Yumie Ono

Occlusion and brain function: mastication as a prevention of cognitive dysfunction

Research in animals and humans has shown that mastication maintains cognitive function in the hippocampus, a brain area important for learning and memory. Reduced mastication, an epidemiological risk factor for the development of dementia in humans, attenuates spatial memory and causes hippocampal neurons to deteriorate morphologically and functionally, especially in aged animals. Active mastication rescues the stress-attenuated hippocampal memory process in animals and attenuates the perception of stress in humans by suppressing endocrinological and autonomic stress responses. Active mastication further improves the performance of sustained cognitive tasks by increasing the activation of the hippocampus and the prefrontal cortex, the brain regions that are essential for cognitive processing. Abnormal mastication caused by experimental occlusal disharmony in animals produces chronic stress, which in turn suppresses spatial learning ability. The negative correlation between mastication and corticosteroids has raised the hypothesis that the suppression of the hypothalamic-pituitary-adrenal (HPA) axis by masticatory stimulation contributes, in part, to preserving cognitive functions associated with mastication. In the present review, we examine research pertaining to the mastication-induced amelioration of deficits in cognitive function, its possible relationship with the HPA axis, and the neuronal mechanisms that may be involved in this process in the hippocampus.

CHEWING AMELIORATES STRESS-INDUCED SUPPRESSION OF HIPPOCAMPAL LONG-TERM POTENTIATION

Research has established that severe stress adversely affects hippocampal memory, and chewing has been suggested to restore impaired cognitive functions in the hippocampus. To address how chewing involves stress-attenuated hippocampal memory process, we measured the long-term potentiation (LTP) of hippocampal slices of adult male rats that had experienced restraint stress, including some rats that were allowed to chew a wooden stick during the stress period and other rats that were not. The three experimental conditions were: 1) restraint stress without chewing (ST), 2) restraint stress with chewing (SC), and 3) no treatment (CT). We prepared hippocampal slices and collected trunk blood from all experimental animals. For rats in the two stressed groups, we collected tissue and blood at one of three post-stress time points: immediately after, 24 h after, or 48 h after exposure to the stressor. We found that the magnitude of LTP in both group ST and SC was significantly attenuated immediately after stress exposure. However, within 24 h after the end of the stress period, LTP had returned to the control level in group SC whereas it remained low in group ST. At the same post-stress time point, we found that facilitation of N-methyl-D-aspartate (NMDA) receptors by bath-applied glycine had less effect on the magnitude of LTP in group SC than on group ST, suggesting that most NMDA receptors had already become functionally restored in group SC by that time. Plasma concentration of adrenocorticotropic hormone was significantly elevated only in group ST immediately after exposure to the stressor, reflecting the involvement of chewing in decreasing subsequent corticosterone secretion. Thus, the present study demonstrates that chewing ameliorates the stress-induced impairment of NMDA receptor-mediated LTP, suggesting chewing as a good strategy to cope with severe stress by suppressing excessive endocrine responses.

Parietal and temporal activity during a multimodal dance video game: An fNIRS study

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.

Chewing-induced regional brain activity in edentulous patients who received mandibular implant-supported overdentures: A preliminary report

PURPOSE 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. METHODS Four edentulous patients (3 males and 1 female, aged 64 to 79 years) participated in the study. All subjects received a set of new maxillary and mandibular complete dentures (CD), followed by a maxillary complete denture and a new mandibular implant-supported removable overdentures (IOD). A 3-T fMRI scanner produced images of the regional brain activity for each subject that showed changes in the blood-oxygenation-level-dependent (BOLD) contrast in the axial orientation during gum-chewing with CD and IOD. RESULTS Region-of-interest analysis showed that IOD treatment significantly suppressed chewing-induced brain activity in the prefrontal cortex. The chewing-induced brain activities in the primary sensorimotor cortex and cerebellum tended to decrease with IOD treatment, however they did not reach to significance level. There was no change in brain activity in the supplementary motor area, thalamus and insula between gum chewing with CD and IOD. Group comparison using statistical parametrical mapping further showed that, within the prefrontal cortex, the neural activity of the frontal pole significantly decreased during gum-chewing with IOD when compared to that with CD (P<0.05). CONCLUSION Despite the limitation of a small sample size, these results suggest that the gum-chewing task in elderly edentulous patients resulted in differential neural activity in the frontal pole within the prefrontal cortex between the 2 prosthodontic therapies-mandibular CD and IOD.

