In JoVE (1)

Other Publications (14)

Articles by Yumie Ono in JoVE

 JoVE Behavior

fMRI Validation of fNIRS Measurements During a Naturalistic Task

1Department of Psychiatry, Yale School of Medicine, 2Department of Electronics and Bioinformatics, Meiji University, 3Department of Histology and Neurobiology, Dokkyo Medical University School of Medicine, 4ADAM Center, Department of Physical Therapy, Movement and Rehabilitation Sciences, Northeastern University, 5Department of Neurobiology, Yale School of Medicine

JoVE 52116

Other articles by Yumie Ono on PubMed

Chewing Rescues Stress-suppressed Hippocampal Long-term Potentiation Via Activation of Histamine H1 Receptor

Neuroscience Research. Aug, 2009  |  Pubmed ID: 19393269

We have previously found in rats that chewing, an active behavioral strategy to cope with a stressful situation, rescues long-term potentiation (LTP) in the hippocampus through activating stress-suppressed N-methyl-D-aspartate (NMDA) receptor function. To further examine the mechanisms underlying this ameliorative effect of chewing, we studied the involvement of the histaminergic system, which has been shown to be activated by mastication, in the LTP of hippocampal slices of rats that were allowed to chew a wooden stick during exposure to immobilization stress. Chewing failed to rescue stress-suppressed LTP in the rats treated with histamine H1 receptor (H1R) antagonist pyrilamine (5 mg/kg, i.p.) before exposure to stress, although administration of pyrilamine did not affect LTP in naive rats and in stressed rats that did not chew. However, when pyrilamine was administrated immediately after exposure to stress, chewing rescued LTP whose magnitude was statistically comparable to that in the rats that chewed without drug treatment. These results suggest that chewing-induced histamine release in the hippocampus and the subsequent H1 receptor activation may be essential to rescue stress-suppressed synaptic plasticity.

Chewing Under Restraint Stress Inhibits the Stress-induced Suppression of Cell Birth in the Dentate Gyrus of Aged SAMP8 Mice

Neuroscience Letters. Dec, 2009  |  Pubmed ID: 19686806

To investigate the mechanisms underlying impaired hippocampal function resulting from masticatory dysfunction, we examined the effects of the molarless condition on cell proliferation and the effect of the administration of metyrapone, which suppresses the stress-induced rise in plasma corticosterone levels, on cell proliferation in the hippocampal dentate gyrus (DG) of aged senescence-accelerated prone (SAMP8) mice. In addition, we examined whether chewing under restraint stress prevents the stress-induced suppression of cell proliferation. In aged mice, the molarless condition suppressed cell proliferation in the hippocampal DG. Vehicle-injected molarless mice had significantly higher plasma corticosterone levels than vehicle-injected control and metyrapone-injected molarless mice, in association with decreased cell proliferation in the hippocampal DG. Pretreatment with metyrapone inhibited the increase in plasma corticosterone levels induced by the bite-raised condition, and also attenuated the reduction in cell proliferation. Immobilization stress suppressed cell proliferation in the hippocampal DG, but chewing under restraint stress blocked the stress-induced suppression of cell proliferation in the DG. These results suggest that the morphologic deficits induced by the molarless condition in aged SAMP8 mice are a result of increased plasma corticosterone levels, and that chewing under restraint stress prevents the stress-induced suppression of cell birth in the DG.

Chewing-induced Regional Brain Activity in Edentulous Patients Who Received Mandibular Implant-supported Overdentures: a Preliminary Report

Journal of Prosthodontic Research. Apr, 2011  |  Pubmed ID: 20951664

We used functional magnetic resonance imaging (fMRI) to investigate the change in brain regional activity during gum chewing when edentulous subjects switched from mandibular complete dentures to implant-supported removable overdentures.

