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Deep brain stimulation

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Abstract

During the last decade deep brain stimulation (DBS) has become a routine method for the treatment of advanced Parkinson’s disease (PD), leading to striking improvements in motor function and quality of life of PD patients. It is associated with minimal morbidity. The rationale of targeting specific structures within basal ganglia such as the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi) is strongly supported by the current knowledge of the basal ganglia pathophysiology, which is derived from extensive experimental work and which provides the theoretical basis for surgical therapy in PD. In particular, the STN has advanced to the worldwide most used target for DBS in the treatment of PD, due to the marked improvement of all cardinal symptoms of the disease. Moreover on-period dyskinesias are reduced in parallel with a marked reduction of the equivalent daily levodopa dose following STN–DBS. The success of the therapy largely depends on the selection of the appropriate candidate patients and on the precise implantation of the stimulation electrode, which necessitates careful imaging-based pre-targeting and extensive electrophysiological exploration of the target area. Despite the clinical success of the therapy, the fundamental mechanisms of high-frequency stimulation are still not fully elucidated. There is a large amount of evidence from experimental and clinical data that stimulation frequency represents a key factor with respect to clinical effect of DBS. Interestingly, high-frequency stimulation mimics the functional effects of ablation in various brain structures. The main hypotheses for the mechanism of high-frequency stimulation are: (1) depolarization blocking of neuronal transmission through inactivation of voltage dependent ion-channels, (2) jamming of information by imposing an efferent stimulation-driven high-frequency pattern, (3) synaptic inhibition by stimulation of inhibitory afferents to the target nucleus, (4) synaptic failure by stimulation-induced neurotransmitter depletion. As the hyperactivity of the STN is considered a functional hallmark of PD and as there is experimental evidence for STN-mediated glutamatergic excitotoxicity on neurons of the substantia nigra pars compacta (SNc), STN–DBS might reduce glutamatergic drive, leading to neuroprotection. Further studies will be needed to elucidate if STN–DBS indeed provides a slow-down of disease progression.

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References

  • Abosch A, Hutchison WD, Saint-Cyr JA, Dostrovsky JO, Lozano AM (2002) Movement-related neurons of the subthalamic nucleus in patients with Parkinson disease. J Neurosurg 97:1167–1172

    Google Scholar 

  • Albin RL, Young AB, Penney JB (1989) The functional anatomy of basal ganglia disorders. Trends Neurosci 12:366–375

    Google Scholar 

  • Alegret M, Junque C, Valldeoriola F, Vendrell P, Pilleri M, Rumia J, Tolosa E (2001) Effects of bilateral subthalamic stimulation on cognitive function in Parkinson disease. Arch Neurol 58:1223–1227

    Google Scholar 

  • Alexander GE, Crutcher MD (1990) Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci 13:266–271

    Google Scholar 

  • Alexander GE, Crutcher MD, DeLong MR (1990) Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, “prefrontal” and “limbic” functions. Prog Brain Res 85:119–146

    Google Scholar 

  • Anderson ME, Postupna N, Ruffo M (2003) Effects of high-frequency stimulation in the internal globus pallidus on the activity of thalamic neurons in the awake monkey. J Neurophysiol 89:1150–1160

    Google Scholar 

  • Ardouin C, Pillon B, Peiffer E, Bejjani P, Limousin P, Damier P, Arnulf I, Benabid AL, Agid Y, Pollak P (1999) Bilateral subthalamic or pallidal stimulation for Parkinson’s disease affects neither memory nor executive functions: a consecutive series of 62 patients. Ann Neurol 46:217–223

    Google Scholar 

  • Arnulf I, Bejjani BP, Garma L, Bonnet AM, Houeto JL, Damier P, Derenne JP, Agid Y (2000) Improvement of sleep architecture in PD with subthalamic nucleus stimulation. Neurology 55:1732–1734

    Google Scholar 

  • Aziz TZ, Peggs D, Sambrook MA, Crossman AR (1991) 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 6:288–292

    Google Scholar 

  • Baron MS, Wichmann T, Ma D, DeLong MR (2002) Effects of transient focal inactivation of the basal ganglia in parkinsonian primates. J Neurosci 22:592–599

    Google Scholar 

  • Bejjani BP, Arnulf I, Demeret S, Damier P, Bonnet AM, Houeto JL, Agid Y (2000a) Levodopa-induced dyskinesias in Parkinson’s disease: is sensitization reversible? Ann Neurol 47:655–658

    Google Scholar 

  • Bejjani BP, Gervais D, Arnulf I, Papadopoulos S, Demeret S, Bonnet AM, Cornu P, Damier P, Agid Y (2000b) Axial parkinsonian symptoms can be improved: the role of levodopa and bilateral subthalamic stimulation. J Neurol Neurosurg Psychiatry 68:595–600

    Google Scholar 

  • Benabid AL, Pollak P, Louveau A, Henry S, de Rougemont J (1987) Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl Neurophysiol 50:344–346

    Google Scholar 

  • Benabid AL, Pollak P, Hommel M, Gaio JM, de Rougemont J, Perret J (1989) Treatment of Parkinson tremor by chronic stimulation of the ventral intermediate nucleus of the thalamus. Rev Neurol (Paris) 145:320–323

    Google Scholar 

  • Benabid AL, Pollak P, Gervason C, Hoffmann D, Gao DM, Hommel M, Perret JE, de Rougemont J (1991) Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet 337:403–406

    Google Scholar 

  • Benabid AL, Pollak P, Gross C, Hoffmann D, Benazzouz A, Gao DM, Laurent A, Gentil M, Perret J (1994) Acute and long-term effects of subthalamic nucleus stimulation in Parkinson’s disease. Stereotact Funct Neurosurg 62:76–84

    Google Scholar 

  • Benabid AL, Pollak P, Gao D, Hoffmann D, Limousin P, Gay E, Payen I, Benazzouz A (1996) Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as a treatment of movement disorders. J Neurosurg 84:203–214

