A Review of Brain Imaging Studies on Classical Fear Conditioning and Extinction in Healthy Adults

Fear conditioning and extinction, which are adaptive processes to learn and avoid potential threats, have essential roles in the pathophysiology of anxiety disorders. Experimental fear conditioning and extinction have been used to identify the mechanism of fear and anxiety in humans. However, the brain-based mechanisms of fear conditioning and extinction are yet to be established. In the current review, we summarized the results of neuroimaging studies that examined the brain changes—functional activity and structures—regarding fear conditioning or extinction in healthy individuals. The functional activity of the amygdala, insula, anterior cingulate gyrus, ventromedial prefrontal cortex, and hippocampus changed dynamically with both fear conditioning and extinction. This review may provide an up-to-date summary that may broaden our understanding of pathophysiological mechanisms of anxiety disorder. In addition, the brain regions that are involved in the fear conditioning and extinction may be considered as potential treatment targets in the future studies.

A Review on Neural Mechanisms of Transcranial Direct Current Stimulation on Cognitive Enhancement : Focused on Functional Magnetic Resonance Imaging Studies / 생물치료정신의학

Transcranial direct current stimulation (tDCS) is a non-invasive and effective neuromodulatory technique to modulate cortical activities by applying 1 to 2 milliamps electric current. The use of tDCS to enhance cognitive function such as executive function and memory has attracted much attention in recent years, and a lot of studies have been carried out to identify neural mechanisms underlying cognitive enhancement effects of tDCS. In this review, we discussed the previous neuroimaging studies on applications of tDCS for cognitive enhancement using functional magnetic resonance imaging (fMRI). Previous tDCS studies for neurological or psychiatric conditions and elderly individuals suggested that cognitive enhancement effects of tDCS were associated with normalizing aberrant brain networks and activities related to pathophysiology. Moreover, tDCS-induced cognitive enhancement in healthy individuals was associated with functional changes in brain activations and network connectivity. Furthermore, cognitive enhancement effects of tDCS were varied depending on the neurological structure and functional characteristics between individuals. The current review may provide critical insights into functional activity and connectivity of the brain regarding cognitive enhancement effects of tDCS, which could give direction for further studies on identifying the specific neural mechanisms and clinical strategies of tDCS.

Brain Perfusion Correlates of Apathy in Alzheimer's Disease

BACKGROUND AND PURPOSE: Apathy is one of the most common neuropsychiatric symptoms in patients with Alzheimer's disease (AD). It may have adverse impacts on the progression of AD. However, its neurobiological underpinnings remain unclear. The objective of this study was to investigate differences in regional cerebral blood flow (rCBF) between AD patients with apathy and those without apathy. METHODS: Sixty-six apathetic AD patients and 66 AD patients without apathy completed Neuropsychiatric Inventory (NPI) and underwent technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT) scans. Voxel-wise differences in rCBF between the 2 groups were examined. Association between rCBF and levels of apathy in the apathetic group was also assessed. RESULTS: AD patients with apathy showed lower rCBF in the bilateral orbitofrontal cortex, left putamen, left nucleus accumbens, left thalamus, and bilateral insula than those without (all p < 0.005). Mean perfusion across all significant clusters showed a negative linear correlation with NPI apathy score in AD patients with apathy (β = −0.25; p = 0.04). CONCLUSIONS: Hypoperfusion in the prefrontal, striatal, and insular areas may be neural correlates of apathy in AD patients.

Deleterious Effects of Shift Work in the Realm of Cognitive and Behavioral Domains : A Critical Review

Shift workers experience a disruption in the circadian sleep-wake rhythm, which brings upon adverse health effects such as fatigue, insomnia and decreased sleep quality. Moreover, shift work has deleterious effects on both work productivity and safety. In this review, we present a brief overview of the current literature on the consequences of shift work, especially focusing on attention-associated cognitive decline and related behavioral changes. We searched two electronic databases, PubMed and RISS, using key search terms related to cognitive domains, deleterious effects, and shift work. Twenty studies were eligible for the final review. The consequences of shift work can be classified into the following three categories extracted from the literature review : 1) work accidents ; 2) commuting accidents such as car accidents that occur on the way to and from work ; and 3) attendance management at work (i.e., absenteeism, tardiness, and unscheduled early departure). These cognitive and behavioral consequences of shift work were also found to be associated with sleep disorders in shift workers. Thus, improvements in the shift work system are necessary in order to enhance workers' health conditions, work productivity, and safety.

