Abnormal sleep and sleepiness in Parkinson's disease

PURPOSE OF REVIEW: Sleep problems are frequent and disabling in patients with Parkinson's disease. Recent data provide major advances in the mechanisms and consequences of rapid eye movement sleep behavior disorders, insomnia and narcolepsy-like daytime sleepiness. RECENT FINDINGS: A large series confirms that rapid eye movement sleep behavior disorders may precede parkinsonism or dementia (particuarly, but not exclusively, Lewy bodies dementia) for several years. In Parkinson's disease, rapid eye movement sleep behavior disorders expose patients to higher risks of dementia and hallucinations. Surprisingly, parkinsonism disappears during rapid eye movement sleep behavior disorders, suggesting basal ganglia are bypassed. The interest for structures controlling atonia during rapid eye movement sleep switches from the pedunculopontine nuclei to the locus subcoeruleus. The neuropathology of hypothalamus in Parkinson's disease indicates a massive hypocretin loss, probably underlying the narcolepsy phenotype. The benefit of the new, 24-h long acting ropinirole and transdermal rotigotine on sleep and sleepiness is modest. Eventually, the dopamine release in the mesocorticolimbic pathway is increased during rapid eye movement sleep, supporting its role in dopaminergic-induced vivid dreams. SUMMARY: In clinical practice, rapid eye movement sleep behavior disorders should be looked at as heralding neurodegenerative diseases in patients with mild cognitive impairment and as a risk factor for dementia and hallucinations in patients with Parkinson's disease.     

Abnormal visual activation in Parkinson's disease patients

Among nonmotor symptoms observed in Parkinson's disease (PD) dysfunction in the visual system, including hallucinations, has a significant impact in their quality of life. To further explore the visual system in PD patients we designed two fMRI experiments comparing 18 healthy volunteers with 16 PD patients without visual complaints in two visual fMRI paradigms: the flickering checkerboard task and a facial perception paradigm. PD patients displayed a decreased activity in the primary visual cortex (Broadmann area 17) bilaterally as compared to healthy volunteers during flickering checkerboard task and increased activity in fusiform gyrus (Broadmann area 37) during facial perception paradigm. Our findings confirm the notion that PD patients show significant changes in the visual cortex system even before the visual symptoms are clinically evident. Further studies are necessary to evaluate the contribution of these abnormalities to the development visual symptoms in PD. © 2010 Movement Disorders Society     

Implicit and explicit emotional processing in Parkinson's disease

Recent semantic priming investigations conducted by Spicer, Brown and Gorell (1994) and McDonald, Brown and Gorell (1996) reported hyperpriming in persons with Parkinson's disease (PD) and provided evidence supporting impaired set-shifting as the underlying cause. This paper discusses notable priming behaviours exhibited by the normal control groups employed by Spicer and McDonald and colleagues. The argument is developed that these studies only measured attention-dependent semantic processing and, therefore, their results do not speak to issues of automatic semantic activation in PD as originally proposed by Spicer et al. nor to putative deficits in set-shifting as proposed by McDonald et al. The implications for future priming research in PD are also discussed.     

Perception of emotional speech in Parkinson's disease.

Nonmotor symptoms in Parkinson's disease (PD) involving cognition and emotionality have progressively received attention. The objective of the present study was to investigate recognition of emotional prosody in patients with PD (n = 14) in comparison to healthy control subjects (HC, n = 14). Event-related brain potentials (ERP) were recorded in a modified oddball paradigm under passive listening and active target detection instructions. Results showed a poorer performance of PD patients in classifying emotional prosody. ERP generated by emotional deviants (happy/sad) during passive listening revealed diminished amplitudes of the mismatch-related negativity for sad deviants, indicating an impairment of early preattentive processing of emotional prosody in PD.     

