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The vertebrate basal ganglia play an important role in action selection—the resolution of conflicts between alternative motor programs. The effective operation of basal ganglia circuitry is also known to rely on appropriate levels of the neurotransmitter dopamine. We investigated reducing or increasing the tonic level of simulated dopamine in a prior model of the basal ganglia integrated into a robot control architecture engaged in a foraging task inspired by animal behaviour. The main findings were that progressive reductions in the levels of simulated dopamine caused slowed behaviour and, at low levels, an inability to initiate movement. These states were partially relieved by increased salience levels (stronger sensory/motivational input). Conversely, increased simulated dopamine caused distortion of the robot's motor acts through partially expressed motor activity relating to losing actions. This could also lead to an increased frequency of behaviour switching. Levels of simulated dopamine that were either significantly lower or higher than baseline could cause a loss of behavioural integration, sometimes leaving the robot in a 'behavioral trap'. That some analogous traits are observed in animals and humans affected by dopamine dysregulation suggests that robotic models could prove useful in understanding the role of dopamine neurotransmission in basal ganglia function and dysfunction. [ABSTRACT FROM AUTHOR]

The vertebrate basal ganglia play an important role in action selection—the resolution of conflicts between alternative motor programs. The effective operation of basal ganglia circuitry is also known to rely on appropriate levels of the neurotransmitter dopamine. We investigated reducing or increasing the tonic level of simulated dopamine in a prior model of the basal ganglia integrated into a robot control architecture engaged in a foraging task inspired by animal behaviour. The main findings were that progressive reductions in the levels of simulated dopamine caused slowed behaviour and, at low levels, an inability to initiate movement. These states were partially relieved by increased salience levels (stronger sensory/motivational input). Conversely, increased simulated dopamine caused distortion of the robot’s motor acts through partially expressed motor activity relating to losing actions. This could also lead to an increased frequency of behaviour switching. Levels of simulated dopamine that were either significantly lower or higher than baseline could cause a loss of behavioural integration, sometimes leaving the robot in a ‘behavioral trap’. That some analogous traits are observed in animals and humans affected by dopamine dysregulation suggests that robotic models could prove useful in understanding the role of dopamine neurotransmission in basal ganglia function and dysfunction.

Background: The most frequent behavioral manifestations in Parkinson’s disease (PD) are attributed to the dopaminergic dysregulation syndrome (DDS), which is considered to be secondary to the iatrogenic effects of the drugs that replace dopamine. Over the past few years some cases of patients improving their creative abilities after starting treatment with dopaminergic pharmaceuticals have been reported. These effects have not been clearly associated to DDS, but a relationship has been pointed out. Methods: Case study of a patient with PD. The evolution of her paintings along medication changes and disease advance has been analyzed. Results: The patient showed a compulsive increase of pictorial production after the diagnosis of PD was made. She made her best paintings when treated with cabergolide, and while painting, she reported a feeling of well-being, with loss of awareness of the disease and reduction of physical limitations. Conclusions: Dopaminergic antagonists (DA) trigger a dopaminergic dysfunction that alters artistic creativity in patients having a predisposition for it. The development of these skills might be due to the dopaminergic overstimulation due to the therapy with DA, which causes a neurophysiological alteration that globally determines DDS.

In recent years, levodopa-induced behavioral changes have received increased attention in the medical literature and in clinical practice. The spectrum of these symptoms includes non-motor fluctuations with neuropsychiatric symptoms, compulsive behaviors such as punding, dopamine dysregulation syndrome, and impulse control disorders, psychosis and hallucinations, as well as hypomania and mania. Despite knowledge of the clinical features associated with these behaviors, many of them are probably underdiagnosed. Although the mechanisms underlying behavioral symptoms are still incompletely understood, recent data from imaging and pathological studies have increased our understanding and guided new treatment strategies. Appropriate management remains challenging, because reduction of levodopa ( l-dopa) and dopaminergic treatment is often recommended; however, doses required for control of motor symptoms may still induce behavioral changes. Newer modes of delivery of dopaminergic treatment, deep brain stimulation, and nondopaminergic agents may either provide alternatives for treatment of these behavioral problems or permit treatment of parkinsonism with less risk of these behavioral disorders. © 2014 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Objective: The pathophysiology of restless legs syndrome (RLS) involves a dopaminergic dysregulation that remains poorly understood, with controversial data from the literature. Stroke-related RLS is a rare condition that involves primarily the basal ganglia, the paramedian pons, and the thalamus. Given these elements, we studied dopaminergic metabolism in patients with RLS secondary to lenticulostriate infarction using structural and nuclear imaging in the striatum ipsilateral to the infarction area, as compared to the contralateral side. We hypothesized that dopaminergic metabolism would be impaired in the striatum ipsilateral to stroke.Methods: In this observational case-control study, we aimed to prospectively include patients with RLS secondary to lenticulo-striate infarction, for analyses of dopamine dysfunction ipsilateral to stroke as compared to the contralateral striatum and to a control population. Four patients fulfilled inclusion criteria with either de novo RLS or major exacerbation of RLS existing prior to stroke, and all four patients were included. Structural imaging was performed using brain magnetic resonance imaging, and the stroke-induced metabolic modifications were assessed by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). Dopamine reuptake via DAT was explored using 123I-FP-CIT SPECT. PET with 18F-FDOPA was used to evaluate the functional integrity of the presynaptic dopaminergic synthesis.Results: The only structure damaged in all patients was the body of the caudate nucleus, right-sided for three and left-sided for one, as illustrated by magnetic resonance imaging. 18F-FDG PET showed a hypometabolism in the infarcted area, the ipsilateral thalamus, and the contralateral cerebellum. All patients displayed, in the ipsilateral putamen, increased dopaminergic tone.Conclusion: The present findings suggest that increased dopaminergic tone in the striatum may participate in the pathogenesis of RLS. These observations should encourage further research on RLS symptomatic with well-defined lesions as a promising way to further improve our understanding of its pathophysiology. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To investigate hypomania and mania related to dopamine replacement therapy (DRT) in Parkinson's disease (PD). Methods: We recruited 108 non-demented PD patients without deep brain stimulation from a movement disorders in and outpatient clinic. Forty-five age- and gender-matched controls were also included. Disease characteristics, cognitive functioning, comorbid psychiatric diseases, dopaminergic and psychiatric medication were evaluated. Diagnosis of DRT-related hypomania and mania was based on DSM-IV-TR criteria with supplementary assessment of two mania self-rating scales. First, patients and controls were compared. Patients with DRT-related hypomania or mania were then compared to the remaining patients. A binary logistic regression analysis was performed to identify correlates of DRT-related hypomania. Results: Patients scored significantly higher on mania self-rating scales than controls. Twelve patients (11.1%) had DRT-related hypomania and six patients (5.6%) had DRT-related mania. Both groups had significantly higher self-rating mania-scores than patients without these mood states. DRT-related hypomania was significantly related to younger age, younger age at PD onset, dyskinesias, higher levodopa equivalent daily dose, dopamine dysregulation, and amantadine treatment. In contrast, DRT-related mania was significantly associated with hallucinations and delusions, history of levodopa-induced psychosis, quetiapine treatment, higher depression and daily levodopa dose, and cognitive deficits. Regression analysis revealed dopamine dysregulation, dyskinesias, amantadine treatment, and younger age at PD onset as significant correlates of DRT-related hypomania. Conclusion: DRT-related hypomania and mania are relevant comorbidities in PD. DRT-related hypomania may exist as a distinct psychiatric symptom complex in young patients with early disease onset. Different patient profiles likely underlie DRT-related hypomania and mania. [Copyright &y& Elsevier]

