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Objective: Restless legs syndrome (RLS) patients compared to controls have been found to have abnormal patterns in the default mode network (DMN) in the morning when symptom threshold is the highest and symptoms are least likely to occur. If these morning abnormalities in DMN are pertinent to disease expression, then similar or further detectable differences may be expected on a nighttime assessment when RLS symptom threshold is at its lowest. The purpose of this study was to elucidate the potential neural mechanisms underlying the circadian aspect of RLS symptom expression by assessing diurnal changes in DMN., Methods: Fifteen drug-naïve subjects with idiopathic RLS and 15 age- and gender-matched healthy subjects had fMRI scans in the morning and evening. The DMN patterns were compared both for differences between morning and evening and between RLS and controls., Results: RLS patients compared to the healthy controls showed significant differences in morning and evening DMN. In particular, RLS patients showed consistent increased connectivity in the parietal lobule in both the morning and evening. In contrast, connectivity in the thalamus was increased in the morning and reduced in the evening. In addition, there were negative correlations between thalamic connectivity and the Korean versions of the international RLS scale and the quality-of-life subscore., Conclusions: The results indicated diurnal disturbances of the DMN in RLS subjects are consistent with both the circadian rhythm and severity of RLS. The circadian expression of RLS may relate to changes in arousal cortical-activation thresholds occurring with diurnal changes in the thalamic circuits of the DMN., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Previous studies have suggested that early-onset RLS (EOR) and late-onset RLS (LOR) might have different etiopathophysiologies. Few previous studies have examined accumulation of cerebrovascular ischemic changes as a potential cause of LOR., Methods: We recruited 39 RLS subjects (LOR: defined as age of RLS onset ≥45, n = 18 and EOR: age of onset <45; n = 21); and 39 healthy control subjects matched on age and sex. Structural magnetic resonance imaging (MRI) of the brain was performed for each subject, and images were graded for severity of periventricular white matter hyperintensities (PVH) and deep white matter hyperintensities (DWMH) independently by trained raters according to standardized methods., Results: Interrater reliabilities were 0.861 (p <0.001) for PVH and 0.900 (p <0.001) for DWMH. LOR subjects had a significantly higher grade of DWMH than the EOR subjects (p = 0.043) and age- and sex-matched controls (p = 0.015). In contrast, there was no difference in DWMH severity rating between the EOR group and the EC group or in PVH severity between the LOR or EOR groups and their age-matched controls., Conclusion: Our findings suggest that the presence and severity of DWMH is associated with LOR, but not with EOR. Further examination of the contribution of cerebrovascular disease to the etiopathogenesis of LOR is warranted., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background/objectives: Although hypertension is known to be a risk factor for AD, the effects of hypertension on brain function in AD patients are not well understood. We investigated alterations in resting-state functional connectivity according to the presence of hypertension in AD patients by using a method of correlation analysis based on a seed region in the posterior cingulate cortex (PCC). We also determined whether differences in resting-state connectivity were associated with gray matter atrophy., Methods: Thirty-seven AD patients (18 patients with hypertension and 19 patients without hypertension) underwent the resting-state functional magnetic resonance imaging. We obtained the PCC maps by a temporal correlation method, to identify alterations in the functional connectivity of the PCC in hypertensive group relative to non-hypertensive group. Voxel-based morphometry analysis was also applied to adjust the confounding effect of gray matter atrophy., Results: We detected a decreased connectivity to the PCC in the regions of subgenual anterior cingulated cortex (ACC) in hypertensive group relative to non-hypertensive group. However, we observed a pattern of increased connectivity between the PCC and the left inferior parietal cortex in hypertensive group. After correction for gray matter atrophy, all detected regions still remained significant., Conclusions: Altered connectivity in AD patients with hypertension suggests the possibility that hypertension impairs resting-state functional connectivity of the AD brain, inducing a compensational process outside the impaired networks or disequilibrium in brain connectivity. This finding may account for an additional contribution of hypertension to the pathophysiology of AD., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The purpose of this study was to demonstrate whether or not restless legs syndrome (RLS) is associated with any morphological change in gray matter. Forty-six RLS subjects and 46 controls were enrolled. We performed voxel-based morphometry analysis and compared the results of the two groups. The RLS subjects showed significant regional decreases of gray matter volume in the left hippocampal gyrus, both parietal lobes, medial frontal areas and cerebellum (uncorrected, P<.001). We found that RLS patients showed structural alteration in the brain and alterations in certain parts of the brain in RLS patients are relevant to RLS., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To demonstrate the usefulness of 3-tesla (3T) magnetic resonance imaging (MRI) including T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), time-of-flight (TOF) magnetic resonance angiography (MRA), T2*-weighted gradient recalled echo (GRE), and susceptibility weighted imaging (SWI) in diagnosing brain death., Materials and Methods: Magnetic resonance imaging findings for 10 patients with clinically verified brain death (group I) and seven patients with comatose or stuporous mentality who did not meet the clinical criteria of brain death (group II) were retrospectively reviewed., Results: Tonsilar herniation and loss of intraarterial flow signal voids (LIFSV) on T2WI were highly sensitive and specific findings for the diagnosis of brain death (p < 0.001 and < 0.001, respectively). DWI, TOF-MRA, and GRE findings were statistically different between the two groups (p = 0.015, 0.029, and 0.003, respectively). However, cortical high signal intensities in T2WI and SWI findings were not statistically different between the two group (p = 0.412 and 1.0, respectively)., Conclusion: T2-weighted imaging, DWI, and MRA using 3T MRI may be useful for diagnosing brain death. However, SWI findings are not specific due to high false positive findings.

