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. Using 18F-FE-PE2I PET imaging, we measured dopamine transporter (DAT) availability in the striatum and substantia nigra. Using NM-MRI, we evaluated the neuromelanin content in the substantia nigra. Exercise reversed the expected decrease in DAT availability into a significant increase in both the substantia nigra and putamen. Exercise also reversed the expected decrease in neuromelanin concentration in the substantia nigra into a significant increase. These findings suggest improved functionality in the remaining dopaminergic neurons after exercise. Further research is needed to validate our findings and to pinpoint the source of any true neuromodulatory and neuroprotective effects of exercise in PD in large clinical trials.

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). For this purpose, we asked participants to wear a chest strap HR monitor (Polar Electro Oy) and the Fitbit Charge 4 (Fitbit Inc) wrist-worn HR monitor as a potential proxy due to its convenience. Polar H10 has been shown to provide highly accurate R-R interval measurements. Therefore, we treated it as the gold standard in this study. It has been shown that Fitbit Charge 4 has comparable accuracy to Polar H10 in healthy participants. It has yet to be determined if the Fitbit is as accurate as Polar H10 in patients with PD during rest and exercise. OBJECTIVE: This study aimed to compare Fitbit Charge 4 to Polar H10 for monitoring HR in patients with PD at rest and during an intensive exercise program. METHODS: A total of 596 exercise sessions from 11 (6 male and 5 female) participants were collected simultaneously with both devices. Patients with early-stage PD (Hoehn and Yahr ≤2) were enrolled in a 6-month exercise program designed for patients with PD. They participated in 3 one-hour exercise sessions per week. They wore both Fitbit and Polar H10 during each session. Sessions included rest, warm-up, intense exercise, and cool-down periods. We calculated the bias in the HR of the Fitbit Charge 4 at rest (5 min) and during intense exercise (20 min) by comparing the mean HR during each of the periods to the respective means measured by Polar H10 (HRFitbit - HRPolar). We also measured the sensitivity and specificity of Fitbit Charge 4 to detect average HRs that exceed the threshold for intensive exercise, defined as 70% of an individual's theoretical maximum HR. Different types of correlations between the 2 devices were investigated. RESULTS: The mean bias was 1.68 beats per minute (bpm) at rest and 6.29 bpm during high-intensity exercise, with an overestimation by Fitbit Charge 4 in both conditions. The mean bias of the Fitbit across both rest and intensive exercise periods was 3.98 bpm. The device's sensitivity in identifying high-intensity exercise sessions was 97.14%. The correlation between the 2 devices was nonlinear, suggesting Fitbit's tendency to saturate at high values of HR. CONCLUSIONS: The performance of Fitbit Charge 4 is comparable to Polar H10 for assessing exercise intensity in a cohort of patients with PD (mean bias 3.98 bpm). The device could be considered a reasonable surrogate for more cumbersome chest-worn devices in future studies of clinical cohorts.

Systemic inflammation enhances stimulant-induced striatal dopamine elevation in tobacco smokers.

Immune-brain interactions influence the pathophysiology of addiction. Lipopolysaccharide (LPS)-induced systemic inflammation produces effects on reward-related brain regions and the dopamine system. We previously showed that LPS amplifies dopamine elevation induced by methylphenidate (MP), compared to placebo (PBO), in eight healthy controls. However, the effects of LPS on the dopamine system of tobacco smokers have not been explored. The goal of Study 1 was to replicate previous findings in an independent cohort of tobacco smokers. The goal of Study 2 was to combine tobacco smokers with the aforementioned eight healthy controls to examine the effect of LPS on dopamine elevation in a heterogenous sample for power and effect size determination. Eight smokers were each scanned with [11C]raclopride positron emission tomography three times-at baseline, after administration of LPS (0.8 ng/kg, intravenously) and MP (40 mg, orally), and after administration of PBO and MP, in a double-blind, randomized order. Dopamine elevation was quantified as change in [11C]raclopride binding potential (ΔBPND) from baseline. A repeated-measures ANOVA was conducted to compare LPS and PBO conditions. Smokers and healthy controls were well-matched for demographics, drug dosing, and scanning parameters. In Study 1, MP-induced striatal dopamine elevation was significantly higher following LPS than PBO (p = 0.025, 18 ± 2.9 % vs 13 ± 2.7 %) for smokers. In Study 2, MP-induced striatal dopamine elevation was also significantly higher under LPS than under PBO (p < 0.001, 18 ± 1.6 % vs 11 ± 1.5 %) in the combined sample. Smoking status did not interact with the effect of condition. This is the first study to translate the phenomenon of amplified dopamine elevation after experimental activation of the immune system to an addicted sample which may have implications for drug reinforcement, seeking, and treatment.