Animal Models of Demyelination and ¹H-Magnetic Resonance Spectroscopy

The proton magnetic resonance spectroscopy (¹H-MRS) is a tool used to detect concentrations of brain metabolites such as N-acetyl aspartate, choline, creatine, glutamate, and gamma-amino butyric acid (GABA). It has been widely used because it does not require additional devices other than the conventional magnetic resonance scanner and coils. Demyelination, or the neuronal damage due to loss of myelin sheath, is one of the common pathologic processes in many diseases including multiple sclerosis, leukodystrophy, encephalomyelitis, and other forms of autoimmune diseases. Rodent models mimicking human demyelinating diseases have been induced by using virus (e.g., Theiler's murine encephalomyelitis virus) or toxins (e.g., cuprizon or lysophosphatidyl choline). This review is an overview of the MRS findings on brain metabolites in demyelination with a specific focus on rodent models.

Reliability and Validity of the Korean Version of the Post-Traumatic Stress Disorder Checklist in Public Firefighters and Rescue Workers

OBJECTIVES: Firefighters and rescue workers are likely to be exposed to a variety of traumatic events; as such, they are vulnerable to the risk of post-traumatic stress disorder (PTSD). The psychometric properties of the Korean version of the PTSD Checklist (PCL), a widely used self-report screening tool for PTSD, were assessed in South Korean firefighters and rescue workers. METHODS: Data were collected via self-report questionnaires and semi-structured clinical interviews administered to 221 firefighters. Internal consistency, item-total correlation, one-week test-retest reliability, convergent validity, and divergent validity were examined. Content validity of the PCL was evaluated using factor analysis and receiver operating characteristic (ROC) analyses were used to estimate the optimal cutoff point and area under the curve. RESULTS: The PCL demonstrated excellent internal consistency (alpha = 0.97), item-total correlation (r = 0.72-0.88), test-retest reliability (r = 0.95), and convergent and divergent validity. The total score of PCL was positively correlated with the number of traumatic events experienced (p < 0.001). Factor analysis revealed two theoretically congruent factors: re-experience/avoidance and numbing/hyperarousal. The optimal cutoff was 45 and the area under the ROC curve was 0.97. CONCLUSIONS: The Korean version of the PCL may be a useful PTSD screening instrument for firefighters and rescue workers, further maximizing opportunities for accurate PTSD diagnosis and treatment.

Neurocriminology : A Review on Aggression and Criminal Behaviors Using Brain Imaging

Criminology has been understood within a sociological framework until the emergence of neurocriminology, which describes, understands and predicts criminal behaviors from a neurobiological point of view. Not only using biological factors including genes and hormones to understand criminal behaviors, but also using neuroimaging techniques, the field of neurocriminology aims to delve into both structural and functional differences in the brain of individuals with aggression, antisocial personalities, and even the criminals. Various studies have been conducted based on this idea, however, there still are limitations for the knowledge from these studies to be used in the court. In this review article, we provide an overview of the various research in neurocriminology, and provide insight into the future direction and implication of the field.

Aggression and Neurotransmitters

Aggression and aggressive behaviors, often explained as harmful social interaction with the intention of hurting or inflicting damage upon another, have been considered as an adaptive mechanism from the evolutionary psychological point of view. However, various studies on aggression and aggressive behaviors have been done with psychopathological approach as the extreme aggressive behaviors may harm themselves and others at the same time. Recently, researchers have attempted to explain aggression in terms of neurobiological substrates rather than based on traditional psychopathological and/or behavioral concept. In this regard, there have been findings of differences in neurotransmitters and their receptors, and genetic polymorphisms. In this review article, we provide a brief overview of the literature about seven most frequently reported neurotransmitters including neurohormones (serotonin, norepinephrine, dopamine, gamma-aminobutyric acid, nitric oxide, oxytocin and vasopressin) and an associated enzyme (monoamine oxidase A), which are known to be related with aggression and aggressive behaviors.

Prefrontal Cortical Thickness Deficit in Detoxified Alcohol-dependent Patients

Alcohol dependence is a serious disorder that can be related with a number of potential health-related and social consequences. Cortical thickness measurements would provide important information on the cortical structural alterations in patients with alcohol dependence. Twenty-one patients with alcohol dependence and 22 healthy comparison subjects have been recruited and underwent high-resolution brain magnetic resonance (MR) imaging and clinical assessments. T1-weighted MR images were analyzed using the cortical thickness analysis program. Significantly thinner cortical thickness in patients with alcohol dependence than healthy comparison subjects was noted in the left superior frontal cortical region, correcting for multiple comparisons and adjusting with age and hemispheric average cortical thickness. There was a significant association between thickness in the cluster of the left superior frontal cortex and the duration of alcohol use. The prefrontal cortical region may particularly be vulnerable to chronic alcohol exposure. It is also possible that the pre-existing deficit in this region may have rendered individuals more susceptible to alcohol dependence.

