Takeyuki Mori

Impaired self-awareness and theory of mind: An fMRI study of mentalizing in alexithymia

Alexithymic individuals have difficulty in recognizing and describing emotions in themselves. We investigated the neuronal basis of mentalizing in alexithymia to determine whether there is a common neuronal substrate associated with knowing the mental states of the self and others. Individuals high in alexithymia (n = 16) and low in alexithymia (n = 14) were selected from a pool of 310 college students using a combination of the Toronto Alexithymia Scale (TAS-20) and the Structured Interview version of the Beth Israel Questionnaire (SIBIQ). We compared the two groups on psychological measures, including ratings of mentalizing and the Interpersonal Reactivity Index (IRI), and regional brain activation using functional magnetic resonance imaging (fMRI) during a mentalizing animation task. The results for both groups showed activation in regions associated with mentalizing: medial prefrontal cortices (MPFC), temporo-parietal junctions (TPJ), and the temporal pole (TP). Alexithymics had lower mentalizing and IRI perspective-taking scores and less activation in the right MPFC. Activity in the MPFC was positively correlated with the mentalizing score and the IRI perspective-taking score. Although there were no group differences in cerebral activity in the TPJ and the TP, the activity in the right TP had a positive correlation with mentalizing and IRI personal distress scores. These results suggest that alexithymic individuals have an impairment in mentalizing associated with an inability to take the perspective of others. Thus, the skills involved in comprehending the self and others are inter-related and play an important role in emotion regulation.

The prediction of rapid conversion to Alzheimer's disease in mild cognitive impairment using regional cerebral blood flow SPECT

Mild cognitive impairment (MCI) comprises a heterogeneous group with a variety of clinical outcomes and they are at risk for developing Alzheimers disease (AD). The prediction of conversion from MCI to AD using the initial neuroimaging studies is an important research topic. We investigated the initial regional cerebral blood flow (rCBF) measurements using single photon emission computed tomography (SPECT) in individuals with 76 amnesic MCI (52 subjects converted to AD and 24 subjects did not convert to AD at 3-year follow-up) and 57 age- and gender-matched controls. We sought functional profiles associated with conversion to AD, then evaluated the predictive value of the initial rCBF SPECT. As compared with controls, AD converters demonstrated reduced blood flow in the bilateral parahippocampal gyri, precunei, posterior cingulate cortices, bilateral parietal association areas, and the right middle temporal gyrus. Non-converters also demonstrated significant reduction of rCBF in the posterior cingulated cortices and the right caudate nucleus when compared to controls. As compared with non-converters, converters showed reductions of rCBF in the bilateral temporo-parietal areas and the precunei. The logistic regression model revealed that reduced rCBF in the inferior parietal lobule, angular gyrus, and precunei has high predictive value and discriminative ability. Although a cross-validation study is needed to conclude the usefulness of rCBF SPECT for the prediction of AD conversion in individuals with MCI, our data suggest that the initial rCBF SPECT studies of individuals with MCI may be useful in predicting who will convert to AD in the near future.

The Val66Met polymorphism of the brain-derived neurotrophic factor gene affects age-related brain morphology.

We investigated the effects of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on age-associated changes of brain morphology in 109 Japanese healthy subjects using MRI with optimized voxel-based morphometry technique. A significant age-related volume reduction was found in the dorsolateral prefrontal cortices (DLPFC), anterior cingulate cortices, and temporal and parietal cortices in all subjects. Further analysis revealed a significantly negative correlation between age and the volume of the bilateral DLPFC only in the Met-BDNF carriers, and a significant interaction between the polymorphism and age-associated volume changes in the bilateral DLPFC. Furthermore, Met-carriers showed a significant interaction (p<0.0001) between the gender and the genotype on the gray matter volume in the DLPFC, and female Met-carriers showed more widespread age-associated volume reduction in DLPFC than male Met-carriers. Our data suggest that the Val66Met polymorphism may impact on age-related changes of the brain, which might be associated with the functional variance of neuroprotective effects of the BDNF. Furthermore, we suggest that genotype effects of the BDNF gene on brain morphology might differ in female from in male.

Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia

Pituitary adenylate cyclase-activating polypeptide (PACAP, ADCYAP1: adenylate cyclase-activating polypeptide 1), a neuropeptide with neurotransmission modulating activity, is a promising schizophrenia candidate gene. Here, we provide evidence that genetic variants of the genes encoding PACAP and its receptor, PAC1, are associated with schizophrenia. We studied the effects of the associated polymorphism in the PACAP gene on neurobiological traits related to risk for schizophrenia. This allele of the PACAP gene, which is overrepresented in schizophrenia patients, was associated with reduced hippocampal volume and poorer memory performance. Abnormal behaviors in PACAP knockout mice, including elevated locomotor activity and deficits in prepulse inhibition of the startle response, were reversed by treatment with an atypical antipsychotic, risperidone. These convergent data suggest that alterations in PACAP signaling might contribute to the pathogenesis of schizophrenia.

