• Journal of Yeungnam Medical Science
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• v.17 no.2
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• pp.108-122
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• 2000

Background: Models of attention deficit hyperactivity disorder(ADHD) that have proposed a hypodopaminergic state resulting in hypofunction of the prefrontal circuitry have assumed a unitary dopamine system, which largely ignores the distinct functional differences between mesocortical dopamine system and nigrostriatal dopamine system. Purpose: The author's goal was to develop a pathophysiological model for ADHD with greater explanotory power than dopaminergic hypofunction hypothesis in prefronal circuitry. Material and Methods: Published clinical findings on ADHD were integrated with data from genetic, pharmacological, neuroimaging studies in human and animals. Results: Molecular genetic studies suggest that three genes may increase the susceptibility to ADHD. The three candidate genes associated with ADHD are each involved in dopaminergic function, and this consistent with the neurobiologic studies implicating catecholamines in the etiology of ADHD. Pharmacological data also provide compelling support for dopamine and noradrenergic hypothesis of ADHD. Neuroimaging studies lend substantial support for the hypothesis that right-sided abnormalities of prefrontal-basal ganglia circuit would be found in ADHD. Conclusions: The present hypothesis takes advantage of the major differences between the two pertinent dopamine systems. Mesocortical dopamine system, which largely lacks inhibitory autoreceptors, is ideally positioned to regulate cortical inputs, thus improving the signal-to-noise ratio for biologically valued signals. In this circuit, therapeutic doses of stimulants are hypothesized to increase postsynaptic dopamine effects and enhance executive functions. By contrast, symptoms of hyperactivity/impulsivity in ADHD are hypothesized to be associated with relative overactivity of nigrostriatal circuit. This nigrostriatal circuit is tightly regulated by inhibitory autoreceptoors as well as by long distance feedback from the cortex, and slow diffusion of therapeutic doses of stimulant via oral administration is hypothesized to produce a net inhibition of dopaminergic neurotransmission and improves hyperactivity.

• Applied Microscopy
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• v.35 no.3
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• pp.135-152
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• 2005

Prefrontal cortex is a psychological and metaphysical cortex, which deals with feeling, memory, planning, attention, personality, etc. And it also integrates above-mentioned events with motor control and locomotor activities. Prefrontal cortex works as a highest CNS center, since the above mentioned functions are very important for one's successful life, and further more they are upgraded every moments through memory and learning. Many of these highest functions are supposed to be generated via forebrain basal nuclei (caudate nucleus, fundus striati nucleus, accumbens septi nucleus, septal nucleus, etc.). In this experiment, prefrontal efferent terminals within basal forebrain nuclei were ultrastructurally studied. Spraque Dawley rats, weighing $250{\sim}300g$ each, were anesthetized and their heads were fixed on the stereotaxic apparatus (experimental model, David Kopf Co.). Rats were incised their scalp, perforated a 3mm-wide hole on the right side of skull at the 11mm anterior point from the frontal O point (Ref. 13, Fig. 1), suctioned out the prefrontal cortex including cortex of the frontal pole, with suction instrument. Two days following the operations, small tissue blocks of basal forebrain nuclei were punched out, fixed in 1% glutaraldehyde-1% paraformaldehyde solution followed by 2% osmium tetroxide solutions. Ultrathin sections were stained with 1% borax-toluidin blue solution, and the stained sections were obserbed with an electron microscope. Degenerating axon terminals were found within all the basal forbrain nuclei. Numbers of degenerated terminals were largest in the caudate nucleus, next in order, in the fundus striati nucleus, in the accumbens septi nucleus, and the least in the septal nucleus. Only axospinous terminals were degenerated within the caudate nucleus and the fundus striati nucleus, and they showed the characters of striatal motor control system. Axodendritic and axospinous terminals were degenerated within the accumbens septi nucleus and the lateral septal nucleus, and they showed the characters of visceral limbic system. Prefrontal role in integrating the limbic system with the striatal system, en route basal forebrain nuclei, was discussed.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.1-8
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• 2016

Damage in the periphery or spinal cord induces maladaptive plastic changes along the somatosensory nervous system from the periphery to the cortex, often leading to chronic pain. Although the role of neural circuit remodeling and structural synaptic plasticity in the 'pain matrix' cortices in chronic pain has been thought as a secondary epiphenomenon to altered nociceptive signaling in the spinal cord, progress in whole brain imaging studies on human patients and animal models has suggested a possibility that plastic changes in cortical neural circuits may actively contribute to chronic pain symptoms. Furthermore, recent development in two-photon microscopy and fluorescence labeling techniques have enabled us to longitudinally trace the structural and functional changes in local circuits, single neurons and even individual synapses in the brain of living animals. These technical advances has started to reveal that cortical structural remodeling following tissue or nerve damage could rapidly occur within days, which are temporally correlated with functional plasticity of cortical circuits as well as the development and maintenance of chronic pain behavior, thereby modifying the previous concept that it takes much longer periods (e.g. months or years). In this review, we discuss the relation of neural circuit plasticity in the 'pain matrix' cortices, such as the anterior cingulate cortex, prefrontal cortex and primary somatosensory cortex, with chronic pain. We also introduce how to apply long-term in vivo two-photon imaging approaches for the study of pathophysiological mechanisms of chronic pain.

