Appetitive motivational deficits in individuals with Parkinson's Disease

Parkinson's disease is known for its effects on sensorimotor coordination caused by degeneration of the nigrostriatal dopamine pathway. Dopamine‐innervated areas of the ventral striatum also become compromised in Parkinson's disease, and little is known about the potential impact of this pathology on motivational processes mediated by the mesolimbic dopamine system. The current study tested the hypothesis that patients with Parkinson's disease would show a deficit in appetitive motivational arousal. Patients with Parkinson's disease and age‐matched healthy controls completed a visual discrimination task in which control and appetitive food images (incidental to the task) were presented in the background. Response rate changes indicated appetitive motivational arousal. The healthy controls showed an increase in response rate on the task when appetitive food cues were present compared with control stimuli. In contrast, the Parkinson's disease group showed an inverse pattern to the healthy controls. The reduction in appetitive motivation correlated with an individual's Parkinsonian symptomology. Patients with Parkinson's disease demonstrated an impairment in appetitive motivational arousal consistent with the progression of dopaminergic degeneration across the course of the disease. Dysfunction of this system affects quality of life in Parkinson's disease, and a blunting of the anticipatory motivation may contribute to the high prevalence of depression in Parkinson's disease. © 2011 Movement Disorder Society     

The effect of speed-accuracy strategy on response interference control in Parkinson's disease

Studies that used conflict paradigms such as the Eriksen Flanker task show that many individuals with Parkinson's disease (PD) have pronounced difficulty resolving the conflict that arises from the simultaneous activation of mutually exclusive responses. This finding fits well with contemporary views that postulate a key role for the basal ganglia in action selection. The present experiment aims to specify the cognitive processes that underlie action selection deficits among PD patients in the context of variations in speed-accuracy strategy. PD patients (n = 28) and healthy controls (n = 17) performed an arrow version of the flanker task under task instructions that either emphasized speed or accuracy of responses. Reaction time (RT) and accuracy rates decreased with speed compared to accuracy instructions, although to a lesser extent for the PD group. Differences in flanker interference effects among PD and healthy controls depended on speed-accuracy strategy. Compared to the healthy controls, PD patients showed larger flanker interference effects under speed stress. RT distribution analyses suggested that PD patients have greater difficulty suppressing incorrect response activation when pressing for speed. These initial findings point to an important interaction between strategic and computational aspects of interference control in accounting for cognitive impairments of PD. The results are also compatible with recent brain imaging studies that demonstrate basal ganglia activity to co-vary with speed-accuracy adjustments.     

Pathological Gambling in Parkinson's disease: Autonomic measures supporting impaired decision‐making

According to the somatic marker hypothesis, autonomic measures and arousal modulation can reveal a difference in subgroups of patients developing impaired decision‐making because of addictions. Previously, pathological gambling (PG) and Parkinson's disease (PD) have been associated with differential arousal levels during gambling behavior. However, no research considered the specific autonomic responses of Parkinson's disease patients with pathological gambling and with a previous history of gambling. Thus, this study investigated skin conductance responses (SCRs), skin conductance level (SCL) and heart rate (HR) during the Iowa Gambling Task (IGT) in two groups of PD patients with gambling disorder, active (PD Gamblers; n = 14) or remitted (PD Non‐Gamblers; n = 13) and a control group of patients with Parkinson's disease only (n = 13). Anticipatory autonomic responses to disadvantageous decks and advantageous decks during the Iowa Gambling Task were measured for each participant. The PD Gamblers group performed worse than the PD Non‐Gamblers and the control groups at the IGT task and exhibited lower SCRs, SCL, and HR during the decision‐making processing of cards belonging to disadvantageous decks. The role of autonomic and behavioral measures was considered.     

