Hyeongrae Lee

Neural network functional connectivity during and after an episode of delirium.

OBJECTIVE Delirium is a common and potentially life-threatening clinical syndrome. The authors investigated resting-state functional connectivity in patients with delirium to elucidate possible neural mechanisms underlying this disorder. METHOD Twenty-two patients underwent initial functional MRI at rest during an episode of delirium. Of these patients, 14 completed follow-up scans after the episode resolved. Twenty-two comparison subjects without delirium also underwent scanning. The authors assessed cortical functional connectivity using the seed region of the posterior cingulate cortex and functional connectivity strengths between a priori subcortical regions related to acetylcholine and dopamine on data from 20 initial and 13 follow-up scans. RESULTS Dorsolateral prefrontal cortex activity and posterior cingulate cortex activity were inversely correlated in comparison subjects but strongly correlated in patients during an episode of delirium as indicated by increased functional connectivity between the two regions. Although precuneus activity was positively correlated with posterior cingulate cortex activity in comparison subjects, the correlation was further increased in patients during an episode of delirium, and the increment was associated with less severity and shorter duration of delirium. Functional connectivity strengths of the intralaminar thalamic and caudate nuclei with other subcortical regions were reduced during an episode of delirium but recovered after resolution of the episode. CONCLUSIONS These findings suggest that the disruption in reciprocity of the dorsolateral prefrontal cortex with the posterior cingulate cortex and reversible reduction of functional connectivity of subcortical regions may underlie the pathophysiology of delirium. In addition, enhanced integration in the posteromedial cortices may account for facilitating the rapid improvement of delirium.

Functional and effective connectivity of anterior insula in anorexia nervosa and bulimia nervosa.

The anterior insula has been proposed to play a crucial role in eating disorders. However, it is still poorly understood how the anterior insula is involved in anorexia nervosa (AN) and bulimia nervosa (BN), which are characterized by opposite motivational responses to food. We applied a cue-reactivity paradigm using blood oxygen level-dependent functional magnetic resonance imaging in women with AN (N=18) and BN (N=20) and age-matched healthy controls (N=20). We defined the left anterior insula as a region-of-interest and performed seed-based functional connectivity and effective connectivity MRI analysis. In response to food images compared to non-food images, both the AN group and BN group demonstrated increased activity in the left anterior insula. In the AN group, the left anterior insula demonstrated significant interactions with the right insula and right inferior frontal gyrus. In the BN group, the left anterior insula demonstrated significant interactions with the medial orbitofrontal cortex. The distinct patterns of functional and effective connectivity of the anterior insula may contribute to the different clinical features of AN and BN.

Increased personal space of patients with schizophrenia in a virtual social environment

Virtual reality may be a good alternative method for measuring personal space and overcoming some limitations in previous studies on the social aspects of schizophrenia. Using this technology, we aimed to investigate the characteristics of personal space in patients with schizophrenia and evaluate the relationship between their social behaviors and schizophrenic symptoms. The distance from a virtual person and the angle of head orientation while talking to a virtual person in a virtual environment were measured in 30 patients with schizophrenia and 30 normal controls. It was found that patients with schizophrenia had longer distances and larger angles than did normal controls. The severity of the negative syndrome had significant inverse correlations with the distance from the angry and neutral virtual persons and with the angle of head orientation toward the happy and angry virtual persons, suggesting that negative symptoms may have a close relationship with personal space, including distancing and eye gaze. The larger personal space of patients may reflect their discomfort in close situations or cognitive deficits. Showing these profiles to patients could help them realize the amount of personal space they need.

