DEEP BRAIN STIMULATION
Ethical brain stimulation – neuroethics of deep brain
stimulation in research and clinical practice
Jens Clausen
University of Tu¨bingen, Institute for Ethics and History in Medicine, Gartenstr. 47, 72074 Tu¨bingen, Germany
Keywords: DBS, depression, enhancement, ethics, Parkinson’s disease, psychosurgery
Abstract
Deep brain stimulation (DBS) is a clinically established procedure for treating severe motor symptoms in patients suffering from end-
stage Parkinson’s disease, dystonia and essential tremor. Currently, it is tested for further indications including psychiatric disorders
like major depression and a variety of other diseases. However, ethical issues of DBS demand continuing discussion. Analysing
neuroethical and clinical literature, five major topics concerning the ethics of DBS in clinical practice were identified: thorough
examination and weighing of risks and benefits; selecting patients fairly; protecting the health of children in paediatric DBS; special
issues concerning patients’ autonomy; and the normative impact of quality of life measurements. In exploring DBS for further
applications, additionally, issues of research ethics have to be considered. Of special importance in this context are questions such
as what additional value is generated by the research, how to realise scientific validity, which patients should be included, and how to
achieve an acceptable risk–benefit ratio. Patients’ benefit is central for ethical evaluation. This criterion can outweigh very serious
side-effects, and can make DBS appropriate even in paediatrics. Because standard test procedures evade central aspects of
patients’ benefits, measuring quality of life should be supplemented by open in-depth interviews to provide a more adequate picture of
patients’ post-surgical situation. To examine its entire therapeutic potential, further research in DBS is needed. Studies should be
based on solid scientific hypotheses and proceed cautiously to benefit severely suffering patients without putting them to undue risks.
Introduction
Deep brain stimulation (DBS) is the most frequently applied method
of electrical brain stimulation. It achieves impressive therapeutic
effects in treating severe motor symptoms like tremors, rigor and
bradykinesia in patients suffering from advanced idiopathic Parkin-
son’s disease (PD), dystonia and essential tremor. Therefore, DBS is
currently a promising therapeutic alternative if even optimal medical
treatment with dopamine agonists and levodopa no longer achieves
sufficient therapeutic effects and side-effects become too severe. For
DBS, special electrodes each with four contacts are bilaterally
implanted into areas deep inside the brain, such as the globus pallidus
internus or the subthalamic nucleus (STN). The electrodes are then
connected to a pulse generator, which is usually placed subcutane-
ously in the chest area. Once high-frequency stimulation commences,
motor symptoms usually improve within moments and allow for a
significant reduction of medication (Krause et al., 2001). Compared
with ablative procedures, which have been so far the method of choice
at this stage of the disease, advantages of DBS include: it is less
invasive; reversible to a very high degree; and can be adjusted by
varying the stimulation parameters depending on the circumstances
(Grill, 2005).
The impressive achievements in symptom control for PD (Deuschl
et al., 2006; Weaver et al., 2009) and the observed side-effects (Kuhn
et al., 2010) have now led to attempts to expand the spectrum of
indication for DBS. The expansion in assay of DBS targets the
treatment of patients with PD in the earlier stages of the disease
(Schu¨pbach et al., 2007) and the stimulation of other nuclei such as
the pedunculopontine nucleus (Pereira et al., 2008; Weinberger et al.,
2008). Furthermore, the use of DBS is now being explored for entirely
different diseases, for example psychiatric disorders (Greenberg et al.,
2008), such as severe depression (Mayberg et al., 2005; Schlaepfer
et al., 2007), obsessive-compulsive disorders (Nuttin et al., 1999;
Sturm et al., 2003; Mallet et al., 2008; Plewnia et al., 2008;
Greenberg et al., 2010), as well as forms of cluster headaches (Leone
et al., 2008), epilepsy (Kahane et al., 2003; Hamani et al., 2005a) and
disorders of consciousness like the minimal conscious state (Yamam-
oto et al., 2005; Schiff et al., 2007).
Brain-implantable devices like deep brain stimulators seem to have
a promising future. However, they raise several ethical questions that
need continuing discussion (Clausen, 2009). This article gives an
overview of the current debate on the ethical aspects of DBS. Previous
contributions approached the issue of the ethical implications of DBS
either with a focus on the already established treatment of motor
symptoms, especially in PD (Kubu & Ford, 2007; Farris et al., 2008;
Bell et al., 2009; Glannon, 2009), or they concentrate on particular
questions that are associated with the experimental exploration (Fins,
Correspondence: Dr J. Clausen, as above.
E-mail: jens.clausen@uni-tuebingen.de
Received 21 April 2010, revised 21 July 2010, accepted 22 July 2010
European Journal of Neuroscience, Vol. 32, pp. 1152–1162, 2010 doi:10.1111/j.1460-9568.2010.07421.x
ª 2010 The Author. European Journal of Neuroscience ª 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience

2003; Glannon, 2008a; Synofzik & Schlaepfer, 2008; Kuhn et al.,
2009). Here, the ethical questions of established clinical use will be
discussed together with the research-ethical questions of DBS.
Ethical implications of DBS in clinical practice
The overwhelming majority of DBS interventions are carried out for
treating motor impairments in PD. Although motor symptoms are the
most obvious impairment of this neurodegenerative disease, it also
includes cognitive, neuro-psychiatric and other non-motor symptoms.
