Moral competence (MC) refers to the ability to apply certain moral orientations in a consistent a... more Moral competence (MC) refers to the ability to apply certain moral orientations in a consistent and differentiated manner when judging moral issues. People greatly differ in terms of MC, however, little is known about how these differences are implemented in the brain. To investigate this question, we used functional magnetic resonance imaging and examined resting-state functional connectivity (RSFC) in n=31 individuals with MC scores in the highest 15% of the population and n=33 individuals with MC scores in the lowest 15%, selected from a large sample of 730 Master of Business Administration (MBA) students. Compared to individuals with lower MC, individuals with higher MC showed greater amygdala-ventromedial prefrontal connectivity, which may reflect better ability to cope with emotional conflicts elicited by moral dilemmas. Moreover, individuals with higher MC showed less inter-network connectivity between the amygdalar and fronto-parietal networks, suggesting a more independent ...
BACKGROUND Anterior cingulate cortex (ACC) abnormalities have been implicated consistently in the... more BACKGROUND Anterior cingulate cortex (ACC) abnormalities have been implicated consistently in the pathophysiology of obsessive-compulsive disorder (OCD), yet it remains unclear whether these abnormalities originated during early neurodevelopment. In this study, we examined the ACC sulcal/gyral patterns to investigate whether neurodevelopmental anomalies of the ACC were present in patients with OCD. We hypothesized that patients with OCD would show reduced cortical folding of the ACC compared with controls. METHODS We used magnetic resonance imaging (MRI) of 169 healthy volunteers and 110 patients with OCD to examine the paracingulate sulcus and cingulate sulcus. We assessed cortical folding patterns according to established classification criteria and constructed 3 categories of paracingulate sulcus morphology according to its presence and anteroposterior extent: "prominent," "present" and "absent." We classified the cingulate sulcus as "interrupte...
Disrupted thalamo-cortical connectivity is regarded as a core psychopathology in patients diagnos... more Disrupted thalamo-cortical connectivity is regarded as a core psychopathology in patients diagnosed with schizophrenia. However, whether the thalamo-cortical white matter connectivity is disrupted before the onset of psychosis is still unknown. To determine this gap in knowledge, the strength of thalamo-cortical white matter anatomical connectivity in subjects at clinical-high risk for psychosis (CHR) was compared to that of first-episode psychosis (FEP) and healthy controls. A total of 37 CHR, 21 FEP, and 37 matched healthy controls underwent diffusion-weighted magnetic resonance imaging to examine the number of probabilistic tractography "counts" representing thalamo-cortical white matter connectivity. We also investigated the relationship with psychopathology. For FEP, the connectivity between the thalamus and parietal cortex was significantly increased (F = 5.65, P < .05) compared to that of healthy controls. However, the connectivity between thalamus and orbitofron...
Journal of psychiatry & neuroscience : JPN, Jan 19, 2015
Frontostriatal and frontoamygdalar connectivity alterations in patients with obsessive-compulsive... more Frontostriatal and frontoamygdalar connectivity alterations in patients with obsessive-compulsive disorder (OCD) have been typically described in functional neuroimaging studies. However, structural covariance, or volumetric correlations across distant brain regions, also provides network-level information. Altered structural covariance has been described in patients with different psychiatric disorders, including OCD, but to our knowledge, alterations within frontostriatal and frontoamygdalar circuits have not been explored. We performed a mega-analysis pooling structural MRI scans from the Obsessive-compulsive Brain Imaging Consortium and assessed whole-brain voxel-wise structural covariance of 4 striatal regions (dorsal and ventral caudate nucleus, and dorsal-caudal and ventral-rostral putamen) and 2 amygdalar nuclei (basolateral and centromedial-superficial). Images were preprocessed with the standard pipeline of voxel-based morphometry studies using Statistical Parametric Mappi...
