Earticle

이 글은 청소년들의 자기 조절 능력 개발을 위한 제안을 신경과학적 입장에서 탐구하였다. 청소년기는 어른이 되어 가고 있는 중요한 변화의 시기이다. 청소년들의 심리적, 신체적, 그리고 행동적 변화는 그들의 뇌 변화와 연관이 있다. 청소년기 뇌 발달의 큰 변화는 전두엽과 변연계에서 일어난다. 전두엽은 인간을 이성적으로 만드는 자기 조절 능력과 연관이 되어 있고 변연계는 감정을 생기게 하는 중요한 역할을 감당한다. 변연계 안에 위치한 편도체(Amygdala)와 해마(Hippocampus)는 충동적이고 본능적인 감정과 연관된 체계로서 전두엽이 온전히 발달이 되지 않을 때 활성화가 된다. 전두엽이 미완성된 상태인 많은 청소년들은 이성적이기 보다는 충동적이며 즉각적 만족을 위해 행동한다. 또한 청소년기 때 증가하는 호르몬인 도파민은 즐거움을 추구하게 만드는 화학작용으로서 청소년들로 하여금 즐거움을 추구하여 도파민을 받아들이는데 집중하게 한다. 그 결과 많은 청소년들은 충동적이고 감정적으로 행동함으로 중독과 같은 심리적 문제를 경험하기 시작한다. 이러한 충동을 조절 할 수 있는 것이 자기 조절 능력이다. 자기 조절 능력은 청소년들의 충동과 감정을 조절하여 이성적으로 생각하는 것을 도울 뿐만 아니라 많은 심리적 문제를 예방하는데 중요한 역할을 한다. 그래서 이 글은 청소년들의 자기 조절 능력이 개발되기 위해 필요한 방법들을 제안하고 있다. 자녀들의 자기 조절 능력 개발에 필요한 부모들의 양육태도(따뜻함, 엄격함, 지지적인)와 뇌를 변화 시키는 뇌 훈련들(작업 기억 능력 향상훈련, 명상, 유산소 운동, 전략 개발)이 그것이다. 또한, 청소년들의 자기 조절 능력 개발을 위해 교회가 청소년들에게 제공할 수 있는 종교적 실천들을 신경심리학적 관점에서 살펴보았다.

This article explored suggestions for developing the self-regulation ability of adolescence from a neuroscience perspective. Adolescence is an important period of change that is becoming an adult. Psychological, physical and behavioral changes in adolescences are related to changed in their brains. Major changes in brain development during adolescence occur in the frontal cortex and limbic system. The frontal cortex is associated with the self-regulation ability to make human beings rational, while limbic system is associated with creating basic emotions. The amygdala and hippocampus located in the limbic system are associated with impulsive, instinctive emotions, and are activated when frontal cortex is not activated. But since the frontal cortex of adolescence is still incomplete, many teenagers exercise for impulsive and immediate gratification due to the influence of limbic system. Also, dopamine, an increasing hormone in adolescence, is a chemical process that allows adolescence to pursue pleasure, and thus focus on accepting dopamine. As a result, many adolescence start experiencing psychological problems such as addiction because it is difficult to control their impulses and urges. The self-regulation ability can control these impulsive and emotional urges and desire. The self-regulation ability plays on important role in preventing many psychological problems as well as helping adolescence to think rationally by controlling their impulses and emotions. So, this article is suggesting two ways for adolescence to develop their self-regulation ability. That is the parenting attitude that need to improve their children’s self-regulation ability and brain training that change the brain’s structure and function. Also, this article looked at the religious practices that the Church could provided to adolescences in order to develop their self-regulation of adolescences from a neuroscience perspective.

