Involvement of the subthalamic nucleus in impulse control disorders associated with Parkinson's disease.

Behavioural abnormalities such as impulse control disorders may develop when patients with Parkinson's disease receive dopaminergic therapy, although they can be controlled by deep brain stimulation of the subthalamic nucleus. We have recorded local field potentials in the subthalamic nucleus of 28 patients with surgically implanted subthalamic electrodes. According to the predominant clinical features of each patient, their Parkinson's disease was associated with impulse control disorders (n = 10), dyskinesias (n = 9) or no dopaminergic mediated motor or behavioural complications (n = 9). Recordings were obtained during the OFF and ON dopaminergic states and the power spectrum of the subthalamic activity as well as the subthalamocortical coherence were analysed using Fourier transform-based techniques. The position of each electrode contact was determined in the postoperative magnetic resonance image to define the topography of the oscillatory activity recorded in each patient. In the OFF state, the three groups of patients had similar oscillatory activity. By contrast, in the ON state, the patients with impulse control disorders displayed theta-alpha (4-10 Hz) activity (mean peak: 6.71 Hz) that was generated 2-8 mm below the intercommissural line. Similarly, the patients with dyskinesia showed theta-alpha activity that peaked at a higher frequency (mean: 8.38 Hz) and was generated 0-2 mm below the intercommissural line. No such activity was detected in patients that displayed no dopaminergic side effects. Cortico-subthalamic coherence was more frequent in the impulsive patients in the 4-7.5 Hz range in scalp electrodes placed on the frontal regions anterior to the primary motor cortex, while in patients with dyskinesia it was in the 7.5-10 Hz range in the leads overlying the primary motor and supplementary motor area. Thus, dopaminergic side effects in Parkinson's disease are associated with oscillatory activity in the theta-alpha band, but at different frequencies and with different topography for the motor (dyskinesias) and behavioural (abnormal impulsivity) manifestations. These findings suggest that the activity recorded in parkinsonian patients with impulse control disorders stems from the associative-limbic area (ventral subthalamic area), which is coherent with premotor frontal cortical activity. Conversely, in patients with l-dopa-induced dyskinesias such activity is recorded in the motor area (dorsal subthalamic area) and it is coherent with cortical motor activity. Consequently, the subthalamic nucleus appears to be implicated in the motor and behavioural complications associated with dopaminergic drugs in Parkinson's disease, specifically engaging different anatomo-functional territories.

[1]  B. Croisile,et al.  Hémiballisme avec libération thymo-affective et logorrhée par hématome du noyau sous-thalamique gauche. , 1995 .

[2]  Erwan Bezard,et al.  Chronic dopaminergic stimulation in Parkinson's disease: from dyskinesias to impulse control disorders , 2009, The Lancet Neurology.

[3]  G. Deuschl,et al.  Subthalamic nucleus deep brain stimulation: Summary and meta‐analysis of outcomes , 2006, Movement disorders : official journal of the Movement Disorder Society.

[4]  Sacha Jennifer van Albada,et al.  Transformation of arbitrary distributions to the normal distribution with application to EEG test–retest reliability , 2007, Journal of Neuroscience Methods.

[5]  Michael J. Frank,et al.  Hold Your Horses: Impulsivity, Deep Brain Stimulation, and Medication in Parkinsonism , 2007, Science.

[6]  G. Deuschl,et al.  A randomized trial of deep-brain stimulation for Parkinson's disease. , 2006, The New England journal of medicine.

[7]  A. Oliviero,et al.  Dopamine Dependency of Oscillations between Subthalamic Nucleus and Pallidum in Parkinson's Disease , 2001, The Journal of Neuroscience.

[8]  Daniel Weintraub,et al.  Validation of the questionnaire for impulsive‐compulsive disorders in Parkinson's disease , 2009, Movement disorders : official journal of the Movement Disorder Society.

[9]  H. Bergman,et al.  The primate subthalamic nucleus. I. Functional properties in intact animals. , 1994, Journal of neurophysiology.

[10]  Vesna Sossi,et al.  Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson's disease: implications for dyskinesias. , 2004, Brain : a journal of neurology.

[11]  U Sabatini,et al.  Cortical motor overactivation in parkinsonian patients with L-dopa-induced peak-dose dyskinesia. , 1998, Brain : a journal of neurology.

[12]  C B Saw,et al.  Coordinate transformations and calculation of the angular and depth parameters for a stereotactic system. , 1987, Medical physics.

[13]  Y. Agid,et al.  Stimulation of subterritories of the subthalamic nucleus reveals its role in the integration of the emotional and motor aspects of behavior , 2007, Proceedings of the National Academy of Sciences.