Reduced Gray Matter Density in the Posterior Cerebellum of Patients with Panic Disorder: A Voxel-Based Morphometry Study

OBJECTIVES: It is increasingly thought that the human cerebellum plays an important role in emotion and cognition. Although recent evidence suggests that the cerebellum may also be implicated in fear learning, only a limited number of studies have investigated the cerebellar abnormalities in panic disorder. The aim of this study was to evaluate the cerebellar gray matter deficits and their clinical correlations among patients with panic disorder. METHODS: Using a voxel-based morphometry approach with a high-resolution spatially unbiased infratentorial template, regional cerebellar gray matter density was compared between 23 patients with panic disorder and 33 healthy individuals. RESULTS: The gray matter density in the right posterior-superior (lobule Crus I) and left posterior-inferior (lobules Crus II, VIIb, VIIIa) cerebellum was significantly reduced in the panic disorder group compared to healthy individuals (p < 0.05, false discovery rate corrected, extent threshold = 100 voxels). Additionally, the gray matter reduction in the left posterior-inferior cerebellum (lobule VIIIa) was significantly associated with greater panic symptom severity (r = -0.55, p = 0.007). CONCLUSIONS: Our findings suggest that the gray matter deficits in the posterior cerebellum may be involved in the pathogenesis of panic disorder. Further studies are needed to provide a comprehensive understanding of the cerebro-cerebellar network in panic disorder.

Effects of the Combination Herbal Extract on Working Memory and White Matter Integrity in Healthy Individuals with Subjective Memory Complaints : A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

OBJECTIVES: The combination extract of four kinds of herbs, Gastrodia elata, Liriope platyphylla, Dimocarpus longan, and Salvia miltiorrhiza, has shown to have memory improving effects in mice. The aim of this study was to investigate the efficacy and safety of the herbal mixture for improving working memory as well as microstructural changes in white matter integrity in individuals with subjective memory complaints. METHODS: Seventy-five individuals with subjective memory complaints were assigned to receive either placebo (n = 15) or herbal mixture (low-dose group, n = 30 and high-dose group, n = 30) supplementation in an 8-week, randomized, double-blind, placebo-controlled clinical trial. Changes in working memory performance and fractional anisotropy (FA) values reflecting white matter integrity from baseline to 8-week endpoint were assessed. RESULTS: The herbal mixture group showed an increase in working memory performance compared to the placebo group (p for interaction = 0.001). In addition, the herbal mixture group showed an increase in FA values in the temporo-parietal regions (corrected p < 0.05), which are crucially involved in working memory function and are among the most affected regions in patients with cognitive impairments. CONCLUSIONS: Findings from this study indicate that the herbal mixture may be a promising therapeutic option for individuals with subjective memory complaints.

Effects of Korean Red Ginseng on White Matter Microstructure and Cognitive Functions: A Focus on Intrusion Errors

OBJECTIVES: Although ginseng has been reported to protect neuronal cells and improve various cognitive functions, relationship between ginseng supplementation and response inhibition, one of the important cognitive domains has not been explored. In addition, effects of ginseng on in vivo human brain have not been investigated using the diffusion tensor imaging (DTI). The purpose of the current study is to investigate changes in intrusion errors and white matter microstructure after Korean Red Ginseng supplementation using standardized neuropsychological tests and DTI. METHODS: Fifty-one healthy participants were randomly allocated to the Korean Red Ginseng (n = 26) or placebo (n = 25) groups for 8 weeks. The California Verbal Learning Test was used to assess the number of intrusion errors. Intelligence quotient (IQ) was measured with the Korean Wechsler Adult Intelligence Scale. Depressive and anxiety symptoms were evaluated using Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and Hopkins Symptom Checklist-25. The fractional anisotropy (FA) was measured from the brain DTI data. RESULTS: After the 8-week intervention, Korean Red Ginseng supplementation significantly reduced intrusion errors after adjusting age, sex, IQ, and baseline score of the intrusion errors (p for interaction = 0.005). Change in FA values in the left anterior corona radiata was greater in the Korean Red Ginseng group compared to the placebo group (t = 4.29, p = 0.04). CONCLUSIONS: Korean Red Ginseng supplementation may be efficacious for improving response inhibition and white matter microstructure integrity in the prefrontal cortex.