The Anterior Piriform Cortex and Predator Odor Responses: Modulation by Inhibitory Circuits.

Rodents acquire more information from the sense of smell than humans because they have a nearly fourfold greater variety of olfactory receptors. They use olfactory information not only for obtaining food, but also for detecting environmental dangers. Predator-derived odor compounds provoke instinctive fear and stress reactions in animals. Inbred lines of experimental animals react in an innate stereotypical manner to predators even without prior exposure. Predator odors have also been used in models of various neuropsychiatric disorders, including post-traumatic stress disorder following a life-threatening event. Although several brain regions have been reported to be involved in predator odor-induced stress responses, in this mini review, we focus on the functional role of inhibitory neural circuits, especially in the anterior piriform cortex (APC). We also discuss the changes in these neural circuits following innate reactions to odor exposure. Furthermore, based on the three types of modulation of the stress response observed by our group using the synthetic fox odorant 2,5-dihydro-2,4,5-trimethylthiazoline, we describe how the APC interacts with other brain regions to regulate the stress response. Finally, we discuss the potential therapeutic application of odors in the treatment of stress-related disorders. A clearer understanding of the odor-stress response is needed to allow targeted modulation of the monoaminergic system and of the intracerebral inhibitory networks. It would be improved the quality of life of those who have stress-related conditions.

Simultaneous activities in both mirror-image glomerular maps in the olfactory bulb may have an important role in stress-related neuronal responses in mice.

In the mouse olfactory bulb (OB), odor input from the olfactory epithelium innervates topographically to form odorant maps, which are mirror-image arrangements of glomerular clusters with domain organization. However, the functional role of the mirror-image representation in the OB remains unknown. Predator odors induce stress responses, and the dorsal domain of the dorsolateral wall of the olfactory bulb (dlOB) is known to be involved in this process. However, it remains unclear whether the activities in the medial wall of the OB (mOB), the other mirror half, are also involved in stress responses. Therefore, in this study, we investigated whether the mOB and dlOB are required for the induction of stress responses using lesioning or electrical stimulation. Although there were no significant differences in the number of activated neurons in the bed nucleus of the stria terminalis, posterior piriform cortex or amygdalo-piriform transition area, fewer activated neurons were observed in the anterior piriform cortex (APC) following lesion of both the mOB and dlOB combined. No changes were observed in the density of activated cells in any examined brain region following stimulation of either the mOB or dlOB alone. However, activated neurons in the APC were significantly more numerous following simultaneous stimulation of the mOB and dlOB. Collectively, our results suggest that simultaneous activation in both the mOB and dlOB is needed to induce APC neural activities that produce stress-like behavior. These findings provide insight into olfactory information processing, and may also help in the development of therapies for odor-induced stress behaviors.

Cortical Regions Encoding Hardness Perception Modulated by Visual Information Identified by Functional Magnetic Resonance Imaging With Multivoxel Pattern Analysis.

Recent studies have revealed that hardness perception is determined by visual information along with the haptic input. This study investigated the cortical regions involved in hardness perception modulated by visual information using functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis (MVPA). Twenty-two healthy participants were enrolled. They were required to place their left and right hands at the front and back, respectively, of a mirror attached to a platform placed above them while lying in a magnetic resonance scanner. In conditions SFT, MED, and HRD, one of three polyurethane foam pads of varying hardness (soft, medium, and hard, respectively) was presented to the left hand in a given trial, while only the medium pad was presented to the right hand in all trials. MED was defined as the control condition, because the visual and haptic information was congruent. During the scan, the participants were required to push the pad with the both hands while observing the reflection of the left hand and estimate the hardness of the pad perceived by the right (hidden) hand based on magnitude estimation. Behavioral results showed that the perceived hardness was significantly biased toward softer or harder in >73% of the trials in conditions SFT and HRD; we designated these trials as visually modulated (SFTvm and HRDvm, respectively). The accuracy map was calculated individually for each of the pair-wise comparisons of (SFTvm vs. MED), (HRDvm vs. MED), and (SFTvm vs. HRDvm) by a searchlight MVPA, and the cortical regions encoding the perceived hardness with visual modulation were identified by conjunction of the three accuracy maps in group analysis. The cluster was observed in the right sensory motor cortex, left anterior intraparietal sulcus (aIPS), bilateral parietal operculum (PO), and occipito-temporal cortex (OTC). Together with previous findings on such cortical regions, we conclude that the visual information of finger movements processed in the OTC may be integrated with haptic input in the left aIPS, and the subjective hardness perceived by the right hand with visual modulation may be processed in the cortical network between the left PO and aIPS.

