), as well as our own team in Cologne (11), the study design included a randomized double-blind on–off phase as control mechanism. In other words, in certain segments of the study neither the treating physicians nor the patients knew whether the stimulation was turned on or off (1, 2).

For stimulation in the area of the nucleus accumbens/caudate nucleus (11, e20e22) and the adjacent internal capsule (1, 410) and in the subthalamic nucleus (3), good effects were achieved despite divergent positioning of electrodes.

In all research groups at least 50% of previously refractory patients exhibited improvement within a year in terms of partial response (improvement of ≥25% on the Yale-Brown Obsessive Compulsive Scale [YBOCS]). Long-term observation showed further improvements in both the extent of symptom reduction and the proportion of patients with obsessive-compulsive disorder who benefit from stimulation. In Cologne we initially restricted ourselves to stimulation of the right nucleus accumbens (Figure 2 jpg ppt). The decision in favor of unilateral stimulation was based on the findings of preliminary studies, where the best effect was achieved by right-sided stimulation and additional left-sided stimulation produced no essential further improvement (e23). Although we attained significant amelioration of the obsessive-compulsive symptoms, we did not quite match the comparable 1-year results of the other research groups (11).

The preliminary findings of the multicenter study conducted by Mallet’s group (3) are also worthy of note. This team chose to stimulate the subthalamic nucleus, an established target for Parkinson’s disease but a new target for the treatment of obsessive-compulsive disorder. Positive results were achieved in the 3-month on–off phase, but caution is advised in view of the -unusually high rate of transient adverse effects (Box 1 gif ppt). The intense scientific activity on the subject of DBS is underlined by the recent publication of a further case study with a new target area, the inferior thalamic peduncle. Because this article was published after the end of the chosen search period, it can be mentioned only briefly here. It can be reported, however, that a significant reduction in obsessive-compulsive symptoms within a year was found in patients treated with DBS (e24).

Tourette syndrome
Tourette syndrome is characterized by the chronic but often fluctuating occurrence of vocal (throat clearing, coughing, coprolalia) and motor (blinking, grimacing, jumping) tics. The illness usually manifests at early school age, and around 40% of patients show partial resolution of symptoms or even spontaneous remission with the transition into adulthood. In view of this natural course of the illness, the decision to go ahead with an invasive procedure such as DBS must be weighed up particularly carefully in patients under the age of 21 years.

In almost all cases, Tourette syndrome is comorbid with obsessive-compulsive disorder, attention deficit hyperactivity disorder (ADHD), or depression (e25). The etiology of Tourette syndrome remains to be satisfactorily explained. It was long thought to be a psychogenic disorder, but the prevailing opinion is that Tourette syndrome has been confirmed to have a neurobiological basis. Complex interactions among vulnerability genes and environmental factors are assumed.

The fact that neuroleptics are the class of drugs most effective against tics points to the special role of the dopaminergic system. Imaging procedures have repeatedly shown abnormalities in the ventral striatum (e26). Finally, a dysfunction within specific basal ganglia neuronal circuits in the pathophysiological final pathway is considered probable, involving the thalamus and globus pallidus internus as core structures of motor loops. Based on this knowledge DBS was used in previously treated Tourette patients, with implantation of electrodes in three target areas, all of which have proved effective (Table 2 gif ppt):

- The nucleus accumbens as part of the ventral striatum
- The globus pallidus internus
- The thalamus.

In terms of numbers of patients, the greatest experience in the DBS treatment of Tourette syndrome has been assembled in the thalamus—the internal ventro-oral nucleus, centromedian nucleus, and parafascicular nucleus. In a large open prospective study involving 18 patients, the average improvement rate for tic symptoms was around 70%, as measured using the most frequently employed scale, the Yale Global Tic Severity Scale (YGTSS) (12). It should be pointed out, however, that this study was not carried out under control conditions. Recently—although outside the search period defined above—the same group published the 24-month results of 15 of the 18 patients, documenting continued amelioration of the symptoms (e27).

The first prospective double-blind study to be carried out in patients with Tourette syndrome showed statistically significant improvement in all target parameters in the 4-week blinded phase with stimulation and also after the subsequent 3-month period of open stimulation, although in the long term only two of five patients experienced significant relief (13).

The Cologne group is investigating the problem of response, alongside the absolute degree of efficacy, in various anatomical target structures in the framework of an open prospective pilot study (1416). In the eight patients enrolled to date, stimulation of the thalamic structures has proved most effective in relieving the Tourette symptoms. In most patients who underwent stimulation, amelioration of the cardinal symptom, the tics, was accompanied by amelioration of the comorbid obsessive-compulsive traits. Nevertheless, the question of the ideal target area for the DBS treatment of Tourette syndrome cannot yet be answered definitively, -because the most recent study, carried out in three patients each with four electrodes implanted—bilaterally in the thalamus and in the globus pallidus—has found that pallidal stimulation is more effective than thalamic stimulation (17).

Severe depressive disorders
Severe depressive disorders constitute the most frequent form of psychiatric illness, with a lifetime prevalence of around 15% (e28). In most cases the disease can be effectively treated with a combination of the available drugs such as antidepressants (including augmentation strategies) and psychotherapy. In approximately a tenth of cases, however, the disease becomes chronic and largely refractory (e29). These patients are candidates for non-pharmacological measures, in particular electroconvulsive therapy (ECT) or, in specialized centers, stimulation of the vagal nerve or transcranial magnetic stimulation. ECT is effective but has fundamental disadvantages, e.g., a high recurrence rate and rejection, often vehement, by the patient. DBS could, if proved efficacious, potentially open new therapeutic opportunities as an effective long-term treatment strategy with few adverse effects.

Similar to the illnesses discussed above, the knowledge that severely depressed patients can benefit from lesional neurosurgery motivated the adoption of DBS as a reversible and adaptable form of treatment. Based on the presence of neuronal dysregulation in limbic circuits and positive lesional effects, various target areas for DBS in depressive disorders have been discussed:

- Ventral striatum—nucleus accumbens
- Subgenual cingulum
- Globus pallidus internus
- Inferior thalamic peduncle
- Rostral cingulate cortex (BA24a)
- Lateral habenula.

