Reward Processing in the Brain: A Prerequisite for Movement Preparation?

In the last decade, expanding animal studies on the cerebral organization of reward processing toward human in vivo situations has become possible. In this review, we define some of the concepts associated with reward, summarize the crucial importance of the dopaminergic system, and discuss the currently available neuroimaging studies in man. We will show that abstract concepts of human behavior like emotions, drive, arousal, and reinforcement are now open for further exploration in man at the level of neuronal circuit organization. The cerebral dopaminergic neurotransmitter circuitry does play an important role in the organization of both the motor and motivational system

Treatment of Parkinson’s Disease:Early, Late, and Combined

Medical therapy in de novo Parkinson’s disease typically starts with a dopamine agonist or levodopa in combination with a decarboxylase inhibitor or if symptoms are still very mild with a MAO-B inhibitor. When patients do not (or no longer) respond satisfactorily to these initial therapies, different drugs can be initiated or combined (i.e., “add-on” treatments). These add-on therapies not only comprise oral agents but also intra-jejunal and intra-cutaneous treatments and functional neurosurgical procedures. This chapter starts with the treatment of de novo Parkinson’s disease whereafter indications and expected effects of the different “add-on” therapies will be described. The “add-on” therapies will be described in a hierarchical way and treatment algorithms will be provided based on prevailing symptoms including non-motor symptoms. The symptoms that will be discussed are: (1) bradykinesia and “wearing-OFF, " (2) tremor at rest, (3) dyskinesia, (4) gait and postural symptoms including freezing of gait, and (5) important non-motor symptoms. Finally, a comprehensive add-on treatment algorithm will be provided that takes into account non-motor symptoms that may limit the efficacy and tolerability of the different add-on therapies.</p

Human phosphodiesterase 4D7 (PDE4D7) expression is increased in TMPRSS2-ERG positive primary prostate cancer and independently adds to a reduced risk of post-surgical disease progression

background: There is an acute need to uncover biomarkers that reflect the molecular pathologies, underpinning prostate cancer progression and poor patient outcome. We have previously demonstrated that in prostate cancer cell lines PDE4D7 is downregulated in advanced cases of the disease. To investigate further the prognostic power of PDE4D7 expression during prostate cancer progression and assess how downregulation of this PDE isoform may affect disease outcome, we have examined PDE4D7 expression in physiologically relevant primary human samples. methods: About 1405 patient samples across 8 publically available qPCR, Affymetrix Exon 1.0 ST arrays and RNA sequencing data sets were screened for PDE4D7 expression. The TMPRSS2-ERG gene rearrangement status of patient samples was determined by transformation of the exon array and RNA seq expression data to robust z-scores followed by the application of a threshold &gt;3 to define a positive TMPRSS2-ERG gene fusion event in a tumour sample. results: We demonstrate that PDE4D7 expression positively correlates with primary tumour development. We also show a positive association with the highly prostate cancer-specific gene rearrangement between TMPRSS2 and the ETS transcription factor family member ERG. In addition, we find that in primary TMPRSS2-ERG-positive tumours PDE4D7 expression is significantly positively correlated with low-grade disease and a reduced likelihood of progression after primary treatment. Conversely, PDE4D7 transcript levels become significantly decreased in castration resistant prostate cancer (CRPC). conclusions: We further characterise and add physiological relevance to PDE4D7 as a novel marker that is associated with the development and progression of prostate tumours. We propose that the assessment of PDE4D7 levels may provide a novel, independent predictor of post-surgical disease progression

Exploring the impact of social network change:Experiences of older adults ageing in place

Social networks are sources of support and contribute to the well-being of older adults who are ageing in place. As social networks change, especially when accompanied by health decline, older adults' sources of support change and their well-being is challenged. Previous studies predominantly used quantitative measures to examine how older adults' social networks change. Alternatively, this study explores the impact of changing social networks on older adults' lives by examining their personal experiences. We held four focus groups, two with a total of 14 older adults who are ageing in place and receiving home care and two with a total of 20 home-care nurses from different regions and organisations in the Netherlands. Subsequently, an expert team of home-care professionals and managers discussed and verified the results. Procedures for grounded theory building were used for analysis. We revealed four themes of high-impact experiences: (a) struggling with illness/death of the spouse; (b) working out a changing relationship with (grand)children; (c) regretting the loss of people they have known for so long and (d) feeling dependent and stressed when helpers enter the network. Also, network dynamics were found to follow three consecutive stages: (a) awareness of social network change; (b) surprise when social network change actually occurs and (c) acceptance and adjusting to new circumstances. Together, the four themes of experiences and three stages of network change form an integrative model of the role of social network dynamics for older adults' lives when ageing in place

