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Mini Review ARTICLE

Front. Behav. Neurosci., 21 November 2017 | https://doi.org/10.3389/fnbeh.2017.00230

Cognitive, Emotional, and Auto-Activation Dimensions of Apathy in Parkinson's Disease

  • 1Social Psychology Laboratory EA 849, Aix-Marseille and Nîmes Universities, Nîmes, France
  • 2Epsylon, Laboratory Dynamic of Human Abilities & Health Behaviors, Department of Sport Sciences, Psychology and Medicine, Montpellier University, Montpellier, France

Apathy is one of the most frequent non-motor manifestations in Parkinson's disease (PD) that can lead to a whole range of deleterious outcomes. In 2006, Levy and Dubois proposed a model that distinguishes three different apathy aetiologies in PD divided into three subtypes of disrupted processing: “emotional-affective,” “cognitive,” and “auto-activation.” These three dimensions associated with dopamine depletion present in the pathology would lead to the emergence of apathy in PD. The aim of this mini-review was to describe and discuss studies that have explore links between apathy and the three subtypes of disrupted processing proposed by Levy and Dubois (2006) and as well as the links between these dimensions and dopamine depletion in Parkinson's disease. The lack of consensus regarding the emotional-affective correlates of apathy and the lack of evidence supporting the hypothesis of the auto-activation deficit, do not clearly confirm the validity of Levy and Dubois's model. Furthermore, the suggested association between dopaminergic depletion and apathy must also be clarified.

Introduction

Apathy is one of the most frequent non-motor manifestations in PD with a range between 7 and 70% (Leentjens et al., 2008; Pagonabarraga et al., 2015). Apathy is generally defined as a lack of initiative and effort to perform everyday-life activities. Furthermore, there is a lack of intellectual interest and initiative regarding personal or social issues and an indifference or flattening of affect (Marin, 1991). Diagnostic criteria proposed by Robert et al. (2009), define dimensions (emotional, behavioral, and cognitive) related to the emergence of apathy. For Levy and Dubois (2006), apathy is a quantitative reduction of goal-directed behaviors (GDB) despite the patient's environmental or physical constraints. This syndrome is clearly distinct from other symptoms such as depression (Marin et al., 1994; Andersson et al., 1999; Kuzis et al., 1999; Kirsch-Darrow et al., 2006; Dujardin, 2007; Pedersen et al., 2009; Oguru et al., 2010; Ziropadja et al., 2012) despite a symptomatic overlap (Marin et al., 1993, 1994; Landes et al., 2001; Boyle and Malloy, 2004). Recently, Thobois et al. (2017) have proposed several aetiologies of apathy, anxiety and depression in PD. The authors have emphasized the role of anatomical, metabolic and neurotransmission abnormalities in these three syndromes. The etiology overlaps, in particular limbic loop dysfunction and neurotransmission abnormalities must lead the research to study more precisely the phenomena involved in apathy in PD. In 2006, Levy and Dubois proposed a specific model that distinguishes three different apathy aetiologies in PD divided into three subtypes of disrupted processing: “emotional-affective,” “cognitive,” and “auto-activation.” These three dimensions associated with dopamine depletion present in the pathology would lead to the emergence of apathy in PD. However, the lack of consensus regarding the emotional-affective correlates of apathy and the lack of evidence supporting the hypothesis of the auto-activation deficit, do not clearly confirm the validity of Levy and Dubois's model. Furthermore, the suggested association between dopaminergic depletion and apathy must also be clarified.

The aim of this mini review was to describe and discuss studies that have explore links between apathy and the three subtypes of disrupted processing proposed by Levy and Dubois (2006) and as well as the links between these dimensions and dopamine depletion in PD.

Selection Method

We identified references through searches of PubMed using the terms “Cognitive functions and apathy,” “Emotion recognition and apathy,” “Motor behavior and apathy,” “Dopamine depletion and apathy” and through searching the lists of references of selected papers. We restrict our search to studies in English and we also searched the reference lists within identified studies. We selected papers on the basis of their relevance to the purpose of this mini-review (Tables 1, 2).

TABLE 1
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Table 1. Studies assessing links between cognitive dimension and apathy in PD.

TABLE 2
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Table 2. Studies assessing links between emotional dimension, auto-activation dimension, dopamine depletion and apathy in PD.

Cognitive Dimension of Apathy in PD

“Cognitive inertia” refers to the reduction of GDB due to decrease of the cognitive functions needed to elaborate the plan of actions. Several executive functions (EF) play a fundamental role in the activation, maintenance and stopping of GDB. EF are classically associated with activation of lateral prefrontal areas, particularly dorsolateral involved in working memory and cognitive flexibility (Goldman-Rakic, 1987; Petrides and Pandya, 1999; Rolls, 2000). However, EF are multi-localized on several brain regions (Cowey and Green, 1996; Vilkki et al., 1996; Andrès and Van der Linden, 1998, 2001) and would rest on a distributed cerebral network that is not limited to the anterior cerebral areas (Collette et al., 2006). For example, cognitive flexibility was associated with bilateral increase of activity in dorsolateral, inferior parietal, occipital and temporal regions (Berman et al., 1995; Nagahama et al., 1996; Ragland et al., 1997). Inhibition process was associated with various regions located in cingulate, prefrontal, parietal and temporal regions (Taylor et al., 1997; Bush et al., 1998; Garavan and Stein, 1999; Chee et al., 2000; Collette et al., 2001).

Several studies have shown an alteration of the cognitive functioning in PD (Kudlicka et al., 2011; Alzahrani and Venneri, 2015; Mak et al., 2015; Veselý and Rektor, 2016). Apathy was significantly associated with cognitive deficits. More specifically, results showed that apathetic patients had a significant decrease in memory, working memory and EF compared to non-apathetic patients (Alzahrani and Venneri, 2015). Varanese et al. (2011) showed that apathy was a predictor of cognitive decline in PD. However, the link between apathy and cognitive abilities is not so obvious. Some research did not find any link between apathy and cognitive impairments in PD (Robert et al., 2012; Bogdanova and Cronin-Golomb, 2013). Bogdanova and Cronin-Golomb (2013) showed that only alexithymia, but not apathy, correlated with neuropsychological performances. These opposite results could be explained by the different methodologies used. Indeed, Collette et al. (2006), noted that measures for executive tasks implicated non-executive processing that influenced patient performances. Functional neuroimaging techniques may be more relevant to identify the specific relationships between behavior and brain activity (Collette et al., 2006). In this sense, many studies suggested that brain areas activations involved in the cognitive dimensions, could play a fundamental role in the development of apathy (Alzahrani and Venneri, 2015). Several studies showed significant correlations between apathy and low gray matter density values in the bilateral precentral, parietal and frontal gyri (Reijnders et al., 2010) and bilateral temporal lobe (Isella et al., 2002). Positron emission tomography studies (Robert et al., 2012) also showed that a high apathy score was correlated with right prefrontal cortex (PFC) activation and with left dorsolateral prefrontal cortex metabolism. Several studies demonstrated that dopamine depletion was correlated with cognitive impairments in PD (Sawamoto et al., 2008; Jokinen et al., 2009; Ekman et al., 2012). Polito et al. (2012) showed that the level of dopamine in caudate nucleus modulated the glucose metabolism in frontostriatal circuits affecting executive function domains. Impairment prefrontal dopamine signals would play in cognitive dysfunctions (Dubois and Pillon, 1995; Aalto et al., 2005; Ekman et al., 2012; Narayanan et al., 2013; Matsumoto, 2015). The blockade of dopamine receptors of cortico-basal ganglia loops induced cognitive dysfunctions in animals' studies (Sawaguchi and Goldman-Rakic, 1994; Landau et al., 2009; Cools, 2011) suggesting the fundamental role of dopamine to cognitive processing in this circuit.

