Multiple Modes of Impulsivity in Parkinson's Disease

Cognitive problems are a major factor determining quality of life of patients with Parkinson's disease. These include deficits in inhibitory control, ranging from subclinical alterations in decision-making to severe impulse control disorders. Based on preclinical studies, we proposed that Parkinson's disease does not cause a unified disorder of inhibitory control, but rather a set of impulsivity factors with distinct psychological profiles, anatomy and pharmacology. We assessed a broad set of measures of the cognitive, behavioural and temperamental/trait aspects of impulsivity. Sixty adults, including 30 idiopathic Parkinson's disease patients (Hoehn and Yahr stage I–III) and 30 healthy controls, completed a neuropsychological battery, objective behavioural measures and self-report questionnaires. Univariate analyses of variance confirmed group differences in nine out of eleven metrics. We then used factor analysis (principal components method) to identify the structure of impulsivity in Parkinson's disease. Four principal factors were identified, consistent with four different mechanisms of impulsivity, explaining 60% of variance. The factors were related to (1) tests of response conflict, interference and self assessment of impulsive behaviours on the Barrett Impulsivity Scale, (2) tests of motor inhibitory control, and the self-report behavioural approach system, (3) time estimation and delay aversion, and (4) reflection in hypothetical scenarios including temporal discounting. The different test profiles of these four factors were consistent with human and comparative studies of the pharmacology and functional anatomy of impulsivity. Relationships between each factor and clinical and demographic features were examined by regression against factor loadings. Levodopa dose equivalent was associated only with factors (2) and (3). The results confirm that impulsivity is common in Parkinson's disease, even in the absence of impulse control disorders, and that it is not a unitary phenomenon. A better understanding of the structure of impulsivity in Parkinson's disease will support more evidence-based and effective strategies to treat impulsivity.

[1]  A. Bonnet,et al.  [The Unified Parkinson's Disease Rating Scale]. , 2000, Revue neurologique.

[2]  Jan Peters,et al.  The neural mechanisms of inter-temporal decision-making: understanding variability , 2011, Trends in Cognitive Sciences.

[3]  R. Carpenter,et al.  Saccadometry: A novel clinical tool for quantification of the motor effects of subthalamic nucleus stimulation in Parkinson's disease , 2009, Experimental Neurology.

[4]  Emma S. J. Robinson,et al.  Dissociable effects of noradrenaline, dopamine, and serotonin uptake blockade on stop task performance in rats , 2009, Psychopharmacology.

[5]  D. Royall,et al.  The FAB: A frontal assessment battery at bedside , 2001, Neurology.

[6]  Andrew T. Morgan,et al.  Behavioral/systems/cognitive Striatal Dopamine D 2 /d 3 Receptors Mediate Response Inhibition and Related Activity in Frontostriatal Neural Circuitry in Humans Impulsive Behavior Is Thought to Reflect a Traitlike Characteristic That Can Have Broad Consequences for an Individual's Success and Well-be , 2022 .

[7]  R. Barker,et al.  The val158met COMT polymorphism's effect on atrophy in healthy aging and Parkinson's disease , 2010, Neurobiology of Aging.

[8]  C. Frith,et al.  The functional anatomy of verbal initiation and suppression using the Hayling Test , 1997, Neuropsychologia.

[9]  R. Dolan,et al.  Dopamine-dependent prediction errors underpin reward-seeking behaviour in humans , 2006, Nature.

[10]  M. Bouvard,et al.  Étude du tempérament et de la personnalité chez l’enfant souffrant d’un trouble déficit d’attention/hyperactivité (TDAH) , 2012 .

[11]  F. Fera,et al.  Dopaminergic modulation of cognitive interference after pharmacological washout in Parkinson's disease , 2007, Brain Research Bulletin.

[12]  Andrew J Lees,et al.  Intact Reward Learning but Elevated Delay Discounting in Parkinson's Disease Patients With Impulsive-Compulsive Spectrum Behaviors , 2010, Neuropsychopharmacology.