• Korean Journal of Biological Psychiatry
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• v.12 no.2
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• pp.123-135
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• 2005

Objectives:EEG coherence could imply the connectivity between two different areas of the brain, which is known to be important in the pathophysiology of bipolar I disorder(BPD I) and schizophrenia. The authors investigated EEG coherence in patients with BPD I and schizophrenia to examine the connectivity of the neural circuit. Methods:EEGs were recorded in 15 schizophrenia and 14 bipolar disorder patients, and 14 age-matched normal control subjects from 16 electrodes with linked-ear reference. Spectral parameters and coherence were calculated for the alpha bandwidth(8-13Hz) by a multi-channel autoregressive model using 20 artifact-free 2-seconds epochs and the differences were compared among three groups by two different statistical methods;F-test and Kruskal-Wallis test. Furthermore, when there were significant differences among three groups, Scheffe's multiple comparison tests were provided and Jonckheere-Terpstra tests for the ordered alternative were given. Results:In the intra-hemispheric comparison, left frontal coherence was increased in order of control, BPD I and schizophrenia. In the inter-hemispheric comparison, 1) inter-prefrontal coherence in BPD I was signifi- cantly higher than in normal controls, and 2) inter-prefrontal coherence in schizophrenia was significantly lower than in controls. Conclusion:These results suggest that 1) both schizophrenia and BPD I are diseases having the abnormality of neural circuit connectivity in both frontal and prefrontal lobes, and 2) the abnormality is more severe in schizophrenia than in BPD I. Furthermore, the data support that a common pathogenetic process may reside in both schizophrenia and BPD I.

• The Korean Journal of Nuclear Medicine
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• v.39 no.6
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• pp.438-444
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• 2005

Purpose: Anhedonia has been proposed to be the result of a basic neurophysiologic dysfunction and a vulnerability marker that precede and contribute to the liability of developing schizophrenia. We hypothesized that anhedonia, as a construct reflecting the decreased capacity to experience pleasure, should be associated with decreased positive hedonic affect trait. This study examined the relationship between anhedonia and positive hedonic affect trait and searched for the brain legions which correlate with anhedonia in normal subjects. Materials and Methods: Using $^{18}F$-FDG PET scan, we investigated the brain activity of twenty one subjects during resting state. Questionnaires were administrated after the scan in order to assess the self-rated individual differences in physical/social anhedonia and positive/negative affect traits. Results: Negative correlation between physical anhedonia score and positive affect trait score was significant (Pearson coefficient =-0.440, p<0.05). The subjects physical and social anhedonia scores showed positive correlation with metabolic rates in the cerebellum and negative correlation with metabolic rates in the inferior temporal gyrus and middie frontal gyrus. In addition, the positive affect trait score positively correlated with various areas, most prominent with the inferior temporal gyrus. Conclusion: These results suggest that neural substrates, such as the inferior temporal gyrus and prefrontal-cerebellar circuit, which dysfunction has been proposed to be involved with the cognitive deficits of schizophrenia, may also play a significant role in the liability of affective deficits like anhedonia.

• Korean Journal of Biological Psychiatry
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• v.18 no.1
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• pp.15-24
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• 2011

Mood disorder is unlikely to be a disease of a single brain region or a neurotransmitter system. Rather, it is now generally viewed as a multidimensional disorder that affects many neural pathways. Growing neuroimaging evidence suggests the anterior cingulate-pallidostriatal-thalamic-amygdala circuit as a putative cortico-limbic mood regulating circuit that may be dysfunctional in mood disorders. Brain-imaging techniques have shown increased activation of mood-generating limbic areas and decreased activation of cortical areas in major depressive disorder(MDD). Furthermore, the combination of functional abnormalities in limbic subcortical neural regions implicated in emotion processing together with functional abnormalities of prefrontal cortical neural regions probably result in the emotional lability and impaired ability to regulate emotion in bipolar disorder. Here we review the biological correlates of MDD and bipolar disorder as evidenced by neuroimaging paradigms, and interpret these data from the perspective of endophenotype. Despite possible limitations, we believe that the integration of neuroimaging research findings will significantly advance our understanding of affective neuroscience and provide novel insights into mood disorders.