Abnormal psychophysical visual perception in Parkinson's disease patients

Several visual dysfunctions in Parkinson's disease (PD) are described. Most of them are subtle or only demonstrated by stimulus-specific electrophysiologic or psychophysical testing. However, these minor deficits are thought to be of clinical relevance as they are related to direct or indirect complaints. Special emphasis is laid on visual hallucinations. These are most likely of multifactorial origin. The relation between hallucinations in PD and in dementia with Lewy bodies has to be elaborated further. Visual loss, as a possible and reversible cause of visual hallucinations should be actively sought and corrected as far as possible. An underlying role of dopaminergic retinal cells in visual dysfunction of PD patients is widely recognised. However, whether the basic abnormality resides also in the visual cortex remains to be elucidated. Other neurotransmitters may also be involved. It has not been answered whether visual dysfunction might distinguish PD from other forms of parkinsonism.     

Generative word fluency skills in adults with Parkinson's disease

Background: Studies addressing cognitive function of adults with Parkinson's disease (PD) have revealed inconsistencies relative to language disturbances. Whereas some researchers have observed no evidence to support language dysfunction on semantic/generative naming tasks, others have found that adults with PD display decreased performance on these tasks. Generative naming may be problematic for adults with PD but its usefulness as a predictor for identifying cognitive impairment in this population is unclear. Aims: The purpose of the investigation was to examine performance of a group of 20 PD individuals and an age‐, education‐, and gender‐matched control group of 20 individuals on generative naming tasks for nouns, verbs, and adjectives. The primary hypothesis was that the adults with PD would demonstrate a deficit in verb generation. Methods & Procedures: All participants with PD had a diagnosis based on the presence of two of three classic PD signs, bradykinesia, resting tremor, and rigidity, as determined by a neurologist. All participants were native English speakers, had normal or corrected vision, passed a hearing screening, and had no history of developmental disabilities, head injury, or substance abuse. There were no significant differences between groups on premorbid Full Scale IQ or cognitive functioning as measured by the MMSE. The experimental procedure consisted of noun, verb, and adjective fluency tasks. Participants were instructed to name as many exemplars as possible in 60 seconds for each part of speech. Scores were based on total number and percentage of accurate responses. Outcomes & Results: Both groups produced significantly more nouns than verbs and adjectives. Percentage of accuracy data revealed that: (1) the control group was significantly more accurate than the Parkinson's group; (2) the Parkinson's group was significantly less accurate than controls on adjective generation; and (3) significantly higher accuracy was observed for nouns and verbs than adjectives across groups. Overall word retrieval performance as measured by the Test of Adolescent/Adult Word Finding was significantly related to adjective generation only. Conclusions: The group with PD exhibited an impairment in adjective generation as compared to controls. Mental representations for adjectives appear to be more multifaceted than representations for nouns and verbs. The increased complexity of semantic networks for adjectives may be vulnerable to the effects of brain damage associated with PD.     

Deficits in decoding emotional facial expressions in Parkinson's disease

INTRODUCTION: The basal ganglia have numerous connections not only with the motor cortex but also with the prefrontal and limbic cortical areas. Therefore, basal ganglia lesions can disturb motor function but also cognitive function and emotion processing. The aim of the present study was to assess the consequences of Parkinson's disease (PD) on ability to decode emotional facial expressions (EFEs)-a method commonly used to investigate non-verbal emotion processing. METHODS: Eighteen PD patients participated in the study, together with 18 healthy subjects strictly matched with respect to age, education and sex. The patients were early in the course of the disease and had not yet received any antiparkinsonian treatment. Decoding of EFEs was assessed using a standardized, quantitative task where the expressions were of moderate intensity, i.e. quite similar to those experienced in everyday life. A set of tests also assessed executive function. Visuospatial perception, depression and anxiety were measured. RESULTS: Early in the course of the disease, untreated PD patients were significantly impaired in decoding EFEs, as well as in executive function. The deficits were significantly interrelated, although neither was significantly related to severity of the motor symptoms. Visuospatial perception was not impaired, and the patients' impairment was related neither to their depression nor to their anxiety score. The PD patients' impairment in decoding EFEs was related to a systematic response bias. CONCLUSION: Early in the course of PD, non-verbal emotional information processing is disturbed. This suggests that in PD, nigrostriatal dopaminergic depletion leads not only to motor and cognitive disturbances but also to emotional information processing deficits. The observed correlation pattern does not enable adoption of a clear-cut position in the debate over totally or partially segregated functional organization of the basal ganglia circuits.     