Psychometric properties of the apathy evaluation scale in patients with Parkinson's disease

Parkinson's disease (PD) frequently entails non‐motor symptoms, worsening the course of the disease. Apathy is one of the core neuropsychiatric symptoms that has been investigated in recent years; research is however hampered by the limited availability of well‐evaluated apathy scales for these patients. We evaluated the psychometric properties of the Apathy Evaluation Scale (AES) in a sample of PD patients. Psychometric properties, convergent and discriminant validity and sensitivity/specificity were evaluated in patients with (n = 582) or without dementia/depression (n = 339). Internal consistency was high in the entire sample as well as in patients without dementia/depression. Correlations were moderate for convergent validity (UPDRS I item 4: motivation). While apathy could be differentiated from cognitive decline, it was related to depression (Geriatric Depression Scale, GDS‐15). The overall classification accuracy based on the UPDRS I item 4 was comparable for AES and GDS scores. The AES exhibits good psychometric properties in PD patients with and without dementia and/or depression. Commonly used screenings on the presence of apathy had low detection rates compared to the AES and reflected both apathetic and depressive symptoms. Psychometric evaluation of available instruments will support further research on the clinical relevance of apathy for disease progression and treatment approaches in PD patients.     

Are the EEG microstates correlated with motor and non-motor parameters in patients with Parkinson's disease?

ObjectivesThis study compared electroencephalography microstates (EEG-MS) of patients with Parkinson's disease (PD) to healthy controls and correlated EEG-MS with motor and non-motor aspects of PD.MethodsThis cross-sectional exploratory study was conducted with patients with PD (n = 10) and healthy controls (n = 10) matched by sex and age. We recorded EEG-MS using 32 channels during eyes‐closed and eyes‐open conditions and analyzed the four classic EEG-MS maps (A, B, C, D). Clinical information (e.g., disease duration, medications, levodopa equivalent daily dose), motor (Movement Disorder Society - Unified Parkinson Disease Rating Scale II and III, Timed Up and Go simple and dual-task, and Mini-Balance Evaluation Systems Test) and non-motor aspects (Mini-Mental State Exam [MMSE], verbal fluency, Hospital Anxiety and Depression Scale, and Parkinson's Disease Questionnaire-39 [PDQ-39]) were assessed in the PD group. Mann-Whitney U test was used to compare groups, and Spearman's correlation coefficient to analyze the correlations between coverage of EEG-MS and clinical aspects of PD.ResultsThe PD group showed a shorter duration of EEG-MS C in the eyes-closed condition than the control group. We observed correlations (rho = 0.64 to 0.82) between EEG-MS B, C, and D and non-motor aspects of PD (MMSE, verbal fluency, PDQ-39, and levodopa equivalent daily dose).ConclusionAlterations in EEG-MS and correlations between topographies and cognitive aspects, quality of life, and medication dose indicate that EEG could be used as a PD biomarker. Future studies should investigate these associations using a longitudinal design.     

Pavlovian‐to‐instrumental transfer in Anorexia Nervosa: A pilot study on conditioned learning and instrumental responding to low‐ and high‐calorie food stimuli

Anorexia Nervosa is characterized by persistent restraint eating despite severe negative consequences and often a chronic course of the disease. Recent theoretical models suggest that abnormalities in reward processing and incentive salience of disorder‐compatible stimuli as observed in addictive behaviours contribute to the development and maintenance of Anorexia Nervosa. The aim of the present study was to investigate the process of the acquisition of food‐related conditioned responses and the influence of conditioned low‐calorie and high‐calorie food stimuli on instrumental responding for different foods. A Pavlovian‐to‐instrumental transfer paradigm and questionnaires on eating disorder psychopathology (EDE‐Q, EDI‐2) were administered to patients with Anorexia Nervosa (n = 39) and healthy controls (n = 41). Results indicated that patients with Anorexia Nervosa showed deficits of the acquisition of knowledge of the experimental contingencies. Nevertheless, in patients with Anorexia Nervosa and healthy controls instrumental responding for low‐ and high‐calorie food rewards was affected by stimuli conditioned to these rewards; no group differences were observed. Importantly, in Anorexia Nervosa, instrumental responding for low‐calorie food increased with increasing severity of eating disorder psychopathology suggesting weight‐loss directed behaviour. Future studies are warranted to enhance our understanding of deficits of reward‐associated learning and to replicate and extend findings with regard to the impact of conditioned stimuli on instrumental responding. At present, our findings suggest that cognitive treatment interventions might be warranted that challenge dysfunctional beliefs about weight loss.     

