Masatoshi Itoh

Deceiving Others: Distinct Neural Responses of the Prefrontal Cortex and Amygdala in Simple Fabrication and Deception with Social Interactions

Brain mechanisms for telling lies have been investigated recently using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography. Although the advent of these techniques has gradually enabled clarification of the functional contributions of the prefrontal cortex in deception with respect to executive function, the specific roles of subregions within the prefrontal cortex and other brain regions responsible for emotional regulation or social interactions during deception are still unclear. Assuming that the processes of falsifying truthful responses and deceiving others are differentially associated with the activities of these regions, we conducted a positron emission tomography experiment with 2 (truth, lie) 2 (honesty, dishonesty) factorial design. The main effect of falsifying the truthful responses revealed increased brain activity of the left dorsolateral and right anterior prefrontal cortices, supporting the interpretation of previous studies that executive functions are related to making untruthful responses. The main effect of deceiving the interrogator showed activations of the ventromedial prefrontal (medial orbitofrontal) cortex and amygdala, adding new evidence that the brain regions assumed to be responsible for emotional processing or social interaction are active during deceptive behavior similar to that in real-life situations. Further analysis revealed that activity of the right anterior prefrontal cortex showed both effects of deception, indicating that this region has a pivotal role in telling lies. Our results provide clear evidence of functionally dissociable roles of the prefrontal subregions and amygdala for human deception.

Central Effects of Fexofenadine and Cetirizine: Measurement of Psychomotor Performance, Subjective Sleepiness, and Brain Histamine H1‐Receptor Occupancy Using 11C‐Doxepin Positron Emission Tomography

Histamine H1‐receptor (H1R) antagonists, or antihistamines, often induce sedative side effects when used for the treatment of allergic disorders. This study compared the sedative profiles of the second‐generation antihistamines, fexofenadine and cetirizine, using 3 different criteria: subjective sleepiness evaluated by the Stanford Sleepiness Scale, objective psychomotor tests (simple and choice reaction time tests and visual discrimination tests at 4 different exposure durations), and measurement of histamine H1‐receptor occupancy (H1RO) in the brain. Subjective sleepiness and psychomotor performance were measured in 20 healthy Japanese volunteers at baseline and 90 min after administration of fexofenadine 120 mg or cetirizine 20 mg in a double‐blind, placebo‐controlled crossover study. Hydroxyzine 30 mg was included as a positive control. H1RO was measured using positron emission tomography (PET) with 11C‐doxepin in 12 of the 20 subjects, and a further 11 volunteers were recruited to act as controls. In psychomotor tests, fexofenadine was not significantly different from placebo and significantly less impairing than cetirizine on some tasks, as well as significantly less impairing than hydroxyzine on all tasks. For subjective sleepiness, fexofenadine was not significantly different from placebo, whereas cetirizine showed a trend toward increased sleepiness compared with fexofenadine and placebo. H1RO was negligible with fexofenadine (−0.1%) but moderately high with cetirizine (26.0%). In conclusion, fexofenadine 120 mg is distinguishable from cetirizine 20 mg, as assessed by H1RO and psychomotor testing.

Decreased histamine H1 receptor binding in the brain of depressed patients

The central histaminergic neuron system modulates the wakefulness, sleep–awake cycle, appetite control, learning and memory, and emotion. Previous studies have reported changes in neuronal histamine release and its metabolism under stress conditions in the mammalian brain. In this study, we examined, using positron emission tomography (PET) and [11C]‐doxepin, whether the histaminergic neuron system is involved in human depression. Cerebral histamine H1 receptor (H1R) binding was measured in 10 patients with major depression and in 10 normal age‐matched subjects using PET and [11C]‐doxepin. Data were calculated by a graphical analysis on voxel‐by‐voxel and ROI (region of interests) basis. Binding potential (BP) values for [11C]‐doxepin binding in the frontal and prefrontal cortices, and cingulate gyrus were significantly lower in the depressed patients than those in the normal control subjects. There was no area of the brain where [11C]‐doxepin binding was significantly higher in the depressed patients than in the controls. ROI‐based analysis also revealed that BP values for [11C]‐doxepin binding in the frontal cortex and cingulate gyrus decreased in proportion to self‐rating depressive scales scores. The results of this study demonstrate that depressed patients have decreased brain H1R binding and that this decrease correlates with the severity of depression symptoms. It is therefore suggested that the histaminergic neuron system plays an important role in the pathophysiology of depression and that its modulation may prove to be useful in the treatment of depression.

Functional brain mapping of actual car driving using [18F]FDG-PET

AimsThis study aims at identifying the brain activation during actual car-driving on the road, and at comparing the results to those of previous studies on simulated car-driving.MethodsThirty normal volunteers, aged 20 to 56 years, were divided into three subgroups, active driving, passive driving and control groups, for examination by positron emission tomography (PET) and [18F]2-deoxy-2-fluoro-D-glucose (FDG). The active driving subjects (n = 10) drove for 30 minutes on quiet normal roads with a few traffic signals. The passive driving subjects (n = 10) participated as passengers on the front seat. The control subjects (n = 10) remained seated in a lit room with their eyes open. Voxel-basedt-statistics were applied using SPM2 to search brain activation among the subgroups mentioned above.ResultsSignificant brain activation was detected during active driving in the primary and secondary visual cortices, primary sensorimotor areas, premotor area, parietal association area, cingulate gyrus, the parahippocampal gyrus as well as in thalamus and cerebellum. The passive driving manifested a similar-looking activation pattern, lacking activations in the premotor area, cingulate and parahippocampal gyri and thalamus. Direct comparison of the active and passive driving conditions revealed activation in the cerebellum.ConclusionThe result of actual driving looked similar to that of simulated driving, suggesting that visual perception and visuomotor coordination were the main brain functions while driving. In terms of attention and autonomic arousal, however, it seems there was a significant difference between simulated and actual driving possibly due to risk of accidents. Autonomic and emotional aspects of driving should be studied using an actual driving study-design.

