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.     

Functional connectivity abnormalities during contextual processing in schizophrenia and in Parkinson’s disease

Functional connectivity was evaluated in patients with schizophrenia (SC) and in patients with Parkinson’s disease (PD) during the performance of a local contextual processing paradigm, to investigate the proposition that functional disconnection is involved with contextual processing deficits in these populations. To this end, we utilized event-related EEG signals, synchronization likelihood and graph theoretical analysis. Local context was defined as the occurrence of a predictive sequence of stimuli before the presentation of a target event. In the SC patients, we observed a decrease in path length (L) in the beta band, for the predictive sequence and for predicted and random targets, compared with controls. These abnormalities were associated with weaker frontal-temporal-parietal connections. In the PD patients we found longer L (theta band) for predicted targets, and higher cluster coefficients for both the predictive sequence (theta band) and predicted targets (alpha and theta bands), compared with controls. Detection of predicted targets was associated with weaker frontal-parietal connections in PD. No group differences were found for randomized standard stimuli in both SC and PD patients. These findings provide evidence of task-specific functional connectivity abnormalities within frontal networks during local contextual processing.     

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.     

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.     

Parkinson’s disease disrupts both automatic and controlled processing of action verbs

The problem of how word meaning is processed in the brain has been a topic of intense investigation in cognitive neuroscience. While considerable correlational evidence exists for the involvement of sensory-motor systems in conceptual processing, it is still unclear whether they play a causal role. We investigated this issue by comparing the performance of patients with Parkinson’s disease (PD) with that of age-matched controls when processing action and abstract verbs. To examine the effects of task demands, we used tasks in which semantic demands were either implicit (lexical decision and priming) or explicit (semantic similarity judgment). In both tasks, PD patients’ performance was selectively impaired for action verbs (relative to controls), indicating that the motor system plays a more central role in the processing of action verbs than in the processing of abstract verbs. These results argue for a causal role of sensory-motor systems in semantic processing.     

Benefits of physical exercise on executive functions in older people with Parkinson’s disease

The benefits of physical exercise on cognitive functioning have been reported in the literature, but the potential benefits to slow the eventual decline in executive functioning (EF) caused by neurodegeneration from Parkinson’s Disease (PD) have rarely been studied. Thus the objective of this study was to analyze the effects of a multimodal physical exercise program on EF in older people with Parkinson’s disease. The EF of the older people was evaluated by neuropsychological testing, and for confounding variables such as attention, depressive symptoms and anxiety, before and after intervention. The 20 participants were assigned into Control (CG) and Trained (TG) Groups. The TG participated in generalized physical training for 6 months. The ANOVA showed a significant interaction (p < .05) that indicated a beneficial contribution of training on EF. No significant interactions were found in the results for confounding variables between groups and pre- and post-intervention, which supports the beneficial findings of physical exercise training on EF.     

The effects of clinical motor variables and medication dosage on working memory in Parkinson’s disease

In this study, we investigate the interrelationship between clinical variables and working memory (WM) in Parkinson’s disease (PD). Specifically, the aim of the study was to investigate the relationship between disease duration, dopaminergic medication dosage, and motor disability (UPDRS score) with WM in individuals with PD. Accordingly, we recruited three groups of subjects: unmedicated PD patients, medicated PD patients, and healthy controls. All subjects were tested on three WM tasks: short-delay WM, long-delay WM, and the n-back task. Further, PD encompasses a spectrum that can be classified either into akinesia/rigidity or resting tremor as the predominant motor presentation of the disease. In addition to studying medication effects, we tested WM performance in tremor-dominant and akinesia-dominant patients. We further correlated WM performance with disease duration and medication dosage. We found no difference between medicated and unmedicated patients in the short-delay WM task, but medicated patients outperformed unmedicated patients in the long-delay WM and n-back tasks. Interestingly, we also found that akinesia-dominant patients were more impaired than tremor-dominant patients at various WM measures, which is in agreement with prior studies of the relationship between akinesia symptom and basal ganglia dysfunction. Moreover, the results show that disease duration inversely correlates with more demanding WM tasks (long-delay WM and n-back tasks), but medication dosage positively correlates with demanding WM performance. In sum, our results show that WM impairment in PD patients depend on cognitive domain (simple vs. demanding WM task), subtype of PD patients (tremor- vs. akinesia-dominant), as well as disease duration and medication dosage. Our results have implications for the interrelationship between motor and cognitive processes in PD, and for understanding the role of cognitive training in treating motor symptoms in PD.     

