Hyeonseok S. Jeong

Network-level structural abnormalities of cerebral cortex in type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) usually begins in childhood and adolescence and causes lifelong damage to several major organs including the brain. Despite increasing evidence of T1DM-induced structural deficits in cortical regions implicated in higher cognitive and emotional functions, little is known whether and how the structural connectivity between these regions is altered in the T1DM brain. Using inter-regional covariance of cortical thickness measurements from high-resolution T1-weighted magnetic resonance data, we examined the topological organizations of cortical structural networks in 81 T1DM patients and 38 healthy subjects. We found a relative absence of hierarchically high-level hubs in the prefrontal lobe of T1DM patients, which suggests ineffective top-down control of the prefrontal cortex in T1DM. Furthermore, inter-network connections between the strategic/executive control system and systems subserving other cortical functions including language and mnemonic/emotional processing were also less integrated in T1DM patients than in healthy individuals. The current results provide structural evidence for T1DM-related dysfunctional cortical organization, which specifically underlie the top-down cognitive control of language, memory, and emotion.

Predisposition to and effects of methamphetamine use on the adolescent brain

Adolescence is a period of heightened vulnerability both to addictive behaviors and drug-induced brain damage. Yet, only limited information exists on the brain mechanisms underlying these adolescent-specific characteristics. Moreover, distinctions in brain correlates between predisposition to drug use and effects of drugs in adolescents are unclear. Using cortical thickness and diffusion tensor image analyses, we found greater and more widespread gray and white matter alterations, particularly affecting the frontostriatal system, in adolescent methamphetamine (MA) users compared with adult users. Among adolescent-specific gray matter alterations related to MA use, smaller cortical thickness in the orbitofrontal cortex was associated with family history of drug use. Our findings highlight that the adolescent brain, which undergoes active myelination and maturation, is more vulnerable to MA-related alterations than the adult brain. Furthermore, MA-use-related executive dysfunction was greater in adolescent MA users than in adult users. These findings may provide explanation for the severe behavioral complications and relapses that are common in adolescent-onset drug addiction. Additionally, these results may provide insights into distinguishing the neural mechanisms that underlie the predisposition to drug addiction from effects of drugs in adolescents.

Altered cortical gyrification patterns in panic disorder: Deficits and potential compensation

Abnormal gyrification patterns may reflect aberrant cortical connectivity during an early period of brain maturation. We here investigated anatomical distribution of cortical gyrification deficits underlying panic disorder and the relationships of these potential neurodevelopmental markers with panic symptom severity. High-resolution three-dimensional T1-weighted structural images were obtained from 23 patients with panic disorder and 33 matched healthy individuals. Local gyrification indices were measured in each genetically-based parcellated cortical subregion and regional gyrification patterns were compared between groups. Cortical areas in which gyrification patterns were associated with panic symptom severity were also determined. Significant reductions in cortical gyrification were observed in panic patients compared with healthy individuals, which were mainly distributed in the lateral brain extending from the fronto-parietal to the temporal areas. In contrast, hyper-gyrification in the posteromedial cortical regions which exert interconnecting roles in the default mode network, was associated with less severe panic symptoms. Post-hoc analysis for the inter-regional covariance of local gyrification indices revealed that interconnections of the posteromedial cortical regions with other cortical areas which belong to the default mode network were reduced in panic patients with severe symptoms relative to either less severe patients or healthy individuals. Our findings suggest not only substantial perturbation in cortical gyrification patterns in panic disorder but also potential contribution of integrated cortical folding pattern of the default mode network to alleviated panic severity.

Morphometric abnormalities of the lateral ventricles in methamphetamine-dependent subjects.

BACKGROUND The presence of morphometric abnormalities of the lateral ventricles, which can reflect focal or diffuse atrophic changes of nearby brain structures, is not well characterized in methamphetamine dependence. The current study was aimed to examine the size and shape alterations of the lateral ventricles in methamphetamine-dependent subjects. METHODS High-resolution brain structural images were obtained from 37 methamphetamine-dependent subjects and 25 demographically matched healthy individuals. Using a combined volumetric and surface-based morphometric approach, the structural variability of the lateral ventricles, with respect to extent and location, was examined. RESULTS Methamphetamine-dependent subjects had an enlarged right lateral ventricle compared with healthy individuals. Morphometric analysis revealed a region-specific pattern of lateral ventricular expansion associated with methamphetamine dependence, which was mainly distributed in the areas adjacent to the ventral striatum, medial prefrontal cortex, and thalamus. CONCLUSIONS Patterns of shape decomposition in the lateral ventricles may have relevance to the structural vulnerability of the prefrontal-ventral striatal-thalamic circuit to methamphetamine-induced neurotoxicity.