    Google Scholar 

  • Benazzouz A, Gross C, Feger J, Boraud T, Bioulac B (1993) Reversal of rigidity and improvement in motor performance by subthalamic high-frequency stimulation in MPTP-treated monkeys. Eur J Neurosci 5:382–389

    Google Scholar 

  • Benazzouz A, Piallat B, Pollak P, Benabid AL (1995) Responses of substantia nigra pars reticulata and globus pallidus complex to high frequency stimulation of the subthalamic nucleus in rats: electrophysiological data. Neurosci Lett 189:77–80

    Google Scholar 

  • Benazzouz A, Boraud T, Feger J, Burbaud P, Bioulac B, Gross C (1996) Alleviation of experimental hemiparkinsonism by high-frequency stimulation of the subthalamic nucleus in primates: a comparison with l-dopa treatment. Mov Disord 11:627–632

    Google Scholar 

  • Benazzouz A, Gao DM, Ni ZG, Piallat B, Bouali-Benazzouz R, Benabid AL (2000) Effect of high-frequency stimulation of the subthalamic nucleus on the neuronal activities of the substantia nigra pars reticulata and ventrolateral nucleus of the thalamus in the rat. Neuroscience 99:289–295

    Google Scholar 

  • Benazzouz A, Breit S, Koudsie A, Pollak P, Krack P, Benabid AL (2002) Intraoperative microrecordings of the subthalamic nucleus in Parkinson’s disease. Mov Disord 17:S145–S149

    Google Scholar 

  • Bergman H, Wichmann T, DeLong MR (1990) Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 249:1436–1438

    Google Scholar 

  • Bergman H, Wichmann T, Karmon B, DeLong MR (1994) The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism. J Neurophysiol 72:507–520

    Google Scholar 

  • Beric A, Kelly PJ, Rezai A, Sterio D, Mogilner A, Zonenshayn M, Kopell B (2001) Complications of deep brain stimulation surgery. Stereotact Funct Neurosurg 77:73–78

    Google Scholar 

  • Berney A, Vingerhoets F, Perrin A, Guex P, Villemure JG, Burkhard PR, Benkelfat C, Ghika J (2002) Effect on mood of subthalamic DBS for Parkinson’s disease: a consecutive series of 24 patients. Neurology 59:1427–1429

    Google Scholar 

  • Beurrier C, Bioulac B, Audin J, Hammond C (2001) High-frequency stimulation produces a transient blockade of voltage-gated currents in subthalamic neurons. J Neurophysiol 85:1351–1356

    Google Scholar 

  • Bikson M, Lian J, Hahn PJ, Stacey WC, Sciortino C, Durand DM (2001) Suppression of epileptiform activity by high frequency sinusoidal fields in rat hippocampal slices. J Physiol 531:181–191

    Google Scholar 

  • Boraud T, Bezard E, Bioulac B, Gross C (1996) High frequency stimulation of the internal globus pallidus (GPi) simultaneously improves parkinsonian symptoms and reduces the firing frequency of GPi neurons in the MPTP-treated monkey. Neurosci Lett 215:17–20

    Google Scholar 

  • Breit S, Bouali-Benazzouz R, Benabid AL, Benazzouz A (2001) Unilateral lesion of the nigrostriatal pathway induces an increase of neuronal activity of the pedunculopontine nucleus, which is reversed by the lesion of the subthalamic nucleus in the rat. Eur J Neurosci 14:1833–1842

    Google Scholar 

  • Brooks DJ, Samuel M (2000) The effects of surgical treatment of Parkinson’s disease on brain function: PET findings. Neurology 55:S52–S59

    Google Scholar 

  • Brown P, Oliviero A, Mazzone P, Insola A, Tonali P, Di Lazzaro V (2001) Dopamine dependency of oscillations between subthalamic nucleus and pallidum in Parkinson’s disease. J Neurosci 21:1033–1038

    Google Scholar 

  • Burchiel KJ, Anderson VC, Favre J, Hammerstad JP (1999) Comparison of pallidal and subthalamic nucleus deep brain stimulation for advanced Parkinson’s disease: results of a randomized, blinded pilot study. Neurosurgery 45:1375–1382

    Google Scholar 

  • Burns JM, Wilkinson S, Kieltyka J, Overman J, Lundsgaarde T, Tollefson T, Koller WC, Pahwa R, Troster AI, Lyons KE, Batnitzky S, Wetzel L, Gordon MA (1997) Analysis of pallidotomy lesion positions using three-dimensional reconstruction of pallidal lesions, the basal ganglia, and the optic tract. Neurosurgery 41:1303–1316

    Google Scholar 

  • Ceballos-Baumann AO, Obeso JA, Vitek JL, Delong MR, Bakay R, Linazasoro G, Brooks DJ (1994) Restoration of thalamocortical activity after posteroventral pallidotomy in Parkinson’s disease. Lancet 344:814

    Google Scholar 

  • Ceballos-Baumann AO, Boecker H, Bartenstein P, von Falkenhayn I, Riescher H, Conrad B, Moringlane JR, Alesch F (1999) A positron emission tomographic study of subthalamic nucleus stimulation in Parkinson disease: enhanced movement-related activity of motor-association cortex and decreased motor cortex resting activity. Arch Neurol 56:997–1003

    Google Scholar 

  • Charles PD, Van Blercom N, Krack P, Lee SL, Xie J, Besson G, Benabid AL, Pollak P (2002) Predictors of effective bilateral subthalamic nucleus stimulation for PD. Neurology 59:932–934

    Google Scholar 

  • Chen L, Liu Z, Tian Z, Wang Y, Li S (2000) Prevention of neurotoxin damage of 6-OHDA to dopaminergic nigral neuron by subthalamic nucleus lesions. Stereotact Funct Neurosurg 75:66–75

    Google Scholar 

  • Chesselet MF, Delfs JM (1996) Basal ganglia and movement disorders: an update. Trends Neurosci 19:417–422