The superior temporal gyrus (STG) is one of the key regions implicated in psychosis, given that a... more The superior temporal gyrus (STG) is one of the key regions implicated in psychosis, given that abnormalities in this region are associated with an increased risk of conversion from an at-risk mental state to psychosis. However, inconsistent results regarding the functional connectivity strength of the STG have been reported, and the regional heterogeneous characteristics of the STG should be considered. To investigate the distinctive functional connection of each subregion in the STG, we parcellated the STG of each hemisphere into three regions: the planum temporale, Heschl's gyrus, and planum polare. Resting-state functional magnetic resonance imaging was obtained from 22 first-episode psychosis (FEP) patients, 41 individuals at ultra-high-risk for psychosis (UHR), and 47 demographically matched healthy controls. Significant group differences (in seed-based connectivity) were demonstrated in the left planum temporale and from both the right and left Heschl's gyrus seeds. F...
Progress in neuro-psychopharmacology & biological psychiatry, Jan 24, 2015
Primary pharmacotherapy regimen for obsessive-compulsive disorder (OCD) named Serotonin reuptake ... more Primary pharmacotherapy regimen for obsessive-compulsive disorder (OCD) named Serotonin reuptake inhibitors (SRIs) does not attain sufficient symptom improvement in 40-60% of OCD. We aimed to decode the differential profile of OCD-related brain pathology per subject in the context of cortical surface area (CSA) or thickness (CT)-based individualized structural covariance (ISC) and to demonstrate the potential of which as a biomarker of treatment response to SRI-based pharmacotherapy in OCD using the support vector machine (SVM). T1-weighted magnetic resonance imaging was obtained at 3T from 56 unmedicated OCD subjects and 75 healthy controls (HCs) at baseline. After 4months of SRI-based pharmacotherapy, the OCD subjects were classified as responders (OCD-R,N=25; ≥35% improvement) or nonresponders (OCD-NR,N=31; <35% improvement) according to the percentage change in the Yale-Brown Obsessive Compulsive Scale total score. Cortical ISCs sustaining between-group difference (p<.001)...
Many of previous neuroimaging studies on neuronal structures in patients with obsessive-compulsiv... more Many of previous neuroimaging studies on neuronal structures in patients with obsessive-compulsive disorder (OCD) used univariate statistical tests on unimodal imaging measurements. Although the univariate methods revealed important aberrance of local morphometry in OCD patients, the covariance structure of the anatomical alterations remains unclear. Motivated by recent developments of multivariate techniques in the neuroimaging field, we applied a fusion method called "mCCA+jICA" on multimodal structural data of T1-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) of 30 unmedicated patients with OCD and 34 healthy controls. Amongst six highly correlated multimodal networks (p < 0.0001), we found significant alterations of the interrelated gray and white matter networks over occipital and parietal cortices, frontal interhemispheric connections and cerebella (False Discovery Rate q ≤ 0.05). In addition, we found white matter networks around bas...
The notion that schizophrenia patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;am... more The notion that schizophrenia patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; (SZ) sense of being detached from external reality is a core feature of the disorder has existed since the early days of its recognition and is still largely emphasized in first person accounts of SZs; however, its etiology, neurophysiological mechanism, and significance for clinical symptoms are unclear. Mind-wandering is a ubiquitous experience of being detached from reality, the underlying neural mechanism of which closely resembles the brain in a resting-state. The resting-state functional magnetic resonance imaging data of 33 SZs and 33 matched healthy controls (CNT) were acquired. All subjects answered the mind-wandering subscale of the Imaginal Processing Inventory Questionnaire. Functional connectivity maps were constructed using 82 regions of interest comprising default-mode, salience, and frontoparietal networks. SZs exhibit significantly higher mind-wandering frequency relative to CNT. The elevated mind-wandering frequency in SZs significantly correlated with positive and general symptom severity. The mind-wandering frequency was inversely correlated with connectivity degree in the right ventromedial prefrontal cortex, the brain region involved in self-experience in SZs. Our results suggest that self-disturbances in SZs can explain SZs&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; disconnection to the external world, leading to the manifestation of positive psychotic symptoms. This study demonstrates strong preliminary evidence that contributes significantly to resolve the complex relationship between self, world, and the brain of SZs, which may lie at the…
Compulsive behaviors in obsessive-compulsive disorder (OCD) may be related to deficits in reward ... more Compulsive behaviors in obsessive-compulsive disorder (OCD) may be related to deficits in reward processing mediated by corticostriatal circuitry, a brain network implicated in the pathophysiology of OCD. Performing compulsive actions can be perceived as a reward to OCD patients because it temporarily reduces the anxiety provoked by obsessions. Although most OCD literature provides evidence of altered regional activity in these corticostriatal circuits, very little is known about the connectivity between individual regions of the corticostriatal-limbic circuits, including the cognitive and affective neural circuitry associated with OCD. Thus, this study investigated the differences in functional connectivity (FC) patterns in this network during resting-state and incentive processing. Nineteen patients with OCD and 18 well-matched healthy controls were scanned during resting-state and a monetary incentive delay task (task state). FC was assessed using both voxel-wise and region-of-in...
