The effect of dopamine on response inhibition in Parkinson's disease relates to age-dependent patterns of nigrostriatal degeneration.

Introduction: Motor but also non-motor effects are modulated by dopamine (DA) in Parkinson's disease (PD). Impaired inhibition has been related to dopamine overdosing of the associative striatum. We compared effects of dopaminergic medication on inhibitory control in patients with young (age at onset <50 years, YOPD) and late onset PD (LOPD) and related them to nigrostriatal degeneration.

A discontinuous Galerkin model for fluorescence loss in photobleaching of intracellular polyglutamine protein aggregates.

Background: Intracellular phase separation and aggregation of proteins with extended poly-glutamine (polyQ) stretches are hallmarks of various age-associated neurodegenerative diseases. Progress in our understanding of such processes heavily relies on quantitative fluorescence imaging of suitably tagged proteins. Fluorescence loss in photobleaching (FLIP) is particularly well-suited to study the dynamics of protein aggregation in cellular models of Chorea Huntington and other polyQ diseases, as FLIP gives access to the full spatio-temporal profile of intensity changes in the cell geometry.

On the Role of Cortex-Basal Ganglia Interactions for Category Learning: A Neurocomputational Approach.

In addition to the prefrontal cortex (PFC), the basal ganglia (BG) have been increasingly often reported to play a fundamental role in category learning, but the circuit mechanisms mediating their interaction remain to be explored. We developed a novel neurocomputational model of category learning that particularly addresses the BG-PFC interplay. We propose that the BG bias PFC activity by removing the inhibition of cortico-thalamo-cortical loop and thereby provide a teaching signal to guide the acquisition of category representations in the corticocortical associations to the PFC.

Functional segregation of basal ganglia pathways in Parkinson's disease.

Dopamine exerts modulatory signals on cortex-basal ganglia circuits to enable flexible motor control. Parkinson's disease is characterized by a loss of dopaminergic innervation in the basal ganglia leading to complex motor and non-motor symptoms. Clinical symptom alleviation through dopaminergic medication and deep brain stimulation in the subthalamic nucleus likely depends on a complex interplay between converging basal ganglia pathways.

Reinforcement magnitudes modulate subthalamic beta band activity in patients with Parkinson's disease.

We set out to investigate whether beta oscillations in the human basal ganglia are modulated during reinforcement learning. Based on previous research, we assumed that beta activity might either reflect the magnitudes of individuals' received reinforcements (reinforcement hypothesis), their reinforcement prediction errors (dopamine hypothesis) or their tendencies to repeat versus adapt responses based upon reinforcements (status-quo hypothesis). We tested these hypotheses by recording local field potentials (LFPs) from the subthalamic nuclei of 19 Parkinson's disease patients engaged in a reinforcement-learning paradigm.

A Discontinuous Galerkin Model for Fluorescence Loss in Photobleaching.

Fluorescence loss in photobleaching (FLIP) is a modern microscopy method for visualization of transport processes in living cells. This paper presents the simulation of FLIP sequences based on a calibrated reaction-diffusion system defined on segmented cell images. By the use of a discontinuous Galerkin method, the computational complexity is drastically reduced compared to continuous Galerkin methods.

Subthalamic nucleus stimulation impairs emotional conflict adaptation in Parkinson's disease.

The subthalamic nucleus (STN) occupies a strategic position in the motor network, slowing down responses in situations with conflicting perceptual input. Recent evidence suggests a role of the STN in emotion processing through strong connections with emotion recognition structures. As deep brain stimulation (DBS) of the STN in patients with Parkinson's disease (PD) inhibits monitoring of perceptual and value-based conflict, STN DBS may also interfere with emotional conflict processing.

Cognitive performance correlates with the degree of dopaminergic degeneration in the associative part of the striatum in non-demented Parkinson's patients.

Parkinson's disease (PD) patients show cognitive deficits that are relevant in terms of prognosis and quality of life. Degeneration of striatal dopaminergic afferents proceeds from dorsal/caudal to anterior/ventral and is discussed to account for some of these symptoms. Treatment with dopamine (DA) has differential effects on cognitive dysfunctions, improving some and worsening others.

Basal Ganglia dysfunctions in movement disorders: What can be learned from computational simulations.

The basal ganglia are a complex neuronal system that is impaired in several movement disorders, including Parkinson's disease, Huntington's disease, and dystonia. Empirical studies have provided valuable insights into the brain dysfunctions underlying these disorders. The systems-level perspective, however, of how patients' motor, cognitive, and emotional impairments originate from known brain dysfunctions has been a challenge to empirical investigations.

Differential contributions of the globus pallidus and ventral thalamus to stimulus-response learning in humans.

The ability to learn associations between stimuli, responses and rewards is a prerequisite for survival. Models of reinforcement learning suggest that the striatum, a basal ganglia input nucleus, vitally contributes to these learning processes. Our recently presented computational model predicts, first, that not only the striatum, but also the globus pallidus contributes to the learning (i.

Open and closed cortico-subcortical loops: A neuro-computational account of access to consciousness in the distractor-induced blindness paradigm.

How the brain decides which information to process 'consciously' has been debated over for decades without a simple explanation at hand. While most experiments manipulate the perceptual energy of presented stimuli, the distractor-induced blindness task is a prototypical paradigm to investigate gating of information into consciousness without or with only minor visual manipulation. In this paradigm, subjects are asked to report intervals of coherent dot motion in a rapid serial visual presentation (RSVP) stream, whenever these are preceded by a particular color stimulus in a different RSVP stream.

