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The stop-signal task is a well-established assessment of response inhibition, and in humans, proficiency is linked to dorsal striatum D2receptor availability. Parkinson's disease (PD) is characterized by changes to efficiency of response inhibition. Here, we studied 17 PD patients (6 female and 11 male) using the stop-signal paradigm in a single-blindedd-amphetamine (dAMPH) study. Participants completed [18F]fallypride positron emission topography (PET) imaging in both placebo and dAMPH conditions. A voxel-wise analysis of the relationship between binding potential (BPND) and stop-signal reaction time (SSRT) revealed that faster SSRT is associated with greater D2-like BPNDin the amygdala and hippocampus (right clusterqFDR-corr= 0.026, left clusterqFDR-corr= 0.002). A region of interest (ROI) examination confirmed this association in both the amygdala (coefficient = −48.26,p= 0.005) and hippocampus (coefficient = −104.94,p= 0.007). As healthy dopaminergic systems in the dorsal striatum appear to regulate response inhibition, we interpret our findings in PD to indicate either nigrostriatal damage unmasking a mesolimbic contribution to response inhibition, or a compensatory adaptation from the limbic and mesial temporal dopamine systems. These novel results expand the conceptualization of action-control networks, whereby limbic and motor loops may be functionally connected.SIGNIFICANCE STATEMENTWhile Parkinson's disease (PD) is characteristically recognized for its motor symptoms, some patients develop impulsive and compulsive behaviors (ICBs), manifested as repetitive and excessive participation in reward-driven activities, including sex, gambling, shopping, eating, and hobbyism. Such cognitive alterations compel a consideration of response inhibition in PD. To investigate inhibitory control and assess the brain regions that may participate, we assessed PD patients using a single-blindedd-amphetamine (dAMPH) study, with [18F]fallypride positron emission topography (PET) imaging, and stop-signal task performance. We find a negative relationship between D2-like binding in the mesial temporal region and top-signal reaction time (SSRT), with greater BPNDassociated with a faster SSRT. These discoveries indicate a novel role for mesolimbic dopamine in response inhibition, and advocate for limbic regulation of action control in this clinical population.

Impulsivity is inherent to behavioral disorders such as substance abuse and binge eating. While the role of dopamine in impulse behavior is well established, γ-aminobutyric acid (GABA) therapies have promise for the treatment of maladaptive behaviors. In Parkinson disease (PD), dopaminergic therapies can result in the development of impulsive and compulsive behaviors, and this clinical syndrome shares similar pathophysiology to that seen in addiction, substance abuse, and binge-eating disorders. We hypothesized that impulsive PD patients have a reduced thalamic GABAergic response to dopamine therapy. To test this hypothesis, we employed GABA magnetic resonance spectroscopy, D2-like receptor PET imaging, and clinical and quantitative measures of impulsivity in PD patients (n = 33), before and after dopamine agonist administration. We find a blunted thalamic GABA response to dopamine agonists in patients with elevated impulsivity (p = 0.027). These results emphasize how dopamine treatment differentially augments thalamic GABA concentrations, which may modify behavioral impulsivity.

Highlights • Photophobia is a common, disabling symptom observed in patients with Progressive Supranuclear Palsy (PSP). • We assessed the functional impacts of photophobia in PSP, and find that bright light is painful. • Symptoms limit participation in activities of daily living, reducing time spent outside the house., Objective To determine the impact of photophobia on persons with Progressive Supranuclear Palsy (pwPSP) by determining the functional impact of light sensitivity using methods established in migraine research. Methods All 60 participants (pwPSP = 15, persons with Parkinson Disease (pwPD) = 15, Older adults = 30) completed a series of questionnaires designed to assess the impact of photophobia on activities of daily living. Group comparisons were controlled for multiple comparisons using a false discovery rate of 0.05. Results Most (14/15) pwPSP participants noted that bright light hurt their eyes, and this proportion was significantly greater than pwPD (6/15; p = 0.03, corrected). PSP participants reported statistically significantly more severe light sensitivity on a subjective 0–100 scale (p = 0.003, corrected), and noted reduced time spent in both indoor and outdoor activities. Some PSP participants (n = 3) noted that they needed to wear sunglasses indoors, but most noted a reluctance to leave their house during the day due to photophobia. PwPSP indicated that they require more help from others to complete daily tasks that require them to be outside during daylight hours. Conclusions Overall, we note a significant debility due to photophobia in PSP, and this impacts outdoor more than indoor activities. The functional disability in PSP caused by photophobia appears to cause a substantive reduction in quality of life. Future studies could consider incorporating specific metrics to evaluate measurable differences with photophobia onset and worsening severity.