Severity of mild cognitive impairment in early Parkinson's disease contributes to poorer quality of life

BackgroundPoor quality of life (QoL) is a feature of people with Parkinson's disease (PD) who develop dementia. The relationship between mild cognitive impairment in PD (PD-MCI) and QoL is less clear. To address this, we studied the impact of varying severities of cognitive impairment on QoL in a cohort of non-demented patients with early PD.MethodPatients with newly diagnosed PD (n = 219) and age and sex matched healthy controls (n = 99) completed a schedule of neuropsychological tests, in addition to scales assessing QoL (PDQ-39), depression, sleep, neuropsychiatric symptoms and a clinical examination. The Movement Disorder Society criteria were used to define and classify PD-MCI.ResultsParticipants with PD-MCI were significantly older than those with normal cognition, had more severe motor symptoms, scored higher for depression and had poorer quality of life. Logistic regression showed that mild cognitive impairment, independent of other factors, was an indicator of poorer QoL. Using cognitive performance 2.0 standard deviations (SD) below normative data as a cut-off to define PD-MCI, there was a significant difference in QoL scores between patients with PD-MCI and those classified as having normal cognition. Subjects with less severe mild cognitive impairment did not exhibit significant differences in QoL.ConclusionsPD-MCI is a significant, independent factor contributing to poorer QoL in patients with newly diagnosed PD. Those classified with greatest impairment (2.0 SD below normal values) have lower QoL. This has implications for clinical practice and future interventions targeting cognitive impairments.     

Reduced neural connectivity but increased task‐related activity during working memory in de novo Parkinson patients

Objective: Patients with Parkinson's disease (PD) often suffer from impairments in executive functions, such as working memory deficits. It is widely held that dopamine depletion in the striatum contributes to these impairments through decreased activity and connectivity between task‐related brain networks. We investigated this hypothesis by studying task‐related network activity and connectivity within a sample of de novo patients with PD, versus healthy controls, during a visuospatial working memory task. Methods: Sixteen de novo PD patients and 35 matched healthy controls performed a visuospatial n‐back task while we measured their behavioral performance and neural activity using functional magnetic resonance imaging. We constructed regions‐of‐interest in the bilateral inferior parietal cortex (IPC), bilateral dorsolateral prefrontal cortex (DLPFC), and bilateral caudate nucleus to investigate group differences in task‐related activity. We studied network connectivity by assessing the functional connectivity of the bilateral DLPFC and by assessing effective connectivity within the frontoparietal and the frontostriatal networks. Results: PD patients, compared with controls, showed trend‐significantly decreased task accuracy, significantly increased task‐related activity in the left DLPFC and a trend‐significant increase in activity of the right DLPFC, left caudate nucleus, and left IPC. Furthermore, we found reduced functional connectivity of the DLPFC with other task‐related regions, such as the inferior and superior frontal gyri, in the PD group, and group differences in effective connectivity within the frontoparietal network. Interpretation: These findings suggest that the increase in working memory‐related brain activity in PD patients is compensatory to maintain behavioral performance in the presence of network deficits. Hum Brain Mapp 36:1554–1566, 2015. © 2015 Wiley Periodicals, Inc.     

How attentional boost interacts with reward: the effect of dopaminergic medications in Parkinson's disease

There is widespread evidence that dopamine is implicated in the regulation of reward and salience. However, it is less known how these processes interact with attention and recognition memory. To explore this question, we used the attentional boost test in patients with Parkinson's disease (PD) before and after the administration of dopaminergic medications. Participants performed a visual letter detection task (remembering rewarded target letters and ignoring distractor letters) while also viewing a series of photos of natural and urban scenes in the background of the letters. The aim of the game was to retrieve the target letter after each trial and to win as much virtual money as possible. The recognition of background scenes was not rewarded. We enrolled 26 drug‐naïve, newly diagnosed patients with PD and 25 healthy controls who were evaluated at baseline and follow‐up. Patients with PD received dopamine agonists (pramipexole, ropinirole, rotigotine) during the 12‐week follow‐up period. At baseline, we found intact attentional boost in patients with PD: they were able to recognize target‐associated scenes similarly to controls. At follow‐up, patients with PD outperformed controls for both target‐ and distractor‐associated scenes, but not when scenes were presented without letters. The alerting, orienting and executive components of attention were intact in PD. Enhanced attentional boost was replicated in a smaller group of patients with PD (n = 15) receiving l ‐3,4‐dihydroxyphenylalanine (L‐DOPA). These results suggest that dopaminergic medications facilitate attentional boost for background information regardless of whether the central task (letter detection) is rewarded or not.     