[14]  K. Josephs,et al.  Unusual compulsive behaviors primarily related to dopamine agonist therapy in Parkinson's disease and multiple system atrophy. , 2007, Parkinsonism & related disorders.

[15]  Rajita Sinha,et al.  Subcortical processes of motor response inhibition during a stop signal task , 2008, NeuroImage.

[16]  Mathematical theory of stereotactic coordinate transformation: elimination of rotational targeting error by addition of a third reference point. Technical note. , 2000, Journal of neurosurgery.

[17]  P. Starr,et al.  Implantation of deep brain stimulators into the subthalamic nucleus: technical approach and magnetic resonance imaging-verified lead locations. , 2002, Journal of neurosurgery.

[18]  P. Brown Oscillatory nature of human basal ganglia activity: Relationship to the pathophysiology of Parkinson's disease , 2003, Movement disorders : official journal of the Movement Disorder Society.

[19]  A. Priori,et al.  Deep brain stimulation for Parkinson's disease: the experience of the Policlinico-San Paolo Group in Milan , 2003, Neurological Sciences.

[20]  M. Sambrook,et al.  Experimental hemichorea/hemiballismus in the monkey. Studies on the intracerebral site of action in a drug-induced dyskinesia. , 1984, Brain : a journal of neurology.

[21]  O. Suchowersky,et al.  Gambling and Parkinson disease. , 2006, Archives of neurology.

[22]  Jorge Iriarte,et al.  Coupling between Beta and High-Frequency Activity in the Human Subthalamic Nucleus May Be a Pathophysiological Mechanism in Parkinson's Disease , 2010, The Journal of Neuroscience.

[23]  J. Régis,et al.  Addiction in Parkinson's disease: Impact of subthalamic nucleus deep brain stimulation , 2005, Movement disorders : official journal of the Movement Disorder Society.

[24]  P. Apicella,et al.  Reward-related neuronal activity in the subthalamic nucleus of the monkey , 2005, Neuroreport.

[25]  P. Doshi,et al.  Hypersexuality following subthalamic nucleus stimulation for Parkinson's disease. , 2008, Neurology India.

[26]  A. Lozano,et al.  Targeting the basal ganglia for deep brain stimulation in Parkinson's disease. , 2000, Neurology.

[27]  M. Silber,et al.  Pathologic gambling in patients with restless legs syndrome treated with dopaminergic agonists , 2007, Neurology.

[28]  J A Obeso,et al.  Movement‐related changes in oscillatory activity in the human subthalamic nucleus: ipsilateral vs. contralateral movements , 2005, The European journal of neuroscience.

[29]  M. Jahanshahi,et al.  STN Stimulation Alters Pallidal—Frontal Coupling during Response Selection under Competition , 2007, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[30]  S. Houle,et al.  Increased striatal dopamine release in Parkinsonian patients with pathological gambling: a [11C] raclopride PET study. , 2009, Brain : a journal of neurology.

[31]  J. Villemure,et al.  l-Dopa-induced dyskinesia improvement after STN-DBS depends upon medication reduction , 2004, Neurology.

[32]  C. Baunez,et al.  Beyond the reward pathway: coding reward magnitude and error in the rat subthalamic nucleus. , 2009, Journal of neurophysiology.

[33]  J. P. Martin HEMICHOREA RESULTING FROM A LOCAL LESION OF THE BRAIN. (THE SYNDROME OF THE BODY OF LUYS , 1927 .

[34]  J. Obeso,et al.  Efficacy of deep brain stimulation of the subthalamic nucleus in Parkinson’s disease 4 years after surgery: double blind and open label evaluation , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[35]  J A Obeso,et al.  Slow oscillatory activity and levodopa-induced dyskinesias in Parkinson's disease. , 2006, Brain : a journal of neurology.

[36]  P. Grunert,et al.  Accuracy of stereotactic coordinate transformation using a localisation frame and computed tomographic imaging , 1999, Neurosurgical Review.

[37]  P. Gatev,et al.  Oscillations in the basal ganglia under normal conditions and in movement disorders , 2006, Movement disorders : official journal of the Movement Disorder Society.

[38]  C. Honey,et al.  Hypomania as an adverse effect of subthalamic nucleus stimulation: report of two cases , 2006, Acta Neurochirurgica.

[39]  J. Artieda,et al.  High frequency oscillations in the somatosensory evoked potentials (SSEP's) are mainly due to phase-resetting phenomena , 2006, Journal of Neuroscience Methods.

[40]  DeLong Mr,et al.  The neurophysiologic basis of abnormal movements in basal ganglia disorders. , 1983 .

[41]  K. Mewes,et al.  The subthalamic nucleus in Parkinson's disease: somatotopic organization and physiological characteristics. , 2001, Brain : a journal of neurology.

