Startling facts about emotion in Parkinson's disease: blunted reactivity to aversive stimuli

Bowers, Dawn; Miller, Kimberly M.; Mikos, Ania; Kirsch-Darrow, Lindsey; Springer, Utaka; Fernández, Hubert H.; Foote, Kelly D.; Okun, Michael S.

doi:10.1093/brain/awl301

Cited by 105 publications

(109 citation statements)

References 56 publications

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“…Thy1-aSyn mice show an agedependent deficit in this task, as well as in fear conditioning, likely to be due to the expression of a-synuclein aggregates in the amygdala (Freichel et al 2007), a brain area known to mediate emotional processes. These data are in line with the presence of Lewy bodies and Lewy neurite deposits in the amygdala of PD patients (Braak et al 1994), as well as the selective impairment in the recognition of facial emotion (Clark et al 2008) and blunted reactivity during aversive/unpleasant events observed in these patients (Bowers et al 2006).…”

Section: -Ohda-and Mptp-based Rodent Modelssupporting

confidence: 80%

Understanding cognitive deficits in Parkinson’s disease: lessons from preclinical animal models

et al. 2013

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Parkinson's disease (PD) has been, until recently, mainly defined by the presence of characteristic motor symptoms, such as rigidity, tremor, bradykinesia/akinesia, and postural instability. Accordingly, pharmacological and surgical treatments have so far addressed these motor disturbances, leaving nonmotor, cognitive deficits an unmet clinical condition. At the preclinical level, the large majority of studies aiming at defining mechanisms and testing novel therapies have similarly focused on the motor aspects of PD. Unfortunately, deterioration of the executive functions, such as attention, recognition, working memory, and problem solving, often appear in an early, premotor phase of the disease and progressively increase in intensity, negatively affecting the quality of life of 50% -60% of PD patients. At present, the cellular mechanisms underlying cognitive impairments in PD patients are largely unknown and an adequate treatment is still missing. The preclinical research has recently developed new animal models that may open new perspectives for a more integrated approach to the treatment of both motor and cognitive symptoms of the disease. This review will provide an overview on the cognitive symptoms occurring in early PD patients and then focus on the rodent and nonhuman primate models so far available for the study of discriminative and spatial memory attention and learning abilities related to this pathological condition. Cognitive deficits in Parkinson's diseaseParkinson's disease (PD) is a chronic neurodegenerative disorder affecting over four million people worldwide (Dorsey et al. 2007). It is classically characterized by the emergence of motor symptoms such as rigidity, tremor, postural unbalance, and bradykinesia/akinesia (Braak et al. 2003;Jankovic 2008). However, PD also involves nonmotor symptoms (NMS) (Chaudhuri et al. 2006;Jankovic 2008) that appear in the early, often premotor, phase of the disease (Abbott et al. 2005;Abbott 2007;Claassen et al. 2010) and significantly contribute to the impairment of the quality of life of 50%-60% of PD patients (Aarsland et al. 2012). Among others, NMS include olfactory dysfunction, REM sleep disorder, neuropsychiatric disturbances, and cognitive deficits (Schrag et al. 2004;Chaudhuri and Odin 2010). All these symptoms develop independently from each other in the early phase of the disease, and progressively increase in intensity, often leading to dementia in the late phase (Cools et al. 2001;Goetz et al. 2008).Neuropsychiatric mood-related disorders are rather common in PD (Cummings 1992;Schrag et al. 2004) with a prevalence of 20% (Reijnders et al. 2008), and manifest as apathy, depression, and anxiety.On the other hand, cognitive impairments associated with PD are mainly related to the executive functions, resulting in a phenotype resembling that of frontal lobe patients (Robbins and Arnsten 2009), with deficits in attention (Ballard et al. 2002), planning, concept formation, and working memory (Kehagia et al. 2010). In particular, memory deterioration aff...

