Subthalamic control of impulsive actions: insights from deep brain stimulation in Parkinson's disease.

Control of actions allows adaptive, goal-directed behaviour. The basal ganglia, including the subthalamic nucleus, are thought to play a central role in dynamically controlling actions through recurrent negative feedback loops with the cerebral cortex. Here, we summarize recent translational studies that used deep brain stimulation to record neural activity from and apply electrical stimulation to the subthalamic nucleus in people with Parkinson's disease. These studies have elucidated spatial, spectral and temporal features of the neural mechanisms underlying the controlled delay of actions in cortico-subthalamic networks and demonstrated their causal effects on behaviour in distinct processing windows. While these mechanisms have been conceptualized as control signals for suppressing impulsive response tendencies in conflict tasks and as decision threshold adjustments in value-based and perceptual decisions, we propose a common framework linking decision-making, cognition and movement. Within this framework subthalamic deep brain stimulation can lead to suboptimal choices by reducing the time that patients take for deliberation before committing to an action. However, clinical studies have consistently shown that the occurrence of impulse control disorders is reduced, not increased, after subthalamic deep brain stimulation surgery. This apparent contradiction can be reconciled when recognizing the multifaceted nature of impulsivity, its underlying mechanisms and modulation by treatment. While subthalamic deep brain stimulation renders patients susceptible to making decisions without proper forethought, this can be disentangled from effects related to dopamine comprising sensitivity to benefits vs. costs, reward delay aversion and learning from outcomes. Alterations in these dopamine-mediated mechanisms are thought to underlie the development of impulse control disorders, and can be relatively spared with reduced dopaminergic medication after subthalamic deep brain stimulation. Together, results from studies using deep brain stimulation as an experimental tool have improved our understanding of action control in the human brain and have important implications for treatment of patients with Neurological disorders.

Multimodal neuroimaging fusion unravel structural-functional-neurotransmitter change in Parkinson's disease with impulse control disorders.

BACKGROUND: Impulse control disorders (ICD) in Parkinson's disease (PD) is highly multifactorial in etiology and has intricate neural mechanisms. Our multimodal neuroimaging study aimed to investigate the specific patterns of structure-function-neurotransmitter interactions underlying ICD. METHODS: Thirty PD patients with ICD (PD-ICD), 30 without ICD (PD-NICD) and 32 healthy controls (HCs) were recruited. Gyrification and perivascular spaces (PVS) were computed to capture the alternations of cortical surface morphology and glymphatic function. Seed-based functional connectivity (FC) were performed to identify the corresponding functional changes. Further, JuSpace toolbox were employed for cross-modal correlations to evaluate whether the spatial patterns of functional alterations in ICD patients were associated with specific neurotransmitter system. RESULTS: Compared to PD-NICD, PD-ICD patients showed hypogyrification and enlarged PVS volume fraction in the left orbitofrontal gyrus (OFG), as well as decreased FC between interhemispheric OFG. The interhemispheric OFG connectivity reduction was associated with spatial distribution of µ-opioid pathway (r = -0.186, p = 0.029, false discovery rate corrected). ICD severity was positively associated with the PVS volume fraction of left OFG (r = 0.422, p = 0.032). Furthermore, gyrification index (LGI) and percent PVS (pPVS) in OFG and their combined indicator showed good performance in differentiating PD-ICD from PD-NICD. CONCLUSIONS: Our findings indicated that the co-altered structure-function-neurotransmitter interactions of OFG might be involved in the pathogenesis of ICD.

Dopamine agonist serum concentrations and impulse control disorders in Parkinson's disease.

