Cortico-muscular synchronization by proprioceptive afferents from the tongue muscles during isometric tongue protrusion.

Tongue movements contribute to oral functions including swallowing, vocalizing, and breathing. Fine tongue movements are regulated through efferent and afferent connections between the cortex and tongue. It has been demonstrated that cortico-muscular coherence (CMC) is reflected at two frequency bands during isometric tongue protrusions: the beta (ß) band at 15-35Hz and the low-frequency band at 2-10Hz. The CMC at the ß band (ß-CMC) reflects motor commands from the primary motor cortex (M1) to the tongue muscles through hypoglossal motoneuron pools. However, the generator mechanism of the CMC at the low-frequency band (low-CMC) remains unknown. Here, we evaluated the mechanism of low-CMC during isometric tongue protrusion using magnetoencephalography (MEG). Somatosensory evoked fields (SEFs) were also recorded following electrical tongue stimulation. Significant low-CMC and ß-CMC were observed over both hemispheres for each side of the tongue. Time-domain analysis showed that the MEG signal followed the electromyography signal for low-CMC, which was contrary to the finding that the MEG signal preceded the electromyography signal for ß-CMC. The mean conduction time from the tongue to the cortex was not significantly different between the low-CMC (mean, 80.9ms) and SEFs (mean, 71.1ms). The cortical sources of low-CMC were located significantly posterior (mean, 10.1mm) to the sources of ß-CMC in M1, but were in the same area as tongue SEFs in the primary somatosensory cortex (S1). These results reveal that the low-CMC may be driven by proprioceptive afferents from the tongue muscles to S1, and that the oscillatory interaction was derived from each side of the tongue to both hemispheres. Oscillatory proprioceptive feedback from the tongue muscles may aid in the coordination of sophisticated tongue movements in humans.

Recovery of Impaired Somatosensory Evoked Fields After Improvement of Tongue Sensory Deficits With Neurosurgical Reconstruction.

Somatosensory evoked fields (SEFs) induced by tongue stimulation can be useful as an objective parameter to assess sensory disturbances in the tongue. However, whether tongue SEFs can be useful as a clinical, objective follow-up assessment method of tongue sensation after oral surgery is unknown. We describe 2 cases in which tongue SEFs were successfully used in clinical assessment. Two patients with unilateral tongue sensory deficits caused by lingual nerve injury during lower third molar extraction were recruited. Both patients underwent surgery to repair the damaged nerve, and all tongue sensory evaluations were performed once before and once after surgery. SEFs were recorded by stimulating the affected and unaffected sides of the tongue separately, and cortical activity was evaluated over the contralateral hemisphere. The unilaterality of the deficit also was assessed. In both patients, stimulation of the unaffected side evoked reproducible cortical responses before and after surgery. Both patients also recovered some sensation after surgery, given that presurgery stimulation of the affected side failed to evoke cortical activity whereas postsurgery stimulation evoked cortical activity on both sides. Sensation was initially highly lateralized in both patients but was restored to approximately normal in the postsurgery evaluation. Finally, both patients rated their subjective tongue sensations on the affected side over 50% better after the surgical intervention. These cases indicate that tongue SEFs may have a clinical use as an objective parameter for assessing the course of tongue sensory recovery.

Contralateral dominance of corticomuscular coherence for both sides of the tongue during human tongue protrusion: an MEG study.

Sophisticated tongue movements contribute to speech and mastication. These movements are regulated by communication between the bilateral cortex and each tongue side. The functional connection between the cortex and tongue was investigated using oscillatory interactions between whole-head magnetoencephalographic (MEG) signals and electromyographic (EMG) signals from both tongue sides during human tongue protrusion compared to thumb data. MEG-EMG coherence was observed at 14-36 Hz and 2-10 Hz over both hemispheres for each tongue side. EMG-EMG coherence between tongue sides was also detected at the same frequency bands. Thumb coherence was detected at 15-33 Hz over the contralateral hemisphere. Tongue coherence at 14-36 Hz was larger over the contralateral vs. ipsilateral hemisphere for both tongue sides. Tongue cortical sources were located in the lower part of the central sulcus and were anterior and inferior to the thumb areas, agreeing with the classical homunculus. Cross-correlogram analysis showed the MEG signal preceded the EMG signal. The cortex-tongue time lag was shorter than the cortex-thumb time lag. The cortex-muscle time lag decreased systematically with distance. These results suggest that during tongue protrusions, descending motor commands are modulated by bilateral cortical oscillations, and each tongue side is dominated by the contralateral hemisphere.

