Executive function in Parkinson’s disease: contributions of the dorsal frontostriatal pathways to action and motivation

Disruption of the dorsal frontostriatal pathways in Parkinson’s disease (PD) is associated with impairments in motivation, as well as in executive function. The goal of this study was to investigate whether these impairments are related and, if so, whether the disruption of frontostriatal pathways compromises the ability to process the motivational aspects of feedback in such tasks. In Experiment 1, informative feedback improved the performance of young, healthy participants in a task-switching paradigm. This task-switching paradigm was then used in Experiment 2 to test whether feedback would improve the performance of 17 PD patients and age-matched controls. The PD group benefitted from feedback to the same degree as control participants; however, depression scores on the Beck Depression Inventory were significantly related to feedback usage, especially when response selection demands were high. Regardless of feedback, PD patients were more impaired when response demands were high than in an equally difficult condition with low action demands. These results suggest that response selection is a core impairment of insufficient dopamine to the dorsal frontal striatal pathways.     

Horizontal and vertical attentional orienting in Parkinson’s disease

Patients with Parkinson’s disease (PD) typically suffer from an asymmetric degeneration of dopaminergic cells in the substantia nigra, resulting in right-sided (RPD) or left-sided (LPD) predominance of motor symptomatology. As the dopaminergic system is also involved in attention, we examined horizontal and vertical orienting of attention in LPD (N = 10), RPD (N = 9) and controls (N = 10). Four LPD patients demonstrated left neglect and three LPD patients demonstrated neglect for the upper visual field. LPD patients demonstrated a slower performance in detecting targets in the left hemifield and did not demonstrate a validity effect, unlike RPD patients and controls. RPD patients performed similar to controls, with the exception of one patient showing left and another showing right neglect, and two RPD patients demonstrated lower neglect. In sum, horizontal and vertical orienting of attention can be affected in Parkinson’s disease – particularly in LPD – from very subtle slowing to clinically detectable horizontal and/or vertical neglect.     

Working memory in healthy aging and in Parkinson’s disease: evidence of interference effects

Focusing on relevant information while suppressing the irrelevant one are critical abilities for different cognitive processes. However, their functioning has been scarcely investigated in the working memory (WM) domain, in both healthy and pathological conditions. The present research aimed to study these abilities in aging and Parkinson’s disease (PD), testing three groups of healthy participants (young, older and elderly) and one of PD patients, employing a new experimental paradigm. Results showed that the transient storing of irrelevant information in WM causes substantial interference effects, which were remarkable in elderly individuals on both response latency and accuracy. Interestingly, PD patients responded faster and were equally accurate compared to a matched control group. Taken together, findings confirm the existence of similar mechanisms for orienting attention inwards to WM contents or outwards to perceptual stimuli, and suggest the suitability of our task to assess WM functioning in both healthy aging and PD.     

Self-unawareness of levodopa induced dyskinesias in patients with Parkinson’s disease

The study analyzes the presence of dyskinesias-reduced-self-awareness in forty-eight patients suffering from Parkinson’s disease (PD). As the association with executive dysfunction is a matter of debate and we hypothesize it plays an important role in dyskinesias self-unawareness, we analyzed the role of dopaminergic treatment on the medial-prefrontal-ventral-striatal circuitry using a neurocognitive approach. Special attention was given to metacognitive abilities related to action-monitoring that represent a novel explanation of the phenomenon.PD patients were assessed using different rating scales that we devised to measure movement awareness disorders. In order to ascertain whether each variable measured at a cognitive-clinical level contributes to predicting the scores of the movement-disorder-awareness-scales, we conducted multiple logistic regression models using the latter as binary dependent variables. We used the Wisconsin Card Sorting Test-metacognitive-version to assess the executive functions of the prefrontal-ventral-striatal circuitry.Data showed that a reduction of self-awareness using the Dyskinesia rating scale was associated with global monitoring (p = .04), monitoring resolution (p = .04) and control sensitivity (p = .04). Patients failed to perceive their performance, distinguish between correct and incorrect sorts, be confident in their choice and consequently decide to gamble during the task.We did not find any association with executive functions using the hypo-bradykinesia rating scale.Our findings indicate that when the comparator mechanism for monitoring attentive performance is compromised at a prefrontal striatal level, patients lose the ability to recognize their motor disturbances that do not achieve conscious awareness.     

