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Selective Stimulation of the Subthalamic Nucleus in Parkinson's Selective stimulation of the subthalamic nucleus in Parkinson’s disease: dream or near future Citation for published version (APA): Janssen, M. L. F. (2015). Selective stimulation of the subthalamic nucleus in Parkinson’s disease: dream or near future. Datawyse / Universitaire Pers Maastricht. https://doi.org/10.26481/dis.20150513mj Document status and date: Published: 01/01/2015 DOI: 10.26481/dis.20150513mj Document Version: Publisher's PDF, also known as Version of record Please check the document version of this publication: • A submitted manuscript is the version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. 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Mark Janssen Mark Janssen Omslag Mark Janssen 351x240mm 198p 100MC silk.indd 1 25-3-2015 16:15:20 Aan mijn ouders Foto omslag: Yara Verstappen Productie: Datawyse | Universitaire Pers Maastricht ISBN 978 94 6159 435 8 © Copyright MLF Janssen, Maastricht 2015 Selective stimulation of the subthalamic nucleus in Parkinson’s disease dream or near future? ter verkrijging van de graad van doctor aan de Universiteit Maastricht, op gezag van de Rector Magnificus, Prof. dr L.L.G. Soete volgens het besluit van het College van Decanen, in het openbaar te verdedigen op woensdag 13 mei 2015 om 16.00 uur door Marcus Leo Franciscus Janssen UMP UNIVERSITAIRE PERS MAASTRICHT Promotores Prof. dr. Y. Temel Prof. dr. V. Visser-Vandewalle Prof. dr. A. Benazzouz, Institut des Maladies Neurodégénératives, Bordeaux, France. Beoordelingscommissie Prof. dr. R. Van Oostenbrugge (voorzitter) Dr. R. Esselink, UMC St Radboud Nijmegen Prof. dr. B. Falkenburger, RWTH University Aachen, Germany Prof. dr. W. Mess Prof. dr J.J. Van Overbeeke Content Abbreviations ...................................................................................................................... 7 General introduction Parkinson’s disease, the subthalamic nucleus and deep brain stimulation. ..................................................................................................... 9 CHAPTER 1 Subthalamic nucleus high frequency stimulation for advanced Parkinson’s disease: motor and neuropsychological outcome after 10 years. ............................................................................................................. 19 CHAPTER 2 High frequency stimulation of the subthalamic nucleus increases c-Fos immunoreactivity in the dorsal raphe nucleus and afferent brain regions .......................................................................................................... 31 CHAPTER 3 Cortico-subthalamic projections in the rat ................................................... 51 CHAPTER 4 The antidepressant effects of ventromedial prefrontal cortex is associated with neural activation in the medial part of the subthalamic nucleus .......................................................................................................... 73 CHAPTER 5 Functional cortico-subthalamic inputs from the motor, limbic and associative areas in normal and dopamine depleted rats ........................... 87 CHAPTER 6 Subthalamic Neuronal Responses to Cortical Stimulation ......................... 105 CHAPTER 7 Cortically evoked potentials in the human subthalamic nucleus .............. 115 CHAPTER 8 Automated gait analysis in bilateral Parkinsonian rats and the role of L-DOPA therapy .......................................................................................... 125 CHAPTER 9 Mild dopaminergic lesions are accompanied by robust changes in subthalamic nucleus activity. ...................................................................... 151 DISCUSSION .................................................................................................................... 165 Summary .................................................................................................................... 173 Samenvatting .................................................................................................................. 179 Valorisation .................................................................................................................... 183 Dankwoord .................................................................................................................... 187 Biography .................................................................................................................... 193 List of publications .......................................................................................................... 195 Oral presentations .......................................................................................................... 197 Poster presentations ....................................................................................................... 197 Abbreviations AI agranular insular ADL activities of daily living AP anteroposterior BDA biotinylated dextran amine BDI Beck depression inventory c-Fos-ir c-Fos immunoreactivity Cg cingulate gyrus CMA cingulate motor area COX cytochrome C oxidase CPu caudate putamen CVLT California verbal learning test DA dopamine DAB 3,3-diaminobenzidine DBS deep brain stimulation DRN dorsal raphe nucleus DTI diffusing tensor imaging EP entepeduncular nucleus FST forced swim test GABA γ-aminobutyric acid GP globus pallidus GPe globus pallidus externus GPi globus pallidus internus HFS high frequency stimulation HRP horseradish peroxide IFC inferior frontal cortex IL infralimbic LED levodopa equivalent dose LFP local field potential LHb lateral habenula LSD least significant difference MC motor cortex MCS motor cortex stimulation ML mediolateral MMSE mini mental state examination mPFC medial prefrontal cortex MSA multi system atrophy 7 MT motor time M1 lateral agranular cortex; primary motor cortex NAc nucleus accumbens NiCL2 nickel chloride PD Parkinson’s disease PHA-L leucoagglutinin PPN peduncular pontine nucleus PR premature responses PrL prelimbic PSTH peristimulus time histogram SD standard deviation SEM standard error of mean SMA supplementary motor area SN substantia nigra SNc substantia nigra compacta SNr substantia nigra reticulata STN subthalamic nucleus TBS tris-buffered saline TBS-T tris-buffered saline -Triton TMS transcranial magnetic stimulation TH tyrosine hydroxylase THir tyrosine hydroxylase immunoreactive UPDRS unified Parkinson’s disease rating scale VD ventrodorsal vmPFC ventromedial prefrontal cortex WGA-HRP wheat germ agglutinin-horseradish peroxidase 5-HT 5-hydroxytryptamine; serotonin 6-OHDA 6-hydroxy-dopamine 8 General introduction Parkinson’s disease, the subthalamic nucleus and deep brain stimulation. 9 INTRODUCTION Parkinson’s disease Parkinson disease (PD) is a prevalent progressive neurodegenerative disorder with a major impact on the quality of life of patients and their families (Albin, et al., 1989, Wichmann and DeLong, 1996). In addition, due to the demographic changes the preva- lence is increasing and leading to a larger socio-economic burden. In Europe 108 out of 100.000 people suffer from PD (Virginia, 2008). The key motor symptoms are tremor, rigidity, bradykinesia and postural instability (Blandini, et al., 2000, Haegelen, et al., 2009). Besides the motor symptoms, PD patients also suffer from non-motor symptoms such as cognitive impairments and mood changes. PD was recognized in 1817 when the British physician James Parkinson published his essay on the ‘shaking palsy (Parkinson, 1817). Loss of neuromelanin-containing dopamine (DA) cells in the substantia nigra pars compacta (SNc) is one of the main neuropathological hallmarks of the disease with the presence of Lewy bodies. Lewy bodies are abnormal aggregates of alpha-synuclein fi- brils inside neurons. In the early stages of the disease motor symptoms can be ade- quately treated by DA replacement therapy,
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