The links between apathy and cognitive disorders would appear to be strongly demonstrated by the literature confirming the first-dimension validity of Levy and Dubois's model in PD.

Emotional-Affective (EA) Dimension of Apathy in PD

The “EA processing” of apathy is a reduction of GDB due to an impossibility of linking affective and emotional (positive or negative) signals with ongoing and forthcoming behaviors. “EA” processes are essential to give motivational value to behavior. For Levy and Dubois, the lack of emotional attribution leads to apathy, either by reducing the desire to perform actions and/or by reducing of ability to assess the consequences of future actions. Apathy related to disruption of “Emotional-Affective” processing would be associated with a dysfunction or a lesion of orbital/medial PFC and limbic territories of basal ganglia. Emotional processing disorders, associated with apathy in PD, could be confused with mood disorders such as depression or alexithymia. Indeed, depression syndrome alters positive emotional treatment and promotes negative emotional treatment while apathy syndrome reduces positive and negative emotional treatment. Several studies have showed that PD patients were affected by alexithymia, defined as “the difficulty to identify and describe own feelings and a more general reduced aptitude to deal with emotions” (Taylor, 2000). Alexithymia affects between 18 and 30% of patients without dementia (Costa et al., 2006, 2007, 2010; Castelli et al., 2014; Goerlich-Dobre et al., 2014; Enrici et al., 2015). In recent literature, Assogna et al. (2016) showed strong links between alexithymia and depression. Out of the ten articles evaluated, nine highlighted the presence of positive correlation. However, depressive symptoms and alexithymia do not overlap completely in PD (Costa et al., 2010) and for Assogna et al. (2016), depression could be considered as predisposing factor for alexithymia. Concerning links between alexithymia and apathy in PD, previous studies have shown that neuroanatomic dysfunctions overlap. Alexithymia was correlated with frontal and anterior cingulate cortex alterations, like apathy (Tekin and Cummings, 2002; Levy and Dubois, 2006). However, few studies have tried to distinguish apathy from alexithymia. Bogdanova and Cronin-Golomb (2013) have used the Toronto Alexithymia Scale (TAS-20) to evaluate alexithymia level and the short version of Apathy Scale in non-demented PD patient. TAS-20 is composed by three factors: (i) difficulty of identifying feeling and bodily sensation discriminations (F1); (ii) difficulty of describing feelings (F2) and iii) externally oriented thinking (F3). In this study, results showed that apathy score correlated only with TAS-20 F3 score. On the other hand, alexithymia was associated with flexibility performances and visuospatial abilities, while apathy was not correlated with these cognitive tasks. These results could be explained by a potential continuum between apathy and alexithymia involving altered processes related to the progress of the pathology. In the sense, Bogdanova and Cronin-Golomb (2013) showed that apathy was a strong predictor of high levels of alexithymia.

Several studies have also shown that facial expression recognition (FER) was impaired in PD (Sprengelmeyer et al., 2003; Dujardin et al., 2004a,b; Lawrence et al., 2007; Clark et al., 2008; Herrera et al., 2011; Wagenbreth et al., 2016). On the other hand, many researches have demonstrated the strong link between FER performances and dopamine depletion (DD) (Sprengelmeyer et al., 2003; Assogna et al., 2008, 2010; Péron and Dondaine, 2012; Carriere et al., 2014). Sprengelmeyer et al. (2003) have compared FER in PD patients without or with medication and healthy controls (HC). FER was assessed using the Ekman 60 Faces test-recognition of prototypical facial expressions. Results demonstrated that PD patients presented FER impairment compared to HC. Fear, sadness, disgust and anger recognition was altered in PD patients without medication while only fear and anger recognition was impaired in PD patient with medication. PD patients without medication were significantly altered for disgust recognition compared to PD patients with medication. According to the authors, disgust recognition could be associated with DD in ventral striatum and the dopamine replacement therapy could restore the emotion recognition process (Sprengelmeyer et al., 2003). However, the role played by dopamine in the FER must be deepened and confirmed due to some studies that not confirm the links between dopamine and emotion recognition (Enrici et al., 2015). On the other hand, the literature also remains cautious about the links between FER and apathy. Robert et al.'s (2014) study showed that apathy correlated negatively with FER impairments and results showed a low significant relationship between overall emotion (β = -0.18), sadness (β = −0.06) and surprise (β = −0.1). Some years earlier, Martínez-Corral et al. (2010) found that apathy was significantly linked with fear, anger and sadness recognition deficits. Finally, several studies have found no link between apathy and FER deficits in PD (Drapier et al., 2008; Albuquerque et al., 2014). The different results of the studies could be explained by different confounding factors insufficiently controlled, such as depression and/or medication types (Robert et al., 2014). However, FER impairments and apathy would share the same neuroanatomic loop involving the subthalamic nucleus (STN) (Drapier et al., 2008; Le Jeune et al., 2009; Thobois et al., 2017) and dopaminergic depletion in STN was strongly associated with apathy severity (Castrioto et al., 2014). DD could play an important role in motor (motor areas and putamen), cognitive (dorsolateral PFC and dorsal caudate nucleus) and emotional (orbitofrontal cortex, ventral caudate nucleus and anterior cingulate cortex, nucleus accumbens) loops affected in PD (Steeves et al., 2009). Dopamine could play also important role in the reward evaluation of given behavior and in providing its motivational value (Aarts et al., 2012). Aarts et al. (2014) showed that dopaminergic medication effects were correlated with increase in BOLD signal in the ventromedial striatum, leading to decreased reward-processing performance in PD. Reward-processing impairments related with increase of dopamine in ventromedial striatum lead to impulse control disorders in PD (Aarts et al., 2014). In fact, impulse control disorder in PD was associated with younger age, treatment with dopamine agonists, and use of high doses of Levodopa (Voon et al., 2009, 2010, 2011a,b). Hyperdopaminergic syndrome would be characterized by several non-motor symptoms such as sensation and pleasure seeking, euphoric, hyperactivity while hypo-dopaminergic syndrome would be characterized by several non-motor symptoms such as apathy, indifferent, dysphoria, sadness, suicidal attempt (Castrioto et al., 2014). A recent review of Castrioto et al. (2014), concerning deep-brain stimulation of STN (STN-DBS), showed an increase of apathy after STN-DBS induced by dopaminergic treatment reduction allowed by STN-DBS (Funkiewiez et al., 2004; Thobois et al., 2010). Finally, apathy strongly associated with mesolimbic dopaminergic denervation (Thobois et al., 2010), disappeared with the introduction of dopamine agonist (Thobois et al., 2013). Previous studies have shown that facial emotional recognition deficits and apathy could share the same altered meso-cortico-limbic circuit. However, there are conflicting results regarding the role of certain limbic regions, such as ventral striatum, in apathy. Recently, Chung et al. (2016) showed no link between the degree of apathy and striatal dopamine transporter binding defect in PD, whereas previous studies seem to show the opposite (Remy et al., 2005; Thobois et al., 2010; Santangelo et al., 2015). For Chung et al. (2016), apathy could be mostly associated with lesions or dopamine depletion in extra-striatal regions, such as thalamus, rather than striatal dopaminergic deficits in PD.

