Hirotaka Kosaka

Neural Interaction of the Amygdala with the Prefrontal and Temporal Cortices in the Processing of Facial Expressions as Revealed by fMRI

Some involvement of the human amygdala in the processing of facial expressions has been investigated in neuroimaging studies, although the neural mechanisms underlying motivated or emotional behavior in response to facial stimuli are not yet fully understood. We investigated, using functional magnetic resonance imaging (fMRI) and healthy volunteers, how the amygdala interacts with other cortical regions while subjects are judging the sex of faces with negative, positive, or neutral emotion. The data were analyzed by a subtractive method, then, to clarify possible interaction among regions within the brain, several kinds of analysis (i.e., a correlation analysis, a psychophysiological interaction analysis and a structural equation modeling) were performed. Overall, significant activation was observed in the bilateral fusiform gyrus, medial temporal lobe, prefrontal cortex, and the right parietal lobe during the task. The results of subtraction between the conditions showed that the left amygdala, right orbitofrontal cortex, and temporal cortices were predominantly involved in the processing of the negative expressions. The right angular gyrus was involved in the processing of the positive expressions when the negative condition was subtracted from the positive condition. The correlation analysis showed that activity in the left amygdala positively correlated with activity in the left prefrontal cortex under the negative minus neutral subtraction condition. The psychophysiological interaction revealed that the neural responses in the left amygdala and the right prefrontal cortex underwent the condition-specific changes between the negative and positive face conditions. The right amygdaloid activity also had an interactive effect with activity in the right hippocampus and middle temporal gyrus. These results may suggest that the left and right amygdalae play a differential role in effective processing of facial expressions in collaboration with other cortical or subcortical regions, with the left being related with the bilateral prefrontal cortex, and the right with the right temporal lobe.

Differential amygdala response during facial recognition in patients with schizophrenia: an fMRI study

Human lesion or neuroimaging studies suggest that amygdala is involved in facial emotion recognition. Although impairments in recognition of facial and/or emotional expression have been reported in schizophrenia, there are few neuroimaging studies that have examined differential brain activation during facial recognition between patients with schizophrenia and normal controls. To investigate amygdala responses during facial recognition in schizophrenia, we conducted a functional magnetic resonance imaging (fMRI) study with 12 right-handed medicated patients with schizophrenia and 12 age- and sex-matched healthy controls. The experiment task was a type of emotional intensity judgment task. During the task period, subjects were asked to view happy (or angry/disgusting/sad) and neutral faces simultaneously presented every 3 s and to judge which face was more emotional (positive or negative face discrimination). Imaging data were investigated in voxel-by-voxel basis for single-group analysis and for between-group analysis according to the random effect model using Statistical Parametric Mapping (SPM). No significant difference in task accuracy was found between the schizophrenic and control groups. Positive face discrimination activated the bilateral amygdalae of both controls and schizophrenics, with more prominent activation of the right amygdala shown in the schizophrenic group. Negative face discrimination activated the bilateral amygdalae in the schizophrenic group whereas the right amygdala alone in the control group, although no significant group difference was found. Exaggerated amygdala activation during emotional intensity judgment found in the schizophrenic patients may reflect impaired gating of sensory input containing emotion.

Individual Trait Anxiety Levels Characterizing the Properties of Zen Meditation

Meditation is a specific consciousness state in which deep relaxation and increased internalized attention coexist. There have been various neurophysiological studies on meditation. However, the personal predispositions/traits that characterize the properties of meditation have not been adequately studied. We analyzed changes in neurophysiological parameters [EEG coherence and autonomic nervous activity using heart rate variability (HRV) as an index] during Zen meditation, and evaluated the results in association with trait anxiety (assessed by Spielberger’s State-Trait Anxiety Inventory) in 22 healthy adults who had not previously practiced any form of meditation. During meditation, in terms of mean values in all subjects, an increase in slow alpha interhemispheric EEG coherence in the frontal region, an increase in high-frequency (HF) power (as a parasympathetic index of HRV), and a decrease in the ratio of low-frequency to HF power (as a sympathetic index of HRV) were observed. Further evaluation of these changes in individuals showed a negative correlation between the percent change (with the control condition as the baseline) in slow alpha interhemispheric coherence reflecting internalized attention and the percent change in HF reflecting relaxation. The trait anxiety score was negatively correlated with the percent change in slow alpha interhemispheric coherence in the frontal region and was positively correlated with the percent change in HF. These results suggest that lower trait anxiety more readily induces meditation with a predominance of internalized attention, while higher trait anxiety more readily induces meditation with a predominance of relaxation.