Chewing Reduces Sympathetic Nervous Response to Stress and Prevents Poststress Arrhythmias in Rats

American Journal of Physiology. Heart and Circulatory Physiology. Oct, 2011  |  Pubmed ID: 21821783

Reducing stress is important in preventing sudden death in patients with cardiovascular disease, as stressful events may cause autonomic imbalance and trigger fatal arrhythmias. Since chewing has been shown to inhibit stress-induced neuronal responses in the hypothalamus, we hypothesized that chewing could ameliorate stress-induced autonomic imbalance and prevent arrhythmias. To test this hypothesis, we analyzed changes in radiotelemetered electrocardiograms in rats that were allowed to chew a wooden stick during a 1-h period of immobilization stress. Chewing significantly reduced the occurrence of ventricular premature beats (VPBs) and complex ventricular ectopy after immobilization and prevented stress-induced prolongation of the QT interval of VPBs throughout the 10-h experimental period. It also prevented prolongation of the QRS complex and fluctuations in the QT interval in normal sinus rhythm beats preceding VPBs during both immobilization and in the poststress period. Fast Fourier transform-based spectral analysis of heart-rate variability further showed that chewing significantly inhibited the stress-induced increase in the power ratio of low-to-high frequency activity (LF/HF: a marker of sympathetic activity) during immobilization and in addition was associated with blunting of the stress-induced increase in plasma noradrenaline observed at the termination of immobilization. Similar suppressive effects on the occurrence of VPBs and the LF/HF were observed in rats that were administered the β-adrenergic blocker propranolol before immobilization. These results indicate that chewing can ameliorate sympathetic hyperactivity during stress and prevent poststress arrhythmias and suggest that chewing may provide a nonpharmacological and cost-effective treatment option for patients with a high risk of stress-induced fatal arrhythmia.

Parietal and Temporal Activity During a Multimodal Dance Video Game: an FNIRS Study

Neuroscience Letters. Oct, 2011  |  Pubmed ID: 21875646

Using functional near infrared spectroscopy (fNIRS) we studied how playing a dance video game employs coordinated activation of sensory-motor integration centers of the superior parietal lobe (SPL) and superior temporal gyrus (STG). Subjects played a dance video game, in a block design with 30s of activity alternating with 30s of rest, while changes in oxy-hemoglobin (oxy-Hb) levels were continuously measured. The game was modified to compare difficult (4-arrow), simple (2-arrow), and stepping conditions. Oxy-Hb levels were greatest with increased task difficulty. The quick-onset, trapezoidal time-course increase in SPL oxy-Hb levels reflected the on-off neuronal response of spatial orienting and rhythmic motor timing that were required during the activity. Slow-onset, bell-shaped increases in oxy-Hb levels observed in STG suggested the gradually increasing load of directing multisensory information to downstream processing centers associated with motor behavior and control. Differences in temporal relationships of SPL and STG oxy-Hb concentration levels may reflect the functional roles of these brain structures during the task period. NIRS permits insights into temporal relationships of cortical hemodynamics during real motor tasks.

Active Coping with Stress Suppresses Glucose Metabolism in the Rat Hypothalamus

Stress (Amsterdam, Netherlands). Mar, 2012  |  Pubmed ID: 21936685

We used 18F-fluorodeoxyglucose small-animal positron-emission tomography to determine whether different styles of coping with stress are associated with different patterns of neuronal activity in the hypothalamus. Adult rats were subjected to immobilization (IMO)-stress or to a non-immobilized condition for 30 min, in random order on separate days, each of which was followed by brain-scanning. Some rats in the immobilized condition were allowed to actively cope with the stress by chewing a wooden stick during IMO, while the other immobilized rats were given nothing to chew on. Voxel-based statistical analysis of the brain imaging data shows that chewing counteracted the stress-induced increased glucose uptake in the hypothalamus to the level of the non-immobilized condition. Region-of-interest analysis of the glucose uptake values further showed that chewing significantly suppressed stress-induced increased glucose uptake in the paraventricular hypothalamic nucleus and the anterior hypothalamic area but not in the lateral hypothalamus. Together with the finding that the mean plasma corticosterone concentration at the termination of the IMO was also significantly suppressed when rats had an opportunity to chew a wooden stick, our results showed that active coping by chewing inhibited the activation of the hypothalamic-pituitary-adrenal axis to reduce the endocrine stress response.