The stop-signal task is a well-established assessment of response inhibition, and in humans, proficiency is linked to dorsal striatum D(2) receptor availability. Parkinson's disease (PD) is characterized by changes to efficiency of response inhibition. Here, we studied 17 PD patients (6 female and 11 male) using the stop-signal paradigm in a single-blinded d-amphetamine (dAMPH) study. Participants completed [(18)F]fallypride positron emission topography (PET) imaging in both placebo and dAMPH conditions. A voxel-wise analysis of the relationship between binding potential (BP(ND)) and stop-signal reaction time (SSRT) revealed that faster SSRT is associated with greater D(2)-like BP(ND) in the amygdala and hippocampus (right cluster q(FDR-corr) = 0.026, left cluster q(FDR-corr) = 0.002). A region of interest (ROI) examination confirmed this association in both the amygdala (coefficient = −48.26, p = 0.005) and hippocampus (coefficient = −104.94, p = 0.007). As healthy dopaminergic systems in the dorsal striatum appear to regulate response inhibition, we interpret our findings in PD to indicate either nigrostriatal damage unmasking a mesolimbic contribution to response inhibition, or a compensatory adaptation from the limbic and mesial temporal dopamine systems. These novel results expand the conceptualization of action-control networks, whereby limbic and motor loops may be functionally connected. SIGNIFICANCE STATEMENT While Parkinson's disease (PD) is characteristically recognized for its motor symptoms, some patients develop impulsive and compulsive behaviors (ICBs), manifested as repetitive and excessive participation in reward-driven activities, including sex, gambling, shopping, eating, and hobbyism. Such cognitive alterations compel a consideration of response inhibition in PD. To investigate inhibitory control and assess the brain regions that may participate, we assessed PD patients using a single-blinded d-amphetamine (dAMPH) study, with [(18)F]fallypride positron emission topography (PET) imaging, and stop-signal task performance. We find a negative relationship between D(2)-like binding in the mesial temporal region and top-signal reaction time (SSRT), with greater BP(ND) associated with a faster SSRT. These discoveries indicate a novel role for mesolimbic dopamine in response inhibition, and advocate for limbic regulation of action control in this clinical population.

INTRODUCTION: Dopamine medication withdrawal in Parkinson’s Disease is commonly employed in clinical practice and can be required for participation in research studies. When asked to withdraw from medications, participants often enquire as to what symptoms they should expect. OBJECTIVES: This study sought to improve the informed consent process by identifying patient-reported symptoms when withholding from dopamine treatment. We also sought to provide clinical guidance regarding the extent of these symptoms and consider participant willingness to undergo these assessments. METHODS: Participants were recruited from community-based PD programs and support groups in Nashville, Tennessee. A patient-based questionnaire determined the frequency and severity of motor and nonmotor symptoms. The questionnaire also assessed if patients would be willing to withhold from medication at a future date and for what purpose. RESULTS: A total of 31/90 participants reported withdrawing from dopaminergic medications for clinical or research purposes. Tremor, walking, and balance was the most common motor symptom that worsened during this time. Sleep dysfunction, constipation, and tremor were noted as the most severe symptoms. Of note, 10% of the participants indicated that they would not be willing to go off medications again, suggesting that to a minority of patients this can be most discomforting. When prompted for a reason that participants would be willing to come off of their medications again, “clinical” purposes were the most selected. CONCLUSIONS: Study teams should list these symptoms in the applications to their institutional review board and in the informed consent to provide guidance for participants.

Pure autonomic failure (PAF) results from an impaired peripheral autonomic nervous system, and clinical symptoms present with orthostatic hypotension. While the impact on cardiovascular indices of orthostatic intolerance are well-characterized, more limited information is available regarding cerebral hemodynamic dysfunction in PAF. The objective of this study was to test the hypothesis that cerebral blood flow (CBF) is reduced in PAF, and to quantify the relationship between CBF and clinical indicators of disease severity, including peripheral supine arterial blood pressure. Participants with PAF (n = 17) and age- and sex-matched normotensive healthy controls (n = 17) were examined using established clinical rating scales, cardiovascular autonomic function tests, and 3T MRI measurements of CBF. CBF-weighted images were also used to determine the prevalence of venous hyperintensities from the major dural sinuses as evidence of abnormal capillary flow. Nonparametric tests and general linear models were used to evaluate differences and correlations between study variables. Gray matter CBF was higher in PAF (51.1 ± 13.4 mL/100 g/min) compared to controls (42.9 ± 6.5 mL/100 g/min, p = 0.007). Venous hyperintensities were more prevalent in PAF relative to controls, and the presence and degree of venous hyperintensities was associated with higher mean CBF (p = 0.027). In PAF participants, CBF and supine systolic blood pressure were inversely related (Spearman’s rho = −0.545, p = 0.024). Findings suggest that PAF patients may exhibit elevated CBF and provide evidence that this condition exerts a hemodynamic impact in the central nervous system.

Background While most opioid use disorder (OUD) treatment providers consider opioid abstinence to be the preferred outcome, little is known about the treatment preferences of the larger population of individuals who engage in nonmedical opioid use and have not yet sought treatment. This study sought to descriptively quantify the proportion of out-of-treatment individuals with nonmedical opioid use that have abstinent and nonabstinent recovery goals. Methods Participants (N = 235) who engage in nonmedical opioid use and met self-reported criteria for OUD were recruited online and participated in a cross-sectional survey on recovery goals and treatment perceptions. Participants were dichotomized as having either abstinent (70.6%) or nonabstinent (29.4%) recovery goals. Participants were presented with 13 treatment options and asked which treatment they would "try first" and which treatment they thought would be the best option for long-term recovery. Results Persons in the nonabstinent group were more likely to want to continue use of prescription opioids as prescribed by a physician compared with the abstinent group (χ[1] = 9.71, P = 0.002). There were no group differences regarding preference for individual OUD treatments. The most frequently endorsed treatments that participants would "try first" were physician visits (23.4%), one-on-one counseling (18.7%), and 12-step groups (13.2%), whereas the most frequently endorsed treatments for long-term recovery were one-on-one counseling (17.4%), residential treatment (16.7%), and buprenorphine (15.3%). Conclusion Public health initiatives to engage out-of-treatment individuals should take into account recovery goals and treatment preferences to maximize treatment initiation and retention.