Neurophysiological Basis of Deep Brain Stimulation and Botulinum Neurotoxin Injection for Treating Oromandibular Dystonia.

Oromandibular dystonia (OMD) induces severe motor impairments, such as masticatory disturbances, dysphagia, and dysarthria, resulting in a serious decline in quality of life. Non-invasive brain-imaging techniques such as electroencephalography (EEG) and magnetoencephalography (MEG) are powerful approaches that can elucidate human cortical activity with high temporal resolution. Previous studies with EEG and MEG have revealed that movements in the stomatognathic system are regulated by the bilateral central cortex. Recently, in addition to the standard therapy of botulinum neurotoxin (BoNT) injection into the affected muscles, bilateral deep brain stimulation (DBS) has been applied for the treatment of OMD. However, some patients' OMD symptoms do not improve sufficiently after DBS, and they require additional BoNT therapy. In this review, we provide an overview of the unique central spatiotemporal processing mechanisms in these regions in the bilateral cortex using EEG and MEG, as they relate to the sensorimotor functions of the stomatognathic system. Increased knowledge regarding the neurophysiological underpinnings of the stomatognathic system will improve our understanding of OMD and other movement disorders, as well as aid the development of potential novel approaches such as combination treatment with BoNT injection and DBS or non-invasive cortical current stimulation therapies.

Singing Experience Influences RSST Scores.

It has recently been shown that the aging population is refractory to the maintenance of swallowing function, which can seriously affect quality of life. Singing and vocal training contribute to mastication, swallowing and respiratory function. Previous studies have shown that singers have better vocal cord health. No consensus has been reached as to how vocal training affects swallowing ability. Our study was designed to establish evidence that singers are statistically superior at inducing the swallowing reflex. To test our hypothesis, we undertook a clinical trial on 55 singers and 141 non-singers (mean age: 60.1 ± 11.7 years). This cross-sectional study with propensity score matching resulted in significant differences in a repetitive saliva swallowing test among singers: 7.1 ± 2.4, n = 53 vs. non-singers: 5.9 ± 1.9, n = 53, p < 0.05. We conclude that singing can serve an important role in stabilizing the impact of voluntary swallowing on speech.

Functional cortical localization of tongue movements using corticokinematic coherence with a deep learning-assisted motion capture system.

Corticokinematic coherence (CKC) between magnetoencephalographic and movement signals using an accelerometer is useful for the functional localization of the primary sensorimotor cortex (SM1). However, it is difficult to determine the tongue CKC because an accelerometer yields excessive magnetic artifacts. Here, we introduce a novel approach for measuring the tongue CKC using a deep learning-assisted motion capture system with videography, and compare it with an accelerometer in a control task measuring finger movement. Twelve healthy volunteers performed rhythmical side-to-side tongue movements in the whole-head magnetoencephalographic system, which were simultaneously recorded using a video camera and examined using a deep learning-assisted motion capture system. In the control task, right finger CKC measurements were simultaneously evaluated via motion capture and an accelerometer. The right finger CKC with motion capture was significant at the movement frequency peaks or its harmonics over the contralateral hemisphere; the motion-captured CKC was 84.9% similar to that with the accelerometer. The tongue CKC was significant at the movement frequency peaks or its harmonics over both hemispheres. The CKC sources of the tongue were considerably lateral and inferior to those of the finger. Thus, the CKC with deep learning-assisted motion capture can evaluate the functional localization of the tongue SM1.

A Swallowing Decoder Based on Deep Transfer Learning: AlexNet Classification of the Intracranial Electrocorticogram.