[42]  P. Zhuang,et al.  Stimulation-Induced Dyskinesia in the Early Stage after Subthalamic Deep Brain Stimulation , 2009, Stereotactic and Functional Neurosurgery.

[43]  J. Kulisevsky,et al.  Mania following deep brain stimulation for Parkinson's disease. , 2002, Neurology.

[44]  D J Brooks,et al.  Neuroimaging of dyskinesia. , 2000, Annals of neurology.

[45]  H. Butzkueven,et al.  Dopamine agonist‐induced pathological gambling in restless legs syndrome due to multiple sclerosis , 2007, Movement disorders : official journal of the Movement Disorder Society.

[46]  Y. Agid,et al.  Clinical predictive factors of subthalamic stimulation in Parkinson's disease. , 2002, Brain : a journal of neurology.

[47]  A. Lang,et al.  Prospective prevalence of pathologic gambling and medication association in Parkinson disease , 2006, Neurology.

[48]  Shailendra Kapoor,et al.  Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. , 2009, The New England journal of medicine.

[49]  T. Robbins,et al.  Bilateral Lesions of the Subthalamic Nucleus Induce Multiple Deficits in an Attentional Task in Rats , 1997, The European journal of neuroscience.

[50]  J. Ghika,et al.  Subthalamic DBS replaces levodopa in Parkinson’s disease: Two-year follow-up , 2002, Neurology.

[51]  L. Tremblay,et al.  Non-motor dopamine withdrawal syndrome after surgery for Parkinson's disease: predictors and underlying mesolimbic denervation. , 2010, Brain : a journal of neurology.

[52]  J. Obeso,et al.  Bilateral deep brain stimulation of the subthalamic nucleus in Parkinson's disease. , 2000, Neurology.

[53]  Tyrone D. Cannon,et al.  Markers of Basal Ganglia Dysfunction and Conversion to Psychosis: Neurocognitive Deficits and Dyskinesias in the Prodromal Period , 2010, Biological Psychiatry.

[54]  Paul Krack,et al.  Mirthful laughter induced by subthalamic nucleus stimulation , 2001, Movement disorders : official journal of the Movement Disorder Society.

[55]  T. Robbins,et al.  Enhanced Food-Related Motivation after Bilateral Lesions of the Subthalamic Nucleus , 2002, The Journal of Neuroscience.

[56]  A L Benabid,et al.  From off-period dystonia to peak-dose chorea. The clinical spectrum of varying subthalamic nucleus activity. , 1999, Brain : a journal of neurology.

[57]  [Hemiballismus with logorrhea and thymo-affective disinhibition caused by hematoma of the left subthalamic nucleus]. , 1995, Revue neurologique.

[58]  J. Yelnik Functional anatomy of the basal ganglia , 2002, Movement disorders : official journal of the Movement Disorder Society.

[59]  R. Katzenschlager,et al.  Punding and dyskinesias , 2006, Movement disorders : official journal of the Movement Disorder Society.

[60]  O. Suchowersky,et al.  Pathological gambling associated with dopamine agonist use in restless legs syndrome. , 2007, Parkinsonism & related disorders.

[61]  Theodor Landis,et al.  Compulsive singing: another aspect of punding in Parkinson's disease , 2007, Annals of neurology.

[62]  A. Lawrence,et al.  Dopamine dysregulation syndrome, impulse control disorders and punding after deep brain stimulation surgery for Parkinson’s disease , 2009, Journal of Clinical Neuroscience.

[63]  A. Lawrence,et al.  Compulsive use of dopamine replacement therapy in Parkinson's disease: reward systems gone awry? , 2003, The Lancet Neurology.

[64]  F. Limosin,et al.  Manic episode with psychotic symptoms in a patient with Parkinson's disease treated by subthalamic nucleus stimulation: Improvement on switching the target , 2008, Journal of the Neurological Sciences.

[65]  G. Deuschl,et al.  Deep brain stimulation of the subthalamic nucleus improves cognitive flexibility but impairs response inhibition in Parkinson disease. , 2004, Archives of neurology.

[66]  Matteo Pizzorno,et al.  Using STN DBS and medication reduction as a strategy to treat pathological gambling in Parkinson's disease. , 2007, Parkinsonism & related disorders.

[67]  J. Hughes,et al.  Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. , 1992, Journal of neurology, neurosurgery, and psychiatry.

[68]  A. Lang,et al.  Utility of an objective dyskinesia rating scale for Parkinson's disease: Inter‐ and intrarater reliability assessment , 1994, Movement disorders : official journal of the Movement Disorder Society.