BACKGROUND AND PURPOSE: Impulse control disorders (ICDs) are common among Parkinson's disease patients using dopamine agonists. We wanted to determine whether ICD patients have higher dopamine agonist serum concentrations than those without any sign of ICD. METHODS: Patients who used either pramipexole or ropinirole depot once daily were screened for ICDs using the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale. Those who scored above the cut-off for one or more of the four defined ICDs (gambling, compulsive sexual behavior, compulsive shopping, and binge-eating) were compared in a case-control study to patients who scored zero points (no evidence of ICD) on the same items. They were examined clinically and evaluated using relevant scales. Three blood samples were taken on the same day: before daily dose, and then 6 and 12 h later. RESULTS: Forty-six patients were included: 19 ICD-positive and 27 controls. Ropinirole serum concentrations 6 h after daily intake (Cmax ) were higher in the case group compared to the control group, as was the daily ropinirole dosage. No differences were observed in serum concentrations, dosage or total drug exposure for pramipexole. Disease duration and length of dopamine agonist treatment was significantly longer among ICD patients for ropinirole, but not for pramipexole. CONCLUSIONS: The use of pramipexole may in itself confer high ICD risk, whereas ICDs among ropinirole users depend more on serum concentration and drug exposure. The pharmacokinetic properties of ropinirole make it challenging to predict its effects on patients, which supports the need for therapeutic drug monitoring to reduce risk of ICD.

Impulse control disorders in patients with dopamine agonist-treated pituitary adenomas: a cross-sectional multicenter study.

BACKGROUND: Impulse control disorders (ICDs) have been described as underrecognized side effects of dopamine agonists (DAs) in neurological disorders but are not sufficiently understood in endocrine conditions. OBJECTIVE: To identify the prevalence of DAs induced ICDs and determine potential risk factors related to these disorders in patients with prolactinoma and non-function pituitary adenomas (NFPAs). METHODS: This is a cross-sectional multicenter study involving 200 patients with prolactinoma and NFPAs, who received follow-ups in tertiary referral centers. DA-induced ICDs were assessed using ICD questionnaires modified from prior studies. RESULT: At least one ICD was reported by 52% of participants, among whom 28.5% mentioned compulsive shopping, 24.5% punding, and 24.5% hypersexuality. Furthermore, 33% of the patients reported the presence of one type of ICD behavior, while 12% specified two and 7% had three types of such behavior. The multivariable logistic regression showed that the significant risk factors of ICD were younger age (adjusted odds ratio [AOR]: 0.92, 95% confidence interval [CI]: 0.88-0.97, p 0.001), being single (AOR: 0.15, 95%CI: 0.03-0.84, p 0.03), and a positive history of psychiatric illness (AOR: 7.67, 95% CI: 1.37-42.97, p 0.021). CONCLUSION: ICDs with a broad range of psychiatric symptoms are common in individuals with DA-treated prolactinoma and NFPAs. Endocrinologists should be aware of this potential side effect, particularly in patients with a personal history of psychiatric disorder.

Impulse control disorders in Parkinson's disease patients treated with pramipexole and ropinirole: a systematic review and meta-analysis.

BACKGROUND: This analysis is the first systematic review and meta-analysis assessing occurrences of ICD in PD patients treated with oral DAs: ropinirole (ROP) and pramipexole (PRX). This study compares the two oral DAs to a transdermal patch, rotigotine (RTG). METHODS: We performed an extensive systematic search for eligible studies from PubMed, Embase, Cochrane Library, and Google Scholar. The data was analyzed by various software, including EndNote, Rayyan, PRISM, and RevMan. Two studies incorporating 658 patients collectively were assessed. RESULTS: This meta-analysis shows a significant correlation between the usage of PRX (25.3%) or ROP (21.8%) and the development of ICD in PD patients. Compared to the transdermal patch, RTG, PRX was found to have a significant relative risk (P < 0.0001) of 3.46 (95% CI 2.07-5.76), and ROP was found to have a significant relative risk (P < 0.0001) of 2.98 (95% CI 1.77-5.02). The data collected shows RTG is approximately three times less likely to cause ICDs than oral PRX and ROP. CONCLUSION: The present investigation provides insight into ICD occurrences with PRX, ROP, and RTG to allow physicians to make more informed decisions on risk versus reward when deciding how to treat a PD patient with these drugs. However, related to various disclosed limitations, our conclusion cannot provide definitive practice protocols.

Pramipexole Hyperactivates the External Globus Pallidus and Impairs Decision-Making in a Mouse Model of Parkinson's Disease.

