Swallow-related Brain Activity in Post-total Laryngectomy Patients: A Case Series Study.

Background: Total laryngectomy is a surgical procedure to completely remove the hyoid bone, larynx, and associated muscles as a curative treatment for laryngeal cancer. This leads to insufficient swallowing function with compensative movements of the residual tongue to propel the food bolus to the pharynx and esophagus. However, the neurophysiological mechanisms of compensative swallowing after total laryngectomy remain unclear. Recently, swallowing-related cortical activation such as event-related desynchronization (ERD) during swallowing has been reported in healthy participants and neurological patients with dysphagia. Abnormal ERD elucidates the pathophysiological cortical activities that are related to swallowing. No report has investigated ERD in post-total laryngectomy patients. Case: We investigated ERD during volitional swallowing using electroencephalography in three male patients after total laryngectomy for laryngeal cancer (age and time after surgery: Case 1, 75 years, 10 years; Case 2, 85 years, 19 years; Case 3, 73 years, 19 years). In video fluorographic swallowing studies, we observed compensatory tongue movements such as posterior-inferior retraction of the tongue and contact on the posterior pharyngeal wall in all three cases. Significant ERD was localized in the bilateral medial sensorimotor areas and the left lateral parietal area in Case 1, in the bilateral frontal and left temporal areas in Case 2, and in the left prefrontal and premotor areas in Case 3. Discussion: These results suggest that cortical activities related to swallowing might reflect cortical reorganization for modified swallowing movements of residual tongue muscles to compensate for reduced swallowing pressure in patients after total laryngectomy.

Distinctive modes of cortical communications in tactile temporal order judgment.

Temporal order judgment of two successive tactile stimuli delivered to our hands is often inverted when we cross our hands. The present study aimed to identify time-frequency profiles of the interactions across the cortical network associated with the crossed-hand tactile temporal order judgment task using magnetoencephalography. We found that the interactions across the cortical network were channeled to a low-frequency band (5-10 Hz) when the hands were uncrossed. However, the interactions became activated in a higher band (12-18 Hz) when the hands were crossed. The participants with fewer inverted judgments relied mainly on the higher band, whereas those with more frequent inverted judgments (reversers) utilized both. Moreover, reversers showed greater cortical interactions in the higher band when their judgment was correct compared to when it was inverted. Overall, the results show that the cortical network communicates in two distinctive frequency modes during the crossed-hand tactile temporal order judgment task. A default mode of communications in the low-frequency band encourages inverted judgments, and correct judgment is robustly achieved by recruiting the high-frequency mode.

Case Report: Event-Related Desynchronization Observed During Volitional Swallow by Electroencephalography Recordings in ALS Patients With Dysphagia.

Dysphagia is a severe disability affecting daily life in patients with amyotrophic lateral sclerosis (ALS). It is caused by degeneration of both the bulbar motor neurons and cortical motoneurons projecting to the oropharyngeal areas. A previous report showed decreased event-related desynchronization (ERD) in the medial sensorimotor areas in ALS dysphagic patients. In the process of degeneration, brain reorganization may also be induced in other areas than the sensorimotor cortices. Furthermore, ALS patients with dysphagia often show a longer duration of swallowing. However, there have been no reports on brain activity in other cortical areas and the time course of brain activity during prolonged swallowing in these patients. In this case report, we investigated the distribution and the time course of ERD and corticomuscular coherence (CMC) in the beta (15-25 Hz) frequency band during volitional swallow using electroencephalography (EEG) in two patients with ALS. Case 1 (a 71-year-old man) was diagnosed 2 years before the evaluation. His first symptom was muscle weakness in the right hand; 5 months later, dysphagia developed and exacerbated. Since his dietary intake decreased, he was given an implantable venous access port. Case 2 (a 64-year-old woman) was diagnosed 1 year before the evaluation. Her first symptom was open-nasal voice and dysarthria; 3 months later, dysphagia developed and exacerbated. She was given a percutaneous endoscopic gastrostomy. EEG recordings were performed during volitional swallowing, and the ERD was calculated. The average swallow durations were 7.6 ± 3.0 s in Case 1 and 8.3 ± 2.9 s in Case 2. The significant ERD was localized in the prefrontal and premotor areas and lasted from a few seconds after the initiation of swallowing to the end in Case 1. The ERD was localized in the lateral sensorimotor areas only at the initiation of swallowing in Case 2. CMC was not observed in either case. These results suggest that compensatory processes for cortical motor outputs might depend on individual patients and that a new therapeutic approach using ERD should be developed according to the individuality of ALS patients with dysphagia.

