The core concept for pathophysiology in panic disorder (PD) is the fear network model (FNM). The alterations in FNM might be linked with disturbances in the autonomic nervous system (ANS), which is a common phenomenon in PD. The traditional FNM included the frontal and limbic regions, which were dysregulated in the feedback mechanism for cognitive control of frontal lobe over the primitive response of limbic system. The exaggerated responses of limbic system are also associated with dysregulation in the neurotransmitter system. The neuroimaging studies also corresponded to FNM concept. However, more extended areas of FNM have been discovered in recent imaging studies, such as sensory regions of occipital, parietal cortex and temporal cortex and insula. The insula might integrate the filtered sensory information via thalamus from the visuospatial and other sensory modalities related to occipital, parietal and temporal lobes. In this review article, the traditional and advanced FNM would be discussed. I would also focus on the current evidences of insula, temporal, parietal and occipital lobes in the pathophysiology. In addition, the white matter and functional connectome studies would be reviewed to support the concept of advanced FNM. An emerging dysregulation model of fronto-limbic-insula and temporooccipito-parietal areas might be revealed according to the combined results of recent neuroimaging studies. The future delineation of advanced FNM model can be beneficial from more extensive and advanced studies focusing on the additional sensory regions of occipital, parietal and temporal cortex to confirm the role of advanced FNM in the pathophysiology of PD.
Autonomic Nervous System ; Connectome ; Frontal Lobe ; Limbic System ; Neuroimaging ; Neurotransmitter Agents ; Occipital Lobe ; Panic Disorder ; Panic ; Parietal Lobe ; Rabeprazole ; Temporal Lobe ; Thalamus ; White Matter

Injury to the thalamocortical tract (one in the Papez circuit) that leads to memory impairment following brain injury is very rare. In this study, we present a case of partial injury to the thalamocortical tract that causes memory impairment after concurrent thalamic and hippocampal infarct. A 20-year-old male complained of memory impairment 1 month after partial injury to the thalamocortical tract. Using a probabilistic diffusing tensor tractography, it was found that the right thalamocortical tract was thinner than the left thalamocortical tract. However, all other neural tracts including the fornix, cingulum, and mammillothalamic tract were intact on both hemispheres. Therefore, the memory impairment in this patient was considered as being due to thalamic infarct based on the observation that the fornix from hippocampal infarct was intact. This case suggests that the assessment of lesions in the neural tracts of the Papez circuit might be useful for understanding the mechanism of memory impairment following cerebral infarction.
Brain Injuries ; Cerebral Infarction ; Humans ; Limbic System ; Male ; Memory Disorders ; Memory* ; Young Adult

The seeds of addiction are typically sown years prior to the onset of addictive substance use or engagement in addictive behaviors, due to the priming of the reward pathway (RewP) by alterations in the mechanism of stress-signaling from the hypothalamic-pituitary-adrenal axis (HPA) and related pathways. Excessive stress from a single-event and/or cumulative life experiences during childhood, such as those documented in the Adverse Childhood Experiences Study, is translated into neurobiological toxicity that alters the set-point of the HPA axis and limbic system homeostasis [suggested new term: regulation pathway (RegP)]. The resultant alteration of the RegP not only increases the risk for psychiatric and physical illness, but also that for early onset and chronic addictions by dysregulating the RewP. This paper reviews the interface of these symbiotic pathways that result in the phenotypic pathology of emotional dysregulation, cognitive impairment, and compulsive behaviors, as well as morbidity and shorter life expectancy when dysregulated by chronic stress.
Behavior, Addictive ; Cognition Disorders ; Compulsive Behavior ; Homeostasis ; Life Change Events ; Life Expectancy ; Limbic System ; Pathology ; Reward