Muscle co-activity tuning in Parkinsonian hand movement : disease-specific changes at behavioral and cerebral level

We investigated different degrees of muscle co-activity in simple hand movement at behavioral and cerebral level in healthy subjects and Parkinson’s disease (PD) patients. We compared 'singular' movements, dominated by the activity of one agonist muscle, to 'composite' movements, requiring conjoint activity of multiple muscles, in a center-out (right hand) step-tracking task. Behavioral parameters were obtained by EMG and kinematic recordings. fMRI was used to investigate differences in underlying brain activations between PD patients (N= 12) and healthy (age-matched) subjects (N= 18). In healthy subjects, composite movements recruited the striatum and cortical areas comprising bilaterally the supplementary motor area and premotor cortex, contralateral medial prefrontal cortex, primary motor cortex, primary visual cortex, and ipsilateral superior parietal cortex. Contrarily, the ipsilateral cerebellum was more involved in singular movements. This striking dichotomy between striatal and cortical recruitment versus cerebellar involvement may reflect the complementary roles of these areas in motor control, in which the basal ganglia are involved in movement selection and the cerebellum in movement optimization. Compared to healthy subjects, PD patients showed decreased activation of the striatum and cortical areas in composite movement, while performing worse at behavioral level. This implies that PD patients are especially impaired on tasks requiring highly tuned muscle co-activity. Singular movement, on the other hand, was characterized by a combination of increased activation of the ipsilateral parietal cortex and left cerebellum. As singular movement performance was only slightly compromised, we interpret this as a reflection of increased visuospatial processing, possibly as a compensational mechanism

Effect of H-Bonding on Order Amplification in the Growth of a Supramolecular Polymer in Water

While a great deal of knowledge on the roles of hydrogen bonding and hydrophobicity in proteins has resulted in the creation of rationally designed and functional peptidic structures, the roles of these forces on purely synthetic supramolecular architectures in water have proven difficult to ascertain. Focusing on a 1,3,5-benzenetricarboxamide (BTA)-based supramolecular polymer, we have designed a molecular modeling strategy to dissect the energetic contributions involved in the self-assembly (electrostatic, hydrophobic, etc.) upon growth of both ordered BTA stacks and random BTA aggregates. Utilizing this set of simulations, we have unraveled the cooperative mechanism for polymer growth, where a critical size must be reached in the aggregates before emergence and amplification of order into the experimentally observed fibers. Furthermore, we have found that the formation of ordered fibers is favored over disordered aggregates solely on the basis of electrostatic interactions. Detailed analysis of the simulation data suggests that H-bonding is a major source of this stabilization energy. Experimental and computational comparison with a newly synthesized 1,3,5-benzenetricarboxyester (BTE) derivative, lacking the ability to form the H-bonding network, demonstrated that this BTE variant is also capable of fiber formation, albeit at a reduced persistence length. This work provides unambiguous evidence for the key 1D driving force of hydrogen bonding in enhancing the persistency of monomer stacking and amplifying the level of order into the growing supramolecular polymer in water. Our computational approach provides an important relationship directly linking the structure of the monomer to the structure and properties of the supramolecular polymer

An exploratory study looking at the relationship marketing techniques used in the music festival industry