Event-Related Desynchronization and Corticomuscular Coherence Observed During Volitional Swallow by Electroencephalography Recordings in Humans.

Swallowing in humans involves many cortical areas although it is partly mediated by a series of brainstem reflexes. Cortical motor commands are sent to muscles during swallow. Previous works using magnetoencephalography showed event-related desynchronization (ERD) during swallow and corticomuscular coherence (CMC) during tongue movements in the bilateral sensorimotor and motor-related areas. However, there have been few analogous works that use electroencephalography (EEG). We investigated the ERD and CMC in the bilateral sensorimotor, premotor, and inferior prefrontal areas during volitional swallow by EEG recordings in 18 healthy human subjects. As a result, we found a significant ERD in the beta frequency band and CMC in the theta, alpha, and beta frequency bands during swallow in those cortical areas. These results suggest that EEG can detect the desynchronized activity and oscillatory interaction between the cortex and pharyngeal muscles in the bilateral sensorimotor, premotor, and inferior prefrontal areas during volitional swallow in humans.

Neural Correlates of Temporal Presentness in the Precuneus: A Cross-linguistic fMRI Study based on Speech Stimuli.

The position of any event in time could be in the present, past, or future. This temporal discrimination is vitally important in our daily conversations, but it remains elusive how the human brain distinguishes among the past, present, and future. To address this issue, we searched for neural correlates of presentness, pastness, and futurity, each of which is automatically evoked when we hear sentences such as "it is raining now," "it rained yesterday," or "it will rain tomorrow." Here, we show that sentences that evoked "presentness" activated the bilateral precuneus more strongly than those that evoked "pastness" or "futurity." Interestingly, this contrast was shared across native speakers of Japanese, English, and Chinese languages, which vary considerably in their verb tense systems. The results suggest that the precuneus serves as a key region that provides the origin (that is, the Now) of our time perception irrespective of differences in tense systems across languages.

Modulation of Illusory Reversal in Tactile Temporal Order by the Phase of Posterior α Rhythm.

The subjective temporal order of tactile stimuli, delivered sequentially to each hand with an interval of 100-300 ms, is often inverted when the arms are crossed. Based on data from behavioral and neuroimaging studies, it has been proposed that the reversal is due to a conflict between anatomical and spatial representations of the tactile signal or to the production of an inverted apparent motion signal. Because the α rhythms, which consist of a few distinct components, reportedly modulate tactile perception and apparent motion and serve as a 10 Hz timer, we hypothesized that the illusory reversal would be regulated by some of the α rhythms. To test this hypothesis, we conducted magnetoencephalographic recordings in both male and female participants during the tactile temporal order judgment task. We decomposed the α rhythms into five independent components and discovered that the illusory reversal was modulated by the phase of one independent component with strong current sources near the parieto-occipital (PO) sulcus (peri-PO component). As expected, the estimated current sources distributed over the human MST implicated to represent tactile apparent motion, in addition to the intraparietal region implicated in mapping tactile signals in space. However, the strongest source was located in the precuneus that occupies a central hub region in the cortical networks and receives tactile inputs through a tecto-thalamic pathway. These results suggest that the peri-PO component plays an essential role in regulating tactile temporal perception by modulating the thalamic nuclei that interconnect the superior colliculus with the cortical networks.SIGNIFICANCE STATEMENT Despite a long-held hypothesis that the posterior α rhythm serves as a 10 Hz timer that regulates human temporal perception, the contribution of the α rhythms in temporal perception is still unclear. We examined how the α rhythms influence tactile temporal order judgment. Judgment reversal depended on the phase of one particular α rhythm with its source near the parieto-occipital sulcus. The peri-parieto-occipital α rhythm may play a crucial role in organizing tactile temporal perception.

