Measuring Heart Rate Accurately in Patients With Parkinson Disease During Intense Exercise: Usability Study of Fitbit Charge 4.

Background: Parkinson disease (PD) is the second most common neurodegenerative disease, affecting approximately 1% of the world's population. Increasing evidence suggests that aerobic physical exercise can be beneficial in mitigating both motor and nonmotor symptoms of the disease. In a recent pilot study of the role of exercise on PD, we sought to confirm exercise intensity by monitoring heart rate (HR).

Intense exercise increases dopamine transporter and neuromelanin concentrations in the substantia nigra in Parkinson's disease.

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons. Exercise has been reported to slow the clinical progression of PD. We evaluated the dopaminergic system of patients with mild and early PD before and after a six-month program of intense exercise.

SLIC-Occ: functional segmentation of occupancy images improves precision of EC images.

Background: Drug occupancy studies with positron emission tomography imaging are used routinely in early phase drug development trials. Recently, our group introduced the Lassen Plot Filter, an extended version of the standard Lassen plot to estimate voxel-level occupancy images. Occupancy images can be used to create an EC image by applying an E model at each voxel.

Clustering of KOR PET images separates people with AUD into distinct responses to naltrexone.

Striatal kappa opioid receptor (KOR) availability in 48 subjects with Alcohol Use Disorder (AUD) was previously found to be associated with degree of drinking following a week of naltrexone treatment (de Laat et al. Biological Psychiatry, 86(11), 864-871, 2019). The purpose of the current study was to determine if spectral clustering applied to previously acquired KOR images (with [11C]LY2795050 PET) could identify meaningful groupings of different responses to naltrexone and to assess the robustness of the finding.

Differences in the association between kappa opioid receptors and pain among Black and White adults with alcohol use disorders.

Background: The relationship between alcohol and pain is complex. Associations between pain and alcohol use disorder (AUD) vary by race, but the underlying biological basis is not understood. We examined the association of the kappa opioid receptor (KOR) with responses to the cold-pressor test (CPT), before and after treatment with the opioid antagonist naltrexone, among individuals with AUD who self-identified as Black or White.

EC images, a novel endpoint from PET target occupancy studies, reveal spatial variation in apparent drug affinity.

Purpose: We recently introduced voxel-level images of drug occupancy from PET via our "Lassen plot filter." Occupancy images revealed clear dependence of C-flumazenil displacement on dose of GABAa inhibitor, CVL-865, but with different scales in different brain regions. We hypothesized that regions requiring higher drug concentrations to achieve desired occupancy would have higher EC values.

Effects of chronic voluntary alcohol consumption on PDE10A availability: a longitudinal behavioral and [F]JNJ42259152 PET study in rats.

Purpose: Phosphodiesterase 10A (PDE10A) is a dual substrate enzyme highly enriched in dopamine-receptive striatal medium spiny neurons, which are involved in psychiatric disorders such as alcohol use disorders (AUD). Although preclinical studies suggest a correlation of PDE10A mRNA expression in neuronal and behavioral responses to alcohol intake, little is known about the effects of alcohol exposure on in vivo PDE10A activity in relation to apparent risk factors for AUD such as decision-making and anxiety.

Methods: We performed a longitudinal [F]JNJ42259152 microPET study to evaluate PDE10A changes over a 9-week intermittent access to alcohol model, including 6 weeks of alcohol exposure, 2 weeks of abstinence followed by 1 week relapse.

A local-neighborhood Lassen plot filter for creating occupancy and non-displaceable binding images.

For radioligands without a reference region, the Lassen plot can be used to estimate receptor occupancy by an exogenous drug (). However, the Lassen plot is not well-suited for spatial variation in . To overcome this limitation, we introduce a Lassen plot filter, i.

Occupancy of the kappa opioid receptor by naltrexone predicts reduction in drinking and craving.