Visual exploration of emotional facial expressions in Parkinson's disease

Parkinson's disease (PD) is associated with impairments in facial emotion recognition as well as visual and executive dysfunction. We investigated whether facial emotion categorization impairments in PD are attributable to visual scanning abnormalities by recording the eye movements of 16 non-demented PD and 20 healthy control (HC) participants during an emotion recognition task. We examined the influence of several factors that can affect visual scanning, including oculomotor, basic visual, and cognitive abilities (executive function). Increases in the number and duration of fixations in the top regions of surprise facial expressions were related to increases in recognition accuracy for this emotion in PD participants with left-sided motor-symptom onset. Compared to HC men, HC women spent less time fixating on fearful expressions. PD participants displayed oculomotor abnormalities (antisaccades), but these were unrelated to scanning patterns. Performance on visual measures (acuity, contrast sensitivity) correlated with scanning patterns in the PD group only. Poorer executive function was associated with longer fixation times in PD and with a greater number of fixations in HC. Our findings indicate a specific relation between facial emotion categorization impairments and scanning of facial expressions in PD. Furthermore, PD and HC participants’ scanning behaviors during an emotion categorization task were driven by different perceptual processes and cognitive strategies. Our results underscore the need to consider differences in perceptual and cognitive abilities in studies of visual scanning, particularly when examining this ability in patient populations for which both vision and cognition are impaired.     

Abnormal eye movement behavior during reading in Parkinson's disease

IntroductionReading difficulties are common in Parkinson's disease (PD) but not well studied. We report a case of reading difficulties in a 40-year-old man with 6-year history of PD on dopamine replacement therapy.MethodsWe performed detailed neuro-ophthalmic examination and assessment of reading with and without infrared oculography.ResultsClinical examination revealed visual acuity of 20/20, no evidence of vision loss, and normal eye movement and ocular alignment with normal saccades, pursuit, and normal convergence. During King-Devick test, a rapid number reading task performed on a book, patient had normal number reading speed. More detailed study of number and word reading using infrared oculography revealed that while this patient had normal speed and eye movement behavior during number reading, he had dramatic slowing and eye movement abnormality during word reading. The slower reading speed during word reading was due to increased number of progressive saccades, smaller saccade amplitudes, increased number of regressive saccades, and longer fixation durations.ConclusionsThis case nicely illustrated the importance of comprehensive neuro-ophthalmic evaluations in Parkinson's disease and shows that reading difficulties can arise even when there is good visual acuity, ocular motor abilities necessary to read, and accommodation. In this case, reading difficulty was due to higher order ocular motor planning or cognitive abilities involved in word reading since the patient had no difficulty with ocular motor planning while reading numbers. These findings may have important implications towards our understanding of PD and can serve to spark further research in this important area.     

Abnormal cortical facilitation and L-dopa-induced dyskinesia in Parkinson's disease