Brain perfusion alterations in depressed patients with Parkinson’s disease

ObjectiveAlthough Parkinson’s disease (PD) is frequently accompanied by depression, brain perfusion deficits in PD with depression remain unclear. This study aimed to assess alterations in regional cerebral blood flow (rCBF) in depressed PD patients using 99mTc hexamethyl-propylene-amine-oxime single-photon emission computed tomography (SPECT).MethodsAmong 78 patients with PD, 35 patients were classified into the depressed PD group, while the rest (43 patients) was assigned to the nondepressed PD group based on the scores of the Geriatric Depressive Scale (GDS). All participants underwent brain SPECT imaging. The voxel-wise whole-brain analysis and region-of-interest (ROI) analysis of the limbic areas were conducted to compare rCBF between the depressed and nondepressed PD groups.ResultsThe depressed PD patients demonstrated higher GDS scores than nondepressed patients, whereas between-group differences in the PD severity and cognitive function were not significant. Perfusion in the left cuneus was increased, while that in the right superior temporal gyrus and right medial orbitofrontal cortex was reduced in the depressed PD patients as compared with nondepressed PD patients. In addition, the ROI analysis demonstrated rCBF decreases in the amygdala, anterior cingulate cortex, hippocampus, and parahippocampal gyrus in the depressed PD group. A positive correlation was found between the GDS scores and rCBF in the left cuneus cluster in the depressed PD patients.ConclusionThis study identified the regional pattern of brain perfusion that distinguished depressed from nondepressed PD patients. Hyperperfusion in the occipital areas and hypoperfusion in the fronto-temporo-limbic regions may be potential imaging biomarkers for depression in PD.

Validation of the Korean version of the Connor–Davidson Resilience Scale-2 in firefighters and rescue workers

OBJECTIVE Resilience has been considered as a protective factor against stress. Evaluating resilience in firefighters and rescue workers, who are frequently exposed to traumatic events, is important and relevant. This study examined the psychometric properties of the Korean version of the Connor-Davidson Resilience Scale-2 (CD-RISC2). METHODS Two-hundred twenty-two current professional firefighters and rescue workers were assessed by standardized, semi-structured clinical interviews and self-report questionnaires. Internal consistency, correlation with the CD-RISC, convergent validity, divergent validity, and predictive validity of posttraumatic stress disorder (PTSD) symptom severity were analyzed. RESULTS The CD-RISC2 demonstrated good internal consistency (α=0.75), item-total correlation (r=0.89-0.90), and convergent and divergent validity. The total score of the CD-RISC2 showed significant correlations with the subtotal of the remaining 23 CD-RISC items (r=0.77, p<0.001) and with the score of each CD-RISC item (r=0.15-0.66, all p<0.05). The magnitude of the relationship between the number of traumatic experiences and PTSD symptom severity was greater in the low resilience group than in the high resilience group (p for interaction=0.002). The likelihood-ratio test confirmed that the model predicting PTSD symptom severity based on the CD-RISC2 total score was not improved by the inclusion of subtotal scores of the remaining 23 CD-RISC items (χ(2)=0.31, p=0.58). CONCLUSIONS These results suggest that the CD-RISC2 would be a valuable tool in evaluating resilience quickly and efficiently in firefighters and rescue workers.