Anterior cingulate cortex (ACC) abnormalities have been implicated consistently in the pathophysi... more Anterior cingulate cortex (ACC) abnormalities have been implicated consistently in the pathophysiology of obsessive-compulsive disorder (OCD), yet it remains unclear whether these abnormalities originated during early neurodevelopment. In this study, we examined the ACC sulcal/gyral patterns to investigate whether neurodevelopmental anomalies of the ACC were present in patients with OCD. We hypothesized that patients with OCD would show reduced cortical folding of the ACC compared with controls. We used magnetic resonance imaging (MRI) of 169 healthy volunteers and 110 patients with OCD to examine the paracingulate sulcus and cingulate sulcus. We assessed cortical folding patterns according to established classification criteria and constructed 3 categories of paracingulate sulcus morphology according to its presence and anteroposterior extent: "prominent," "present" and "absent." We classified the cingulate sulcus as "interrupted" or "co...
As the main input hub of the basal ganglia, the striatum receives projections from the cerebral c... more As the main input hub of the basal ganglia, the striatum receives projections from the cerebral cortex. Many studies have provided evidence for multiple parallel corticostriatal loops based on the structural and functional connectivity profiles of the human striatum. A recent resting-state fMRI study revealed the topography of striatum by assigning each voxel in the striatum to its most strongly correlated cortical network among the cognitive, affective, and motor networks. However, it remains unclear what patterns of striatal parcellation would result from performing the clustering without subsequent assignment to cortical networks. Thus, we applied unsupervised clustering algorithms to parcellate the human striatum based on its functional connectivity patterns to other brain regions without any anatomically or functionally defined cortical targets. Functional connectivity maps of striatal subdivisions, identified through clustering analyses, were also computed. Our findings were c...
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2013
Functional imaging studies of obsessive-compulsive disorder (OCD) have reported altered fronto-st... more Functional imaging studies of obsessive-compulsive disorder (OCD) have reported altered fronto-striatal activity during executive tasks. Additionally, altered connectivity of these regions during resting state was found. However, the relationship between brain activity during tasks and resting state remains poorly understood. The present study investigated neural correlates associated with abnormal response inhibition in OCD and to examine how resting state functional connectivity relates to task-related activity. Eighteen unmedicated adult OCD patients and 18 age- and sex-matched control subjects underwent functional magnetic resonance imaging scans during both resting state and a response inhibition task. Brain activation during response inhibition was compared between groups. Fronto-striatal regions showing altered task-related activity were used as seeds for connectivity analyses during resting state. During the response inhibition task, OCD patients had lower activation in areas including the cingulate cortex and basal ganglia regions. Compared with control subjects, patients with OCD showed increased functional connectivity of the caudate nucleus with the middle cingulate cortex and precentral gyrus during rest, suggesting hyperactive striatal-cortical connections. This study found altered function in fronto-striatal regions during response inhibition and its relation to resting state functional connectivity in OCD. Our results suggest that dysfunctional striatal-cortical connections even during rest may result in the failure of response inhibition and error monitoring observed in OCD patients.