Despite impressive effects in improving motor symptoms and quality
of life of seriously affected patients, DBS in clinical practice is
confronted with several ethical issues. An analysis of the literature on
the ethics of DBS for improving motor functions brought up five
major issues: weighing of risks and benefits; fair patient selection; how
to adequately protect children in paediatric DBS; special challenges in
respecting patient’s autonomy; and the question what should count as
a normatively relevant benefit.
Effects, side-effects, and weighing of risks and benefits
Even optimal medical treatment of PD is often subject to uncontrol-
lable fluctuations and severe side-effects. Many patients who respond
well to levodopa initially show variable drug effects over time. The
patients alternate between an off-state, in which the medication does
not work and which is associated with severe symptoms of PD, and an
on-state, in which levodopa works and leads to increased mobility.
The latter is often so pronounced that the patients suffer from
improved mobility (hyperkinesia) and involuntary movements (dys-
kinesia; Limousin et al., 1998). For many patients – especially if they
have been medicinally treated for a long time – the stimulation is a
favourable alternative treatment that reduces the motor symptoms in
the off-phases and allows for a reduction of medication (Hamani et al.,
2005b). The effectiveness of DBS is well-documented for these
patients (Deuschl et al., 2006; Weaver et al., 2009). Though stereo-
taxic surgery for DBS is held to be relatively safe, this intervention –
like every other neurosurgical procedure – is not free of risk.
Complications related to surgery or the implanted hardware are
distinguished from undesired side-effects resulting from the potency of
the intervention itself (Morishita et al., 2010). While Table 1
summarizes common complications of DBS surgery and their
incidence, Table 2 does so for side-effects of the procedure itself.
Reviewing the literature from 2001 to 2002, Warren Grill showed that
complications during surgery can affect more than 25% of the patients
(Grill, 2005). According to a more recent study, however, the overall
complication rate is about 6.8% (Voges et al., 2007). As shown in
Table 1, most frequent perioperative complications are bleeding and
epileptic seizures, in rare cases even deaths are reported (Hamani
et al., 2005b). Hardware-related problems include infections, lead
migration sometimes necessitating repositioning and lead breakage. A
study considering 922 patients in 10 publications from 2001 to 2006
identified infections to be the most common complication, occurring
in 6.1% of interventions (Hamani & Lozano, 2006). Sometimes
(4.5%) hardware has to be removed due to infections, as reported by
another study (Sillay et al., 2008).
DBS is considered to be an effective and safe intervention for treating
advanced PD. Nevertheless, many side-effects related to the interven-
tion have been documented. These include cognitive impairments,
changes in behaviour, as well as psychiatric and psychosocial effects
(Funkiewiez et al., 2004; Schu¨pbach et al., 2006; Voon et al., 2006;
Frank et al., 2007; Castelli et al., 2010). Table 2 summarizes the most
common adverse effects of DBS treatment. The STN is the preferred
target for DBS for PD. Because STN is a central structure for controlling
complex behaviour, including motor as well as cognitive and emotional
aspects (Mallet et al., 2007), it does not come as a surprise that
stimulating the STN – although solely directed towards treating motor
symptoms – causes effects also on cognition and emotion.
However, side-effects of DBS are heterogeneous. While some
studies could not detect any signs of dementia 5 years after surgery
(Contarino et al., 2007), others report that 24.5% of patients develop
dementia within 3 years after DBS intervention (Aybek et al., 2007).
Because dementia is a symptom of PD itself, however, it is not easy to
decide whether post-surgical dementia is caused by stimulation or
occurs due to the underlying progression of neurodegeneration.
Behavioural side-effects are equally heterogenous; while some
patients develop a (usually transient) hypomanic state (Mandat et al.,
2006), others show signs of apathy even as long as 5 years after
surgery (Krack et al., 2003). A more recent study did not find any
statistically significant changes in motivational drive in DBS patients
(Witt et al., 2008). Effects on mood and psychiatric side-effects are
reported for up to a quarter of stimulated patients (Berney et al., 2002;
Houeto et al., 2002), even increased suicide rates were reported
following STN-DBS (Voon et al., 2008). Comparing the incidence of
psychiatric side-effects in DBS patients with the rate occurring in
patients with optimal medical treatment showed just a minor
Table 1. Complications of DBS
Perioperative risks, %
Haemorrhage 1.3–4
Epileptic seizures 0.4–2.8
Pneumonia 0.4–0.6
Death 0.4
Liquor leakage 0–0.9
Hardware related problems, %
Infection 2.8–6.1
Lead migration or misplacement 5.1
Lead breakage 5.0
Leads needing repositioning 2.3
Skin erosion 1.3–2.0
Malfunction of pulse generator 0.4–9.7
References: Grill (2005); Hamani et al. (2005b); Hamani & Lozano (2006);
Witt et al. (2008); Morishita et al. (2010).
Table 2. Side-effects of DBS
Cognitive, %
Speech disturbances 10.8–33
Memory impairment 1.1–20
Dementia 6.1–24.5
Behavioural, %
Aggression 2
Hypomania 4.2–10.2
Increased libido ⁄ hypersexuality 0.8
Apathy 1.3
Psychiatric, %
Depression 1.5–25
Mania 2–18
Suicide 0.5–2
Psycho-social, %
Patient’s perception of themselves 66
Familial problems 50–71
Professional life 0–43
References: Alegret et al. (2001); Krack et al. (2003); Hamani et al. (2005b);
Hamani & Lozano (2006); Schu¨pbach et al. (2006); Witt et al. (2008); Weaver
et al. (2009).
Ethical brain stimulation 1153
ª 2010 The Author. European Journal of Neuroscience ª 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience, 32, 1152–1162