Limbic grey matter changes in early Parkinson's disease

The purpose of this study was to investigate local and network‐related changes of limbic grey matter in early Parkinson's disease (PD) and their inter‐relation with non‐motor symptom severity. We applied voxel‐based morphometric methods in 538 T1 MRI images retrieved from the Parkinson's Progression Markers Initiative website. Grey matter densities and cross‐sectional estimates of age‐related grey matter change were compared between subjects with early PD (n = 366) and age‐matched healthy controls (n = 172) within a regression model, and associations of grey matter density with symptoms were investigated. Structural brain networks were obtained using covariance analysis seeded in regions showing grey matter abnormalities in PD subject group. Patients displayed focally reduced grey matter density in the right amygdala, which was present from the earliest stages of the disease without further advance in mild‐moderate disease stages. Right amygdala grey matter density showed negative correlation with autonomic dysfunction and positive with cognitive performance in patients, but no significant interrelations were found with anxiety scores. Patients with PD also demonstrated right amygdala structural disconnection with less structural connectivity of the right amygdala with the cerebellum and thalamus but increased covariance with bilateral temporal cortices compared with controls. Age‐related grey matter change was also increased in PD preferentially in the limbic system. In conclusion, detailed brain morphometry in a large group of early PD highlights predominant limbic grey matter deficits with stronger age associations compared with controls and associated altered structural connectivity pattern. This provides in vivo evidence for early limbic grey matter pathology and structural network changes that may reflect extranigral disease spread in PD. Hum Brain Mapp 38:3566–3578, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

Longitudinal brain atrophy distribution in advanced Parkinson's disease: What makes the difference in “cognitive status” converters?

We investigated the brain atrophy distribution pattern and rate of regional atrophy change in Parkinson's disease (PD) in association with the cognitive status to identify the morphological characteristics of conversion to mild cognitive impairment (MCI) and dementia (PDD). T1‐weighted longitudinal 3T MRI data (up to four follow‐up assessments) from neuropsychologically well‐characterized advanced PD patients (n = 172, 8.9 years disease duration) and healthy elderly controls (n = 85) enrolled in the LANDSCAPE study were longitudinally analyzed using a linear mixed effect model and atlas‐based volumetry and cortical thickness measures. At baseline, PD patients presented with cerebral atrophy and cortical thinning including striatum, temporoparietal regions, and primary/premotor cortex. The atrophy was already observed in “cognitively normal” PD patients (PD‐N) and was considerably more pronounced in cognitively impaired PD patients. Linear mixed effect modeling revealed almost similar rates of atrophy change in PD and controls. The group comparison at baseline between those PD‐N whose cognitive performance remained stable (n = 42) and those PD‐N patients who converted to MCI/PDD (“converter” cPD‐N, n = 26) indicated suggested cortical thinning in the anterior cingulate cortex in cPD‐N patients which was correlated with cognitive performance. Our results suggest that cortical brain atrophy has been already expanded in advanced PD patients without overt cognitive deficits while atrophy progression in late disease did not differ from “normal” aging regardless of the cognitive status. It appears that cortical atrophy begins early and progresses already in the initial disease stages emphasizing the need for therapeutic interventions already at disease onset.     