Soft-food Diet Induces Oxidative Stress in the Rat Brain

Neuroscience Letters. Feb, 2012  |  Pubmed ID: 22206840

Decreased dopamine (DA) release in the hippocampus may be caused by dysfunctional mastication, although the mechanisms involved remain unclear. The present study examined the effects of soft- and hard-food diets on oxidative stress in the brain, and the relationship between these effects and hippocampal DA levels. The present study showed that DA release in the hippocampus was decreased in rats fed a soft-food diet. Electron spin resonance studies using the nitroxyl spin probe 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl directly demonstrated a high level of oxidative stress in the rat brain due to soft-food diet feeding. In addition, we confirmed that DA directly react with reactive oxygen species such as hydroxyl radical and superoxide. These observations suggest that soft-food diet feeding enhances oxidative stress, which leads to oxidation and a decrease in the release of DA in the hippocampus of rats.

Activation of Dorsolateral Prefrontal Cortex in a Dual Neuropsychological Screening Test: an FMRI Approach

Behavioral and Brain Functions : BBF. 2012  |  Pubmed ID: 22640773

The Kana Pick-out Test (KPT), which uses Kana or Japanese symbols that represent syllables, requires parallel processing of discrete (pick-out) and continuous (reading) dual tasks. As a dual task, the KPT is thought to test working memory and executive function, particularly in the prefrontal cortex (PFC), and is widely used in Japan as a clinical screen for dementia. Nevertheless, there has been little neurological investigation into PFC activity during this test.

Effect of Bite-raised Condition on the Hippocampal Cholinergic System of Aged SAMP8 Mice

Neuroscience Letters. Jun, 2012  |  Pubmed ID: 22640898

Occlusal disharmony induces chronic stress, which results in learning deficits in association with the morphologic changes in the hippocampus, e.g., neuronal degeneration and increased hypertrophied glial fibrillary acidic protein-positive cells. To investigate the mechanisms underlying impaired hippocampal function resulting from occlusal disharmony, we examined the effects of the bite-raised condition on the septohippocampal cholinergic system by assessing acetylcholine release in the hippocampus and choline acetyltransferase immunoreactivity in the medial septal nucleus in aged SAMP8 mice that underwent the bite raising procedure. Aged bite-raised mice showed decreased acetylcholine release in the hippocampus and a reduced number of choline acetyltransferase-immunopositive neurons in the medial septal nucleus compared to age-matched control mice. These findings suggest that the bite-raised condition in aged SAMP8 mice enhances the age-related decline in the septohippocampal cholinergic system, leading to impaired learning.

WITHDRAWN: Chewing During Chronic Stress Ameliorates Stress-induced Suppression of Neurogenesis in the Hippocampal Dentate Gyrus in Aged SAMP8 Mice

Neuroscience Letters. Jun, 2012  |  Pubmed ID: 22750151

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at

Pursuing the Flow of Information: Connectivity Between Bilateral Premotor Cortices Predicts Better Accuracy in the Phonological Working Memory Task

Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference. 2013  |  Pubmed ID: 24111456

Using Magnetoencephalography (MEG) we studied functional connectivity of cortical areas during phonological working memory task. Six subjects participated in the experiment and their neuronal activity was measured by a 306-channel MEG system. We used a modified version of the visual Sternberg paradigm, which required subjects to memorize 8 alphabet letters in 2s for a late recall period. We estimated functional connectivity of oscillatory regional brain activities during the encoding session for each trial of each subject using beamformer source reconstruction and Granger causality analysis. Regional brain activities were mostly found in the bilateral premotor cortex (Brodmann area (BA) 6: PMC), the right dorsolateral prefrontal cortex (BA 9: DLPFC), and the right frontal eye field (BA 8). Considering that the left and right PMCs participate in the functions of phonological loop (PL) and the visuospatial sketchpad (VS) in the Baddeley's model of working memory, respectively, our result suggests that subjects utilized either single function or both functions of working memory circuitry to execute the task. Interestingly, the accuracy of the task was significantly higher in the trials where the alpha band oscillatory activities in the bilateral PMCs established functional connectivity compared to those where the PMC was not working in conjunction with its counterpart. Similar relationship was found in the theta band oscillatory activities between the right PMC and the right DLPFC, however in this case the establishment of functional connectivity significantly decreased the accuracy of the task. These results suggest that sharing the memory load with both PL- and VS- type memory storage circuitries contributed to better performance in the highly-demanding cognitive task.