[13]  Masaru Mimura,et al.  Decision making in Parkinson's disease: Analysis of behavioral and physiological patterns in the Iowa gambling task , 2008, Movement disorders : official journal of the Movement Disorder Society.

[14]  M. S. Lee,et al.  The effect of age on motor deficits and cerebral glucose metabolism of Parkinson’s disease , 2011, Acta neurologica Scandinavica.

[15]  M. Hoehn,et al.  Parkinsonism , 1967, Neurology.

[16]  E. Barratt Impulsiveness and aggression. , 1994 .

[17]  B. Averbeck,et al.  Novelty seeking behaviour in Parkinson's disease , 2011, Neuropsychologia.

[18]  U. Bonuccelli,et al.  Impulse control disorders in Parkinson's disease: definition, epidemiology, risk factors, neurobiology and management. , 2009, Parkinsonism & related disorders.

[19]  Rebecca Elliott,et al.  The Effect of Citalopram Pretreatment on Neuronal Responses to Neuropsychological Tasks in Normal Volunteers: An fMRI Study , 2005, Neuropsychopharmacology.

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

[21]  P. Krack,et al.  Deep brain stimulation: from neurology to psychiatry? , 2010, Trends in Neurosciences.

[22]  E. Petrusa,et al.  A Multicenter Study to Provide Evidence of Construct Validity in a Computer-Based Outcome Measure of Neurology Clinical Skills , 2005, Academic medicine : journal of the Association of American Medical Colleges.

[23]  T. Robbins,et al.  A neuropsychological comparison of obsessive–compulsive disorder and trichotillomania , 2007, Neuropsychologia.

[24]  M. Rieger,et al.  Inhibition of ongoing responses in patients with Parkinson’s disease , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[25]  R. H. S. Carpenter,et al.  Neural computation of log likelihood in control of saccadic eye movements , 1995, Nature.

[26]  M. Zapata,et al.  [Risk of pathological gambling, Associated factors and mental disorders in youth from Medellin - Colombia]. , 2011, Adicciones.

[27]  Dawn M Eagle,et al.  Contrasting Roles for Dopamine D1 and D2 Receptor Subtypes in the Dorsomedial Striatum but Not the Nucleus Accumbens Core during Behavioral Inhibition in the Stop-Signal Task in Rats , 2011, The Journal of Neuroscience.

[28]  F. Meneghello,et al.  Brain volume changes in Parkinson's disease and their relationship with cognitive and behavioural abnormalities , 2011, Journal of the Neurological Sciences.

[29]  S. Calugi,et al.  Effects of cognitive-behavioral therapy on Eating Disorders: Neurotransmitter secretory response to treatment , 2010, Psychoneuroendocrinology.

[30]  Kaarin J Anstey,et al.  Hippocampal volume is positively associated with behavioural inhibition (BIS) in a large community-based sample of mid-life adults: the PATH through life study. , 2008, Social cognitive and affective neuroscience.

[31]  K. Chaudhuri,et al.  The impact of non‐motor symptoms on health‐related quality of life of patients with Parkinson's disease , 2011, Movement disorders : official journal of the Movement Disorder Society.

[32]  Karl J. Friston,et al.  Frontal, midbrain and striatal dopaminergic function in early and advanced Parkinson's disease A 3D [(18)F]dopa-PET study. , 1999, Brain : a journal of neurology.

[33]  B. Wollschlaeger Impulse Control Disorders: A Clinician’s Guide to Understanding and Treating Behavioral Addictions , 2008 .

[34]  Viviane Pouthas,et al.  Effects of internal clock and memory disorders on duration reproductions and duration productions in patients with Parkinson’s disease , 2005, Brain and Cognition.

[35]  W. Dauer,et al.  Parkinson's Disease Mechanisms and Models , 2003, Neuron.

[36]  T. Braver,et al.  Anterior cingulate cortex and response conflict: effects of response modality and processing domain. , 2001, Cerebral Cortex.

[37]  J. Kenemans,et al.  Methylphenidate Restores Link Between Stop-Signal Sensory Impact and Successful Stopping in Adults with Attention-Deficit/Hyperactivity Disorder , 2009, Biological Psychiatry.

