Amyloid Burden in Obstructive Sleep Apnea.

To test the hypothesis that excessive amyloid deposition is a biological link between obstructive sleep apnea (OSA) and Alzheimer's disease, we determined whether OSA increases cerebral amyloid burden, relative to controls, using Pittsburgh Compound B (PiB) PET imaging. The subjects were adult participants (age 50-65 years) from the Korean Genome and Epidemiology Study. Polysomnography, brain MRI including 3D images, and a detailed neuro-cognitive function test battery were done in 2011-2012. Nineteen OSA subjects (Apnea-Hypopnea Index [AHI] ≥15/h, 21.2±5.1/h; age 58.5±4.1 years; 9 male) and 19 controls (AHI 1.8±1.3/h; age 58.5±4.2 years; 9 male) underwent 60-min dynamic 11C-PiB PET. All subjects were right-handed with normal cognitive function and brain MRI. Controls were matched by age, gender, education, and APOE genotype. A voxel-wise comparison of PiB-PET images between the two groups was performed after spatial and count normalization with cerebellar gray matter as a reference. Covariates included the status of sleep duration, hypertension, diabetes, body mass index, exercise, depressive mood, smoking, and alcohol drinking. Cortical thickness on 3D MRI was also measured and compared between the two groups. The OSA group showed a higher PiB deposition in the right posterior cingulate gyrus and right temporal cortex (corrected p < 0.05). There was no area of higher uptake in the control compared with OSA. Regional differences in cortical thickness were not significant. The study suggests that OSA accelerates amyloid deposition and may contribute to the development or progression of Alzheimer's disease.

Neuropsychological, Metabolic, and GABAA Receptor Studies in Subjects with Repetitive Traumatic Brain Injury.

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 (18)F-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.

Altered regional cerebral glucose metabolism in internet game overusers: a 18F-fluorodeoxyglucose positron emission tomography study.

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 precentral 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.

Acute high-frequency rTMS of the left dorsolateral prefrontal cortex and attentional control in healthy young men.

Previous studies have shown that high-frequency repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex induces neuromodulation in prefrontal and striatal regions. We hypothesized that high-frequency rTMS over the dorsolateral prefrontal cortex would influence attentional control, which has been associated with neural activity in the same region. Seventeen healthy young men volunteered to participate in a sham-controlled rTMS study. Participants received both rTMS and sham stimulation on separate days and the Conners' continuous performance test was used to assess response inhibition and attentional vigilance. Results indicated that participants showed fewer commission errors during trials after rTMS as compared with sham stimulation, at longer interstimulus intervals (ISIs), which suggests that high-frequency rTMS may have the potential to improve response inhibition. This finding contributes to the understanding of the relationship between the dorsolateral prefrontal cortex and attentional control and suggests possible therapeutic applications for high-frequency rTMS.

Effect of nitric oxide synthase inhibitor and NMDA receptor antagonist on the development of nicotine sensitization of nucleus accumbens dopamine release: an in vivo microdialysis study.

We have previously found that the neuronal nitric oxide synthase inhibitor N-nitro-L-arginine (L-NNA) and the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 prevent behavioral sensitization to nicotine. This study aimed to investigate the effect of L-NNA and MK-801 on a neurochemical component of nicotine sensitization by evaluating the effect of the drugs on nicotine sensitization of nucleus accumbens dopamine (DA) release. Sprague-Dawley rats were pretreated with L-NNA (15 mg/kg, i.p.), MK-801 (0.3mg/kg, i.p.), or saline 30 min before injection of nicotine (0.4 mg/kg, s.c., once daily) for seven consecutive days. Twenty-four hours after the last drug injection, animals were challenged with local perfusion of 5 mM nicotine into the shell of nucleus accumbens for 60 min and DA release was monitored using in vivo microdialysis. In rats treated with repeated nicotine, acute nicotine challenge induced a greater increase of accumbal DA release than in saline-treated animals (maximal DA response=969+/-235% (mean+/-S.E.M.) of basal level versus 520+/-93%, p=0.042). Co-administration of L-NNA or MK-801 with nicotine attenuated an increase of DA release elicited by acute nicotine challenge, compared with nicotine alone (maximal DA response=293+/-58% and 445+/-90% of basal level, respectively versus 969+/-235%, p=0.004 and p=0.013, respectively). These data demonstrate that L-NNA and MK-801 block the development of nicotine sensitization of nucleus accumbens DA release, further supporting the involvement of nitric oxide and NMDA receptors in the development of behavioral sensitization to nicotine.