    Google Scholar 

  • Daniele A, Albanese A, Contarino MF, Zinzi P, Barbier A, Gasparini F, Romito LM, Bentivoglio AR, Scerrati M (2003) Cognitive and behavioural effects of chronic stimulation of the subthalamic nucleus in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 74:175–182

    Google Scholar 

  • Davis KD, Taub E, Houle S, Lang AE, Dostrovsky JO, Tasker RR, Lozano AM (1997) Globus pallidus stimulation activates the cortical motor system during alleviation of parkinsonian symptoms. Nat Med 3:671–674

    Google Scholar 

  • Deep-brain stimulation for Parkinson’s disease study group (2001) Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson’s disease. N Engl J Med 345:956–963

    Google Scholar 

  • Deiber MP, Pollak P, Passingham R, Landais P, Gervason C, Cinotti L, Friston K, Frackowiak R, Mauguiere F, Benabid AL (1993) Thalamic stimulation and suppression of parkinsonian tremor. Evidence of a cerebellar deactivation using positron emission tomography. Brain 116:267–279

    Google Scholar 

  • Delwaide PJ, Pepin JL, De Pasqua V, de Noordhout AM (2000) Projections from basal ganglia to tegmentum: a subcortical route for explaining the pathophysiology of Parkinson’s disease signs? J Neurol 247:II75–II81

    Google Scholar 

  • DeLong MR (1990) Primate models of movement disorders of basal ganglia origin. Trends Neurosci 13:281–285

    Google Scholar 

  • DeLong MR, Coyle JT (1979) Globus pallidus lesions in the monkey produced by kainic acid: histologic and behavioral effects. Appl Neurophysiol 42:95–97

    Google Scholar 

  • Dostrovsky JO, Levy R, Wu JP, Hutchison WD, Tasker RR, Lozano AM (2000) Microstimulation-induced inhibition of neuronal firing in human globus pallidus. J Neurophysiol 84:570–574

    Google Scholar 

  • Dujardin K, Defebvre L, Krystkowiak P, Blond S, Destee A (2001) Influence of chronic bilateral stimulation of the subthalamic nucleus on cognitive function in Parkinson’s disease. J Neurol 248:603–611

    Google Scholar 

  • Eidelberg D, Moeller JR, Ishikawa T, Dhawan V, Spetsieris P, Silbersweig D, Stern E, Woods RP, Fazzini E, Dogali M, Beric A (1996) Regional metabolic correlates of surgical outcome following unilateral pallidotomy for Parkinson’s disease. Ann Neurol 39:450–459

    Google Scholar 

  • Feger J, Robledo P (1991) The effects of activation or inhibition of the subthalamic nucleus on the metabolic and electrophysiological activities within the pallidal complex and substantia nigra in the rat. Eur J Neurosci 3:947–952

    Google Scholar 

  • Feger J, Bevan M, Crossman AR (1994) The projections from the parafascicular thalamic nucleus to the subthalamic nucleus and the striatum arise from separate neuronal populations: a comparison with the corticostriatal and corticosubthalamic efferents in a retrograde fluorescent double-labelling study. Neuroscience 60:125–132

    Google Scholar 

  • Filion M (1979) Effects of interruption of the nigrostriatal pathway and of dopaminergic agents on the spontaneous activity of globus pallidus neurons in the awake monkey. Brain Res 178:425–441

    Google Scholar 

  • Filion M, Tremblay L, Bedard PJ (1991) Effects of dopamine agonists on the spontaneous activity of globus pallidus neurons in monkeys with MPTP-induced parkinsonism. Brain Res 547:152–161

    Google Scholar 

  • Forster GL, Blaha CD (2003) Pedunculopontine tegmental stimulation evokes striatal dopamine efflux by activation of acetylcholine and glutamate receptors in the midbrain and pons of the rat. Eur J Neurosci 17:751–762

    Google Scholar 

  • Fraix V, Pollak P, Van Blercom N, Xie J, Krack P, Koudsie A, Benabid AL (2000) Effect of subthalamic nucleus stimulation on levodopa-induced dyskinesia in Parkinson’s disease. Neurology 55:1921–1923

    Google Scholar 

  • Franzini A, Ferroli P, Leone M, Broggi G (2003) Stimulation of the posterior hypothalamus for treatment of chronic intractable cluster headaches: first reported series. Neurosurgery 52:1095–1099; discussion 1099–1101

    Google Scholar 

  • Fukuda M, Mentis MJ, Ma Y, Dhawan V, Antonini A, Lang AE, Lozano AM, Hammerstad J, Lyons K, Koller WC, Moeller JR, Eidelberg D (2001) Networks mediating the clinical effects of pallidal brain stimulation for Parkinson’s disease: a PET study of resting-state glucose metabolism. Brain 124:1601–1609

    Google Scholar 

  • Funkiewiez A, Ardouin C, Krack P, Fraix V, Van Blercom N, Xie J, Moro E, Benabid AL, Pollak P (2003) Acute psychotropic effects of bilateral subthalamic nucleus stimulation and levodopa in Parkinson’s disease. Mov Disord 18:524–530

    Google Scholar 

  • Garcia L, Audin J, D’Alessandro G, Bioulac B, Hammond C (2003) Dual effect of high-frequency stimulation on subthalamic neuron activity. J Neurosci 23:8743–8751

    Google Scholar 

  • Groenewegen HJ, Berendse HW (1990) Connections of the subthalamic nucleus with ventral striatopallidal parts of the basal ganglia in the rat. J Comp Neurol 294:607–622

    Google Scholar 

  • Gross C, Rougier A, Guehl D, Boraud T, Julien J, Bioulac B (1997) High-frequency stimulation of the globus pallidus internalis in Parkinson’s disease: a study of seven cases. J Neurosurg 87:491–498

    Google Scholar 

  • Gross RE, Lombardi WJ, Lang AE, Duff J, Hutchison WD, Saint-Cyr JA, Tasker RR, Lozano AM (1999) Relationship of lesion location to clinical outcome following microelectrode-guided pallidotomy for Parkinson’s disease. Brain 122:405–416