OBJECTIVES: Recent neuroimaging studies focus on dysfunctions in connectivity between cognitive circuits and emotional circuits: anterior cingulate cortex that connects dorsolateral orbitofrontal cortex and prefrontal cortex to limbic system. Previous studies on pediatric depression using DTI have reported decreased neural connectivity in several brain regions, including the amygdala, anterior cingulate cortex, superior longitudinal fasciculus. We compared the neural connectivity of psychotropic drug naïve adolescent patients with a first onset of major depressive episode with healthy controls using DTI. METHODS: Adolescent psychotropic drug naïve patients(n=26, 10 men, 16 women; age range, 13–18 years) who visited the Korea University Guro Hospital and were diagnosed with first onset major depressive disorder were registered. Healthy controls(n=27, 5 males, 22 females; age range, 12–17 years) were recruited. Psychiatric interviews, complete psychometrics including IQ and HAM-D, MRI including diffusion weighted image acquisition were conducted prior to antidepressant administration to the patients. Fractional anisotropy(FA), radial, mean, and axial diffusivity were estimated using DTI. FMRIB Software Library-Tract Based Spatial Statistics was used for statistical analysis. RESULTS: We did not observe any significant difference in whole brain analysis. However, ROI analysis on right superior longitudinal fasciculus resulted in 3 clusters with significant decrease of FA in patients group. CONCLUSIONS: The patients with adolescent major depressive disorder showed statistically significant FA decrease in the DTI-based structure compared with healthy control. Therefore we suppose DTI can be used as a biomarker in psychotropic drug-naïve adolescent patients with first onset major depressive disorder.
Adolescent ; Amygdala ; Brain ; Depression ; Depressive Disorder, Major ; Diffusion ; Diffusion Tensor Imaging ; Female ; Gyrus Cinguli ; Humans ; Korea ; Limbic System ; Magnetic Resonance Imaging ; Male ; Neuroimaging ; Prefrontal Cortex ; Psychometrics ; White Matter

Relapsing polychondritis (RP) is an autoimmune disorder characterized by inflammation in cartilaginous structures including the ears, noses, peripheral joints, and tracheobronchial tree. It rarely involves the central nervous system (CNS) but diagnosis of CNS complication of RP is challenging because it can present with varying clinical features. Herein we report 3 cases of relapsing polychondritis involving CNS with distinct manifestations and clinical courses. The first patient presented with rhombencephalitis resulting in brain edema and death. The second patient had acute cognitive dysfunction due to limbic encephalitis. He was treated with steroid pulse therapy and recovered without sequelae. The third patient suffered aseptic meningitis that presented as dementia, which was refractory to steroid and immune suppressive agents. We also reviewed literature on CNS complications of RP.
Brain Edema ; Central Nervous System* ; Dementia ; Diagnosis ; Ear ; Humans ; Inflammation ; Joints ; Limbic Encephalitis ; Meningitis, Aseptic ; Meningoencephalitis ; Nose ; Polychondritis, Relapsing* ; Trees

Anti-Ma2-associated encephalitis is one of the paraneoplastic neurological syndromes. It has been shown to be associated with various neoplasms, mainly testicular, lung, and breast cancers. Most patients with anti-Ma2-associated encephalitis present limbic-diencephalic-brainstem dysfunctions such as seizure, mood disorder, excessive daytime sleepiness, and ophthalmoparesis. Some patients develop symptoms indicating the multifocal involvement of the limbic system, diencephalon, or brainstem. However, there are few case studies of anti-Ma2-associated encephalitis presenting as isolated hypersomnia. We report a case of anti-Ma2-associated encephalitis presenting as hypersomnia.
Brain Stem ; Breast ; Diencephalon ; Disorders of Excessive Somnolence* ; Encephalitis* ; Humans ; Limbic System ; Lung ; Mood Disorders ; Ophthalmoplegia ; Paraneoplastic Syndromes ; Seizures

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders characterized by a deficit in social behaviors and nonverbal interactions such as reduced eye contact, facial expression, and body gestures in the first 3 years of life. It is not a single disorder, and it is broadly considered to be a multi-factorial disorder resulting from genetic and non-genetic risk factors and their interaction. Genetic studies of ASD have identified mutations that interfere with typical neurodevelopment in utero through childhood. These complexes of genes have been involved in synaptogenesis and axon motility. Recent developments in neuroimaging studies have provided many important insights into the pathological changes that occur in the brain of patients with ASD in vivo. Especially, the role of amygdala, a major component of the limbic system and the affective loop of the cortico-striatothalamo-cortical circuit, in cognition and ASD has been proved in numerous neuropathological and neuroimaging studies. Besides the amygdala, the nucleus accumbens is also considered as the key structure which is related with the social reward response in ASD. Although educational and behavioral treatments have been the mainstay of the management of ASD, pharmacological and interventional treatments have also shown some benefit in subjects with ASD. Also, there have been reports about few patients who experienced improvement after deep brain stimulation, one of the interventional treatments. The key architecture of ASD development which could be a target for treatment is still an uncharted territory. Further work is needed to broaden the horizons on the understanding of ASD.
Amygdala ; Autistic Disorder* ; Axons ; Brain ; Child ; Autism Spectrum Disorder* ; Cognition ; Deep Brain Stimulation ; Facial Expression ; Gestures ; Humans ; Limbic System ; Neurobiology ; Neuroimaging ; Nucleus Accumbens ; Reward ; Risk Factors ; Social Behavior