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.     

Linguistic correlates of asymmetric motor symptom severity in Parkinson’s Disease

Asymmetric motor severity is common in Parkinson’s Disease (PD) and provides a method for examining the neurobiologic mechanisms underlying cognitive and linguistic deficits associated with the disorder. In the present research, PD participants (N = 31) were assessed in terms of the asymmetry of their motor symptoms. Interviews with the participants were analyzed with the Linguistic Inquiry and Word Count (LIWC) program. Three measures of linguistic complexity – the proportion of verbs, proportion of function words, and sentence length – were found to be affected by symptom asymmetry. Greater left-side motor severity (and hence greater right-hemisphere dysfunction) was associated with the production of significantly fewer verbs, function words, and shorter sentences. Hence, the production of linguistic complexity in a natural language context was associated with relatively greater right hemisphere involvement. The potential neurobiological mechanisms underlying this effect are discussed.     

Co-ordination of bimanual movements in a centrally deafferented patient executing open loop reach-to-grasp movements

Many everyday tasks require that we use our hands co-operatively. For tasks where both hands are required to perform the same action, a common motor program can be used. But, where each hand must perform a different action, some degree of independent control of each hand is required. In this paper we examine the co-ordination of bimanual movement kinematics in a female patient recovering from brain injury involving anterior regions of the parietal lobe of the right hemisphere, which has resulted in a dense hemianaesthesia of her left arm. A particular focus of this paper is the co-ordination of bimanual movements for reaches executed without visual feedback. Specifically we present new data, which quantify the synchronisation of patient D.B.'s hands by comparing their relative time lag at the start and the end of her bimanual reaches. The results are discussed with particular reference to the role played by limb proprioception in the planning and control of prehension movements.     

Decomposition of warning effects in Parkinson's disease

ABSTRACT

Neutral warning signals speed voluntary reactions by reducing temporal uncertainty and by triggering a brief burst of arousal. We attempted to isolate the phasic arousal mechanism in people with Parkinson's disease (PD) using a clock display to minimize temporal uncertainty. In this condition, the speeding of responses in a color-discrimination task by an accessory stimulus was the fully equivalent to the effect in age-matched control subjects. This indicates preserved phasic arousal in PD. Temporal preparation based on warning cues also appeared to be normal. By contrast, in a condition with high temporal uncertainty, the accessory stimulus (an air puff to the foot) impaired accuracy for the patients but not the neurologically normal subjects. The data are consistent with the view that PD disrupts internal but not external control of alertness.     

A computational model of Parkinsonian handwriting that highlights the role of the indirect pathway in the basal ganglia

Parkinsonian handwriting is typically characterized by micrographia, jagged line contour, and unusual fluctuations in pen velocity. In this paper we present a computational model of handwriting generation that highlights the role of the basal ganglia, particularly the indirect pathway. Whereas reduced dopamine levels resulted in reduced letter size, transition of STN–GPe dynamics from desynchronized (normal) to synchronized (PD) condition resulted in increased fluctuations in velocity in the model. We also present handwriting data from PD patients (n = 34) who are at various stages of disease and had taken medication various lengths of time before the handwriting sessions. The patient data are compared with those of age-matched controls. PD handwriting statistically exhibited smaller size and larger velocity fluctuation compared to normal handwriting.     

Language deficits in pre-symptomatic Huntington's disease: evidence from Hungarian

A limited number of studies have investigated language in Huntington’s disease (HD). These have generally reported abnormalities in rule-governed (grammatical) aspects of language, in both syntax and morphology. Several studies of verbal inflectional morphology in English and French have reported evidence of over-active rule processing, such as over-suffixation errors (e.g., walkeded) and over-regularizations (e.g., digged). Here we extend the investigation to noun inflection in Hungarian, a Finno-Ugric agglutinative language with complex morphology, and to genetically proven pre-symptomatic Huntington’s disease (pre-HD). Although individuals with pre-HD have no clinical, motor or cognitive symptoms, the underlying pathology may already have begun, and thus sensitive behavioral measures might reveal already-present impairments. Indeed, in a Hungarian morphology production task, pre-HD patients made both over-suffixation and over-regularization errors. The findings suggest the generality of over-active rule processing in both HD and pre-HD, across languages from different families with different morphological systems, and for both verbal and noun inflection. Because the neuropathology in pre-HD appears to be largely restricted to the caudate nucleus and related structures, the findings further implicate these structures in language, and in rule-processing in particular. Finally, the need for effective treatments in HD, which will likely depend in part on the ability to sensitively measure early changes in the disease, suggests the possibility that inflectional morphology, and perhaps other language measures, may provide useful diagnostic, tracking, and therapeutic tools for assessing and treating early degeneration in pre-HD and HD.     