To realize a brain-machine interface to assist swallowing, neural signal decoding is indispensable. Eight participants with temporal-lobe intracranial electrode implants for epilepsy were asked to swallow during electrocorticogram (ECoG) recording. Raw ECoG signals or certain frequency bands of the ECoG power were converted into images whose vertical axis was electrode number and whose horizontal axis was time in milliseconds, which were used as training data. These data were classified with four labels (Rest, Mouth open, Water injection, and Swallowing). Deep transfer learning was carried out using AlexNet, and power in the high-[Formula: see text] band (75-150[Formula: see text]Hz) was the training set. Accuracy reached 74.01%, sensitivity reached 82.51%, and specificity reached 95.38%. However, using the raw ECoG signals, the accuracy obtained was 76.95%, comparable to that of the high-[Formula: see text] power. We demonstrated that a version of AlexNet pre-trained with visually meaningful images can be used for transfer learning of visually meaningless images made up of ECoG signals. Moreover, we could achieve high decoding accuracy using the raw ECoG signals, allowing us to dispense with the conventional extraction of high-[Formula: see text] power. Thus, the images derived from the raw ECoG signals were equivalent to those derived from the high-[Formula: see text] band for transfer deep learning.

Motor and sensory cortical processing of neural oscillatory activities revealed by human swallowing using intracranial electrodes.

Swallowing is attributed to the orchestration of motor output and sensory input. We hypothesized that swallowing can illustrate differences between motor and sensory neural processing. Eight epileptic participants fitted with intracranial electrodes over the orofacial cortex were asked to swallow a water bolus. Mouth opening and swallowing were treated as motor tasks, whereas water injection was treated as a sensory task. Phase-amplitude coupling between lower-frequency and high γ (HG) bands (75-150 Hz) was investigated. An α (10-16 Hz)-HG coupling appeared before motor-related HG power increases (burst), and a θ (5-9 Hz)-HG coupling appeared during sensory-related HG bursts. The peaks of motor-related coupling were 0.6-0.7 s earlier than that of HG power. The motor-related HG was modulated at the trough of the α oscillation, and the sensory-related HG amplitude was modulated at the peak of the θ oscillation. These contrasting results can help to elucidate the brain's sensory motor functions.

Swallowing-related neural oscillation: an intracranial EEG study.

OBJECTIVE: Swallowing is a unique movement due to the indispensable orchestration of voluntary and involuntary movements. The transition from voluntary to involuntary swallowing is executed within milliseconds. We hypothesized that the underlying neural mechanism of swallowing would be revealed by high-frequency cortical activities. METHODS: Eight epileptic participants fitted with intracranial electrodes over the orofacial cortex were asked to swallow a water bolus and cortical oscillatory changes, including the high γ band (75-150 Hz) and ß band (13-30 Hz), were investigated at the time of mouth opening, water injection, and swallowing. RESULTS: Increases in high γ power associated with mouth opening were observed in the ventrolateral prefrontal cortex (VLPFC) with water injection in the lateral central sulcus and with swallowing in the region along the Sylvian fissure. Mouth opening induced a decrease in ß power, which continued until the completion of swallowing. The high γ burst of activity was focal and specific to swallowing; however, the ß activities were extensive and not specific to swallowing. In the interim between voluntary and involuntary swallowing, swallowing-related high γ power achieved its peak, and subsequently, the power decreased. INTERPRETATION: We demonstrated three distinct activities related to mouth opening, water injection, and swallowing induced at different timings using high γ activities. The peak of high γ power related to swallowing suggests that during voluntary swallowing phases, the cortex is the main driving force for swallowing as opposed to the brain stem.

Entrainment of chewing rhythm by gait speed during treadmill walking in humans.

It remains unclear whether the rhythmic processes of chewing and gait synchronize during concurrent execution in humans. To evaluate the entrainment of chewing rhythm by gait speed, we measured electromyography from the masseter and tibialis anterior muscles during chewing at a habitual rhythm while walking on a linear treadmill in 12 healthy volunteers. Vertical movement of the head was also measured using an accelerometer. Each 5-min session included gait tasks using a treadmill at three speeds: Auto: the participant's self-selected gait speed, High: Auto × 1.3, and Low: Auto ÷ 1.3. Electromyography from the masseter muscles were also measured during chewing while stationary (Chew-Only). Chewing rhythm during walking was the same as that for head movement, occurring at twice the speed of the walking rhythm, in nine participants (Low), eight participants (Auto), and eight participants (High). For these participants, chewing rhythm in the Auto and High conditions differed significantly from that in the Chew-Only condition. Significant differences in chewing rhythm were also observed among gait speeds　(Low vs. Auto vs. High). Our findings demonstrate that entrainment of habitual chewing rhythm to gait speed is a significant phenomenon, and that the dominant ratio of chewing-walking-head movement rhythms is 2:1:2.