Decision making in de novo Parkinson's disease

The aim is to study decision making in patients with de novo Parkinson's disease (PD). Recent studies reported that medicated patients with PD have poor performances compared with age‐matched healthy controls in decision making tasks, specially in the Iowa Gambling Task. Two principal causal hypotheses have been proposed to explain this phenomenon: the overdosing effects of dopaminergic therapy on the orbital frontostriatal circuit that is involved in reward processing, or an amygdala dysfunction, as suggested by similar Skin Conductance Responses of patients with PD and amygdala‐damaged patients while performing this task. The assessment of decision making with the Iowa Gambling Task was conducted in 30 nondemented and nondepressed patients with de novo PD and in 25 age‐matched healthy controls. No statistically significant difference emerged between performances of de novo PD patients and performances of healthy controls. De novo PD patients have performances in the Iowa Gambling Task similar to those of age‐matched healthy controls, suggesting that difficulties in decision making emerge, at least in de novo PD patients, by dopaminergic overstimulation of the orbital frontostriatal circuits. © 2010 Movement Disorder Society     

Apathy dimensions in Parkinson's disease

Objective

Apathy is a prominent and disabling symptom in Parkinson's disease (PD) and is a multidimensional behaviour, but which dimensions are specifically affected is unclear. Therefore, the aim of this preliminary study was to determine the psychometric properties of the Dimensional Apathy Scale (DAS) and explore the multidimensional profile of apathy in PD patients.

Methods

Thirty‐four PD patients, with 30 of their informants/carers, and 34 healthy controls, with 30 of their informants, completed the DAS, Apathy Evaluation Scale and the Geriatric Depression Scale Short Form. Motor staging and independent living status were recorded.

Results

Comparative group analyses revealed that PD patients were significantly more apathetic on self‐rated executive (p = 0.01) and initiation (p = 0.03) dimensions than controls, where only executive apathy was significantly higher in ratings of patients' informants/carers compared with controls' informants (p = 0.02). A third of patients were impaired on at least one apathy dimension. Additionally, patients with apathy tended to have more impaired activities of daily living, while none of the apathy dimensions related to motor disability.

Conclusion

Our findings show the DAS is a valid and reliable multidimensional apathy tool for use in PD. PD is characterised by an executive apathy profile as determined by informants/carers, although patients described both executive and initiation apathy. This indicates a lack of motivation for planning, organisation and attention and lack of initiation of thoughts or behaviours. Further research is needed to determine the cognitive underpinnings of this emerging apathy profile and the clinical impact in PD. Copyright © 2017 John Wiley & Sons, Ltd.     

Ventral striatal network connectivity reflects reward learning and behavior in patients with Parkinson's disease

A subgroup of Parkinson's disease (PD) patients treated with dopaminergic therapy develop compulsive reward‐driven behaviors, which can result in life‐altering morbidity. The mesocorticolimbic dopamine network guides reward‐motivated behavior; however, its role in this treatment‐related behavioral phenotype is incompletely understood. Here, mesocorticolimbic network function in PD patients who develop impulsive and compulsive behaviors (ICB) in response to dopamine agonists was assessed using BOLD fMRI. The tested hypothesis was that network connectivity between the ventral striatum and the limbic cortex is elevated in patients with ICB and that reward‐learning proficiency reflects the extent of mesocorticolimbic network connectivity. To evaluate this hypothesis, 3.0T BOLD‐fMRI was applied to measure baseline functional connectivity on and off dopamine agonist therapy in age and sex‐matched PD patients with (n = 19) or without (n = 18) ICB. An incentive‐based task was administered to a subset of patients (n = 20) to quantify positively or negatively reinforced learning. Whole‐brain voxelwise analyses and region‐of‐interest‐based mixed linear effects modeling were performed. Elevated ventral striatal connectivity to the anterior cingulate gyrus (P = 0.013), orbitofrontal cortex (P = 0.034), insula (P = 0.044), putamen (P = 0.014), globus pallidus (P < 0.01), and thalamus (P < 0.01) was observed in patients with ICB. A strong trend for elevated amygdala‐to‐midbrain connectivity was found in ICB patients on dopamine agonist. Ventral striatum‐to‐subgenual cingulate connectivity correlated with reward learning (P < 0.01), but not with punishment‐avoidance learning. These data indicate that PD‐ICB patients have elevated network connectivity in the mesocorticolimbic network. Behaviorally, proficient reward‐based learning is related to this enhanced limbic and ventral striatal connectivity. Hum Brain Mapp 39:509–521, 2018. © 2017 Wiley Periodicals, Inc.     