Impaired facial emotion recognition is a core deficit in schizophrenia. Oxytocin has been shown t... more Impaired facial emotion recognition is a core deficit in schizophrenia. Oxytocin has been shown to improve social perception in patients with schizophrenia; however, the effect of oxytocin on the neural activity underlying facial emotion recognition has not been investigated. This study was aimed to assess the effect of a single dose of intranasal oxytocin on brain activity in patients with schizophrenia using an implicit facial emotion recognition paradigm. Sixteen male patients with schizophrenia and 16 age-matched healthy male control subjects participated in a randomized, double blind, placebo-controlled crossover trial at Seoul National University Hospital. Delivery of a single dose of 40 IU intranasal oxytocin and the placebo was separated by 1 week. Drug conditions were compared by performing a region of interest (ROI) analysis of the bilateral amygdala on responses to the emotion recognition test. It was found that nasal spray decreased amygdala activity for fearful emotion and increased activity for happy faces. Further, oxytocin elicited differential effects between the patient and control groups. Intranasal oxytocin attenuated amygdala activity for emotional faces in patients with schizophrenia, whereas intranasal oxytocin significantly increased amygdala activity in healthy controls. Oxytocin-induced BOLD signal changes in amygdala in response to happy faces was related to attachment style in the control group. Our result provides new evidence of a modulatory effect of oxytocin on neural response to emotional faces for patients with schizophrenia. Future studies are needed to investigate the effectiveness of long-term treatment with intranasal oxytocin on neural activity in patients with schizophrenia.Neuropsychopharmacology accepted article preview online, 10 February 2015. doi:10.1038/npp.2015.41.
The default mode network (DMN) represents neuronal activity that is intrinsically generated durin... more The default mode network (DMN) represents neuronal activity that is intrinsically generated during a resting state. The present study used resting-state fMRI to investigate whether functional connectivity is altered in pathological gambling (PG). Fifteen drug-naive male patients with PG and 15 age-matched male control subjects participated in the present study. The pathological gambling modification of the Yale-Brown Obsessive Compulsive Scale (PG-YBOCS), the Beck Depression Inventory, and the Beck Anxiety Inventory were used to determine symptom severity in all participants. Participants were instructed to keep their eyes closed and not to focus on any particular thoughts during the 4.68-min resting-state functional scan. The patients with PG displayed decreased default mode connectivity in the left superior frontal gyrus, right middle temporal gyrus, and precuneus compared with healthy controls. The severity of PG symptoms in patients with PG was negatively associated with connectivity between the posterior cingulate cortex seed region and the precuneus (r=-0.599, p=0.018). Decreased functional connectivity within DMN suggests that PG may share similar neurobiological abnormalities with other addictive disorders. Moreover, the severity of PG symptoms was correlated with decreased connectivity in the precuneus, which may be important in the response to treatment in patients with PG.
Although recent studies have revealed regional cortical thinning in patients with schizophrenia, ... more Although recent studies have revealed regional cortical thinning in patients with schizophrenia, it is not clear whether cortical thinning reflects a genetic liability for schizophrenia. The present study investigated the change of cortical thickness in subjects at genetic high risk (GHR) for schizophrenia with a relatively high genetic loading compared with healthy controls (HC) and patients with schizophrenia. The effect of genetic loading on cortical thinning was also measured by comparing GHR subgroups according to the levels of genetic loading. Cortical thickness was measured by the Constrained Laplacian-based Automated Segmentation with Proximities algorithm using 1.5-T structural MRI scans. The cortical thickness of the subjects at GHR (n=31) was compared with that of HC (n=29) and patients with schizophrenia (n=31). We then compared the cortical thickness of the GHR subgroups according to the number of first-degree relatives with schizophrenia to measure the effect of genetic loading. Relative to HC, GHR subjects showed significant cortical thinning in the right anterior cingulate cortex (ACC), left paracingulate and posterior cingulate regions; bilateral frontal regions including frontal pole and ventromedial prefrontal cortex; bilateral temporal regions including the left parahippocampal gyrus; and bilateral inferior parietal and occipital regions; however, patients with schizophrenia showed more widespread cortical thinning in the fronto-temporo-parietal region. GHR subjects who had two or more first-degree relatives with schizophrenia showed a greater reduction in cortical thickness in the right ACC and in the left paracingulate cortex than did those who had only one first-degree relative with schizophrenia. Our findings suggest that the level of genetic loading may have a dose-dependent effect on cortical thinning in the right ACC and in the left paracingulate cortex and that cortical thinning in GHR subjects may represent neurodevelopmental alterations that result from genetic liability for schizophrenia.