    Google Scholar 

  • Hamel W, Fietzek U, Morsnowski A, Schrader B, Weinert D, Muller D, Deuschl G, Mehdorn HM (2003) Subthalamic nucleus stimulation in Parkinson’s disease: correlation of active electrode contacts with intraoperative microrecordings. Stereotact Funct Neurosurg 80:37–42

    Google Scholar 

  • Hariz MI, Shamsgovara P, Johansson F, Hariz G, Fodstad H (1999) Tolerance and tremor rebound following long-term chronic thalamic stimulation for parkinsonian and essential tremor. Stereotact Funct Neurosurg 72:208–218

    Google Scholar 

  • Hashimoto T, Elder CM, Okun MS, Patrick SK, Vitek JL (2003) Stimulation of the subthalamic nucleus changes the firing pattern of pallidal neurons. J Neurosci 23:1916–1923

    Google Scholar 

  • Herzog J, Volkmann J, Krack P, Kopper F, Potter M, Lorenz D, Steinbach M, Klebe S, Hamel W, Schrader B, Weinert D, Muller D, Mehdorn HM, Deuschl G (2003) Two-year follow-up of subthalamic deep brain stimulation in Parkinson’s disease. Mov Disord 18:1332–1337

    Google Scholar 

  • Hilker R, Voges J, Thiel A, Ghaemi M, Herholz K, Sturm V, Heiss WD (2002) Deep brain stimulation of the subthalamic nucleus versus levodopa challenge in Parkinson’s disease: measuring the on- and off-conditions with FDG-PET. J Neural Transm 109:1257–1264

    Google Scholar 

  • Hilker R, Voges J, Weisenbach S, Kalbe E, Burghaus L, Ghaemi M, Lehrke R, Koulousakis A, Herholz K, Sturm V, Heiss WD (2004) Subthalamic nucleus stimulation restores glucose metabolism in associative and limbic cortices and in cerebellum: evidence from a FDG-PET study in advanced Parkinson’s disease. J Cereb Blood Flow Metab 24:7–16

    Google Scholar 

  • Houeto JL, Bejjani PB, Damier P, Staedler C, Bonnet AM, Pidoux B, Dormont D, Cornu P, Agid Y (2000a) Failure of long-term pallidal stimulation corrected by subthalamic stimulation in PD. Neurology 55:728–730

    Google Scholar 

  • Houeto JL, Damier P, Bejjani PB, Staedler C, Bonnet AM, Arnulf I, Pidoux B, Dormont D, Cornu P, Agid Y (2000b) Subthalamic stimulation in Parkinson disease: a multidisciplinary approach. Arch Neurol 57:461–465

    Google Scholar 

  • Houeto JL, Mesnage V, Mallet L, Pillon B, Gargiulo M, du Moncel ST, Bonnet AM, Pidoux B, Dormont D, Cornu P, Agid Y (2002) Behavioural disorders, Parkinson’s disease and subthalamic stimulation. J Neurol Neurosurg Psychiatry 72:701–707

    Google Scholar 

  • Hurtado JM, Gray CM, Tamas LB, Sigvardt KA (1999) Dynamics of tremor-related oscillations in the human globus pallidus: a single case study. Proc Natl Acad Sci USA 96:1674–1679

    Google Scholar 

  • Hutchison WD, Lozano AM, Tasker RR, Lang AE, Dostrovsky JO (1997a) Identification and characterization of neurons with tremor-frequency activity in human globus pallidus. Exp Brain Res 113:557–563

    Google Scholar 

  • Hutchison WD, Levy R, Dostrovsky JO, Lozano AM, Lang AE (1997b) Effects of apomorphine on globus pallidus neurons in parkinsonian patients. Ann Neurol 42:767–775

    Google Scholar 

  • Hutchison WD, Allan RJ, Opitz H, Levy R, Dostrovsky JO, Lang AE, Lozano AM (1998) Neurophysiological identification of the subthalamic nucleus in surgery for Parkinson’s disease. Ann Neurol 44:622–628

    Google Scholar 

  • Jahanshahi M, Ardouin CM, Brown RG, Rothwell JC, Obeso J, Albanese A, Rodriguez-Oroz MC, Moro E, Benabid AL, Pollak P, Limousin-Dowsey P (2000) The impact of deep brain stimulation on executive function in Parkinson’s disease. Brain 123:1142–1154

    Google Scholar 

  • Kishore A, Panikar D, Balakrishnan S, Joseph S, Sarma S (2000) Evidence of functional somatotopy in GPi from results of pallidotomy. Brain 123:2491–2500

    Google Scholar 

  • Kiss ZH, Mooney DM, Renaud L, Hu B (2002) Neuronal response to local electrical stimulation in rat thalamus: physiological implications for mechanisms of deep brain stimulation. Neuroscience 113:137–143

    Google Scholar 

  • Krack P, Pollak P, Limousin P, Hoffmann D, Xie J, Benazzouz A, Benabid AL (1998a) Subthalamic nucleus or internal pallidal stimulation in young onset Parkinson’s disease. Brain 121:451–457

    Google Scholar 

  • Krack P, Pollak P, Limousin P, Hoffmann D, Benazzouz A, Le Bas JF, Koudsie A, Benabid AL (1998b) Opposite motor effects of pallidal stimulation in Parkinson’s disease. Ann Neurol 43:180–192

    Google Scholar 

  • Krack P, Benazzouz A, Pollak P, Limousin P, Piallat B, Hoffmann D, Xie J, Benabid AL (1998c) Treatment of tremor in Parkinson’s disease by subthalamic nucleus stimulation. Mov Disord 13:907–914

    Google Scholar 

  • Krack P, Pollak P, Limousin P, Benazzouz A, Deuschl G, Benabid AL (1999) From off-period dystonia to peak-dose chorea. The clinical spectrum of varying subthalamic nucleus activity. Brain 122:1133–1146