The lack of consensus regarding the emotional-affective correlates of apathy do not clearly confirm the validity of Levy and Dubois's model. However, studies results are in line with the implication of this dimension in apathy in PD.

Auto-Activation (AA) Dimension of Apathy in PD

The last dimension “AA” could be characterized by the dissociation between spontaneous and voluntary behavioral production induced by an external element. Levy and Dubois suggested that the destruction of limbic system and associative territories of basal ganglions would prevent amplification and transfer to the PFC of the signal playing a role in selection and validation of thoughts or behaviors. “AA” disruption would not influence the emotional processing of a situation but would limit the association between a reward and a given behavior and thus switch off that behavior's production. In 2012, Louis et al. have compared apathy and depression level in Essential Tremor cases (ET), Dystonia cases, Parkinson' disease cases (PD) and Normal controls. After control of depressive symptoms, results showed that apathy level was higher in ET, Dystonia and PD cases compared to normal controls, with the PD patients having the highest score. However, this study has not shown a link between apathy and motor troubles. A few years later, Hassan et al. (2014) assessed links between apathy level, depression level and postural instability in PD. This study showed that hierarchical regression revealed that only apathy predicted postural instability. For Levy and Dubois “AA” disruption could share the same neuroanatomic loops that motor signs, such as akinesia. Indeed, the motor cortico-striatal circuit would be a closed loop organized between the motor cortex, premotor cortex and supplementary motor areas, putamen, globus pallidus (GP), substantia nigra pars reticulata, STN and thalamus. The motor loop would consist of direct and indirect pathways. The direct pathway would involve projections from the putamen to the internal segment of the GP (GPi) and then the thalamus. The indirect pathways would involve projections from the putamen first to the external segment of the GP (GPe), then the STN, and finally back to the GPi before relaying to the thalamus (Martinu and Monchi, 2012). Motor and cognitive symptoms could appear in parallel with the disruption of normal function of the putamen and caudate nucleus, associated with almost complete DD in the putamen. In PD, nigrostriatal DD would result a net increase in STN and GPi discharge, but a decrease in GPe discharge, creating an imbalance between the direct and indirect pathways (DeLong and Wichmann, 2007). Specifically, the indirect pathway would become hyperactive and the direct pathway would become hypoactive, resulting in an excess of inhibitory output from the GPus, leading to bradykinesia and rigidity (Bergman et al., 1994). Apathy associated with “AA” alteration may result from basal ganglia lesions located in the associative and limbic territories, in particular in the internal segment of the GP. García-Cabezas et al. (2007) showed that limbic territories were influenced by the efferent projections of innervated nuclei depending of thalamic dopamine action. In primate, thalamic dopamine would act on the whole cerebral cortex, specifically on to frontal and limbic areas, motor areas, dorsal striatum and amygdala. Thalamic dopamine could modulate emotion, cognition and motors functions. McFarland and Haber (2000) showed that interconnected ventral thalamic and cortical motor areas projected to the same dorsal striatum region suggesting that both areas modulate motor information integration in the striatum. Ventral thalamic would play a role in the corticobasal ganglia loop by giving positive feedback to the striatum to reinforce this circuits necessary for attaining a selected behavior. Rat model of PD confirms this hypothesis by showing that striatal dopamine depletion is associated with several deficits movements-related motor thalamus neural activity (Bosch-Bouju et al., 2014).

Despite the lack of studies confirming the role played by “AA” disruption in apathy, this hypothesis cannot be rejected in PD. Ventral thalamus activity could be an interesting way to better understand the dimension “AA” of apathy in PD.

Conclusion

Apathy is a complex phenomenon that could find its etiology in three subtypes of disrupted processing: “cognitive,” “emotional-affective,” and “auto-activation.” Nevertheless, contrary to the strong link between “cognitive” dimension and apathy, the lack of consensus regarding the emotional-affective correlates of apathy and the lack of evidence supporting the hypothesis of the auto-activation deficit, do not confirm the role of these dimensions in the emergence of apathy in PD. However, studies highlighting the role of dopaminergic depletion in motor, cognitive and emotional behavioral inhibition, suggest a strong association between hypo-dopaminergic syndrome and apathy in PD. Future research will have to explore these two-possible aetiologies of apathy, in particular by studying the links between stage of disease, dopamine depletion and level of non-motor symptoms. Finally, the potential confusion between non-motor symptoms such as alexithymia or depression, should lead to better specification of the diagnostic criteria of apathy neurodegenerative diseases and more specifically in PD.