Research articles have been published on DBS of the ventral striatum—nucleus accumbens and the subgenual cingulum (1922) (Table 3 gif ppt), but only case reports are available for the inferior thalamic peduncle and the globus pallidus internus (e30e32).

In depressive disorders the area of the cingulate gyrus below the genu of the corpus callosum displays measurable activity that regresses with antidepressant medication (20). Mayberg’s group therefore chose the subgenual cingulum as target area for DBS. In four of six patients with otherwise refractory depression DBS achieved clear relief of symptoms after 6 months. There was an average 71% reduction in score on the Hamilton Rating Scale for Depression (HAM-D). Furthermore, a drop in the previously elevated cerebral blood flow in the subgenual cingulate gyrus (22) indicated treatment success. No cognitive impairment was detected after 12 months; memory functions, sometimes negatively impacted by ECT, remained unaffected (e33). The recruitment of 14 more refractory patients confirmed the findings of the pilot study: After 6 months there was a reduction of at least 50% in the HAM-D score in 12 of the 20 participants, and seven patients fulfilled the criteria for remission (HAM-D score <7). Analogous to the first investigation, the findings were verified by positron emission tomography (PET). None of the patients exhibited cognitive impairment (21).

The nucleus accumbens constitutes a central interface between emotional, limbic, and motor neuronal circuits and is crucial in the experience of reward and hedonistic stimuli. This motivated the Cologne–Bonn group under the leadership of Sturm and Schläpfer to employ this structure as target area for DBS in depressive disorders (20). After the commencement of stimulation, all three patients spontaneously showed positive effects. Within a week the HAM-D score decreased by an average of 42%. When the stimulation was discontinued under double-blind conditions, two of the three patients deteriorated so much that the study had to be stopped. The correlation between stimulation and depression (HAM-D score) was significant (r = –0.54, p <0.01), demonstrating the efficacy of stimulation in the nucleus accumbens. All three patients responded to the treatment without severe adverse effects. Positron emission tomography (PET) illustrated the modulation of fronto-striatal networks by bilateral stimulation in the nucleus accumbens. This group recently published expanded data on the first ten patients treated in this way. Alongside a 50% reduction in HAM-D score in five patients, there was distinct anxiolysis (measured using the Hamilton Anxiety Scale) in the 1-year observation period. Because the results were published outside the search period defined above, no further detail is given here (e34).

The group led by Malone and Dougherty reported the DBS treatment of 15 depressed patients in a multicenter study. The target area, the ventral internal capsule/ventral striatum, was very similar to that chosen by Schläpfer et al. (e35). In this study, too, the symptoms decreased over the 6-month observation period: the HAM-D score went down by 42%.

Outlook
In addition to the applications discussed above, recent publications have described notable alterations in addictive behavior in patients with substance-related dependence who were subjected to DBS of the nucleus accumbens (23, 24, e36). The treated individuals apparently found it easier to remain abstinent. However, these promising findings, attributed in part to modulation of the addict’s craving, have not yet been supported by studies. Therefore, no substantiated conclusions can yet be drawn.

With regard to the anatomic target structures, ongoing studies are investigating how current and future psychiatric indications can be more clearly defined by means of further image analysis techniques, e.g., diffusion-based tractography to depict cortical and subcortical connectivity (e37, e38).

Conclusions
Although no “global power of effect” can currently be determined, the published results of the treatment of refractory psychiatric diseases with DBS can be considered promising. In the majority of cases there has been a distinct improvement in the psychiatric status of these severely ill and previously untreatable patients. The many case reports have been complemented by an increasing number of pilot studies, some of them with randomized, blinded stimulation phases.

To date, the documented adverse effects of DBS in patients with psychiatric diseases are minor, often reversible by adjustment of the treatment parameters or well tolerated by the patients. Nevertheless, there are no long-term data.

Although no definitive conclusion can be drawn, deep brain stimulation seems to provide new options for the treatment of refractory psychiatric diseases. When deciding whether to implant electrodes for DBS, international recommendations should be taken into consideration (e39) (Box 2 gif ppt), and above all the potential benefits of treatment must be weighed against the risks involved in the surgical intervention.


Acknowledgement
The authors thank Prof. Markus Ullsperger, head of the Max Planck Research Group “Cognitive Neurology” at the Max Planck Institute for Neurological Research in Cologne and Professor of Biological Psychology at Radboud University Nijmegen, for his help in planning and writing this article.

Conflict of interest statement
Doris Lenartz received financial assistance for travel to congresses from Medtronic AG.
Volker Sturm received financial support for studies and travel to congresses and payment for lectures from Medtronic AG and Advanced Neuromodulation Systems, Inc. He is also co-holder of patents on desynchronized brain stimulation and joint founder of ANM-GmbH Jülich, a company that intends to develop new stimulators.
Jens Kuhn, Theo Gründler, Joachim Klosterkötter, and Wolfgang Huff declare that no conflict of interest exists according to the guidelines of the International Committee of Medical Journal Editors.

Manuscript received on 20 May 2009, revised version accepted on 27 August 2009.

Translated from the original German by David Roseveare.