    Google Scholar 

  • Krack P, Batir A, Van Blercom N, Chabardes S, Fraix V, Ardouin C, Koudsie A, Limousin PD, Benazzouz A, LeBas JF, Benabid AL, Pollak P (2003) Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N Engl J Med 349:1925–1934

    Google Scholar 

  • Krause M, Fogel W, Heck A, Hacke W, Bonsanto M, Trenkwalder C, Tronnier V (2001) Deep brain stimulation for the treatment of Parkinson’s disease: subthalamic nucleus versus globus pallidus internus. J Neurol Neurosurg Psychiatry 70:464–470

    Google Scholar 

  • Krauss JK, Desaloms JM, Lai EC, King DE, Jankovic J, Grossman RG (1997) Microelectrode-guided posteroventral pallidotomy for treatment of Parkinson’s disease: postoperative magnetic resonance imaging analysis. J Neurosurg 87:358–367

    Google Scholar 

  • Kulisevsky J, Berthier ML, Gironell A, Pascual-Sedano B, Molet J, Pares P (2002) Mania following deep brain stimulation for Parkinson’s disease. Neurology 59:1421–1424

    Google Scholar 

  • Kumar R, Lozano AM, Montgomery E, Lang AE (1998) Pallidotomy and deep brain stimulation of the pallidum and subthalamic nucleus in advanced Parkinson’s disease. Mov Disord 13:73–82

    Google Scholar 

  • Laitinen LV, Bergenheim AT, Hariz MI (1992a) Ventroposterolateral pallidotomy can abolish all parkinsonian symptoms. Stereotact Funct Neurosurg 58:14–21

    Google Scholar 

  • Laitinen LV, Bergenheim AT, Hariz MI (1992b) Leksell’s posteroventral pallidotomy in the treatment of Parkinson’s disease. J Neurosurg 76:53–61

    Google Scholar 

  • Lavoie B, Parent A (1994) Pedunculopontine nucleus in the squirrel monkey: projections to the basal ganglia as revealed by anterograde tract-tracing methods. J Comp Neurol 344:210–231

    Google Scholar 

  • Lee BH, Lee KH, Chung SS, Chang JW (2003) Neurophysiological identification and characterization of thalamic neurons with single unit recording in essential tremor patients. Acta Neurochir Suppl 87:133–136

    Google Scholar 

  • Lenz FA, Tasker RR, Kwan HC, Schnider S, Kwong R, Murayama Y, Dostrovsky JO, Murphy JT (1988) Single unit analysis of the human ventral thalamic nuclear group: correlation of thalamic “tremor cells” with the 3–6 Hz component of parkinsonian tremor. J Neurosci 8:754–764

    Google Scholar 

  • Lenz FA, Kwan HC, Martin RL, Tasker RR, Dostrovsky JO, Lenz YE (1994) Single unit analysis of the human ventral thalamic nuclear group. Tremor-related activity in functionally identified cells. Brain 117:531–543

    Google Scholar 

  • Levy R, Hazrati LN, Herrero MT, Vila M, Hassani OK, Mouroux M, Ruberg M, Asensi H, Agid Y, Feger J, Obeso JA, Parent A, Hirsch EC (1997) Re-evaluation of the functional anatomy of the basal ganglia in normal and Parkinsonian states. Neuroscience 76:335–343

    Google Scholar 

  • Levy R, Hutchison WD, Lozano AM, Dostrovsky JO (2000) High-frequency synchronization of neuronal activity in the subthalamic nucleus of parkinsonian patients with limb tremor. J Neurosci 20:7766–7775

    Google Scholar 

  • Levy R, Dostrovsky JO, Lang AE, Sime E, Hutchison WD, Lozano AM (2001) Effects of apomorphine on subthalamic nucleus and globus pallidus internus neurons in patients with Parkinson’s disease. J Neurophysiol 86:249–260

    Google Scholar 

  • Limousin P, Pollak P, Benazzouz A, Hoffmann D, Le Bas JF, Broussolle E, Perret JE, Benabid AL (1995) Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation. Lancet 345:91–95

    Google Scholar 

  • Limousin P, Greene J, Pollak P, Rothwell J, Benabid AL, Frackowiak R (1997) Changes in cerebral activity pattern due to subthalamic nucleus or internal pallidum stimulation in Parkinson’s disease. Ann Neurol 42:283–291

    Google Scholar 

  • Limousin P, Krack P, Pollak P, Benazzouz A, Ardouin C, Hoffmann D, Benabid AL (1998) Electrical stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N Engl J Med 339:1105–1111

    Google Scholar 

  • Limousin P, Speelman JD, Gielen F, Janssens M (1999) Multicentre European study of thalamic stimulation in parkinsonian and essential tremor. J Neurol Neurosurg Psychiatry 66:289–296

    Google Scholar 

  • Lombardi WJ, Gross RE, Trepanier LL, Lang AE, Lozano AM, Saint-Cyr JA (2000) Relationship of lesion location to cognitive outcome following microelectrode-guided pallidotomy for Parkinson’s disease: support for the existence of cognitive circuits in the human pallidum. Brain 123:746–758

    Google Scholar 

  • Lozano AM, Hutchison WD (2002) Microelectrode recordings in the pallidum. Mov Disord 17:S150–S154

    Google Scholar 

  • Lozano AM, Lang AE, Levy R, Hutchison W, Dostrovsky J (2000) Neuronal recordings in Parkinson’s disease patients with dyskinesias induced by apomorphine. Ann Neurol 47:S141–S146

    Google Scholar 

  • Luo J, Kaplitt MG, Fitzsimons HL, Zuzga DS, Liu Y, Oshinsky ML, During MJ (2002) Subthalamic GAD gene therapy in a Parkinson’s disease rat model. Science 298:425–429