Risperidone is effective for wandering and disturbed sleep/wake patterns in Alzheimer's disease

Behavioral and psychological symptoms of dementia (BPSD), especially aggressiveness, wandering, and sleep disturbance, are a major burden for caregivers. Daily sleep/wake patterns and wandering of institutionalized patients with Alzheimer’s disease (AD) were visually monitored, and 34 patients who manifested wandering were selected and randomly classified into 2 groups: the risperidone group and the nonrisperidone group. After an administration of low-dose risperidone for the risperidone group, the BPSD were reassessed. The binding potentials of dopamine D2 receptor for preadministration and postadministration of risperidone were assessed using positron emission tomography (PET) for 1 case. After the use of risperidone, aggressiveness and wandering were reduced and the nighttime sleeping hours were increased. The PET revealed that the binding potential of dopamine receptor was increased after administration of the drug, associated with improved sleep/wake patterns and behavioral abnormality. Possible serotonergic modulation of dopaminergic function might explain the neurobiological basis of the effect of risperidone.

Reactivation of medial temporal lobe and occipital lobe during the retrieval of color information: A positron emission tomography study.

It is widely accepted that memory traces of an event include various types of information about the content of the event and about the circumstances in which the individual experienced it. However, how these various types of information are stored and later retrieved is poorly understood. One hypothesis postulates that the retrieval of specific event information reactivates regions that were active during the encoding of this information, with the aid of binding functions of the medial temporal lobe (MTL) structures. We used positron emission tomography to identify the brain regions related to the encoding and retrieval of color information. Specifically, we assessed whether overlapping activity was found in both the MTL structures and color-related cortical regions during the encoding and retrieval of color information attached with meaningless shapes. During the study, subjects were asked to encode colored (red or green) and achromatic random shapes. At subsequent testing, subjects were presented with only achromatic shapes, which had been presented with or without colors during encoding, and were engaged in retrieval tasks of shapes and colors. Overlapping activity was found in the MTL and occipital lobe (the lingual and inferior occipital gyri) in the right hemisphere during the encoding and retrieval of meaningless shapes with color information compared with those without color information. Although there are some limitations to be considered, the present findings seem to support the view that the retrieval of specific event information is associated with reactivation of both the MTL structures and the regions involved during encoding of the information.

Medial frontal cortex perfusion abnormalities as evaluated by positron emission tomography in women with climacteric symptoms.

Objective: To identify functional changes in the brains of women with climacteric symptoms. Images of regional cerebral blood flow (rCBF) were compared statistically between women with and women without symptoms to identify changes in rCBF. Results may provide a better understanding of the neural basis of the symptoms, which are divided into three symptom clusters: vasomotor, psychological, and somatic. Design: The study participants consisted of 12 women with moderate to severe climacteric symptoms (age 47.5 ± 5.9 years, mean ± SD) and 7 women with no symptoms (control group; age 49.6 ± 4.2 years, mean ± SD). The study participants were patients at a menopause clinic, and the latter were healthy volunteer nurses and hospital staff. Climacteric symptoms were evaluated by an assessment of the severity of 17 symptoms immediately before positron emission tomography examination of rCBF. The symptoms had been used previously to generate the Kupperman Kohnenki Shogai Index, a modified Kupperman Menopausal Index adapted to Japanese women. rCBF was measured by positron emission tomography with the C15O2 dynamic inhalation method. Results: Reductions in relative rCBF in the patient group were observed in the bilateral rectal gyrus and in the left subcallosal gyrus on a voxel-by-voxel basis as compared with the control group. Conclusions: The present study revealed reductions in relative rCBF of the prefrontal cortex of Japanese women with moderate to severe climacteric symptoms. This area is close to that previously addressed in studies of familial bipolar depression and familial unipolar depression, although our participants did not satisfy criteria for depression. This reduction of rCBF may be related to the three climacteric symptom clusters, but further studies are needed for evaluation of its significance. Our results should stimulate investigations into the positron emission tomography rCBF change of these women as to the integration of multiple entities in climacteric symptoms.

Classical conditioned response of rectosigmoid motility and regional cerebral activity in humans

Abstractu2002 The relationship between the central processes of classical conditioning and conditioned responses of the gastrointestinal function is incompletely understood in humans. We tested the hypothesis that the rectosigmoid motility becomes conditioned with anticipatory painful somatosensory stimulus and that characteristic brain areas become activated during anticipation. In nine right‐handed healthy male subjects, a loud buzzer (CS, conditional stimulus) was paired with painful transcutaneus electrical nerve stimulation to the right hand (unconditional stimulus). Rectosigmoid muscle tone measured by the barostat as the intrabag volume, phasic contractions of the bowel measured as the number of phasic volume events (PVEs), and regional cerebral blood flow assessed by positron emission tomography (PET), were measured before and after conditioning. Following conditional trials, the bag volume after CS alone did not show significant changes between before and after the stimulus, but the number of PVEs after 2‐minute interval of the CS alone was significantly greater than that before the stimulus (Pu2003<u20030.05). The PET data showed the conditioning elicited significant cerebral activation of the prefrontal, anterior cingulate, parietal and insula cortices (Pu2003≤u20030.001, uncorrected). Rectosigmoid motility can be conditioned with increase in phasic contractions in humans.