548437 research-article2014
JOP0010.1177/0269881114548437Journal of PsychopharmacologyDjamshidian et al.
Original Paper
Perceptual decision-making in patients with Parkinson’s disease Atbin Djamshidian1,2, Sean S O’Sullivan3, Andrew D Lawrence4, Thomas Foltynie5, Iciar Aviles-Olmos5, Nadia Magdalinou1, Alessandro Tomassini5, Thomas T Warner1, Andrew J Lees1 and Bruno B Averbeck6
Journal of Psychopharmacology 1–6 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0269881114548437 jop.sagepub.com
Abstract Impulsive choice and poor information sampling have been found to be key behavioural mechanisms linked to impulse control disorders (ICDs) in Parkinson’s disease (PD). Perceptual decision-making is intimately related to information sampling. Therefore, we wanted to determine whether dopaminergic medication or ICDs influence perceptual decision-making in PD. All participants performed two tasks. One was a simple reaction time task, where subjects needed to respond as quickly as possible. The second was a perceptual decision-making task, in which participants had to estimate whether a stimulus contained either more red or more blue pixels. We tested three groups of patients, one treated with levodopa monotherapy, one additionally treated with dopamine agonists, and a third group had ICDs. Results were compared to healthy controls. We found that all patients made more errors than controls. Further, patients with ICDs responded fastest on the reaction time task and also in incorrect trials on the perceptual decisionmaking task. Similarly, patients with dopamine agonists responded faster than those on levodopa monotherapy and controls. Our results demonstrate that all patients have deficits in perceptual decision-making. However, patients treated with dopamine agonists closely resembled patients with ICDs.
Keywords Compulsivity, dopamine, impulse control disorders, impulsivity, Parkinson’s disease, decision-making, reaction time
Introduction Impulse control disorders (ICDs) such as gambling disorder, hypersexuality and compulsive shopping have been identified in a significant proportion of Parkinson’s disease (PD) patients treated with dopamine agonists (Weintraub et al., 2010). The specific behavioural mechanism that underlies these behaviours is, however, unclear. Previous studies have demonstrated faster reaction time (RT) and more impulsive choice (Voon et al., 2010), higher novelty seeking personality traits (Djamshidian et al., 2011a; Voon et al., 2011a), increased risk taking (Claassen et al., 2011; Djamshidian et al., 2010; Voon et al., 2011b) and increased temporal discounting (Housden et al., 2010) in PD patients with ICDs compared to PD patients without ICDs. Further, poor information sampling and irrational decision making have been found in PD patients with and without ICDs who were treated with dopamine agonists, regardless of whether they were also treated with deep brain stimulation (Djamshidian et al., 2012, 2013). Interestingly PD patients without ICDs who were treated with Levodopa (L-dopa) monotherapy performed similarly to healthy controls (Djamshidian et al., 2013). Thus, deficient information sampling may lie at the core of ICDs. Whether or not these results would generalise to other information sampling tasks is unclear. In this study we used a perceptual inference task and measured RT, which indexes (inversely) the amount of information that is sampled before decisions are made (Drugowitsch et al., 2012). Generally, perceptual decision making tasks assess the ability to filter relevant information from a noisy background. Observing the task longer provides additional information, and therefore should improve the ability of the participant to make a
correct decision (Seo et al., 2012). Evidence from electrophysiological recordings in primates is consistent with an account in which sensory information (from sensory brain areas) is integrated in higher level brain structures until a certain threshold of activity is reached, at which point a choice is made (Gold and Shadlen, 2007). The basal ganglia and its dopaminergic irrigation may play a major role in perceptual decision making, regulating this decision threshold (Lo and Wang, 2006; Ding and Gold, 2013; Nagano-Saito et al., 2012). We hypothesised that all PD patients who were taking a dopamine agonist (regardless of whether or not they also had ICDs) would take less time to make a decision than PD patients treated