Somatosensory evoked magnetic fields following electric tongue stimulation using pin electrodes.

Quantitative evaluation of the sensory disturbance of the tongue is important clinically. However, because the conventional electrophysiological approach to the peripheral nerve cannot be used in the mandible owing to the deep route of the lingual nerve, we applied evoked potentials in the central nervous system. Somatosensory evoked magnetic fields (SEFs) following electric stimulation were recorded in 10 healthy subjects by means of pin electrodes placed on the tongue mucosa. Three or four components (P25m, P40m, P60m, and P80m) were identified over the contralateral hemisphere with unilateral stimulation. Because none of the components were consistently detected in all subjects, we evaluated the root mean square (RMS) of 18 channels over the contralateral hemisphere. To estimate the activated cortical response, we calculated the difference in mean RMS amplitude between 10 and 150 ms and that of the baseline period (aRMS=RMS[10, 150]-RMS[-50, -5]). The aRMS values for right-sided and left-sided stimulation were 10.18+/-7.92 and 10.99+/-8.98 fT/cm, respectively, and the mean laterality index, expressed by [(left-right)/(left+right)] was 0.025+/-0.104. This parameter can be useful for evaluating patients with unilateral sensory abnormality of the tongue.

Neurofeedback Control of the Human GABAergic System Using Non-invasive Brain Stimulation.

Neurofeedback has been a powerful method for self-regulating brain activities to elicit potential ability of human mind. GABA is a major inhibitory neurotransmitter in the central nervous system. Transcranial magnetic stimulation (TMS) is a tool that can evaluate the GABAergic system within the primary motor cortex (M1) using paired-pulse stimuli, short intracortical inhibition (SICI). Herein we investigated whether neurofeedback learning using SICI enabled us to control the GABAergic system within the M1 area. Forty-five healthy subjects were randomly divided into two groups: those receiving SICI neurofeedback learning or those receiving no neurofeedback (control) learning. During both learning periods, subjects made attempts to change the size of a circle, which was altered according to the degree of SICI in the SICI neurofeedback learning group, and which was altered independent of the degree of SICI in the control learning group. Results demonstrated that the SICI neurofeedback learning group showed a significant enhancement in SICI. Moreover, this group showed a significant reduction in choice reaction time compared to the control group. Our findings indicate that humans can intrinsically control the intracortical GABAergic system within M1 and can thus improve motor behaviors by SICI neurofeedback learning. SICI neurofeedback learning is a novel and promising approach to control our neural system and potentially represents a new therapy for patients with abnormal motor symptoms caused by CNS disorders.

Anodal transcranial patterned stimulation of the motor cortex during gait can induce activity-dependent corticospinal plasticity to alter human gait.

The corticospinal system and local spinal circuits control human bipedal locomotion. The primary motor cortex is phase-dependently activated during gait; this cortical input is critical for foot flexor activity during the swing phase. We investigated whether gait-combined rhythmic brain stimulation can induce neuroplasticity in the foot area of the motor cortex and alter gait parameters. Twenty-one healthy subjects participated in the single-blinded, cross-over study. Each subject received anodal transcranial patterned direct current stimulation over the foot area of the right motor cortex during gait, sham stimulation during gait, and anodal transcranial patterned direct current stimulation during rest in a random order. Six subjects were excluded due to a failure in the experimental recording procedure. Complete-case analysis was performed using the data from the remaining 15 subjects. Self-paced gait speed and left leg stride length were significantly increased after the stimulation during gait, but not after the sham stimulation during gait or the stimulation during rest. In addition, a significant increase was found in the excitability of the corticospinal pathway of the left tibialis anterior muscle 30 min after stimulation during gait. Anodal transcranial patterned direct current stimulation during gait entrained the gait cycle to enhance motor cortical activity in some subjects. These findings suggest that the stimulation during gait induced neuroplasticity in corticospinal pathways driving flexor muscles during gait.