• Korean Journal of Biological Psychiatry
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• v.24 no.4
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• pp.225-234
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• 2017

Objectives Local gyrification reflects the early neural development of cortical connectivity, and is regarded as a potential neural endophenotype in psychiatric disorders. Several studies have suggested altered local gyrification in patients with bipolar I disorder (BD-I). The purpose of the present study was to investigate the alterations in the cortical gyrification of whole brain cortices in patients with BD-I. Methods Twenty-two patients with BD-I and age and sex-matched 22 healthy controls (HC) were included in this study. All participants underwent T1-weighted structural magnetic resonance imaging (MRI). The local gyrification index (LGI) of 66 cortical regions were analyzed using the FreeSurfer (Athinoula A. Martinos Center for Biomedical Imaging). One-way analysis of covariance (ANCOVA) was used to analyze the difference of LGI values between two groups adjusting for age and sex as covariates. Results The patients with BD-I showed significant hypogyria in the left pars opercularis (uncorrected-p = 0.049), the left rostral anterior cingulate gyrus (uncorrected-p = 0.012), the left caudal anterior cingulate gyrus (uncorrected-p = 0.033). However, these findings were not significant after applying the multiple comparison correction. Severity or duration of illness were not significantly correlated with LGI in the patients with BD-I. Conclusions Our results of lower LGI in the anterior cingulate cortex and the ventrolateral prefrontal cortex in the BD-I group implicate that altered cortical gyrification in neural circuits involved in emotion-processing may contribute to pathophysiology of BD-I.

• The Journal of Korean Academy of Sensory Integration
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• v.14 no.1
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• pp.50-59
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• 2016

Objective : The goal of this study was to investigate neurological mechanism of emotional regulation and to examine the relationship between the regulation and sensory processing. Subjective : Emotional regulations are mainly processed in limbic system, particularly the basal-lateral group of amygdala takes on a major role in the regulations. The basal-lateral group of amygdala links to thalamus directly and/or indirectly which processes sensory information together. This sensory information connects to orbital and medial prefrontal cortex. Inadequate sensory processing may cause difficulties in emotional regulations and behaviors because of a circuit linking the amygdala, the thalamus, and the orbital and medial prefrontal cortex. These difficulties and impairments has been reported in neurological studies for children with ASD and ADHD. Conclusion : Neurological states are different between the normal children and children with ASD and ADHD and these represent various aspects in sensory processing, emotional regulations and behaviors. Thus, therapists working with children with ASD and ADHD need to understand mechanisms of sensory processing and emotional regulations in order to provide adequate treatments.

• Korean Journal of Biological Psychiatry
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• v.18 no.2
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• pp.61-71
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• 2011

Substance addiction is a chronically relapsing disorder that has been characterized by a vicious cycle composed of intoxication, craving/anticipation, withdrawal, and response inhibition/bingeing. Here we summarize the findings from neuroimaging studies in addiction according to these behavioral components and suggest the integrated neurobiological model of drug addiction and related brain correlates. The roles of various prefrontal regions, thalamus, memory circuit, anterior cingulated, and insula were also suggested in addition to those of classical mesolimbic dopaminergic system and its responsivity. Limited studies of behavioral addiction demonstrated a similarity with substance addiction on the neurobiological basis. Based on the current understanding of neurobiology of addiction, further researches on interactions of behavioral components and their brain correlates, behavioral addiction, and therapeutic applications will be desired.

• Korean Journal of Biological Psychiatry
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• v.28 no.2
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• pp.36-49
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• 2021

Suicide is a leading cause of death worldwide, especially among adolescents and young adults. Considering this fact, it is imperative that we understand the neural mechanisms underlying suicidal thoughts and behaviors in youth from a neurodevelopmental perspective. In this review, we focused on the magnetic resonance imaging studies that examined the neural correlates of suicidal ideations (SI) or attempts (SA) in youth. We reviewed twenty-three cross-sectional studies reporting the structural and functional alterations in association with SI or SA among adolescents and young adults with various mental disorders. The previous literature suggests that the dorsolateral prefrontal cortex, anterior cingulate cortex, and ventral frontolimbic circuit, may play an important role in the pathophysiology of suicidal behavior in youth through altered top-down control over emotion and impulsivity. Future studies with a longitudinal design and using multimodal imaging techniques may be of help to identify novel therapeutic targets specific for youth with suicidal thoughts and behaviors.