Effects of pseudoexperience on the understanding of hemiplegic movements in physical therapists: An fMRI study.

Physical therapists (PTs) are required to obtain an accurate understanding of the physical and mental states of their patients through observational assessment. To perform comprehensive observational assessments of patients' movements, PTs likely need to engage their own neural systems involved in action understanding and theory of mind, such as the action observation network (AON) and the right temporoparietal junction (rTPJ). Both systems are modulated by the observer's actual experience with the observed movements. Although, most PTs do not have physical experience with neurological disabilities, they routinely examine hemiplegic movements in stroke patients, and are thus considered to have acquired pseudoexperience with hemiplegia. We hypothesized that the PTs' pseudoexperience with hemiplegia would modulate the neural system associated with the understanding of others to elaborately comprehend the physical and mental states associated with hemiplegia. To investigate our hypothesis, we recruited 19 PTs and 19 naïve participants (NPs) to undergo functional MRI (fMRI) for cortical activity measurement while viewing videos of hemiplegic (HHM) and non-hemiplegic (non-HHM) hand movements. The participants subsequently viewed the same videos again outside the MRI scanner, and evaluated the observed hand movements via a questionnaire. Compared to the NPs, the PTs showed greater activation in the AON and rTPJ while observing HHMs. Psychophysiological interaction analyses revealed increased connectivity between the rTPJ and AON when the PTs viewed the HHMs. Behavioral analyses further indicated that the PTs more accurately assessed feeling states associated with HHMs than did NPs. These findings suggest that the PTs' pseudoexperience modulates the AON and rTPJ, enabling them to better understand hemiplegia-associated feeling states.

Effect of Visual Information on Active Touch During Mirror Visual Feedback.

Several studies have demonstrated that observation of a dummy or mirror-reflected hand being stroked or moving at the same time as the hidden hand evokes a feeling that the dummy hand is one's own, such as the rubber hand illusion (RHI) and mirror visual feedback (MVF). Under these conditions, participants also report sensing the tactile stimulation applied to the fake hands, suggesting that tactile perception is modulated by visual information during the RHI and MVF. Previous studies have utilized passive stimulation conditions; however, active touch is more common in real-world settings. Therefore, we investigated whether active touch is also modulated by visual information during an MVF scenario. Twenty-three participants (13 men and 10 women; mean age ± SD: 21.6 ± 2.0 years) were required to touch a polyurethane pad with both hands synchronously, and estimate the hardness of the pad while observing the mirror reflection. When participants observed the mirror reflection of the other hand pushing a softer or harder pad, perceived hardness estimates were significantly biased toward softer or harder, respectively, even though the physical hardness of the pad remained constant. Furthermore, perceived hardness exhibited a strong correlation with finger displacement of the mirrored, but not hidden, hand. The modulatory effects on perceived hardness diminished when participants touched the pad with both hands asynchronously or with their eyes closed. Moreover, participants experienced ownership of the mirrored hand when they touched the pad with both hands synchronously but not asynchronously. These results indicate that hardness estimates were modulated by observation of the mirrored hand during synchronous touch conditions. The present study demonstrates that, similar to passive touch, active touch is also modulated by visual input.

Effects of oral stimulation with capsaicin on salivary secretion and neural activities in the autonomic system and the brain.

BACKGROUND/PURPOSE: Although it has been reported that capsaicin ingestion has effects of protecting stomach mucosa and promoting energy consumption, physiological responses to oral stimulation with capsaicin has not been elucidated. Therefore, we investigated the effect of oral capsaicin stimulation on oral health and mental conditions by measuring changes in salivation, autonomic nervous activity and electroencephalogram (EEG). MATERIALS AND METHODS: Eighteen healthy adults participated in this study. The stimulus concentrations of capsaicin and five basic taste solutions were determined based on the measured threshold of each stimulus in each subject. The weight of secreted saliva and the changes in concentrations of salivary secretory immunoglobulin A (SIgA) induced by capsaicin and taste stimuli were measured. Salivary α-amylase activity and heart rate variability (HRV) were measured as indicators of autonomic nervous activity. From EEG, psychological condition was analyzed by measuring the powers of theta, alpha, and beta bands. RESULTS: The salivary secretion rate was significantly increased by stimulation with capsaicin, NaCl, and citric acid compared with deionized water, and capsaicin demonstrated the most potent effect among tested stimuli. The secreted amount of SIgA per minute was elevated by capsaicin stimulation. Salivary α-amylase activity and HRV analysis demonstrated an elevation of sympathetic nervous activity induced by capsaicin. EEG analysis showed a significant increase in beta band power. CONCLUSION: These results suggest that oral stimulation with capsaicin may be effective in improving oral conditions by increasing salivary flow and SIgA secretion, and in enhancing physical and mental conditions as indicated by sympathetic nerve and EEG changes.

