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Clinical Implications of Neuroscience Research
May 19, 2008

Subthalamic nucleus and its connections
Anatomic substrate for the network effects of deep brain stimulation

May 20, 2008 issue
70 (21) 1991-1995


GLOSSARY: GP = globus pallidus; GPe = external segment of the globus pallidus; GPi = internal segment of the globus pallidus; PD = Parkinson disease; PPT = pedunculopontine tegmental nucleus; SNc = substantia nigra pars compacta; SNr = substantia nigra pars reticulata; STN = subthalamic nucleus.

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DeLong MR, Wichmann T. Circuits and circuit disorders of the basal ganglia. Arch Neurol 2007;64:20–24.
Parent A, Hazrati LN. Functional anatomy of the basal ganglia, II: the place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain Res Brain Res Rev 1995;20:128–154.
Teagarden MA, Rebec GV. Subthalamic and striatal neurons concurrently process motor, limbic, and associative information in rats performing an operant task. J Neurophysiol 2007;97:2042–2058.
Romanelli P, Esposito V, Schaal DW, Heit G. Somatotopy in the basal ganglia: experimental and clinical evidence for segregated sensorimotor channels. Brain Res Brain Res Rev 2005;48:112–128.
Tan SK, Temel Y, Blokland A, Steinbusch HW, Visser-Vandewalle V. The subthalamic nucleus: from response selection to execution. J Chem Neuroanat 2006;31:155–161.
Temel Y, Blokland A, Steinbusch HW, Visser-Vandewalle V. The functional role of the subthalamic nucleus in cognitive and limbic circuits. Prog Neurobiol 2005;76:393–413.
Bevan MD, Atherton JF, Baufreton J. Cellular principles underlying normal and pathological activity in the subthalamic nucleus. Curr Opin Neurobiol 2006;16:621–628.
Alexander GE, Crutcher MD, DeLong MR. Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, “prefrontal” and “limbic” functions. Prog Brain Res 1990;85:119–146.
Mallet L, Schupbach M, N′Diaye K, et al. Stimulation of subterritories of the subthalamic nucleus reveals its role in the integration of the emotional and motor aspects of behavior. Proc Natl Acad Sci USA 2007;104:10661–10666.
Mena-Segovia J, Bolam JP, Magill PJ. Pedunculopontine nucleus and basal ganglia: distant relatives or part of the same family? Trends Neurosci 2004;27:585–588.
Pahapill PA, Lozano AM. The pedunculopontine nucleus and Parkinson’s disease Brain 2000;123(Pt 9):1767–1783.
Muthusamy KA, Aravamuthan BR, Kringelbach ML, et al. Connectivity of the human pedunculopontine nucleus region and diffusion tensor imaging in surgical targeting. J Neurosurg 2007;107:814–820.
Francois C, Savy C, Jan C, Tande D, Hirsch EC, Yelnik J. Dopaminergic innervation of the subthalamic nucleus in the normal state, in MPTP-treated monkeys, and in Parkinson’s disease patients. J Comp Neurol 2000;425:121–129.
Grace AA, Floresco SB, Goto Y, Lodge DJ. Regulation of firing of dopaminergic neurons and control of goal-directed behaviors. Trends Neurosci 2007; 30:220–227.
Gatev P, Darbin O, Wichmann T. Oscillations in the basal ganglia under normal conditions and in movement disorders. Mov Disord 2006;21:1566–1577.
Hammond C, Bergman H, Brown P. Pathological synchronization in Parkinson’s disease: networks, models and treatments. Trends Neurosci 2007;30:357–364.
Baufreton J, Zhu ZT, Garret M, Bioulac B, Johnson SW, Taupignon AI. Dopamine receptors set the pattern of activity generated in subthalamic neurons. Faseb J 2005;19:1771–1777.
Rodriguez-Oroz MC, Obeso JA, Lang AE, et al. Bilateral deep brain stimulation in Parkinson’s disease: a multicentre study with 4 years follow-up. Brain 2005;128(Pt 10):2244–2249.
Lozano AM, Dostrovsky J, Chen R, Ashby P. Deep brain stimulation for Parkinson’s disease: disrupting the disruption. Lancet Neurol 2002;1:225–231.
Welter ML, Houeto JL, Bonnet AM, et al. Effects of high-frequency stimulation on subthalamic neuronal activity in parkinsonian patients. Arch Neurol 2004;61:89–96.
Maltete D, Jodoin N, Karachi C, et al. Subthalamic stimulation and neuronal activity in the substantia nigra in Parkinson’s disease. J Neurophysiol 2007;97:4017–4022.
Galati S, Mazzone P, Fedele E, et al. Biochemical and electrophysiological changes of substantia nigra pars reticulata driven by subthalamic stimulation in patients with Parkinson’s disease. Eur J Neurosci 2006;23:2923–2928.
Wallace BA, Ashkan K, Heise CE, et al. Survival of midbrain dopaminergic cells after lesion or deep brain stimulation of the subthalamic nucleus in MPTP-treated monkeys. Brain 2007;130(Pt 8):2129–2145.
Plaha P, Gill SS. Bilateral deep brain stimulation of the pedunculopontine nucleus for Parkinson’s disease. Neuroreport 2005;16:1883–1887.
Stefani A, Lozano AM, Peppe A, et al. Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson’s disease. Brain 2007;130(Pt 6):1596–1607.
Deransart C, Depaulis A. The control of seizures by the basal ganglia? A review of experimental data. Epileptic Disord 2002;4 suppl 3:S61–72.
Paz JT, Chavez M, Saillet S, Deniau JM, Charpier S. Activity of ventral medial thalamic neurons during absence seizures and modulation of cortical paroxysms by the nigrothalamic pathway. J Neurosci 2007;27:929–941.
Paz JT, Deniau JM, Charpier S. Rhythmic bursting in the cortico-subthalamo-pallidal network during spontaneous genetically determined spike and wave discharges. J Neurosci 2005;25:2092–2101.
Handforth A, DeSalles AA, Krahl SE. Deep brain stimulation of the subthalamic nucleus as adjunct treatment for refractory epilepsy. Epilepsia 2006;47:1239–1241.
Vesper J, Steinhoff B, Rona S, et al. Chronic high-frequency deep brain stimulation of the STN/SNr for progressive myoclonic epilepsy. Epilepsia 2007;48:1984–1989.
Feddersen B, Vercueil L, Noachtar S, David O, Depaulis A, Deransart C. Controlling seizures is not controlling epilepsy: a parametric study of deep brain stimulation for epilepsy. Neurobiol Dis 2007;27:292–300.
Castelli L, Perozzo P, Zibetti M, et al. Chronic deep brain stimulation of the subthalamic nucleus for Parkinson’s disease: effects on cognition, mood, anxiety and personality traits. Eur Neurol 2006;55:136–144.
Voon V, Kubu C, Krack P, Houeto JL, Troster AI. Deep brain stimulation: neuropsychological and neuropsychiatric issues. Mov Disord 2006;21 suppl 14:S305–327.
Mallet L, Mesnage V, Houeto JL, et al. Compulsions, Parkinson’s disease, and stimulation. Lancet 2002;360:1302–1304.
Fontaine D, Mattei V, Borg M, et al. Effect of subthalamic nucleus stimulation on obsessive-compulsive disorder in a patient with Parkinson disease: case report. J Neurosurg 2004;100:1084–1086.
Kaplitt MG, Feigin A, Tang C, et al. Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson’s disease: an open label, phase I trial. Lancet 2007;369:2097–2105.
Letters to the Editor
14 July 2008
Reply from the author
Eduardo E. Benarroch, Mayo Clinic, Rochester, MN

