Ji Won Chun

Cortical surface-based analysis of 18F-FDG PET: Measured metabolic abnormalities in schizophrenia are affected by cortical structural abnormalities

The purpose of the study is to propose a new framework for surface-based statistical parametric mapping of PET images using MRI-based cortical surface analysis, including partial volume correction, intensity normalization and spatial normalization on the cortical surface. Maximum PET intensities along the path between inner and outer layer of the cortical gray matter are mapped onto the cortical surface to generate a metabolic activity surface map. For the partial volume correction, the metabolic activity surface map was divided by the partial volume effect map. The regional metabolic activity was normalized by the global activity iteratively calculated at the surface nodes, statistically independent of the group, as measured by F statistics. After surface-based spatial normalization, a statistical evaluation of both cortical thickness and cortical metabolic activity was conducted on the normalized surfaces of 16 patients with schizophrenia and 16 age- and gender-matched healthy controls. The patients with schizophrenia were found to have significant cortical thinning in the temporal and inferior frontal cortices. Accordingly, their PET imaging was significantly affected by the partial volume effect, indicating that partial volume correction could change the statistical results. After correction of the partial volume effects, the patients showed hyperactivity in the temporal cortex, whereas hypoactivity in the prefrontal cortex, predominantly in the left hemisphere. Our results demonstrate that anatomical factors affect an analysis for functional data from the PET, and therefore the importance of combining anatomy and function in the analysis of imaging data for schizophrenia should be considered.

Volumetric abnormalities in connectivity-based subregions of the thalamus in patients with chronic schizophrenia

OBJECTIVEnThe thalamus, which consists of multiple subnuclei, has been of particular interest in the study of schizophrenia. This study aimed to identify abnormalities in the connectivity-based subregions of the thalamus in patients with schizophrenia.nnnMETHODSnThalamic volume was measured by a manual tracing on superimposed images of T1-weighted and diffusion tensor images in 30 patients with schizophrenia and 22 normal volunteers. Cortical regional volumes automatically measured by a surface-based approach and thalamic subregional volumes measured by a connectivity-based technique were compared between the two groups and their correlations between the connected regions were calculated in each group.nnnRESULTSnVolume reduction was observed in the bilateral orbitofrontal cortices and the left cingulate gyrus on the cortical side, whereas in subregions connected to the right orbitofrontal cortex and bilateral parietal cortices on the thalamic side. Significant volumetric correlations were identified between the right dorsal prefrontal cortex and its related thalamic subregion and between the left parietal cortex and its related thalamic subregion only in the normal group.nnnCONCLUSIONSnOur results suggest that patients with schizophrenia have a structural deficit in the corticothalamic systems, especially in the orbitofrontal-thalamic system. Our findings may present evidence of corticothalamic connection problems in schizophrenia.

Neuroanatomical correlates of trait anhedonia in patients with schizophrenia: A voxel-based morphometric study

The aim of this study was to characterize the association between trait anhedonia and regional gray matter volume in patients with schizophrenia. Forty-six patients with schizophrenia and 56 healthy controls underwent magnetic resonance imaging (MRI) to acquire high-resolution T1-weighted images. Trait anhedonia was measured using the Chapman Revised Physical Anhedonia Scale (PAS). Voxel-based morphometry was performed to investigate brain volume correlates of trait anhedonia. Several brain regions in the patient group, including the left precuneus and right posterior cingulate (PCC), were found to show significantly less correlation with PAS scores than those of the control group. Post-hoc analysis revealed that negative correlations between the regional gray matter volume and the PAS scores in the patient group were found at a trend level in the left precuneus and the right PCC. In conclusion, these findings suggest that trait anhedonia in patients with schizophrenia could possibly be associated with a volume deficit in brain regions related to default-mode, which reflects the impairment of self-referential processing and reward anticipation.

