Proprioceptive impairment and postural orientation control in Parkinson's disease

Impairment of postural control is a common consequence of Parkinson’s disease (PD). Increasing evidences demonstrate that the pathophysiology of postural disorders in PD includes deficits in proprioceptive processing and integration. However, the nature of these deficits has not been thoroughly examined. We propose to establish a link between proprioceptive impairments and postural deficits in PD using two different experimental approaches manipulating proprioceptive information. In the first one, the subjects stood on a platform that tilted slowly with oscillatory angular movements in the frontal or sagittal planes. The amplitude and frequency of these movements were kept below the semicircular canal perception threshold. Subjects were asked to maintain vertical body posture with and without vision. The orientations of body segments were analyzed. In the second one, the postural control was tested using the tendon-vibration method, which is known to generate illusory movement sensations and postural reactions. Vibrations were applied to ankle muscles. The subject’s whole-body motor responses were analyzed from center of pressure displacements.In the first experiment, the parkinsonian patients (PP) were unable to maintain the vertical trunk orientation without vision. Their performances with vision improved, without fully reaching the level of control subjects (CS). In the second experiment, the postural reactions of the PP were similar to those of the CS at the beginning of the perturbation and increased drastically at the end of the perturbation’s period as compared to those of CS and could induce fall.These results will bring new concepts to the sensorimotor postural control, to the physiopathology of posture, equilibrium and falls in PD and to the role of basal ganglia pathways in proprioception integration. Nevertheless, in order to assess precisely the role played by sensorimotor integration deficits in postural impairments in PD, further studies establishing the links between clinical features and abnormalities are now required.     

Pragmatic communication skills in patients with Parkinson's disease

BACKGROUND: Pragmatic communication abilities may depend on intact frontal lobe systems. Independent evidence suggests that some persons with Parkinson's disease (PD) are impaired on measures of frontal lobe function. HYPOTHESIS: We therefore hypothesized in Study 1 that pragmatic communication skills would be impaired in some persons with PD and would be linked to frontal dysfunction in these patients. In Study 2 we hypothesized that PD patients would be unaware of their pragmatic communication deficits. METHODS: In Study 1 we administered tests of pragmatic abilities and frontal lobe functioning to twenty-two persons with Parkinson's disease (PD) and 10 healthy controls. In Study 2 we obtained self-ratings of pragmatic abilities from 11 PD patients and then checked these self-ratings against ratings of these same abilities by the patient's spouses. RESULTS: We found in Study 1 that patients with PD were: (a) significantly impaired on measures of pragmatic communication abilities, especially in the areas of conversational appropriateness, turn-taking, prosodics and proxemics, and that this impairment was significantly related to measures of frontal lobe function. In study 2 we found that PD patients overestimated their own abilities relative to spousal ratings of those abilities and thus were unaware of the extent of their problems with pragmatic social communication skills. CONCLUSION: We conclude that pragmatic social communication skills are impaired in PD and that this impairment may be related to frontal lobe dysfunction.     

Alzheimer’s disease and impairment of the Self

Impairment of the Self has been described in frontal–temporal dementia but little research has been carried out in patients with Alzheimer’s disease (AD).

Objective

The aim of this study was to explore changes in the self in patients with AD.

Method

Forty-seven patients with mild to moderate AD were examined using a semi-structured scale designed to assess the self-concept along three dimensions, namely, the Material Self, the Social Self and the Spiritual Self.

Results

The majority of patients (43 out of 47) presented impairment of at least one dimension of the Self. When only one dimension was affected, it was always the Social Self. The severity of impairment of the Self was correlated to the impairment of the semantic autobiographical memory and apathy.

Conclusion

The Self is impaired in AD and the Social Self dimension appears to be more vulnerable in AD than other dimensions.     

Review of first trial responses in balance control: influence of vestibular loss and Parkinson's disease