I appreciate Dr. Mark's comments on my short review where I focused on subthalamic nucleus connections that have been best characterized in experimental animals using modern neuroanatomical techniques.

However, this does not exclude the presence and potential functional significance of commissural subthalamic nucleus connections, as reported by Mark et al. [2]

I appreciate Dr Mark's emphasizing the potential significance of these connections for the effects of deep brain stimulation and rehabilitation techniques.

Disclosures: The author has no disclosures

14 July 2008
Subthalamic nucleus and its connections: Anatomic substrate for the network effects of deep brain
Victor W. Mark, University of Alabama at Birmingham

Benarroch's review on the anatomical connections of the subthalamic nucleus (STN) and their clinical correspondences does not mention the interhemispheric relays between the STN with the contralateral STN or other basal ganglia. [1]

We reported bilateral ballism following unilateral STN infarction and interpreted our findings with respect to the bilateral interconnections of the STN. [2] We noted the tendency among contemporary reviews to omit discussing interhemispheric relays of the STN.

Our study provided several references for these interhemispheric connections and their basic neuroscience and clinical relevance, including deep-brain stimulation. I believe a clinico-anatomical discussion of the STN is incomplete without referring to its interhemispheric connections.


1. Benarroch EE. Subthalamic nucleus and its connections: Anatomic substrate for the network effects of deep brain stimulation [review]. Neurology 2008;70:1991-1995.

2. Mark VW, Oberheu AM, Henderson C, Woods AJ. Ballism following stroke responds to simple therapeutic interventions. Arch Phys Med Rehabil 2005;86:1226-1233. Disclosures: The author has no disclosures

Information & Authors


Published In

Volume 70Number 21May 20, 2008
Pages: 1991-1995
PubMed: 18490619

Publication History

Published online: May 19, 2008
Published in print: May 20, 2008


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Affiliations & Disclosures

Eduardo E. Benarroch, MD
From the Department of Neurology, Mayo Clinic, Rochester, MN.


Address correspondence and reprint requests to Dr. Eduardo E. Benarroch, Mayo Clinic, Department of Neurology, 200 First Street SW, West 8A Mayo Bldg., Rochester, MN 55905 [email protected]

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