Corresponding author
Dr. med. Jens Kuhn
Klinik für Psychiatrie und Psychotherapie
Klinikum der Universität zu Köln
Kerpener Straße 62
50924 Köln, Germany
Jens.Kuhn@uk-koeln.de

@For eReferences please refer to:
www.aerzteblatt-international.de/ref0710

eSupplements 1, 2, and eTable (gif ppt) available at:
www.aerzteblatt-internaional.de/article10m0105
1.
Nuttin BJ, Gabriels LA, Cosyns PR, et al.: Long-term electrical capsular stimulation in patients with obsessive-compulsive disorder. Neurosurgery 2003; 52: 1263–72; discussion 1272–4. MEDLINE
2.
Abelson JL., Curtis G, Sagher O, et al.: Deep brain stimulation for refractory obsessive-compulsive disorder. Biol Psychiatry 2005; 57: 510–6. MEDLINE
3.
Mallet L, Polosan M, Jaafari N, et al.: Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med 2008; 359: 2121–34. MEDLINE
4.
Gabriels L, Cosyns P, Nuttin B, Demeulemeester H, Gybels J: Deep brain stimulation for treatment-refractory obsessive-compulsive disorder: psychopathological and neuropsychological outcome in three cases. Acta Psychiatrica Scandinavica 2003; 107: 275–82. MEDLINE
5.
Nuttin B, Cosyns P, Demeulemeester H, Gybels J, Meyerson B: Electrical stimulation in anterior limbs of internal capsules in patients with obsessive-compulsive disorder. Lancet 1999; 354: 1526. MEDLINE
6.
Nuttin BJ, Gabriels L, van Kuyck K, Cosyns P: Electrical stimulation of the anterior limbs of the internal capsules in patients with severe obsessive-compulsive disorder: anecdotal reports. Neurosurg Clin N Am 2003; 14: 267–74. MEDLINE
7.
van Laere K, Nuttin B, Gabriels L, et al.: Metabolic imaging of anterior capsular stimulation in refractory obsessive-compulsive disorder: A key role for the subgenual anterior cingulate and ventral striatum. J Nucl Med 2006; 47: 740–7. MEDLINE
8.
Cosyns P, Gabriels L, Nuttin B: Deep brain stimulation in treatment refractory obsessive compulsive disorder. Verh K Acad Geneeskd Belg 2003; 65: 385–99; discussion 399–400. MEDLINE
9.
Nuttin B, Gybels J, Cosyns P, Gabriels L, et al.: Deep brain stimula-tion for psychiatric disorders. Neurosurg Clin N Am 2003; 14: xv-xvi. MEDLINE
10.
Greenberg BD, Malone DA, Friehs GM, et al.: Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. Neuropsychopharmacology 2006; 31: 2384–93. MEDLINE
11.
Huff W, Lenartz D, Schormann M, et al.: Unilateral deep brain stimulation of the nucleus accumbens in patients with treatment resistant obsessive compulsive disorder – outcomes after one-year stimu-lation. CNN, in press.
12.
Servello D, Porta M, Sassi M, Brambilla A, Robertson MM.: Deep brain stimulation in 18 patients with severe Gilles de la Tourette syndrome refractory to treatment: the surgery and stimulation. J Neurol Neurosurg Psychiatr 2008; 79: 136–42. MEDLINE
13.
Maciunas RJ, Maddux BN, Riley DE, et al.: Prospective randomized double-blind trial of bilateral thalamic deep brain stimulation in adults with Tourette syndrome. J Neurosurg 2007; 107: 1004–14. MEDLINE
14.
Kuhn J, Lenartz D, Mai JK, et al.: Deep brain stimulation of the nucleus accumbens and the internal capsule in therapeutically refractory Tourette-syndrome. J Neurol 2007; 254: 963–5. MEDLINE
15.
Kuhn J, Lenartz D, Heuckmann J, Huff W, Klosterkötter J, Sturm V: Deep brain stimulation of different anatomic structures in therapeutically refractory Tourette-syndrome. Klinische Neurophysiologie 2008; 120: e81–e82.
16.
Kuhn J, Lenartz D, Huff W, et al.: Transient manic-like episode following bilateral DBS of the nucleus accumbens and the internal capsule in a patient with Tourette-syndrome. Neuromodulation 2008; 11: 128–31.
17.
Welter ML, Mallet L, Houeto JL, et al.: Internal pallidal and thalamic stimulation in patients with Tourette syndrome. Arch Neurol 2008; 65: 952–7. MEDLINE
18.
Visser-Vandewalle V, Temel Y, Boon P, et al.: Chronic bilateral thalamic stimulation: a new therapeutic approach in intractable Tourette syndrome. Report of three cases. J Neurosurg 2003; 99: 1094–100. MEDLINE
19.
Malone DA Jr, Dougherty DD, Rezai AR, et al.: Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression. Biol Psychiatry 2009; 65: 267–75. MEDLINE
20.
Schlaepfer TE, Cohen MX, Frick C, et al.: Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression. Neuropsychopharmacology 2008; 33: 368–77. MEDLINE
21.
Lozano AM, Mayberg HS, Giacobbe P, et al.: Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression. Biol Psychiatry 2008; 64: 461–7. MEDLINE
22.
Mayberg HS, Lozano AM, Voon V, et al., Deep brain stimulation for treatment-resistant depression. Neuron 2005; 45: 651–60. MEDLINE
23.
Kuhn J, Bauer R, Pohl S, et al.: Deep Brain Stimulation of the nucleus accumbens and its influence on nicotine consumption through cigarette smoking: a retrospective study. Eur Addict Res 2009; 15: 196–201. MEDLINE
24.
Kuhn J, Lenartz D, Huff W, et al.: Remission of alcohol dependency following deep brain stimulation of the nucleus accumbens: valuable therapeutic implications? J Neurol Neurosurg Psychiatry 2007; 78: 1152–3. MEDLINE
e1.
Benabid AL, Pollak P, Louveau A, Henry S, de Rougemont J: Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl Neurophysiol 1987; 50: 344–6. MEDLINE