[38]  John C. Rothwell,et al.  The right dorsolateral prefrontal cortex is essential in time reproduction: an investigation with repetitive transcranial magnetic stimulation , 2004, Experimental Brain Research.

[39]  C. Kruse,et al.  Modulation of midbrain dopamine neurotransmission by serotonin, a versatile interaction between neurotransmitters and significance for antipsychotic drug action. , 2006, Current neuropharmacology.

[40]  Michael J. Frank,et al.  Dynamic Dopamine Modulation in the Basal Ganglia: A Neurocomputational Account of Cognitive Deficits in Medicated and Nonmedicated Parkinsonism , 2005, Journal of Cognitive Neuroscience.

[41]  T. Robbins,et al.  Serotonin Depletion Impairs Waiting but not Stop-Signal Reaction Time in Rats: Implications for Theories of the Role of 5-HT in Behavioral Inhibition , 2009, Neuropsychopharmacology.

[42]  T. Münte,et al.  Intertemporal choice in Parkinson's disease , 2011, Movement disorders : official journal of the Movement Disorder Society.

[43]  T. Boult,et al.  The eyes have it , 2003, WBMA '03.

[44]  Y. Agid,et al.  Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson's disease , 1983, Brain Research.

[45]  Y. D. Werf,et al.  Parkinson’s disease-related disorders in the impulsive-compulsive spectrum , 2008, Journal of Neurology.

[46]  Melissa J. Allman,et al.  Pathophysiological distortions in time perception and timed performance. , 2012, Brain : a journal of neurology.

[47]  A. Antonini,et al.  Functional abnormalities underlying pathological gambling in Parkinson disease. , 2008, Archives of neurology.

[48]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[49]  Tim Shallice,et al.  The Hayling and Brixton Tests , 1997 .

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

[51]  J. Ridley Studies of Interference in Serial Verbal Reactions , 2001 .

[52]  G. Logan,et al.  Converging Evidence for a Fronto-Basal-Ganglia Network for Inhibitory Control of Action and Cognition , 2007, The Journal of Neuroscience.

[53]  Yasuyuki Taki,et al.  Regional gray and white matter volume associated with Stroop interference: Evidence from voxel-based morphometry , 2012, NeuroImage.

[54]  Trevor W Robbins,et al.  Motor inhibition and cognitive flexibility in obsessive-compulsive disorder and trichotillomania. , 2006, The American journal of psychiatry.

[55]  T. Robbins,et al.  Catechol O-Methyltransferase val158met Genotype Influences Frontoparietal Activity during Planning in Patients with Parkinson's Disease , 2007, The Journal of Neuroscience.

[56]  Daniel Weintraub,et al.  Drug Insight: impulse control disorders and dopamine therapies in Parkinson's disease , 2007, Nature Clinical Practice Neurology.

[57]  T. Robbins,et al.  The neuropsychopharmacology of action inhibition: cross-species translation of the stop-signal and go/no-go tasks , 2008, Psychopharmacology.

[58]  S. Mobini,et al.  Effect of central 5-hydroxytryptamine depletion on inter-temporal choice: a quantitative analysis , 2000, Psychopharmacology.

[59]  R. Barker,et al.  The Addenbrooke's Cognitive Examination for the differential diagnosis and longitudinal assessment of patients with parkinsonian disorders , 2013, Journal of Neurology, Neurosurgery & Psychiatry.

[60]  W. Gibb,et al.  The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[61]  D. Eckstein,et al.  Parkinson's disease and dopaminergic therapy—differential effects on movement, reward and cognition , 2008, Brain : a journal of neurology.

[62]  E. Esposito,et al.  Serotonin-dopamine interaction: electrophysiological evidence. , 2008, Progress in brain research.

[63]  M. Rietschel,et al.  Adolescent impulsivity phenotypes characterized by distinct brain networks , 2012, Nature Neuroscience.

[64]  Catalin V. Buhusi,et al.  Effect of clozapine on interval timing and working memory for time in the peak-interval procedure with gaps , 2007, Behavioural Processes.

