Colosimo, Carlo

Fuentes, Romulo

Wojtecki, Lars

English

PubMed

Lars Wojtecki

Carlo Colosimo

Romulo Fuentes

Frontiers - Publisher Connector

INTEGRATIVE NEUROSCIENCE
A commentary on
Deep brain stimulation for movement 
disorders
by Pizzolato, G., and Mandat, T. (2012). 
Front. Integr. Neurosci. 6:2. doi: 10.3389/
fnint.2012.00002
Up to date, tens of thousands patients 
have undergone implantation of deep 
brain stimulation electrodes – mainly 
for the treatment of Parkinson’s dis-
ease, Essential Tremor, and Idiopathic 
Dystonia. Pizzolato and Mandat (2012) 
give a short and comprehensive review on 
the current status of deep brain stimula-
tion for these movement disorders. For 
this special issue “The development of 
deep brain stimulation for neurologi-
cal and psychiatric disorders: clinical, 
societal, and ethical issues” the reviews 
of Pizzolato and Mandat (2012) and of 
Sarem-Aslani and Mullett (2011) give 
an overview of the state of the art and 
currently approved indications for this 
therapy. There is no doubt, that especially 
in the field of movement disorders, deep 
brain stimulation is a history of great suc-
cess in neurological therapy and a most 
valuable tool for research.
However, especially in the light of other 
articles of this special issue that deal, e.g., 
with ethical issues, modulation of affect, 
cognition, and behavior, or possible changes 
of personality by deep brain stimulation, 
there remain some major challenges and 
questions for the future. We will have to 
conquer these challenges in order to under-
stand and improve the technique – to finally 
transfer it to a successful therapy for other 
disorders especially in the neuro-psychiatric 
domain.
These challenges are:
(1) To understand the natural history of 
the diseases and the underlying fun-
ctional networks and circuits to select 
the best targets for neuromodulation.
Beneficial motor effects of DBS are 
well described, e.g., there is class one 
evidence for the usefulness of DBS 
for Parkinson’s disease (Deuschl et al., 
2006; Weaver et al., 2009; Williams 
et al., 2010). However, to determine 
the real value in improving quality of 
life we have to gain more insight into 
the dynamics of the diseases. What is 
the right time point for implantation? 
Current data suggest that despite stable 
long terms effects on motor fluctua-
tions in PD, we might miss the right 
time window in elderly patients as DBS 
will not manage to improve axial motor 
symptoms (Fasano et al., 2010b). On 
the other hand, prospective studies to 
examine the benefits of earlier implan-
tation are still on the way. Furthermore, 
the interactions of disease state, ope-
ration, and implantation on cognitive 
side effects are not fully understood. 
Although there are many publications 
that show “on/off” effects on cognitive 
measurements, some data suggest that 
the implantation per se – and not the 
stimulation – might be the main cause 
of the decline in executive function 
(Okun et al., 2012). In line with this 
discussion we have to further study the 
right stimulation targets for to gain the 
best outcome. For example, GPI sti-
mulation recognizes a renaissance, as 
it might be a cognitive safer target for 
some patients. In order to efficiently 
access and modulate the neural net-
works, many findings point into the 
direction that fiber tracts rather than 
nuclei might be the right target of 
choice – not only in PD, but also in tha-
lamic stimulation for essential tremor: 
some findings suggest that differential 
stimulation of fiber tracts can be cru-
cial for modulation of distinct sym-
ptoms like tremor versus ataxia (Fasano 
et al., 2010a).
(2) To disentangle the mechanisms of 
action of deep brain stimulation.
The discussion about the effects of 
stimulating different fiber pathways 
leads to the point were we need a refi-
ned understanding of the connections 
and relationship between the different 
neural circuits involved in the desi-
red output behavior. When it comes 
to STN stimulation, stimulation of 
afferents from cortical areas might be 
the main mechanism – as studies that 
used the optogenetic method suggest 
(Gradinaru et al., 2009). Additionally, 
volume of tissue activated studies, other 
functional imaging, microelectrode 
multi-site recordings, local field poten-
tial-, EEG-, and magnetoencephalo-
graphic studies, alone or combined, 
might provide guides to understand the 
stimulation effects on local and long 
range neuronal networks.
(3) To improve stimulation techniques
On the basis of a better understan-
ding of the mechanisms underlying 
DBS, we have to tailor new stimula-
tion techniques. New programming 
options as interleaving (Wojtecki et al., 
2011) and constant current devices 
(Okun et al., 2012) are on the market 
now. Furthermore, new electrodes with 
improved variability of stimulation 
Deep brain stimulation for movement disorders – a history of 
success and challenges to conquer
Lars Wojtecki1,2*, Carlo Colosimo3 and Romulo Fuentes4