Repeated morphine administration for managing persistent pain frequently induces both physical and psychological dependence, accompanied by alterations in cortical gene expression. To elucidate the molecular underpinnings of morphine dependence, gene expression in the frontal cortex of mice subjected to acute and chronic morphine treatment was profiled using microarray analysis and validated by semi-quantitative PCR. Genes including Drd2, Adora2a, Olfr767, Egr2, Gng7, and Gpr6 were upregulated following both acute and chronic morphine treatment. Gene ontology analysis revealed significant enrichment of differentially expressed genes in membrane components, GPCR signaling pathways, and neurological system processes, indicating integrated alterations in receptor-mediated signaling and downstream transcriptional regulation. Consistent with this, selective phosphorylation of CREB was observed during naloxone-precipitated withdrawal, highlighting CREB-dependent transcription as a key molecular correlate of cortical neuroadaptation. Behavioral assays confirmed robust physical and psychological dependence, supporting the functional relevance of these molecular changes. Collectively, these findings identify a GPCR-centered molecular framework in which coordinated regulation and functional interaction of receptors such as DRD2 and ADORA2A, along with associated signaling components, contribute to morphine-induced neuroplasticity and dependence. These insights may provide a foundation for the development of targeted therapeutic strategies to mitigate opioid dependence.

Cerebral monoamines play important roles as neurotransmitters that are associated with various stressful stimuli. Some components such as ginsenosides (triterpenoidal glycosides derived from the Ginseng Radix) may interact with monoamine systems. The aim of this study was to determine whether ginsenoside Rb1 can modulate levels of the monoamines such as dihydroxyphenylalanine (DOPA), dopamine (DA), norepinephrine (NE), epinephrine (EP), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydorxytryptamine (5-HT), 5-hydroxindole-3-acetic acid (5-HIAA), and 5-hydroxytryptophan (5-HTP) in mice frontal cortex and cerebellum in response to immobilization stress. Mice were treated with ginsenoside Rb1 (10 mg/kg, oral) before a single 30 min immobilization stress. Acute immobilization stress resulted in elevation of monoamine levels in frontal cortex and cerebellum. Pretreatment with ginsenoside Rb1 attenuated the stress-induced changes in the levels of monoamines in each region. The present findings showed the anti-stress potential of ginsenoside Rb1 in relation to regulation effects on the cerebral monoaminergic systems. Therefore, the ginsenoside Rb1 may be a useful candidate for treating several brain symptoms related with stress.

Glycan plays numerous roles in the nervous system during development, regeneration and synaptic plasticity, forming of a complex meshwork at the cell surface. We newly established an analytical platform for exploring two molecules- glycan attached to proteins and glycan attached to lipids- from human brain using mass spectrometry. 69 brain samples were obtained from the University of Cambridge. Glycan extraction method from previous study, and new ganglioside extraction method were paired with MS. Briefly, each brain tissues were grinded by sonication. Then for glycans, the membrane was pelleted by ultracentrifugation. N-glycan release and associated processing steps were performed by previously optimized procedures. For sphingolipids, homogenized brain is mixed with chloroform/methanol/water and centrifuged. Total lipids extracts were partitioned again with chloroform/methanol to collect gangliosides. After further enrichment by SPE, N-glycans and gangliosides were profiled by positive and negative ion mode nano-LC/MS respectively. Stucture information was obtained by nano-LC/MS/MS. Brain samples were divided into the 7 groups: neonates, infants, toddlers, school-ages, teenagers, young adults. We successfully profiled brain glycome and sphingolipids, identifying approximately 100 N-glycan compositions and 120 ganglioside compounds with several unique “brain type” characters. This study promise insights into involvement of glycans to massive flow of information that underpins brain, with providing meaningful understanding to neuropathology related with aging.