According to the Jastreboff's neurophysiological model of tinnitus, if negative associations are attached to the tinnitus signal, tinnitus is perceived to be a threat or a danger and it activates the autonomic nervous and limbic systems. Consequently patient's awareness of tinnitus is heightened and so patient perceives it to be louder and more persistent. Jastreboff and Hazell started tinnitus retraining therapy (TRT) based on the neurophysiological model of tinnitus. The purpose of TRT is blocking tinnitus from activating the sympathetic nervous and limbic systems (habituation of reaction) and from reaching the cerebral cortex (habituation of perception). TRT is composed of two components directive counseling that tries to reclassify tinnitus into the meaningless stimuli and sound therapy that decreases the relative strength of the tinnitus signal. Physicians try to put patient's tinnitus into the territory of meaningless stimuli through retraining the brain (habituation of reaction). Because the brain habituates all unimportant stimuli, if habituation of reaction is fully achieved, habituation of perception will follow automatically. In most clinical results, clinical success rates of TRT approach or exceed 80% improvement. Early improvement can be achieved during the first few months, followed by additional progressive improvement. It should be recommended that the patient continue treatment at least 18 months.
Brain ; Cerebral Cortex ; Directive Counseling ; Humans ; Limbic System ; Tinnitus*

Based on the limitation of biomedical model of tinnitus, more attention has been paid to personalities or psychological aspects. Depressive disorder, anxiety disorder, and sleep disturbance were comorbid illnesses of tinnitus and research showed that neurobiological mechanisms such as dysfunction of limbic system or HPA axis were common in tinnitus and affective disorders and that comorbid psychiatric disorders enhanced the negative outcome of tinnitus. Recently, more attention is being paid to the relation of tinnitus with personality and the role of stress. Although the causal relation of personality and tinnitus is unclear, stress in itself showed that it can be a trigger in the development of tinnitus, and stress of tinnitus can cause adverse effects. Since the effect of fear-related cognition such as catastrophic thought about tinnitus was revealed more recently, its therapeutic implication should be explored. This review will describe the product of previous research and discuss future direction about psychological factors related to tinnitus.
Anxiety Disorders ; Cognition ; Depressive Disorder ; Limbic System ; Mood Disorders ; Psychology* ; Tinnitus*

Tinnitus is an auditory phantom characterized by the perception of sound without the presence of an external acoustical source. The peripheral auditory system is considered to contribute to the initiation of tinnitus but only explains the severity and distress level to a limited degree. The neuropsychological models of tinnitus have been developed to explain the pathophysiology of tinnitus as a malfunctioning feedforward/feedback signal in the central neural system including the auditory brainstem, limbic system, auditory cortices, and other anatomical features. Functional neuroimaging techniques have been introduced in recent decades and have provided non-invasive tools to assess the working human brain in vivo. Researchers have found these techniques valuable in examining the neural correlates of tinnitus and have been able to not only support the neuropsychological model but to expand it. Though neuroimaging studies on tinnitus only began in 1990s, they have been increasing exponentially in number. In this review, we investigate the current state of functional neuroimaging studies on tinnitus in humans. The characteristics of commonly used functional neuroimaging techniques including positron emission tomography (PET), functional magnetic resonance imaging (fMRI), electroencephalography (EEG) and magnetoencephalography (MEG) are also discussed. We briefly review recent studies on the tinnitus-brain relationship that have used those research tools.
Brain ; Brain Stem ; Electroencephalography ; Functional Neuroimaging ; Humans ; Limbic System ; Magnetic Resonance Imaging ; Magnetoencephalography ; Neuroimaging ; Positron-Emission Tomography ; Tinnitus*