BackgroundAnimal models of Parkinson's Disease (PD) demonstrated increased facilitatory cortico-striatal activity, reflecting overactive glutamatergic neurotransmission and contributing to the pathophysiology of l-dopa induced dyskinesias (LIDs).ObjectiveTo assess different facilitatory intracortical circuits in the primary motor cortex (M1) in patients with PD and LIDs by means of a combination of transcranial magnetic stimulation (TMS) protocols.MethodsWe tested the Input/Output (I/O) curve, intracortical facilitation (ICF) and short-interval intracortical facilitation (SICF) at baseline (T0), ‘OFF’ and ‘ON’ state, in 20 PD patients with LIDs. The same parameters were examined after 2 weeks of chronic intake of 50 mg (T1) and 100 mg/day (T2) of safinamide. Finally, we tested SICF in a further group of patients without LIDs.ResultsAt T0, patients with LIDs showed increased I/O curve steepness, which was partly ameliorated by l-dopa. These patients also had normal ICF, and abnormally increased SICF, which did not change with l-dopa. Safinamide improved the I/O curve both at T1 and T2, it reduced SICF at T1 and normalized this measure at T2. In patients with PD and LIDs, SICF correlated with the severity of dyskinesia. In patients without LIDs, SICF was less prominently abnormal and responsive to l-dopa.ConclusionsPatients with PD and LIDs have abnormal cortical facilitation, possibly suggesting overactive glutamatergic neurotransmission in specific circuits within M1. Although not responsive to l-dopa, this dysfunction is restored by the anti-glutamatergic properties of safinamide 100 mg. The results suggest that the abnormal cortical facilitation in M1 contributes to the pathophysiology of LIDs.     

Involuntary emotional expression disorder (IEED) in Parkinson's disease

ObjectiveTo estimate the frequency and correlates of involuntary emotional expression disorder (IEED) in Parkinson's disease (PD) using the Center for Neurologic Study-Lability Scale (CNS-LS) and recently-proposed diagnostic criteria for IEED.BackgroundIEED is characterized by uncontrollable emotional episodes, typically unrelated to or in excess of the underlying mood, and occurring with minimal or no stimulus. IEED has been reported to occur in many neurological disorders and neurodegenerative diseases, but its prevalence and correlates in PD have not been well studied. Additionally, there is no published research using recently-proposed IEED diagnostic criteria in any population.Methods193 patients with idiopathic PD were assessed with a neuropsychiatric battery, including the CNS-LS and the 15-item Geriatric Depression Scale (GDS-15). A subset (N = 100) was also administered a diagnostic interview by a blinded rater that applied criteria for both IEED and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) depressive disorders.ResultsApplying formal diagnostic criteria, 7.0% of patients were diagnosed with IEED, and an additional 7.0% had subsyndromal IEED symptoms. Applying recommended CNS-LS cutoff scores from other populations, either 42.5% (cutoff ≥13) or 16.6% (cutoff ≥17) screened positive for IEED. Depressive symptoms were associated with higher CNS-LS scores (B[SE] = 0.27[.08], P = .001) but not with a diagnosis of IEED (odds ratio = 1.1, [95% CI = 1.0–1.3], P = .16). The CNS-LS had poor discriminant validity for an IEED diagnosis (AUC = .79, no cutoff value with sensitivity and specificity both >60%).ConclusionsIEED and depression are overlapping but distinct disorders in PD. IEED symptoms may occur in up to 15% of PD patients, but a disorder occurs in only half of those, suggesting that often IEED symptoms are not clinically significant in this population. The CNS-LS does not appear to be a good screening instrument for IEED in PD, in part due to its high correlation with depressive symptoms.     

Abnormal gaze strategies during problem solving in Parkinson's disease.

We have taken a novel approach to the study of problem solving involving the detailed analysis of natural scanning eye movements during the 'one touch' Tower of London task. Control subjects and patients with idiopathic Parkinson's disease (PDs) viewed a series of pictures depicting two arrangements of coloured balls in pockets within the upper and lower halves of a computer display. The task was to plan (but not execute) the shortest movement sequence required to rearrange the balls in one half of the display (the Workspace) to match the arrangement in the opposite half (the Goalspace) and indicate the number of moves required for problem solution. As problem complexity increased, control subjects spent proportionally more time fixating the Workspace region. This pattern was found regardless of whether subjects were instructed to solve problems by rearranging balls in the lower or upper visual fields. The distribution of gaze within the Workspace was also found to be problem dependent, with gaze being selectively directed towards the problem critical balls. In contrast, PDs were found to make more errors in the task and failed to show any dissociation in the amount of time fixating the two halves of the display. This pattern suggests that the patients had difficulty in encoding and/or maintaining current goals during problem solving, consistent with a role for fronto-striatal circuits in mechanisms of working memory and attention.     

