An increasing amount of research has suggested that Internet addiction is associated with abnormalities in the dopaminergic brain system. We hypothesized that Internet addiction would be associated with reduced levels of dopaminergic receptor availability in the striatum compared with controls. To test this hypothesis, a radiolabeled ligand [¹¹C]raclopride and positron emission tomography was used to assess dopamine D2 receptor binding potential in men with and without Internet addiction. Consistent with our prediction, individuals with Internet addiction showed reduced levels of dopamine D2 receptor availability in subdivisions of the striatum including the bilateral dorsal caudate and right putamen. This finding contributes to the understanding of neurobiological mechanism of Internet addiction.

Introduction: Internet game overuse is an emerging disorder and features diminished impulse control and poor reward-processing. In an attempt to understand the neurobiological bases of Internet game overuse, we investigated the differences in regional cerebral glucose metabolism at resting state between young individuals with Internet game overuse and those with normal use using ¹⁸F-fluorodeoxyglucose positron emission tomography study.Methods: Twenty right-handed male participants (9 normal users: 24.7±2.4 years of age, 11 overusers: 23.5±2.9 years of age) participated. A trait measure of impulsivity was also completed after scanning.Results: Internet game overusers showed greater impulsiveness than the normal users and there was a positive correlation between the severity of Internet game overuse and impulsiveness. Imaging data showed that the overusers had increased glucose metabolism in the right middle orbitofrontal gyrus, left caudate nucleus, and right insula, and decreased metabolism in the bilateral postcentral gyrus, left precentrai gyrus, and bilateral occipital regions compared to normal users.Conclusion: Internet game overuse may be associated with abnormal neurobiological mechanisms in the orbitofrontal cortex, striatum, and sensory regions, which are implicated in impulse control, reward processing, and somatic representation of previous experiences. Our results support the idea that Internet game overuse shares psychological and neural mechanisms with other types of impulse control disorders and substance/non-substance-related addiction.

For the successful clinical advancement of exosome therapeutics, the biodistribution and pharmacokinetic profile of exogenous exosomes in various animal models must be determined. Compared with fluorescence or bioluminescence imaging, radionuclide imaging confers multiple advantages for the in vivo tracking of biomolecular therapeutics because of its excellent sensitivity for deep tissue imaging and potential for quantitative measurement. Herein, we assessed the quantitative biodistribution and pharmacokinetics of good manufacturing practice-grade therapeutic exosomes labeled with zirconium-89 (⁸⁹Zr) after systemic intravenous administration in mice and rats. Quantitative biodistribution analysis by positron emission tomography/computed tomography and gamma counting in mice and rats revealed that the total ⁸⁹Zr signals in the organs were lower in rats than in mice, suggesting a higher excretion rate of exosomes in rats. A prolonged ⁸⁹Zr signal for up to 7 days in most organs indicated that substantial amounts of exosomes were taken up by the parenchymal cells in those organs, highlighting the therapeutic potential of exosomes for the intracellular delivery of therapeutics. Exosomes were mainly distributed in the liver and to a lesser extent in the spleen, while a moderately distributed in the kidney, lung, stomach, intestine, urinary bladder, brain, and heart. Exosomes were rapidly cleared from the blood circulation, with a rate greater than that of free ⁸⁹Zr, indicating that exosomes might be rapidly taken up by cells and tissues.

Repetitive traumatic brain injury (rTBI) occurs as a result of mild and accumulative brain damage. A prototype of rTBI is chronic traumatic encephalopathy (CTE), which is a degenerative disease that occurs in patients with histories of multiple concussions or head injuries. Boxers have been the most commonly studied patient group because they may experience thousands of subconcussive hits over the course of a career. This study examined the consequences of rTBI with structural brain imaging and biomolecular imaging and investigated whether the neuropsychological features of rTBI were related to the findings of the imaging studies. Five retired professional boxers (mean age, 46.8 ± 3.19 years) and four age-matched controls (mean age, 48.5 ± 3.32 years) were studied. Cognitive-motor related functional impairment was assessed, and all subjects underwent neuropsychological evaluation and behavioral tasks, as well as structural brain imaging and functional-molecular imaging. In neuropsychological tests, boxers showed deficits in delayed retrieval of visuospatial memory and motor coordination, which had a meaningful relationship with biomolecular imaging results indicative of neuronal injury. Morphometric abnormalities were not found in professional boxers by structural magnetic resonance imaging (MRI). Glucose metabolism was impaired in frontal areas associated with cognitive dysfunction, similar to findings in Alzheimer's disease. Low binding potential (BP) of ¹⁸F-flumazenil (FMZ) was found in the angular gyrus and temporal cortical regions, revealing neuronal deficits. These results suggested that cognitive impairment and motor dysfunction reflect chronic damage to neurons in professional boxers with rTBI.