Smaller insula and inferior frontal volumes in young adults with pervasive developmental disorders

Enlarged head circumference and increased brain weight have been reported in infants with pervasive developmental disorders (PDD), and volumetric studies suggest that children with PDD have abnormally enlarged brain volumes. However, little is known about brain volume abnormalities in young adults with PDD. We explored gray matter (GM) volume in young adults with PDD. T1-weighted volumetric images were acquired with a 3-T magnetic resonance scanner from 32 males with high-functioning PDD (23.8+/-4.2 years; Full Scale Intelligence Quotient [FSIQ]=101.6+/-15.6) and 40 age-matched normal male control subjects (22.5+/-4.3 years; FSIQ=109.7+/-7.9). Regional GM volumes were compared between the two groups using voxel-based morphometry (VBM) with the Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL). Compared with the control group, the high-functioning PDD group showed significantly less GM in the right insula, the right inferior frontal gyrus, and the right inferior parietal lobule. A conservative threshold confirmed considerably smaller volumes in the right insula and inferior frontal gyrus. In these areas, negative correlations were found between Autism Spectrum Quotient scores and GM volume, although no significant correlations were found between each subjects FSIQ and GM volume. No regions showed greater GM volumes in the high-functioning PDD group. The insular cortex, which works as a relay area for multiple neurocognitive systems, may be one of the key regions underlying the complex clinical features of PDD. These smaller GM volumes in high-functioning PDD subjects may reflect the clinical features of PDD itself, rather than FSIQ.

“Stay Tuned”: Inter-Individual Neural Synchronization During Mutual Gaze and Joint Attention

Eye contact provides a communicative link between humans, prompting joint attention. As spontaneous brain activity might have an important role in the coordination of neuronal processing within the brain, their inter-subject synchronization might occur during eye contact. To test this, we conducted simultaneous functional MRI in pairs of adults. Eye contact was maintained at baseline while the subjects engaged in real-time gaze exchange in a joint attention task. Averted gaze activated the bilateral occipital pole extending to the right posterior superior temporal sulcus, the dorso-medial prefrontal cortex, and the bilateral inferior frontal gyrus. Following a partners gaze toward an object activated the left intraparietal sulcus. After all the task-related effects were modeled out, inter-individual correlation analysis of residual time-courses was performed. Paired subjects showed more prominent correlations than non-paired subjects in the right inferior frontal gyrus, suggesting that this region is involved in sharing intention during eye contact that provides the context for joint attention.

Neural substrates participating in acquisition of facial familiarity: an fMRI study

The amygdala is related to recognition of faces and emotions, and functional magnetic resonance imaging (fMRI) studies have reported that the amygdala is habituated over time with repetition of facial stimuli. When subjects are presented repeatedly with unfamiliar faces, they come to gradually recognize the unfamiliar faces as familiar. To investigate the brain areas participating in the acquisition of familiarity to repeatedly presented unfamiliar faces, we conducted an fMRI study in 16 healthy subjects. During the task periods, the subjects were instructed to see presented unfamiliar faces repeatedly and to judge whether the face was male or female or whether the face had emotional valences. The experiment consisted of nine sessions. To clarify the brain areas that showed increasing or decreasing activation as the experimental session proceeded, we analyzed the fMRI data using specified linear covariates in the face recognition task from the first session to the ninth session. Imaging data were investigated on a voxel-by-voxel basis for single-group analysis according to the random effect model using Statistical Parametric Mapping. The bilateral posterior cingulate cortices showed significant increases in activity as the experimental sessions proceeded, while the activation in the right amygdala and the left medial fusiform gyrus decreased. Thus, the posterior cingulate cortex may play an important role in the acquisition of facial familiarity.