Author Contributions

JD-M was involved in the conception, writing, critical review and approval of the final version to be submitted. SB, PG, and MG-N were involved in critical review and approval of the final version to be submitted.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

Aalto, S., Brück, A., Laine, M., Någren, K., and Rinne, J. O. (2005). Frontal and temporal dopamine release during working memory and attention tasks in healthy humans: a positron emission tomography study using the high-affinity dopamine D2 receptor ligan [11C]FLB 457. J. Neurosci. 25, 2471–2477. doi: 10.1523/JNEUROSCI.2097-04.2005

CrossRef Full Text | Google Scholar

Aarts, E., Helmich, R. C., Janssen, M. J., Oyen, W. J., Bloem, B. R., and Cools, R. (2012). Aberrant reward processing in Parkinson's disease is associated with dopamine cell loss. Neuroimage 59, 3339–3346. doi: 10.1016/j.neuroimage.2011.11.073

PubMed Abstract | CrossRef Full Text | Google Scholar

Aarts, E., Nusselein, A. A., Smittenaar, P., Helmich, R. C., Bloem, B. R., and Cools, R. (2014). Greater striatal responses to medication in Parkinson's disease are associated with better task-switching but worse reward performance. Neuropsychologia 62, 390–397. doi: 10.1016/j.neuropsychologia.2014.05.023

CrossRef Full Text | Google Scholar

Albuquerque, L., Coelho, M., Martins, M., Guedes, L. C., Rosa, M. M., Ferreira, J. J., et al. (2014). STN-DBS does not change emotion recognition in advanced Parkinson's disease. Parkinsonism Relat. Disord. 20, 166–169. doi: 10.1016/j.parkreldis.2013.10.010

PubMed Abstract | CrossRef Full Text | Google Scholar

Alzahrani, H., and Venneri, A. (2015). Cognitive and neuroanatomical correlates of neuropsychiatric symptoms in Parkinson's disease: a systematic review. J. Neurol. Sci. 356, 32–44. doi: 10.1016/j.jns.2015.06.037

PubMed Abstract | CrossRef Full Text | Google Scholar

Andersson, S., Krogstad, J. M., and Finset, A. (1999). Apathy and depressed mood in acquired brain damage: relationship to lesion localization and psychophysiological reactivity. Psychol. Med. 29, 447–456. doi: 10.1017/S0033291798008046

PubMed Abstract | CrossRef Full Text | Google Scholar

Andrès, P., and Van der Linden, M. (1998). Les capacités d'inhibition: une fonction frontale ? Eur. Rev. Appl. Psychol. 48, 33–38.

Andrès, P., and Van der Linden, M. (2001). Supervisory attentional system in patients with focal frontal lesions. J. Clin. Exp. Neuropsychol. 23, 225–239. doi: 10.1076/jcen.23.2.225.1212

PubMed Abstract | CrossRef Full Text | Google Scholar

Assogna, F., Cravello, L., Orfei, M. D., Cellupica, N., Caltagirone, C., and Spalletta, G. (2016). Alexithymia in Parkinson's disease: a systematic review of the literature. Parkinsonism Relat. Disord. 28, 1–11. doi: 10.1016/j.parkreldis.2016.03.021

PubMed Abstract | CrossRef Full Text | Google Scholar

Assogna, F., Pontieri, F. E., Caltagirone, C., and Spalletta, G. (2008). The recognition of facial emotion expressions in Parkinson's disease. Eur. Neuropsychopharmacol. 18, 835–848. doi: 10.1016/j.euroneuro.2008.07.004

PubMed Abstract | CrossRef Full Text | Google Scholar

Assogna, F., Pontieri, F. E., Cravello, L., Peppe, A., Pierantozzi, M., Stefani, A., et al. (2010). Intensity-dependent facial emotion recognition and cognitive functions in Parkinson's disease. J. Int. Neuropsychol. Soc. 16, 867–876. doi: 10.1017/S1355617710000755

PubMed Abstract | CrossRef Full Text | Google Scholar

Bergman, H., Wichmann, T., Karmon, B., and DeLong, M. R. (1994). The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism. J. Neurophysiol. 72, 507–520.

PubMed Abstract | Google Scholar

Berman, K. F., Ostrem, J. L., Randolph, C., Gold, J. M., Goldberg, T. E., Coppola, R., et al. (1995). Physiological activation of a cortical network during performance of the Wisconsin Card Sorting Test. Neuropsychologia 33, 1027–1046. doi: 10.1016/0028-3932(95)00035-2

PubMed Abstract | CrossRef Full Text | Google Scholar

Bogdanova, Y., and Cronin-Golomb, A. (2013). Alexithymia and apathy in Parkinson's disease: neurocognitive correlates. Behav. Neurol. 27, 535–545. doi: 10.1155/2013/682393

PubMed Abstract | CrossRef Full Text | Google Scholar

Bosch-Bouju, C., Smither, R. A., Hyland, B. I., and Parr-Brownlie, L. C. (2014). Reduced reach-related modulation of motor thalamus neural activity in a rat model of Parkinson's disease. J. Neurosci. 34, 15836–15850. doi: 10.1523/JNEUROSCI.0893-14.2014

PubMed Abstract | CrossRef Full Text | Google Scholar

Boyle, P. A., and Malloy, P. F. (2004). Treating apathy in Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 17, 91–99. doi: 10.1159/000074280

PubMed Abstract | CrossRef Full Text | Google Scholar

Bush, G., Whalen, P. J., Rosen, B. R., Jenike, M. A., McInerney, S. C., and Rauch, S. L. (1998). The counting stroop: an interference task specialized for functional neuroimaging. validation study with functional MRI. Hum. Brain Mapp. 6, 270–282. doi: 10.1002/(SICI)1097-0193(1998)6:4<270::AID-HBM6>3.0.CO;2-0

PubMed Abstract | CrossRef Full Text | Google Scholar

Carriere, N., Besson, P., Dujardin, K., Duhamel, A., Defebvre, L., Delmaire, C., et al. (2014). Apathy in Parkinson's disease is associated with nucleus accumbens atrophy: a magnetic resonance imaging shape analysis. Mov. Disord. 29, 897–903. doi: 10.1002/mds.25904

PubMed Abstract | CrossRef Full Text | Google Scholar

Castelli, L., Tonello, D., Rizzi, L., Zibetti, M., Lanotte, M., and Lopiano, L. (2014). Alexithymia in patients with Parkinson's disease treated with DBS of the subthalamic nucleus: a case-control study. Front. Psychol. 5:1168. doi: 10.3389/fpsyg.2014.01168

PubMed Abstract | CrossRef Full Text | Google Scholar

Castrioto, A., Lhommée, E., Moro, E., and Krack, P. (2014). Mood and behavioural effects of subthalamic stimulation in Parkinson's disease. Lancet Neurol. 13, 287–305. doi: 10.1016/S1474-4422(13)70294-1

PubMed Abstract | CrossRef Full Text | Google Scholar

Chee, M. W. L., Sriram, N., Siong Soon, C., and Ming Lee, K. (2000). Dorsolateral prefrontal cortex and the implicit association of concepts and attributes. Neuroreport 11, 135–140. doi: 10.1097/00001756-200001170-00027

PubMed Abstract | CrossRef Full Text | Google Scholar

Chung, S. J., Lee, J. J., Ham, J. H., Lee, P. H., and Sohn, Y. H. (2016). Apathy and striatal dopamine defects in non-demented patients with Parkinson's disease. Parkinsonism Relat. Disord. 23, 62–65. doi: 10.1016/j.parkreldis.2015.12.003