    Google Scholar 

  • Maesawa S, Kaneoke Y, Kajita Y, Usui N, Misawa N, Nakayama A, Yoshida J (2004) Long-term stimulation of the subthalamic nucleus in hemiparkinsonian rats: neuroprotection of dopaminergic neurons. J Neurosurg 100:679–687

    Google Scholar 

  • Magarinos-Ascone CM, Figueiras-Mendez R, Riva-Meana C, Cordoba-Fernandez A (2000) Subthalamic neuron activity related to tremor and movement in Parkinson’s disease. Eur J Neurosci 12:2597–2607

    Google Scholar 

  • Magarinos-Ascone C, Pazo JH, Macadar O, Buno W (2002) High-frequency stimulation of the subthalamic nucleus silences subthalamic neurons: a possible cellular mechanism in Parkinson’s disease. Neuroscience 115:1109–1117

    Google Scholar 

  • Marsden CD, Obeso JA (1994) The functions of the basal ganglia and the paradox of stereotaxic surgery in Parkinson’s disease. Brain 117:877–897

    Google Scholar 

  • Maurice N, Thierry AM, Glowinski J, Deniau JM (2003) Spontaneous and evoked activity of substantia nigra pars reticulata neurons during high-frequency stimulation of the subthalamic nucleus. J Neurosci 23:9929–9936

    Google Scholar 

  • McIntyre CC, Grill WM (1999) Excitation of central nervous system neurons by nonuniform electric fields. Biophys J 76:878–888

    Google Scholar 

  • McIntyre CC, Grill WM (2002) Extracellular stimulation of central neurons: influence of stimulus waveform and frequency on neuronal output. J Neurophysiol 88:1592–1604

    Google Scholar 

  • McIntyre CC, Grill WM, Sherman DL, Thakor NV (2004a) Cellular effects of deep brain stimulation: model-based analysis of activation and inhibition. J Neurophysiol 91:1457–1469

    Google Scholar 

  • McIntyre CC, Mori S, Sherman DL, Thakor NV, Vitek JL (2004b) Electric field and stimulating influence generated by deep brain stimulation of the subthalamic nucleus. Clin Neurophysiol 115:589–595

    Google Scholar 

  • Mink JW, Thach WT (1991) Basal ganglia motor control. III. Pallidal ablation: normal reaction time, muscle cocontraction, and slow movement. J Neurophysiol 65:330–351

    Google Scholar 

  • Miyawaki E, Perlmutter JS, Troster AI, Videen TO, Koller WC (2000) The behavioral complications of pallidal stimulation: a case report. Brain Cogn 42:417–434

    Google Scholar 

  • Moro E, Scerrati M, Romito LM, Roselli R, Tonali P, Albanese A (1999) Chronic subthalamic nucleus stimulation reduces medication requirements in Parkinson’s disease. Neurology 53:85–90

    Google Scholar 

  • Nambu A, Takada M, Inase M, Tokuno H (1996) Dual somatotopical representations in the primate subthalamic nucleus: evidence for ordered but reversed body-map transformations from the primary motor cortex and the supplementary motor area. J Neurosci 16:2671–2683

    Google Scholar 

  • Nandi D, Stein JF, Aziz TZ (2002a) Exploration of the role of the upper brainstem in motor control. Stereotact Funct Neurosurg 78:158–167

    Google Scholar 

  • Nandi D, Aziz TZ, Liu X, Stein JF (2002b) Brainstem motor loops in the control of movement. Mov Disord 17:S22–S27

    Google Scholar 

  • Nandi D, Aziz TZ, Giladi N, Winter J, Stein JF (2002c) Reversal of akinesia in experimental parkinsonism by GABA antagonist microinjections in the pedunculopontine nucleus. Brain 125:2418–2430

    Google Scholar 

  • Nandi D, Liu X, Winter JL, Aziz TZ, Stein JF (2002d) Deep brain stimulation of the pedunculopontine region in the normal non-human primate. J Clin Neurosci 9:170–174

    Google Scholar 

  • Obeso JA, Guridi J, DeLong M (1997) Surgery for Parkinson’s disease. J Neurol Neurosurg Psychiatry 62:2–8

    Google Scholar 

  • Obeso JA, Rodriguez-Oroz MC, Rodriguez M, DeLong MR, Olanow CW (2000) Pathophysiology of levodopa-induced dyskinesias in Parkinson’s disease: problems with the current model. Ann Neurol 47:S22–S32

    Google Scholar 

  • Oh MY, Abosch A, Kim SH, Lang AE, Lozano AM (2002) Long-term hardware-related complications of deep brain stimulation. Neurosurgery 50:1268–1274; discussion 1274–1276

    Google Scholar 

  • Ohye C, Maeda T, Narabayashi H (1976) Physiologically defined VIM nucleus. Its special reference to control of tremor. Appl Neurophysiol 39:285–295

    Google Scholar 

  • Ohye C, Fukamachi A, Miyazaki M, Isobe I, Nakajima H, Shibazaki T (1977) Physiologically controlled selective thalamotomy for the treatment of abnormal movement by Leksell’s open system. Acta Neurochir (Wien) 37:93–104

    Google Scholar 

  • Pahapill PA, Lozano AM (2000) The pedunculopontine nucleus and Parkinson’s disease. Brain 123:1767–1783

    Google Scholar 

  • Pahwa R, Wilkinson SB, Overman J, Lyons KE (2003) Bilateral subthalamic stimulation in patients with Parkinson disease: long-term follow up. J Neurosurg 99:71–77

    Google Scholar 

  • Parent A, Hazrati LN (1995) Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain Res Brain Res Rev 20:128–154

    Google Scholar 

  • Parent A, Cicchetti F (1998) The current model of basal ganglia organization under scrutiny. Mov Disord 13:199–202

    Google Scholar 

  • Parker F, Tzourio N, Blond S, Petit H, Mazoyer B (1992) Evidence for a common network of brain structures involved in parkinsonian tremor and voluntary repetitive movement. Brain Res 584:11–17