Brain activity in patients with unilateral sensorineural hearing loss during auditory perception in noisy environments.

Patients with unilateral sensorineural hearing loss (UHL) often complain of hearing difficulties in noisy environments. To clarify this, we compared brain activation in patients with UHL with that of healthy participants during speech perception in a noisy environment, using functional magnetic resonance imaging (fMRI). A pure tone of 1 kHz, or 14 monosyllabic speech sounds at 65‒70 dB accompanied by MRI scan noise at 75 dB, were presented to both ears for 1 second each and participants were instructed to press a button when they could hear the pure tone or speech sound. Based on the activation areas of healthy participants, the primary auditory cortex, the anterior auditory association areas, and the posterior auditory association areas were set as regions of interest (ROI). In each of these regions, we compared brain activity between healthy participants and patients with UHL. The results revealed that patients with right-side UHL showed different brain activity in the right posterior auditory area during perception of pure tones versus monosyllables. Clinically, left-side and right-side UHL are not presently differentiated and are similarly diagnosed and treated; however, the results of this study suggest that a lateralityspecific treatment should be chosen.

Activation of the Human MT Complex by Motion in Depth Induced by a Moving Cast Shadow.

A moving cast shadow is a powerful monocular depth cue for motion perception in depth. For example, when a cast shadow moves away from or toward an object in a two-dimensional plane, the object appears to move toward or away from the observer in depth, respectively, whereas the size and position of the object are constant. Although the cortical mechanisms underlying motion perception in depth by cast shadow are unknown, the human MT complex (hMT+) is likely involved in the process, as it is sensitive to motion in depth represented by binocular depth cues. In the present study, we examined this possibility by using a functional magnetic resonance imaging (fMRI) technique. First, we identified the cortical regions sensitive to the motion of a square in depth represented via binocular disparity. Consistent with previous studies, we observed significant activation in the bilateral hMT+, and defined functional regions of interest (ROIs) there. We then investigated the activity of the ROIs during observation of the following stimuli: 1) a central square that appeared to move back and forth via a moving cast shadow (mCS); 2) a segmented and scrambled cast shadow presented beside the square (sCS); and 3) no cast shadow (nCS). Participants perceived motion of the square in depth in the mCS condition only. The activity of the hMT+ was significantly higher in the mCS compared with the sCS and nCS conditions. Moreover, the hMT+ was activated equally in both hemispheres in the mCS condition, despite presentation of the cast shadow in the bottom-right quadrant of the stimulus. Perception of the square moving in depth across visual hemifields may be reflected in the bilateral activation of the hMT+. We concluded that the hMT+ is involved in motion perception in depth induced by moving cast shadow and by binocular disparity.

Depth perception from moving cast shadow in macaque monkey.

In the present study, we investigate whether the macaque monkey can perceive motion in depth using a moving cast shadow. To accomplish this, we conducted two experiments. In the first experiment, an adult Japanese monkey was trained in a motion discrimination task in depth by binocular disparity. A square was presented on the display so that it appeared with a binocular disparity of 0.12 degrees (initial position), and moved toward (approaching) or away from (receding) the monkey for 1s. The monkey was trained to discriminate the approaching and receding motion of the square by GO/delayed GO-type responses. The monkey showed a significantly high accuracy rate in the task, and the performance was maintained when the position, color, and shape of the moving object were changed. In the next experiment, the change in the disparity was gradually decreased in the motion discrimination task. The results showed that the performance of the monkey declined as the distance of the approaching and receding motion of the square decreased from the initial position. However, when a moving cast shadow was added to the stimulus, the monkey responded to the motion in depth induced by the cast shadow in the same way as by binocular disparity; the reward was delivered randomly or given in all trials to prevent the learning of the 2D motion of the shadow in the frontal plane. These results suggest that the macaque monkey can perceive motion in depth using a moving cast shadow as well as using binocular disparity.