PubMed Abstract | CrossRef Full Text | Google Scholar

Clark, U. S., Neargarder, S., and Cronin-Golomb, A. (2008). Specific impairments in the recognition of emotional facial expressions in Parkinson's disease. Neuropsychologia 46, 2300–2309. doi: 10.1016/j.neuropsychologia.2008.03.014

PubMed Abstract | CrossRef Full Text | Google Scholar

Collette, F., Hogge, M., Salmon, E., and Van der Linden, M. (2006). Exploration of the neural substrates of executive functioning by functional neuroimaging. Neuroscience 139, 209–221. doi: 10.1016/j.neuroscience.2005.05.035

PubMed Abstract | CrossRef Full Text | Google Scholar

Collette, F., Van der Linden, M., Delfiore, G., Degueldre, C., Luxen, A., and Salmon, E. (2001). The functional anatomy of inhibition processes investigated with the Hayling task. Neuroimage 14, 258–267. doi: 10.1006/nimg.2001.0846

PubMed Abstract | CrossRef Full Text | Google Scholar

Cools, R. (2011). Dopaminergic control of the striatum for high-level cognition. Curr. Opin. Neurobiol. 21, 402–407. doi: 10.1016/j.conb.2011.04.002

PubMed Abstract | CrossRef Full Text | Google Scholar

Costa, A., Peppe, A., Carlesimo, G. A., Pasqualetti, P., and Caltagirone, C. (2006). Alexithymia in Parkinson's disease is related to severity of depressive symptoms. Eur. J. Neurol. 13, 836–841. doi: 10.1111/j.1468-1331.2006.01216.x

PubMed Abstract | CrossRef Full Text | Google Scholar

Costa, A., Peppe, A., Carlesimo, G. A., Salamone, G., and Caltagirone, C. (2007). Neuropsychological correlates of alexithymia in Parkinson's disease. J. Int. Neuropsychol. Soc. 13, 980–992. doi: 10.1017/S1355617707071329

PubMed Abstract | CrossRef Full Text | Google Scholar

Costa, A., Peppe, A., Carlesimo, G. A., Salamone, G., and Caltagirone, C. (2010). Prevalence and characteristics of alexithymia in Parkinson's disease. Psychosomatics 51, 22–28. doi: 10.1016/S0033-3182(10)70655-1

PubMed Abstract | CrossRef Full Text | Google Scholar

Cowey, C. M., and Green, S. (1996). The hippocampus: a “working memory” structure? The effect of hippocampal sclerosis on working memory. Memory 4, 19–30. doi: 10.1080/741940668

PubMed Abstract | CrossRef Full Text | Google Scholar

DeLong, M. R., and Wichmann, T. (2007). Circuits and circuit disorders of the basal ganglia. Arch. Neurol. 64, 20–24. doi: 10.1001/archneur.64.1.20

PubMed Abstract | CrossRef Full Text | Google Scholar

Drapier, D., Péron, J., Leray, E., Sauleau, P., Biseul, I., Drapier, S., et al. (2008). Emotion recognition impairment and apathy after subthalamic nucleus stimulation in Parkinson's disease have separate neural substrates. Neuropsychologia 46, 2796–2801. doi: 10.1016/j.neuropsychologia.2008.05.006

PubMed Abstract | CrossRef Full Text | Google Scholar

Dubois, B., and Pillon, B. (1995). Do cognitive changes of Parkinson's disease result from dopamine depletion? J. Neural. Transm. Suppl. 45, 27–34.

PubMed Abstract | Google Scholar

Dujardin, K. (2007). [Apathy in neurodegenerative diseases: pathophysiology, diagnostic evaluation, and treatment]. Rev. Neurol. 163, 513–521. doi: 10.1016/S0035-3787(07)90458-0

PubMed Abstract | CrossRef Full Text | Google Scholar

Dujardin, K., Blairy, S., Defebvre, L., Duhem, S., Noël, Y., Hess, U., et al. (2004a). Deficits in decoding emotional facial expressions in Parkinson's disease. Neuropsychologia 42, 239–250. doi: 10.1016/S0028-3932(03)00154-4

PubMed Abstract | CrossRef Full Text | Google Scholar

Dujardin, K., Blairy, S., Defebvre, L., Krystkowiak, P., Hess, U., Blond, S., et al. (2004b). Subthalamic nucleus stimulation induces deficits in decoding emotional facial expressions in Parkinson's disease. J. Neurol. Neurosurg. Psychiatry 75, 202–208.

PubMed Abstract | Google Scholar

Ekman, U., Eriksson, J., Forsgren, L., Mo, S. J., Riklund, K., and Nyberg, L. (2012). Functional brain activity and presynaptic dopamine uptake in patients with Parkinson's disease and mild cognitive impairment: a cross-sectional study. Lancet Neurol. 11, 679–687. doi: 10.1016/S1474-4422(12)70138-2

PubMed Abstract | CrossRef Full Text | Google Scholar

Enrici, I., Adenzato, M., Ardito, R. B., Mitkova, A., Cavallo, M., Zibetti, M., et al. (2015). Emotion processing in Parkinson's disease: a three-level study on recognition, representation, and regulation. PLoS ONE 10:e0131470. doi: 10.1371/journal.pone.0131470

PubMed Abstract | CrossRef Full Text | Google Scholar

Funkiewiez, A., Ardouin, C., Caputo, E., Krack, P., Fraix, V., Klinger, H., et al. (2004). Long-term effects of bilateral subthalamic nucleus stimulation on cognitive function, mood, and behaviour in Parkinson's disease. J. Neurol. Neurosurg. Psychiatry 75, 834–839. doi: 10.1136/jnnp.2002.009803

PubMed Abstract | CrossRef Full Text | Google Scholar

Garavan, H., and Stein, E. A. (1999). Right hemispheric dominance of inhibitory control: an event-related functional MRI study. Proc. Natl. Acad. Sci. U.S.A. 96, 8301–8306. doi: 10.1073/pnas.96.14.8301

PubMed Abstract | CrossRef Full Text | Google Scholar

García-Cabezas, M. A., Rico, B., Sánchez-González, M. A., and Cavada, C. (2007). Distribution of the dopamine innervation in the macaque and human thalamus. Neuroimage 34, 965–984. doi: 10.1016/j.neuroimage.2006.07.032

PubMed Abstract | CrossRef Full Text | Google Scholar

Goerlich-Dobre, K. S., Probst, C., Winter, L., Witt, K., Deuschl, G., Möller, B., et al. (2014). Alexithymia-an independent risk factor for impulsive-compulsive disorders in Parkinson's disease. Mov. Disord. 29, 214–220. doi: 10.1002/mds.25679

PubMed Abstract | CrossRef Full Text | Google Scholar

Goldman-Rakic, P. S. (1987). Circuitry of the frontal association cortex and its relevance to dementia. Arch. Gerontol. Geriatr. 6, 299–309. doi: 10.1016/0167-4943(87)90029-X

