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.     

Dissociation between numerosity and duration processing in aging and early Parkinson's disease

Numerosity and duration processing have been shown to be underlain by a single representational mechanism, namely an accumulator, and to rely on a common cerebral network located principally in areas around the right intraparietal sulcus. However, recent neuropsychological findings reveal a dissociation between numerosity and duration processing, which suggests the existence of partially distinct mechanisms. In this study, we tested the idea of partially common and distinct mechanisms by investigating, for the first time, both numerical and temporal processing abilities in non-demented Parkinson's disease (PD) patients known to suffer from duration impairment and in healthy elderly adults known to have impaired performance in duration tasks. The aim was to assess whether this impaired duration processing would extend to numerosity processing. The participants had to compare either the numerosity of flashed dot sequences or the duration of single dot displays. The results demonstrate an effect of aging on duration comparison, healthy elderly participants making significantly more errors than healthy young participants. Importantly, the performance of PD patients on the duration task was worse than that of the healthy young and elderly groups, whereas no difference was found for numerosity comparison. This dissociation supports the idea that partly independent systems underlie the processing of numerosity and duration.     

Researching a differential impairment of frontal functions and explicit memory in early Parkinson's disease.

An impairment at tasks sensitive to frontal lobe damage has been repeatedly reported in Parkinson's disease, but the exact nature of these deficits has not yet been clarified. Similarly, deficits of visuo-spatial functions have been frequently observed, but it is still debated whether verbal and visuo-spatial memory can be differentially affected. In this study we have compared the performance of 20 mild Parkinson's disease patients (I-II Hoehn and Yahr stage) and 18 matched normal controls, at tasks assessing frontal functions and explicit memory. We detected a selective deficit in set shifting and maintaining, without impairment in categorization and set formation. The lack of a selective increase in perseverative errors might indicate that perseverations either measure something different from set shifting or that they do not represent an index sensitive enough to set shifting impairment. Parkinson's disease patients were also significantly impaired at Raven's Progressive Matrices, a task assessing both frontal and visuo-spatial aspects. However, they did not show any differential impairment of visuo-spatial memory. Indeed, despite a trend of lower performance in visuo-spatial learning, memory performance of Parkinson's disease patients was significantly different from that of controls only at a free recall test which involved both verbal and visuo-spatial memory. We suggest the exploration of set shifting and maintaining to detect 'frontal' deficits in mild Parkinson's disease. We argue that Raven's Progressive Matrices is a valuable task for detecting subclinical cognitive deficits in Parkinson's disease, even if it does not show a specific profile of impairment in these patients. According to our results, a differential evaluation of verbal vs. visuo-spatial memory is not necessary in clinical practice, whilst free recall confirms its usefulness to detect subclinical impairments of memory functions.     

A dissociation between real and simulated movements in Parkinson's disease

Subcortical lesions have been simultaneously implicated in both real and simulated movement deficits. However, the analysis of the simulated opposition axis in precision grasping reveals that, in individuals with idiopathic bilateral Parkinson' disease motor imagery is impaired and that execution of overt movements is spared. This constitutes the first lesion observation congruent with the anatomical and functional dichotomy between real and simulated movements seen in experimental studies. These results underline the modality-specific nature of motor imagery and show that subcortical damage differentially impacts on motor activity.     

Emotion processing in Parkinson's disease: a blood oxygenation level-dependent functional magnetic resonance imaging study

Parkinson's disease is a neurodegenerative disorder caused by loss of dopamine neurons in the substantia nigra pars compacta. Tremor, rigidity, and bradykinesia are the major symptoms of the disease. These motor impairments are often accompanied by affective and emotional dysfunctions which have been largely studied over the last decade. The aim of this study was to investigate emotional processing organization in the brain of patients with Parkinson's disease and to explore whether there are differences between recognition of different types of emotions in Parkinson's disease. We examined 18 patients with Parkinson's disease(8 men, 10 women) with no history of neurological or psychiatric comorbidities. All these patients underwent identical brain blood oxygenation level-dependent functional magnetic resonance imaging for emotion evaluation. Blood oxygenation level-dependent functional magnetic resonance imaging results revealed that the occipito-temporal cortices, insula, orbitofrontal cortex, basal ganglia, and parietal cortex which are involved in emotion processing, were activated during the functional control. Additionally, positive emotions activate larger volumes of the same anatomical entities than neutral and negative emotions. Results also revealed that Parkinson's disease associated with emotional disorders are increasingly recognized as disabling as classic motor symptoms. These findings help clinical physicians to recognize the emotional dysfunction of patients with Parkinson's disease.     