Effects of cortical activations on enhancement of handgrip force during teeth clenching: an fMRI study.

We assessed the effect of teeth clenching on handgrip force behaviorally, and investigated cortical activity during the occurrence of facilitatory effects using functional magnetic resonance imaging (fMRI). Twenty-three participants were assessed as to whether they had habitual teeth clenching during maximal voluntary contraction (MVC) exertion, and 21 of them were identified to have such a habit. For those participants, behavioral testing showed that MVC with clenching was greater compared with without clenching (approximately 108% greater on average). Next, cortical activity was measured under gripping with clenching (GwC), gripping without clenching (GwoC), and teeth clenching (C) conditions. We found that the activity of the hand region in primary motor cortex (M1), cingulate motor area/supplementary motor area (CMA/SMA) and anterior cerebellum (AC) was greater in contrast of GwC vs. (GwoC+C). Furthermore, significant correlation was observed between the increasing ratio of the handgrip force and the % signal change in the hand region of M1 and AC, but not in CMA/SMA. These results suggest that the activation in the hand region of M1 and AC may facilitate the spinal motoneurons, and the activation in the hand region in M1 by clenching may be due to a signal from CMA/SMA.

Stress-related activities induced by predator odor may become indistinguishable by hinokitiol odor.

Predator odors, such as 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), induce a stress-like behavior in some rodents, and there is activation of a complex mix of brain regions including the anterior piriform cortex (APC) and the bed nucleus of stria terminalis (BST). In contrast, rose odor can counteract TMT-induced activation of the ventrorostral part of APC and the medial part of BST. In the present study, two novel odors, woody (hinokitiol) and caraway [S(+)-carvone] odors, were evaluated to determine whether they have an antistress effect. Plasma adrenocorticotropic hormone levels, a marker of stress, and the number of c-Fos-immunopositive cells were determined in APC and BST. Plasma adrenocorticotropic hormone levels were increased by TMT alone and in combination with S(+)-carvone; however, hinokitiol with or without TMT did not have an effect. The number of activated cells in the medial part of BST was increased by TMT alone and in combination with S(+)-carvone or hinokitiol. Although TMT alone activated the medial part of BST, a mixture of TMT and hinokitiol activated both the medial and the lateral part of BST. These data suggest that the selective responses to TMT in the medial part of BST were obscured by activation of more odor-related regions by hinokitiol with TMT. In addition, the ratio of medial to lateral BST activation may be critical in stress-related behavior. In conclusion, hinokitiol can alleviate TMT-induced stress; however, the underlying mechanism appears to be different from that of the rose odor, as found in our previous study.

Perception of object motion in three-dimensional space induced by cast shadows.

Cast shadows can be salient depth cues in three-dimensional (3D) vision. Using a motion illusion in which a ball is perceived to roll in depth on the bottom or to flow in the front plane depending on the slope of the trajectory of its cast shadow, we investigated cortical mechanisms underlying 3D vision based on cast shadows using fMRI techniques. When modified versions of the original illusion, in which the slope of the shadow trajectory (shadow slope) was changed in 5 steps from the same one as the ball trajectory to the horizontal, were presented to participants, their perceived ball trajectory shifted gradually from rolling on the bottom to floating in the front plane as the change of the shadow slope. This observation suggests that the perception of the ball trajectory in this illusion is strongly affected by the motion of the cast shadow. In the fMRI study, cortical activity during observation of the movies of the illusion was investigated. We found that the bilateral posterior-occipital sulcus (POS) and right ventral precuneus showed activation related to the perception of the ball trajectory induced by the cast shadows in the illusion. Of these areas, it was suggested that the right POS may be involved in the inferring of the ball trajectory by the given spatial relation between the ball and the shadow. Our present results suggest that the posterior portion of the medial parietal cortex may be involved in 3D vision by cast shadows.

Cortical activation during color discrimination task in macaques as revealed by positron emission tomography.