PubMed Abstract | CrossRef Full Text | Google Scholar

Hassan, A., Vallabhajosula, S., Zahodne, L. B., Bowers, D., Okun, M. S., Fernandez, H. H., et al. (2014). Correlations of apathy and depression with postural instability in Parkinson disease. J. Neurol. Sci. 338, 162–165. doi: 10.1016/j.jns.2013.12.040

PubMed Abstract | CrossRef Full Text | Google Scholar

Herrera, E., Cuetos, F., and Rodríguez-Ferreiro, J. (2011). Emotion recognition impairment in Parkinson's disease patients without dementia. J. Neurol. Sci. 310, 237–240. doi: 10.1016/j.jns.2011.06.034

PubMed Abstract | CrossRef Full Text | Google Scholar

Isella, V., Melzi, P., Grimaldi, M., Iurlaro, S., Piolti, R., Ferrarese, C., et al. (2002). Clinical, neuropsychological, and morphometric correlates of apathy in Parkinson's disease. Mov. Disord. 17, 366–371. doi: 10.1002/mds.10041

PubMed Abstract | CrossRef Full Text | Google Scholar

Jokinen, P., Brück, A., Aalto, S., Forsback, S., Parkkola, R., and Rinne, J. O. (2009). Impaired cognitive performance in Parkinson's disease is related to caudate dopaminergic hypofunction and hippocampal atrophy. Parkinsonism Relat. Disord. 15, 88–93. doi: 10.1016/j.parkreldis.2008.03.005

PubMed Abstract | CrossRef Full Text | Google Scholar

Kirsch-Darrow, L., Fernandez, H. H., Marsiske, M., Okun, M. S., and Bowers, D. (2006). Dissociating apathy and depression in Parkinson disease. Neurology 67, 33–38. doi: 10.1212/01.wnl.0000230572.07791.22

PubMed Abstract | CrossRef Full Text | Google Scholar

Kudlicka, A., Clare, L., and Hindle, J. V. (2011). Executive functions in Parkinson's disease: systematic review and meta-analysis. Mov. Disord. 26, 2305–2315. doi: 10.1002/mds.23868

PubMed Abstract | CrossRef Full Text | Google Scholar

Kuzis, G., Sabe, L., Tiberti, C., Merello, M., Leiguarda, R., and Starkstein, S. E. (1999). Explicit and implicit learning in patients with Alzheimer disease and Parkinson disease with dementia. Neuropsychiatry Neuropsychol. Behav. Neurol. 12, 265–269.

PubMed Abstract | Google Scholar

Landau, S. M., Lal, R., O'Neil, J. P., Baker, S., and Jagust, W. J. (2009). Striatal dopamine and working memory. Cereb. Cortex 19, 445–454. doi: 10.1093/cercor/bhn095

PubMed Abstract | CrossRef Full Text | Google Scholar

Landes, A. M., Sperry, S. D., Strauss, M. E., and Geldmacher, D. S. (2001). Apathy in Alzheimer's disease. J. Am. Geriatr. Soc. 49, 1700–1707. doi: 10.1046/j.1532-5415.2001.49282.x

PubMed Abstract | CrossRef Full Text | Google Scholar

Lawrence, A. D., Goerendt, I. K., and Brooks, D. J. (2007). Impaired recognition of facial expressions of anger in Parkinson's disease patients acutely withdrawn from dopamine replacement therapy. Neuropsychologia 45, 65–74. doi: 10.1016/j.neuropsychologia.2006.04.016

PubMed Abstract | CrossRef Full Text | Google Scholar

Leentjens, A. F., Dujardin, K., Marsh, L., Martinez-Martin, P., Richard, I. H., Starkstein, S. E., et al. (2008). Apathy and anhedonia rating scales in Parkinson's disease: critique and recommendations. Mov. Disord. 23, 2004–2014. doi: 10.1002/mds.22229

PubMed Abstract | CrossRef Full Text | Google Scholar

Le Jeune, F., Drapier, D., Bourguignon, A., Péron, J., Mesbah, H., Drapei, S., et al. (2009). Subthalamic nucleus stimulation in Parkinson disease induces apathy: a PET study. Neurology 73, 1746–1751. doi: 10.1212/WNL.0b013e3181c34b34

PubMed Abstract | CrossRef Full Text | Google Scholar

Levy, R., and Dubois, B. (2006). Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits. Cereb. Cortex 16, 916–928. doi: 10.1093/cercor/bhj043

PubMed Abstract | CrossRef Full Text | Google Scholar

Louis, E. D., Huey, E. D., Gerbin, M., and Viner, A. S. (2012). Apathy in essential tremor, dystonia, and Parkinson's disease: a comparison with normal controls. Mov. Disord. 27, 432–434. doi: 10.1002/mds.24049

PubMed Abstract | CrossRef Full Text | Google Scholar

Mak, E., Su, L., Williams, G. B., and O'Brien, J. T. (2015). Neuroimaging correlates of cognitive impairment and dementia in Parkinson's disease. Parkinsonism Relat. Disord. 21, 862–870. doi: 10.1016/j.parkreldis.2015.05.013

PubMed Abstract | CrossRef Full Text | Google Scholar

Marin, R. S. (1991). Apathy: a neuropsychiatric syndrome. J. Neuropsychiatry Clin. Neurosci. 3, 243–254. doi: 10.1176/jnp.3.3.243

PubMed Abstract | CrossRef Full Text | Google Scholar

Marin, R. S., Firinciogullari, S., and Biedrzycki, R. C. (1993). The sources of convergence between measures of apathy and depression. J. Affect. Disord. 28, 117–124. doi: 10.1016/0165-0327(93)90040-Q

CrossRef Full Text | Google Scholar

Marin, R. S., Firinciogullari, S., and Biedrzycki, R. C. (1994). Group differences in the relationship between apathy and depression. J. Nerv. Ment. Dis. 182, 235–239. doi: 10.1097/00005053-199404000-00008

PubMed Abstract | CrossRef Full Text | Google Scholar

Martínez-Corral, M., Pagonabarraga, J., Llebaria, G., Pascual-Sedano, B., García-Sánchez, C., Gironell, A., et al. (2010). Facial emotion recognition impairment in patients with Parkinson's disease and isolated apathy. Parkinsons. Dis. 2010:930627. doi: 10.4061/2010/930627

PubMed Abstract | CrossRef Full Text | Google Scholar

Martinu, K., and Monchi, O. (2012). Cortico-basal ganglia and cortico-cerebellar circuits in Parkinson's disease: pathophysiology or compensation? Behav. Neurosci. 127, 222–236. doi: 10.1037/a0031226

CrossRef Full Text | Google Scholar

Matsumoto, M. (2015). Dopamine signals and physiological origin of cognitive dysfunction in Parkinson's disease. Mov. Disord. 30, 472–483. doi: 10.1002/mds.26177

PubMed Abstract | CrossRef Full Text | Google Scholar

McFarland, N. R., and Haber, S. N. (2000). Convergent inputs from thalamic motor nuclei and frontal cortical areas to the dorsal striatum in the primate. J. Neurosci. 20, 3798–3813.