Emotion and ocular responses in Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disease that affects motor, cognitive, and emotional functioning. Previous studies reported reduced skin conductance responses in PD patients, compared to healthy older adults when viewing emotionally arousing pictures. Attenuated skin conductance changes in PD may reflect peripheral autonomic dysfunction (e.g., reduced nerve endings at the sweat gland) or, alternatively, a more central emotional deficit. The aim of the current study was to investigate a second measure of sympathetic arousal—change in pupil dilation. Eye movements, a motor-based correlate of emotional processing, were also assessed. Results indicated that pupil dilation was significantly greater when viewing emotional, compared to neutral pictures for both PD patients and controls. On the other hand, PD patients made fewer fixations with shorter scan paths, particularly when viewing pleasant pictures. These results suggest that PD patients show normal sympathetic arousal to affective stimuli (indexed by pupil diameter), but differences in motor correlates of emotion (eye movements).     

Abnormal emotional word ratings in Parkinson's disease

Blunted facial expressions and diminished expressions of emotional prosody associated with Parkinson's disease (PD) could be attributed to motor rigidity/akinesia. Although impaired recognition of emotional faces and prosody in PD suggests emotional dysfunction is not entirely motor-efferent, comprehension might depend upon imitation with motor feedback. Thus, to learn if patients with PD have an emotional conceptual defect, we examined their ratings for the emotional connotations of words on a 1-9 scale for valence and arousal. When compared to control participants the valence (positive-negative) and arousal (excited-calm) ratings of the PD patients were blunted, but their ratings of the control expense words (expensive-cheap) were not. These blunted emotion ratings suggest that patients with PD have a degradation of their emotional conceptual-semantic system.     

Emotion recognition in patients with idiopathic Parkinson's disease.

Emotion recognition (ER) was examined in 64 patients with idiopathic Parkinson's disease (PD; 56 bilateral and 8 right-sided) and 64 matched healthy volunteers. Participants were administered an ER battery, consisting of the following subscores: overall ER (OER), overall facial ER, facial emotion identification (FEI) and discrimination, overall prosodic ER, and prosodic emotion identification (PEI) and discrimination. Measures of visuospatial functions, auditory attention, and depression were also administered. After controlling for visuospatial functions, auditory attention and depression, results indicated that patients with bilateral PD had poorer performance on all ER subscores, regardless of the modality and type of experimental task involved, relative to healthy volunteers. However, patients with right-sided PD had difficulty on FEI and PEI only. Whereas none of the clinical variables examined in this study predicted any of the ER subscores, visual organization and auditory attention positively predicted OER in patients with PD. In addition, visual organization also positively predicted FEI in these patients. Implications are discussed in terms of the neural substrates underlying ER.     

Implicit and explicit memory in Alzheimer's disease and Parkinson's disease

Several tasks examined implicit and explicit memory in demographically matched samples of Alzheimer's (AD) and Parkinson's disease (PD) patients, and healthy elderly subjects. A fragmented pictures test, word stem-completion repetition priming, and a pursuit-rotor tracking task, followed by explicit memory tests, were given. AD patients were impaired on all explicit tests and on word stem-completion priming, but were intact on pursuit-rotor tracking and the skill learning (SL) component of the fragmented pictures test. PD patients were significantly better than AD patients on all explicit memory tests, but were selectively impaired on the SL component of the fragmented pictures test. Finally, a mirror-reading test was given to the PD patients and control subjects, with no significant differences found in performances between the two groups. Results are discussed in terms of hypothetical cognitive processes and brain circuits underlying different implicit and explicit memory domains.     