In patients with Parkinson's disease (PD), dopamine replacement therapy with dopamine D2/D3 receptor agonists induces impairments in decision-making, including pathological gambling. The neurobiological mechanisms underlying these adverse effects remain elusive. Here, in a mouse model of PD, we investigated the effects of the dopamine D3 receptor (D3R)-preferring agonist pramipexole (PPX) on decision-making. PD model mice were generated using a bilateral injection of the toxin 6-hydroxydopamine into the dorsolateral striatum. Subsequent treatment with PPX increased disadvantageous choices characterized by a high-risk/high-reward in the touchscreen-based Iowa Gambling Task. This effect was blocked by treatment with the selective D3R antagonist PG-01037. In model mice treated with PPX, the number of c-Fos-positive cells was increased in the external globus pallidus (GPe), indicating dysregulation of the indirect pathway in the corticothalamic-basal ganglia circuitry. In accordance, chemogenetic inhibition of the GPe restored normal c-Fos activation and rescued PPX-induced disadvantageous choices. These findings demonstrate that the hyperactivation of GPe neurons in the indirect pathway impairs decision-making in PD model mice. The results provide a candidate mechanism and therapeutic target for pathological gambling observed during D2/D3 receptor pharmacotherapy in PD patients.

Performance on the balloon analogue risk task and anticipatory response inhibition task is associated with severity of impulse control behaviours in people with Parkinson's disease.

Dopamine agonist medication is one of the largest risk factors for development of problematic impulse control behaviours (ICBs) in people with Parkinson's disease. The present study investigated the potential of dopamine gene profiling and individual performance on impulse control tasks to explain ICB severity. Clinical, genetic and task performance data were entered into a mixed-effects linear regression model for people with Parkinson's disease taking (n = 50) or not taking (n = 25) dopamine agonist medication. Severity of ICBs was captured via the Questionnaire for Impulsive-compulsive disorders in Parkinson's disease Rating Scale. A cumulative dopamine genetic risk score (DGRS) was calculated for each participant from variance in five dopamine-regulating genes. Objective measures of impulsive action and impulsive choice were measured on the Anticipatory Response Inhibition Task and Balloon Analogue Risk Task, respectively. For participants on dopamine agonist medication, task performance reflecting greater impulsive choice (p = 0.014), and to a trend level greater impulsive action (p = 0.056), as well as a longer history of DA medication (p < 0.001) all predicted increased ICB severity. DGRS however, did not predict ICB severity (p = 0.708). No variables could explain ICB severity in the non-agonist group. Our task-derived measures of impulse control have the potential to predict ICB severity in people with Parkinson's and warrant further investigation to determine whether they can be used to monitor ICB changes over time. The DGRS appears better suited to predicting the incidence, rather than severity, of ICBs on agonist medication.

Rapid Eye Movement Sleep Behavior Disorder in Parkinson's Disease: A Survey-Based Study.

OBJECTIVE: To characterize Parkinson's disease (PD) symptoms based on the presence, onset time, and severity of rapid eye movement sleep behavior disorder (RBD) and their association with impulse control disorders (ICD). BACKGROUND: RBD is a frequent non-motor symptom in PD, usually described as prodromal. The severity of RBD according to the start time and its relationship with ICD in PD needs further clarification. METHODS: A survey-based study was performed to determine the presence of RBD symptoms, their severity, and the temporal relationship with the PD onset. The survey included RBD1Q, the Mayo Sleep, and the RBDQ-HK questionnaires and questions about clinical characteristics, including ICD. Only PD patients with care partners spending night hours in the same room were included. RESULTS: 410 PD patients were included: 206 with RBD (50.2%) and 204 non-RBD (49.8%). The PD-RBD patients were younger and their daily levodopa dose was higher than the non-RBD group. Most of these patients developed RBD symptoms after the onset of clinical PD were younger at motor symptom onset and had higher scores in the hallucinations and psychosis subsection of MDS-UPDRS-I. RBD group had a more severe non-motor phenotype, including more ICD than those without RBD, mainly due to higher compulsive eating. CONCLUSIONS: In our study, most patients recognized RBD symptoms after the onset of the PD motor symptoms and the clinical features of PD with and without RBD were distinctive, supporting the hypothesis that PD-RBD might represent a variant pattern of neurodegeneration.