PubMed Abstract | Google Scholar

Nagahama, Y., Fukuyama, H., Yamauchi, H., Matsuzaki, S., Konishi, J., Shibasaki, H., et al. (1996). Cerebral activation during performance of a card sorting test. Brain 119, 1667–1675. doi: 10.1093/brain/119.5.1667

PubMed Abstract | CrossRef Full Text | Google Scholar

Narayanan, N. S., Rodnitzky, R. L., and Uc, E. Y. (2013). Prefrontal dopamine signaling and cognitive symptoms of Parkinson's disease. Rev. Neurosci. 24, 267–278. doi: 10.1515/revneuro-2013-0004

PubMed Abstract | CrossRef Full Text | Google Scholar

Oguru, M., Tachibana, H., Toda, K., Okuda, B., and Oka, N. (2010). Apathy and depression in Parkinson disease. J. Geriatr. Psychiatry Neurol. 23, 35–41. doi: 10.1177/0891988709351834

PubMed Abstract | CrossRef Full Text | Google Scholar

Pagonabarraga, J., Kulisevsky, J., Strafella, A. P., and Krack, P. (2015). Apathy in Parkinson's disease: clinical features, neural substrates, diagnosis, and treatment. Lancet Neurol. 14, 518–531. doi: 10.1016/S1474-4422(15)00019-8

PubMed Abstract | CrossRef Full Text | Google Scholar

Pedersen, K. F., Alves, G., Aarsland, D., and Larsen, J. P. (2009). Occurrence and risk factors for apathy in Parkinson disease: a 4-year prospective longitudinal study. J. Neurol. Neurosurg. Psychiatry 80, 1279–1282. doi: 10.1136/jnnp.2008.170043

PubMed Abstract | CrossRef Full Text | Google Scholar

Péron, J., and Dondaine, T. (2012). [Emotion and basal ganglia (II): what can we learn from subthalamic nucleus deep brain stimulation in Parkinson's disease?]. Rev. Neurol. 168, 642–648. doi: 10.1016/j.neurol.2012.06.012

PubMed Abstract | CrossRef Full Text | Google Scholar

Petrides, M., and Pandya, D. N. (1999). Dorsolateral prefrontal cortex: comparative cytoarchitectonic analysis in the human and the macaque brain and corticocortical connection patterns. Eur. J. Neurosci. 11, 1011–1036. doi: 10.1046/j.1460-9568.1999.00518.x

PubMed Abstract | CrossRef Full Text | Google Scholar

Polito, C., Berti, V., Ramat, S., Vanzi, E., De Cristofaro, M. T., Pellicanò, G., et al. (2012). Interaction of caudate dopamine depletion and brain metabolic changes with cognitive dysfunction in early Parkinson's disease. Neurobiol Aging 33, 206.e29-39. doi: 10.1016/j.neurobiolaging.2010.09.004

PubMed Abstract | CrossRef Full Text | Google Scholar

Ragland, J. D., Glahn, D. C., Gur, D. C., Censits, D. M., Smith, R. J., Mozley, P. D., et al. (1997). PET regional cerebral blood flow change during working and declarative memory: relationship with task performance. Neuropsychology 11, 222–231. doi: 10.1037/0894-4105.11.2.222

PubMed Abstract | CrossRef Full Text | Google Scholar

Reijnders, J. S., Scholtissen, B., Weber, W. E., Aalten, P., Verhey, F. R., and Leentjens, A. F. (2010). Neuroanatomical correlates of apathy in Parkinson's disease: a magnetic resonance imaging study using voxel-based morphometry. Mov. Disord. 25, 2318–2325. doi: 10.1002/mds.23268

PubMed Abstract | CrossRef Full Text | Google Scholar

Remy, P., Doder, M., Lees, A., Turjanski, N., and Brooks, D. (2005). Depression in Parkinson's disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain 128(Pt 6), 1314–1322. doi: 10.1093/brain/awh445

PubMed Abstract | CrossRef Full Text | Google Scholar

Robert, G., Le Jeune, F., Lozachmeur, C., Drapier, S., Dondaine, T., Peron, J., et al. (2012). Apathy in patients with Parkinson disease without dementia or depression A PET study. Neurology 79, 1155–1160. doi: 10.1212/WNL.0b013e3182698c75

CrossRef Full Text | Google Scholar

Robert, G., Le Jeune, F., Dondaine, T., Drapier, S., Péron, J., Lozachmeur, C., et al. (2014). Apathy and impaired emotional facial recognition networks overlap in Parkinson's disease: a PET study with conjunction analyses. J. Neurol. Neurosurg. Psychiatry 85, 1153–1158. doi: 10.1136/jnnp-2013-307025

PubMed Abstract | CrossRef Full Text | Google Scholar

Robert, P. H., Onyike, P. U., Leentjens, A. F. G., Dujardin, K., Aalten, P., Starkstein, S. E., et al. (2009). Proposed diagnostic criteria for apathy in alzheimer's disease and other neuropsychiatric disorders. Eur. Psychiatry 24, 98–104. doi: 10.1016/j.eurpsy.2008.09.001

PubMed Abstract | CrossRef Full Text | Google Scholar

Rolls, E. T. (2000). Precis of the brain and emotion. Behav. Brain Sci. 23, 177–191. doi: 10.1017/S0140525X00002429

PubMed Abstract | CrossRef Full Text | Google Scholar

Santangelo, G., Vitale, C., Picillo, M., Cuoco, S., Moccia, M., Pezzella, D., et al. (2015). Apathy and striatal dopamine transporter levels in de-novo, untreated Parkinson's disease patients. Parkinsonism Relat. Disord. 21, 489–493. doi: 10.1016/j.parkreldis.2015.02.015

PubMed Abstract | CrossRef Full Text | Google Scholar

Sawaguchi, T., and Goldman-Rakic, P. S. (1994). The role of D1-dopamine receptor in working memory: local injections of dopamine antagonists into the prefrontal cortex of rhesus monkeys performing an oculomotor delayed-response task. J. Neurophysiol. 71, 515–528.