e2.
Benabid AL, Pollak P, Gervason C, et al.: Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet 1991; 337: 403–6. MEDLINE
e3.
Benabid AL, Charbardes S, Mitrofanis J, Pollak P: Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson’s disease. Lancet Neurologie 2009; 8: 67–81. MEDLINE
e4.
Theodore W H, Fisher R: Brain stimulation for epilepsy. Acta Neurochir Suppl 2007; 97(Pt 2): 261–72. MEDLINE
e5.
Schulz-Bonhage A: Deep brain stimulation as a new treatment for epilepsy [Tiefe Hirnstimulation als neuer Therapieansatz bei Epilepsien]. Dtsch Arztebl Int 2009; 106(24): 407–12. VOLLTEXT
e6.
Kiss ZH, Doig-Beyaert K, Eliasziw M, et al.: The Canadian multicentre study of deep brain stimulation for cervical dystonia. Brain, 2007. 130(Pt 11): 2879–86. MEDLINE
e7.
Loher TJ, Capelle HH, Kaelin-Lang A, et al.: Deep brain stimula-tion for dystonia: outcome at long-term follow-up. J Neurol 2008; 255; 881–4. MEDLINE
e8.
Schoenen J, Di Clemente L, Vandenheede M, et al.: Hypothalamic stimulation in chronic cluster headache: a pilot study of efficacy and mode of action. Brain 2005; 128(Pt 4): 940–7. MEDLINE
e9.
Starr PA, Barbaro NM, Raskin NH, Ostrem JL: Chronic stimulation of the posterior hypothalamic region for cluster headache: tech-nique and 1-year results in four patients. J Neurosurg 2007; 106: 999–1005. MEDLINE
e10.
Bejjani BP, Damier P, Arnulf I, et al.: Transient acute depression induced by high-frequency deep-brain stimulation. N Engl J Med 1999; 340: 1476–80. MEDLINE
e11.
Mallet L, Mesnage V, Houeto JL, Pelissolo A, et al.: Compulsions, Parkinson’s disease, and stimulation. Lancet 2002; 360: 1302–4. MEDLINE
e12.
Temel und Visser-Vanderwalle V: Surgery in Tourette syndrome. Mov Dis 2004; 19: 3–14. MEDLINE
e13.
Jung HH, Kim CH, Chang JH, Park YG, Chung SS, Chang JW: Bilateral anterior cingulotomy for refractory obsessive-compulsive disorder: Long-term follow-up results. Stereotact Funct Neurosurg 2006; 84: 184–9. MEDLINE
e14.
Sasson Y, Zohar J, Chopra M, et al.: Epidemiology of obsessive-compulsive disorder: a world view. J Clin Psychiatry 1997; 58 (Suppl 12): 7–10. MEDLINE
e15.
Voderholzer U.: Obsessive-compulsive disorders. Fortschr Neurol Psychiatr 2005; 73: 526–42. MEDLINE
e16.
Abramowitz JS: Effectiveness of psychological and pharmacological treatments for obsessive-compulsive disorder: a quantitative review. J Consult Clin Psychol 1997; 65: 44–52. MEDLINE
e17.
Jenike MA.: Neurosurgical treatment of obsessive-compulsive disorder. Br J Psychiatry Suppl 1998; 35: 79–90. MEDLINE
e18.
Rauch SL, Dougherty DD, Cosgrove GR, et al.: Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for obsessive compulsive disorder. Biol Psychiatry 2001; 50: 659–67. MEDLINE
e19.
Dougherty DD, Baer L, Cosgrove GR, Cassem EH, et al.: Prospective long-term follow-up of 44 patients who received cingulotomy for treatment-refractory obsessive-compulsive disorder. Am J Psychiatry 2002; 159: 269–75. MEDLINE
e20.
Aouizerate B, Cuny E, Martin-Guehl C, et al.: Deep brain stimula-tion of the ventral caudate nucleus in the treatment of obsessive-compulsive disorder and major depression. Case report. J Neurosurg 2004; 101: 682–6. MEDLINE
e21.
Aouizerate B, Martin-Guehl C, Cuny E, et al.: Deep brain stimula-tion of the ventral striatum in the treatment of obsessive-compulsive disorder and major depression. Med Sci (Paris) 2005; 21: 811–3. MEDLINE
e22.
Aouizerate B, Martin-Guehl C, Cuny E, et al.: Deep brain stimula-tion for OCD and major depression. Am J Psychiatry 2005; 162: 2192. MEDLINE
e23.
Sturm V, Lenartz D, Koulousakis A, et al.: The nucleus accumbens: a target for deep brain stimulation in obsessive-compul-sive- and anxiety-disorders. J Chem Neuroanatomy 2003; 26: 293–9. MEDLINE
e24.
Jiménez-Ponce F, Velasco-Campos F, Castro-Farfán G, et al.: Preliminary study in patients with obsessive-compulsive disorder treated with electrical stimulation in the inferior thalamic peduncle. Neurosurgery 2009; 65(6 Suppl): 203–9; discussion 209. MEDLINE
e25.
Jankovic, J.: Tourette’s syndrome. N Engl J Med 2001; 345: 1184–92. MEDLINE
e26.
Albin RL, Koeppe RA, Bohnen NI, et al.: Increased ventral striatal monoaminergic innervation in Tourette syndrome. Neurology 2003; 61: 310–5. MEDLINE
e27.
Porta M, Brambilla A, Cavanna AE, Servello D, Sassi M, Rickards H, Robertson MM: Thalamic deep brain stimulation for treatment-refractory Tourette syndrome: two-year outcome. Neurology 2009; 73: 1375–80. MEDLINE
e28.
Alonso J, Lépine JP, E.M.S. Committee: Overview of key data from the European Study of the Epidemiology of Mental Disorders (ESEMeD). The Journal of clinical psychiatry 2007; 68 Suppl 2: 3–9. MEDLINE
e29.
Keller MB, Lavori PW, Mueller TI, et al.:Time to recovery, chronicity, and levels of psychopathology in major depression. A 5-year prospective follow-up of 431 subjects. Arch Gen Psychiatry 1992; 49; 809–16. MEDLINE
e30.
Kosel M, Sturm V, Frick C, et al.: Mood improvement after deep brain stimulation of the internal globus pallidus for tardive dyskinesia in a patient suffering from major depression. Journal of psychiatric research 2007; 41: 801–3. MEDLINE
