Elsevier

Progress in Neurobiology

Volume 89, Issue 1, September 2009, Pages 79-123
Progress in Neurobiology

Deep brain stimulation in neurological diseases and experimental models: From molecule to complex behavior

https://doi.org/10.1016/j.pneurobio.2009.06.003Get rights and content

Abstract

Deep brain stimulation (DBS) has proven to be capable of providing significant benefits for several neuropathologies. It is highly effective in reducing the motor symptoms of Parkinson's disease, essential tremor, and dystonia, and in alleviating chronic pain. Recently, also Tourette syndrome, obsessive–compulsive disorder and treatment-resistant depression have been treated by DBS with encouraging results. However, despite these clinical achievements, the precise action mechanisms of DBS still need to be fully characterized. For this reason, several animal models of DBS have been developed, bringing new insights on the effects of this treatment at molecular and cellular level, and providing new evidence on its physiological and behavioral consequences. In parallel, physiological and imaging studies in patients have contributed to better understanding DBS impact on the function of brain circuits. Here we review the clinical data and experimental work in vitro, ex vivo and in vivo (mostly arisen from studies on DBS of the subthalamic nucleus) in the treatment of PD, which led to the actual knowledge of DBS mechanisms, from molecular to complex behavioral levels.

Introduction

Deep brain stimulation (DBS) is now widely utilized as a functional surgical strategy for the treatment of a variety of neurological and psychiatric disorders. DBS at high frequency, also called high-frequency stimulation (HFS), has been shown to mimic the effects of lesioning the targeted structure and has thus widely replaced the ablative procedures. For example, the tremor characterizing Parkinson's disease (PD) as well as essential tremor is reduced by delivering DBS at high frequency to the ventral intermediate nucleus of the thalamus (VIM). A great improvement of the cardinal PD motor symptoms is achieved by HFS of the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi), two structures of the basal ganglia (BG). DBS is also applied for the treatment of pain, dystonia, Tourette syndrome, refractory epilepsy, depression, obsessive–compulsive disorder (OCD), obesity and minimal conscious states.

Electrical stimulation assisted by stereotaxy was developed in the late 1940s in order to help identify and map deep brain structures (Spiegel et al., 1947). Since the 1950s, DBS has been utilized for intrasurgical localization prior to therapeutic lesion of several brain structures, in particular for pallidotomy and thalamotomy (Spiegel and Wycis, 1952), and anecdotally reported as a therapy for untreatable pain syndromes (Bittar et al., 2005, Tasker and Vilela, 1995). Although nowadays DBS is mainly used to alleviate neurological motor disorders, it was only in the 1960s that DBS of the ventrolateral thalamus was first reported to alleviate tremor (Hassler et al., 1960, Ohye et al., 1964). However, during this decade DBS was still utilized for targeting a brain region prior to its lesion: in some cases, DBS was delivered with chronically implanted electrodes over a period that could reach several days, in order to best define the target to be lesioned. In the 1970–1980s, the therapeutic use of chronic DBS of the cerebellum emerged for treating movement disorders or epilepsy (Brice and McLellan, 1980, Cooper, 1973, Cooper et al., 1973, Cooper et al., 1976), and thalamic DBS was used for alleviating pain (Hosobuchi et al., 1973). In particular, Benabid et al. (1987) reported that stimulating the VIM at high frequency could ameliorate PD tremor during the targeting procedure for surgical lesioning of this structure. Such observation led to the application of chronic VIM HFS for the treatment of PD, essential tremor and extra-pyramidal dyskinesias, which was the first example of DBS at high frequency delivered by chronically implanted electrodes connected to a pacemaker-like portable stimulator (Benabid et al., 1989, Benabid et al., 1991). Since then, this surgical technique, applied to several brain structures, has become widespread for the treatment of a variety of brain disorders. However, despite its undoubtedly therapeutic efficacy, there are still several controversies about its action mechanisms and the long-term impact on neuronal circuits. A considerable amount of data has thus been produced experimentally in order to address this issue. Here we will provide a wide review of the data obtained from experimental models of DBS at molecular, cellular, physiological and behavioral levels, which contributed to a better understanding of the mechanisms and the consequences of this treatment. We will also refer to the accumulating functional investigations performed in patients with DBS neurosurgery. A comprehensive list of stimulation parameters, electrode features, experimental models, and DBS targets described in the scientific reports reviewed here is provided in Table 1.