Objective Given the association between the pathophysiology of panic disorder and prefrontal cortex function, we aimed to perform a volumetric MRI study in patients with panic disorder and healthy controls focusing on the in vivo neuroanatomy of the OFC. Methods Twenty right-handed patients with panic disorder and 20 right-handed healthy control subjects were studied. The volumes of whole brain, total white and gray matters, and OFC were measured by using T1-weighted coronal MRI images, with 1.5-mm-thick slices, at 1.5T. In addition, for psychological valuation, Hamilton Depression Rating (HDRS) and Panic Agoraphobia Scales (PAS) were administered. ResultsaaUnadjusted mean volumes of the whole brain volume, total white and gray matter were not different between the patients and healthy controls while the patient group had significantly smaller left (t=-6.70, p<0.0001) and right (t=-5.86, p<0.0001) OFC volumes compared with healthy controls. Conclusion Our findings indicate an alteration of OFC morphology in the panic disorder and suggest that OFC abnormalities may be involved in the pathophysiology of panic disorder.

Purpose: Contrary to the human study, it has rarely investigated metabolic alterations in the dorsolateral prefrontal cortex (DLPFC) of depressed rats versus age and sex-matched controls using proton magnetic resonance spectroscopy (MRS). Thus, the purpose of this research was to verify the feasibility of metabolic differences between the normal rat and the depression model rat. Materials and Methods: A homogeneous group of 20 SD male rats was used for MRI and in vivo 1H MRS. To induce a depressed status in SD rats, we performed the forced swimming test (FST). Using image-guide, water suppressed in vivo 1H MRS with 4.7 T MRI/MRS system, NAA/Cr and Cho/Cr ratios were mainly measured between depressed rats and normal subjects. Results: In depressed rats, increased Cho/Cr ratio was measured versus control subjects. However, no significant group effect for NAA/Cr was observed between case-control pairs. Discussion and Conclusions: The present 1H MRS study shows significant brain metabolic alterations of dorsolateral prefrontal cortex with experimental depressed status of SD rat induced by FST compared to normal subjects. This result provides new evidence that in vivo 1 H MRS may be a useful modality for detecting localized functional neurochemical markers alterations in left DLPFC in SD rats.

Objective Although the importance of orbito-frontal cortex (OFC) is established in the pathogenesis of obsessive compulsive disorder (OCD), no study have evaluated its relation to the traditional psychodynamic perspective. In the present study, we aimed to evaluate the relationship between the defense styles consisting of mature, immature and neurotic defenses and OFC volumes of patients with OCD. Methods Subjects were selected among those of our previous study, and so eighteen patients with OCD and same number of healthy controls were took into the study. The patients and controls had underwent magnetic resonance imaging (MRI). In addition, the Defense Style Questionnaire-40 was administered to obtain defense styles of patients and controls. Results No significant relationship was found between the right OFC volumes of both the patient and control groups and their scores of mature, neurotic, or immature defense mechanisms. As for the left OFC volumes, the only significant relationship for the scores of immature defense mechanism was found in the patient group. Conclusion The results of the present study indicated that there was no significant relationship between OFC volumes of the patient group and their scores of mature, neurotic, or immature defense mechanisms, except a significant relation with the scores of immature defense mechanisms.

Serotonin (5-hydroxytroptamine, 5-HT) has been shown to affect the induction of long-term potentiation (LTP) in the cortex such as the hippocampus, the visual cortex and the prefrontal cortex. Fluoxetine, as a selective serotonin reuptake inhibitor, is used in the management of a wide variety of psychological diseases. To study the effect of fluoxetine on the induction of LTP, we recorded the field potential in layer II/III of the frontal cortex from 3-wk-old. LTP was induced in horizontal input by theta burst stimulation (TBS). TBS with two-folds intensity of the test stimulation induced LTP, which was blocked by application of D-AP5 $(50 {\mu}M)$, an NMDA receptor antagonist. Whereas bath application of 5-HT $(10 {\mu}M)$ inhibited the induction of LTP, treatment with the 5-HT depleting agent, para-chloroamphetamine $(PCA,\;10{\mu}M)$, for 2hr did not affect the induction of LTP. Bath application of fluoxetine (1, 3, and $10 {\mu}M)$ suppressed the induction of LTP in concentration-dependent manner, however, fluoxetine did not inhibit the induction of LTP in 5-HT-depleted slices. These results indicate that fluoxetine may inhibit the induction of LTP by modulating serotonergic mechanism in the rat frontal cortex.