Physiological and lesion studies have shown that the anterior inferior temporal (IT) cortex (aITC) is involved in the color vision of macaque monkeys. However, some functional imaging studies using awake monkeys contradicted the involvement of aITC in color vision. Thus, in most of the imaging studies, cortical activation has been observed during a fixation task. However, because the neuronal activity of aITC is highly affected by the behavioral task, it is desirable to investigate cortical activity during a color discrimination task to determine the functional role of aITC in the color vision of macaque monkeys. In this study, we investigated the cortical activity of aITC of macaque monkeys during color discrimination by positron emission tomography. Two monkeys were trained in a color discrimination task. Cortical areas involved in color processing were investigated by comparing activities during the color discrimination and lever release tasks. In addition to area V4 and the posterior IT cortex (pITC), we found color-related activities in the anterior IT gyrus. Consistent activation was observed in the region posterior to the anterior medial temporal sulcus (AMTS), although the exact location and the size of activations differed between monkeys and hemispheres. We also found color-related activities in the anterior portion of the superior temporal sulcus (STS), suggesting its involvement in the color vision. The present results revealed that aITC is involved in the color vision of macaque monkeys by a functional imaging technique.

Cortical areas related to performance of WAIS Digit Symbol Test: a functional imaging study.

Many neuropsychological studies have shown that the Digit Symbol Test (DST) of the Wechsler Adult Intelligence Scale (WAIS) is useful for screening for dysfunctions of the brain. However, it remains unclear which brain areas are actually involved in the performance of DST and what brain functions are used for executing this test. In this study, we examined the cortical areas related to cognitive aspects of DST using functional magnetic resonance imaging (fMRI) and determined executive brain functions involved in this test on the basis of fMRI results. Eleven healthy young adults (mean=21.6 years) performed a modified DST (mDST) task and its control task, which required a simple graphomotor response during fMRI data acquisition. The direct comparison of brain activations between the mDST task and the control task revealed greater activations in a fronto-parietal cortical network, including the bilateral inferior frontal sulci, left middle frontal gyrus (close to the frontal eye field) and left posterior parietal cortex. These activations are interpreted as reflecting the visual search process and/or the updating process of working memory during the mDST task execution. Furthermore, we found a positive correlation between the number of correct responses and activations in the bilateral inferior frontal regions, suggesting that these prefrontal areas have a crucial role in the performance of DST in a healthy young adult population.

Topical capsaicin application causes cold hypersensitivity in awake monkeys.

Recent animal studies have demonstrated that many trigeminal ganglion neurons co-express TRPV1 and TRPA1 receptors following peripheral inflammation. In the present study, we examined whether cold receptors were sensitized by capsaicin in awake monkeys. Two monkeys were trained to detect a change in cold stimulus temperature (30 degrees C to 0.5, 1.0, 1.5 or 2.0 degrees C) applied to the facial skin. A total of 589 trials were studied, and the number of escape and hold-through trials and detection latency were measured. The number of escape trials was increased after capsaicin treatment, whereas that of hold-through trials was decreased. Detection latency was significantly decreased after capsaicin treatment. The present findings suggest that topical application of capsaicin to the facial skin induces reversible hypersensitivity to a facial cold stimulus in behaving monkeys.

Information processing of geometrical features of a surface based on binocular disparity cues: an fMRI study.

Cortical areas related to the information processing of binocular disparity-defined geometrical features of a surface, such as depth, orientation and shape are examined by functional magnetic resonance imaging while subjects discriminated these three types of geometrical feature in random dot stereograms. Results indicate that disparity-defined information of depth and that of orientation are processed in the parietal area. Furthermore, the visual system for 3D vision in the parietal area may be organized in a hierarchical manner and the posterior part of the right intraparietal sulcus may be involved in cognitive process of 3D vision. On the other hand, disparity-defined shape information seems to be processed in the occipital visual areas and the crucial involvement of human LOS for this process is suggested.

Design of a head fixation device for experiments in behaving monkeys.

We have designed a new device for head fixation of behaving monkeys. The fixation device consists of a duralumin head ring mounted with four screw holders. It is firmly fixed to the animal's skull with four stainless steel screw pins. The head ring is then attached to a primate chair in any desirable position and angle using a set of adjustable plates. The device has been used for behavioral training that requires accurate gaze monitoring and for recording single-unit activity over a several-month period. The advantage of our device is that it is simple to use; it can be attached readily without major surgical procedures and it can be quickly removed when experiments are not running. This head fixation system is suitable for behavioral experiments and single-unit recording studies. It may also be applicable for studies on functional imaging of the macaque brain, by constructing it of non-magnetic materials.