Subjective emotional experience at different stages of Parkinson's disease

Subjective emotional experience is thought to rely on a large cortical-subcortical network including orbitofrontal and cingulate frontostriatal circuits together with the mesolimbic dopaminergic system that modulates their activity. Parkinson's disease (PD) provides a model for exploring this issue. By using an original emotion induction procedure, the present study examined to what extent subjective experience of emotion of PD patients at different stages of the disease was modulated by emotion in the same way as healthy individuals. A battery of film excerpts was used to elicit different emotional feelings (happiness, anger, fear, sadness, disgust, and neutral) in 15 newly diagnosed PD patients, 18 patients with advanced PD and 15 matched controls. The newly diagnosed patients were examined in two conditions: "on" and "off" dopaminergic medication. Participants reported the intensity of their emotional feelings on a scale consisting of 10 emotional categories. Results indicated that PD patients at different stages of the disease did not significantly differ from the controls in the self-reported emotional experience to the presented film excerpts. Moreover, analyses conducted within the newly diagnosed PD group (on-dopa vs. off-dopa conditions) indicated that the patients' emotional reactivity to the presented film excerpts was not significantly modulated by dopaminergic medication. These results thus question the possible role of dopaminergic pathways in subjective emotional experience, at least in this sample and in the context of emotion induction.     

False recognition of emotional word lists in aging and Alzheimer disease.

OBJECTIVE: To examine 3 different aspects of the emotional memory effect in aging and Alzheimer disease (AD): item-specific recollection, gist memory, and recognition response bias. METHOD: Younger adults, older adults, and patients with AD performed a false recognition memory test in which participants were tested on "lure" items that were not seen at study, but were semantically related to the study items. Participants were tested on 5 emotional and 5 non-emotional lists. RESULTS: In addition to finding an increase in true recognition for emotional versus non-emotional items in healthy younger and older adults but not in patients with AD, and confirming that emotional items led younger adults to shift their response bias to a more liberal one, 3 novel findings were observed. First, the emotional effect on response bias was also observed in healthy older adults. Second, the opposite emotional effect on response bias was observed in patients with AD. Third, emotional items did not lead to an improvement in item-specific recollection or gist memory. CONCLUSIONS: Although healthy older adults show the normal amygdala-modulated criterion shift for emotional items-influencing their subjective feeling that information has been previously encountered, the amygdala pathology present in early AD may disrupt this influence.     

Subthalamic nucleus stimulation affects subjective emotional experience in Parkinson's disease patients

A number of studies have reported impaired facial emotion recognition following subthalamic nucleus (STN) stimulation in Parkinson's disease (PD), and have related these changes to a limbic dysfunction induced by STN stimulation. The present study examined the effect of STN stimulation in PD patients on a specific component of emotion, namely the subjective experience of emotion. Thirteen post-operative PD patients, 13 pre-operative PD patients matched on clinical and neuropsychological characteristics, and 16 controls matched on age and education, were administered a validated battery of film excerpts known to primarily induce specific emotional feelings (anger, happiness, sadness, fear, disgust, and neutral), and self-rated the intensity of their emotional feelings on a discrete emotions questionnaire. The post-operative group showed a significant lower level of differentiation between the target feeling (i.e., the more likely to be reported) and non-target feelings for the film excerpts intended to induce “sadness” and “fear” respectively, as compared with the pre-operative and healthy control groups. Moreover, the post-operative group reported significantly less intense feelings of fear, anxiety and disgust for the excerpt intended to induce “fear” as compared with the pre-operative and the control groups, while no significant difference was observed between the pre-operative and control groups. Finally, the post-operative group reported significantly less intense feelings of sadness and anxiety during the excerpt intended to induce “sadness” as compared to the control group, although the differences between the pre- and post-operative groups and between the pre-operative and the control groups did not reach significance. Our study suggests that STN stimulation affects the subjective experience of emotion, thus providing a preliminary account of the modulation induced by STN stimulation of a distributed neuronal network underlying the subjective experience of emotion, although the exact contribution of the STN within such network remains to be specified.     