Individuals sometimes experience an illusory or hallucinatory perception. This unreal perception is usually resolved after the individual recognizes that the perception was not real. In this study, we investigated the brain mechanisms involved in the process to an illusory or hallucinatory perception through 'obtaining insight into unreality'. We used a novel and intuitive paradigm designed by combining functional magnetic resonance imaging and augmented reality technology to simulate visual illusory stimuli that mimic hallucinations during brain scanning. The results showed various brain activations, predominantly in the amygdala in the early phase, the medial frontal cortex and the occipitotemporal junction in the middle phase, and the thalamus in the late phase, which correlated with a subject's proneness to hallucinating. These activations may correspond to a 'responding stage' for a perception-based immediate emotional reaction, a 'monitoring stage' for integration and recalibration to ascertain that the perception was not real, and a 'resolving stage' for controlling the information and finally settling it, respectively. Our paradigm and findings may be useful in understanding the mechanisms for discriminating and coping with hallucinatory perceptions.

Spatial smoothing is an important post-processing procedure that is used to increase the signal-to-noise ratio (SNR) of blood oxygenation level-dependent signals (BOLD) in common functional magnetic resonance imaging (fMRI) applications. However, recent studies have shown that smoothing artificially shifts probabilistic local maxima of fMRI activations. In this study, we show shifting of the localization of functional centers in hand motor areas of the cerebral cortex by three-dimensional isotropic Gaussian kernel smoothing or two-dimensional heat kernel smoothing in volume- and surface-based fMRI analyses. Activation maps derived from smoothed echo planar imaging (EPI) data by volume- and surface-based analyses were assigned to the nodes of individual cortical surface models, and local maxima in the primary motor area (M1) and the primary somatosensory cortex (S1) were compared with those derived from non-smoothed risk map analysis, which is commonly used in presurgical applications. For each analysis, the Euclidean and geodesic distances between the correlation coefficients of local maxima derived from smoothed and non-smoothed EPI data were measured. The results show that the correlation coefficients derived from the volume- and surface-based analyses were about 29.4% and 42.9% higher for smoothed than for non-smoothed risk map analyses, and show minimum shifting of localizations by 12.1 mm and 6.9 mm on average in Euclidean distance, respectively, and about 9.5 mm and 5.7 mm on average in geodesic distance, respectively.