Frontotemporal oxyhemoglobin dynamics predict performance accuracy of dance simulation gameplay: Temporal characteristics of top-down and bottom-up cortical activities

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.

fMRI Validation of fNIRS Measurements During a Naturalistic Task

We present a method to compare brain activity recorded with near-infrared spectroscopy (fNIRS) in a dance video game task to that recorded in a reduced version of the task using fMRI (functional magnetic resonance imaging). Recently, it has been shown that fNIRS can accurately record functional brain activities equivalent to those concurrently recorded with functional magnetic resonance imaging for classic psychophysical tasks and simple finger tapping paradigms. However, an often quoted benefit of fNIRS is that the technique allows for studying neural mechanisms of complex, naturalistic behaviors that are not possible using the constrained environment of fMRI. Our goal was to extend the findings of previous studies that have shown high correlation between concurrently recorded fNIRS and fMRI signals to compare neural recordings obtained in fMRI procedures to those separately obtained in naturalistic fNIRS experiments. Specifically, we developed a modified version of the dance video game Dance Dance Revolution (DDR) to be compatible with both fMRI and fNIRS imaging procedures. In this methodology we explain the modifications to the software and hardware for compatibility with each technique as well as the scanning and calibration procedures used to obtain representative results. The results of the study show a task-related increase in oxyhemoglobin in both modalities and demonstrate that it is possible to replicate the findings of fMRI using fNIRS in a naturalistic task. This technique represents a methodology to compare fMRI imaging paradigms which utilize a reduced-world environment to fNIRS in closer approximation to naturalistic, full-body activities and behaviors. Further development of this technique may apply to neurodegenerative diseases, such as Parkinson’s disease, late states of dementia, or those with magnetic susceptibility which are contraindicated for fMRI scanning.

Development of biomagnetic measurement system for mice with high spatial resolution

We have been developing a mice biomagnetic measurement system using a dc superconducting quantum interference device magnetometer for a comparative magnetoencephalogram study of transgenic and wild mice. In this study, we adopted a magnetometer with a pickup coil of 1.0mm diameter and 0.7mm lift-off distance to improve spatial resolution and magnetic field sensitivity. The magnetocardiogram of a wild mouse was measured as the initial application of the system. The bipolar peak positions in a magnetic field map separated by 5.6mm were clearly detected with the maximum amplitude of 88pT.

Chewing rescues stress-suppressed hippocampal long-term potentiation via activation of histamine H1 receptor

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.

Loss of molars early in life develops behavioral lateralization and impairs hippocampus-dependent recognition memory

BackgroundUsing 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.ResultsThe body weight of molarless mice was reduced significantly compared to that of molar-intact mice after the extraction and did not recover to the weight of age-matched molar-intact mice throughout the experimental period. At 12 weeks of age, molarless mice showed significantly greater locomotor activity in the OFT than molar-intact mice. However, the ability of molarless mice to discriminate a novel object in the ORT was impaired compared to that of molar-intact mice. The ability of both molarless and molar-intact SAMP8 mice to recognize objects was impaired at 24 weeks of age. These results suggest that molarless SAMP8 mice develop a deficit of cognitive function earlier than molar-intact SAMP8 mice. Interestingly, both at 12 and 24 weeks of age, molarless mice showed a lateralized preference of object location in the encoding session of the ORT, in which two identical objects were presented. Their lateralized preference of object location was positively correlated with the rightward turning-direction preference, which reached statistical significance at 24 weeks of age.ConclusionsLoss of masticatory function in early life causes malnutrition and chronic stress and impairs the ability to recognize novel objects. Hyperactivation and lateralized rotational behavior are commonly observed with dysfunction of the dopaminergic system, therefore, reduced masticatory function may deplete the mesolimbic and mesocorticolimbic dopaminergic systems to impair the cognitive functions of selective attention and recognition memory in the prefrontal cortex and the hippocampus.

Chewing reduces sympathetic nervous response to stress and prevents poststress arrhythmias in rats

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.