1Reta
Lila Weston Institute of Neurological Studies, University of London, London, UK 2Department of Neurology, Medical University Innsbruck, Innsbruck, Austria 3Department of Neurology, University College Cork, Cork, Ireland 4School of Psychology, Cardiff University, Cardiff, UK 5Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London, UK 6Laboratory of Neuropsychology, National Institutes of Health, Bethesda, MD, USA Corresponding author: Atbin Djamshidian, Reta Lila Weston Institute for Neurological Studies, University College London, 1 Wakefield Street, London, WC1 N1PJ, UK. Email: [email protected]
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2
Journal of Psychopharmacology
Table 1. Demographic characteristics for controls, Parkinson’s disease (PD) patients with dopamine agonist (DA) therapy and without DA therapy and PD patients with impulse control disorders (ICDs). Controls Participants (n) 17 Gender (m/f) 14/3 Age (years) 59.9±10.4 Age at PD diagnosis PD disease duration (years) LEU dose (mg/day) UPDRS ‘on’ ICD type (n)b Gambling Hypersexuality Shopping Punding DA agonist (n) Pramipexole Ropinirole Rotigotine Apomorphine
PD-DA
PD+DA
PD+ICD
χ2 or F-statistic
p value
12 10/2 66.1±7.9 57±6.6 9.1±6.7
17 15/2 62.6±8.0 52.1±8.1 9.9±4.4
15 14/1 58.1±9.7 47.1±8.6 11.1±5.4
χ2 =2.1 F=2.0 F=5.3 F=0.44
0.56 0.12 0.009a 0.64
627.0±97 13.0±1.1
671.6±82 12.8±1.0
935.0±87 13.5±1.1
F=3.5 F=0.08
5 7 5 3 11 6
4 3 1 1
0.039a 0.92
LEU: Levodopa equivalent units; UPDRS: Unified Parkinson’s Disease Rating Scale. All values are mean±standard deviation (SD). All PD patients who had punding had at least one other ICD. aSignificant differences, bNote that due to co-morbidity, these ns are not independent.
with levodopa monotherapy. Further, we predicted that PD patients with ICDs would have faster RTs than all other patients, and speculated, based on our previous work, that they would make more errors than all other patients.
Methods All participants provided written informed consent according to the Declaration of Helsinki. The study was approved by the University College London Hospital (UCLH) Trust Research Ethics Committee. Healthy controls were recruited from amongst patient’s partners.
Patients All patients were recruited from the National Hospital for Neurology and Neurosurgery London, fulfilled the Queen Square Brain Bank criteria for the diagnosis of PD (Gibb and Lees, 1988), and were taking L-dopa. Twenty-nine PD patients without ICDs were recruited, 17 of who were taking L-dopa in combination with a dopamine agonist (PD+DA) (either pramipexole or ropinirole) and 12 who were on L-dopa monotherapy (PD-DA) and had never been treated with DAs. None of these two patient groups had a present or past history of ICDs. Further, we included a group of 15 PD patients with ICDs of whom nine were taking a dopamine agonist. Individual ICDs are listed in Table 1. Consistent with clinical guidelines (Averbeck et al., 2014) DA therapy had been recently stopped in six PD patients with ICDs. These six patients still fulfilled the criteria of ICDs at the time of testing. All participants completed a semi-structured interview to assess for the presence of ICDs using accepted diagnostic criteria
for disordered gambling (American Psychiatric Association, 2013), compulsive shopping, hypersexuality (Voon et al., 2006) and punding (complex stereotyped behaviour) (Evans et al., 2004). Other co-morbid psychiatric diagnoses including major depression, anxiety and psychosis in accordance with the DSM-V criteria (American Psychiatric Association, 2013) were excluded. Further, potential participants with cognitive impairment (scoring 0.6). We found a significant difference in age of PD onset (F(2,41)=5.33, p
JOP0010.1177/0269881114548437Journal of PsychopharmacologyDjamshidian et al.
