اختلال معنایی برای افعال در بیماران مبتلا به بیماری پارکینسون بدون مصرف دارو

Word-association tasks are considered useful tools to assess the normal functioning of the lexico-semantic system in healthy people and patients suffering from neurological disorders. Parkinson's Disease (PD) patients usually present some language dysfunction related to the functioning of the semantic system as a consequence of dopamine depletion. The aim of this study was to check if there were differences in the strength of association of the words generated by a group of non-demented PD patients on and off dopamine medication using a word-association task. In the study, 20 PD patients and 20 healthy-matched controls performed a word association task consisting of 10 nouns and 10 verbs matched by psycholinguistic variables. The participants were asked to generate the first word that came to mind given a specific single target. The results revealed that PD patients off medication said words less associated with the target compared with when they were on medication. Interestingly, comparisons between PD off patients and healthy controls revealed statistical differences only in response to verbs, while differences between PD on and controls were not found. Regarding nouns, we did not find any difference between PD off or PD on and healthy controls. This experiment adds more evidence to the assumption that the lexico-semantic system is disrupted in the absence of dopamine, resulting in poor spreading activation among associative words.

When a person is asked to produce the first word that comes to mind when a single word is provided, people usually say a word semantically associated with the given word. For example, given “cat” people will be more likely to say “dog” than “can” or “bat” (Postman & Keppel, 1970). As result of this finding, Collins and Loftus (1975) proposed the spreading-activation theory of semantic processing. This theory assumed that semantic memories are represented as nodes (e.g. dogs, cats) and organized into a larger network of concepts (e.g. animals). In addition, these specific semantic memories are interconnected through associative and bidirectional links. According to this theory, the normal functioning of the semantic system requires that the activation of any semantic node will spread along the associative links to other related nodes located into the conceptual network. It is assumed that the links between two nodes are determined by their common properties; this means that the more common properties between concepts, the more closely related they are within the semantic network (Collins & Loftus, 1975). To prove this assumption, psycholinguistics have been using word-association tasks based on the notion that word stimuli drive responses related to meaning. The word-association task is widely used to assess the normal function of the semantic network in different kinds of people. Thus, experiments with bilingual participants have found that word association performance was comparable between the first and the second language (Sheng, McGregor, & Marian, 2006). For example, participants will say “dog” in the presence of “cat” in the same manner in both English and Mandarin, supporting the notion that words are stored by meanings. Numerous studies have also used this task with patients with brain damage, such as Alzheimer's disease (AD), a neurodegenerative disorder typically involved in semantic memory deterioration (Hodges, 2006), to test the hypothesis of gradual semantic memory loss (Chertkow & Bub, 1990). Gollan, Salmon, and Paxton (2006) used a spoken word-association test with weakly and strongly associated pairs of words. They found that AD patients produced less common responses than normal controls for those pairs with a high strength of association. For the pairs of words with weak associations, the performance of AD patients was similar to that of the healthy controls. These results suggested that AD patients could have a disruption in the links of the semantic system, modulated by meanings. The normal connections within the semantic store of AD patients seem to be partially damaged, resulting in unusual responses when a word is given. In fact, weak association words are less dependent on meaning than strong associations, supporting the semantic degradation hypothesis in AD patients. Furthermore, previous findings have demonstrated the role of dopamine as a neuromodulator within the semantic system. Kischka et al. (1996) measured the performance of healthy volunteers who ingested levodopa or a placebo in a lexical decision task with a long and a short SOA and direct (prime and target are closely related e.g. “dog – cat”) and indirect priming (the connection is made by a mediating associated word e.g. “cat – bone” with the mediating word “dog”). They found that hyper-dopamine causes a more focussed activation, consisting of a decrease of indirect semantic priming effects. That is, while direct semantic priming effects were present in both groups and SOAs conditions, they found priming effects in the indirect semantic condition at the long SOA in the placebo group but not in participants under l-Dopa. These results suggest that the access to directly related words is not disrupted by dopamine. However, the spread of activation to words indirectly related within the semantic system is disrupted by dopamine intake in healthy volunteers. Similar results were found by Roesch-Ely et al. (2006) with dopamine agonists probably mediated by D1 receptors (Pederzolli