e31.
Jiménez F, Velasco F, Salín-Pascual R, et al.: Neuromodulation of the inferior thalamic peduncle for major depression and obsessive compulsive disorder. Acta Neurochir Suppl 2007; 97(Pt 2): 393–8. MEDLINE
e32.
Jiménez F, Velasco F, Salin-Pascual R, et al.: A patient with a resistant major depression disorder treated with deep brain stimulation in the inferior thalamic peduncle. Neurosurgery 2005; 57: 585–93; discussion 585–93. MEDLINE
e33.
McNeely HE, Mayberg HS, Lozano AM, Kennedy SH: Neuropsychological impact of Cg25 deep brain stimulation for treatment-resistant depression: preliminary results over 12 months. J Nerv Ment Dis 2008; 196: 405–10. MEDLINE
e34.
Bewernick BH, Hurlemann R, Matusch A, et al.: Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression. Biol Psychiatry 2009; 67: 110–6. MEDLINE
e35.
Schlaepfer TE, Lieb K: Deep brain stimulation for treatment of refractory depression. Lancet 2005; 366: 1420–2. MEDLINE
e36.
Bauer R, Pohl S, Klosterkötter J, Kuhn J: Deep brain stimulation in the context of addiction—a literature-based systematic evaluation. Fortschr Neurol Psychiatr 2008; 76: 396–401. MEDLINE
e37.
Gutman DA, Holtzheimer PE, Behrens TE, Johansen-Berg H, Mayberg HS: A Tractography analysis of two deep brain stimulation white matter targets for depression. Biol Psychiatry 2009; 56: 276–82. MEDLINE
e38.
Johansen-Berg H, Gutman DA, Behrens TE, et al.: Anatomical connectivity of the subgenual cingulate region targeted with deep brain stimulation for treatment-resistant depression. Cereb Cortex 2008; 18: 1374–83. MEDLINE
e39.
Kuhn J, Gaebel W, Klosterkoetter J, Woopen C: Deep brain stimulation as a new therapeutic approach in therapy-resistant mental disorders: Ethical aspects of investigational treatment. Eur Arch Psychiatry Clin Neurosci 2009; 259 Suppl. 2: S135–41. MEDLINE
e40.
Mink JW, Walkup J, Frey KA: Patient selection and assessment recommendations for deep brain stimulation in Tourette syn-drome. Mov Disord 2006; 21: 1831–8. MEDLINE
e41.
The Deep-Brain Stimulation for Parkinson’s Disease Study Group: Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson’s disease. N Engl J Med 2001; 345: 956–63. MEDLINE
e42.
Krack P, Batir A, Blercom N van, et al.: Five-year follow-up of bi-lateral stimulation of the subthalamic nucleus in advanced parkinson’s disease. N Engl J Med 2003; 349: 1925–34. MEDLINE
e43.
Oh MY, Abosch A, Kim SH, Lang AE, Lozano AM: Long-term hardware-related complications of deep brain stimulation. Neurosurgery 2002; 50: 1268–74. MEDLINE
e44.
Schüpbach WM, Maltête D, Houeto JL, et al.: Neurosurgery at an earlier stage of Parkinson disease: a randomized, controlled trial. Neurology 2007; 68: 267–71. MEDLINE
e45.
Doshi PK, Chhaya N, Bhatt MH: Depression leading to attempted suicide after bilateral subthalamic nucleus stimulation for Parkinson’s disease. Mov Disord 2002; 17: 1084–5. MEDLINE
e46.
Kulisevsky J, Berthier ML, Gironell A, Pascual−Sedano B, Molet J, Pares P: Mania following deep brain stimulation for Parkinson’s disease. Neurology 2002; 59: 1421–4. MEDLINE
e47.
Appleby BS, Duggan PS, Regenberg A, Rabins PV: Psychiatric and neuropsychiatric adverse events associated with deep brain stimulation: A meta-analysis of ten years’ experience. Mov Disord 2007; 15: 1722–8. MEDLINE
e48.
Voon V, Krack P, Lang AE, et al.: A multicentre study on suicide outcomes following subthalamic stimulation for Parkinson’s disease. Brain 2008; 131(Pt 10): 2720–8. MEDLINE
e49.
Woopen C.: Ethische Fragen im Zusammenhang mit tiefer Hirnstimulation. Neuro Aktuell 2009; 23(184): 25–8.
e50.
Beurrier C, Bioulac B, Audin J, Hammond C: High-frequency stim-ulation produces a transient blockade of voltage-gated currents in subthalamic neurons. J Neurophysiol 2001; 85: 1351–6. MEDLINE
e51.
Dostrovsky JO, Levy R, Wu JP, Hutchison WD, Tasker RR, Lozano AM: Microstimulation-induced inhibition of neuronal firing in human globus pallidus. J Neurophysiol 2000; 84: 570–4. MEDLINE
e52.
Zucker RS, Regehr WG: Short-term synaptic plasticity. Annu Rev Physiol 2002; 64: 355–405 MEDLINE
e53.
McCracken CB, Grace AA: Nucleus accumbens deep brain stimulation produces region-specific alterations in local field potential oscillations and evoked responses in vivo. J Neurosci 2009; 29: 5354–63. MEDLINE
e54.
Jech R, Urgosik D, Tintera J, et al.: Functional magnetic reso-nance imaging during deep brain stimulation: A pilot study in four patients with Parkinson’s disease. Movement Disorders 2001; 16: 1126–32. MEDLINE
e55.
Haslinger B, Boecker H, Buchel C, et al.: Differential modulation of subcortical target and cortex during deep brain stimulation. Neuroscience 2003; 18: 517–24. MEDLINE
e56.
Perlmutter JS, Mink JW: Deep brain stimulation. Ann Rev of Neuroscience 2006; 29: 229–57. MEDLINE
e57.
McIntyre CC, Grill WM: Extracellular stimulation of central neurons: influence of stimulus waveform and frequency on neuronal output. J Neurophysiol 2002; 88: 1592–604. MEDLINE
e58.
Vitek J: Mechanisms of deep brain stimulation: Excitation or inhibition. Movement Disorders 2002; 17: 69–72. MEDLINE