A neural model of hippocampal–striatal interactions in associative learning and transfer generalization in various neurological and psychiatric patients

Building on our previous neurocomputational models of basal ganglia and hippocampal region function (and their modulation by dopamine and acetylcholine, respectively), we show here how an integration of these models can inform our understanding of the interaction between the basal ganglia and hippocampal region in associative learning and transfer generalization across various patient populations. As a common test bed for exploring interactions between these brain regions and neuromodulators, we focus on the acquired equivalence task, an associative learning paradigm in which stimuli that have been associated with the same outcome acquire a functional similarity such that subsequent generalization between these stimuli increases. This task has been used to test cognitive dysfunction in various patient populations with damages to the hippocampal region and basal ganglia, including studies of patients with Parkinson’s disease (PD), schizophrenia, basal forebrain amnesia, and hippocampal atrophy. Simulation results show that damage to the hippocampal region—as in patients with hippocampal atrophy (HA), hypoxia, mild Alzheimer’s (AD), or schizophrenia—leads to intact associative learning but impaired transfer generalization performance. Moreover, the model demonstrates how PD and anterior communicating artery (ACoA) aneurysm—two very different brain disorders that affect different neural mechanisms—can have similar effects on acquired equivalence performance. In particular, the model shows that simulating a loss of dopamine function in the basal ganglia module (as in PD) leads to slow acquisition learning but intact transfer generalization. Similarly, the model shows that simulating the loss of acetylcholine in the hippocampal region (as in ACoA aneurysm) also results in slower acquisition learning. We argue from this that changes in associative learning of stimulus–action pathways (in the basal ganglia) or changes in the learning of stimulus representations (in the hippocampal region) can have similar functional effects.     

Hallucinations and REM sleep behaviour disorder in Parkinson's disease: dream imagery intrusions and other hypotheses

REM sleep behaviour disorder (RBD) is a REM sleep-related parasomnia which may be considered a “dissociated state of wakefulness and sleep”, given that conflicting elements of REM sleep (dreaming) and of wakefulness (sustained muscle tone and movements) coexist during the episodes, leading to motor and behavioural manifestations reminiscent of an enacted dream. RBD has been reported in association with α-synucleinopathies: around a third of patients with Parkinson’s disease (PD) have full-blown RBD.Recent data indicate that PD patients with RBD are more prone to hallucinations than PD patients without this parasomnia. However it is still not clear why RBD in PD is associated with an increased prevalence of VHs.Data exist which suggest that visual hallucinations in PD may be the result of untimely intrusions of REM visual imagery into wakefulness. RBD, which is characterised by a REM sleep dissociation pattern, might be a condition that particularly favours such intrusions. However, other hypotheses may be advanced. In fact, deficits in attentional, executive, visuoperceptual and visuospatial abilities have been documented in RBD and found to occur far more frequently in PD with RBD than in PD without RBD. Neuropsychological deficits involving visual perception and attentional processes are thought to play an important role in the pathophysiology of VHs. On this basis, RBD in PD could be viewed as a contributory risk factor for VHs.     

Impaired finger dexterity in Parkinson's disease is associated with praxis function

A controversial concept suggests that impaired finger dexterity in Parkinson’s disease may be related to limb kinetic apraxia that is not explained by elemental motor deficits such as bradykinesia. To explore the nature of dexterous difficulties, the aim of the present study was to assess the relationship of finger dexterity with ideomotor praxis function and parkinsonian symptoms. Twenty-five patients with Parkinson’s disease participated in the study. Their left and right arms were tested independently. Testing was done in an OFF and ON state as defined by a modified version of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Finger dexterity was assessed by a coin rotation (CR) task and ideomotor praxis using a novel test of upper limb apraxia (TULIA), in which the patients were requested to imitate and pantomime 48 meaningless, as well as communicative and tool-related gestures. Coin rotation significantly correlated with TULIA irrespective of the motor state and arm involved, but not with the MDS-UPDRS. This association was significantly influenced by Hoehn and Yahr stage.The strong association of finger dexterity with praxis function but not the parkinsonian symptoms indicates that impaired finger dexterity in Parkinson’s disease may be indeed apraxic in nature, yet, predominantly in advanced stages of the disease when cortical pathology is expected to develop. The findings are discussed within a cognitive-motor model of praxis function.     