Moral competence (MC) refers to the ability to apply certain moral orientations in a consistent a... more Moral competence (MC) refers to the ability to apply certain moral orientations in a consistent and differentiated manner when judging moral issues. People greatly differ in terms of MC, however, little is known about how these differences are implemented in the brain. To investigate this question, we used functional magnetic resonance imaging and examined resting-state functional connectivity (RSFC) in n=31 individuals with MC scores in the highest 15% of the population and n=33 individuals with MC scores in the lowest 15%, selected from a large sample of 730 Master of Business Administration (MBA) students. Compared to individuals with lower MC, individuals with higher MC showed greater amygdala-ventromedial prefrontal connectivity, which may reflect better ability to cope with emotional conflicts elicited by moral dilemmas. Moreover, individuals with higher MC showed less inter-network connectivity between the amygdalar and fronto-parietal networks, suggesting a more independent ...
BACKGROUND Anterior cingulate cortex (ACC) abnormalities have been implicated consistently in the... more BACKGROUND Anterior cingulate cortex (ACC) abnormalities have been implicated consistently in the pathophysiology of obsessive-compulsive disorder (OCD), yet it remains unclear whether these abnormalities originated during early neurodevelopment. In this study, we examined the ACC sulcal/gyral patterns to investigate whether neurodevelopmental anomalies of the ACC were present in patients with OCD. We hypothesized that patients with OCD would show reduced cortical folding of the ACC compared with controls. METHODS We used magnetic resonance imaging (MRI) of 169 healthy volunteers and 110 patients with OCD to examine the paracingulate sulcus and cingulate sulcus. We assessed cortical folding patterns according to established classification criteria and constructed 3 categories of paracingulate sulcus morphology according to its presence and anteroposterior extent: "prominent," "present" and "absent." We classified the cingulate sulcus as "interrupte...
Disrupted thalamo-cortical connectivity is regarded as a core psychopathology in patients diagnos... more Disrupted thalamo-cortical connectivity is regarded as a core psychopathology in patients diagnosed with schizophrenia. However, whether the thalamo-cortical white matter connectivity is disrupted before the onset of psychosis is still unknown. To determine this gap in knowledge, the strength of thalamo-cortical white matter anatomical connectivity in subjects at clinical-high risk for psychosis (CHR) was compared to that of first-episode psychosis (FEP) and healthy controls. A total of 37 CHR, 21 FEP, and 37 matched healthy controls underwent diffusion-weighted magnetic resonance imaging to examine the number of probabilistic tractography "counts" representing thalamo-cortical white matter connectivity. We also investigated the relationship with psychopathology. For FEP, the connectivity between the thalamus and parietal cortex was significantly increased (F = 5.65, P < .05) compared to that of healthy controls. However, the connectivity between thalamus and orbitofron...
Journal of psychiatry & neuroscience : JPN, Jan 19, 2015
Frontostriatal and frontoamygdalar connectivity alterations in patients with obsessive-compulsive... more Frontostriatal and frontoamygdalar connectivity alterations in patients with obsessive-compulsive disorder (OCD) have been typically described in functional neuroimaging studies. However, structural covariance, or volumetric correlations across distant brain regions, also provides network-level information. Altered structural covariance has been described in patients with different psychiatric disorders, including OCD, but to our knowledge, alterations within frontostriatal and frontoamygdalar circuits have not been explored. We performed a mega-analysis pooling structural MRI scans from the Obsessive-compulsive Brain Imaging Consortium and assessed whole-brain voxel-wise structural covariance of 4 striatal regions (dorsal and ventral caudate nucleus, and dorsal-caudal and ventral-rostral putamen) and 2 amygdalar nuclei (basolateral and centromedial-superficial). Images were preprocessed with the standard pipeline of voxel-based morphometry studies using Statistical Parametric Mappi...