Despite the prominent loss of motor skills, artistic capacities remain preserved in Parkinson's disease (PD). Furthermore, artistic creativity may emerge in art-naïve PD patients treated with levodopa and dopamine agonists. The present review discusses reported PD patients who developed enhanced artistic skills under anti-Parkinsonian therapy and the course of this phenomenon in the clinical context. It is unclear whether creative drive is related to dopamine dysregulation, and the mechanisms remain speculative. The delineation of the particular constellation that enables this emergence in PD patients may shed light on the comprehension of the concept of creativity in general. [ABSTRACT FROM AUTHOR]

Abstract: Young-onset Parkinson''s disease (YOPD) patients have psychosocial issues that create more challenges than for older patients. They are diagnosed during the most productive years of their lives, live longer with the disease, and are at increased risk for non-motor symptoms of PD. This article describes issues that health care professionals may need to address, including anxiety, depression, cognitive disturbances, breakdown of relationships, and employment. These psychosocial problems require as much attention as the medical problems; they negatively impact the emotional stability of both the patient and family, interfering with all relationships. YOPD patients can benefit from a team approach to their treatment. [Copyright &y& Elsevier]

One of the frequent but under-recognized side effects of antipsychotic medications is the subtle subjective changes including feelings of anxiety, distress and lack of pleasure, which are collectively labeled as neuroleptic-induced dysphoria and, ultimately, often lead to dislike and aversions to medications, with serious clinical consequences. Yet, those very patients take to frequent abuse of illicit drugs. Several surveys estimated the association of drug abuse in schizophrenia as ranging somewhere between 10–70%. One popular and frequently accepted explanation for such high association has been the self-medication hypothesis. In other words, patients take to illicit drugs as a way of alleviating symptoms of the illness as well as medication-induced side effects, particularly neuroleptic dysphoria. Recent clinical and neuro-imaging studies have, for the first time, directly linked the genesis of neuroleptic dysphoria to the dopamine-binding ratios in the nigrostriatal complex. This recent evidence comes from the study of dopamine receptor occupancy using PET scanning as well as from dopamine depletion SPECT studies. Meanwhile, emerging evidence from research in the addiction field has implicated dopamine in the same neural circuitry in motivational and reinforcement behaviour, which is central to initiation and continuation of dependency states. As the self-medication hypothesis proved incapable of explaining all the varied pictures of dysphoria and comorbid addictions, a unifying hypothesis is put forward to argue that both vulnerability to drug addictions and medication-induced dysphoria vary on independent facets of the illness itself. The mechanism that possibly links both lies in a dysregulated dopamine signaling in the nucleus accumbens resulting from frontal/cortical and hippocampal dysfunction. Besides the neurochemical argument, clinical and epidemiological data seem also to add support to this proposition. Such proposal not only represents a major rethinking of the concept of schizophrenia and its varied domains and manifestations but has also significant clinical implications in understanding and better management of comorbid drug abuse in the context of the illness itself. The recent intensified research efforts to understand the central mechanisms related to the role of dopamine in reward, punishment and pleasurable experiences as well as motivational and reinforcement behaviour, opens a new vista ill understanding how and why patients like or dislike their medications based on their subjective responses to medication-taking. It is possible that the field is on the verge of a new science, which can collectively be called: ‘The Science of Subjective Tolerability Disorders.’ [ABSTRACT FROM AUTHOR]

Abstract: Impulse-control disorders (ICDs) are becoming more commonly recognized in the Parkinson disease (PD) population. To date, there are no definitive methods of treating dopamine dysregulation syndromes in PD patients. We sought to uncover an effective treatment option for future study. We report a series of 3 PD patients with ICDs who were effectively treated with valproate. Based on these encouraging preliminary observations, future controlled clinical trials investigating the efficacy of valproate for ICDs in PD are recommended. [Copyright &y& Elsevier]