Development and Verification of an Alcohol Craving–Induction Tool Using Virtual Reality: Craving Characteristics in Social Pressure Situation

Alcoholism is a disease that affects parts of the brain that control emotion, decisions, and behavior. Therapy for people with alcoholism must address coping skills for facing high-risk situations. Therefore, it is important to develop tools to mimic such conditions. Cue exposure therapy (CET) provides high-risk situations during treatment, which raises the individuals ability to recognize that alcohol craving is being induced. Using CET, it is hard to simulate situations that induce alcohol craving. By contrast, virtual reality (VR) approaches can present realistic situations that cannot be experienced directly in CET. Therefore, we hypothesized that is possible to model social pressure situations using VR. We developed a VR system for inducing alcohol craving under social pressure situations and measured both the induced alcohol craving and head gaze of participants. A 2 x 2 experimental model (alcohol-related locality vs. social pressure) was designed. In situations without an avatar (no social pressure), more alcohol craving was induced if alcohol was present than if it was not. And more alcohol craving was induced in situations with an avatar (social pressure) than in situations without an avatar (no social pressure). The difference of angle between the direction of head gazing and the direction of alcohol or avatar was smaller in situations with an avatar alone (social pressure) than in situations with alcohol alone. In situations with both alcohol and an avatar, the angle between the direction of head gaze and the direction of the avatar was smaller than between the direction of head gaze and the direction of the alcohol. Considering the results, this VR system induces alcohol craving using an avatar that can express various social pressure situations.

Nonverbal social behaviors of patients with bipolar mania during interactions with virtual humans.

It has been proposed that positive emotional biases could make bipolar manic (BM) patients maintain abnormally approaching behaviors during social interactions. To test this hypothesis, we measured interpersonal distance (IPD) and gaze angle of BM patients and normal controls (NCs) during social interaction in immersive virtual environment. Overall, IPDs of BM patients (n = 20) were greater than those of normal controls (n = 20). The IPD difference was even greater between NCs and BM patients with psychotic features (n = 11) than those without psychotic features (n = 9). Regardless of the presence of psychotic features, BM patients averted their gazes more than NCs, and even more while speaking than while listening. Our results might suggest negativistic social cognition of bipolar patients, as was previously found even during a manic phase, or the role of paranoid symptoms in avoidant social behaviors, in agreement with prior studies with schizophrenic patients. Use of proper space and gaze might have psychotherapeutic implication in developing secure, two-person relationship with bipolar patients regardless of the presence of disrupting manic symptoms.

Neural evidence for emotional involvement in pathological alcohol craving

AIMS Reducing craving is a key to success in the treatment of alcohol dependence. The emotion circuit may be involved in pathological craving for alcohol. In this study, we investigated neural correlates of emotional involvement in craving in alcohol dependence. METHODS The study included 17 detoxified alcoholic patients and 25 social drinkers. We used functional magnetic resonance imaging to examine brain activation (blood oxygen level-dependent signals) while participants reported craving and emotion in response to visually presented, alcohol-related stimuli and emotional stimuli. RESULTS In the craving-rating paradigm, negative emotional stimuli as well as alcohol cues activated craving-related brain regions in alcoholic patients. Activations of the inferior parietal lobule and dorsolateral prefrontal cortex by negative emotional stimuli were negatively correlated with craving; meanwhile limbic activation was positively correlated with craving. For the emotion paradigm, greater limbic activation was evident by alcohol-related stimuli in the alcohol-dependent group. CONCLUSIONS Our findings constitute neural evidence for emotional involvement in pathological craving for alcohol, underscoring the importance of emotion management in abstinent alcoholic patients for relapse prevention.

Frontostriatal Connectivity Changes in Major Depressive Disorder After Repetitive Transcranial Magnetic Stimulation: A Randomized Sham-Controlled Study.

OBJECTIVE The aim of this randomized, sham-controlled study was to investigate the therapeutic effects of underlying neurobiological changes after 2-week repetitive transcranial magnetic stimulation (rTMS) treatment using functional connectivity magnetic resonance imaging in patients with major depression. METHODS Twenty-four patients with major depressive disorder diagnosed with DSM-IV-TR criteria were randomly assigned to the active rTMS (n = 13) or sham (n = 11) groups from January 2009 to June 2011. rTMS was given for 2 weeks at 110% of the motor threshold for 10 minutes at 10 Hz over the left dorsolateral prefrontal cortex (DLPFC). Resting state functional connectivity was evaluated before and after rTMS. The 17-item Hamilton Depression Rating Scale (HDRS) was administered, and neurocognitive tasks were performed. We examined between-group differences in functional connectivity changes from the bilateral DLPFC. RESULTS Participants in the active rTMS group showed significant clinical improvement in HDRS scores compared to those in the sham group (P < .001). After 2-week rTMS, there were significant differences in changes in DLPFC-left caudate connectivity (corrected P < .05): the active group showed a greater reduction of connectivity strength between the DLPFC and left caudate compared to the sham group. Reduced levels of DLPFC-left caudate connectivity predicted improvement in depressive symptoms (r = 0.58, P = .001). Additionally, a positive correlation between residual depressive symptoms and connectivity strength after 2-week rTMS was found (r = 0.46, P = .023). CONCLUSIONS High-frequency rTMS over the left DLPFC showed therapeutic effects in patients with major depression. The therapeutic effect of rTMS is related to the modulation of functional connectivity in the frontostriatal network. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01325831​.