Section snippets

Basic principles of DBS

At the beginning of the 20th century, Georges Weiss was the first to investigate quantitatively the basic principles of electrostimulation (Weiss, 1901). In his pioneering 1901 paper “Sur la possibilité de rendre comparables entre eux les appareils servant à l’excitation électrique” (On the possibility of rendering mutually comparable the devices used for electrical excitation), Weiss tried to find an answer to the following questions, some of which are still open today: “Coming to nerves and

Deep brain stimulation and Parkinson's disease

PD is a debilitating neurodegenerative movement disorder with a long course and a high prevalence (1–2 over 1000 individuals in the European Union) that increases with demographic ageing. It is widely accepted that the progressive loss of DAergic SNc neurons leads to the manifestation of the main symptoms of PD (muscle rigidity, tremor and bradykinesia/akinesia) due to a disturbance of the dynamic balance between excitatory and inhibitory neurotransmitters in the BG. SNc neurons innervate

Dystonia

Dystonia is characterized by involuntary muscle contractions causing twisting and repetitive movements and abnormal postures (Fahn, 1988). It affects few (focal dystonia) to most (generalized dystonia) of the muscle groups of the body with variable severity. Etiological classification includes two wide categories: primary (or idiopathic) and secondary (or symptomatic). Primary dystonias, especially generalized, are often hereditary and respond poorly to medical treatment. Their pathophysiology

Deep brain stimulation and psychiatric disorders

Tourette syndrome, OCD, and treatment-resistant depression (TRD) are the three major disorders currently under investigation with DBS in psychosurgery (Larson, 2008). For these psychiatric disorders, as for movement disorders, there was sometimes a background of responsiveness to lesioning procedures that provided the rationale for their treatment by functional surgery and the basis for some target selection. The identification of new candidate targets, although limited by the lack of

Deep brain stimulation and epilepsy

Epilepsy is a common chronic neurological disorder characterized by recurrent unprovoked seizures, affecting 0.5–1% of mankind. An epileptic seizure is caused by an excessive and/or hypersynchronous electrical neuronal activity, which can affect a specific brain area or structure (focal seizure), or can be largely distributed (generalized seizures). Usually seizures are self-limiting and can manifest as an alteration in mental state, tonic or clonic movements, convulsions, and various other

Acknowledgments

This work has been supported by grants from the Centre National de la Recherche Scientifique (CNRS) and the Université de la Méditerranée, the European Community (contract QLK6-1999-02173, 5th PCRDT, attributed to LK), the Agence Nationale pour la Recherche (ANR-05-NEUR-021, ANR-05-NEUR-013 and ANR-JC05-48262 attributed, respectively, to PG, PS and CB), the Action Concertée Incitative (ACI) program of the French Research Ministry (ACI Grant 04 2 91, project NIC0057 attributed to LK), the

References (475)

  • O. Bergmann et al.

    Subthalamic high frequency stimulation induced rotations are differentially mediated by D1 and D2 receptors

    Neuropharmacology

    (2004)
  • M.D. Bevan et al.

    Cellular principles underlying normal and pathological activity in the subthalamic nucleus

    Curr. Opin. Neurobiol.

    (2006)
  • M.D. Bevan et al.

    Move to the rhythm: oscillations in the subthalamic nucleus-external globus pallidus network

    Trends Neurosci.

    (2002)
  • R.G. Bittar et al.

    Deep brain stimulation for pain relief: a meta-analysis

    J. Clin. Neurosci.

    (2005)
  • T. Boraud et al.

    From single extracellular unit recording in experimental and human Parkinsonism to the development of a functional concept of the role played by the basal ganglia in motor control

    Prog. Neurobiol.

    (2002)
  • J. Brice et al.

    Suppression of intention tremor by contingent deep-brain stimulation

    Lancet

    (1980)
  • P. Brown et al.

    Effects of stimulation of the subthalamic area on oscillatory pallidal activity in Parkinson's disease

    Exp. Neurol.

    (2004)
  • L.A. Bullara et al.

    A microelectrode for delivery of defined charge densities

    J. Neurosci. Methods

    (1983)
  • M. Carlsson et al.

    Interactions between glutamatergic and monoaminergic systems within the basal ganglia—implications for schizophrenia and Parkinson's disease

    Trends Neurosci.

    (1990)
  • D. Centonze et al.

    Subthalamic nucleus lesion reverses motor abnormalities and striatal glutamatergic overactivity in experimental parkinsonism

    Neuroscience

    (2005)
  • S.R. Chamberlain et al.

    The neuropsychology of obsessive compulsive disorder: the importance of failures in cognitive and behavioural inhibition as candidate endophenotypic markers

    Neurosci. Biobehav. Rev.

    (2005)
  • J.Y. Chang et al.

    High frequency stimulation of the subthalamic nucleus improves treadmill locomotion in unilateral 6-hydroxydopamine lesioned rats

    Brain Res.

    (2003)
  • L. Ackermans et al.

    Deep brain stimulation in Tourette's syndrome: two targets?

    Mov. Disord.