Implicit and explicit memory in Alzheimer's disease and Parkinson's disease

Abstract

Several tasks examined implicit and explicit memory in demographically matched samples of Alzheimer's (AD) and Parkinson's disease (PD) patients, and healthy elderly subjects. A fragmented pictures test, word stem-completion repetition priming, and a pursuit-rotor tracking task, followed by explicit memory tests, were given. AD patients were impaired on all explicit tests and on word stem-completion priming, but were intact on pursuit-rotor tracking and the skill learning (SL) component of the fragmented pictures test. PD patients were significantly better than AD patients on all explicit memory tests, but were selectively impaired on the SL component of the fragmented pictures test. Finally, a mirror-reading test was given to the PD patients and control subjects, with no significant differences found in performances between the two groups. Results are discussed in terms of hypothetical cognitive processes and brain circuits underlying different implicit and explicit memory domains.     

Emotion processing in Alzheimer's disease

To date, there have been few studies of emotion processing in those suffering from Alzheimer's disease, yet this may have an important effect on the quality of life of both sufferers and their families. This paper describes an investigation of the relative changes in cognition and in recognition and identification of non-verbal communicative signals of emotion in those suffering from Alzheimer's disease, and seeks to address the implications for clinical practice. Twelve adults with a diagnosis of "probable" Alzheimer's disease and 12 matched older adult healthy comparison participants undertook a series of tasks involving face and prosody discrimination. Facial stimuli were presented on cards, and prosodic stimuli on audiotape. Scores were compared with a measure of general cognitive ability. There was a significant difference between the Alzheimer's disease group and healthy older adult group on emotion and cognition tasks respectively. However, the ability to recognize and identify non-verbal affect cues in emotional facial expression and emotional prosody was preserved relative to general cognitive ability in those suffering from Alzheimer's disease. In addition, there were no differences found in the recognition of different emotions (happiness, sadness, anger, fear or neutral). This relative sparing of non-verbal emotional processing skills has implications for provision of assessment and interventions based on the creation of effective forms of communication that are less reliant on cognitive ability.     

Visual inspection time in Parkinson's disease: deficits in early stages of cognitive processing

Inspection time (IT) is a simple information processing paradigm dependent on a participant's ability to identify physical properties of a stimulus presented for a specified time interval. In contrast with reaction time (RT) studies, the dependent variable of interest in IT is not related to the motoric speed with which the individual is able to respond, but rather the minimum presentation time necessary for participants to reliably identify physical properties of the stimulus. It is well documented that individuals with Parkinson's disease (PD) experience significant impairment on tests of simple RT, but it is unclear whether such deficits can be interpreted as 'pure' slowness of information processing, or a delay in the selection and output of a motor response. In the first experiment described here, a sample of 'optimally medicated' PD patients was compared with an age-matched control group, on an IT task. Results of this experiment suggested that individuals with PD required significantly longer stimulus presentation times than healthy participants. The second experiment compared a sample of PD patients (tested both "ON" and "OFF" their typical dopaminergic medications), with an age-matched control group, on the same test of IT. Results again indicated a significant IT deficit in participants with PD, and suggested that these deficits do not significantly resolve with levodopa treatment. Overall, the results of these two experiments suggest that information processing deficits associated with PD are distinct from motor impairment. These findings are further discussed in terms of existing neurochemical models of information processing ability.     

Reaction times and visuospatial processing in Parkinson's disease.

Three motor reaction time tasks which differed in visuospatial complexity but not in motor demands were completed by a group of Parkinson's disease patients and a group of matched control subjects. Response initiation times increased with visuospatial difficulty, whereas movement times remained within a similar range. The two groups differed in response initiation and movement execution times across all reaction time conditions. However, there was no disproportionate increase in response initiation times between an initial nonspatial condition and more complex visuospatial conditions in Parkinson disease patients, and the patients did not make more errors than control subjects. The results do not give support to the hypothesis of a generalised visuospatial deficit in Parkinson's disease.     