Original Paper
Perceptual decision-making in patients with Parkinson’s disease Atbin Djamshidian1,2, Sean S O’Sullivan3, Andrew D Lawrence4, Thomas Foltynie5, Iciar Aviles-Olmos5, Nadia Magdalinou1, Alessandro Tomassini5, Thomas T Warner1, Andrew J Lees1 and Bruno B Averbeck6
Journal of Psychopharmacology 1–6 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0269881114548437 jop.sagepub.com
Abstract Impulsive choice and poor information sampling have been found to be key behavioural mechanisms linked to impulse control disorders (ICDs) in Parkinson’s disease (PD). Perceptual decision-making is intimately related to information sampling. Therefore, we wanted to determine whether dopaminergic medication or ICDs influence perceptual decision-making in PD. All participants performed two tasks. One was a simple reaction time task, where subjects needed to respond as quickly as possible. The second was a perceptual decision-making task, in which participants had to estimate whether a stimulus contained either more red or more blue pixels. We tested three groups of patients, one treated with levodopa monotherapy, one additionally treated with dopamine agonists, and a third group had ICDs. Results were compared to healthy controls. We found that all patients made more errors than controls. Further, patients with ICDs responded fastest on the reaction time task and also in incorrect trials on the perceptual decisionmaking task. Similarly, patients with dopamine agonists responded faster than those on levodopa monotherapy and controls. Our results demonstrate that all patients have deficits in perceptual decision-making. However, patients treated with dopamine agonists closely resembled patients with ICDs.
Keywords Compulsivity, dopamine, impulse control disorders, impulsivity, Parkinson’s disease, decision-making, reaction time
Introduction Impulse control disorders (ICDs) such as gambling disorder, hypersexuality and compulsive shopping have been identified in a significant proportion of Parkinson’s disease (PD) patients treated with dopamine agonists (Weintraub et al., 2010). The specific behavioural mechanism that underlies these behaviours is, however, unclear. Previous studies have demonstrated faster reaction time (RT) and more impulsive choice (Voon et al., 2010), higher novelty seeking personality traits (Djamshidian et al., 2011a; Voon et al., 2011a), increased risk taking (Claassen et al., 2011; Djamshidian et al., 2010; Voon et al., 2011b) and increased temporal discounting (Housden et al., 2010) in PD patients with ICDs compared to PD patients without ICDs. Further, poor information sampling and irrational decision making have been found in PD patients with and without ICDs who were treated with dopamine agonists, regardless of whether they were also treated with deep brain stimulation (Djamshidian et al., 2012, 2013). Interestingly PD patients without ICDs who were treated with Levodopa (L-dopa) monotherapy performed similarly to healthy controls (Djamshidian et al., 2013). Thus, deficient information sampling may lie at the core of ICDs. Whether or not these results would generalise to other information sampling tasks is unclear. In this study we used a perceptual inference task and measured RT, which indexes (inversely) the amount of information that is sampled before decisions are made (Drugowitsch et al., 2012). Generally, perceptual decision making tasks assess the ability to filter relevant information from a noisy background. Observing the task longer provides additional information, and therefore should improve the ability of the participant to make a
correct decision (Seo et al., 2012). Evidence from electrophysiological recordings in primates is consistent with an account in which sensory information (from sensory brain areas) is integrated in higher level brain structures until a certain threshold of activity is reached, at which point a choice is made (Gold and Shadlen, 2007). The basal ganglia and its dopaminergic irrigation may play a major role in perceptual decision making, regulating this decision threshold (Lo and Wang, 2006; Ding and Gold, 2013; Nagano-Saito et al., 2012). We hypothesised that all PD patients who were taking a dopamine agonist (regardless of whether or not they also had ICDs) would take less time to make a decision than PD patients treated