et al., 2008). These results suggested that increased levels of dopamine are capable of focussing semantic associations. In this line, an interesting study was conducted by Copland, McMahon, Silburn, and de Zubicaray (2009) to examine the neuromodulation of semantic processing by dopamine. They assessed a group of healthy volunteers who ingested l-Dopa using a priming task while undergoing brain imaging acquisition with fMRI. The results provided further evidence in favour of focussing semantic activation (or restricted spreading of activation) in participants who ingested l-Dopa. Moreover, the imaging data showed that the automatic priming could be modulated by the influence of dopamine in the anterior cingulate which enables increases in attentional mechanisms during the task. Therefore, if dopamine decreased the spreading of activation in the semantic system, what could be occurring under dopamine depletion? The answer could be reached by measuring patients with loss of dopamine diseases such as Parkinson's. Parkinson's disease (PD) is a neurodegenerative disorder mainly associated with dopamine depletion in the fronto-estriatal network (Alexander, DeLong, & Strick, 1986). Recent studies of healthy volunteers and PD patients using linguistic tasks have showed that dopamine acts as a neuromodulator within the frontal lobe and may alter the normal activation of the semantic system (Angwin et al., 2009, 2004; Arnott et al., 2011; Copland et al., 2009; Kischka et al., 1996). Although the main cognitive impairment of PD patients is associated with executive functions (Muslimovic, Post, Speelman, & Schmand, 2005; Owen, 2004; Rodríguez-Ferreiro, Cuetos, Herrera, Menéndez, & Ribacoba, 2010), there is also evidence of semantic disturbance in PD patients assessed with semantic verbal fluency tasks (Henry & Crawford, 2004; Rodríguez-Ferreiro et al., 2010) and lexical decision tasks (Angwin et al., 2006; Angwin, Chenery, Copland, Murdoch, & Silburn, 2007; Arnott, Chenery, Murdoch, & Silburn, 2001; Boulenger et al., 2008). Moreover, recent evidence has pointed to the existence of a specific deficit within the lexico-semantic system related to verb processing in PD patients. Thus, experiments using action picture naming have found that people with PD have more problems in naming action pictures than objects (Cotelli et al., 2007; Rodríguez-Ferreiro, Menéndez, Ribacoba, & Cuetos, 2009). Similar results were found by Péran et al. (2009) when they asked patients to generate action words compared to the names of objects (Péran et al., 2009). In addition, Piatt, Fields, Paolo, Koller, and Tröster (1999) using a verbal fluency task, showed that PD patients with dementia had a poor performance in action fluency compared to a lexical and semantic verbal fluency task (Piatt et al., 1999). Only few experiments had been carried out to explore the performance of PD patients on/off dopamine medication (Angwin et al., 2009; Arnott et al., 2011; Boulenger et al., 2008; Herrera & Cuetos, 2012). Angwin et al. (2009) used a lexical decision task with a priming paradigm in PD patients on/off dopamine. The task included directly and indirectly related semantic words and short and long SOAs. The results revealed the absence of any priming effect in PD patients off dopamine medication at any SOA. On the other hand, direct and indirect facilitation effects emerged in the PD patients on medication, but again slower than in healthy controls. These results suggested a slower automatic activation in the PD group, which was not present in the off stage. Furthermore, Boulenger et al. (2008) measured the performance of PD patients on and off dopamine medication using nouns and verbs with a lexical decision task and a priming paradigm. The results showed that PD patients off medication did not present any priming effect for verbs, but presented prime effects for nouns similar to those of the healthy controls. Interestingly, prime effects for verbs emerged when levodopa was restored, equivalent to the prime effects for nouns. In regards to verb processing, Herrera and Cuetos (2012) assessed the performance of a group of PD patients on/off medication using an action naming task. The action pictures had different semantic motor content-associations. The authors found that PD patients had more difficulties naming pictures with a high degree of motor content when they were dopamine deprived compared to pictures with a low degree of motor content-association verbs. Indeed there were no differences when PD patients were on medication compared to healthy controls. These results suggest a semantic origin in the specific verb impairment of PD patients. Though the lexico-semantic system has been partially measured in PD patients, only a few experiments have been carried out taking into account the level of dopamine. Moreover, word-association tasks are a useful tool to assess the semantic networks and they have not been used before to test PD patients on/off dopamine medication. Thus, the objective of this study was to test a group of non-demented PD patients with and without dopamine medication in order to further understand the role of dopamine medication within the semantic system. If dopamine modulates the normal function of the semantic system, PD patients off medication should have some degree of disruption in retrieving words. Moreover, since verb processing is more impaired in PD patients under dopamine depletion, performance should be worse in generating an associated word when given a verb rather than a noun.