The efficacy of naltrexone to treat alcohol use disorder (AUD) is modest. A better understanding of the neurobiology underlying naltrexone effects could optimize treatments. We evaluated the occupancy of the kappa opioid receptor (KOR) by naltrexone measured with [C]-LY2795050 positron emission tomography (PET) as a predictor of response to naltrexone.

Recovery of Decreased Metabotropic Glutamate Receptor 5 Availability in Abstinent Alcohol-Dependent Patients.

Animal models of alcohol dependence and relapse demonstrate an important role of the glutamatergic system, in particular, cerebral metabotropic glutamate receptor 5 (mGluR5). F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile (F-FPEB) PET has revealed that chronic alcohol use leads to decreased limbic mGluR5 availability, which was associated with less craving. Here, we tested whether the state of decreased mGluR5 availability in alcohol-dependent patients normalizes during abstinence (at 2 and 6 mo of detoxification) and whether initial mGluR5 imaging parameters can predict individual relapse.

The Kappa Opioid Receptor Is Associated With Naltrexone-Induced Reduction of Drinking and Craving.

Background: Naltrexone is a nonselective opioid receptor antagonist used as a treatment for alcohol use disorder. However, only modest clinical effects have been observed, possibly because of limited knowledge about the biological variables affecting the efficacy of naltrexone. We investigated the potential role of the kappa opioid receptor (KOR) in the therapeutic effect of naltrexone.

PET imaging reveals lower kappa opioid receptor availability in alcoholics but no effect of age.

Opioid receptors are implicated in alcoholism, other addictions, withdrawal, and depression, and are considered potential pharmacological targets for treatment. Our goal in the present study was to compare the availability of kappa opioid receptors (KOR) between an alcohol-dependent cohort (AD) and a healthy control cohort (HC). Sixty-four participants-36 AD and 28 HC-underwent PET scans with [C]LY2795050, a selective kappa antagonist tracer.

Effects of alcohol exposure on the glutamatergic system: a combined longitudinal F-FPEB and H-MRS study in rats.

In a longitudinal rat model of alcohol consumption, we showed that exposure to alcohol decreased the concentration of glutamate in the prefrontal cortex, whereas a normalization occurred during abstinence. 18F-FPEB PET scans revealed that pre-exposure mGluR5 availability in the nucleus accumbens was associated with future alcohol preference. Finally, alcohol exposure induced a decrease in mGluR5 availability in the bilateral hippocampus and amygdala compared with baseline, and in the hippocampus and striatum compared with saccharin (Figure).

Glutamatergic Biomarkers for Cocaine Addiction: A Longitudinal Study Using MR Spectroscopy and mGluR5 PET in Self-Administering Rats.

Cocaine addiction is a disorder that still lacks diagnostic biomarkers or effective pharmacotherapy. We present findings on a rat model of cocaine self-administration that was followed up longitudinally using the metabotropic glutamate receptor type 5 (mGluR5) tracer F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile (F-FPEB) PET, proton MR spectroscopy (H-MRS), and behavioral tests. Forty-two Wistar rats were scanned with F-FPEB PET and H-MRS before and after sucrose or intravenous cocaine self-administration, during withdrawal, and during relapse.

Lower Limbic Metabotropic Glutamate Receptor 5 Availability in Alcohol Dependence.

Animal studies suggest an important role for the metabotropic glutamate receptor subtype 5 (mGlu5) in the pathophysiology of alcohol dependence, but direct human evidence is lacking. The goal of this study was to investigate cerebral mGlu5 availability in alcohol-dependent subjects versus controls using F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile (F-FPEB) PET. Dynamic 90-min F-FPEB scans combined with arterial blood sampling were acquired for 16 recently abstinent alcohol-dependent subjects and 32 age-matched controls.

Cerebral dopaminergic and glutamatergic transmission relate to different subjective responses of acute alcohol intake: an in vivo multimodal imaging study.