Reliability and Validity of the Korean Version of the Lifespan Sibling Relationship Scale

The sibling relationship and its potential impact on neurodevelopment and mental health are important areas of neuroscientific research. Validation of the tools assessing the quality of the sibling relationship would be the first essential step for conducting neurobiological and psychosocial studies related to the sibling relationship. However, to the best of our knowledge, no sibling relationship assessment tools have been empirically validated in Korean. We aimed to evaluate the psychometric properties of the Korean version of the Lifespan Sibling Relationship Scale (LSRS), which is one of the most commonly used self-report questionnaires to assess the quality of the sibling relationship. A total of 109 adults completed a series of self-report questionnaires including the LSRS, the mental health subscale of the Medical Outcomes Study-Short Form 36 version 2 (SF36v2), the Satisfaction with Life Scale (SLS), and the Marlowe-Crowne Social Desirability Scale (MC-SDS). The internal consistency, subscale intercorrelations, one-week test-retest reliability, convergent validity, divergent validity, and the construct validity were assessed. All six subscale scores and the total score of the LSRS demonstrated good internal consistency (Cronbachs α=0.85-0.94) and good test-retest reliability (intraclass correlation coefficient=0.77-0.92). Correlations of the LSRS with the SF36v2 mental health score (r=0.32, p=0.01) and with the SLS (r=0.27, p=0.04) supported the good convergent validity. The divergent validity was shown by the non-significant correlation of the LSRS with the MC-SDS (r=0.15, p=0.26). Two factors were extracted through factor analysis, which explained 78.63% of the total variance. The three Adult subscales loaded on the first factor and the three Child subscales loaded on the second factor. Results suggest that the Korean version of the LSRS is a reliable and valid tool for examining the sibling relationship.

Contribution of neuroimaging in the diagnosis of brain disorders: Recent findings and future applications

Brain disorders including neurological and psychiatric disorders have become a major global public health issue due to their high prevalence and burden. However, elucidating ultimate causes and improving strategies for diagnosis and treatment of these disorders remain challenging due to limited accessibility to living human brain. In addition, there has been a great need for robust biomarkers for them at a very early stage. Neuroimaging technologies have demonstrated the potential in investigating the pathophysiology and developing the biomarkers. The current review discusses the potential diagnostic applications of neuroimaging in brain disorders. We summarized major findings in recent neuroimaging meta‐analyses, which could be used as future biomarkers, in Alzheimers disease, Parkinsons disease, central nervous system inflammation, depression, and schizophrenia. New possibilities of novel imaging techniques were also demonstrated. Finally, future directions for the imaging‐based diagnosis were suggested. In spite of promising results from preliminary studies and rapid technological advances, further studies on the reliability and validity of potential imaging biomarkers in larger patient populations and the development of new guidelines for the clinical applications would be required.

Astrocytic water channel aquaporin-4 modulates brain plasticity in both mice and humans: a potential gliogenetic mechanism underlying language-associated learning

The role of astrocytes in brain plasticity has not been extensively studied compared with that of neurons. Here we adopted integrative translational and reverse-translational approaches to explore the role of an astrocyte-specific major water channel in the brain, aquaporin-4 (AQP4), in brain plasticity and learning. We initially identified the most prevalent genetic variant of AQP4 (single nucleotide polymorphism of rs162008 with C or T variation, which has a minor allele frequency of 0.21) from a human database (n=60 706) and examined its functionality in modulating the expression level of AQP4 in an in vitro luciferase reporter assay. In the following experiments, AQP4 knock-down in mice not only impaired hippocampal volumetric plasticity after exposure to enriched environment but also caused loss of long-term potentiation after theta-burst stimulation. In humans, there was a cross-sectional association of rs162008 with gray matter (GM) volume variation in cortices, including the vicinity of the Perisylvian heteromodal language area (Sample 1, n=650). GM volume variation in these brain regions was positively associated with the semantic verbal fluency. In a prospective follow-up study (Sample 2, n=45), the effects of an intensive 5-week foreign language (English) learning experience on regional GM volume increase were modulated by this AQP4 variant, which was also associated with verbal learning capacity change. We then delineated in mice mechanisms that included AQP4-dependent transient astrocytic volume changes and astrocytic structural elaboration. We believe our study provides the first integrative evidence for a gliogenetic basis that involves AQP4, underlying language-associated brain plasticity.

Changes in cognitive function and brain glucose metabolism in elderly women with subjective memory impairment: a 24-month prospective pilot study.

Subjective memory impairment (SMI) may precede mild cognitive impairment (MCI) stage and would offer an earlier therapeutic opportunity than MCI would. However, it is not clear whether complaints of forgetfulness are truly reflective of objective memory dysfunction or of impairments in other cognitive domains. The aim of this current longitudinal study was to investigate changes in various cognitive functions and in regional cerebral metabolic rate of glucose (rCMRglc) among elderly women with SMI.