Cortical Mechanisms of Tongue Sensorimotor Functions in Humans: A Review of the Magnetoencephalography Approach.

The tongue plays important roles in a variety of critical human oral functions, including speech production, swallowing, mastication and respiration. These sophisticated tongue movements are in part finely regulated by cortical entrainment. Many studies have examined sensorimotor processing in the limbs using magnetoencephalography (MEG), which has high spatiotemporal resolution. Such studies have employed multiple methods of analysis, including somatosensory evoked fields (SEFs), movement-related cortical fields (MRCFs), event-related desynchronization/synchronization (ERD/ERS) associated with somatosensory stimulation or movement and cortico-muscular coherence (CMC) during sustained movement. However, the cortical mechanisms underlying the sensorimotor functions of the tongue remain unclear, as contamination artifacts induced by stimulation and/or muscle activity within the orofacial region complicates MEG analysis in the oral region. Recently, several studies have obtained MEG recordings from the tongue region using improved stimulation methods and movement tasks. In the present review, we provide a detailed overview of tongue sensorimotor processing in humans, based on the findings of recent MEG studies. In addition, we review the clinical applications of MEG for sensory disturbances of the tongue caused by damage to the lingual nerve. Increased knowledge of the physiological and pathophysiological mechanisms underlying tongue sensorimotor processing may improve our understanding of the cortical entrainment of human oral functions.

Movement-related cortical magnetic fields associated with self-paced tongue protrusion in humans.

Sophisticated tongue movements are coordinated finely via cortical control. We elucidated the cortical processes associated with voluntary tongue movement. Movement-related cortical fields were investigated during self-paced repetitive tongue protrusion. Surface tongue electromyograms were recorded to determine movement onset. To identify the location of the primary somatosensory cortex (S1), tongue somatosensory evoked fields were measured. The readiness fields (RFs) over both hemispheres began prior to movement onset and culminated in the motor fields (MFs) around movement onset. These signals were followed by transient movement evoked fields (MEFs) after movement onset. The MF and MEF peak latencies and magnitudes were not different between the hemispheres. The MF current sources were located in the precentral gyrus, suggesting they were located in the primary motor cortex (M1); this was contrary to the MEF sources, which were located in S1. We conclude that the RFs and MFs mainly reflect the cortical processes for the preparation and execution of tongue movement in the bilateral M1, without hemispheric dominance. Moreover, the MEFs may represent proprioceptive feedback from the tongue to bilateral S1. Such cortical processing related to the efferent and afferent information may aid in the coordination of sophisticated tongue movements.

Effects of intraperitoneally administered L-histidine on food intake, taste, and visceral sensation in rats.

To evaluate relative factors for anorectic effects of L-histidine, we performed behavioral experiments for measuring food and fluid intake, conditioned taste aversion (CTA), taste disturbance, and c-Fos immunoreactive (Fos-ir) cells before and after i.p. injection with L-histidine in rats. Animals were injected with saline (9 ml/kg, i.p.) for a control group, and saline (9 ml/kg, i.p.) containing L-histidine (0.75, 1.5, 2.0 g/kg) for a L-histidine group. Injection of L-histidine decreased the average value of food intake, and statistically significant anorectic effects were found in animals injected with 1.5 or 2.0 g/kg L-histidine but not with 0.75 g/kg L-histidine. Taste abnormalities were not detected in any of the groups. Animals injected with 2.0 g/kg L-histidine were revealed to present with nausea by the measurement of CTA. In this group, a significant increase in the number of Fos-ir cells was detected both in the area postrema and the nucleus tractus solitarius (NTS). In the 0.75 g/kg L-histidine group, a significant increase in the number of Fos-ir cells was detected only in the NTS. When the ventral gastric branch vagotomy was performed, recovery from anorexia became faster than the sham-operated group, however, vagotomized rats injected with 2.0 g/kg L-histidine still acquired CTA. These data indicate that acute anorectic effects induced by highly concentrated L-histidine are partly caused by induction of nausea and/or visceral discomfort accompanied by neuronal activities in the NTS and the area postrema. We suggest that acute and potent effects of L-histidine on food intake require substantial amount of L-histidine in the diet.