Plasma levels of adiponectin and tumor necrosis factor-alpha in patients with remitted major depression receiving long-term maintenance antidepressant therapy

Adiponectin, an adipose tissue-specific plasma protein, is involved in insulin sensitization and has anti-atherosclerotic properties, whereas tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory protein, plays important roles in inflammatory endothelial injury and atherosclerotic changes. It has been reported that adiponectin and TNF-alpha inhibit each others expression and production in adipocytes. Several in vitro studies indicated that antidepressant medications decreased the production of pro-inflammatory cytokines including TNF-alpha, but the effect of antidepressants on the expression of adiponectin is still unknown. We examined the plasma levels of TNF-alpha and adiponectin in patients with remitted depression receiving maintenance antidepressant therapy for longer than half a year, and compared the levels with those in healthy controls. The plasma levels of TNF-alpha and adiponectin in the remitted depression group were significantly lower and higher than those in the control group, respectively. This preliminary cross-sectional study suggests the possibility that maintenance antidepressant therapy may have anti-inflammatory effects and prevent the development of atherosclerosis.

Long-term oxytocin administration improves social behaviors in a girl with autistic disorder

BackgroundPatients with autism spectrum disorders (ASDs) exhibit core autistic symptoms including social impairments from early childhood and mostly show secondary disabilities such as irritability and aggressive behavior based on core symptoms. However, there are still no radical treatments of social impairments in these patients. Oxytocin has been reported to play important roles in multiple social behaviors dependent on social recognition, and has been expected as one of the effective treatments of social impairments of patients with ASDs.Case presentationWe present a case of a 16-year-old girl with autistic disorder who treated by long-term administration of oxytocin nasal spray. Her autistic symptoms were successfully treated by two month administration; the girl’s social interactions and social communication began to improve without adverse effects. Her irritability and aggressive behavior also improved dramatically with marked decreases in aberrant behavior checklist scores from 69 to 7.ConclusionThis case is the first to illustrate long-term administration of oxytocin nasal spray in the targeted treatment of social impairments in a female with autistic disorder. This case suggests that long-term nasal oxytocin spray is promising and well-tolerated for treatment of social impairments of patients with ASDs.

Relationship between plasma leptin level and brain structure in elderly: a voxel-based morphometric study.

BACKGROUND Recent accumulating lines of evidence reveal that leptin is associated with synaptic plasticity and neuroprotective activity in the brain. METHODS In this preliminary study with a cross-sectional design, we examined the relationship between plasma leptin level and total or regional gray matter (GM) volume in 34 elderly subjects (mean age 64.5 years) with normal fasting glucose level and without dementia and metabolic syndrome by voxel-based morphometry of magnetic resonance imaging scans. RESULTS Plasma leptin level showed no significant correlation with total GM volume but showed a significantly positive correlation with GM volumes in the right hippocampus, left parahippocampus, and right cerebellum with adjustments for age, gender, body mass index (BMI), and waist-to-hip ratio (W/H). Also, after adjustments for age, gender, BMI, W/H, and intracranial volume, plasma leptin level significantly positively correlated with GM volumes in the right hippocampus and bilateral cerebella but not with that in the left parahippocampus. CONCLUSIONS The results of this pilot study would be beneficial for our understanding of the neuroprotective effects of leptin on human brain aging.

Quantitative evaluation of age-related white matter microstructural changes on MRI by multifractal analysis

Multifractal analysis has been applied to evaluate biological tissues, which are composed of complex structures. We carried out multifractal analyses in a group of healthy young and elderly subjects to examine age-related white matter microstructural changes on T2-weighted MR images without any visible abnormal intensity, and to correlate such changes with age-related cognitive decline. Comparison between the two age groups showed that Deltaalpha (established as the most suitable index of heterogeneity in our previous report) in the frontal region was significantly higher in the elderly group, but no significant group difference was found in Deltaalpha in the parieto-occipital region. The Trail-Making Test score (a measure of executive dysfunction) was significantly higher in the elderly group. In the elderly group, the Trail-Making Test score was positively correlated with Deltaalpha in the frontal region, but not in the parieto-occipital region. These results suggest that microstructural changes in the white matter preferentially occur in the frontal region with normal aging, and these changes are associated with executive cognitive decline reflective of frontal-subcortical dysfunction.