Kunihiko Asai

Brain activation associated with evaluative processes of guilt and embarrassment: an fMRI study

We aimed to investigate the neural substrates associated with evaluative process of moral emotions. Using functional magnetic resonance imaging (fMRI), we examined the similarities and differences between evaluative process of guilt and that of embarrassment at the neural basis level. Study of the neural basis of judgments of moral emotions might contribute to a better understanding of the amoral behavior observed in neurological and psychiatric disorders. Nineteen healthy volunteers were studied. The participants read sentences carrying neutral, guilty, or embarrassing contents during the scans. Both guilt and embarrassment conditions commonly activated the medial prefrontal cortex (MPFC), left posterior superior temporal sulcus (STS), and visual cortex. Compared to guilt condition, embarrassment condition produced greater activation in the right temporal cortex (anterior), bilateral hippocampus, and visual cortex. Most of these regions have been implicated in the neural substrate of social cognition or Theory of Mind (ToM). Our results support the idea that both are self-conscious emotions, which are social emotions requiring the ability to represent the mental states of others. At the same time, our functional fMRI data are in favor of the notion that evaluative process of embarrassment might be a more complex process than that of guilt.

An fMRI study of differential neural response to affective pictures in schizophrenia.

Although emotional dysfunction is considered a fundamental symptom of schizophrenia, studies investigating the neural basis of emotional dysfunction in schizophrenia are few. Using functional magnetic resonance imaging (fMRI) and a task viewing affective pictures, we aimed to examine automatic emotional response and to elucidate the neural basis of impaired emotional processing in schizophrenia. Fifteen healthy volunteers and 15 schizophrenics were studied. During the scans, the subjects were instructed to indicate how each of the presented pictures made them feel. Whole brain activities in response to the affective pictures were measured by fMRI. Controls recruited the neural circuit including amygdaloid-hippocampal region, prefrontal cortex, thalamus, basal ganglia, cerebellum, midbrain, and visual cortex while viewing unpleasant pictures. Despite an equal behavioral result to controls, the patients showed less activation in the components of the circuit (right amygdala, bilateral hippocampal region, medial prefrontal cortex (MPFC), basal ganglia, thalamus, cerebellum, midbrain, and visual cortex). This study demonstrated functional abnormalities in the neural circuit of emotional processing in schizophrenia. In particular, decreased activation in the right amygdala and MPFC appears to be an important finding related to dysfunctional emotional behavior in schizophrenia.

Effects of dopaminergic and serotonergic manipulation on emotional processing: A pharmacological fMRI study

Recent neuroimaging studies have demonstrated abnormal central emotional processing in psychiatric disorders. The dopamine (DA) systems and serotonin (5-HT) systems are the main target of psychopharmacotherapy. DA D2 receptor antagonists and selective serotonin reuptake inhibitors (SSRIs) are widely used in psychiatric practice. Investigating the effects of these drugs on emotional processing should lead to a better understanding of the pathophysiology and pharmacotherapy of neuropsychiatric disorders. We aimed to examine effects of dopaminergic and serotonergic manipulation on neural responses to unpleasant pictures in healthy volunteers using pharmacological fMRI. Thirteen healthy male subjects participated in a single-blind, randomized, placebo-controlled design study. Each subject participated in three fMRI sessions. In each session, participants were orally administered either 25 mg of sultopride or 50 mg of fluvoxamine or placebo prior to scanning, and neural responses to unpleasant and neutral pictures were recorded. Despite no significant differences being found in the subjective ratings of affective pictures across three sessions, compared to placebo, acute treatments of DA D2 receptor antagonists and SSRIs commonly attenuated the amygdala activity, although both treatments had slightly different modulatory effects on other components of the neural circuit of emotional processing. This study has shown that even acute treatment of drugs that manipulate neurotransmitter systems could affect brain activation associated with emotional processing in human brain. At the same time, our findings suggest that pharmacological fMRI could be a powerful tool for investigating the neurophysiological properties of drugs targeting neuropsychiatric disorders.

