Abstract
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) was proposed as an effective way to improve the symptoms of Parkinson’s disease (PD). We studied metabolic modulation in the brain by bilateral STN stimulation using FDG PET. Five PD patients (age 61.6 ± 3.9 years) at advanced stage were scanned under OFF and ON conditions of stimulation. Network analysis was used to evaluate the effect of stimulation on the expression of an abnormal Parkinson’s disease-related spatial covariance pattern (PDRP). In addition, statistical parametric mapping was used to assess the effect of this intervention on regional glucose metabolism. We found that bilateral STN DBS led to a significant reduction (P < 0.02) in the PDRP network activity on an individual subject basis between OFF and ON conditions, parallel to significant improvement (P < 0.002) of clinical symptoms in these patients. The treatment also decreased glucose metabolism in the right lentiform nucleus and cerebellum, and in the bilateral ventral thalamus and precuneus, but increased metabolism in the left midbrain and pons. This was consistent with the notion that clinical benefit in a PD patient was associated with the suppression of hyperactive motor circuitry following STN stimulation. These findings suggest that DBS is more likely to function by regulating the entire neural network rather than merely exciting or inhibiting certain nuclei.
Similar content being viewed by others
References
Asanuma K, Tang C, Ma Y, Dhawan V, Mattis P, Edwards C, Kaplitt MG, Feigin A, Eidelberg D (2006) Network modulation in the treatment of Parkinson’s disease. Brain 129:2667–2678
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
Djaldetti R, Ziv I, Melamed E (2006) The mystery of motor asymmetry in Parkinson’s disease. Lancet Neurol 5:796–802
Eckert T, Barnes A, Dhawan V, Frucht S, Gordon MF, Feigin AS, Eidelberg D (2005) FDG PET in the differential diagnosis of parkinsonian disorders. Neuroimage 26:912–921
Eidelberg D, Moeller JR, Dhawan V, Spetsieris P, Takikawa S, Ishikawa T, Chaly T, Robeson W, Margouleff D, Przedborski S et al (1994) The metabolic topography of parkinsonism. J Cereb Blood Flow Metab 14:783–801
Eidelberg D, Moeller JR, Ishikawa T, Dhawan V, Spetsieris P, Chaly T, Robeson W, Dahl JR, Margouleff D (1995) Assessment of disease severity in parkinsonism with fluorine-18-fluorodeoxyglucose and PET. J Nucl Med 36:378–383
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
Fahn S, Oakes D, Shoulson I, Kieburtz K, Rudolph A, Lang A, Olanow CW, Tanner C, Marek K (2004) Levodopa and the progression of Parkinson’s disease. N Engl J Med 351:2498–2508
Feigin A, Fukuda M, Dhawan V, Przedborski S, Jackson-Lewis V, Mentis MJ, Moeller JR, Eidelberg D (2001) Metabolic correlates of levodopa response in Parkinson’s disease. Neurology 57:2083–2088
Feigin A, Kaplitt MG, Tang C, Lin T, Mattis P, Dhawan V, During MJ, Eidelberg D (2007) Modulation of metabolic brain networks after subthalamic gene therapy for Parkinson’s disease. Proc Natl Acad Sci USA 104:19559–19564
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
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
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
Huang C, Tang C, Feigin A, Lesser M, Ma Y, Pourfar M, Dhawan V, Eidelberg D (2007) Changes in network activity with the progression of Parkinson’s disease. Brain 130:1834–1846
Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184
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
Limousin P, Pollak P, Benazzouz A, Hoffmann D, Broussolle E, Perret JE, Benabid AL (1995) Bilateral subthalamic nucleus stimulation for severe Parkinson’s disease. Mov Disord 10:672–674
Lin TP, Carbon M, Tang C, Mogilner AY, Sterio D, Beric A, Dhawan V, Eidelberg D (2008) Metabolic correlates of subthalamic nucleus activity in Parkinson’s disease. Brain 131:1373–1380
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
Ma Y, Tang C, Spetsieris PG, Dhawan V, Eidelberg D (2007) Abnormal metabolic network activity in Parkinson’s disease: test-retest reproducibility. J Cereb Blood Flow Metab 27:597–605
Neal JW, Pearson RC, Powell TP (1990) The ipsilateral corticocortical connections of area 7 with the frontal lobe in the monkey. Brain Res 509:31–40
Pahwa R, Wilkinson S, Smith D, Lyons K, Miyawaki E, Koller WC (1997) High-frequency stimulation of the globus pallidus for the treatment of Parkinson’s disease. Neurology 49:249–253
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
Pollak P, Benabid AL, Limousin P, Benazzouz A, Hoffmann D, Le Bas JF, Perret J (1996) Subthalamic nucleus stimulation alleviates akinesia and rigidity in parkinsonian patients. Adv Neurol 69:591–594
Strafella AP, Dagher A, Sadikot AF (2003) Cerebral blood flow changes induced by subthalamic stimulation in Parkinson’s disease. Neurology 60:1039–1042
Su PC, Ma Y, Fukuda M, Mentis MJ, Tseng HM, Yen RF, Liu HM, Moeller JR, Eidelberg D (2001) Metabolic changes following subthalamotomy for advanced Parkinson’s disease. Ann Neurol 50:514–520
Taktakishvili O, Sivan-Loukianova E, Kultas-Ilinsky K, Ilinsky IA (2002) Posterior parietal cortex projections to the ventral lateral and some association thalamic nuclei in Macaca mulatta. Brain Res Bull 59:135–150
Trost M, Su S, Su P, Yen RF, Tseng HM, Barnes A, Ma Y, Eidelberg D (2006) Network modulation by the subthalamic nucleus in the treatment of Parkinson’s disease. Neuroimage 31:301–307
Vafaee MS, ØStergaard K, Sunde N, Gjedde A, Dupont E, Cumming P (2004) Focal changes of oxygen consumption in cerebral cortex of patients with Parkinson’s disease during subthalamic stimulation. Neuroimage 22:966–974
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
Yeterian EH, Pandya DN (1985) Corticothalamic connections of the posterior parietal cortex in the rhesus monkey. J Comp Neurol 237:408–426
Zuo CT, Guan YH, Li DY, Sun BM (2005) The effect of bilateral subthalamic nucleus stimulation in the treatment of advanced PD. J Nucl Med 46(Suppl 1):189
Author information
Authors and Affiliations
Corresponding author
Additional information
J. Wang and Y. Ma contributed equally to this work.
Rights and permissions
About this article
Cite this article
Wang, J., Ma, Y., Huang, Z. et al. Modulation of metabolic brain function by bilateral subthalamic nucleus stimulation in the treatment of Parkinson’s disease. J Neurol 257, 72–78 (2010). https://doi.org/10.1007/s00415-009-5267-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-009-5267-3