Impaired leg extensor strength in individuals with Parkinson disease and relatedness to functional mobility

Previous investigations have demonstrated leg strength deficits in persons with Parkinson's disease (PD) as compared to neurologically-normal adults. However, the exact mode of contraction by which strength is assessed may determine how closely such deficits are related to functional performance. The purpose of this study was to better understand the relationship of strength and functional mobility in persons with PD (n = 17, mean H&Y stage = 2.0) via comparison to a group of similar age healthy controls (n = 10) using a multi-joint isometric test of strength and various measures of functional mobility. Tests included isometric leg press maximum force relative to body mass, the Activities-specific Balance Confidence scale (ABC), postural sway under various unilateral stance and visual conditions, and the timed up and go (TUG). Relative force (p = 0.044) and ABC questionnaire mean scores (p < 0.001), showed controls performing better than PD subjects. The control group performed better than the PD group for length of path of the center of pressure except in the eyes closed positions (p < 0.05 for all). TUG time (p = 0.052) was not significantly different between the PD group and healthy controls. Leg press maximum force relative to body mass was however significantly correlated with TUG time (r = ?0.68, p = 0.003) in persons with PD. There were no gender differences for any variables. These results suggest that some balance and functional mobility task performances are more worse for persons with mild-to-moderate PD than for neurologically-normal age-matched controls, which may be influenced by lessened lower extremity multi-joint strength. Strength training of the lower extremity utilizing such multi-joint actions may be beneficial for this population.     

Resting state functional connectivity of the subthalamic nucleus in Parkinson's disease assessed using arterial spin‐labeled perfusion fMRI

Neurophysiological changes within the cortico‐basal ganglia‐thalamocortical circuits appear to be a characteristic of Parkinson's disease (PD) pathophysiology. The subthalamic nucleus (STN) is one of the basal ganglia components showing pathological neural activity patterns in PD. In this study, perfusion imaging data, acquired noninvasively using arterial spin‐labeled (ASL) perfusion MRI, were used to assess the resting state functional connectivity (FC) of the STN in 24 early‐to‐moderate PD patients and 34 age‐matched healthy controls, to determine whether altered FC in the very low frequency range of the perfusion time signal occurs as a result of the disease. Our results showed that the healthy STN was functionally connected with other nuclei of the basal ganglia and the thalamus, as well as with discrete cortical areas including the insular cortex and the hippocampus. In PD patients, connectivity of the STN was increased with two cortical areas involved in motor and cognitive processes. These findings suggest that hyperconnectivity of the STN could underlie some of the motor and cognitive deficits often present even at early stages of the disease. The FC measures provided good discrimination between controls and patients, suggesting that ASL‐derived FC metrics could be a putative PD biomarker. Hum Brain Mapp 36:1937–1950, 2015. © 2015 Wiley Periodicals, Inc .     

Dissociations among daytime sleepiness,nighttime sleep,and cognitive status in Parkinson's disease

BackgroundDaytime and nighttime sleep disturbances and cognitive impairment occur frequently in Parkinson's disease (PD), but little is known about the interdependence of these non-motor complications. Thus, we examined the relationships among excessive daytime sleepiness, nighttime sleep quality and cognitive impairment in PD, including severity and specific cognitive deficits.MethodsNinety-three PD patients underwent clinical and neuropsychological evaluations including the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). Patients were classified as having normal cognition (PD-NC), mild cognitive impairment (PD-MCI), or dementia (PDD) using recently proposed Movement Disorder Society PD-MCI and PDD criteria. Relationships between the sleep and cognitive measures and PD cognitive groups were examined.ResultsThe PD cohort included PD-NC (n = 28), PD-MCI (n = 40), and PDD (n = 25) patients. ESS scores, as a measure of daytime sleepiness, were significantly worse (p = 0.005) in cognitively impaired PD patients, particularly PDD patients. ESS scores correlated significantly with Mini-Mental State Examination scores and also with cognitive domain scores for attention/working memory, executive function, memory, and visuospatial function. In contrast, PSQI scores, as a measure of nighttime sleep quality, neither differed among cognitive groups nor correlated with any cognitive measures.ConclusionsDaytime sleepiness in PD, but not nighttime sleep problems, is associated with cognitive impairment in PD, especially in the setting of dementia, and attention/working memory, executive function, memory, and visuospatial deficits. The presence of nighttime sleep problems is pervasive across the PD cognitive spectrum, from normal cognition to dementia, and is not independently associated with cognitive impairment or deficits in cognitive domains.     