Decoding emotional prosody in Parkinson's disease and its potential neuropsychological basis

Parkinson's disease patients may have difficulty decoding prosodic emotion cues. These data suggest that the basal ganglia are involved, but may reflect dorsolateral prefrontal cortex dysfunction. An auditory emotional n-back task and cognitive n-back task were administered to 33 patients and 33 older adult controls, as were an auditory emotional Stroop task and cognitive Stroop task. No deficit was observed on the emotion decoding tasks; this did not alter with increased frontal lobe load. However, on the cognitive tasks, patients performed worse than older adult controls, suggesting that cognitive deficits may be more prominent. The impact of frontal lobe dysfunction on prosodic emotion cue decoding may only become apparent once frontal lobe pathology rises above a threshold.     

Abnormal bone and calcium metabolism in immobilized Parkinson's disease patients.

To elucidate the influence of immobilization-induced hypercalcemia on bone metabolism in Parkinson's disease (PD), we measured serum biochemical indexes and bone mineral density (BMD) in the second metacarpals of 142 elderly PD patients and 99 age-matched healthy controls. Serum concentrations of 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25-[OH](2)D), ionized calcium, intact parathyroid hormone (PTH), and intact bone Gla protein (BGP) were measured. Urinary deoxypyridinoline (D-Pyr) was also measured. Increased serum calcium levels (mean, 1.27 mmol/L) were observed in PD patients, and the levels correlated negatively with the Unified Parkinson's Disease Rating Scale III (UPDRS III), indicating the presence of immobilization-induced bone resorption with resultant hypercalcemia. Decreased serum concentrations of 1,25-[OH](2)D (mean, 88.7 pmol/L) and 25-OHD (mean, 29.7 nmol/L) were noted. Serum PTH was decreased (mean, 25.2 ng/L). Serum BGP was decreased while urinary D-Pyr concentration elevated. A negative correlation was observed between 1,25-[OH](2)D levels and serum calcium or UPDRS III (P < 0.0001). In disabled PD patients, immobilization-induced hypercalcemia may inhibit secretion of PTH, which in turn suppresses 1,25-[OH](2)D production. 25-OHD insufficiency may also contribute to decreased 1,25-[OH](2)D. These abnormalities may be corrected by the suppression of bone resorption with bisphoshonate, and supplementations of calcium and vitamin D should be avoided in these patients.     

Specific impairments in the recognition of emotional facial expressions in Parkinson's disease

Studies investigating the ability to recognize emotional facial expressions in non-demented individuals with Parkinson's disease (PD) have yielded equivocal findings. A possible reason for this variability may lie in the confounding of emotion recognition with cognitive task requirements, a confound arising from the lack of a control condition using non-emotional stimuli. The present study examined emotional facial expression recognition abilities in 20 non-demented patients with PD and 23 control participants relative to their performance on a non-emotional landscape categorization test with comparable task requirements. We found that PD participants were normal on the control task but exhibited selective impairments in the recognition of facial emotion, specifically for anger (driven by those with right hemisphere pathology) and surprise (driven by those with left hemisphere pathology), even when controlling for depression level. Male but not female PD participants further displayed specific deficits in the recognition of fearful expressions. We suggest that the neural substrates that may subserve these impairments include the ventral striatum, amygdala, and prefrontal cortices. Finally, we observed that in PD participants, deficiencies in facial emotion recognition correlated with higher levels of interpersonal distress, which calls attention to the significant psychosocial impact that facial emotion recognition impairments may have on individuals with PD.