Klinik für Psychiatrie und Psychotherapie, Klinikum der Universität zu Köln: Dr. med. Kuhn, Prof. Dr. med. Klosterkötter, Dr. med. Huff
Klinik für Stereotaxie und funktionelle Neurochirurgie, Klinikum der Universität zu Köln: Dr. med. Lenartz, Prof. Dr. med. Sturm
Max-Planck-Institut für neurologische Forschung, Köln: Dipl.-Psych. Gründler
Universität Trier: Dipl.-Psych. Gründler
* The authors Kuhn and Gründler have equally contributed to the manuscript.
1. Nuttin BJ, Gabriels LA, Cosyns PR, et al.: Long-term electrical capsular stimulation in patients with obsessive-compulsive disorder. Neurosurgery 2003; 52: 1263–72; discussion 1272–4. MEDLINE
2. Abelson JL., Curtis G, Sagher O, et al.: Deep brain stimulation for refractory obsessive-compulsive disorder. Biol Psychiatry 2005; 57: 510–6. MEDLINE
3. Mallet L, Polosan M, Jaafari N, et al.: Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med 2008; 359: 2121–34. MEDLINE
4. Gabriels L, Cosyns P, Nuttin B, Demeulemeester H, Gybels J: Deep brain stimulation for treatment-refractory obsessive-compulsive disorder: psychopathological and neuropsychological outcome in three cases. Acta Psychiatrica Scandinavica 2003; 107: 275–82. MEDLINE
5. Nuttin B, Cosyns P, Demeulemeester H, Gybels J, Meyerson B: Electrical stimulation in anterior limbs of internal capsules in patients with obsessive-compulsive disorder. Lancet 1999; 354: 1526. MEDLINE
6. Nuttin BJ, Gabriels L, van Kuyck K, Cosyns P: Electrical stimulation of the anterior limbs of the internal capsules in patients with severe obsessive-compulsive disorder: anecdotal reports. Neurosurg Clin N Am 2003; 14: 267–74. MEDLINE
7. van Laere K, Nuttin B, Gabriels L, et al.: Metabolic imaging of anterior capsular stimulation in refractory obsessive-compulsive disorder: A key role for the subgenual anterior cingulate and ventral striatum. J Nucl Med 2006; 47: 740–7. MEDLINE
8. Cosyns P, Gabriels L, Nuttin B: Deep brain stimulation in treatment refractory obsessive compulsive disorder. Verh K Acad Geneeskd Belg 2003; 65: 385–99; discussion 399–400. MEDLINE
9. Nuttin B, Gybels J, Cosyns P, Gabriels L, et al.: Deep brain stimula-tion for psychiatric disorders. Neurosurg Clin N Am 2003; 14: xv-xvi. MEDLINE
10. Greenberg BD, Malone DA, Friehs GM, et al.: Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. Neuropsychopharmacology 2006; 31: 2384–93. MEDLINE
11. Huff W, Lenartz D, Schormann M, et al.: Unilateral deep brain stimulation of the nucleus accumbens in patients with treatment resistant obsessive compulsive disorder – outcomes after one-year stimu-lation. CNN, in press.
12. Servello D, Porta M, Sassi M, Brambilla A, Robertson MM.: Deep brain stimulation in 18 patients with severe Gilles de la Tourette syndrome refractory to treatment: the surgery and stimulation. J Neurol Neurosurg Psychiatr 2008; 79: 136–42. MEDLINE
13. Maciunas RJ, Maddux BN, Riley DE, et al.: Prospective randomized double-blind trial of bilateral thalamic deep brain stimulation in adults with Tourette syndrome. J Neurosurg 2007; 107: 1004–14. MEDLINE
14. Kuhn J, Lenartz D, Mai JK, et al.: Deep brain stimulation of the nucleus accumbens and the internal capsule in therapeutically refractory Tourette-syndrome. J Neurol 2007; 254: 963–5. MEDLINE
15. Kuhn J, Lenartz D, Heuckmann J, Huff W, Klosterkötter J, Sturm V: Deep brain stimulation of different anatomic structures in therapeutically refractory Tourette-syndrome. Klinische Neurophysiologie 2008; 120: e81–e82.
16. Kuhn J, Lenartz D, Huff W, et al.: Transient manic-like episode following bilateral DBS of the nucleus accumbens and the internal capsule in a patient with Tourette-syndrome. Neuromodulation 2008; 11: 128–31.
17. Welter ML, Mallet L, Houeto JL, et al.: Internal pallidal and thalamic stimulation in patients with Tourette syndrome. Arch Neurol 2008; 65: 952–7. MEDLINE
18. Visser-Vandewalle V, Temel Y, Boon P, et al.: Chronic bilateral thalamic stimulation: a new therapeutic approach in intractable Tourette syndrome. Report of three cases. J Neurosurg 2003; 99: 1094–100. MEDLINE
19. Malone DA Jr, Dougherty DD, Rezai AR, et al.: Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression. Biol Psychiatry 2009; 65: 267–75. MEDLINE
20. Schlaepfer TE, Cohen MX, Frick C, et al.: Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression. Neuropsychopharmacology 2008; 33: 368–77. MEDLINE
21. Lozano AM, Mayberg HS, Giacobbe P, et al.: Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression. Biol Psychiatry 2008; 64: 461–7. MEDLINE
22. Mayberg HS, Lozano AM, Voon V, et al., Deep brain stimulation for treatment-resistant depression. Neuron 2005; 45: 651–60. MEDLINE
23. Kuhn J, Bauer R, Pohl S, et al.: Deep Brain Stimulation of the nucleus accumbens and its influence on nicotine consumption through cigarette smoking: a retrospective study. Eur Addict Res 2009; 15: 196–201. MEDLINE
24. Kuhn J, Lenartz D, Huff W, et al.: Remission of alcohol dependency following deep brain stimulation of the nucleus accumbens: valuable therapeutic implications? J Neurol Neurosurg Psychiatry 2007; 78: 1152–3. MEDLINE