[69]  Antonio Daniele,et al.  Transient mania with hypersexuality after surgery for high frequency stimulation of the subthalamic nucleus in Parkinson's disease , 2002, Movement disorders : official journal of the Movement Disorder Society.

[70]  J. Obeso,et al.  Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up. , 2005, Brain : a journal of neurology.

[71]  D. Brooks,et al.  Core assessment program for intracerebral transplantations (CAPIT) , 1992, Movement disorders : official journal of the Movement Disorder Society.

[72]  S. Houle,et al.  Stimulation of the subthalamic nucleus and impulsivity: Release your horses , 2009, Annals of neurology.

[73]  J. Obeso,et al.  Homocysteine and cognitive impairment in Parkinson's disease: A biochemical, neuroimaging, and genetic study , 2009, Movement disorders : official journal of the Movement Disorder Society.

[74]  T. Reinehr,et al.  Plasma Levels of Coenzyme Q10 in Children with Hyperthyroidism , 2004, Hormone Research in Paediatrics.

[75]  D. Grosset,et al.  Problematic gambling on dopamine agonists: Not such a rarity , 2006, Movement disorders : official journal of the Movement Disorder Society.

[76]  D. Grosset,et al.  Switching from ergot to nonergot dopamine agonists in Parkinson's disease: A clinical series and five‐drug dose conversion table , 2004, Movement disorders : official journal of the Movement Disorder Society.

[77]  J F Dicello,et al.  A simple and accurate coordinate transformation for a stereotactic radiotherapy system. , 1999, Medical physics.

[78]  I Litvan,et al.  Bilateral subthalamotomy in Parkinson's disease: initial and long-term response. , 2005, Brain : a journal of neurology.

[79]  P. Brown,et al.  The subthalamic region is activated during valence‐related emotional processing in patients with Parkinson's disease , 2007, The European journal of neuroscience.

[80]  Bettina Schrader,et al.  Manic episode with psychotic symptoms induced by subthalamic nucleus stimulation in a patient with Parkinson's disease , 2003, Movement disorders : official journal of the Movement Disorder Society.

[81]  Yen F. Tai,et al.  Compulsive drug use linked to sensitized ventral striatal dopamine transmission , 2006, Annals of neurology.

[82]  V. Leirer,et al.  Development and validation of a geriatric depression screening scale: a preliminary report. , 1982, Journal of psychiatric research.

[83]  Niels Sunde,et al.  Effects of bilateral stimulation of the subthalamic nucleus in patients with severe Parkinson's disease and motor fluctuations , 2002, Movement disorders : official journal of the Movement Disorder Society.

[84]  L. Hazrati,et al.  Functional anatomy of the basal ganglia , 1995 .

[85]  A. Benabid,et al.  Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson's disease. , 2003, The New England journal of medicine.

[86]  A. Berney,et al.  Rapid Resolution of Dopamine Dysregulation Syndrome (DDS) After Subthalamic DBS for Parkinson Disease (PD): A Case Report , 2008, Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology.

[87]  M R DeLong,et al.  The neurophysiologic basis of abnormal movements in basal ganglia disorders. , 1983, Neurobehavioral toxicology and teratology.

[88]  L Lopiano,et al.  Deep brain stimulation of the subthalamic nucleus: anatomical, neurophysiological, and outcome correlations with the effects of stimulation , 2002, Journal of neurology, neurosurgery, and psychiatry.

[89]  A M Amjad,et al.  A framework for the analysis of mixed time series/point process data--theory and application to the study of physiological tremor, single motor unit discharges and electromyograms. , 1995, Progress in biophysics and molecular biology.

[90]  R. Poldrack,et al.  Cortical and Subcortical Contributions to Stop Signal Response Inhibition: Role of the Subthalamic Nucleus , 2006, The Journal of Neuroscience.

[91]  P. Moberg,et al.  Association of dopamine agonist use with impulse control disorders in Parkinson disease. , 2006, Archives of neurology.

[92]  Okihide Hikosaka,et al.  Visual and oculomotor functions of monkey subthalamic nucleus. , 1992 .

[93]  Thomas Wichmann,et al.  Effects of Transient Focal Inactivation of the Basal Ganglia in Parkinsonian Primates , 2002, The Journal of Neuroscience.

[94]  A. Strafella,et al.  Reduced dopamine transporter density in the ventral striatum of patients with Parkinson's disease and pathological gambling , 2010, Neurobiology of Disease.

[95]  V. Brown,et al.  Anticipatory errors after unilateral lesions of the subthalamic nucleus in the rat: evidence for a failure of response inhibition. , 2000, Behavioral neuroscience.

[96]  J. Jankowski,et al.  Distinct striatal regions for planning and executing novel and automated movement sequences , 2009, NeuroImage.