The superior temporal gyrus (STG) is one of the key regions implicated in psychosis, given that a... more The superior temporal gyrus (STG) is one of the key regions implicated in psychosis, given that abnormalities in this region are associated with an increased risk of conversion from an at-risk mental state to psychosis. However, inconsistent results regarding the functional connectivity strength of the STG have been reported, and the regional heterogeneous characteristics of the STG should be considered. To investigate the distinctive functional connection of each subregion in the STG, we parcellated the STG of each hemisphere into three regions: the planum temporale, Heschl's gyrus, and planum polare. Resting-state functional magnetic resonance imaging was obtained from 22 first-episode psychosis (FEP) patients, 41 individuals at ultra-high-risk for psychosis (UHR), and 47 demographically matched healthy controls. Significant group differences (in seed-based connectivity) were demonstrated in the left planum temporale and from both the right and left Heschl's gyrus seeds. F...
Progress in neuro-psychopharmacology & biological psychiatry, Jan 24, 2015
Primary pharmacotherapy regimen for obsessive-compulsive disorder (OCD) named Serotonin reuptake ... more Primary pharmacotherapy regimen for obsessive-compulsive disorder (OCD) named Serotonin reuptake inhibitors (SRIs) does not attain sufficient symptom improvement in 40-60% of OCD. We aimed to decode the differential profile of OCD-related brain pathology per subject in the context of cortical surface area (CSA) or thickness (CT)-based individualized structural covariance (ISC) and to demonstrate the potential of which as a biomarker of treatment response to SRI-based pharmacotherapy in OCD using the support vector machine (SVM). T1-weighted magnetic resonance imaging was obtained at 3T from 56 unmedicated OCD subjects and 75 healthy controls (HCs) at baseline. After 4months of SRI-based pharmacotherapy, the OCD subjects were classified as responders (OCD-R,N=25; ≥35% improvement) or nonresponders (OCD-NR,N=31; <35% improvement) according to the percentage change in the Yale-Brown Obsessive Compulsive Scale total score. Cortical ISCs sustaining between-group difference (p<.001)...
Many of previous neuroimaging studies on neuronal structures in patients with obsessive-compulsiv... more Many of previous neuroimaging studies on neuronal structures in patients with obsessive-compulsive disorder (OCD) used univariate statistical tests on unimodal imaging measurements. Although the univariate methods revealed important aberrance of local morphometry in OCD patients, the covariance structure of the anatomical alterations remains unclear. Motivated by recent developments of multivariate techniques in the neuroimaging field, we applied a fusion method called "mCCA+jICA" on multimodal structural data of T1-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) of 30 unmedicated patients with OCD and 34 healthy controls. Amongst six highly correlated multimodal networks (p < 0.0001), we found significant alterations of the interrelated gray and white matter networks over occipital and parietal cortices, frontal interhemispheric connections and cerebella (False Discovery Rate q ≤ 0.05). In addition, we found white matter networks around bas...
The notion that schizophrenia patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;am... more The notion that schizophrenia patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; (SZ) sense of being detached from external reality is a core feature of the disorder has existed since the early days of its recognition and is still largely emphasized in first person accounts of SZs; however, its etiology, neurophysiological mechanism, and significance for clinical symptoms are unclear. Mind-wandering is a ubiquitous experience of being detached from reality, the underlying neural mechanism of which closely resembles the brain in a resting-state. The resting-state functional magnetic resonance imaging data of 33 SZs and 33 matched healthy controls (CNT) were acquired. All subjects answered the mind-wandering subscale of the Imaginal Processing Inventory Questionnaire. Functional connectivity maps were constructed using 82 regions of interest comprising default-mode, salience, and frontoparietal networks. SZs exhibit significantly higher mind-wandering frequency relative to CNT. The elevated mind-wandering frequency in SZs significantly correlated with positive and general symptom severity. The mind-wandering frequency was inversely correlated with connectivity degree in the right ventromedial prefrontal cortex, the brain region involved in self-experience in SZs. Our results suggest that self-disturbances in SZs can explain SZs&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; disconnection to the external world, leading to the manifestation of positive psychotic symptoms. This study demonstrates strong preliminary evidence that contributes significantly to resolve the complex relationship between self, world, and the brain of SZs, which may lie at the…
Compulsive behaviors in obsessive-compulsive disorder (OCD) may be related to deficits in reward ... more Compulsive behaviors in obsessive-compulsive disorder (OCD) may be related to deficits in reward processing mediated by corticostriatal circuitry, a brain network implicated in the pathophysiology of OCD. Performing compulsive actions can be perceived as a reward to OCD patients because it temporarily reduces the anxiety provoked by obsessions. Although most OCD literature provides evidence of altered regional activity in these corticostriatal circuits, very little is known about the connectivity between individual regions of the corticostriatal-limbic circuits, including the cognitive and affective neural circuitry associated with OCD. Thus, this study investigated the differences in functional connectivity (FC) patterns in this network during resting-state and incentive processing. Nineteen patients with OCD and 18 well-matched healthy controls were scanned during resting-state and a monetary incentive delay task (task state). FC was assessed using both voxel-wise and region-of-in...