Distinct functional connectivity of limbic network in the washing type obsessive-compulsive disorder

Neurobiological models of obsessive-compulsive disorder (OCD) emphasize disturbances of the corticostriatal circuit, but it remains unclear as to how these complex network dysfunctions correspond to heterogeneous OCD phenotypes. We aimed to investigate corticostriatal functional connectivity alterations distinct to OCD characterized predominantly by contamination/washing symptoms. Functional connectivity strengths of the striatal seed regions with remaining brain regions during the resting condition and the contamination symptom provocation condition were compared among 13 OCD patients with predominant contamination/washing symptoms (CON), 13 OCD patients without these symptoms (NCON), and 18 healthy controls. The CON group showed distinctively altered functional connectivity between the ventral striatum and the insula during both the resting and symptom-provoking conditions. Also, the connectivity strength between the ventral striatum and the insula significantly correlated with contamination/washing symptom severity. As common connectivity alterations of the whole OCD subjects, corticostriatal circuits involving the orbitofrontal and temporal cortices were again confirmed. To our knowledge, this is the first study that examined specific abnormalities in functional connectivity of contamination/washing symptom dimension OCD. The findings suggest limbic network dysfunctions to play a pivotal role in contamination/washing symptoms, possibly associated with emotionally salient error awareness. Our study sample allowed us to evaluate the corticostriatal network dysfunction underlying the contamination/washing symptom dimension, which leaves other major symptom dimensions to be explored in the future.

Restoration of mammillothalamic functional connectivity through thiamine replacement therapy in Wernicke's encephalopathy.

Resting-state functional MRI (fMRI) is now providing further understanding of neuropsychiatric illnesses. However, its practical applicability in the clinical realms is still questionable. Here we report three consecutive followed-up resting-state fMRI data in a single case with Wernicke encephalopathy before and after high-dose thiamine replacement therapy ranging over 20 months. We measured the mammillothalamic functional connectivity strength between the first ROI (mammillary body) and a voxel which showed the highest co-activation among voxels within the anterior thalamus (the second ROI) to enhance the specificity of the functional connectivity data. We found that the time-series changes in the mammillothalamic functional connectivity generally paralleled to the changes in delayed verbal and nonverbal recall memory scores in the left and right hemisphere, respectively. Among these, the left-side connectivity and delayed verbal recall score seemed to be related to the overall clinical status change. Modified directed transfer function (dDTF) analysis also identified significant information flows with mammillary-to-thalamic direction except at the acute illness state. Our findings, though preliminary in nature, suggest the practical applicability of resting-state fMRI to trace an effect of thiamine replacement therapy on the memory tract function in Wernicke encephalopathy at single-patient level.

Effect of Proprioception Training of patient with Hemiplegia by Manipulating Visual Feedback using Virtual Reality: The Preliminary results

In this study, we confirmed proprioception training effect of patients with hemiplegia by manipulating visual feedback. Six patients with hemiplegia were participated in the experiment. Patients have trained with the reaching task with visual feedback without visual feedback for two weeks. Patients were evaluated with pre-, middle test and post-test with the task with and without visual feedback. In the results, the first-click error distance after the training of the reaching task was reduced when they got the training with the task removed visual feedback. In addition, the performance velocity profile of reaching movement formed an inverse U shape after the training. In conclusion, visual feedback manipulation using virtual reality could provide a tool for training reaching movement by enforcing to use their proprioception, which enhances reaching movement skills for patients with hemiplegia.