Objective Electroconvulsive therapy (ECT) is the most effective treatment for mood disorders. Accumulating evidence has suggested the important role of circadian genes in mood disorders. However, the effects of ECT on circadian genes have not been systemically investigated. Methods We examined the expression and daily oscillation of major circadian genes in the rat frontal cortex after electroconvulsive seizure (ECS). Results Firstly, mRNA and protein level were investigated at 24 hr after single ECS (E1X) and repeated ECS treatements for 10 days (E10X), which showed more remarkable changes after E10X than E1X. mRNA expression of Rorα, Bmal1, Clock, Per1, and Cry1 was decreased, while Rev-erbα expression was increased at 24 hr after E10X compared to sham. The proteins showed similar pattern of changes. Next, the effects on oscillation and rhythm properties (mesor, amplitude, and acrophase) were examined, which also showed more prominent changes after E10X than E1X. After E10X, mesor of Rorα, Bmal1, and Cry1 was reduced, and that of Rev-erbα was increased. Five genes, Rev-erbα, Bmal1, Per1, Per2, and Cry2, showed earlier acrophase after E10X. Conclusion The findings suggest that repeated ECS induces reduced expression and phase advance of major circadian genes in the in vivo rat frontal cortex.

Repeated electroconvulsive seizure (ECS), a model for electroconvulsive therapy (ECT), exerts neuroprotective and proliferative effects in the brain. This trophic action of ECS requires inhibition of apoptotic activity, in addition to activation of survival signals. c-Myc plays an important role in apoptosis of neurons, in cooperation with the Bcl-2 family proteins, and its activity and stability are regulated by phosphorylation and ubiquitination. We examined c-Myc and related proteins responsible for apoptosis after repeated ECS. In the rat frontal cortex, repeated ECS for 10 days reduced the total amount of c-Myc, while increasing phosphorylation of c-Myc at Thr58, which reportedly induces degradation of c-Myc. As expected, ubiquitination of both phosphorylated and total c-Myc increased after 10 days ECS, suggesting that ECS may reduce c-Myc protein level via ubiquitination-proteasomal degradation. Bcl-2 family proteins, caspase, and poly(ADP-ribose) polymerase (PARP) were investigated to determine the consequence of down-regulating c-Myc. Protein levels of Bcl-2, Bcl-XL, Bax, and Bad showed no change, and cleavage of caspase-3 and PARP were not induced. However, phosphorylation of Bad at Ser-155 and binding of Bad to 14-3-3 increased without binding to Bcl-XL after repeated ECS, implying that repeated ECS sequesters apoptotic Bad and frees pro-survival Bcl-XL. Taken together, c-Myc down-regulation via ubiquitination-proteasomal degradation and Bad inactivation by binding to 14-3-3 may be anti-apoptotic mechanisms elicited by repeated ECS in the rat frontal cortex. This finding further supports the trophic effect of ECS blocking apoptosis as a possible therapeutic effect of ECT.

Glycogen synthase kinase 3 (GSK3) was recently suggested to be a potential target of psychotropics used in psychiatric illn esses such as schizophrenia and bipolar disorder. Relevant studies have found that antipsychotic drugs regulate GSK3 activity via an increase in either in hibitory serine phospho-rylation or amount of GSK3 after acute or subchronic treatment. Recent evidence shows that GSK3 is regulated by dopaminergic or serotonergic systems implicated in the pathophysiology and treatment mechanisms of schizophrenia and bipolar disorder. Therefore, antipsychotics may regulate GSK3 via antagonizing dopaminergic or serotonergic activity. However, the signaling pathway that is involved in GSK3 regulation by dopaminergic or serotonergic established. Haloperidol is a typical antipsychotic with potent dopamine D2 receptor antagonism. Clozapine is an atypical antip-sychotic with potent serotonin 5HT2 receptor anta-gonism. We injected rats with haloperidol or clo-zapine and examined the phosphorylation and amount of GSK3α/β and its well-known upstream regulators Akt and Dvl in the rat frontal cortex by Western blotting. Both haloperidol and clozapine induced Ser21/9 phosphorylation of GSK3 α/β. Halo-peridol increased the Ser473 phosphorylation of Akt transiently, whereas clozapine maintained the in-phorylation and amount of Dvl, whereas clozapine increased both phosphorylation and the amount of Dvl. Our results suggest that GSK3 activity may be regulated by both typical and atypical antipsychotics and that Akt or Dvl, depending on the D2- or 5HT2- receptor antagonism properties of typical and aty-pical antipsychotics, mediate the regulation differently.