Screening for impulse control disorders in Parkinson's disease and dopamine agonist use: a study of pharmacokinetic and psychological risk factors.

INTRODUCTION: Dopamine agonist (DA) use is considered the main risk factor for impulse control disorder (ICD) development in Parkinson's disease (PD). Besides DAs, personality traits and cognitive features may represent risk factors for ICDs. The primary aim of this study was to investigate differences in DA plasma concentrations in PD patients with and without a positive screening for ICDs according to validated tools. The secondary aim was to compare the psychological profile between ICD positive and negative screened patients. METHODS: PD patients receiving chronic DA therapy were screened for ICDs according to the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP). Blood samples for measurement of DA (pramipexole, ropinirole, rotigotine) trough plasma concentrations were drawn in the morning, at mean 16-19 h from the last DA dose. Patients' psychological profile was investigated by Millon Clinical Multiaxal Inventory III and Barratt Impulsiveness Scale (BIS-11). RESULTS: One hundred and five PD patients were enrolled. Forty-one patients (39%) were QUIP positive, mainly for binge eating and hobbyism. Median plasma concentrations of pramipexole (n = 71, 66%), ropinirole (n = 21, 19%), and rotigotine (n = 16, 15%) were similar between QUIP positive and negative patients. QUIP positive patients showed higher motor impulsiveness (p = 0.04) and tended to higher total impulsiveness (p = 0.05). CONCLUSION: This is the first prospective study to evaluate the relationship between DA plasma concentrations and ICDs risk in PD patients. DA plasma levels were overlapping between QUIP positive and negative patients. BIS-11, particularly the motor impulsiveness subscale, might be a useful screening tool in PD patients eligible for DA therapy.

The mediating effects of depression, anxiety, and rapid eye movement sleep behavior disorder on the association between dopaminergic replacement therapy and impulse control disorders in Parkinson's disease.

OBJECTIVES: This study aims to longitudinally explore whether and how rapid eye movement sleep behavior disorder (RBD), depression, and anxiety mediate the association between dopaminergic replacement therapy (DRT) and impulse control disorders (ICDs) in patients with Parkinson's disease (PD). METHODS: Subjects were selected from the Parkinson's Progression Markers Initiative. After excluding missing data, 268, 223, 218, 238, and 219 patients with PD diagnosed at 12, 24, 36, 48, and 60 months prior, respectively, were included. We used the Questionnaire for Impulsive-Compulsive Disorders, RBD Screening Questionnaire, Geriatric Depression Scale, and State-Trait-Anxiety Inventory to assess ICBs, RBD, depression, and anxiety, respectively. We constructed three causal mediation analysis models to infer potential contingent pathways from DRT to ICD mediated by depression, anxiety, and RBD separately. RESULTS: DRT was associated with an increased risk of PD incidence. Aggravation of ICDs was partly explained by improvements in depression (the average causal mediation effect accounted for 8.0% of the total effect) and RBD (the average causal mediation effect of RBD accounted for 16.4% of the total effect). This suggested that anxiety (the average causal mediation effect accounted for 12.7% of the total effect) plays a mediating role. CONCLUSIONS: Focusing on changes in RBD, depression, and anxiety associated with hyperdopaminergic status should be an essential part of strategies to prevent ICDs in patients with Parkinson's disease.

A circuit-based approach to modulate hypersexuality in Parkinson's disease.