Differences in the Pulsatile Component of the Skin Hemodynamic Response to Verbal Fluency Tasks in the Forehead and the Fingertip.

Several studies have claimed that hemodynamic signals measured by near-infrared spectroscopy (NIRS) on the forehead exhibit different patterns during a verbal fluency task (VFT) in various psychiatric disorders, whereas many studies have noted that NIRS signals can reflect task-related changes in skin blood flow. If such a task-related skin hemodynamic response is also observed in the fingertip, a simpler biomarker may be developed. Furthermore, determining the difference in the response pattern may provide physiological insights into the condition. We found that the magnitude of the pulsatile component in skin hemodynamic signals increased on the forehead (p < 0.001 for N = 50, p = 0.073 for N = 8) but decreased on the fingertip (p < 0.001, N = 8) during the VFT, whereas the rate in both areas increased (p < 0.02, N = 8). We also did not find a repetition effect in both the rate and the magnitude on the fingertip, whereas the effect was present in the magnitude (p < 0.02, N = 8) but not in the rate on the forehead. These results suggest that the skin vasomotor system in the forehead could have a different vessel mechanism to psychological tasks compared to the fingertip.

Decoding the timing and target locations of saccadic eye movements from neuronal activity in macaque oculomotor areas.

OBJECTIVE: The control of movement timing has been a significant challenge for brain-machine interfaces (BMIs). As a first step toward developing a timing-based BMI, we aimed to decode movement timing and target locations in a visually guided saccadic eye movement task using the activity of neurons in the primate frontal eye field (FEF) and supplementary eye field (SEF). APPROACH: For this purpose, we developed a template-matching method that could recruit a variety of neurons in these areas. MAIN RESULTS: As a result, we were able to achieve a favorable estimation of saccade onset: for example, data from 20 randomly sampled FEF neurons or 40 SEF neurons achieved a median estimation error of ∼10 ms with an interquartile range less than 50 ms (± ∼25 ms). In the best case, seven simultaneously recorded SEF neurons using a multi-electrode array achieved a comparable accuracy (10 ± 30 ms). The method was significantly better than a heuristic method that used only a group of movement cells with sharp discharges at the onset of saccades. The estimation of target location was less accurate but still favorable, especially when we estimated target location at a timing of 200 ms after the onset of saccade: the method was able to discriminate 16 targets with an accuracy of 90%, which differed not only in their directions (eight directions) but also in amplitude (10/20°) when we used data from 61 randomly sampled FEF neurons. SIGNIFICANCE: The results show that the timing, amplitude and direction of saccades can be decoded from neuronal activity in the FEF and SEF and further suggest that timing-based BMIs can be developed by decoding timing information using the template-matching method.

Neural correlates of tactile temporal-order judgment in humans: an fMRI study.

Little is known about the neuronal mechanisms underlying the temporal ordering of tactile signals. We examined the brain regions involved in judgments of the temporal order of successive taps delivered to both hands. Participants received identical stimuli while engaging in 2 different tasks: Judging the temporal order and judging the numerosity of points of tactile stimulation. Comparisons of the functional magnetic resonance imaging data obtained during the 2 tasks revealed regions that were more strongly activated with the judgments of the temporal order than with the judgments of numerosity under both arms-uncrossed and -crossed conditions: The bilateral premotor cortices, the bilateral middle frontal gyri, the bilateral inferior parietal cortices and supramarginal gyri, and the bilateral posterior part of the superior and middle temporal gyri. Stronger activation was found in some of these areas that implicated for remapping tactile stimuli to spatial coordinates after the participants crossed their arms. The activation in the perisylvian areas overlapped with the human visual-motion-sensitive areas in the posterior part. Based on these results, we propose that the temporal order of tactile signals is determined by combining spatial representations of stimuli in the parietal and prefrontal cortices with representations of "motion" or "changes" in the multisensory perisylvian cortex.

Analysis of brain activity during visceral stimulation.