Epileptiform EEG Discharges in Healthy Children: Prevalence, Emotional and Behavioral Correlates, and Genetic Influences

Summary: Epileptiform discharges in 8 electrode waking EEGs at rest and during hyperventilation in 1,057 healthy children aged 6–12 years from an elementary school were studied: Epileptiform discharges, detected in 53 children (5.0%), consisted of centrotemporal spikes (37 cases), generalized spike ahd slow wave complexes (10 cases), occipital spikes (2 cases), frontal spikes (1 case), and a combination of multiple spike and slow wave complexes and focal spikes (2 cases). The occurrence of a positive past history of febrile convulsions was higher in children with epileptiform discharges (18.9%) than in those without epileptiform discharges (9.4%). Using the Rutter scales for teachers and parents, we compared the emotional and behavioral problems of children with epileptiform EEG discharges with those of children without epileptiform discharges. No statistically significant differences were noted, indicating that the emotional and behavioral problems existing are most probably coincidental and not directly related to the epileptiform discharges. A genetic basis for generalized epileptiform discharges was postulated because the occurrence of generalized discharges in siblings of probands with generalized discharges was higher (4 of 9, 44.4%) than the prevalence in all subjects. However, the occurrence of centrotemporat spikes in the siblings of probands with centrotemporal spikes was not higher (2/38, 5.3%) and an autosomaldominant genetic factor for centrotemporal spikes in waking EEGs of healthy children could not be confirmed.

Ten year progressive ventricular enlargement in schizophrenia: an MRI morphometrical study.

Abstract Recent studies of the brain using magnetic resonance imaging (MRI) have suggested progressive structural changes in schizophrenics. However, those studies were conducted over periods of less than 5 years and thus lacked sufficient capacity to determine the course and nature of this process. In this study, MRI scans were obtained in 15 schizophrenics and 12 controls at baseline and after 4‐ and 10‐year follow ups. Volumes of the lateral ventricles were measured. Patients were assessed by the Brief Psychiatric Rating Scale (BPRS) at the same two time points: at baseline and at 10‐year follow up. After 10 years, a significant lateral ventricular enlargement was found in patients (mean percentage change: +22.9%) but not in controls (5.1%). Although our results are not in disagreement with the neurodevelopmental hypothesis, they do provide strong evidence that in schizophrenia progressive brain reduction occurs even in its chronic stage.

GABAA/Benzodiazepine receptor binding in patients with schizophrenia using [11C]Ro15-4513, a radioligand with relatively high affinity for α5 subunit

Dysfunction of the GABA system is considered to play a role in the pathology of schizophrenia. Individual subunits of GABA(A)/Benzodiazepine (BZ) receptor complex have been revealed to have different functional properties. alpha5 subunit was reported to be related to learning and memory. Changes of alpha5 subunit in schizophrenia were reported in postmortem studies, but the results were inconsistent. In this study, we examined GABA(A)/BZ receptor using [(11)C]Ro15-4513, which has relatively high affinity for alpha5 subunit, and its relation to clinical symptoms in patients with schizophrenia. [(11)C]Ro15-4513 bindings of 11 patients with schizophrenia (6 drug-naïve and 5 drug-free) were compared with those of 12 age-matched healthy control subjects using positron emission tomography. Symptoms were assessed using the Positive and Negative Syndrome Scale. [(11)C]Ro15-4513 binding was quantified by binding potential (BP) obtained by the reference tissue model. [(11)C]Ro15-4513 binding in the prefrontal cortex and hippocampus was negatively correlated with negative symptom scores in patients with schizophrenia, although there was no significant difference in BP between patients and controls. GABA(A)/BZ receptor including alpha5 subunit in the prefrontal cortex and hippocampus might be involved in the pathophysiology of negative symptoms of schizophrenia.

Platelet 3H-paroxetine binding in control subjects and depressed patients: Relationship to serotonin uptake and age

3H-paroxetine is regarded as a better ligand for the serotonin (5-hydroxytryptamine; 5-HT) uptake site than 3H-imipramine. In the present study, platelet 14C-5-HT uptake and 3H-paroxetine binding were simultaneously measured in 12 control subjects. There was a significant positive correlation between the individual Bmax value for 3H-paroxetine binding and the Vmax value for 14C-5-HT uptake. Platelet 3H-paroxetine binding was also determined in 21 drug-free patients who satisfied DSM-III-R criteria for major depression and 21 control subjects. A negative correlation was found between the Bmax values for 3H-paroxetine binding with age in control subjects. There was no change in 3H-paroxetine binding in depressed patients compared with control subjects. Our results indicated that 3H-paroxetine was a good ligand for evaluating 5-HT uptake sites, and the influence of age ought to be taken into consideration in the study of 3H-paroxetine binding. The present study indicated that there was no change in 5-HT uptake sites in platelets from depressed patients.