The reaction to an unexpected balance disturbance is unpractised, often startling and frequently associated with falls. This everyday situation can be reproduced in an experimental setting by exposing standing humans to sudden, unexpected and controlled movements of a support surface. In this review, we focus on the responses to the very first balance perturbation, the so-called first trial reactions (FTRs). Detailed analysis of FTRs may have important implications, both for clinical practice (providing new insights into the pathophysiological mechanisms underlying accidental falls in real life) and for understanding human physiology (what triggers and mediates these FTRs, and what is the relation to startle responses?). Several aspects of the FTRs have become clear. FTRs are characterized by an exaggerated postural reaction, with large EMG responses and co-contracting muscles in multiple body segments. This balance reaction is associated with marked postural instability (greater body sway to the perturbation). When the same perturbation is repeated, the size of the postural response habituates and the instability disappears. Other issues about FTRs remain largely unresolved, and these are addressed here. First, the functional role of FTRs is discussed. It appears that FTRs produce primarily increased trunk flexion during the multi-segmental response to postural perturbations, thus producing instability. Second, we consider which sensory signals trigger and modulate FTRs, placing specific emphasis on the role of vestibular signals. Surprisingly, vestibular signals appear to have no triggering role, but vestibular loss leads to excessive upper body FTRs due to loss of the normal modulatory influence. Third, we address the question whether startle-like responses are contributing to FTRs triggered by proprioceptive signals. We explain why this issue is still unresolved, mainly because of methodological difficulties involved in separating FTRs from ‘pure’ startle responses. Fourth, we review new work about the influence of perturbation direction on FTRs. Recent work from our group shows that the largest FTRs are obtained for toe-up support surface rotations which perturb the COM in the posterior direction. This direction corresponds to the directional preponderance for falls seen both in the balance laboratory and in daily life. Finally, we briefly touch upon clinical diagnostic issues, addressing whether FTRs (as opposed to habituated responses) could provide a more ecologically valid perspective of postural instability in patients compared to healthy subjects. We conclude that FTRs are an important source of information about human balance performance, both in health and disease. Future studies should no longer discard FTRs, but routinely include these in their analyses. Particular emphasis should be placed on the link between FTRs and everyday balance performance (including falls), and on the possible role played by startle reactions in triggering or modulating FTRs.     

Response speed, contingent negative variation and P300 in Alzheimer’s disease and MCI

Background

Decreased speed of information processing is a hallmark of Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Recent studies suggest that response speed (RS) measures are very sensitive indicators of changes in longitudinal follow-up studies. Insight into the psycho-physiological underpinnings of slowed RS can be provided by measuring the associated event-related potentials (ERP).

Aims

The current study aims to investigate the relation between RS and its psycho-physiological correlates in AD and MCI.

Methods

Fifteen psychoactive drug-naïve AD patients, 20 MCI patients and twenty age-matched, healthy control subjects participated. Response speed was measured during a simple (SRT) and choice reaction time task (CRT). An oddball and contingent negative variation (CNV) paradigm were used to elicit ERP. To evaluate test-retest reliability (TRR), subjects underwent a similar assessment one week after the first.

Results

The SRT and CRT distinguished the patient groups significantly. The P300 amplitude and latency also distinguished the groups and showed a significant correlation with response speed. The CNV amplitude did not reveal a significant difference between groups and also showed a low TRR.The TRR of the SRT, CRT and P300 amplitude and latency in general was moderate to high.The current study suggests that response speed measures on a behavioural and psycho-physiological level deserve attention as a possible marker in the diagnosis and follow-up of AD.     

Flanker compatibility effects in patients with Parkinson's disease: impact of target onset delay and trial-by-trial stimulus variation

Parkinson’s disease (PD) patients and healthy controls were administered a flanker task that consisted of the presentation of colored targets and distractors. Participants were required to attend to the center target and identify its color. The stimulus displays were either congruent (i.e., the target and flankers were the same color) or incongruent. The time between the onset of the flanker and the target color (the target onset delay) was either short or long. Results indicated that PD patients and controls did not differ in the magnitude of the flanker effect within individual trials in that both groups demonstrated a typical flanker effect at the short target onset delay and neither group demonstrated a flanker effect at the longer delay. However, when performance was examined on a trial-by-trial basis, PD patients demonstrated a slowing of reaction time relative to controls when having to make the same response across consecutive trials at longer inter-trial intervals when the flankers were incongruent across consecutive trials and the display on the second of two trials was incongruent. These results indicate that PD patients are impaired in inhibiting the distractors over an extended delay and that this deficit may impact motor responding in these patients, suggesting that the basal ganglia contribute to the interface of attention and action.     