Frontotemporal Oxyhemoglobin Dynamics Predict Performance Accuracy of Dance Simulation Gameplay: Temporal Characteristics of Top-down and Bottom-up Cortical Activities

NeuroImage. Jan, 2014  |  Pubmed ID: 23707582

We utilized the high temporal resolution of functional near-infrared spectroscopy to explore how sensory input (visual and rhythmic auditory cues) are processed in the cortical areas of multimodal integration to achieve coordinated motor output during unrestricted dance simulation gameplay. Using an open source clone of the dance simulation video game, Dance Dance Revolution, two cortical regions of interest were selected for study, the middle temporal gyrus (MTG) and the frontopolar cortex (FPC). We hypothesized that activity in the FPC would indicate top-down regulatory mechanisms of motor behavior; while that in the MTG would be sustained due to bottom-up integration of visual and auditory cues throughout the task. We also hypothesized that a correlation would exist between behavioral performance and the temporal patterns of the hemodynamic responses in these regions of interest. Results indicated that greater temporal accuracy of dance steps positively correlated with persistent activation of the MTG and with cumulative suppression of the FPC. When auditory cues were eliminated from the simulation, modifications in cortical responses were found depending on the gameplay performance. In the MTG, high-performance players showed an increase but low-performance players displayed a decrease in cumulative amount of the oxygenated hemoglobin response in the no music condition compared to that in the music condition. In the FPC, high-performance players showed relatively small variance in the activity regardless of the presence of auditory cues, while low-performance players showed larger differences in the activity between the no music and music conditions. These results suggest that the MTG plays an important role in the successful integration of visual and rhythmic cues and the FPC may work as top-down control to compensate for insufficient integrative ability of visual and rhythmic cues in the MTG. The relative relationships between these cortical areas indicated high- to low-performance levels when performing cued motor tasks. We propose that changes in these relationships can be monitored to gauge performance increases in motor learning and rehabilitation programs.

Loss of Molars Early in Life Develops Behavioral Lateralization and Impairs Hippocampus-dependent Recognition Memory

BMC Neuroscience. 2014  |  Pubmed ID: 24387332

Using senescence-accelerated mouse prone 8 (SAMP8), we examined whether reduced mastication from a young age affects hippocampal-dependent cognitive function. We anesthetized male SAMP8 mice at 8 weeks of age and extracted all maxillary molar teeth of half the animals. The other animals were treated similarly, except that molar teeth were not extracted. At 12 and 24 weeks of age, their general behavior and their ability to recognize novel objects were tested using the open-field test (OFT) and the object-recognition test (ORT), respectively.

Chewing Suppresses the Stress-induced Increase in the Number of PERK-immunoreactive Cells in the Periaqueductal Grey

Neuroscience Letters. May, 2015  |  Pubmed ID: 25980997

We investigated the effects of chewing under immobilization stress on the periaqueductal gray (PAG) matter using phosphorylated extracellular signal-regulated kinase (pERK) as a marker of responding cells. Immobilization stress increased pERK-immunoreactive cells in the PAG. Among four subdivisions of the PAG, the increase of immunoreactive cells was remarkable in the dorsolateral and ventrolateral subdivisions. However, increase of pERK-immunoreactive cells by the immobilization stress was not so evident in the dorsomedial and lateral subdivisions. The chewing under immobilization stress prevented the stress-induced increase of pERK-immunoreactive cells in the dorsolateral and ventrolateral subdivisions with statistical significances (p<0.05). Again, chewing effects on pERK-immunoreactive cells were not visible in the dorsomedial and lateral subdivisions. These results suggest that the chewing alleviates the PAG (dorsolateral and ventrolateral subdivisions) responses to stress.

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