1 Center for Movement Disorders and Neuromodulation, Department of Neurology, Medical Faculty, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
2 Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
3 Department of Neurology and Psychiatry, “Sapienza” University, Rome, Italy
4 Edmond and Lily Safra International Institute of Neuroscience of Natal, Natal, Brazil
*Correspondence: wojtecki@uni-duesseldorf.de
Frontiers in Integrative Neuroscience www.frontiersin.org February 2012 | Volume 6 | Article 6 | 1
General Commentary
published: 23 February 2012
doi: 10.3389/fnint.2012.00006
S., Mehdorn, H. M., Moringlane, J. R., Oertel, 
W., Pinsker, M. O., Reichmann, H., Reuss, A., 
Schneider, G. H., Schnitzler, A., Steude, U., Sturm, 
V., Timmermann, L., Tronnier, V., Trottenberg, 
T., Wojtecki, L., Wolf, E., Poewe, W., Voges, J., and 
German Parkinson Study Group, Neurostimulation 
Section. (2006). A randomized trial of deep-brain 
stimulation for Parkinson’s disease. N. Engl. J. Med. 
355, 896–908.
Fasano, A., Herzog, J., Raethjen, J., Rose, F. E. M., 
Muthuraman, M., Volkmann, J., Falk, D., Elble, R., and 
Deuschl, G. (2010a). Gait ataxia in essential tremor 
is differentially modulated by thalamic stimulation. 
Brain 133, 3635–3648.
Fasano, A., Romito, L. M., Daniele, A., Piano, C., Zinno, 
M., Bentivoglio, A. R., and Albanese, A. (2010b). 
Motor and cognitive outcome in patients with 
Parkinson’s disease 8 years after subthalamic implants. 
Brain 133, 2664–2676.
Gradinaru, V., Mogri, M., Thompson, K. R., Henderson, 
J. M., and Deisseroth, K. (2009). Optical deconstruc-
tion of parkinsonian neural circuitry. Science 324, 
354–359.
Okun, M. S., Gallo, B. V., Mandybur, G., Jagid, J., Foote, K. 
D., Revilla, F. J., Alterman, R., Jankovic, J., Simpson, R., 
Junn, F., Verhagen, L., Arle, J. E., Ford, B., Goodman, 
R. R., Stewart, R. M., Horn, S., Baltuch, G. H., Kopell, 
B. H., Marshall, F., Peichel, D., Pahwa, R., Lyons, K. 
E., Tröster, A. I., Vitek, J. L., Tagliati, M., and for the 
SJM DBS Study Group. (2012). Subthalamic deep 
brain stimulation with a constant-current device in 
Parkinson’s disease: an open-label randomised con-
trolled trial. Lancet Neurol. 11, 140–149.
Pizzolato, G., and Mandat, T. (2012). Deep brain stimula-
tion for movement disorders. Front. Integr. Neurosci. 
6:2. doi: 10.3389/fnint.2012.00002
Rouse, A. G., Stanslaski, S. R., Cong, P., Jensen, R. 
M., Afshar, P., Ullestad, D., Gupta, R., Molnar, 
G. F., Moran, D. W., and Denison, T. J. (2011). 
A chronic generalized bi-directional brain-
direction will be helpful. Finally, as a 
result of disentangling the neuronal 
network codes (e.g., beta and high fre-
quency oscillations in PD), closed-loop 
devices (Rouse et al., 2011), that could 
provide stimulation “on demand,” will 
hopefully be a major step forward to 
improve these therapies.
(4) To learn from the history of DBS in 
movement disorders.
Especially when discussing modulation 
of complex behavior in patients with 
DBS and when we aim to increase the 
usage and indication of the technique, 
we have to learn from the lessons of the 
past. What was the reason for success 
of DBS in movement disorders? We 
think that there are four main points: 
determining the right patients with a 
distinct diagnosis for therapy, a detai-
led knowledge of the involved neural 
circuits, good designed and ethical 
clinical studies, and interdisciplinary 
cooperation between specialists (e.g., 
neurology, neurosurgery). On this 
basis, the future will be open for more 
indications and better understanding.
RefeRences
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Patel, S., Wheatley, K., and PD SURG Collaborative 
Group. (2010). Deep brain stimulation plus best 
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Wojtecki, L., Vesper, J., and Schnitzler, A. (2011). 
Interleaving programming of subthalamic deep 
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Received: 30 January 2012; accepted: 08 February 2012; 
published online: 23 February 2012.
Citation: Wojtecki L, Colosimo C and Fuentes R (2012) 
Deep brain stimulation for movement disorders – a history 
of success and challenges to conquer. Front. Integr. Neurosci. 
6:6. doi: 10.3389/fnint.2012.00006
Copyright © 2012 Wojtecki, Colosimo and Fuentes. This 
is an open-access article distributed under the terms of the 
Creative Commons Attribution Non Commercial License, 
which permits non-commercial use, distribution, and repro-
duction in other forums, provided the original authors and 
source are credited.
Wojtecki et al. DBS for movement disorders
Frontiers in Integrative Neuroscience www.frontiersin.org February 2012 | Volume 6 | Article 6 | 2


Deep Brain Stimulation for Movement Disorders – A History of Success and Challenges to Conquer

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Deep Brain Stimulation for Movement Disorders – A History of Success and Challenges to Conquer

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