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Section: -Ohda-and Mptp-based Rodent Modelssupporting

confidence: 80%

Understanding cognitive deficits in Parkinson’s disease: lessons from preclinical animal models

et al. 2013

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“…In nondemented PD patients, these alterations have been mainly associated with the concurrent progression of executive dysfunction resulting from progressive dopaminergic denervation along the frontalsubcortical circuitry and/or from pharmacological treatment (Starkstein et al, 1992;Aarsland et al, 1999;Isella et al, 2002;Pluck and Brown, 2002). However, recent research in the field of apathy as a syndrome has shown impaired emotion and reward processing in the absence of deficits of higher cognition (Bowers et al, 2006;Rowe et al, 2008;Martínez-Corral et al, 2010;Lawrence et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Apathy in Parkinson's Disease: Neurophysiological Evidence of Impaired Incentive Processing

et al. 2014

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Apathy is one of the most common and debilitating nonmotor manifestations of Parkinson's disease (PD) and is characterized by diminished motivation, decreased goal-directed behavior, and flattened affect. Despite its high prevalence, its underlying mechanisms are still poorly understood, having been associated with executive dysfunction, and impaired emotional processing and decision making. Apathy, as a syndrome, has recently been associated with reduced activation in the ventral striatum, suggesting that early-to middlestage Parkinson's disease patients with this manifestation may have a compromised mesocorticolimbic dopaminergic pathway and impaired incentive processing. To test this hypothesis, we measured the amplitude of the feedback-related negativity, an event-related brain potential associated with performance outcome valence, following monetary gains and losses in human PD patients (12 women) and healthy controls (6 women) performing a gambling task. Early-to middle-stage PD patients presenting clinically meaningful symptoms of apathy were compared with nonapathetic PD patients and healthy controls. Patients with cognitive impairment, depression, and other psychiatric disturbances were excluded. Results showed that the amplitude of the feedback-related negativity, measured as the difference wave in the event-related brain potential between gains and losses, was significantly reduced in PD patients with apathy compared with nonapathetic patients and healthy controls. These findings indicate impaired incentive processing and suggest a compromised mesocorticolimbic pathway in cognitively intact PD patients with apathy.

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“…PD is also associated with abnormal autonomic (Bowers et al, 2006;Dietz, Bradley, Okun, & Bowers, 2011) and emotional responses (Ariatti, Benuzzi, & Nichelli, 2008) that may have affected our pattern of SCRs. Interestingly, we found that PD patients responded differently to correctly performed pairs compared to incorrectly performed pairs, but responded similarly to correctly performed rewarded and unrewarded pairs.…”

Section: Parkinson's Disease and Learningmentioning

confidence: 99%

Separating the effect of reward from corrective feedback during learning in patients with Parkinson’s disease

Freedberg

Schacherer

Chen

et al. 2017

Cogn Affect Behav Neurosci

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Parkinson's disease (PD) is associated with procedural learning deficits. Nonetheless, studies have demonstrated that reward-related learning is comparable between patients with PD and controls (Bódi et al., Brain, 132(9), 2385-2395 Frank, Seeberger, & O'Reilly, Science, 306(5703), 1940-1943, 2004; Palminteri et al., Proceedings of the National Academy of Sciences of the United States of America, 106(45), 19179-19184, 2009). However, because these studies do not separate the effect of reward from the effect of practice, it is difficult to determine whether the effect of reward on learning is distinct from the effect of corrective feedback on learning. Thus, it is unknown whether these group differences in learning are due to reward processing or learning in general. Here, we compared the performance of medicated PD patients to demographically matched healthy controls (HCs) on a task where the effect of reward can be examined separately from the effect of practice. We found that patients with PD showed significantly less reward-related learning improvements compared to HCs. In addition, stronger learning of rewarded associations over unrewarded associations was significantly correlated with smaller skin-conductance responses for HCs but not PD patients. These results demonstrate that when separating the effect of reward from the effect of corrective feedback, PD patients do not benefit from reward.

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Startling facts about emotion in Parkinson's disease: blunted reactivity to aversive stimuli

Cited by 105 publications

References 56 publications

Understanding cognitive deficits in Parkinson’s disease: lessons from preclinical animal models

Understanding cognitive deficits in Parkinson’s disease: lessons from preclinical animal models

Apathy in Parkinson's Disease: Neurophysiological Evidence of Impaired Incentive Processing

Separating the effect of reward from corrective feedback during learning in patients with Parkinson’s disease

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