Effects of sports participation on psychiatric symptoms and brain activations during sports observation in schizophrenia

Weight gain has been identified as being responsible for increased morbidity and mortality rates of schizophrenia patients. For the management of weight gain, exercise is one of the most acknowledged interventions. At the same time, exercise and sports have been recognized for their positive impact on psychiatric symptoms of schizophrenia. However, the neurobiological basis for this remains poorly understood. We aimed to examine the effect of sports participation on weight gain, psychiatric symptoms and brain activation during sports observation in schizophrenia patients. Thirteen schizophrenia patients who participated in a 3-month program, including sports participation and 10 control schizophrenia patients were studied. In both groups, body mass index (BMI), Positive and Negative Syndrome Scale (PANSS), and brain activation during observation of sports-related actions measured by functional magnetic resonance imaging were accessed before and after a 3-month interval. BMI and general psychopathology scale of PANSS were significantly reduced in the program group but not in the control group after a 3-month interval. Compared with baseline, activation of the body-selective extrastriate body area (EBA) in the posterior temporal-occipital cortex during observation of sports-related actions was increased in the program group. In this group, increase in EBA activation was associated with improvement in the general psychopathology scale of PANSS. Sports participation had a positive effect not only on weight gain but also on psychiatric symptoms in schizophrenia. EBA might mediate these beneficial effects of sports participation. Our findings merit further investigation of neurobiological mechanisms underlying the therapeutic effect of sports for schizophrenia.

Language Processing and Human Voice Perception in Schizophrenia: A Functional Magnetic Resonance Imaging Study

BACKGROUND Neuroimaging studies have demonstrated either reduced left-lateralized activation or reversed language dominance in schizophrenia. These findings of left hemispheric dysfunction could be attributed to language processing tasks, which activate mainly left hemispheric function. Recent functional magnetic resonance imaging studies reported right-lateralized temporal activation by human voice perception, but few studies have investigated activation by human voice in schizophrenia. We aimed to clarify the cerebral function of language processing in schizophrenia patients by considering cerebral activation of human voice perception. METHODS Fourteen right-handed schizophrenia patients and 14 right-handed controls with matched handedness, sex, and education level were scanned by functional magnetic resonance imaging while listening to sentences (SEN), reverse sentences (rSEN), and identifiable non-vocal sounds (SND). RESULTS Under the SEN-SND and SEN-rSEN contrasts including language processing, patients showed less activation of the left hemisphere than controls in the language-related fronto-tempo-parietal region, hippocampus, thalamus and cingulate gyrus. Under the rSEN-SND contrast including human voice perception, patients showed less activation than controls in the right-lateralized temporal cortices and bilateral posterior cingulate. CONCLUSIONS Our results indicate that schizophrenia patients have impairment of broader bilateral cortical-subcortical regions related to both the semantic network in the left hemisphere and the voice-specific network in the right hemisphere.

Functional deficits in the extrastriate body area during observation of sports-related actions in schizophrenia.

Exercise and sports are increasingly being implemented in the management of schizophrenia. The process of action perception is as important as that of motor execution for learning and acquiring new skills. Recent studies have suggested that body-selective extrastriate body area (EBA) in the posterior temporal-occipital cortex is involved not only in static visual perception of body parts but also in the planning, imagination, and execution of actions. However, functional abnormality of the EBA in schizophrenia has yet to be investigated. Using functional magnetic resonance imaging (fMRI) with a task designed to activate the EBA by sports-related actions, we aimed to elucidate functional abnormality of the EBA during observation of sports-related actions in patients with schizophrenia. Twelve schizophrenia patients and 12 age-sex-matched control participants participated in the study. Using sports-related motions as visual stimuli, we examined brain activations during observation of context-congruent actions relative to context-incongruent actions by fMRI. Compared with controls, the patients with schizophrenia demonstrated diminished activation in the EBA during observation of sports-related context-congruent actions. Furthermore, the EBA activation in patients was negatively correlated with the severity of negative and general psychopathology symptoms measured by the Positive and Negative Syndrome Scale. Dysfunction of the EBA might reflect a difficulty in representing dynamic aspects of human actions and possibly lead to impairments of simulation, learning, and execution of actions in schizophrenia.