Combined lesions of direct and indirect basal ganglia pathways but not changes in dopamine levels explain learning deficits in patients with Huntington's disease.

Huntington's disease (HD) is a hereditary neurodegenerative disease of the basal ganglia that causes severe motor, cognitive and emotional dysfunctions. In the human basal ganglia, these dysfunctions are accompanied by a loss of striatal medium spiny neurons, dysfunctions of the subthalamic nucleus and globus pallidus, and changes in dopamine receptor binding. Here, we used a neuro-computational model to investigate which of these basal ganglia dysfunctions can explain patients' deficits in different stimulus-response learning paradigms.

Patients with Parkinson׳s disease are less affected than healthy persons by relevant response-unrelated features in visual search.

Patients with Parkinson׳s disease (PD) respond more readily than healthy controls to irrelevant stimuli that contain task-relevant, response-priming features. This behavior may reflect oversensitivity to response-relevant features of irrelevant stimuli or failure to select relevant stimuli. To decide between these alternatives, we investigated in a "contingent-capture" paradigm whether PD patients are also oversensitive to task-relevant features that do not prime responses.

Computational models of basal-ganglia pathway functions: focus on functional neuroanatomy.

Over the past 15 years, computational models have had a considerable impact on basal-ganglia research. Most of these models implement multiple distinct basal-ganglia pathways and assume them to fulfill different functions. As there is now a multitude of different models, it has become complex to keep track of their various, sometimes just marginally different assumptions on pathway functions.

Dysfunctional and compensatory synaptic plasticity in Parkinson's disease.

In Parkinson's disease, a loss of dopamine neurons causes severe motor impairments. These motor impairments have long been thought to result exclusively from immediate effects of dopamine loss on neuronal firing in basal ganglia, causing imbalances of basal ganglia pathways. However, motor impairments and pathway imbalances may also result from dysfunctional synaptic plasticity - a novel concept of how Parkinsonian symptoms evolve.

The unstable bridge from stimulus processing to correct responding in Parkinson's disease.

It has been assumed that the basal ganglia implement links between stimulus (S) processing and motor response (R). It has also been proposed that the P3b component of the event-related EEG potential, which is usually as large in R- as in S-locked averages over trials, is a candidate marker to reveal integrity of S-R links. Therefore, the P3 complex (consisting of P3a and P3b) was here measured in averages over trials time-locked either to S or to the key-press R.

Association between fee-for-service expenditures and morbidity burden in primary care.

Background: In primary care, fee-for-services (FFS) tariffs are often based on political negotiation rather than costing systems. The potential for comprehensive measures of patient morbidity to explain variation in negotiated FFS expenditures has not previously been examined.

Objectives: To examine the relative explanatory power of morbidity measures and related general practice (GP) clinic characteristics in explaining variation in politically negotiated FFS expenditures.

Quantitative fluorescence loss in photobleaching for analysis of protein transport and aggregation.

Background: Fluorescence loss in photobleaching (FLIP) is a widely used imaging technique, which provides information about protein dynamics in various cellular regions. In FLIP, a small cellular region is repeatedly illuminated by an intense laser pulse, while images are taken with reduced laser power with a time lag between the bleaches. Despite its popularity, tools are lacking for quantitative analysis of FLIP experiments.

The Danish Centre for Strategic Research in Type 2 Diabetes (DD2): organization of diabetes care in Denmark and supplementary data sources for data collection among DD2 study participants.

This paper provides a short overview of the Danish health care system and the organization of care for type 2 diabetes patients in Denmark. It also describes the supplementary data sources that are used for collection of baseline data in the nationwide Danish Centre for Strategic Research in Type 2 Diabetes (DD2) Project. The Danish National Health Service provides tax-funded medical care for all 5.

The danish model for improvement of diabetes care in general practice: impact of automated collection and feedback of patient data.

Background. Sentinel Data Capture is an IT program designed to collect data automatically from GPs' electronic health record system. Data include ICPC diagnoses, National Health Service disbursement codes, laboratory analysis, and prescribed drugs.

Open and closed loops: A computational approach to attention and consciousness.

Within recent years, researchers have proposed the independence of attention and consciousness on both empirical and conceptual grounds. However, the elusive nature of these constructs complicates progress in the investigation of their interaction. We present a framework within which we conceptualize attention and consciousness in computational terms.

Multimorbidity and blood pressure control in 37 651 hypertensive patients from Danish general practice.

Background: Patients with hypertension are primarily treated in general practice. However, major studies of patients with hypertension are rarely based on populations from primary care. Knowledge of blood pressure (BP) control rates in patients with diabetes and/or cardiovascular diseases (CVDs), who have additional comorbidities, is lacking.

Working memory and response selection: a computational account of interactions among cortico-basalganglio-thalamic loops.

Cortico-basalganglio-thalamic loops are involved in both cognitive processes and motor control. We present a biologically meaningful computational model of how these loops contribute to the organization of working memory and the development of response behavior. Via reinforcement learning in basal ganglia, the model develops flexible control of working memory within prefrontal loops and achieves selection of appropriate responses based on working memory content and visual stimulation within a motor loop.