[65]  Julio Acosta-Cabronero,et al.  Social cognitive deficits and their neural correlates in progressive supranuclear palsy , 2012, Brain : a journal of neurology.

[66]  John R Hodges,et al.  The Addenbrooke's Cognitive Examination Revised (ACE‐R): a brief cognitive test battery for dementia screening , 2006, International journal of geriatric psychiatry.

[67]  T. Robbins,et al.  Impulsivity, Compulsivity, and Top-Down Cognitive Control , 2011, Neuron.

[68]  Timothy E. J. Behrens,et al.  Dissociable Reward and Timing Signals in Human Midbrain and Ventral Striatum , 2011, Neuron.

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

[70]  Marjan Jahanshahi,et al.  Deficits in inhibitory control and conflict resolution on cognitive and motor tasks in Parkinson’s disease , 2011, Experimental Brain Research.

[71]  A. Beck,et al.  Psychometric properties of the Beck Depression Inventory: Twenty-five years of evaluation , 1988 .

[72]  T. Robbins,et al.  Methylphenidate (‘Ritalin’) can Ameliorate Abnormal Risk-Taking Behavior in the Frontal Variant of Frontotemporal Dementia , 2006, Neuropsychopharmacology.

[73]  P. Barone,et al.  Impulsivity and compulsivity in drug‐naïve patients with Parkinson's disease , 2011, Movement disorders : official journal of the Movement Disorder Society.

[74]  Jae-on Kim,et al.  Introduction to Factor Analysis , 1978 .

[75]  L. Montoya,et al.  Riesgo de Juego Patológico. Factores y trastornos mentales asociados en jóvenes de Medellín - Colombia , 2011 .

[76]  M Vidailhet,et al.  Mixing pro- and antisaccades in patients with parkinsonian syndromes. , 2006, Brain : a journal of neurology.

[77]  J. Gibbon,et al.  Scalar expectancy theory and peak-interval timing in humans. , 1998, Journal of experimental psychology. Animal behavior processes.

[78]  Emanuele Lo Gerfo,et al.  Impaired reproduction of second but not millisecond time intervals in Parkinson's disease , 2008, Neuropsychologia.

[79]  C. Huang-Pollock,et al.  Examining Relationships Between Executive Functioning and Delay Aversion in Attention Deficit Hyperactivity Disorder , 2011, Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53.

[80]  W. Schultz Book Review: Reward Signaling by Dopamine Neurons , 2001, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[81]  R. Barker,et al.  “The eyes have it”. Saccadometry and Parkinson's disease , 2009, Experimental Neurology.

[82]  T. Robbins,et al.  Prefrontal and Monoaminergic Contributions to Stop-Signal Task Performance in Rats , 2011, The Journal of Neuroscience.

[83]  M. Leboyer,et al.  Prefrontal cortex dysfunction in patients with suicidal behavior , 2006, Psychological Medicine.

[84]  John Monahan,et al.  Violence and mental disorder: Developments in risk assessment. , 1994 .

[85]  K. Kirby,et al.  Delay-discounting probabilistic rewards: Rates decrease as amounts increase , 1996, Psychonomic bulletin & review.

[86]  M J Stokes,et al.  EEG-based communication: a pattern recognition approach. , 2000, IEEE transactions on rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society.

[87]  A. Antonini,et al.  The relationship between impulsivity and impulse control disorders in Parkinson's disease , 2008, Movement disorders : official journal of the Movement Disorder Society.

[88]  T. Braver,et al.  Anterior Cingulate Cortex and Response Conflict : Effects of Response Modality and Processing Domain , 2022 .

[89]  D. Marazziti,et al.  Decreased Density of the Platelet Serotonin Transporter in Pathological Gamblers , 2008, Neuropsychobiology.

[90]  Lynn Rochester,et al.  Gait variability in Parkinson’s disease: an indicator of non-dopaminergic contributors to gait dysfunction? , 2011, Journal of Neurology.

[91]  T. Roth,et al.  Sleepiness in Parkinson's disease: A controlled study , 2003, Movement disorders : official journal of the Movement Disorder Society.

