Biology subjects

Choi, H.-N.

Publications and source records attributed to Choi, H.-N..

2 recordsLinked to original sources

bioRxiv2023

Neural correlates of model-based behavior in internet gaming disorder and alcohol use disorder

BackgroundAn imbalance between model-based and model-free decision-making systems is a common feature in addictive disorders. However, little is known about whether similar decision-making deficits appear in internet gaming disorder (IGD). This study compared neurocognitive features associated with model-based and model-free systems in IGD and alcohol use disorder (AUD). MethodParticipants diagnosed with IGD (n=22) and AUD (n=22), and healthy controls (n=30) performed the two-stage task inside the functional magnetic resonance imaging (fMRI) scanner. We used computational modeling and hierarchical Bayesian analysis to provide a mechanistic account of their choice behavior. Then, we performed a model-based fMRI analysis and functional connectivity analysis to identify neural correlates of the decision-making processes in each group. ResultsThe computational modeling results showed similar levels of model-based behavior in the IGD and AUD groups. However, we observed distinct neural correlates of the model-based reward prediction error (RPE) between the two groups. The IGD group exhibited insula-specific activation associated with model-based RPE, while the AUD group showed prefrontal activation, particularly in the orbitofrontal cortex and superior frontal gyrus. Furthermore, individuals with IGD demonstrated hyper-connectivity between the insula and brain regions in the salience network in the context of model-based RPE. Discussion and ConclusionsThe findings suggest potential differences in the neurobiological mechanisms underlying model-based behavior in IGD and AUD, albeit shared cognitive features observed in computational modeling analysis. As the first neuroimaging study to compare IGD and AUD in terms of the model-based system, this study provides novel insights into distinct decision-making processes in IGD.

neuroscience↗

bioRxiv2023

Parkin is not required to sustain OXPHOS function in adult mammalian tissues

Loss-of-function variants in the PRKN gene encoding the ubiquitin E3 ligase PARKIN cause autosomal recessive early-onset Parkinsons disease (PD). Extensive in vitro and in vivo studies have reported that PARKIN is involved in multiple pathways of mitochondrial quality control, including mitochondrial degradation and biogenesis. However, these findings are surrounded by substantial controversy due to conflicting experimental data. In addition, the existing PARKIN-deficient mouse models have failed to faithfully recapitulate PD phenotypes. Therefore, we have investigated the mitochondrial role of PARKIN during ageing and in response to stress by employing a series of conditional Parkin knockout mice. We report that PARKIN loss does not affect oxidative phosphorylation (OXPHOS) capacity and mitochondrial DNA (mtDNA) levels in the brain, heart, and skeletal muscle of aged mice. We also demonstrate that PARKIN deficiency does not exacerbate the brain defects and the pro-inflammatory phenotype observed in mice carrying high levels of mtDNA mutations. To rule out compensatory mechanisms activated during embryonic development of Parkin-deficient mice, we generated a mouse model where loss of PARKIN was induced in adult dopaminergic (DA) neurons. Surprisingly, also these mice did not show motor impairment or neurodegeneration, and no major transcriptional changes were found in isolated midbrain DA neurons. Finally, we report a patient with compound heterozygous PRKN pathogenic variants that lacks PARKIN and has developed PD. The PARKIN deficiency did not impair OXPHOS activities or induce mitochondrial pathology in skeletal muscle from the patient. Altogether, our results argue that PARKIN is dispensable for OXPHOS function in adult mammalian tissues.

cell biology↗