BACKGROUND AND AIM: Functional magnetic resonance imaging (fMRI) is a useful technology for investigating regional metabolic activity in the brain. Many experiments using fMRI have been performed, but because of variations in protocols and analytic techniques, the results vary. When a priori information of the task is known, a model-based technique, such as statistical parametric mapping, is often used for analysis. In the case of acid stimulation of the esophagus the task model is unclear, so we analyzed brain activity during an acid or isotonic saline infusion to the esophagus using independent component analysis (ICA), which does not depend on a priori information of the task. METHODS: Six healthy male volunteers (29-45 years) participated in the study. A multi-lumen catheter was inserted transnasally and side-hole infusions ports were approximately 15 cm proximal to the lower esophageal sphincter. The experimental protocol was 5-min interval, 5-min saline infusion, 5-min interval, 5-min 0.1 N HCl, and a final 5-min interval. After magnetic resonance scanning, fMRI image data were analyzed using group ICA. RESULTS: The cerebral regions activated during the first interval, saline infusion, and HCl infusion were the thalamus, insula, cingulate gyri, temporal pole and some parts of the frontal, parietal, temporal and occipital lobes. Activation of the postcentral and precentral gyri occurred during both infusions, but was not observed during the first interval. CONCLUSION: ICA, which can show the cerebral areas activated in relation to liquid in the esophagus, may be a powerful technique for studying the brain's response to visceral stimulation.

Applying independent component analysis to detect silent speech in magnetic resonance imaging signals.

Independent component analysis (ICA) can be usefully applied to functional imaging studies to evaluate the spatial extent and temporal profile of task-related brain activity. It requires no a priori assumptions about the anatomical areas that are activated or the temporal profile of the activity. We applied spatial ICA to detect a voluntary but hidden response of silent speech. To validate the method against a standard model-based approach, we used the silent speech of a tongue twister as a 'Yes' response to single questions that were delivered at given times. In the first task, we attempted to estimate one number that was chosen by a participant from 10 possibilities. In the second task, we increased the possibilities to 1000. In both tasks, spatial ICA was as effective as the model-based method for determining the number in the subject's mind (80-90% correct per digit), but spatial ICA outperformed the model-based method in terms of time, especially in the 1000-possibility task. In the model-based method, calculation time increased by 30-fold, to 15 h, because of the necessity of testing 1000 possibilities. In contrast, the calculation time for spatial ICA remained as short as 30 min. In addition, spatial ICA detected an unexpected response that occurred by mistake. This advantage was validated in a third task, with 13 500 possibilities, in which participants had the freedom to choose when to make one of four responses. We conclude that spatial ICA is effective for detecting the onset of silent speech, especially when it occurs unexpectedly.

Influence of skin blood flow on near-infrared spectroscopy signals measured on the forehead during a verbal fluency task.

Brain activity during a verbal fluency task (VFT) has been the target of many functional imaging studies. Most studies using near-infrared spectroscopy (NIRS) have reported major activation in the frontal pole, but those using PET or fMRI have not. This led us to hypothesize that changes in the NIRS signals measured in the forehead during VFT were due to changes in skin blood flow. To test this hypothesis, we measured NIRS signals and the Doppler tissue blood flow signals in the foreheads of 50 participants. The measurements were performed while each participant produced words during two 60-s periods with an interval of 100 s. In addition to a conventional optode separation distance of 30 mm (FAR channels), we used a short distance--5mm (NEAR channels)--to measure NIRS signals that originated exclusively from surface tissues. The oxygenated hemoglobin (oxyHb) concentration in the FAR and NEAR channels, as well as the Doppler blood flow signal, increased in a similar manner during the two periods of word production; the signal increase in the first period was twice as high as that in the second period. Accordingly, the mean changes in oxyHb concentration in the FAR channels were correlated closely with the changes in the NEAR channels (R(2) = 0.91) and with the integrated Doppler skin blood flow signal (R(2) = 0.94). Furthermore, task-related NIRS responses disappeared when we blocked skin blood flows by pressing a small area that covered a pair of optodes. Additionally, changes in the FAR channel signals were correlated closely with the magnitude of pulsatile waves in the Doppler signal (R(2) = 0.92), but these signals were not highly correlated with the pulse rate (R(2) = 0.43). These results suggest that a major part of the task-related changes in the oxyHb concentration in the forehead is due to task-related changes in the skin blood flow, which is under different autonomic control than heart rate.