PubMed Abstract | Google Scholar

Sawamoto, N., Piccini, P., Hotton, G., Pavese, N., Thielemans, K., and Brooks, D. J. (2008). Cognitive deficits and striato-frontal dopamine release in Parkinson's disease. Brain 131(Pt 5), 1294–1302. doi: 10.1093/brain/awn054

PubMed Abstract | CrossRef Full Text | Google Scholar

Sprengelmeyer, R., Young, A. W., Mahn, K., Schroeder, U., Woitalla, D., Buttner, T., et al. (2003). Facial expression recognition in people with medicated and unmedicated Parkinson's disease. Neuropsychologia 41, 1047–1057. doi: 10.1016/S0028-3932(02)00295-6

PubMed Abstract | CrossRef Full Text | Google Scholar

Steeves, T. D., Miyasaki, J., Zurowski, M., Lang, A. E., Pellecchia, G., Van Eimeren, T., et al. (2009). Increased striatal dopamine release in Parkinsonian patients with pathological gambling: a [11C] raclopride PET study. Brain 132, 1376–1385. doi: 10.1093/brain/awp054

CrossRef Full Text | Google Scholar

Taylor, G. J. (2000). Recent developments in alexithymia theory and research. Can. J. Psychiatry 45, 134–142. doi: 10.1177/070674370004500203

PubMed Abstract | CrossRef Full Text | Google Scholar

Taylor, S. F., Kornblum, S., Lauber, E. J., Minoshima, S., and Koeppe, R. A. (1997). Isolation of specific interference processing in the Stroop task: PET activation studies. Neuroimage 6, 81–92. doi: 10.1006/nimg.1997.0285

PubMed Abstract | CrossRef Full Text | Google Scholar

Tekin, S., and Cummings, J. L. (2002). Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update. J. Psychosom. Res. 53, 647–654. doi: 10.1016/S0022-3999(02)00428-2

PubMed Abstract | CrossRef Full Text | Google Scholar

Thobois, S., Ardouin, C., Lhommée, E., Klinger, H., Lagrange, C., Xie, J., et al. (2010). Non-motor dopamine withdrawal syndrome after surgery for Parkinson's disease: predictors and underlying mesolimbic denervation. Brain 13, 1111–1127. doi: 10.1093/brain/awq032

CrossRef Full Text | Google Scholar

Thobois, S., Lhommée, E., Klinger, H., Ardouin, C., Schmitt, E., Bichon, A., et al. (2013). Parkinsonian apathy responds to dopaminergic stimulation of D2/D3 receptors with piribedil. Brain 136, 1568–1577. doi: 10.1093/brain/awt067

PubMed Abstract | CrossRef Full Text | Google Scholar

Thobois, S., Prange, S., Sgambato-Faure, V., Tremblay, L., and Broussolle, E. (2017). Imaging the etiology of apathy, anxiety, and depression in parkinson's disease: implication for treatment. Curr. Neurol. Neurosci. Rep. 17:76. doi: 10.1007/s11910-017-0788-0

PubMed Abstract | CrossRef Full Text | Google Scholar

Varanese, S., Perfetti, B., Ghilardi, M. F., and Di Rocco, A. (2011). Apathy, but not depression, reflects inefficient cognitive strategies in Parkinson's disease. PLoS ONE 6:e17846. doi: 10.1371/journal.pone.0017846

CrossRef Full Text | Google Scholar

Veselý, B., and Rektor, I. (2016). The contribution of white matter lesions (WML) to Parkinson's disease cognitive impairment symptoms: a critical review of the literature. Parkinsonism Relat. Disord. 22(Suppl. 1), S166–S170. doi: 10.1016/j.parkreldis.2015.09.019

PubMed Abstract | CrossRef Full Text | Google Scholar

Vilkki, J., Virtanen, S., Surma-Aho, O., and Servo, A. (1996). Dual task performance after focal cerebral lesions and closed head injuries. Neuropsychologia 34, 1051–1056. doi: 10.1016/0028-3932(96)00028-0

PubMed Abstract | CrossRef Full Text | Google Scholar

Voon, V., Fernagut, P. O., Wickens, J., Baunez, C., Rodriguez, M., Pavon, N., et al. (2009). Chronic dopaminergic stimulation in Parkinson's disease: from dyskinesias to impulse control disorders. Lancet Neurol. 8, 1140–1149. doi: 10.1016/S1474-4422(09)70287-X

PubMed Abstract | CrossRef Full Text | Google Scholar

Voon, V., Gao, J., Brezing, C., Symmonds, M., Ekanayake, V., Fernandez, H., et al. (2011a). Dopamine agonists and risk: impulse control disorders in Parkinson's disease. Brain 134(Pt 5), 1438–1446. doi: 10.1093/brain/awr080

PubMed Abstract | CrossRef Full Text | Google Scholar

Voon, V., Reynolds, B., Brezing, C., Gallea, C., Skaljic, M., Ekanayake, V., et al. (2010). Impulsive choice and response in dopamine agonist-related impulse control behaviors. Psychopharmacology 207, 645–659. doi: 10.1007/s00213-009-1697-y

PubMed Abstract | CrossRef Full Text | Google Scholar

Voon, V., Sohr, M., Lang, A. E., Potenza, M. N., Siderowf, A. D., Whetteckey, J., et al. (2011b). Impulse control disorders in Parkinson disease: a multicenter case-control study. Ann. Neurol. 69, 986–996. doi: 10.1002/ana.22356

PubMed Abstract | CrossRef Full Text | Google Scholar

Wagenbreth, C., Wattenberg, L., Heinze, H. J., and Zaehle, T. (2016). Implicit and explicit processing of emotional facial expressions in Parkinson's disease. Behav. Brain Res. 303, 182–190. doi: 10.1016/j.bbr.2016.01.059

PubMed Abstract | CrossRef Full Text | Google Scholar

Ziropadja, L. J., Stefanova, E., Petrovic, M., Stojkovic, T., and Kostic, V. S. (2012). Apathy and depression in Parkinson's disease: the Belgrade PD study report. Parkinsonism Relat. Disord. 18, 339–342. doi: 10.1016/j.parkreldis.2011.11.020

PubMed Abstract | CrossRef Full Text | Google Scholar

Keywords: Parkinson's disease, apathy, cognitive deficits, emotional deficits, auto-activation deficits

Citation: Del-Monte J, Bayard S, Graziani P and Gély-Nargeot MC (2017) Cognitive, Emotional, and Auto-Activation Dimensions of Apathy in Parkinson's Disease. Front. Behav. Neurosci. 11:230. doi: 10.3389/fnbeh.2017.00230

Received: 26 January 2017; Accepted: 07 November 2017;
Published: 21 November 2017.

Edited by:

Francesca Cirulli, Istituto Superiore di Sanità, Italy

Reviewed by:

Gianfranco Spalletta, Fondazione Santa Lucia (IRCCS), Italy
Miguel Angel García-Cabezas, Boston University, United States

Copyright © 2017 Del-Monte, Bayard, Graziani and Gély-Nargeot. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Jonathan Del-Monte, jonathan.del-monte@unimes.fr