    Google Scholar 

  • Perier C, Vila M, Feger J, Agid Y, Hirsch EC (2000) Functional activity of zona incerta neurons is altered after nigrostriatal denervation in hemiparkinsonian rats. Exp Neurol 162:215–224

    Google Scholar 

  • Perier C, Tremblay L, Feger J, Hirsch EC (2002) Behavioral consequences of bicuculline injection in the subthalamic nucleus and the zona incerta in rat. J Neurosci 22:8711–8719

    Google Scholar 

  • Perozzo P, Rizzone M, Bergamasco B, Castelli L, Lanotte M, Tavella A, Torre E, Lopiano L (2001a) Deep brain stimulation of the subthalamic nucleus in Parkinson’s disease: comparison of pre- and post-operative neuropsychological evaluation. J Neurol Sci 192:9–15

    Google Scholar 

  • Perozzo P, Rizzone M, Bergamasco B, Castelli L, Lanotte M, Tavella A, Torre E, Lopiano L (2001b) Deep brain stimulation of subthalamic nucleus: behavioural modifications and familiar relations. Neurol Sci 22:81–82

    Google Scholar 

  • Piallat B, Benazzouz A, Benabid AL (1996) Subthalamic nucleus lesion in rats prevents dopaminergic nigral neuron degeneration after striatal 6-OHDA injection: behavioural and immunohistochemical studies. Eur J Neurosci 8:1408–1414

    Google Scholar 

  • Piallat B, Benazzouz A, Benabid AL (1999) Neuroprotective effect of chronic inactivation of the subthalamic nucleus in a rat model of Parkinson’s disease. J Neural Transm Suppl 55:71–77

    Google Scholar 

  • Pillon B, Ardouin C, Damier P, Krack P, Houeto JL, Klinger H, Bonnet AM, Pollak P, Benabid AL, Agid Y (2000) Neuropsychological changes between “off” and “on” STN or GPi stimulation in Parkinson’s disease. Neurology 55:411–418

    Google Scholar 

  • Pollak P, Fraix V, Krack P, Moro E, Mendes A, Chabardes S, Koudsie A, Benabid AL (2002) Treatment results: Parkinson’s disease. Mov Disord 17:S75–S83

    Google Scholar 

  • Ranck JB Jr (1975) Which elements are excited in electrical stimulation of mammalian central nervous system: a review. Brain Res 98:417–440

    Google Scholar 

  • Rodriguez MC, Obeso JA, Olanow CW (1998) Subthalamic nucleus-mediated excitotoxicity in Parkinson’s disease: a target for neuroprotection. Ann Neurol 44:S175–S188

    Google Scholar 

  • Rodriguez-Oroz MC, Rodriguez M, Guridi J, Mewes K, Chockkman V, Vitek J, DeLong MR, Obeso JA (2001) The subthalamic nucleus in Parkinson’s disease: somatotopic organization and physiological characteristics. Brain 124:1777–1790

    Google Scholar 

  • Romito LM, Raja M, Daniele A, Contarino MF, Bentivoglio AR, Barbier A, Scerrati M, Albanese A (2002) Transient mania with hypersexuality after surgery for high frequency stimulation of the subthalamic nucleus in Parkinson’s disease. Mov Disord 17:1371–1374

    Google Scholar 

  • Saint-Cyr JA, Trepanier LL, Kumar R, Lozano AM, Lang AE (2000) Neuropsychological consequences of chronic bilateral stimulation of the subthalamic nucleus in Parkinson’s disease. Brain 123:2091–2108

    Google Scholar 

  • Saint-Cyr JA, Hoque T, Pereira LC, Dostrovsky JO, Hutchison WD, Mikulis DJ, Abosch A, Sime E, Lang AE, Lozano AM (2002) Localization of clinically effective stimulating electrodes in the human subthalamic nucleus on magnetic resonance imaging. J Neurosurg 97:1152–1166

    Google Scholar 

  • Samuel M, Ceballos-Baumann AO, Turjanski N, Boecker H, Gorospe A, Linazasoro G, Holmes AP, DeLong MR, Vitek JL, Thomas DG, Quinn NP, Obeso JA, Brooks DJ (1997) Pallidotomy in Parkinson’s disease increases supplementary motor area and prefrontal activation during performance of volitional movements an H2(15)O PET study. Brain 120:1301–1313

    Google Scholar 

  • Schneider F, Habel U, Volkmann J, Regel S, Kornischka J, Sturm V, Freund HJ (2003) Deep brain stimulation of the subthalamic nucleus enhances emotional processing in Parkinson disease. Arch Gen Psychiatry 60:296–302

    Google Scholar 

  • Schroeder U, Kuehler A, Lange KW, Haslinger B, Tronnier VM, Krause M, Pfister R, Boecker H, Ceballos-Baumann AO (2003) Subthalamic nucleus stimulation affects a frontotemporal network: a PET study. Ann Neurol 54:445–450

    Google Scholar 

  • Schuurman PR, Bosch DA, Bossuyt PM, Bonsel GJ, van Someren EJ, de Bie RM, Merkus MP, Speelman JD (2000) A comparison of continuous thalamic stimulation and thalamotomy for suppression of severe tremor. N Engl J Med 342:461–468

    Google Scholar 

  • Siegfried J, Lippitz B (1994) Bilateral chronic electrostimulation of ventroposterolateral pallidum: a new therapeutic approach for alleviating all parkinsonian symptoms. Neurosurgery 35:1126–1129; discussion 1129–1130

    Google Scholar 

  • Starr PA, Christine CW, Theodosopoulos PV, Lindsey N, Byrd D, Mosley A, Marks WJ Jr (2002) Implantation of deep brain stimulators into the subthalamic nucleus: technical approach and magnetic resonance imaging-verified lead locations. J Neurosurg 97:370–387

    Google Scholar 

  • Sterio D, Zonenshayn M, Mogilner AY, Rezai AR, Kiprovski K, Kelly PJ, Beric A (2002) Neurophysiological refinement of subthalamic nucleus targeting. Neurosurgery 50:58–67; discussion 67–69