[92]  T. Robbins,et al.  Noradrenergic versus dopaminergic modulation of impulsivity, attention and monitoring behaviour in rats performing the stop-signal task , 2013, Psychopharmacology.

[93]  A. Rotondo,et al.  Clozapine for medication‐related pathological gambling in Parkinson disease , 2010, Movement Disorders.

[94]  E. Barratt,et al.  Anxiety and Impulsiveness Related to Psychomotor Efficiency , 1959 .

[95]  Myrna B. Shure,et al.  The Impulsive client : theory, research, and treatment , 1993 .

[96]  D. Marazziti,et al.  Male axillary extracts modify the affinity of the platelet serotonin transporter and impulsiveness in women , 2010, Physiology & Behavior.

[97]  A. Meyer-Lindenberg,et al.  Antiserotonergic antipsychotics are associated with obsessive–compulsive symptoms in schizophrenia , 2011, Psychological Medicine.

[98]  W. Meck Neuropharmacology of timing and time perception. , 1996, Brain research. Cognitive brain research.

[99]  Hiroyuki Nakahara,et al.  Internal-Time Temporal Difference Model for Neural Value-Based Decision Making , 2010, Neural Computation.

[100]  Roger A. Barker,et al.  White matter pathology in Parkinson's disease: The effect of imaging protocol differences and relevance to executive function , 2012, NeuroImage.

[101]  R. Elliott,et al.  Playing it safe but losing anyway—Serotonergic signaling of negative outcomes in dorsomedial prefrontal cortex in the context of risk-aversion , 2013, European Neuropsychopharmacology.

[102]  A. Wagner,et al.  Cognitive control and right ventrolateral prefrontal cortex: reflexive reorienting, motor inhibition, and action updating , 2011, Annals of the New York Academy of Sciences.

[103]  Antonio P. Strafella,et al.  Impulsivity and Parkinson's disease: More than just disinhibition , 2011, Journal of the Neurological Sciences.

[104]  J. Patton,et al.  Fifty years of the Barratt Impulsiveness Scale: An update and review , 2009 .

[105]  I. McKeith,et al.  Cerebral atrophy in Parkinson's disease with and without dementia: a comparison with Alzheimer's disease, dementia with Lewy bodies and controls. , 2004, Brain : a journal of neurology.

[106]  R. Carpenter,et al.  Saccadic abnormalities in frontotemporal dementia , 2012, Neurology.

[107]  J. Gibbon,et al.  Differential effects of auditory and visual signals on clock speed and temporal memory. , 2000, Journal of experimental psychology. Human perception and performance.

[108]  M. Hallett,et al.  Mechanisms Underlying Dopamine-Mediated Reward Bias in Compulsive Behaviors , 2010, Neuron.

[109]  A. Lawrence,et al.  Factors influencing susceptibility to compulsive dopaminergic drug use in Parkinson disease , 2005, Neurology.

[110]  A. Damasio,et al.  Insensitivity to future consequences following damage to human prefrontal cortex , 1994, Cognition.

[111]  T. Robbins,et al.  Atomoxetine Modulates Right Inferior Frontal Activation During Inhibitory Control: A Pharmacological Functional Magnetic Resonance Imaging Study , 2009, Biological Psychiatry.

[112]  B. Dubois,et al.  Motivation, reward, and Parkinson’s disease: influence of dopatherapy , 2002, Neuropsychologia.

[113]  A. Lang,et al.  Amantadine use associated with impulse control disorders in Parkinson disease in cross‐sectional study , 2010, Annals of neurology.

[114]  Felipe Fregni,et al.  Effect of repetitive TMS and fluoxetine on cognitive function in patients with Parkinson's disease and concurrent depression , 2005, Movement disorders : official journal of the Movement Disorder Society.

[115]  D. Goldstein,et al.  Catechols in post‐mortem brain of patients with Parkinson disease , 2011, European journal of neurology.

[116]  T. Robbins,et al.  Stop-signal inhibition disrupted by damage to right inferior frontal gyrus in humans , 2003, Nature Neuroscience.