AIM: Impulse-control disorder is a common neuropsychiatric complication in Parkinson's disease (PD) under dopamine replacement therapy. Prior studies tested the balance between enhanced desire towards reward and cognitive control deficits, hypothesized to be biased towards the former in impulse control disorders. We provide evidence for this hypothesis by measuring behavioral and neural patterns behind the influence of sexual desire over response inhibition and tools towards functional restoration using repetitive transcranial stimulation in patients with hypersexuality as predominant impulsive disorder. METHODS: The effect of sexual cues on inhibition was measured with a novel erotic stop-signal task under on and off dopaminergic medication. Task-related functional and anatomical connectivity models were estimated in 16 hypersexual and 17 nonhypersexual patients with PD as well as in 17 healthy controls. Additionally, excitatory neuromodulation using intermittent theta-burst stimulation (sham-controlled) was applied over the pre-supplementary motor area in 20 additional hypersexual patients with PD aiming to improve response inhibition. RESULTS: Compared with their nonhypersexual peers, patients with hypersexuality recruited caudate, pre-supplementary motor area, ventral tegmental area, and anterior cingulate cortex while on medication. Reduced connectivity was found between pre-supplementary motor area and caudate nucleus in hypersexual compared with nonhypersexual patients (while medicated), a result paralleled by compensatory enhanced anatomical connectivity. Furthermore, stimulation over the pre-supplementary motor area improved response inhibition in hypersexual patients with PD when exposed to sexual cues. CONCLUSION: This study, therefore, has identified a specific fronto-striatal and mesolimbic circuitry underlying uncontrolled sexual responses in medicated patients with PD where cortical neuromodulation halts its expression.

["Impulsive insanity" according to Emil Kraepelin : A clinical framework for female criminals at the beginning of the twentieth century]. / Das "impulsive Irresein" nach Emil Kraepelin : Ein Krankheitsbild für die Verbrecherinnen am Beginn des 20. Jahrhunderts.

BACKGROUND: In his comprehensive classification of the beginning of the twentieth century, Emil Kraepelin provided a detailed description of an entity he called "impulsive insanity", which had not been elaborated before him. The forms depicted by him largely corresponded to the offences, which were referred to as typically female in their nature in the late nineteenth and early twentieth centuries. QUESTION: How did Kraepelin classify "impulsive insanity" and what forms did he describe? Did Kraepelin also see these disorders predominantly prevailing in women, did he establish a connection with women's criminality and how did this fit into the discourses of the time on femininity, criminal legislation and degeneration? MATERIAL AND METHODS: This study focused on the clinical picture "impulsive insanity" as described by Emil Kraepelin in his main work, the 8th edition of his Textbook of Psychiatry published between 1909 and 1915. His description was analyzed in detail and embedded in a historical context on the basis of secondary literature. RESULTS: In rudiments Kraepelin's clinical classification is still comprehensible today, although there are major differences to how literature in later years treated this issue. Kraepelin clearly sees "impulsive insanity" as a driving disorder predominantly prevailing in women. DISCUSSION: Elaborating his concept of "impulsive insanity", Kraepelin positioned himself in relation to important scientific discourses of the early twentieth century, such as the debate on criminal legislation and the theory of degeneration. On the basis of the individual forms of "impulsive insanity" described by Kraepelin, various concepts of constructing and pathologizing femininity can be identified. Apparently, it also aims to explain common female crimes within the patriarchal hegemony.

Impulse Control Disorders in the Polish Population of Patients with Parkinson's Disease.