    Google Scholar 

  • Taha JM, Favre J, Baumann TK, Burchiel KJ (1996) Characteristics and somatotopic organization of kinesthetic cells in the globus pallidus of patients with Parkinson’s disease. J Neurosurg 85:1005–1012

    Google Scholar 

  • Tai CH, Boraud T, Bezard E, Bioulac B, Gross C, Benazzouz A (2003) Electrophysiological and metabolic evidence that high-frequency stimulation of the subthalamic nucleus bridles neuronal activity in the subthalamic nucleus and the substantia nigra reticulata. FASEB J 17:1820–1830

    Google Scholar 

  • Takada M, Matsumura M, Kojima J, Yamaji Y, Inase M, Tokuno H, Nambu A, Imai H (2000) Protection against dopaminergic nigrostriatal cell death by excitatory input ablation. Eur J Neurosci 12:1771–1780

    Google Scholar 

  • Tavella A, Bergamasco B, Bosticco E, Lanotte M, Perozzo P, Rizzone M, Torre E, Lopiano L (2002) Deep brain stimulation of the subthalamic nucleus in Parkinson’s disease: long-term follow-up. Neurol Sci 23:S111–S112

    Google Scholar 

  • Trepanier LL, Kumar R, Lozano AM, Lang AE, Saint-Cyr JA (2000) Neuropsychological outcome of GPi pallidotomy and GPi or STN deep brain stimulation in Parkinson’s disease. Brain Cogn 42:324–347

    Google Scholar 

  • Umemura A, Jaggi JL, Hurtig HI, Siderowf AD, Colcher A, Stern MB, Baltuch GH (2003) Deep brain stimulation for movement disorders: morbidity and mortality in 109 patients. J Neurosurg 98:779–784

    Google Scholar 

  • Urbano FJ, Leznik E, Llinas RR (2002) Cortical activation patterns evoked by afferent axons stimuli at different frequencies: an in vitro voltage-sensitive dye imaging study. Thalamus Rel Syst 1:371–378

    Google Scholar 

  • Vesper J, Klostermann F, Stockhammer F, Funk T, Brock M (2002) Results of chronic subthalamic nucleus stimulation for Parkinson’s disease: a 1-year follow-up study. Surg Neurol 57:306–311; discussion 311–313

    Google Scholar 

  • Vitek JL (2002) Deep brain stimulation for Parkinson’s disease. A critical re-evaluation of STN versus GPi DBS. Stereotact Funct Neurosurg 78:119–131

    Google Scholar 

  • Vitek JL, Bakay RA, Hashimoto T, Kaneoke Y, Mewes K, Zhang JY, Rye D, Starr P, Baron M, Turner R, DeLong MR (1998) Microelectrode-guided pallidotomy: technical approach and its application in medically intractable Parkinson’s disease. J Neurosurg 88:1027–1043

    Google Scholar 

  • Voges J, Volkmann J, Allert N, Lehrke R, Koulousakis A, Freund HJ, Sturm V (2002) Bilateral high-frequency stimulation in the subthalamic nucleus for the treatment of Parkinson disease: correlation of therapeutic effect with anatomical electrode position. J Neurosurg 96:269–279

    Google Scholar 

  • Volkmann J, Allert N, Voges J, Weiss PH, Freund HJ, Sturm V (2001) Safety and efficacy of pallidal or subthalamic nucleus stimulation in advanced PD. Neurology 56:548–551

    Google Scholar 

  • Wang LY, Kaczmarek LK (1998) High-frequency firing helps replenish the readily releasable pool of synaptic vesicles. Nature 394:384–388

    Google Scholar 

  • Welter ML, Houeto JL, Tezenas du Montcel S, Mesnage V, Bonnet AM, Pillon B, Arnulf I, Pidoux B, Dormont D, Cornu P, Agid Y (2002) Clinical predictive factors of subthalamic stimulation in Parkinson’s disease. Brain 125:575–583

    Google Scholar 

  • Wichmann T, Bergman H, DeLong MR (1994) The primate subthalamic nucleus. III. Changes in motor behavior and neuronal activity in the internal pallidum induced by subthalamic inactivation in the MPTP model of parkinsonism. J Neurophysiol 72:521–530

    Google Scholar 

  • Windels F, Bruet N, Poupard A, Urbain N, Chouvet G, Feuerstein C, Savasta M (2000) Effects of high frequency stimulation of subthalamic nucleus on extracellular glutamate and GABA in substantia nigra and globus pallidus in the normal rat. Eur J Neurosci 12:4141–4146

    Google Scholar 

  • Windels F, Bruet N, Poupard A, Feuerstein C, Bertrand A, Savasta M (2003) Influence of the frequency parameter on extracellular glutamate and gamma-aminobutyric acid in substantia nigra and globus pallidus during electrical stimulation of subthalamic nucleus in rats. J Neurosci Res 72:259–267

    Google Scholar 

  • Wu YR, Levy R, Ashby P, Tasker RR, Dostrovsky JO (2001) Does stimulation of the GPi control dyskinesia by activating inhibitory axons? Mov Disord 16:208–216

    Google Scholar 

  • Xia R, Berger F, Piallat B, Bayle M, Bouamrani A, Benabid AL (2004) Modulation of protein expression in vitro by electrical stimulation as a function of frequency (Abstract). Eighth International Congress on Parkinson’s Disease and Movement Disorders, Rome

  • Yelnik J (2002) Functional anatomy of the basal ganglia. Mov Disord 17:S15–S21

    Google Scholar 

  • Zucker RS, Regehr WG (2002) Short-term synaptic plasticity. Annu Rev Physiol 64:355–405

    Google Scholar 

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Breit, S., Schulz, J.B. & Benabid, AL. Deep brain stimulation. Cell Tissue Res 318, 275–288 (2004). https://doi.org/10.1007/s00441-004-0936-0

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