Parkinson's disease duration determines effect of dopaminergic therapy on ventral striatum function

We investigated the hypothesis that variation in endogenous dopamine (DA) across brain regions explains dissimilar effects of dopaminergic therapy on aspects of cognition in early Parkinson's disease (PD). Extensive degeneration of DA‐producing cells in the substantia nigra cause dorsal striatum (DS) DA deficiency and movement abnormalities. Particularly in early PD, this contrasts with relative sparing of the dopaminergic cells of the ventral tegmental area (VTA). 1 The hypothesis predicts that DS‐mediated cognitive functions are deficient at baseline and improved by DA replacement, whereas functions depending upon VTA‐innervated brain regions are normal off medication and worsen with treatment. The latter pattern presumably owes to overdose of relatively DA‐replete VTA‐supplied brain regions with medication levels titrated to DS‐mediated motor symptoms. 2 , 3 As PD progresses, however, VTA degeneration increases. Impairment in cognitive operations performed by VTA‐innervated brain regions, such as the ventral striatum (VS), is expected. We compared the performance of early and late PD patients, on and off dopaminergic medication, relative to age‐matched controls, on reward learning, previously shown to implicate the VS. As expected, in early PD, stimulus‐reward learning was normal off medication, but worsened with DA replacement. At more advanced disease stages, PD patients learned stimulus‐reward contingencies more poorly than controls and early PD patients off medication. Furthermore, dopaminergic medication did not worsen reward learning in late PD patients, in line with the dopamine overdose hypothesis. Unlike its effect on DS‐mediated functions, however, DA‐replacement therapy did not improve reward learning in late PD patients. © 2012 Movement Disorder Society     

Parkinson disease: Associated disorders in the Norwegian population based incident ParkWest study

Parkinson's disease (PD) may be associated with a number of different diseases due to common risk factors or overlapping symptomatology. We have asked for possible associated disorders in a Norwegian population of incident PD patients and controls, the Norwegian ParkWest study. The patients were diagnosed according to the Gelb criteria. 212 incident PD patients and 175 age and gender matched controls were included. PD patients and controls were asked for information on earlier medical history and family history.PD patients had a higher frequency of self-reported symptoms of depression (p = 0.003) and anxiety disorders (p = 0.004) before baseline. They tended to have a higher frequency of diabetes (p = 0.09) and had a higher frequency of prior stroke or TIA (p = 0.004).     

Functional brain networks and cognitive deficits in Parkinson's disease

Graph‐theoretical analyses of functional networks obtained with resting‐state functional magnetic resonance imaging (fMRI) have recently proven to be a useful approach for the study of the substrates underlying cognitive deficits in different diseases. We used this technique to investigate whether cognitive deficits in Parkinson's disease (PD) are associated with changes in global and local network measures. Thirty‐six healthy controls (HC) and 66 PD patients matched for age, sex, and education were classified as having mild cognitive impairment (MCI) or not based on performance in the three mainly affected cognitive domains in PD: attention/executive, visuospatial/visuoperceptual (VS/VP), and declarative memory. Resting‐state fMRI and graph theory analyses were used to evaluate network measures. We have found that patients with MCI had connectivity reductions predominantly affecting long‐range connections as well as increased local interconnectedness manifested as higher measures of clustering, small‐worldness, and modularity. The latter measures also tended to correlate negatively with cognitive performance in VS/VP and memory functions. Hub structure was also reorganized: normal hubs displayed reduced centrality and degree in MCI PD patients. Our study indicates that the topological properties of brain networks are changed in PD patients with cognitive deficits. Our findings provide novel data regarding the functional substrate of cognitive impairment in PD, which may prove to have value as a prognostic marker. Hum Brain Mapp 35:4620–4634, 2014. © 2014 Wiley Periodicals, Inc .