Insomnia is a common sleep-related symptom which occurs in many populations, however, the neural mechanism underlying insomnia is not yet known. The hyperarousal model explains the neural mechanism of insomnia to some extent, and the frontal cortex dysfunction has been known to be related to primary insomnia. In this review, we discuss studies that applied resting state and/or task-related functional magnetic resonance imaging to demonstrate the deficits/dysfunctions of functional activation and network in primary insomnia. Empirical evidence of the hyperarousal model and proposed relation between the frontal cortex and other brain regions in primary insomnia are examined. Reviewing these studies could provide critical insights regarding the pathophysiology, brain network and cerebral activation in insomnia and the development of novel methodologies for the diagnosis and treatment of insomnia.

본 연구에서는 생활공간에서의 음 환경이 인체에 미치는 영향을 조사하기 위하여 긍정감성을 유발하는 음환경으로서의 '명상음악'과 부정감성을 유발하는 음환경으로서의 '마루가 삐그덕거리는 소음'을'제시하였을 때 전두엽의 부위별 활성화의 변화를 관찰하기 위하여 뇌전도를 측정하였다. 연구결과, 명상음악을 청취시에는 안정상태에 비하여 좌측전두엽이 더 활성화되는 반면에 소음환경에서는 우측전두엽이 더 활성화됨을 관측할 수 있었다.

60세 남자 환자로 좌측 정중 전두엽과 양측 기저절 경색 후 발생한 과잉성욕 증상과 강박 증상을 주소로 내원하였다. 환자는 뇌졸중 후에 발생한 운동 기능 장애는 시간이 경과하면서 호전되어 발병 1개월 이내에 거의 정상화된 반면 과잉성욕 증상과 강박 증상은 호전되지 않았다. 환자에게 과잉성욕 증상과 강박 증상을 목표로 fluvoxamine과 perphenazine을 처방하였으며 치료 시작 후 2개월이 경과하면서 환자의 과잉성욕 증상과 강박 증상은 서서히 사라졌다. 이 증례는 기저절-시상전두엽 회로가 성적 행동과 강박 증상의 조절에 있어 중요한 역할을 하고 있음을 시사한다고 할 수 있다. 과잉성욕 증상은 임상에서 간과하기 쉽고 또한 일반적으로 성적 활동에 대한 변화는 환자들 스스로 보고하지 않는 경향이 많다. 따라서 뇌졸중 환자, 특히 정중 전두엽이나 기저절 병변을 동반한 환자들의 경우에는 비록 그 병변이 측두엽 침범이 없거나 Kluver-Bucy syndrome의 전형적인 증상을 보이지 않는다 할 지라도 성욕등 성적 활동에 대한 체계적인 조사가 필요할 것으로 생각된다. 또한 과잉성욕 증상과 강박 증상을 함께 가지고 있는 경우 선택적인 세로토닌 재흡수 억제제의 사용이 두 증상 모두를 효과적으로 치료하는 데에 도움이 될 수 있을 것이다.