Laterality of repetitive finger movement performance and clinical features of Parkinson’s disease

Impairments in acoustically cued repetitive finger movement often emerge at rates near to and above 2 Hz in persons with Parkinson’s Disease (PD) in which some patients move faster (hastening) and others move slower (bradykinetic). The clinical features impacting this differential performance of repetitive finger movement remain unknown. The purpose of this study was to compare repetitive finger movement performance between the more and less affected side, and the difference in clinical ratings among performance groups. Forty-one participants diagnosed with idiopathic PD completed an acoustically cued repetitive finger movement task while “on” medication. Eighteen participants moved faster, 10 moved slower, and 13 were able to maintain the appropriate rate at rates above 2 Hz. Clinical measures of laterality, disease severity, and the UPDRS were obtained. There were no significant differences between the more and less affected sides regardless of performance group. Comparison of disease severity, tremor, and rigidity among performance groups revealed no significant differences. Comparison of posture and postural instability scores revealed that the participants that demonstrated hastening had worse posture and postural instability scores. Consideration of movement rate during the clinical evaluation of repetitive finger movement may provide additional insight into varying disease features in persons with PD.     

Psychophysiological and behavioral differences as a function of age and Parkinson’s disease

Differences related to age and to specific neurological (Parkinsonian) damage were studied by contrasting, respectively, old (mean age 64 years) and young (27 years) subjects (N=15), and old-normal (N=15) and old-Parkinsonian (N=15) subjects. Both behavioral as well as psychophysiological dependent variables were employed. The behavioral measure was performance on a discrimination learning task, while the psychophysiological measures were based on habituation to a repeated tone stimulus and on a Pavlovian differential conditioning preparation. The behavioral task showed predominantly age-related differences, with the young learning faster. Another age-related difference was interpreted as showing a more insight-like learning process in the young. Response-bias (beta) values did not differ between groups. Age-related differences also emerged more clearly than specific-neurological-damage differences in the psychophysiological data. The older subjects manifested markedly less autonomic conditioning, which was probably due to a lowering of reactivity, as well as the emergence of habituation to the (loud-noise) unconditional stimulus. A correlational analysis of discrimination conditioning also yielded age-related differences. Most notably, reactivity played a greater role in conditioning in the old than in the young subjects. The results illustrated how psychophysiological measures can provide information that complements those provided by behavioral measures.     

Quasi-Realism and Inductive Scepticism in Hume’s Theory of Causation

Interpreters of Hume on causation consider that an advantage of the ‘quasi-realist’ reading is that it does not commit him to scepticism or to an error theory about causal reasoning. It is unique to quasi-realism that it maintains this positive epistemic result together with a rejection of metaphysical realism about causation: the quasi-realist supplies an appropriate semantic theory in order to justify the practice of talking ‘as if’ there were causal powers in the world. In this paper, I problematise the quasi-realist reading of Hume on causation by showing how quasi-realism does not speak to inductive scepticism. I also offer evidence that Hume takes inductive scepticism to result from his theory of causation, and that his scepticism is tied to his rejection of metaphysical causal realism.     

Optimized cuttlefish algorithm for diagnosis of Parkinson’s disease

This paper presents an optimized cuttlefish algorithm for feature selection based on the traditional cuttlefish algorithm, which can be used for diagnosis of Parkinson’s disease at its early stage. Parkinson is a central nervous system disorder, caused due to the loss of brain cells. Parkinson's disease is incurable and could eventually lead to death but medications can help to control symptoms and elongate the patient's life to some extent. The proposed model uses the traditional cuttlefish algorithm as a search strategy to ascertain the optimal subset of features. The decision tree and k-nearest neighbor classifier as a judgment on the selected features. The Parkinson speech with multiple types of sound recordings and Parkinson Handwriting sample’s datasets are used to evaluate the proposed model. The proposed algorithm can be used in predicting the Parkinson’s disease with an accuracy of approximately 94% and help individual to have proper treatment at early stage. The experimental result reveals that the proposed bio-inspired algorithm finds an optimal subset of features, maximizing the accuracy, minimizing number of features selected and is more stable.     