e1. Benabid AL, Pollak P, Louveau A, Henry S, de Rougemont J: Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl Neurophysiol 1987; 50: 344–6. MEDLINE
e2. Benabid AL, Pollak P, Gervason C, et al.: Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet 1991; 337: 403–6. MEDLINE
e3. Benabid AL, Charbardes S, Mitrofanis J, Pollak P: Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson’s disease. Lancet Neurologie 2009; 8: 67–81. MEDLINE
e4. Theodore W H, Fisher R: Brain stimulation for epilepsy. Acta Neurochir Suppl 2007; 97(Pt 2): 261–72. MEDLINE
e5. Schulz-Bonhage A: Deep brain stimulation as a new treatment for epilepsy [Tiefe Hirnstimulation als neuer Therapieansatz bei Epilepsien]. Dtsch Arztebl Int 2009; 106(24): 407–12. VOLLTEXT
e6. Kiss ZH, Doig-Beyaert K, Eliasziw M, et al.: The Canadian multicentre study of deep brain stimulation for cervical dystonia. Brain, 2007. 130(Pt 11): 2879–86. MEDLINE
e7. Loher TJ, Capelle HH, Kaelin-Lang A, et al.: Deep brain stimula-tion for dystonia: outcome at long-term follow-up. J Neurol 2008; 255; 881–4. MEDLINE
e8. Schoenen J, Di Clemente L, Vandenheede M, et al.: Hypothalamic stimulation in chronic cluster headache: a pilot study of efficacy and mode of action. Brain 2005; 128(Pt 4): 940–7. MEDLINE
e9. Starr PA, Barbaro NM, Raskin NH, Ostrem JL: Chronic stimulation of the posterior hypothalamic region for cluster headache: tech-nique and 1-year results in four patients. J Neurosurg 2007; 106: 999–1005. MEDLINE
e10. Bejjani BP, Damier P, Arnulf I, et al.: Transient acute depression induced by high-frequency deep-brain stimulation. N Engl J Med 1999; 340: 1476–80. MEDLINE
e11. Mallet L, Mesnage V, Houeto JL, Pelissolo A, et al.: Compulsions, Parkinson’s disease, and stimulation. Lancet 2002; 360: 1302–4. MEDLINE
e12. Temel und Visser-Vanderwalle V: Surgery in Tourette syndrome. Mov Dis 2004; 19: 3–14. MEDLINE
e13. Jung HH, Kim CH, Chang JH, Park YG, Chung SS, Chang JW: Bilateral anterior cingulotomy for refractory obsessive-compulsive disorder: Long-term follow-up results. Stereotact Funct Neurosurg 2006; 84: 184–9. MEDLINE
e14. Sasson Y, Zohar J, Chopra M, et al.: Epidemiology of obsessive-compulsive disorder: a world view. J Clin Psychiatry 1997; 58 (Suppl 12): 7–10. MEDLINE
e15. Voderholzer U.: Obsessive-compulsive disorders. Fortschr Neurol Psychiatr 2005; 73: 526–42. MEDLINE
e16. Abramowitz JS: Effectiveness of psychological and pharmacological treatments for obsessive-compulsive disorder: a quantitative review. J Consult Clin Psychol 1997; 65: 44–52. MEDLINE
e17. Jenike MA.: Neurosurgical treatment of obsessive-compulsive disorder. Br J Psychiatry Suppl 1998; 35: 79–90. MEDLINE
e18. Rauch SL, Dougherty DD, Cosgrove GR, et al.: Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for obsessive compulsive disorder. Biol Psychiatry 2001; 50: 659–67. MEDLINE
e19. Dougherty DD, Baer L, Cosgrove GR, Cassem EH, et al.: Prospective long-term follow-up of 44 patients who received cingulotomy for treatment-refractory obsessive-compulsive disorder. Am J Psychiatry 2002; 159: 269–75. MEDLINE
e20. Aouizerate B, Cuny E, Martin-Guehl C, et al.: Deep brain stimula-tion of the ventral caudate nucleus in the treatment of obsessive-compulsive disorder and major depression. Case report. J Neurosurg 2004; 101: 682–6. MEDLINE
e21. Aouizerate B, Martin-Guehl C, Cuny E, et al.: Deep brain stimula-tion of the ventral striatum in the treatment of obsessive-compulsive disorder and major depression. Med Sci (Paris) 2005; 21: 811–3. MEDLINE
e22. Aouizerate B, Martin-Guehl C, Cuny E, et al.: Deep brain stimula-tion for OCD and major depression. Am J Psychiatry 2005; 162: 2192. MEDLINE
e23. Sturm V, Lenartz D, Koulousakis A, et al.: The nucleus accumbens: a target for deep brain stimulation in obsessive-compul-sive- and anxiety-disorders. J Chem Neuroanatomy 2003; 26: 293–9. MEDLINE
e24. Jiménez-Ponce F, Velasco-Campos F, Castro-Farfán G, et al.: Preliminary study in patients with obsessive-compulsive disorder treated with electrical stimulation in the inferior thalamic peduncle. Neurosurgery 2009; 65(6 Suppl): 203–9; discussion 209. MEDLINE
e25. Jankovic, J.: Tourette’s syndrome. N Engl J Med 2001; 345: 1184–92. MEDLINE
e26. Albin RL, Koeppe RA, Bohnen NI, et al.: Increased ventral striatal monoaminergic innervation in Tourette syndrome. Neurology 2003; 61: 310–5. MEDLINE
e27. Porta M, Brambilla A, Cavanna AE, Servello D, Sassi M, Rickards H, Robertson MM: Thalamic deep brain stimulation for treatment-refractory Tourette syndrome: two-year outcome. Neurology 2009; 73: 1375–80. MEDLINE
e28. Alonso J, Lépine JP, E.M.S. Committee: Overview of key data from the European Study of the Epidemiology of Mental Disorders (ESEMeD). The Journal of clinical psychiatry 2007; 68 Suppl 2: 3–9. MEDLINE
e29. Keller MB, Lavori PW, Mueller TI, et al.:Time to recovery, chronicity, and levels of psychopathology in major depression. A 5-year prospective follow-up of 431 subjects. Arch Gen Psychiatry 1992; 49; 809–16. MEDLINE
e30. Kosel M, Sturm V, Frick C, et al.: Mood improvement after deep brain stimulation of the internal globus pallidus for tardive dyskinesia in a patient suffering from major depression. Journal of psychiatric research 2007; 41: 801–3. MEDLINE