Anterior cingulate cortex (ACC) abnormalities have been implicated consistently in the pathophysi... more Anterior cingulate cortex (ACC) abnormalities have been implicated consistently in the pathophysiology of obsessive-compulsive disorder (OCD), yet it remains unclear whether these abnormalities originated during early neurodevelopment. In this study, we examined the ACC sulcal/gyral patterns to investigate whether neurodevelopmental anomalies of the ACC were present in patients with OCD. We hypothesized that patients with OCD would show reduced cortical folding of the ACC compared with controls. We used magnetic resonance imaging (MRI) of 169 healthy volunteers and 110 patients with OCD to examine the paracingulate sulcus and cingulate sulcus. We assessed cortical folding patterns according to established classification criteria and constructed 3 categories of paracingulate sulcus morphology according to its presence and anteroposterior extent: "prominent," "present" and "absent." We classified the cingulate sulcus as "interrupted" or "co...
As the main input hub of the basal ganglia, the striatum receives projections from the cerebral c... more As the main input hub of the basal ganglia, the striatum receives projections from the cerebral cortex. Many studies have provided evidence for multiple parallel corticostriatal loops based on the structural and functional connectivity profiles of the human striatum. A recent resting-state fMRI study revealed the topography of striatum by assigning each voxel in the striatum to its most strongly correlated cortical network among the cognitive, affective, and motor networks. However, it remains unclear what patterns of striatal parcellation would result from performing the clustering without subsequent assignment to cortical networks. Thus, we applied unsupervised clustering algorithms to parcellate the human striatum based on its functional connectivity patterns to other brain regions without any anatomically or functionally defined cortical targets. Functional connectivity maps of striatal subdivisions, identified through clustering analyses, were also computed. Our findings were c...
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2013
Functional imaging studies of obsessive-compulsive disorder (OCD) have reported altered fronto-st... more Functional imaging studies of obsessive-compulsive disorder (OCD) have reported altered fronto-striatal activity during executive tasks. Additionally, altered connectivity of these regions during resting state was found. However, the relationship between brain activity during tasks and resting state remains poorly understood. The present study investigated neural correlates associated with abnormal response inhibition in OCD and to examine how resting state functional connectivity relates to task-related activity. Eighteen unmedicated adult OCD patients and 18 age- and sex-matched control subjects underwent functional magnetic resonance imaging scans during both resting state and a response inhibition task. Brain activation during response inhibition was compared between groups. Fronto-striatal regions showing altered task-related activity were used as seeds for connectivity analyses during resting state. During the response inhibition task, OCD patients had lower activation in areas including the cingulate cortex and basal ganglia regions. Compared with control subjects, patients with OCD showed increased functional connectivity of the caudate nucleus with the middle cingulate cortex and precentral gyrus during rest, suggesting hyperactive striatal-cortical connections. This study found altered function in fronto-striatal regions during response inhibition and its relation to resting state functional connectivity in OCD. Our results suggest that dysfunctional striatal-cortical connections even during rest may result in the failure of response inhibition and error monitoring observed in OCD patients.