Understanding the role of configural processing in face emotion recognition in Parkinson’s disease

This investigation examined whether impairment in configural processing could explain deficits in face emotion recognition in people with Parkinson’s disease (PD). Stimuli from the Radboud Faces Database were used to compare recognition of four negative emotion expressions by older adults with PD (n = 16) and matched controls (n = 17). Participants were tasked with categorizing emotional expressions from upright and inverted whole faces and facial composites; it is difficult to derive configural information from these two types of stimuli so featural processing should play a larger than usual role in accurate recognition of emotional expressions. We found that the PD group were impaired relative to controls in recognizing anger, disgust and fearful expressions in upright faces. Then, consistent with a configural processing deficit, participants with PD showed no composite effect when attempting to identify facial expressions of anger, disgust and fear. A face inversion effect, however, was observed in the performance of all participants in both the whole faces and facial composites tasks. These findings can be explained in terms of a configural processing deficit if it is assumed that the disruption caused by facial composites was specific to configural processing, whereas inversion reduced performance by making it difficult to derive both featural and configural information from faces.     

‘Theory of mind’ in animals: ways to make progress

Whether any non-human animal can attribute mental states to others remains the subject of extensive debate. This despite the fact that several species have behaved as if they have a ‘theory of mind’ in various behavioral tasks. In this paper, we review the reasons of skeptics for their doubts: That existing experimental setups cannot distinguish between ‘mind readers’ and ‘behavior readers’, that results that seem to indicate ‘theory of mind’ may come from studies that are insufficiently controlled, and that our own intuitive biases may lead us to interpret behavior more ‘cognitively’ than is necessary. The merits of each claim and suggested solution are weighed. The conclusion is that while it is true that existing setups cannot conclusively demonstrate ‘theory of mind’ in non-human animals, focusing on this fact is unlikely to be productive. Instead, the more interesting question is how sophisticated their social reasoning can be, whether it is about ‘unobservable inner experiences’ or not. Therefore, it is important to address concerns about the setup and interpretation of specific experiments. To alleviate the impact of intuitive biases, various strategies have been proposed in the literature. These include a deeper understanding of associative learning, a better knowledge of the limited ‘theory of mind’ humans actually use, and thinking of animal cognition in an embodied, embedded way; that is, being aware that constraints outside of the brain, and outside of the body, may naturally predispose individuals to produce behavior that looks smart without requiring complex cognition. To enable this kind of thinking, a powerful methodological tool is advocated: Computational modeling, namely agent-based modeling and, particularly, cognitive modeling. By explicitly simulating the rules and representations that underlie animal performance on specific tasks, it becomes much easier to look past one’s own biases and to see what cognitive processes might actually be occurring.     

Eye-Hand Coordination in Aging and in Parkinson’s Disease

Aiming movements to defined target positions were performed as fast and as accurately as possible by younger and older subjects and by patients in the early stages of Parkinson's disease (PD). Movement time and accuracy were tested in two conditions: with and without a centre cue. Older subjects exhibited slower movement time relative to the younger subjects only when the centre cue was present suggesting inefficient feedback processing. The performance of patients with PD was found to be as precise as that of older subjects. The movements of PD subjects, however, were slower in both conditions. Finally, the performance of subjects improved over trials. The data suggest that there is no difference in the nature of the control processes used by older and early-stage PD subjects, but that there is a reduction in the speed of these processes in PD.     

Targeted training of the decision rule benefits rule-guided behavior in Parkinson’s disease

The impact of Parkinson’s disease (PD) on rule-guided behavior has received considerable attention in cognitive neuroscience. The majority of research has used PD as a model of dysfunction in frontostriatal networks, but very few attempts have been made to investigate the possibility of adapting common experimental techniques in an effort to identify the conditions that are most likely to facilitate successful performance. The present study investigated a targeted training paradigm designed to facilitate rule learning and application using rule-based categorization as a model task. Participants received targeted training in which there was no selective-attention demand (i.e., stimuli varied along a single, relevant dimension) or nontargeted training in which there was selective-attention demand (i.e., stimuli varied along a relevant dimension as well as an irrelevant dimension). Following training, all participants were tested on a rule-based task with selective-attention demand. During the test phase, PD patients who received targeted training performed similarly to control participants and outperformed patients who did not receive targeted training. As a preliminary test of the generalizability of the benefit of targeted training, a subset of the PD patients were tested on the Wisconsin card sorting task (WCST). PD patients who received targeted training outperformed PD patients who did not receive targeted training on several WCST performance measures. These data further characterize the contribution of frontostriatal circuitry to rule-guided behavior. Importantly, these data also suggest that PD patient impairment, on selective-attention-demanding tasks of rule-guided behavior, is not inevitable and highlight the potential benefit of targeted training.     