    (2006)
  • G.E. Alexander et al.

    Parallel organization of functionally segregated circuits linking basal ganglia and cortex

    Annu. Rev. Neurosci.

    (1986)
  • R.L. Alterman et al.

    Sixty hertz pallidal deep brain stimulation for primary torsion dystonia

    Neurology

    (2007)
  • R.L. Alterman et al.

    Lower stimulation frequency can enhance tolerability and efficacy of pallidal deep brain stimulation for dystonia

    Mov. Disord.

    (2007)
  • L. Alvarez et al.

    Bilateral subthalamotomy in Parkinson's disease: initial and long-term response

    Brain

    (2005)
  • K.E. Anderson et al.

    Behavioral changes associated with deep brain stimulation surgery for Parkinson's disease

    Curr. Neurol. Neurosci. Rep.

    (2003)
  • T. Anderson et al.

    Mechanisms of deep brain stimulation: an intracellular study in rat thalamus

    J. Physiol.

    (2004)
  • V.C. Anderson et al.

    Pallidal vs subthalamic nucleus deep brain stimulation in Parkinson disease

    Arch. Neurol.

    (2005)
  • T.R. Anderson et al.

    Selective attenuation of afferent synaptic transmission as a mechanism of thalamic deep brain stimulation-induced tremor arrest

    J. Neurosci.

    (2006)
  • A.G. Androulidakis et al.

    Local field potential recordings from the pedunculopontine nucleus in a Parkinsonian patient

    Neuroreport

    (2008)
  • O.J. Andy

    Parafascicular–center median nuclei stimulation for intractable pain and dyskinesia (painful-dyskinesia)

    Appl. Neurophysiol.

    (1980)
  • B. Aouizerate et al.

    Deep brain stimulation of the ventral caudate nucleus in the treatment of obsessive–compulsive disorder and major depression. Case report

    J. Neurosurg.

    (2004)
  • N. Arai et al.

    Mechanisms of unilateral STN-DBS in patients with Parkinson's disease: a PET study

    J. Neurol.

    (2008)
  • M.S. Aymerich et al.

    Consequences of unilateral nigrostriatal denervation on the thalamostriatal pathway in rats

    Eur. J. Neurosci.

    (2006)
  • T.Z. Aziz et al.

    Lesion of the subthalamic nucleus for the alleviation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in the primate

    Mov. Disord.

    (1991)
  • J.J. Bacci et al.

    Differential effects of prolonged high frequency stimulation and of excitotoxic lesion of the subthalamic nucleus on dopamine denervation-induced cellular defects in the rat striatum and globus pallidus

    Eur. J. Neurosci.

    (2004)
  • J.J. Bacci et al.

    Intralaminar thalamic nuclei lesions: widespread impact on dopamine denervation-mediated cellular defects in the rat basal ganglia

    J. Neuropathol. Exp. Neurol.

    (2004)
  • R.J. Bajwa et al.

    Deep brain stimulation in Tourette's syndrome

    Mov. Disord.

    (2007)
  • K.B. Baker et al.

    Subthalamic nucleus deep brain stimulus evoked potentials: physiological and therapeutic implications

    Mov. Disord.

    (2002)
  • M. Barichella et al.

    Body weight gain rate in patients with Parkinson's disease and deep brain stimulation

    Mov. Disord.

    (2003)
  • M.S. Baron et al.

    Effects of transient focal inactivation of the basal ganglia in parkinsonian primates

    J. Neurosci.

    (2002)
  • A.J. Bastian et al.

    Different effects of unilateral versus bilateral subthalamic nucleus stimulation on walking and reaching in Parkinson's disease

    Mov. Disord.

    (2003)
  • J. Baufreton et al.

    Dopamine receptors set the pattern of activity generated in subthalamic neurons

    FASEB J.

    (2005)
  • C. Baunez et al.

    Enhanced food-related motivation after bilateral lesions of the subthalamic nucleus

    J. Neurosci.

    (2002)
  • C. Baunez et al.

    Bilateral high-frequency stimulation of the subthalamic nucleus on attentional performance: transient deleterious effects and enhanced motivation in both intact and parkinsonian rats

    Eur. J. Neurosci.

    (2007)
  • C. Baunez et al.

    The subthalamic nucleus exerts opposite control on cocaine and ‘natural’ rewards

    Nat. Neurosci.

    (2005)
  • C. Baunez et al.

    Effects of STN lesions on simple vs choice reaction time tasks in the rat: preserved motor readiness, but impaired response selection

    Eur. J. Neurosci.

    (2001)
  • C. Baunez et al.

    In a rat model of parkinsonism, lesions of the subthalamic nucleus reverse increases of reaction time but induce a dramatic premature responding deficit

    J. Neurosci.

    (1995)
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