There are current issues and trends in the music festival market, which may affect the success of an event, and market saturation is at the forefront of these issues. Previous literature, maintaining the need for a marketing approach to festivals, identifi es the need for maintaining strong stakeholder relationships in order to succeed in a business environment; attention has been focused to the theory of relationship marketing (RM) because of the recognition that this practice is complementary to the marketing of festivals. The very nature of the music festival as an annual, usually, 4-day event means that effective marketing is needed to keep connections with the consumer throughout the year. This article focuses on the RM techniques utilised within the music festival industry from the viewpoint of the festival organiser in an attempt to establish how festival organisations value and monitor organisational relationships. This article explores the extent to which these relationships are valued and managed; furthermore, the variations between these intricate relationships are considered by focusing on those held with the organisation ’ s consumers and sponsors, the results of which have provided the ability to establish the importance and relevance of RM to the industry and further identify the marketing communication methods employed to establish and maintain such relationships. In-depth, convergent interviews have been conducted with a segment of music festival organisers from a range of events. The results have been integrated with the study of current literature to best exemplify these issues. It has been established that RM has a strong role in today ’ s commercial and independent music festival industry; technological advances are enabling the organiser to support online relationships further and increase consumer loyalty. There is a need to expand the research further because of the complexity of organisational relationships and the varying categories of festivals

A Relational Event Approach to Modeling Behavioral Dynamics

This chapter provides an introduction to the analysis of relational event data (i.e., actions, interactions, or other events involving multiple actors that occur over time) within the R/statnet platform. We begin by reviewing the basics of relational event modeling, with an emphasis on models with piecewise constant hazards. We then discuss estimation for dyadic and more general relational event models using the relevent package, with an emphasis on hands-on applications of the methods and interpretation of results. Statnet is a collection of packages for the R statistical computing system that supports the representation, manipulation, visualization, modeling, simulation, and analysis of relational data. Statnet packages are contributed by a team of volunteer developers, and are made freely available under the GNU Public License. These packages are written for the R statistical computing environment, and can be used with any computing platform that supports R (including Windows, Linux, and Mac).

In Vivo Imaging of Vesicular Monoamine Transporters in Human Brain Using [ 11 C]Tetrabenazine and Positron Emission Tomography

The pharmacokinetics of [ 11 CJtetrabenazine, a high-affinity radioligand for the monoamine vesicular transporter, were determined in living human brain using in vivo imaging by positron emission tomography (PET). The radiotracer showed high brain uptake and rapid washout from all brain regions with relatively slower clearance from regions of highest concentrations of monoamine vesicular transporters (striatum), resulting in clear differential visualization of these structures at short intervals after injection (10–20 min). As the first human PET imaging study of a vesicular neurotransmitter transporter, these experiments demonstrate that external imaging of vesicular transporters forms a new and valuable approach to the in vivo quantification of monoaminergic neurons, with potential application to the in vivo study of neurodegenerative disorders such as Parkinson's disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65743/1/j.1471-4159.1993.tb03521.x.pd

Parkinson's disease-related perfusion and glucose metabolic brain patterns identified with PCASL-MRI and FDG-PET imaging

AbstractIntroductionUnder normal conditions, the spatial distribution of resting cerebral blood flow and cerebral metabolic rate of glucose are closely related. A relatively new magnetic resonance (MR) technique, pseudo-continuous arterial spin labeling (PCASL), can be used to measure regional brain perfusion. We identified a Parkinson's disease (PD)-related perfusion and metabolic covariance pattern in the same patients using PCASL and FDG-PET imaging and assessed (dis)similarities in the disease-related pattern between perfusion and metabolism in PD patients.MethodsNineteen PD patients and seventeen healthy controls underwent [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. Of 14 PD patients and all healthy controls PCASL-MRI could be obtained. Data were analyzed using scaled subprofile model/principal component analysis (SSM/PCA).ResultsUnique Parkinson's disease-related perfusion and metabolic covariance patterns were identified using PCASL and FDG-PET in the same patients. The PD-related metabolic covariance brain pattern is in high accordance with previously reports. Also our disease-related perfusion pattern is comparable to the earlier described perfusion pattern. The most marked difference between our perfusion and metabolic patterns is the larger perfusion decrease in cortical regions including the insula.ConclusionWe identified PD-related perfusion and metabolic brain patterns using PCASL and FDG-PET in the same patients which were comparable with results of existing research. In this respect, PCASL appears to be a promising addition in the early diagnosis of individual parkinsonian patients