Somatosensory evoked magnetic fields to air-puff stimulation on the soft palate.

Impairment of sensory input to the soft palate has been reported in patients with obstructive sleep apnea syndrome. To investigate the reaction in the central nervous system related to soft palate perception, we measured the somatosensory evoked magnetic fields following air-puff stimulation in seven healthy volunteers by using a helmet-shaped 122-channel neuromagnetometer. The air-puffs were produced using compressed nitrogen and directed to the middle of the soft palate with an intraoral device. To evaluate the laterality of responses we used another appliance in which the air-puffs were directed to the middle and right side of the soft palate. In all the subjects, responses were identified symmetrically in the bilateral parietotemporal regions with a mean latency of about 130 ms from the soft palate stimulation. Prior to this peak, no distinct early responses were observed. There was no significant difference in the responses between the middle and right side stimulation. Corresponding equivalent current dipoles were estimated around the Sylvian fissures. These results suggested that the responses were derived from the second somatosensory areas. In conclusion, we could record long-latency responses to air-puff stimulation of the soft palate in the bilateral second somatosensory areas.

Modulation of stimulus-induced 20-Hz activity for the tongue and hard palate during tongue movement in humans.

OBJECTIVE: Modulation of 20-Hz activity in the primary sensorimotor cortex (SM1) may be important for oral functions. Here, we show that 20-Hz event-related desynchronization/synchronization (20-Hz ERD/ERS) is modulated by sensory input and motor output in the oral region. METHODS: Magnetic 20-Hz activity was recorded following right-sided tongue stimulation during rest (Rest) and self-paced repetitive tongue movement (Move). To exclude proprioception effects, 20-Hz activity induced by right-sided hard palate stimulation was also recorded. The 20-Hz activity in the two conditions was compared via temporal spectral evolution analyses. RESULTS: 20-Hz ERD/ERS was detected over bilateral temporoparietal areas in the Rest condition for both regions. Moreover, 20-Hz ERS was significantly suppressed in the Move condition for both regions. CONCLUSIONS: Detection of 20-Hz ERD/ERS during the Rest condition for both regions suggests that the SM1 functional state may be modulated by oral stimulation, with or without proprioceptive effects. Moreover, the suppression of 20-Hz ERS for the hard palate during the Move condition suggests that the stimulation-induced functional state of SM1 may have been modulated by the movement, even though the movement and stimulation areas were different. SIGNIFICANCE: Sensorimotor function of the general oral region may be finely coordinated through 20-Hz cortical oscillation.

Effects of treadmill exercise on the LiCl-induced conditioned taste aversion in rats.

Studies have shown that exercise can enhance learning and memory. Conditioned taste aversion (CTA) is an avoidance behavior induced by associative memory of the taste sensation for something pleasant or neutral with a negative visceral reaction caused by the coincident action of a toxic substance that is tasteless or administered systemically. We sought to measure the effects of treadmill exercise on CTA in rats by investigating the effects of exercise on acquisition, extinction and spontaneous recovery of CTA. We made two groups of rats: an exercise group that ran on a treadmill, and a control group that did not have structured exercise periods. To condition rats to disfavor a sweet taste, consumption of a 0.1% saccharin solution in place of drinking water was paired with 0.15M LiCl (2% body weight, i.p.) to induce visceral discomfort. We measured changes of saccharin consumption during acquisition and extinction of CTA. The exercise and no-exercise groups both acquired CTA to similar levels and showed maximum extinction of CTA around 6 days after acquisition. This result indicates that exercise affects neither acquisition nor extinction of CTA. However, in testing for preservation of CTA after much longer extinction periods that included exercise or not during the intervening period, exercising animals showed a significantly lower saccharin intake, irrespective of having exercised or not during the conditioning phase of the trial. This result suggests that exercise may help to preserve aversive memory (taste aversion in this example) as evidence by the significant spontaneous recovery of aversion in exercising animals.