Background and Objectives: Parkinson's disease (PD) is one of the most common neurodegenerative diseases in the world. It is characterized by the presence of not only typical motor symptoms but also several less known and aware non-motor symptoms (NMS). The group of disorders included in the NMS is Impulse Control Disorders (ICDs). ICDs are a group of disorders in which patients are unable to resist temptations and feel a strong, pressing desire for specific activities such as gambling, hypersexuality, binge eating, and compulsive buying. The occurrence of ICDs is believed to be associated primarily with dopaminergic treatment, with the use of dopamine agonists (DA), and to a lesser extent with high doses of L-dopa. The aim of our study was to develop a profile of Polish ICDs patients and assess the frequency of occurrence of ICDs, as well as determine the risk factors associated with these disorders against the background of the PD population from other countries. Materials and Methods: Our prospective study included 135 patients with idiopathic PD who were hospitalized between 2020 and 2022 at the Neurological Department of University Central Hospital in Katowice. In the assessment of ICDs, we used the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP). Other scales with which we assessed patients with PD were as follows: MDS-UPDRS part III and modified Hoehn-Yahr staging. Clinical data on age, gender, disease duration and onset, motor complications, and medications were collected from electronic records. Results: ICDs were detected in 27.41% of PD patients (binge eating in 12.59%, hypersexuality in 11.11%, compulsive buying in 10.37%, and pathological gambling occurred in only 5.19% of patients. In total, 8.89% had two or more ICDs). The major finding was that ICDs were more common in patients taking DA than in those who did not use medication from this group (83.78% vs. 54.07%, respectively; p = 0.0015). Patients with ICDs had longer disease duration, the presence of motor complications, and sleep disorders. An important finding was also a very low detection of ICDs in a routine medical examination; only 13.51% of all patients with ICDs had a positive medical history of this disorder. Conclusions: ICDs are relatively common in the population of Polish PD patients. The risk factors for developing ICDs include longer duration of the disease, presence of motor complications, sleep disorders, and use of DA and L-dopa. Due to the low detectability of ICDs in routine medical history, it is essential for physicians to pay more attention to the possibility of the occurrence of these symptoms, especially in patients with several risk factors. Further prospective studies on a larger group of PD patients are needed to establish a full profile of Polish PD patients with ICDs.

Impulse control disorders in hyperprolactinemic patients on dopamine agonist therapy.

Dopamine agonists (DAs) represent a mainstay of therapy for hyperprolactinemia and prolactinomas. The widespread use of DAs, including bromocriptine, cabergoline and (in some countries) quinagolide, has led to the emergence and recognition of impulse control disorders (ICDs) that may occur in association with DA therapy.Such ICDs include pathological gambling, compulsive shopping, hypersexuality and punding (the performance of repetitive tasks), among others. These manifestations can lead to substantial harms to patients and their families, if left undiagnosed and untreated. Several risk factors that may increase the risk of ICDs have been proposed, including younger age, male gender, smoking and alcohol use and history of depression.The diagnosis of ICDs in hyperprolactinemic patients treated with DAs requires a high index of suspicion and a systematic approach, using available screening questionnaires. However, it should be noted that available test instruments, including questionnaires and computerized tasks, have not been validated specifically in hyperprolactinemic patients. Hyperprolactinemic patients who develop ICDs should be withdrawn from DA therapy or, at a minimum, undergo a DA dose reduction, and considered for psychiatric consultation and cognitive behavioral therapy. However, the role of psychopharmacotherapy in hyperprolactinemic patients with ICDs remains incompletely characterized.Patient counseling regarding the risk of ICDs occurring in association with DA therapy, early detection and prompt intervention may mitigate potential harms associated with ICDs. Additional studies are needed to fully characterize risk factors, underlying mechanisms and identify effective therapies for ICDs in patients with hyperprolactinemia receiving DAs.

Long-term efficacy of bilateral subthalamic deep brain stimulation in the parkinsonism of SCA 3: A rare case report.

BACKGROUND AND PURPOSE: Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant inherited disorder that manifests as a mixture of cerebellar ataxia, parkinsonism, and polyneuropathy; in type IV SCA3, pure parkinsonism is the only symptom. Currently, no disease-modifying treatment is available, but variable responses to antiparkinsonism agents have been reported. However, the benefits of deep brain stimulation (DBS) for treating parkinsonism in this subtype of SCA3 remain unclear. METHODS: A 39-year-old male patient with a rare disorder of type IV SCA3 presented with pure parkinsonism including unilateral resting tremor, rigidity, and bradykinesia at the age of 30 years. Young-onset Parkinson disease was diagnosed at the age of 32 years. His family history revealed a mild ataxia in his father since the age of 55 years. Genetic testing confirmed an expanded CAG repeated number, with 66 in this case and 63 in his father for SCA3 mutation. Excellent response to levodopa and dopamine agonists in the first 3 years was noted, but wearing-off phenomena, levodopa-induced dyskinesia, and severe impulse control disorders later developed. To alleviate drug-induced complications, he received bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in the absence of cerebellar signs, depression, and cognitive impairment. RESULTS: As of 2019, no impulsive control disorders, motor fluctuations, or DBS-related complications were observed during a 4-year follow-up, with 66% Unified Parkinson's Disease Rating Scale Part III reduction at medication OFF state noted, whereas levodopa equivalent daily dosage decreased by almost half. CONCLUSIONS: STN-DBS may be considered as adjunct treatment for severe dopa-related motor/nonmotor complications in patients with parkinsonian phenotype of SCA 3.