Synchronization of spontaneous eyeblinks while viewing video stories.

Blinks are generally suppressed during a task that requires visual attention and tend to occur immediately before or after the task when the timing of its onset and offset are explicitly given. During the viewing of video stories, blinks are expected to occur at explicit breaks such as scene changes. However, given that the scene length is unpredictable, there should also be appropriate timing for blinking within a scene to prevent temporal loss of critical visual information. Here, we show that spontaneous blinks were highly synchronized between and within subjects when they viewed the same short video stories, but were not explicitly tied to the scene breaks. Synchronized blinks occurred during scenes that required less attention such as at the conclusion of an action, during the absence of the main character, during a long shot and during repeated presentations of a similar scene. In contrast, blink synchronization was not observed when subjects viewed a background video or when they listened to a story read aloud. The results suggest that humans share a mechanism for controlling the timing of blinks that searches for an implicit timing that is appropriate to minimize the chance of losing critical information while viewing a stream of visual events.

Subsecond reward-related dopamine release in the mouse dorsal striatum.

Reward presentation is known to induce transient bursts of midbrain dopamine neurons in monkeys and rats, and the reward-induced dopamine overflow has been detected in the rat ventral striatum. To detect reward-related dopamine release in the dorsal striatum of behaving mice (C57BL/6), we used voltammetry with carbon-fiber microelectrodes implanted into the dorsal striatum. Dopamine signals increased transiently after food delivery with a peak at 0.6 s after the delivery onset. The success in detecting transient reward-response of dopamine in behaving mice opens a wide range of application to studies in mutant mice.

Neuronal activity related to anticipated and elapsed time in macaque supplementary eye field.

It is essential to sense anticipated and elapsed time in our daily life. Several areas of the brain including parietal cortex, prefrontal cortex, basal ganglia and olivo-cerebellar system are known to be related to this temporal processing. We now describe a number of cells in the supplementary eye field (SEF) with phasic, delay activity and postdelay activity modulation that varied with the length of the delay period. This variation occurred in two manners. First, cells became active with the shorter delay periods (GO signal presented earlier). We call these cells "short-delay cells". Second, cells became active with the longer delay periods (GO signal presented later). We call these cells "long-delay cells". However, such changed neuronal activity did not correlate with reaction time. These results suggest that the delay-dependent activity may reflect anticipated and elapsed time during performance of a delayed saccadic eye movement.

Development of the supralaryngeal vocal tract in Japanese macaques: implications for the evolution of the descent of the larynx.

The configuration of the supralaryngeal vocal tract depends on the nonuniform growth of the oral and pharyngeal portion. The human pharynx develops to form a unique configuration, with the epiglottis losing contact with the velum. This configuration develops from the great descent of the larynx relative to the palate, which is accomplished through both the descent of the laryngeal skeleton relative to the hyoid and the descent of the hyoid relative to the palate. Chimpanzees show both processes of laryngeal descent, as in humans, but the evolutionary path before the divergence of the human and chimpanzee lineages is unclear. The development of laryngeal descent in six living Japanese macaque monkeys, Macaca fuscata, was examined monthly during the first three years of life using magnetic resonance imaging, to delineate the present or absence of these two processes and their contributions to the development of the pharyngeal topology. The macaque shows descent of the hyoid relative to the palate, but lacks the descent of the laryngeal skeleton relative to the hyoid and that of the EG from the VL. We argue that the former descent is simply a morphological consequence of mandibular growth and that the latter pair of descents arose in a common ancestor of extant hominoids. Thus, the evolutionary path of the great descent of the larynx is likely to be explained by a model comprising multiple and mosaic evolutionary pathways, wherein these developmental phenomena may have contributed secondarily to the faculty of speech in the human lineage.

Neuronal activity related to reward size and rewarded target position in primate supplementary eye field.