Dysexecutive syndrome in Parkinson’s disease: the GREFEX study

The objectives of this study were to characterize the frequencies and profiles of behavioral and cognitive dysexecutive syndromes in PD (based on validated battery and diagnostic criteria) and to develop a shortened diagnostic battery. Eighty-eight non-demented patients with a diagnosis of PD were examined with an executive validated battery. Using a validated framework, the patients’ test results were interpreted with respect to normative data from 780 controls. A dysexecutive syndrome was observed in 80.6% of the patients [95% confidence interval: 71.1–90.1]. The dysexecutive profile was characterized by prominent impairments in deduction, flexibility, inhibition and initiation in the cognitive domain, and by global hypoactivity with apathy and hyperactivity in the behavioral domain. This finding implies that patients with PD should be assessed with cognitive tests and a validated inventory for behavioral dysexecutive syndromes. A shortened battery (based on three cognitive tests and three behavioral domains) provided high diagnostic accuracy.     

Impulse control disorders in Parkinson’s disease: Predominant role of psychological determinants

Objectives: Impulse Control Disorders (ICDs) in Parkinson’s disease (PD) have previously almost exclusively been considered to result from anti-parkinsonian medication. However, this biomedical perspective has failed to achieve a full understanding of the phenomenon and it is argued that a failure to consider psychological factors is a critical omission.

Design: The present study examined the predictive relationship between ICDs in PD and a range of psychological measures, whilst controlling for a number of biomedical determinants.

Main outcome measures: One hundred participants with idiopathic PD completed questionnaires that assessed demographic and clinical characteristics, psychological measures and the presence of ICDs (QUIP-RS).

Results: Increased use of a ‘negative’ coping strategy, stronger illness identity, more emotional illness representations and stress were found to be significant predictors of ICDs, and different psychological predictors were associated with different ICDs. Medication was not found to predict ICDs in the presence of psychological factors, either when total treatment levels were considered or when agonist dose was considered alone.

Conclusions: This study provides the first quantitative evidence of a predominant predictive relationship between psychological factors and ICDs in PD. The results suggest that psychological interventions may have useful therapeutic role to play for ICDs in PD.     

Tic douloureux, Parkinson’s disease and the herpes connection

Several cases encountered in psychiatric practice are described in which herpetic involvement of the trigeminal nerve appeared to be crucial to the pathophysiology of the patients’s illness. A brief history of herpes is discussed in terms of the anatomy and physiology of the trigeminal nerve. Particular attention is given to the effects of intraneuronal herpes on gasserian ganglion and spinal nuclei discharge threshoolds, as well as viral pathways directly impacting the substantia nigra. Evidence characterizing Parkinson’s disease as one of several important manifestations of CNS herpes is covered. This article will be presented, by invitation, at the Neuroscience Seminar, Department of Medicine, University of Otago, Dunedin, New Zealand, on 19 August 1997.     

Subjective states associated with retrieval failures in Parkinson’s disease

Instances in which we cannot retrieve information immediately but know that the information might be retrieved later are subjective states that accompany retrieval failure. These are expressed in feeling-of-knowing (FOK) and Tip-of-the-tongue (TOT) experiences. In Experiment 1, participants with Parkinson’s disease (PD) and older adult controls were given general questions and asked to report when they experienced a TOT state and to give related information about the missing word. The PD group experienced similar levels of TOTs but provided less correct peripheral information related to the target when in a TOT state. In Experiment 2, participants were given a Semantic (general knowledge questions) and an Episodic (word pairs) FOK task. PD patients failed to accurately predict their future memory performance (FOK) in response to both episodic and semantic cues. Results are interpreted in the context of recent frameworks of memory and metacognition.