Virtual reality (VR) technology is increasingly recognized as a useful tool for the assessment and rehabilitation of neurologic and psychiatric disorders. The hope that VR can accurately mimic real-life events is also of great interest in basic neuroscience, to identify the brain activity that underlies complex behavior by combining VR with techniques such as functional magnetic resonance imaging (fMRI). Toward these applications, in this study we designed and validated an fMRI-compatible data glove with a built-in vibratory stimulus device for tactile feedback during VR experiments. A simple VR-fMRI experiment was performed at 3.0 Tesla on four young healthy adults involving touching a virtual object with and without tactile feedback. The usefulness of the data glove was subsequently assessed using a series of questionnaires, behavioral performance, and the resulting activation images. Questionnaire scores indicated positive opinions with respect to the data glove, the tactile feedback, and the experimental paradigm. All subjects felt comfortable in the scanner during the VR experiment and were able to perform all aspects of the tasks successfully and with reasonable accuracy. In addition, activation maps showed the anticipated modulations in motor, somatosensory, and parietal cortex. These results support that tactile feedback enhances the realism of virtual hand-object interactions, and that the tactile data glove is suitable for use in other VR-fMRI research applications (e.g., VR physical therapy for stroke recovery).

Objectives: Resting-state brain connectivity has been shown to differ for Restless Legs Syndrome (RLS) compared to healthy control (CON) groups. This study evaluates the degree these RLS-CON differences are changed by concurrent treatment.Methods: Resting-state functional MRIs were obtained from 32 idiopathic RLS patients during the morning asymptomatic period and 16 age and gender-matched CON subjects. Of the 32 RLS patients, 16 were drug-naïve (DN-RLS), and 16 were regularly drug-treated using a dopamine agonist (DT-RLS). Various assessments of disease characteristics were also performed. The primary purpose was to assess the replicability of prior results and the effects of treatment on these differences between controls and untreated RLS patients. Resting-state connectivity was analyzed by a seed-based method using the bilateral ventral-posterolateral nuclei (VPLN) in the thalamus.Results: In the DN-RLS group, compared to the CON group, three areas (the bilateral lingual gyri and right middle temporal gyrus) were replicated. The three replicated areas did not significantly differ for DT-RLS compared to DN-RLS. DT-RLS compared to DN-RLS had significantly higher thalamic connectivity for the left uvula, right tuber, left anterior insula, and right declive.Conclusions: Thalamic connectivity to the bilateral lingual gyri and right middle temporal gyrus is a replicable finding in DN-RLS that was not affected by dopamine agonist treatments. Other changes in thalamic connectivity were altered by dopamine agonist treatment. These treatment effects may be pertinent to the known treatment benefits of a dopamine agonist on RLS symptoms. [ABSTRACT FROM AUTHOR]

Background: The unusual sensations of restless legs syndrome/Willis-Ekbom disease (RLS/WED) are induced by rest or a low arousal state with a circadian variation in the threshold for induction. It has been suggested that the emergence of RLS/WED symptoms relates to abnormal brain functions dealing with internally generated stimuli. The purpose of this study was to investigate the changes in the default mode network (DMN) in RLS/WED subjects.Methods: Sixteen drug-naïve, idiopathic, RLS/WED subjects, and 16 age-matched and gender-matched healthy subjects were scanned in an asymptomatic resting state. A comparison of the DMN was conducted between the two groups. Resting state functional magnetic resonance imaging (MRI), Korean versions of the International RLS scale, and other sleep questionnaires were used.Results: The results showed reductions in the DMN connectivity in the left posterior cingulate cortex, the right orbito-frontal gyrus, the left precuneus, and the right subcallosal gyrus of the RLS/WED subjects. The DMN connectivity was increased in sensory-motor-associated circuits, which included the right superior parietal lobule, the right supplementary motor area, and the left thalamus. In addition, the connectivity between the DMN and thalamus was negatively correlated with that in the orbito-frontal gyrus and the subcallosal gyrus in the subjects.Conclusions: The results showed disturbances of the DMN in RLS/WED subjects that influence the thalamic relay sensory-motor-associated circuit. These findings may underscore the fact that RLS/WED subjects have disturbances in default mode network functions involving internal stimuli in the resting state. This may be related to compensatory changes to maintain resting. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Most patients with schizophrenia suffer from various types of hallucinations, which commonly produce distress, functional disability or behavioral dyscontrol. The neural process of adapting to hallucinations in patients with schizophrenia remains unknown. Methods: Functional magnetic resonance imaging (MRI) responses to an unusual threatening visual stimulus designed to simulate a hallucinatory experience were compared between 16 patients with schizophrenia and 17 healthy controls. Linear and quadratic repetition-variant as well as repetition-invariant responses to the stimulus were compared between the two groups. Results: Repetition-invariant responses were similar between patients with schizophrenia and healthy controls. Patients with schizophrenia exhibited a linear activation pattern in the anterior cingulate, whereas healthy controls exhibited a parabolic activation pattern in the anterior prefrontal cortex, occipito-temporal junction and amygdala. Conclusions: These results provide us with a better understanding of the neural processes involved in gaining insight into unreality. Patients with schizophrenia may use a salience-related region instead of reality monitoring-related regions to react to the unusual stimuli, and this peculiarity of the neural processes may be related to vulnerability to psychosis. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Background: Previous studies on patients diagnosed with social anxiety disorder (SAD) reported changed patterns of the resting-state functional connectivity network (rs-FCN) between the prefrontal cortices and other prefrontal, amygdalar or striatal regions. Using a graph theory approach, this study explored the modularity-based community profile and patterns of inter-/intra-modular communication for the rs-FCN in SAD.Methods: In total, for 28 SAD patients and 27 healthy controls (HC), functional magnetic resonance imaging (fMRI) data were acquired in resting-state and subjected to a graph theory analysis.Results: The within-module degree z-score for a hub region [out of a total of 10 hub regions ranked using the participation coefficient] named left middle temporal gyrus was impaired in SAD compared to HC, proportional to the severity of clinician-scored and patient-reported functional impairment in SAD.Limitations: Most of participants included in this study were undergraduate students in their early-to-mid 20's.Conclusions: This study showed the importance of functional communication from the left middle temporal gyrus with other opercular-insular-subcortical regions for better objective functioning and lesser subjective disability in SAD. [ABSTRACT FROM AUTHOR]