Converging preclinical evidence links extrastriatal dopamine release and glutamatergic transmission via the metabotropic glutamate receptor 5 (mGluR5) to the rewarding properties of alcohol. To date, human evidence is lacking on how and where in the brain these processes occur. Mesocorticolimbic dopamine release upon intravenous alcohol administration and mGluR5 availability were measured in 11 moderate social drinkers by single-session [ F]fallypride and [ F]FPEB positron emission tomography, respectively.

The effect of isoflurane on F-FDG uptake in the rat brain: a fully conscious dynamic PET study using motion compensation.

Background: In preclinical positron emission tomography (PET) studies an anaesthetic is used to ensure that the animal does not move during the scan. However, anaesthesia may have confounding effects on the drug or tracer kinetics under study, and the nature of these effects is usually not known.

Method: We have implemented a protocol for tracking the rigid motion of the head of a fully conscious rat during a PET scan and performing a motion compensated list-mode reconstruction of the data.

Positive Association Between Limbic Metabotropic Glutamate Receptor 5 Availability and Novelty-Seeking Temperament in Humans: An 18F-FPEB PET Study.

Unlabelled: Heritable temperament traits have been linked to several neuropsychiatric illnesses, including disorders associated with metabotropic glutamate receptor 5 (mGluR5) and dopaminergic dysfunctions. Considering its modulating effect on neurotransmission, we hypothesized that cerebral mGluR5 availability is associated with temperament traits in healthy humans.

Methods: Forty-four nonsmoking healthy volunteers (mean age ± SD, 40 ± 14 y; age range, 22-66 y; 22 women) were included in this cross-sectional investigation.

Optimising rigid motion compensation for small animal brain PET imaging.

Motion compensation (MC) in PET brain imaging of awake small animals is attracting increased attention in preclinical studies since it avoids the confounding effects of anaesthesia and enables behavioural tests during the scan. A popular MC technique is to use multiple external cameras to track the motion of the animal's head, which is assumed to be represented by the motion of a marker attached to its forehead. In this study we have explored several methods to improve the experimental setup and the reconstruction procedures of this method: optimising the camera-marker separation; improving the temporal synchronisation between the motion tracker measurements and the list-mode stream; post-acquisition smoothing and interpolation of the motion data; and list-mode reconstruction with appropriately selected subsets.

Kinetic modeling and long-term test-retest reproducibility of the mGluR5 PET tracer 18F-FPEB in human brain.

(18)F-FPEB is a promising PET tracer for studying the metabotropic glutamate subtype 5 receptor (mGluR5) expression in neuropsychiatric disorders. To assess the potential of (18)F-FPEB for longitudinal mGluR5 evaluation in patient studies, we evaluated the long-term test-retest reproducibility using various kinetic models in the human brain. Nine healthy volunteers underwent consecutive scans separated by a 6-month period.

Preclinical Evaluation and Quantification of 18F-FPEB as a Radioligand for PET Imaging of the Metabotropic Glutamate Receptor 5.

Unlabelled: The metabotropic glutamate receptor 5 (mGluR5) is a high-interest target for PET imaging because it plays a role in several pathologies, including addiction, schizophrenia, and fragile X syndrome.

Methods: We studied the pharmacokinetics of (18)F-FPEB (3-(18)F-fluoro-5-(2-pyridinylethynyl)benzonitrile), a selective PET radioligand for mGluR5, and used it to quantify mGluR5 in rat brain. Quantification was performed using both arterial sampling in combination with compartment models and simplified reference methods.

Quantification of TSPO overexpression in a rat model of local neuroinflammation induced by intracerebral injection of LPS by the use of [(18)F]DPA-714 PET.

Purpose: [(18)F]DPA-714 is a radiotracer with high affinity for TSPO. We have characterized the kinetics of [(18)F]DPA-714 in rat brain and evaluated its ability to quantify TSPO expression with PET using a neuroinflammation model induced by unilateral intracerebral injection of lipopolysaccharide (LPS).

Methods: Dynamic small-animal PET scans with [(18)F]DPA-714 were performed in Wistar rats on a FOCUS-220 system for up to 3 h.