Harmonization of [11C]raclopride brain PET images from the HR+ and HRRT: method development and validation in human subjects.

BACKGROUND: There has been an ongoing need to compare and combine the results of new PET imaging studies conducted with [11C]raclopride with older data. This typically means harmonizing data across different scanners. Previous harmonization studies have utilized either phantoms or human subjects, but the use of both phantoms and humans in one harmonization study is not common. The purpose herein was (1) to use phantom images to develop an inter-scanner harmonization technique and (2) to test the harmonization technique in human subjects. METHODS: To develop the harmonization technique (Experiment 1), the Iida brain phantom was filled with F-18 solution and scanned on the two scanners in question (HRRT, HR+, Siemens/CTI). Phantom images were used to determine the optimal isotropic Gaussian filter to harmonize HRRT and HR+ images. To evaluate the harmonization on human images (Experiment 2), inter-scanner variability was calculated using [11C]raclopride scans of 3 human subjects on both the HRRT and HR+ using percent difference (PD) in striatal non-displaceable binding potential (BPND) between HR+ and HRRT (with and without Gaussian smoothing). Finally, (Experiment 3), PDT/RT was calculated for test-retest (T/RT) variability of striatal BPND for 8 human subjects scanned twice on the HR+. RESULTS: Experiment 1 identified the optimal filter as a Gaussian with a 4.5 mm FWHM. Experiment 2 resulted in 13.9% PD for unfiltered HRRT and 3.71% for HRRT filtered with 4.5 mm. Experiment 3 yielded 5.24% PDT/RT for HR+. CONCLUSIONS: The PD results show that the variability of harmonized HRRT is less than the T/RT variability of the HR+. The harmonization technique makes it possible for BPND estimates from the HRRT to be compared to (and/or combined with) those from the HR+ without adding to overall variability. Our approach is applicable to all pairs of scanners still in service.

Chronic pain precedes disrupted eating behavior in low-back pain patients.

Chronic pain is associated with anhedonia and decreased motivation. These behavioral alterations have been linked to alterations in the limbic brain and could explain the increased risk for obesity in pain patients. The mechanism of these behavioral changes and how they set in in relation to the development of chronic pain remain however poorly understood. Here we asked how eating behavior was affected in low-back pain patients before and after they transitioned to chronic pain, compared to patients whose pain subsided. Additionally, we assessed how the hedonic perception of fat-rich food, which is altered in chronic pain patients, related to the properties of the nucleus accumbens in this patients' population. We hypothesized that the accumbens would be directly implicated in the hedonic processing of fat-rich food in pain patients because of its well-established role in hedonic feeding and fat ingestion, and its emerging role in chronic pain. Accordingly, we used behavioral assays and structural brain imaging to test sub-acute back pain patients (SBP) and healthy control subjects at baseline and at approximately one-year follow-up. We also studied a sample of chronic low-back pain patients (CLBP) at one time point only. We found that SBP patients who recovered at follow-up (SBPr) and CLBP patients showed disrupted eating behaviors. In contrast, SBP patients who persisted in having pain at follow-up (SBPp) showed intact eating behavior. From a neurological standpoint, only SBPp and CLBP patients showed a strong and direct relationship between hedonic perception of fat-rich food and nucleus accumbens volume. This suggests that accumbens alterations observed in SBPp patients in previous works might protect them from hedonic eating disruptions during the early course of the illness. We conclude that disrupted eating behavior specifically sets in after pain chronification and is accompanied by structural changes in the nucleus accumbens.