Hyposexuality after stroke has been frequently observed, but hypersexuality as a sequela of stroke has not been commonly documented. We report a patient who exhibited hypersexuality and obsessive-compulsive behaviors after stroke in the region of the left mesial frontal cortex and both basal ganglia. At 2 months after stroke, he visited psychiatric unit due to these symptoms. His motor function was almost full recovered. He was treated with fluvoxamine and perphenazine. With two-month medication, his hypersexuality and obsessive-compulsive behavior disappeared. This case may indicate that basal ganglia-thalamocortical circuit plays an important role in the mediation of sexual behavior and obsessive-compulsive behavior. Since changes in sexual activity may not be spontaneously reported, a systemic inquiry into patient's sexual functioning after infarction in frontal lobe or basal ganglia is warranted.

목적: 최근 새로운 뇌 영상화 측정 장비인 기능적 근적외선분광영상(functional near-infrared spectroscopy: fNIR)을 사용하여 말더듬 대상자의 뇌 활성화 양상을 알아보고자 한 연구들이 이루어지고 있다. 이에 본 연구는 fNIR을 사용하여 구어산출 메커니즘 협응을 이용한 치료 전ㆍ후 말더듬 대상자의 유창성 개선과 전두엽 피질의 활성화 양상 혹은 패턴이 달라지는 가를 알아보고자 하였다. 방법: 본 연구는 고등학교 3학년에 재학 중인 남자 1명과 2학년에 재학 중인 남자 1명을 대상으로 사전ㆍ사후 설계를 사용하였다. 즉 치료 실시 전ㆍ후구어 측면에서 유창성 개선 여부를 비교하고, 동시에 fNIR을 이용하여 전두엽 피질 활성화를 비교하였다. 유창성 개선 여부는 말더듬 빈도, 구어속도 및 말더듬 형태 변화를 통해, 전두엽 피질의 활성화는 활성화된 산소 및탈산소 헤모글로빈 측정치를 통해 알아보았다. 결과: 첫째, 유창성 개선 측면에서 구어산출 메커니즘 협응을 이용한 치료 후 대상자 둘 다 말더듬 빈도는 감소하였고, 구어 속도는 향상되었고, 말더듬 주된 형태는 단어 전체반복으로 나타났다. 둘째, 전두엽 피질의 활성화 측면에서 구어산출 메커니즘 협응을 이용한 치료 후 대상자모두 활성화된 산소 및 탈산소 헤모글로빈 측정치가 증가한 것으로 나타났다. 결론: 구어산출 메커니즘 협응을이용한 치료 프로그램은 말더듬 대상자의 유창성 개선에 효과적일 뿐만 아니라 전두엽의 활성화 양상을 변화시키는데, 이러한 변화는 fNIR을 통해 객관적으로 검증할 수 있는 것으로 결론 내릴 수 있다.

Purpose: Current studies have looked at brain activation patterns of subjects with stuttering using functional infrared imaging (fNIR) as a new brain imaging instrument. The aim of this study was to recognize the fluency improvement of pre- and post-treatment using speech production mechanism coordination and how to alter the activation pattern of the frontal lobe cortex using fNIR (functional near-infrared spectroscopy). Methods: This study used a pre- and post-treatment on one male high school senior and one male high school junior. In other words, comparing fluency improvement aspects by using the pre- and post-treatment in spoken language, and simultaneously comparing the frontal lobe cortex activation using fNIR. To recognize fluency improvement through stuttering frequency, speech rates, changing of stuttering, and oxy and deoxy hemoglobin measurements in the frontal lobe cortex were taken. Results: First, in terms of fluency improvement, after using the speech production mechanism coordination in this treatment, both subjects decreased stuttering frequency, increased speech rates, and the main form of stuttering appeared as a whole repetition of words. Secondly, in terms of aspects of frontal lobe cortex activation, after using the speech production mechanism coordination treatment, subjects increased oxy and deoxy hemoglobin measurements. Conclusions: Using the speech production mechanism coordination treatment is not only effective in improving fluency, but also changing the activation pattern of the frontal lobe. These changes were verified objectively through fNIR.