Abnormal brain response during the auditory emotional processing in schizophrenic patients with chronic auditory hallucinations

OBJECTIVEnFew neuroimaging studies have been conducted regarding clinical associations between auditory hallucinations (AHs) and affective disturbances in patients with schizophrenia. This study aimed to elucidate the neurobiological basis of emotional disturbances in schizophrenic patients with persisting AHs.nnnMETHODSnUsing functional magnetic resonance imaging (fMRI), the cortical responsiveness during the processing of laughing and crying sounds was measured and compared between 14 hallucinating schizophrenic patients, 14 nonhallucinating schizophrenic patients and 28 normal controls.nnnRESULTSnThe hallucinating patients showed differential neural activities in various areas including the amygdala, the hippocampus, the cingulate, the prefrontal cortex, and the parietal cortex, compared with the nonhallucinating patients and the normal controls. In particular, compared with the nonhallucinators, the hallucinators revealed reduced activation in the left amygdala and the bilateral hippocampus during the processing of crying sounds.nnnCONCLUSIONnOur findings suggest that the persistence of AHs in schizophrenia may induce functional disturbances of the emotion-related interconnected neural networks, including reduced responsiveness in the amygdala and hippocampus to negative stimuli.

Abnormal neural processing during emotional salience attribution of affective asymmetry in patients with schizophrenia.

Aberrant emotional salience attribution has been reported to be an important clinical feature in patients with schizophrenia. Real life stimuli that incorporate both positive and negative emotional traits lead to affective asymmetry such as negativity bias and positivity offset. In this study, we investigated the neural correlates of emotional salience attribution in patients with schizophrenia when affective asymmetry was processed. Fifteen patients with schizophrenia and 14 healthy controls were scanned using functional magnetic resonance imaging (fMRI) while performing an emotion judgment task in which two pictures were juxtaposed. The task consisted of responding to affective asymmetry condition (ambivalent and neutral) and affective symmetry conditions (positive and negative), and group comparisons were performed for each condition. Significantly higher activity in the medial prefrontal cortex and inferior frontal gyrus was observed for the ambivalent condition than for the other conditions in controls, but not in patients. Compared with controls, patients showed decreased activities in the dorsolateral prefrontal cortex, dorsal anterior cingulate cortex, insula, and putamen for the ambivalent condition, but no changes were observed for the neutral condition. Multiple prefrontal hypoactivities during salience attribution of negativity bias in schizophrenia may underlie deficits in the integrative processing of emotional information. Regional abnormalities in the salience network may be the basis of defective emotional salience attribution in schizophrenia, which is likely involved in symptom formation and social dysfunction.

Involvement of the mirror neuron system in blunted affect in schizophrenia

Blunted affect is a relatively enduring schizophrenic symptom and its presence brings about poor functioning and outcomes. Functional impairment in the mirror neuron system which is involved in both motor execution and imitation may be a neural basis of blunted affect, but it is not proved yet. Fifteen patients with schizophrenia and 16 healthy controls performed the facial expression task during functional magnetic resonance imaging. The task was to reproduce facial expressions in response to the face or word stimuli for happiness, sadness, and meaningless expression. Brain activities during facial expressions in patients compared with controls and their relationship with affective flattening were analyzed. Compared to controls, patients exhibited decreased activity in the widespread dorsal frontal regions and increased activity in the ventral frontal and subcortical regions. Patients also demonstrated significant negative correlation of the severity of affective flattening with activities in the mirror neuron system, such as the premotor cortex, motor cortex, and inferior parietal lobule. Emotional expression in patients with schizophrenia may be related to hypoactivity of the dorsal system and hyperactivity of the ventral system. An imbalance of these two systems may contribute to blunted affect. Directly addressing blunted affect using emotional expression provides a new perspective that functional disturbance of the mirror neuron system may play an important role in manifestation of blunted affect in schizophrenia.

Altered cingulo-striatal function underlies reward drive deficits in schizophrenia

Amotivation in schizophrenia is assumed to involve dysfunctional dopaminergic signaling of reward prediction or anticipation. It is unclear, however, whether the translation of neural representation of reward value to behavioral drive is affected in schizophrenia. In order to examine how abnormal neural processing of response valuation and initiation affects incentive motivation in schizophrenia, we conducted functional MRI using a deterministic reinforcement learning task with variable intervals of contingency reversals in 20 clinically stable patients with schizophrenia and 20 healthy controls. Behaviorally, the advantage of positive over negative reinforcer in reinforcement-related responsiveness was not observed in patients. Patients showed altered response valuation and initiation-related striatal activity and deficient rostro-ventral anterior cingulate cortex activation during reward approach initiation. Among these neural abnormalities, rostro-ventral anterior cingulate cortex activation was correlated with positive reinforcement-related responsiveness in controls and social anhedonia and social amotivation subdomain scores in patients. Our findings indicate that the central role of the anterior cingulate cortex is in translating action value into driving force of action, and underscore the role of the cingulo-striatal network in amotivation in schizophrenia.