Bidirectional Correlations Between Dopaminergic Function and Motivation in Parkinson's Disease.

OBJECTIVE: To test the hypothesis that striatal dopamine function influences motivational alterations in Parkinson disease (PD), we compared vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DaT) imaging data in PD patients with impulse control disorders (ICDs), apathy, or neither. METHODS: We extracted striatal binding ratios (SBR) from VMAT2 PET imaging (18F-AV133) and DaTscans from the Parkinson's Progression Markers Initiative (PPMI) multicenter observational study. Apathy and ICDs were assessed using the Movement Disorders Society-revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP), respectively. We used analysis of variance (ANOVA) and log-linear mixed-effects (LME) regression to model SBRs with neurobehavioral metrics. RESULTS: Among 23 participants (mean age 62.7 years, mean disease duration 1.8 years) with VMAT2 imaging data, 5 had apathy, 5 had an ICD, and 13 had neither. ANOVA indicated strong groupwise differences in VMAT2 binding in right anterior putamen [F(2,20) = 16.2, p < 0.0001), right posterior putamen [F(2,20) = 16.9, p < 0.0001), and right caudate [F(2,20) = 6.8, p = 0.006)]. Post-hoc tests and repeated-measures analysis with LME regression also supported right striatal VMAT2 elevation in the ICD group and reduction in the apathy group relative to the group with neither ICD nor apathy. DaT did not exhibit similar correlations, but normalizing VMAT2 with DaT SBR strengthened bidirectional correlations with ICD (high VMAT2/DaT) and apathy (low VMAT2/DaT) in all striatal regions bilaterally. CONCLUSIONS: Our findings constitute preliminary evidence that striatal presynaptic dopaminergic function helps describe the neurobiological basis of motivational dysregulation in PD, from high in ICDs to low in apathy.

The side effects of dopamine receptor agonist drugs in Chinese prolactinoma patients: a cross sectional study.

BACKGROUND: Recently, side effects from Dopamine Receptor Agonist Drugs (DAs) in treating pituitary prolactinoma have raised widespread concern. This study explores the incidence and influencing factors of DAs-related side effects in Chinese prolactinoma patients. METHODS: A cross-sectional study was conducted. 51 prolactinoma patients treated with DAs, 12 prolactinoma or pituitary microadenoma patients without DAs treatment, and 33 healthy controls were included. The Barratt impulsivity scale-11, Patient Health Questionnaire 9, and the ICD screening questionnaire were all used to evaluate the psychological and physical side effects of DAs. Clinical data of all subjects were collected from their electronic medical records. RESULTS: The incidence of ICDs in the treated group, the untreated group, and control group was 9.8% (5/51), 16.7% (2/12), and 9.1% (3/33), respectively. In the treated group in particular, there were 1 patient (2%, 1/51), 2 patients (3.9%, 2/51), and 2 patients (3.9%, 2/51) with positive screening for punding, compulsive shopping, and hypersexuality, respectively. In terms of depression, the incidence of "minimal", "mild" and "moderate" depression in the treated group was 62.8% (32/51), 25.5% (13/51), and 5.9% (3/51), respectively. The incidence of physical symptoms was 51.0% (26/51) in the treated group and gastrointestinal symptoms were the most common symptoms (33.3%, 17/51). In addition, we found that the various parameters of DAs treatment had no association with the occurrence of physical symptoms or ICDs (all P > 0.05). CONCLUSIONS: Chinese prolactinoma patients treated with DAs had a lower incidence of ICDs (9.8%), while gastrointestinal symptoms were common. In this way, more attention should be paid to side effects, especially physical symptoms, in Chinese prolactinoma patients with DAs therapy during follow-up regardless of dose.