Several areas of the macaque brain are known to be related to the reward during the performance of saccadic eye-movement tasks. Neurons in the supplementary eye field (SEF) have been reported to be involved in the prediction and detection of a reward. We describe a group of neurons in the SEF that became active during the period of reward delivery after saccades toward a specific direction, but showed weaker activity in other directions, although the same amount of reward was given in each direction. Moreover, this directional reward activity was modulated by the reward size. Our results demonstrate that the SEF cells may reflect both reward amount and target positions toward which a movement was rewarded, and suggest that they may play an important role in providing information about the value of each saccade according to the spatial target location.

Effects of visual stimuli on temporal order judgments of unimanual finger stimuli.

Successive tactile stimuli, delivered one to each hand, are referred to spatial representation before they are ordered in time (Yamamoto and Kitazawa in Nat Neurosci 4:759-765 2001a). In the present study, we examined if this applies even when they are delivered unilaterally to fingers of a single hand. Tactile stimuli were delivered left-to-rightward relative to the body (2nd-3rd-4th) or in reverse with stimulus onset asynchrony of 100 ms. Simultaneously with the delivery of tactile stimuli, three of nine small squares arranged in a matrix of 3 x 3 were turned on as if they appeared near the tips of the fingers. Although subjects were instructed to ignore the visual stimuli and make a forced choice between the two orders of tactile stimuli, the correct-judgment probability depended on the direction of visual stimuli. It was greater than 95% when the direction of visual stimuli matched that of the tactile stimuli, but less than 50% when they were opposite to each other. When the right hand was rotated counterclockwise on the horizontal plane (90 degrees ) so that the fingers were pointing to the left, the preferred direction of visual stimuli that yielded the peak correct judgment was also rotated, although not to the full extent. These results show that subjects cannot be basing their tactile temporal order judgment solely on a somatotopic map, but rather on a spatial map on which both visual and tactile signals converge.

Dominance of the left oblique view in activating the cortical network for face recognition.

Faces in portraits are often depicted from the left 3/4 view (an oblique view of the face that is intermediate between the frontal view and left profile). Here, we used functional magnetic resonance imaging (fMRI) to show that, compared with photographs of right 3/4 views of familiar faces, photographs of left 3/4 views of the same faces elicited stronger neural responses in the right middle occipital/inferior parietal cortex, and right inferior frontal gyrus; which are known to be involved in face recognition. By contrast, there was no differential activation in the temporal cortex including the superior temporal sulcus and fusiform gyrus, which are thought to process face-related visual stimuli at a stage that precedes recognition. We suggest that the preference for the left 3/4 view of faces was produced at a later stage of facial information processing that involves attention or memory retrieval.

Medial temporal lobe activation during context-dependent relational processes in episodic retrieval: an fMRI study. Functional magnetic resonance imaging.

Previous studies have reported that the medial temporal lobe (MTL) structures contribute to the processing of relations among multiple stimuli in episodic encoding. There have been few studies, however, on the episodic retrieval requiring processing of relations among multiple components that was involved in our events. We used functional magnetic resonance imaging (fMRI) to investigate neural activities during the retrieval of relations within an organized episode and the recognition of an episodic component. Healthy, normal participants memorized 50 four-scene comic strips before fMRI scanning. In the retrieval phase with fMRI scanning, participants were engaged in three tasks: a visual identification (VI) task, a story recall (SR) task, and a picture recognition (PRe) task. In the VI task, participants were asked to judge whether they could identify at least one female character in the two scenes presented vertically. In the SR task, participants were shown the first and last scenes from strips memorized previously and asked to judge whether or not the two scenes were from the same strip. In the PRe task, participants were shown two scenes and asked to judge whether they both belonged to the memorized scenes. The two contrasts of SR with VI and PRe with VI demonstrated some commonly activated areas, such as the bilateral middle frontal gyrus and cerebellum. More importantly, the SR task differentially activated the bilateral parahippocampal gyrus, whereas the PRe task differentially activated right prefrontal areas, including the inferior frontal and precentral gyri. The results suggest that the activity of the MTL structures may be strongly associated with episodic memory retrieval requiring context-dependent relational processing.