Apoptosis in Parkinson's disease: signals for neuronal degradation

Controversy has surrounded a role for apoptosis in the loss of neurons in Parkinson's disease (PD). Although a variety of evidence has supported an apoptotic contribution to PD neuronal loss particularly in the nigra, two factors have weighed against general acceptance: (1) limitations in the use of in situ 3' end labeling techniques to demonstrate nuclear DNA cleavage; and (2) the insistence that a specific set of nuclear morphological features be present before apoptotic death could be declared. We first review the molecular events that underlie apoptotic nuclear degradation and the literature regarding the unreliability of 3' DNA end labeling as a marker of apoptotic nuclear degradation. Recent findings regarding the multiple caspase-dependent or caspase-independent signaling pathways that mediate apoptotic nuclear degradation and determine the morphological features of apoptotic nuclear degradation are presented. The evidence shows that a single nuclear morphology is not sufficient to identify apoptosis and that a cytochrome c, pro-caspase 9, and caspase 3 pathways is operative in PD nigral apoptosis. BAX-dependent increases in mitochondrial membrane permeability are responsible for the release of mitochondrial factors that signal for apoptotic degradation, and increased BAX levels have been found in a subset of PD nigral neurons. Studies using immunocytochemistry in PD postmortem nigra have begun to define the premitochondrial apoptosis signaling pathways in the disease. Two, possibly interdependent, pathways have been uncovered: (1) a p53-glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-BAX pathway; and (2) FAS receptor-FADD-caspase 8-BAX pathway. Based on the above, it seems unlikely that apoptosis does not contribute to PD neuronal loss, and the definition of the premitochondrial signaling pathways may allow for the development and testing of an apoptosis-based PD therapy.     

FP-CIT and MIBG scintigraphy in early Parkinson's disease.

Methods provided by nuclear medicine may be helpful in diagnosis of Parkinson's disease (PD). For that purpose, the sensitivity of iodine-123 metaiodobenzylguanidine ([123I]MIBG) scintigraphy and [123I]FP-CIT single photon emission computed tomography (SPECT) was studied in patients with PD onset (Hoehn and Yahr Stage 1). Cerebral [123I]FP-CIT and cardiac [123I]MIBG scintigraphy were carried out in 18 patients with idiopathic Parkinson's disease, according to Hoehn and Yahr Stage 1. For quantification purposes, we calculated the striatum/posterior lobe binding of FP-CIT and the heart-to-mediastinum (H/M) count ratio regarding MIBG scintigraphy. In 15 of 18 patients, we observed markedly reduced or asymmetric striatal FP-CIT tracer accumulation. FP-CIT binding of the affected striatum was significantly lower as compared with that of the unaffected side. Striatal FP-CIT binding correlated significantly with the motor part of the Unified Parkinson's disease rating scale (UPDRS) but not with age, disease duration, or gender. MIBG scintigraphy delivered significant pathological results in 13 of 18 patients. There was no significant correlation between the H/M ratio relating to MIBG scintigraphy and the motor part of UPDRS, age, disease duration, or gender; however, binding of striatal FP-CIT correlated significantly with cardiac MIBG accumulation. According to the clinical criteria, it might be difficult to prove the diagnosis of PD in patients with slight symptoms and in these cases, FP-CIT SPECT and MIBG scintigraphy may contribute to the early diagnosis of PD. In addition, the functional loss of nigrostriatal and cardiac sympathetic neurons seems to be coupled closely.     

Distractibility in early Parkinson's disease

Post-mortem evidence has shown a depletion of dopamine in the mesocortical and mesolimbic pathways in brains of Parkinson patients. Since these dopaminergic pathways have been implicated in the control of attention in animals, selective attention to visual stimuli was studied in eight patients with early Parkinson's disease (Stage I or II as defined by the Hoehn and Yahr Scale) and eight normal controls of comparable age, sex and Full Scale Intelligence Quotient. Subjects with dementia, psychiatric disease and other neurological abnormalities were excluded. The Parkinson patients were more prone to interference in the presence of distractor items than the normal controls as shown on the focussing + distraction and switching + distraction of attention paradigms on the Distractor task. There findings are not accounted for by mood, intellectual status or memory and thus may be as a result of the loss of dopamine in the mesocortico-limbic projections.     