1Reta
Lila Weston Institute of Neurological Studies, University of London, London, UK 2Department of Neurology, Medical University Innsbruck, Innsbruck, Austria 3Department of Neurology, University College Cork, Cork, Ireland 4School of Psychology, Cardiff University, Cardiff, UK 5Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London, UK 6Laboratory of Neuropsychology, National Institutes of Health, Bethesda, MD, USA Corresponding author: Atbin Djamshidian, Reta Lila Weston Institute for Neurological Studies, University College London, 1 Wakefield Street, London, WC1 N1PJ, UK. Email: [email protected]
Downloaded from jop.sagepub.com at QUEENS UNIV LIBRARIES on February 3, 2015
2
Journal of Psychopharmacology
Table 1. Demographic characteristics for controls, Parkinson’s disease (PD) patients with dopamine agonist (DA) therapy and without DA therapy and PD patients with impulse control disorders (ICDs). Controls Participants (n) 17 Gender (m/f) 14/3 Age (years) 59.9±10.4 Age at PD diagnosis PD disease duration (years) LEU dose (mg/day) UPDRS ‘on’ ICD type (n)b Gambling Hypersexuality Shopping Punding DA agonist (n) Pramipexole Ropinirole Rotigotine Apomorphine
PD-DA
PD+DA
PD+ICD
χ2 or F-statistic
p value
12 10/2 66.1±7.9 57±6.6 9.1±6.7
17 15/2 62.6±8.0 52.1±8.1 9.9±4.4
15 14/1 58.1±9.7 47.1±8.6 11.1±5.4
χ2 =2.1 F=2.0 F=5.3 F=0.44
0.56 0.12 0.009a 0.64
627.0±97 13.0±1.1
671.6±82 12.8±1.0
935.0±87 13.5±1.1
F=3.5 F=0.08
5 7 5 3 11 6
4 3 1 1
0.039a 0.92
LEU: Levodopa equivalent units; UPDRS: Unified Parkinson’s Disease Rating Scale. All values are mean±standard deviation (SD). All PD patients who had punding had at least one other ICD. aSignificant differences, bNote that due to co-morbidity, these ns are not independent.
with levodopa monotherapy. Further, we predicted that PD patients with ICDs would have faster RTs than all other patients, and speculated, based on our previous work, that they would make more errors than all other patients.
Methods All participants provided written informed consent according to the Declaration of Helsinki. The study was approved by the University College London Hospital (UCLH) Trust Research Ethics Committee. Healthy controls were recruited from amongst patient’s partners.
Patients All patients were recruited from the National Hospital for Neurology and Neurosurgery London, fulfilled the Queen Square Brain Bank criteria for the diagnosis of PD (Gibb and Lees, 1988), and were taking L-dopa. Twenty-nine PD patients without ICDs were recruited, 17 of who were taking L-dopa in combination with a dopamine agonist (PD+DA) (either pramipexole or ropinirole) and 12 who were on L-dopa monotherapy (PD-DA) and had never been treated with DAs. None of these two patient groups had a present or past history of ICDs. Further, we included a group of 15 PD patients with ICDs of whom nine were taking a dopamine agonist. Individual ICDs are listed in Table 1. Consistent with clinical guidelines (Averbeck et al., 2014) DA therapy had been recently stopped in six PD patients with ICDs. These six patients still fulfilled the criteria of ICDs at the time of testing. All participants completed a semi-structured interview to assess for the presence of ICDs using accepted diagnostic criteria
for disordered gambling (American Psychiatric Association, 2013), compulsive shopping, hypersexuality (Voon et al., 2006) and punding (complex stereotyped behaviour) (Evans et al., 2004). Other co-morbid psychiatric diagnoses including major depression, anxiety and psychosis in accordance with the DSM-V criteria (American Psychiatric Association, 2013) were excluded. Further, potential participants with cognitive impairment (scoring 0.6). We found a significant difference in age of PD onset (F(2,41)=5.33, p