Impaired facial emotion recognition is a core deficit in schizophrenia. Oxytocin has been shown t... more Impaired facial emotion recognition is a core deficit in schizophrenia. Oxytocin has been shown to improve social perception in patients with schizophrenia; however, the effect of oxytocin on the neural activity underlying facial emotion recognition has not been investigated. This study was aimed to assess the effect of a single dose of intranasal oxytocin on brain activity in patients with schizophrenia using an implicit facial emotion recognition paradigm. Sixteen male patients with schizophrenia and 16 age-matched healthy male control subjects participated in a randomized, double blind, placebo-controlled crossover trial at Seoul National University Hospital. Delivery of a single dose of 40 IU intranasal oxytocin and the placebo was separated by 1 week. Drug conditions were compared by performing a region of interest (ROI) analysis of the bilateral amygdala on responses to the emotion recognition test. It was found that nasal spray decreased amygdala activity for fearful emotion and increased activity for happy faces. Further, oxytocin elicited differential effects between the patient and control groups. Intranasal oxytocin attenuated amygdala activity for emotional faces in patients with schizophrenia, whereas intranasal oxytocin significantly increased amygdala activity in healthy controls. Oxytocin-induced BOLD signal changes in amygdala in response to happy faces was related to attachment style in the control group. Our result provides new evidence of a modulatory effect of oxytocin on neural response to emotional faces for patients with schizophrenia. Future studies are needed to investigate the effectiveness of long-term treatment with intranasal oxytocin on neural activity in patients with schizophrenia.Neuropsychopharmacology accepted article preview online, 10 February 2015. doi:10.1038/npp.2015.41.
The default mode network (DMN) represents neuronal activity that is intrinsically generated durin... more The default mode network (DMN) represents neuronal activity that is intrinsically generated during a resting state. The present study used resting-state fMRI to investigate whether functional connectivity is altered in pathological gambling (PG). Fifteen drug-naive male patients with PG and 15 age-matched male control subjects participated in the present study. The pathological gambling modification of the Yale-Brown Obsessive Compulsive Scale (PG-YBOCS), the Beck Depression Inventory, and the Beck Anxiety Inventory were used to determine symptom severity in all participants. Participants were instructed to keep their eyes closed and not to focus on any particular thoughts during the 4.68-min resting-state functional scan. The patients with PG displayed decreased default mode connectivity in the left superior frontal gyrus, right middle temporal gyrus, and precuneus compared with healthy controls. The severity of PG symptoms in patients with PG was negatively associated with connectivity between the posterior cingulate cortex seed region and the precuneus (r=-0.599, p=0.018). Decreased functional connectivity within DMN suggests that PG may share similar neurobiological abnormalities with other addictive disorders. Moreover, the severity of PG symptoms was correlated with decreased connectivity in the precuneus, which may be important in the response to treatment in patients with PG.
Although recent studies have revealed regional cortical thinning in patients with schizophrenia, ... more Although recent studies have revealed regional cortical thinning in patients with schizophrenia, it is not clear whether cortical thinning reflects a genetic liability for schizophrenia. The present study investigated the change of cortical thickness in subjects at genetic high risk (GHR) for schizophrenia with a relatively high genetic loading compared with healthy controls (HC) and patients with schizophrenia. The effect of genetic loading on cortical thinning was also measured by comparing GHR subgroups according to the levels of genetic loading. Cortical thickness was measured by the Constrained Laplacian-based Automated Segmentation with Proximities algorithm using 1.5-T structural MRI scans. The cortical thickness of the subjects at GHR (n=31) was compared with that of HC (n=29) and patients with schizophrenia (n=31). We then compared the cortical thickness of the GHR subgroups according to the number of first-degree relatives with schizophrenia to measure the effect of genetic loading. Relative to HC, GHR subjects showed significant cortical thinning in the right anterior cingulate cortex (ACC), left paracingulate and posterior cingulate regions; bilateral frontal regions including frontal pole and ventromedial prefrontal cortex; bilateral temporal regions including the left parahippocampal gyrus; and bilateral inferior parietal and occipital regions; however, patients with schizophrenia showed more widespread cortical thinning in the fronto-temporo-parietal region. GHR subjects who had two or more first-degree relatives with schizophrenia showed a greater reduction in cortical thickness in the right ACC and in the left paracingulate cortex than did those who had only one first-degree relative with schizophrenia. Our findings suggest that the level of genetic loading may have a dose-dependent effect on cortical thinning in the right ACC and in the left paracingulate cortex and that cortical thinning in GHR subjects may represent neurodevelopmental alterations that result from genetic liability for schizophrenia.
Uploads