Hippocampus and nucleus accumbens activity during neutral word recognition related to trait physical anhedonia in patients with schizophrenia: An fMRI study

Emotional memory dysfunction may be associated with anhedonia in schizophrenia. This study aimed to investigate the neurobiological basis of emotional memory and its relationship with anhedonia in schizophrenia specifically in emotional memory relate brain regions of interest (ROIs) including the amygdala, hippocampus, nucleus accumbens, and ventromedial prefrontal cortex. Fourteen patients with schizophrenia and 16 healthy subjects performed a word-image associative encoding task, during which a neutral word was presented with a positive, neutral, or control image. Subjects underwent functional magnetic resonance imaging while performing the recognition task. Correlation analyses were performed between the percent signal change (PSC) in the ROIs and the anhedonia scores. We found no group differences in recognition accuracy and reaction time. The PSC of the hippocampus in the positive and neutral conditions, and the PSC in the nucleus accumbens in the control condition, appeared to be negatively correlated with the Physical Anhedonia Scale (PAS) scores in patients with schizophrenia, while significant correlations with the PAS scores were not observed in healthy subjects. This study provides further evidences of the role of the hippocampus and nucleus accumbens in trait physical anhedonia and possible associations between emotional memory deficit and trait physical anhedonia in patients with schizophrenia.

Reciprocal activation of the orbitofrontal cortex and the ventrolateral prefrontal cortex in processing ambivalent stimuli

The neural basis of ambivalence has not yet been identified. We investigated the prefrontal cortical activations implicated in evaluative processing of ambivalent stimuli under the forced and non-forced response conditions. Cerebral blood flow was measured using H(2)(15)O positron emission tomography in twelve normal volunteers during a modified word-stem completion task that was designed to evoke different conditions of ambivalence. The prefrontal cortical activations were restricted to the orbitofrontal cortex during the non-forced ambivalent condition, whereas the ventrolateral prefrontal cortex and the frontopolar cortex were activated in addition to the orbitofrontal cortex during the forced ambivalent condition. It is remarkable that the orbitofrontal cortex and the ventrolateral prefrontal cortex demonstrated a reciprocal activation pattern, which might be linked to the evaluative attitude toward the ambivalent stimuli.

Anhedonia and Ambivalence in Schizophrenic Patients with Fronto-Cerebellar Metabolic Abnormalities: A Fluoro-D-Glucose Positron Emission Tomography Study

Objective Prefrontal and cerebellar abnormalities have been associated with higher cognitive deficits in schizophrenia. The current study aimed to show whether or not schizophrenic patients with fronto-cerebellar functional abnormalities show more anhedonia or ambivalence. Methods Regional cerebral metabolic activity was measured using fluoro-D-glucose positron emission tomography and was compared between 24 patients with chronic schizophrenia and 22 healthy normal volunteers. The existence of regional prefrontal hypofunction and regional cerebellar hyperfunction was investigated in each patient. Demographic and clinical variables including the emotional self-report scales were compared between the subgroups of the patients categorized according to the existence and the absence of the regional dysfunctions. Results Comparisons between each patient and the total normal controls revealed that 14 of the total twenty-four patients had regional hypofrontal functions, whereas 11 patients had regional hypercerebellar functions. Patients with prefrontal hypofunction showed more severe anhedonia than those without prefrontal hypofunction, whereas patients with cerebellar hyperfunction compared to those without cerebellar hyperfunction had more severe ambivalence. Conclusion It seems that fronto-cerebellar abnormalities may be associated with cardinal emotional features of schizophrenia, such as anhedonia and ambivalence.