Network analysis of impulse dyscontrol in mild cognitive impairment and subjective cognitive decline.

OBJECTIVES: To investigate conditional dependence relationships of impulse dyscontrol symptoms in mild cognitive impairment (MCI) and subjective cognitive decline (SCD). DESIGN: A prospective, observational study. PARTICIPANTS: Two hundred and thirty-five patients with MCI (n = 159) or SCD (n = 76) from the Prospective Study for Persons with Memory Symptoms dataset. MEASUREMENTS: Items of the Mild Behavioral Impairment Checklist impulse dyscontrol subscale. RESULTS: Stubbornness/rigidity, agitation/aggressiveness, and argumentativeness were frequent and the most central symptoms in the network. Impulsivity, the fourth most central symptom in the network, served as the bridge between these common symptoms and less central and rare symptoms. CONCLUSIONS: Impulse dyscontrol in at-risk states for dementia is characterized by closely connected symptoms of irritability, agitation, and rigidity. Compulsions and difficulties in regulating rewarding behaviors are relatively isolated symptoms.

The urge to move: From restless legs syndrome to impulse control disorders in Parkinson's disease.

Impulse control disorders (ICDs) in Parkinson's disease (PD) are defined as a failure to resist an "urge" to behave in a way that may be debilitating for oneself or others. The suggested immobilization test (SIT) has been developed to assess the "urge" to move and support the diagnosis of restless legs syndrome (RLS) in the general population and in PD. A clinical association between RLS and ICDs has been shown in PD and in the general population. We hypothesized that there could be a semiological overlap between RLS and ICDs, and conducted SIT in PD patients with and without ICDs. Fifty PD patients with (n = 17) and without (n = 33) current ICDs were included. SIT, videopolysomnography, demographical treatment, and motor, psycho-behavioural and sleep characteristics, including RLS, were recorded. PD patients with ICDs reported increased subjective discomfort during SIT (SD-SIT) compared to those without ICDs (p = .024). Multivariable analysis confirmed ICDs as an independent factor associated with increased SD-SIT in PD, regardless of the presence of RLS, PD severity and dopamine agonist treatment dose. The discomfort measured by SIT might not only reflect the "urge" to move in RLS but also the ICDs in PD, suggesting that ICDs and RLS in PD could share a common phenomenology.

Integrating genetic and clinical data to predict impulse control disorders in Parkinson's disease.

BACKGROUND AND PURPOSE: Impulse control disorders (ICDs) are frequent in Parkinson's disease (PD), with associated clinical and genetic risk factors. This study was aimed at analyzing the clinical features and the genetic background that underlie ICDs in PD. METHODS: We included 353 patients with PD in this study (58.9% men, mean age 62.4 ± 10.58 years, mean age at disease onset 52.71 ± 11.94 years). We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease for ICDs screening. Motor, nonmotor, and treatment-related features were evaluated according to the presence of ICDs. Twenty-one variants related to dopaminergic, serotonergic, glutamatergic, and opioid neurotransmitter systems were assessed. Association studies between polymorphisms and ICDs were performed. The combination of clinical and genetic variables was analyzed with receiver operating characteristic curves to assess the predictability of experiencing ICDs. RESULTS: Impulse control disorders appeared in 25.1% of the cases. Patients with ICDs were younger and presented a higher rate of anxiety. Treatment with dopamine agonists increased the risk of ICDs and it was dose dependent (P < 0.05). Genetic association studies showed that the DOPA decarboxylase gene (DDC), rs1451375, might modulate the risk of ICDs. Plotting the clinical-genetic model, the predictability of ICDs increased 11% (area under curve = 0.80; z = 3.22, P = 0.001) when adding the genotype data for single nucleotide polymorphisms. CONCLUSIONS: Polymorphisms in DDC might act as risk markers for ICDs in PD. The predictability of experiencing ICDs increased by adding genetic factors to clinical features. It is therefore important to assess the patient's genetic background to identify individuals at risk for ICDs.