Functional and connectivity changes during working memory in Huntington’s disease: 18 month longitudinal data from the IMAGE-HD study

Background

This study aimed to characterize, for the first time, 18 month longitudinal changes in both functional activation and functional connectivity during working memory in premanifest Huntington’s disease (pre-HD) and symptomatic HD (symp-HD).

Methods

Functional magnetic resonance imaging (fMRI) was used to investigate longitudinal changes in neuronal activity during working memory performance via an N-BACK task (0-BACK and 1-BACK) in 27 pre-HD, 17 symp-HD, and 23 control participants. Whole-brain analysis of activation and region-of-interest analysis of functional connectivity was applied to longitudinal fMRI data collected at baseline and 18 months follow-up.

Results

Compared with controls, the pre-HD group showed significantly increased activation longitudinally during 1-BACK versus 0-BACK in the lateral and medial prefrontal, anterior cingulate, primary motor, and temporal areas cortically, and caudate and putamen subcortically. Pre-HD far from onset, compared with controls, showed further longitudinal increases in the right and left dorsolateral prefrontal cortex (DLPFC). Longitudinal increased activation in anterior cingulate and medial primary motor areas were associated with disease burden in the pre-HD group. Moreover, in pre-HD increased activation over time in primary motor and putamen regions were associated with average response time during 1-BACK performance. During 1-BACK, functional connectivity between the right DLPFC and posterior parietal, anterior cingulate, and caudate was significantly reduced over 18 months only in the pre-HD group.

Conclusions

Longitudinal reductions in connectivity over 18 months may represent an early signature of cortico-cortical and cortico-striatal functional disconnectivity in pre-HD, whereas the concomitant increased cortical and subcortical activation may reflect a compensatory response to the demands for cognitive resources required during task performance. Our findings demonstrate that functional imaging modalities have the potential to serve as sensitive methods for the assessment of cortical and subcortical responses to future treatment measures.     

Assessment of postural control in patients with Parkinson’s disease: Sway ratio analysis

Analysis of the postural stability impairments in neurodegenerative diseases is a very demanding task. Age-related declines in posturographic indices are usually superimposed on effects associated with the pathology and its treatment. We present the results of a novel postural sway ratio (SR) analysis in patients with Parkinson’s disease (PD) and age-matched healthy subjects. The sway ratios have been assessed based upon center of foot-pressure (CP) signals recorded in 55 parkinsonians (Hoehn and Yahr: 1-3) and 55 age-matched healthy volunteers while standing quiet with eyes open (EO) and then with eyes closed (EC). Complementing classical sway measure abnormalities, the SR exhibited a high discriminative power for all controlled factors: pathology, vision, and direction of sway. Both the anteroposterior (AP) and mediolateral (ML) sway ratios were significantly increased in PD patients when compared to the control group. An additional SR increase was observed in the response to eyes closure. The sway ratio changes documented here can be attributed to a progressive decline of a postural stability control due to pathology. In fact, a significant correlation between the mediolateral SR under EO conditions and Motor Exam (section III) score of the UPDRS was found. The mediolateral sway ratios computed for EO and EC conditions significantly correlated with the CP path length (r = .87) and the mean anteroposterior CP position within the base of support (r = .38). Both indices reflect postural stability decline and fall tendency # in parkinsonians. The tremor-type PD patients (N = 34) showed more pronounced relationships between the mediolateral SR and selected items from the UPDRS scale, including: falls (Kendall Tau = .47, p < .05), rigidity (.45, p < .05), postural stability (retropulsion) (.52), and the Motor Exam score (.73). The anteroposterior SR correlated only with tremor (Kendal Tau = .77, p < .05). It seems that in force plate posturography the SR can be recommended as a single reliable measure that allows for a better quantitative assessment of postural stability impairments.