• Alterations in cortical thickness fit into the neurocircuitry models of SAD. • Cortical thickening and thinning were observed in the frontoparietal regions. • Changes in cortical thickness were not correlated with social anxiety symptoms. Although functional changes of the frontal and (para)limbic area for emotional hyper-reactivity and emotional dysregulation are well documented in social anxiety disorder (SAD), prior studies on structural changes have shown mixed results. This study aimed to identify differences in cortical thickness between SAD and healthy controls (CON). Thirty-five patients with SAD and forty-two matched CON underwent structural magnetic resonance imaging. A vertex-based whole brain and regional analyses were conducted for between-group comparison. The whole-brain analysis revealed increased cortical thickness in the left insula, left superior parietal lobule, left superior temporal gyrus, and left frontopolar cortex in patients with SAD compared to CON, as well as decreased thickness in the left superior/middle frontal gyrus and left fusiform gyrus in patients (after multiple-correction). The results from the ROI analysis did not align with these findings at the statistically significant level after multiple corrections. Changes in cortical thickness were not correlated with social anxiety symptoms. While consistent results were not obtained from different analysis methods, the results from the whole-brain analysis suggest that patients with SAD exhibit distinct neural deficits in areas involved in salience, attention, and socioemotional processing. [ABSTRACT FROM AUTHOR]

Abstract: Social cognition entails both cognitive and affective processing, and impairments in both have accounted for residual symptoms of bipolar disorder (BD). However, there has been a lack of studies identifying neural substrates responsible for social cognitive difficulties in BD patients. Fourteen euthymic BD patients and 14 healthy normal controls underwent functional MRI while performing a virtual reality social cognition task, which incorporated both cognitive and emotional dimensions, simulating real-world social situations. During the scanning, subjects tried to guess (attribute) possible reasons for expressed emotion of virtual humans (avatars) while viewing their facial expressions, just after observing their verbal and nonverbal (facial) expressions which were emotionally valenced (happy, angry and neutral). BD patients compared to normal controls showed delayed reaction times in emotional conditions, with comparable response accuracy. Healthy normal controls activated the right anterior cingulate cortex, inferior frontal, and insular cortex in emotional conditions contrasted with neutral control conditions, that is, the regions that have been related to empathic processes during viewing others'' emotional expression. Relative to normal controls, BD patients showed reduced activations in the ‘mirror neuron system’, including the right inferior frontal cortex, premotor cortex, and insula, mainly in angry or happy condition. These results may suggest that, even during euthymic state, BD patients have difficulties in recruiting brain regions for the utilization of emotional cues as a means for understanding others. Clinical attention should be paid to emotion-related residual symptoms to help improve social outcomes in these patients. [Copyright &y& Elsevier]