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Hyperscanning functional magnetic resonance imaging (fMRI) was developed to gain deeper insight into the neural basis of social cognition. Simultaneous imaging of brain activity in multiple subjects facilitates analysis of the neural basis of real-time interactions and communication. This method reveals the neural basis of social interactions, including inter-individual synchronization as a phenomenon that cannot be reduced to individuals. This modality enables research into the neural mechanisms underlying social interactions that are integral to many aspects of our lives. I will outline the background, current status, and prospects of development of hyperscanning fMRI, which may be an important methodology in the shift from "first-person" neuroscience (which refers to the interaction between individuals and the environment) to "second-person" neuroscience (which refers to the application of neuroscientific methods to investigate inter-individual associations).

Effective human communication is a complex process that involves transmitting and sharing information, ideas, and attitudes between two or more individuals. Researchers need to explore both transmission and sharing concepts to understand the neural basis of communication. Face-to-face communication refers to changing someone's mental state by sharing information, ideas, or attitudes. This type of communication is characterized by "mutual predictability." Scientists are working to clarify the neural basis of communication by studying how inter-individual synchronization of behavior and neural activity occurs during face-to-face communication.

Social cognition is defined as the capacity to engage in information processing with the aim of accurate cognition of other persons' character or intentions. Development of social cognition can be observed in behavioral patterns. However, their neural basis remains largely unknown. A functional neuroimaging technique has enabled us to observe neural activities in the human brain noninvasively. First the principle and history of functional magnetic resonance imaging (fMRI), and its future perspective are introduced. As an example, presented is our attempt to apply simultaneous fMRI measurements of two individuals to elucidate the neural basis of joint attention, one of the most important behavioral milestones in the development of social cognition. Second, neural substrates of pro-social behavior are discussed. Specifically, it was found that social acceptance or praise is important for human altruistic behavior, and has a neural basis similar to that of basic reward or monetary reward. Lastly, I stress the importance of combining current and ongoing progress in neuroscience, from the 'micro' through 'macro' levels, with scholarship within the humanities. As a connecting node for the different research fields, functional neuroimaging techniques will play a critical for the ultimate goal of comprehensive understanding of human social cognition.

The pharmacokinetics of (S)-5-iodo-7-N-[(1-ethyl- 2-pyrrolidinyl)methyl]carboxamido-2,3-dihydro-benzofuran (123I-IBF) in the brain were studied in 12 healthy male volunteers as a Phase I clinical study. The striatum-to-frontal cortex count ratio (-1) (St/Fc-1), which is a semi-quantitative index of the binding potential of 123I-IBF reached 1.81 +/- 0.19 and 2.21 +/- 0.39 at 90-120 min and 180-210 min after intravenous injection of 123I-IBF. St/Fc-1 obtained by SPECT at these times correlated well with the distribution volume ratio (-1) (Vd(St)/Vd(Fc)-1) based on three-compartment model analysis using an input function obtained by intermittent arterial sampling. The binding potential (BPR), calculated by the curve-fitting method using the time-activity curve in the reference region, also correlated well with the Vd(St)/ Vd(Fc)-1. The intra-observer and inter-observer reproducibilities of the striatum-to-cerebral cortex count ratios obtained using fixed-shape regions of interest (template ROIs) were superior to those obtained using manual ROIs. These results suggest that 123I-IBF is a promising agent for non-invasive quantification of the dopamine D2 receptor (D2-R) binding potential by SPECT.

A Phase 1 clinical study of 123I-IBF, (S)-5-iodo-7- N-[(1-ethyl-2-pyrrolidinyl)methyl]carboxamido-2,3-dihydrobenzofuran, developed for evaluation of dopamine D2 receptor (D2-R) with SPECT, was performed in 12 healthy male volunteers. No side effects due to 123I-IBF (i.v. 167 MBq) injection were observed. In sequential whole-body images, the radioactivity was distributed mainly in the liver, lungs and brain, and decreased gradually. No significant retention of radioactivity was seen in any organ at 24 hr after injection. The absorbed dose of 123I-IBF, calculated based on the whole-body pharmacokinetics, was equal to or less than those of other brain perfusion imaging agents. No significant problems were observed in terms of the safety, pharmacokinetics or absorbed dose of 123I-IBF.

Brain single photon emission computed tomography (SPECT) with 99mTc-d,l-hexamethyl-propyleneamine oxime (HMPAO) was performed twice in a 78-year-old man clinically diagnosed as brain death according to the standard criteria of the Japanese Ministry of Welfare. The first brain SPECT demonstrated the tracer accumulation in the brain, indicating preserved cerebral blood flow. The second brain SPECT performed 3 days later revealed cessation of the blood flow. In patients with preserved cerebral blood flow, the diagnosis of brain death cannot be made, even if they meet the existing criteria, because previous report noted the recovery in some of those patients. Brain perfusion SPECT plays an important role as a confirmatory test for the diagnosis of the brain death.

Adriamycin-Lipiodol suspension was administered to 44 patients with metastatic liver tumor using the transcatheter arterial infusion method. The result revealed 23% in the over all effect (partial response or more) of the therapy which was evaluated by comparing the CT images of the tumor, 47% in the 25% or more of the decrease of the tumor, and 65%, very effective in the decrease of the smaller tumor (less than 50 cm2). Except for a case of hepatic subcapsular hematoma after the infusion of Adriamycin-Lipiodol suspension, minor complications were experienced such as abdominal pain, slight fever, and so on. No serious exacerbation in liver function test and white blood cell count was noted.

We have developed a simple method to quantitate brain perfusion SPECT with N-isopropyl-p-[123I]iodoamphetamine (IMP). After an intravenous bolus injection of IMP, serial dynamic images of the brain and the lung were obtained every 5 sec for 2 min, followed by a SPECT scan at 20 min. Based on the assumption of IMP as chemical microspheres, fractional uptake (FU) of IMP in the brain was calculated from the time-activity curves of the total brain and the total lungs. FU showed a strong positive correlation with inverse of the body surface area which was calculated from the height and weight of the individual subject, suggesting that FU is influenced by cardiac output. Quantification of IMP brain perfusion SPECT was attempted with FU and estimated cardiac output in each subject, providing an index of regional cerebral blood flow. Compared with PET measurement of regional cerebral blood flow, the present method tended to overestimate the flow values. This method has a great advantage that it can be applied in many institutions having large field gamma cameras. However, the accuracy of the measurement may be limited in the tall subjects and in the cases with cardiopulmonary diseases, and further investigation is required to clarify the usefulness and limitation of this approach.