Spermine improves recognition memory deficit in a rodent model of Huntington’s disease

Huntington’s disease (HD) is a progressive neurodegenerative disorder associated with motor and cognitive impairment. Intrastriatal administration of quinolinic acid (QA) causes neurodegeneration, glial proliferation and cognitive impairment in animals, which are similar to these seen in human HD. Since polyamines improve memory in cognitive tasks, we now tested if the post-training intrastriatal administration of spermine, an agonist of the polyamine site at the NMDA receptor, reverses the deficits in the object recognition task induced by QA. Bilateral striatal injections of QA (180 or 360 nmol/site) caused object recognition impairment, neuronal death and reactive astrogliosis. A single injection of spermine (0.1 and 1 nmol/site), 5 days after QA injection, reversed QA-induced impairment of object recognition task. Spermine (0.1 nmol/site) also inhibited QA-induced reactive astrogliosis measured by a semi-quantitative determination of GFAP immunolabelling, but did not alter neuronal death, measured by a semi-quantitative determination of fluoro-Jade C staining. These results suggest that polyamine binding sites may be considered a novel therapeutic target to prevent reactive astrogliosis and mnemonic deficits in HD.     

Past tense formation and comprehension of passive sentences in Parkinson's disease: evidence from Greek

The present study investigates the production of regular and irregular verbs in the past tense and the comprehension of passive sentences by Greek-speaking PD patients, and compares their behavior to that of normal speakers. Although the two groups manifest large scale differences at all the above constructions, the behavior of PDs is not different at regular vs. irregular past tense formation neither did we obtain strong evidence that they do not comprehend passives, most importantly, they certainly do not perform at chance. On the basis of the above, we conclude that there are no indications for a clearly linguistic deficit of the PD group, hence, their difference with the control group should be attributed to other factors, such as the computational demands of the tasks.     

Analyzing feature distinctiveness in the processing of living and non-living concepts in Alzheimer’s disease

The conceptual structure account (CSA) is a model specifying the role of the living and non-living domain dichotomy in the structure of semantic memory. According to this model, feature distinctiveness and the perceptual–functional inter-correlation of concepts are assumed to play a major role in impairing the ability to discriminate between living and non-living concepts in Alzheimer’s disease (AD). The hypothesis was tested in this study by using naming and sorting tasks traditionally considered as assessing distinctiveness, and a property verification task where distinctiveness and perceptual–functional inter-correlation were objectively controlled against norms especially created for this purpose. Alzheimer’s patients (n = 59) with minimal, mild or moderate dementia and normal elderly adults (n = 31) participated in the study. Overall, the findings did not support the CSA predictions. They revealed a distinctiveness effect on response accuracy with shared features dominating distinctive features regardless of domain. They also revealed more difficulties in the tasks involving effortful processes. The results stress the need to consider both cognitive demands of tasks and structural aspects of knowledge in the evaluation of semantic memory in AD.     

Posture recognition in Alzheimer's disease

BACKGROUND: Apraxia is neurologically induced deficit in the ability perform purposeful skilled movements. One of the most common forms is ideomotor apraxia (IMA) where spatial and temporal production errors are most prevalent. IMA can be associated Alzheimer's disease (AD), even early in its course, but is often not identified possibly because the evaluation of IMA by inexperienced judges using performance tests is unreliable. The purpose of this study, therefore, is to learn if the Postural Knowledge Test (PKT), a praxis discrimination test that assesses knowledge of transitive (PKT-T subtest) and intransitive (PKT-I subtest) postures and does not require extensive training, is as sensitive and specific as the praxis performance tests. METHODS: We studied 15 subjects with probable AD as well as 18 age-matched controls by having them perform transitive and intransitive gestures to command and imitation, as well as having them discriminate between correct and incorrect transitive and intransitive postures. RESULTS: Overall on all tests, the control subjects performed better than those with AD. In addition all subjects had more trouble with transitive than intransitive gestures. Using a stepwise discriminative analysis, 81.8% of the subjects could be classified according to Group (94.4% of Controls, 66.7% of AD subjects). In this analysis, the PKT-T (transitive posture subtest) was the only measure that contributed to the discrimination of subjects. CONCLUSION: We found that having subjects select the correct transitive hand postures in this "booklet test" was more sensitive than grading their praxis performances even when using judges with extensive training. This suggests that this discrimination test might be an excellent means for diagnosing and screening patients for AD. The reason why recognition of transitive postures is relatively more difficult for our AD subjects is not known. Two possibilities are that the representations for intransitive movements are stronger than those for transitive movements, and hence, more resistant to degradation, or that intransitive acts are stored in parts of the brain not affected by AD.     