Tremors in early Parkinson's disease

We examined 50 untreated parkinsonian patients with a complaint of tremor for the presence of a resting, postural, or kinetic tremor. Tremors were recorded by an accelerometer to determine amplitude and frequency. A postural tremor was present in 92% and a resting tremor in 76%. The amplitude of postural tremor was greater than resting tremor in 50%, the same in 25%, and less in 25%. The average tremor frequency of resting and postural tremor was not significantly different. Carbidopa/levodopa reduced testing tremor in 58% and postural tremor in 46% of patients. The dopamine agonist naxoglide (PHNO) reduced resting tremor in 77% and postural tremor in 70% of patients. Postural tremor was not worsened by either drug. It is concluded that tremors in both the resting and postural positions are an integral part of the symptoms of Parkinson's disease and that both tremors have a similar frequency and pharmacological responsiveness in the early phases of the disease.     

Reward processing abnormalities in Parkinson's disease

The primary motor cortex is important for motor learning and response selection, functions that require information on the expected and actual outcomes of behavior. Therefore, it should receive signals related to reward. Pathways from reward centers to motor cortex exist in primates. Previously, we showed that gamma aminobutyric acid–A–mediated inhibition in the motor cortex, measured by paired transcranial magnetic stimulation, changes with expectation and uncertainty of money rewards generated by a slot machine simulation. We examined the role of dopamine in this phenomenon by testing 13 mildly affected patients with Parkinson's disease, off and on dopaminergic medications, and 13 healthy, age‐matched controls. Consistent with a dopaminergic mechanism, reward expectation or predictability modulated the response to paired transcranial magnetic stimulation in controls, but not in unmedicated patients. A single dose of pramipexole restored this effect of reward, mainly by increasing the paired transcranial magnetic stimulation response amplitude during low expectation. Levodopa produced no such effect. Both pramipexole and levodopa increased risk‐taking behavior on the Iowa Gambling Task. However, pramipexole increased risk‐taking behavior more in patients showing lower paired transcranial magnetic stimulation response amplitude during low expectation. These results provide evidence that modulation of motor cortex inhibition by reward is mediated by dopamine signaling and that the physiological state of the motor cortex changes with risk‐taking tendency in patients on pramipexole. The cortical response to reward expectation may represent an endophenotype for risk‐taking behavior in patients on agonist treatment. © 2011 Movement Disorder Society     

Double dissociation between familiarity and recollection in Parkinson's disease as a function of encoding tasks

Parkinson's disease (PD) is associated with episodic memory deficits, but their exact nature is unclear. Some dual-process studies have suggested that recollection is impaired and familiarity is spared in PD, yet others have found the opposite. Our goal was to investigate these memory processes in PD and determine whether the inconsistency among existing findings is related to differences in encoding conditions. We used a process-dissociation procedure with word pairs to estimate familiarity and recollection. In Experiment 1, we used a directed, deep, relational encoding condition (i.e., sentence generation), and in Experiment 2, we contrasted this encoding condition with a shallower, non-directed encoding condition (i.e., read condition). We found a double dissociation as a function of the encoding task: In the sentence generation encoding condition, recollection was impaired in the PD patients, but familiarity was spared. In contrast, in the read encoding condition, there was no group difference in recollection, but familiarity was impaired in the PD group. Within-subject comparisons revealed that both control and PD participants benefitted from the provision of a directed, deep relational encoding strategy. However, this benefit was manifested as an increase in recollection in the controls, but an increase in familiarity in the PD patients. These findings help to reconcile the extant literature and suggest that episodic memory deficits in PD are two-fold, involving: (1) difficulties instantiating encoding strategies independently, leading to deficits in familiarity, and (2) impaired recollection when encoding strategies are equated across groups. Our results highlight the importance of controlling encoding conditions between groups and of taking account of other variables that may influence the participants’ performance, such as deficits associated with normal aging, which may mask deficits in neurodegenerative diseases in particular situations. More generally, our study raises the possibility that deficits in recollection or familiarity in patient populations are not immutably linked to the structure that is affected, as is typically assumed, but that such deficits may interact with type of encoding, and possibly with the nature of the retrieval process.