[117]  G. M. Halliday,et al.  Loss of brainstem serotonin- and substance P-containing neurons in Parkinson's disease , 1990, Brain Research.

[118]  S. Faraone,et al.  Atomoxetine and adult attention-deficit/hyperactivity disorder: the effects of comorbidity. , 2006, The Journal of clinical psychiatry.

[119]  Sylvia M. L. Cox,et al.  Tryptophan Depletion Disrupts the Motivational Guidance of Goal-Directed Behavior as a Function of Trait Impulsivity , 2005, Neuropsychopharmacology.

[120]  M Tagliati,et al.  Subthalamic deep brain stimulation and impulse control in Parkinson’s disease , 2009, European journal of neurology.

[121]  Diane C. Tsai Recent Developments in Parkinson's Disease , 1986, The Yale Journal of Biology and Medicine.

[122]  T. Robbins,et al.  Reflection Impulsivity in Current and Former Substance Users , 2006, Biological Psychiatry.

[123]  L. Clark Decision-making during gambling: an integration of cognitive and psychobiological approaches , 2010, Philosophical Transactions of the Royal Society B: Biological Sciences.

[124]  R. Carpenter,et al.  Saccadic latency in Parkinson's disease correlates with executive function and brain atrophy, but not motor severity , 2011, Neurobiology of Disease.

[125]  A. Turken,et al.  Left inferior frontal gyrus is critical for response inhibition , 2008, BMC Neuroscience.

[126]  Mark Hallett,et al.  Impulse control disorders in Parkinson's disease: recent advances. , 2011, Current opinion in neurology.

[127]  P. Cumming,et al.  Molecular imaging and the neuropathologies of Parkinson's disease. , 2012, Current topics in behavioral neurosciences.

[128]  S. Fahn Unified Parkinson's Disease Rating Scale , 1987 .

[129]  T. Robbins,et al.  l-Dopa medication remediates cognitive inflexibility, but increases impulsivity in patients with Parkinson’s disease , 2003, Neuropsychologia.

[130]  B. Averbeck,et al.  Stroop test performance in impulsive and non impulsive patients with Parkinson's disease. , 2011, Parkinsonism & related disorders.

[131]  Jae-On Kim,et al.  Introduction to Factor Analysis: What It Is and How To Do It , 1978 .

[132]  D. Brooks,et al.  Staging of serotonergic dysfunction in Parkinson's Disease: An in vivo 11C-DASB PET study , 2010, Neurobiology of Disease.

[133]  T. Robbins,et al.  Behavioral models of impulsivity in relation to ADHD: Translation between clinical and preclinical studies , 2006, Clinical psychology review.

[134]  H. Lesieur,et al.  The South Oaks Gambling Screen (SaGS): A New Instrument for the Identification of Pathological Gamblers , 2010 .

[135]  Michael Hornberger,et al.  Fronto-striatal atrophy correlates of inhibitory dysfunction in Parkinson's disease versus behavioural variant frontotemporal dementia , 2013, Cortex.

[136]  W. Meck,et al.  Neuroanatomical and Neurochemical Substrates of Timing , 2011, Neuropsychopharmacology.

[137]  T. Robbins,et al.  Inhibition and the right inferior frontal cortex , 2004, Trends in Cognitive Sciences.

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

[139]  Lori J. P. Altmann,et al.  High-Level Language Production in Parkinson's Disease: A Review , 2011, Parkinson's disease.

[140]  T. Robbins,et al.  Similar Effects of the Selective Noradrenaline Reuptake Inhibitor Atomoxetine on Three Distinct Forms of Impulsivity in the Rat , 2008, Neuropsychopharmacology.

[141]  A. Darzi,et al.  Effect of Pharmacological Enhancement on the Cognitive and Clinical Psychomotor Performance of Sleep-Deprived Doctors: A Randomized Controlled Trial , 2012, Annals of surgery.

[142]  Mark Hallett,et al.  Impulsive choice and response in dopamine agonist-related impulse control behaviors , 2009, Psychopharmacology.