An evaluation of recollection and familiarity in Alzheimer’s disease and mild cognitive impairment using receiver operating characteristics

There is a need to investigate exactly how memory breaks down in the course of Alzheimer’s disease (AD). Examining what aspects of memorial processing remain relatively intact early in the disease process will allow us to develop behavioral interventions and possible drug therapies focused on these intact processes. Several recent studies have worked to understand the processes of recollection and familiarity in patients with mild cognitive impairment (MCI) and very mild AD. Although there is general agreement that these patient groups are relatively unable to use recollection to support veridical recognition decisions, there has been some question as to how well these patients can use familiarity. The current study used receiver operating characteristic (ROC) curves and a depth of processing manipulation to understand the effect of MCI and AD on the estimates of recollection and familiarity. Results showed that patients with MCI and AD were impaired in both recollection and familiarity, regardless of the depth of encoding. These results are discussed in relation to disease pathology and in the context of recent conflicting evidence as to whether familiarity remains intact in patients with MCI. The authors highlight differences in stimuli type and task difficulty as possibly modulating the ability of these patients to successfully use familiarity in support of memorial decisions.     

The relationship between executive function and verbal memory in Parkinson's disease

A growing body of evidence suggests that the various cognitive symptoms found in Parkinson's disease (PD) are secondary to executive dysfunction. Studies addressing this possibility for memory impairment specifically have not included measures of working memory nor have they ruled-out potential mediating variables such as overall level of cognitive impairment or depression. The purpose of this study was to include measures of these variables in determining the relationship between multiple aspects of executive function and delayed verbal recall in 32 idiopathic PD patients. Results were consistent with the original hypothesis and further suggest that working memory is a key factor in recall memory and may mediate the relationship between other executive measures and recall in PD.     

A common mechanism in verb and noun naming deficits in Alzheimer’s patients

We tested the ability of Alzheimer’s patients and elderly controls to name living and non-living nouns, and manner and instrument verbs. Patients’ error patterns and relative performance with different categories showed evidence of graceful degradation for both nouns and verbs, with particular domain-specific impairments for living nouns and instrument verbs. Our results support feature-based, semantic representations for nouns and verbs and support the role of inter-correlated features in noun impairment, and the role of noun knowledge in instrument verb impairment.     

Stimulus timing by people with Parkinson's disease

Previous literature suggests that Parkinson’s disease is marked by deficits in timed behaviour. However, the majority of studies of central timing mechanisms in patients with Parkinson’s disease have used timing tasks with a motor component. Since the motor abnormalities are a defining feature of the condition, the status of timing in Parkinson’s disease remains uncertain. Data are reported from patients with mild to moderate Parkinson’s disease (both on and off medication) and age- and IQ-matched controls on a range of stimulus timing tasks without counting. Tasks used were temporal generalization, bisection, threshold determination, verbal estimation, and a memory for duration task. Performance of patients was generally “normal” on all tasks, but significant differences from performance of controls were found on the memory for duration task. Among the “normal” effects noted were arithmetic mean bisection, asymmetric temporal generalization gradients, and subjective shortening on the memory for duration task. The results suggest (a) that some previous reports of timing “deficits” in Parkinson’s patients were possibly due to the use of tasks requiring a timed manual response and (b) small differences between patients and controls may be found on tasks where two stimuli are presented on each trial, whether patients are on medication or off it.     

Asperger’s and musical creativity: The case of Erik Satie

The link between psychopathology and creativity was investigated in the study of one individual: the French composer Erik Satie. The current literature puts much emphasis on the connection between creativity and the psychoses – such as schizophrenia and the affective disorders – but there is relatively little concerning other psychological disorders. Nevertheless, there has been a recent upswing in the study of autism and associated disorders (such as Asperger’s syndrome), and their association with creativity. The literature reviewed here included a number of biographies, books about the autism spectrum disorders, and articles detailing the psychopathology-creativity link. The aim was not to diagnose Satie with a psychological disorder, but to illustrate that he, who was highly creative, innovative and influential in the development of 20th century music, displayed many of the personality traits typical of Asperger’s syndrome. These include perfectionism, perseverance, hatred of conventions, and heightened sensitivity; these combined enabled Satie to devise his own original musical idiom. This case study alone does not – and was not intended to – answer the overall question regarding the existence of a psychopathology-creativity link; but it does support the idea in the context of current literature.     