Changes of brain activity in the neural substrates for theory of mind during childhood and adolescence

Abstract  Theory of mind (ToM) refers to the ability to attribute independent mental states, such as beliefs, preferences and desires, to the self and others. Neuroimaging studies of normal adults have consistently demonstrated the importance of particular brain regions for ToM, the superior temporal sulcus (STS), temporal pole (TP) and the medial prefrontal cortex (MPFC). However, there are little data showing how ToM develops during childhood and adolescence. Such data are important for understanding the development of social functioning and its disorders. The authors used functional magnetic resonance imaging to study age‐related changes in brain activity associated with ToM during childhood and early adolescence (9–16 years). Normally developed children and adolescents demonstrated significant activation in the bilateral STS, the TP adjacent to the amygdala (TP/Amy) and the MPFC. Furthermore, the authors found a positive correlation between age and the degree of activation in the dorsal part of the MPFC; in contrast, a negative correlation was found for the ventral part of the MPFC. The authors also found a positive correlation between the Z coordinate of the peak activation in the MPFC and age. The data indicated that activity in the MPFC associated with ToM shifted from the ventral to the dorsal part of the MPFC during late childhood and adolescence. No age‐related changes were found in the STS and the TP/Amy regions. The authors consider that the age‐related brain activity observed in the present study may be associated with the maturation of the prefrontal cortex and the associated development of cognitive functions.

Specific brain activation in Japanese and Caucasian people to fearful faces

Different regions of brain activation, as measured by fMRI, were evident in Japanese and Caucasian individuals observing facial expressions categorized as fearful according to Ekman criteria. Activation was evident in the posterior cingulate, supplementary motor cortex and the amygdala in Caucasians, while activation was evident in the right inferior frontal, premotor cortex and left insula and in Japanese individuals. The results suggest that Caucasians respond to fearful faces in a more direct, emotional way, whereas Japanese do not attach an emotional valence to the faces and therefore activate a template matching system to identify facial expressions. The faces widely used as emotional stimuli therefore are not universally perceived, and cultural specificity should be taken into consideration in designing facial tasks.

Dose-dependent effect of the Val66Met polymorphism of the brain-derived neurotrophic factor gene on memory-related hippocampal activity.

Brain-derived neurotrophic factor (BDNF) plays a critical role in activity-dependent neuroplasticity underlying learning and memory in the hippocampus. Recent human studies have indicated that a common single nucleotide polymorphism of the BDNF gene, the Val66Met polymorphism, has impact on episodic memory, hippocampal morphology and memory-related hippocampal activity measured by functional magnetic resonance imaging (fMRI). However, two issues remain to be clarified: (1) whether the genotype effect of this polymorphism on memory-related brain activity is allele dose dependent and (2) whether the effect of this polymorphism in Asian population is the same as effects observed in Caucasian sample. To clarify these issues, we studied the relationship of the Val66Met polymorphism genotype and hippocampal activity during episodic memory task using fMRI in healthy 58 biologically unrelated Japanese. Although there was no genotype effect on episodic memory function obtained by behavioral assessments, fMRI measurements revealed a significantly negative correlation between the dose of Met-BDNF allele and encoding related brain activity in the bilateral hippocampi and right parahippocampal gyrus. There was no genotype effect on retrieval related brain activity. These data indicated a genetic mechanism for normal variation in human memory and suggest effects of BDNF signaling on hippocampal function in humans.

Removal of ballistocardiogram artifacts from simultaneously recorded EEG and fMRI data using independent component analysis

Simultaneous recording of electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) has been studied to identify areas related to EEG events. EEG data recorded in the magnetic resonance (MR) scanner with MR imaging is suffered from two specific artifacts, imaging artifact, and ballistocardiogram (BCG). In this paper, we focus on BCG. In preceding studies, average subtraction was often used for this purpose. However, average subtraction requires an assumption that BCG waveforms are precisely periodic, which seems unrealistic because BCG is a biomedical artifact. We propose the application of independent component analysis (ICA) with a postprocessing of high-pass filtering for the removal of BCG. With this approach, it is not necessary to assume that the BCG waveform is periodic. Empirically, we show that our proposed method removes BCG artifacts as well as does the average subtraction method. Power spectral density analysis of the two approaches shows that, with ICA, distortion of recovered EEG data is also as small as that associated with the average subtraction approach. We also propose a hypothesis for how head movement causes BCGs and show why ICA can remove BCG artifacts arising from this source.

Smoking habits in Japanese patients with schizophrenia

Studies from North America and Western Europe have observed a marked increase of smoking in schizophrenia. This preliminary study investigated smoking habits in Japanese patients with schizophrenia (n=137). The prevalence of smokers (34%) was not higher than in the general Japanese population (37%). Variables associated with smoking were also different from those reported in the Western literature. Different cultural backgrounds may underlie the differing results in Western and Japanese populations.

Susceptibility genes for schizophrenia

Abstract  It is well known that genetic factors contribute to the susceptibility for schizophrenia. Recent advances in the molecular genetics of schizophrenia strongly suggest several susceptibility genes (e.g. dysbindin, neuregulin‐1, DISC1, COMT, G72, RGS4 and Akt1). We discuss the evidence and biology of these genes. As glutamate transmission is especially implicated in these genes, neurobiological basis of schizophrenia might be elucidated by investigation of functional interactions between susceptibility genes for schizophrenia and the glutamatergic system.