e31. Jiménez F, Velasco F, Salín-Pascual R, et al.: Neuromodulation of the inferior thalamic peduncle for major depression and obsessive compulsive disorder. Acta Neurochir Suppl 2007; 97(Pt 2): 393–8. MEDLINE
e32. Jiménez F, Velasco F, Salin-Pascual R, et al.: A patient with a resistant major depression disorder treated with deep brain stimulation in the inferior thalamic peduncle. Neurosurgery 2005; 57: 585–93; discussion 585–93. MEDLINE
e33. McNeely HE, Mayberg HS, Lozano AM, Kennedy SH: Neuropsychological impact of Cg25 deep brain stimulation for treatment-resistant depression: preliminary results over 12 months. J Nerv Ment Dis 2008; 196: 405–10. MEDLINE
e34. Bewernick BH, Hurlemann R, Matusch A, et al.: Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression. Biol Psychiatry 2009; 67: 110–6. MEDLINE
e35. Schlaepfer TE, Lieb K: Deep brain stimulation for treatment of refractory depression. Lancet 2005; 366: 1420–2. MEDLINE
e36. Bauer R, Pohl S, Klosterkötter J, Kuhn J: Deep brain stimulation in the context of addiction—a literature-based systematic evaluation. Fortschr Neurol Psychiatr 2008; 76: 396–401. MEDLINE
e37. Gutman DA, Holtzheimer PE, Behrens TE, Johansen-Berg H, Mayberg HS: A Tractography analysis of two deep brain stimulation white matter targets for depression. Biol Psychiatry 2009; 56: 276–82. MEDLINE
e38. Johansen-Berg H, Gutman DA, Behrens TE, et al.: Anatomical connectivity of the subgenual cingulate region targeted with deep brain stimulation for treatment-resistant depression. Cereb Cortex 2008; 18: 1374–83. MEDLINE
e39. Kuhn J, Gaebel W, Klosterkoetter J, Woopen C: Deep brain stimulation as a new therapeutic approach in therapy-resistant mental disorders: Ethical aspects of investigational treatment. Eur Arch Psychiatry Clin Neurosci 2009; 259 Suppl. 2: S135–41. MEDLINE
e40. Mink JW, Walkup J, Frey KA: Patient selection and assessment recommendations for deep brain stimulation in Tourette syn-drome. Mov Disord 2006; 21: 1831–8. MEDLINE
e41. The Deep-Brain Stimulation for Parkinson’s Disease Study Group: Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson’s disease. N Engl J Med 2001; 345: 956–63. MEDLINE
e42. Krack P, Batir A, Blercom N van, et al.: Five-year follow-up of bi-lateral stimulation of the subthalamic nucleus in advanced parkinson’s disease. N Engl J Med 2003; 349: 1925–34. MEDLINE
e43. Oh MY, Abosch A, Kim SH, Lang AE, Lozano AM: Long-term hardware-related complications of deep brain stimulation. Neurosurgery 2002; 50: 1268–74. MEDLINE
e44. Schüpbach WM, Maltête D, Houeto JL, et al.: Neurosurgery at an earlier stage of Parkinson disease: a randomized, controlled trial. Neurology 2007; 68: 267–71. MEDLINE
e45. Doshi PK, Chhaya N, Bhatt MH: Depression leading to attempted suicide after bilateral subthalamic nucleus stimulation for Parkinson’s disease. Mov Disord 2002; 17: 1084–5. MEDLINE
e46. Kulisevsky J, Berthier ML, Gironell A, Pascual−Sedano B, Molet J, Pares P: Mania following deep brain stimulation for Parkinson’s disease. Neurology 2002; 59: 1421–4. MEDLINE
e47. Appleby BS, Duggan PS, Regenberg A, Rabins PV: Psychiatric and neuropsychiatric adverse events associated with deep brain stimulation: A meta-analysis of ten years’ experience. Mov Disord 2007; 15: 1722–8. MEDLINE
e48. Voon V, Krack P, Lang AE, et al.: A multicentre study on suicide outcomes following subthalamic stimulation for Parkinson’s disease. Brain 2008; 131(Pt 10): 2720–8. MEDLINE
e49. Woopen C.: Ethische Fragen im Zusammenhang mit tiefer Hirnstimulation. Neuro Aktuell 2009; 23(184): 25–8.
e50. Beurrier C, Bioulac B, Audin J, Hammond C: High-frequency stim-ulation produces a transient blockade of voltage-gated currents in subthalamic neurons. J Neurophysiol 2001; 85: 1351–6. MEDLINE
e51. Dostrovsky JO, Levy R, Wu JP, Hutchison WD, Tasker RR, Lozano AM: Microstimulation-induced inhibition of neuronal firing in human globus pallidus. J Neurophysiol 2000; 84: 570–4. MEDLINE
e52. Zucker RS, Regehr WG: Short-term synaptic plasticity. Annu Rev Physiol 2002; 64: 355–405 MEDLINE
e53. McCracken CB, Grace AA: Nucleus accumbens deep brain stimulation produces region-specific alterations in local field potential oscillations and evoked responses in vivo. J Neurosci 2009; 29: 5354–63. MEDLINE
e54. Jech R, Urgosik D, Tintera J, et al.: Functional magnetic reso-nance imaging during deep brain stimulation: A pilot study in four patients with Parkinson’s disease. Movement Disorders 2001; 16: 1126–32. MEDLINE
e55. Haslinger B, Boecker H, Buchel C, et al.: Differential modulation of subcortical target and cortex during deep brain stimulation. Neuroscience 2003; 18: 517–24. MEDLINE
e56. Perlmutter JS, Mink JW: Deep brain stimulation. Ann Rev of Neuroscience 2006; 29: 229–57. MEDLINE
e57. McIntyre CC, Grill WM: Extracellular stimulation of central neurons: influence of stimulus waveform and frequency on neuronal output. J Neurophysiol 2002; 88: 1592–604. MEDLINE
e58. Vitek J: Mechanisms of deep brain stimulation: Excitation or inhibition. Movement Disorders 2002; 17: 69–72. MEDLINE