Everyday cognitive failures and memory problems in Parkinson's patients without dementia

There is growing evidence that Parkinson’s disease patients without dementia exhibit cognitive deficits in some executive, memory and selective attention tasks. However, the impact of these deficits on their everyday cognitive functioning remains largely unknown. This issue was explored using self-report questionnaires. Twenty-four Parkinson’s patients and 24 age-matched controls rated how frequently they make particular cognitive errors, such as forgetting what they were about to say. In addition, a partner or significant other also rated each participant’s propensity for making cognitive errors. Rather than simply rating themselves as making more of all types of errors, these results indicate that PD patients make more of specific types of error. Further analysis suggests that some of these errors are related to attentional processes (being more distractible) whereas others are related to retrieval processes (being unable to recall important details from the previous day).     

Impaired awareness of movement disorders in Parkinson’s disease

Background

This study analyzed the presence of awareness of movement disorders (dyskinesias and hypokinesias) in 25 patients with Parkinson’s disease (PD) and motor fluctuations (dyskinesias, wearing off, on–off fluctuations). Of the few studies that have dealt with this topic, none have analyzed the differences in the awareness of motor deficits by comparing the on and off states using motor scales and an extensive battery of tests to assess cognitive and behavioral functioning.

Methods

PD patients were compared on three different scales that we have devised to measure awareness of movement disorders: Global Awareness of Movement (GAM) Disorders, dyskinesia/hypo-bradykinesia rating scales.

Results

Data showed that PD patients had greater awareness and psychological suffering in the off state than in the on state. In particular, they were troubled by motor disabilities related to hypokinesias and had mood-related symptoms and a perception of disability in activities of daily living. Interestingly, patients only showed a selective reduction of awareness of movement disorders associated with executive functions and related to dyskinesias in the on state, compared to a preserved awareness of hypokinesias in the off state. On the contrary, no association with executive functions was found in the off state.

Conclusion

Our findings suggest that the dopaminergic overstimulation of mesocorticolimbic pathways may cause a dysfunction of prefrontal–subcortical connections related to the impaired insight.     

Impaired emotion recognition in music in Parkinson’s disease

Music has the potential to evoke strong emotions and plays a significant role in the lives of many people. Music might therefore be an ideal medium to assess emotion recognition. We investigated emotion recognition in music in 20 patients with idiopathic Parkinson’s disease (PD) and 20 matched healthy volunteers. The role of cognitive dysfunction and other disease characteristics in emotion recognition was also evaluated.     

Emotion and object processing in Parkinson’s disease

The neuropsychological literature on the processing of emotions in Parkinson’s disease (PD) reveals conflicting evidence about the role of the basal ganglia in the recognition of facial emotions. Hence, the present study had two objectives. One was to determine the extent to which the visual processing of emotions and objects differs in PD. The other was to assess the impact of cognitive load on the processing of these types of information. Thirty-one patients with idiopathic PD (IPD) under dopamine replacement therapy (DRT) were compared to 30 control subjects on emotion and object recognition tasks. Recognition of objects was more accurate and faster than recognition of facial expressions of emotion, for both groups of subjects. In a second experiment using an N-back procedure with the same stimuli—a more demanding task with a higher cognitive load—patients with IPD were as accurate as control subjects in detecting the correct sequential presentation of stimuli, but were much slower in their decision responses. This indicates that IPD patients under DRT are not impaired in encoding emotion or object information, but that they have difficulty with the processing demands of the N-back task. Thus, patients with IPD appear to be more sensitive to cognitive load than to type of information, whether facial emotions or objects. In this perspective, one must consider that a deafferented dopaminergic system has problems processing more complex information before one can posit the existence of deficits affecting a specific type of information.     

Testing the effects of end-goal during reach-to-grasp movements in Parkinson’s disease

Previous evidence suggests that hand shaping during reaching is modulated by the presence and the nature of the end-goal following object’s grasp. Here we test whether such modulation is maintained in Parkinson’s disease (PD). Six participants with PD and six healthy participants took part in the study. Participants were requested to reach towards a bottle filled with water, and then: (1) grasp it without performing any subsequent action; (2) grasp it and place it accurately on a target area; (3) grasp it and pour its contents within a container. The results showed that participants shaped their hand differently depending on the presence or absence of an action following object’s grasp. However, the request to perform an action after grasp determined a modulation of hand kinematics which was delayed for PD than for control participants. Further, whereas for control participants the nature of the end-goal determined a modulation of hand shaping, for PD patients such modulation was not evident. Data are discussed in terms of the role played by basal ganglia in implementing anticipatory mechanisms for the control of manipulative activities. We contend that in PD patients these mechanisms are not totally compromised, but their implementation depends on the action information that has to be anticipated.