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.

Detecting passive and active response in patients with behaviourally diagnosed unresponsive wakefulness syndrome.

The diagnosis of unresponsive wakefulness syndrome depends mostly on the motor response following verbal commands. However, there is a potential for misdiagnosis in patients who understand verbal commands (passive response) but cannot perform voluntary movements (active response). To evaluate passive and active responses in such patients, this study used an approach combining functional magnetic resonance imaging and passive listening tasks to evaluate the level of speech comprehension, with portable brain-computer interface modalities that were applied to elicit an active response to attentional modulation tasks at the bedside. We included ten patients who were clinically diagnosed as unresponsive wakefulness syndrome. Two of ten patients showed no significant activation, while limited activation in the auditory cortex was found in six patients. The remaining two patients showed significant activation in language areas, and were able to control the brain-computer interface with reliable accuracy. Using a combined passive/active approach, we identified unresponsive wakefulness syndrome patients who showed both active and passive neural responses. This suggests that some patients with unresponsive wakefulness syndrome diagnosed behaviourally are both wakeful and responsive, and the combined approach is useful for distinguishing a minimally conscious state from unresponsive wakefulness syndrome physiologically.

Chronic corticosterone deteriorates latrine and nesting behaviours in mice.

Self-care behaviours are actions that help maintain good health and surroundings. For example, appropriate toileting, sleeping in the bed, and bathing and washing are among self-care behaviours in humans. Animals also perform similar self-care behaviours such as latrine, nesting and self-grooming. Studies have shown that chronic stress disrupts nesting and self-grooming behaviours. However, the effect of chronic stress on latrine behaviour, preferential, repeated defecation at specific locations, has not yet been clarified. This study aimed to investigate the influence of chronic corticosterone administration on latrine and nesting behaviours in mice. The variation in defecation location was quantified as the degree of the latrine behaviour by using Shannon entropy. The nest quality was scored based on shape. The study showed that mice exposed to chronic corticosterone had scattered defecation sites and lower nest quality compared to the control group. Furthermore, results showed that more scattered defecation behaviour was associated with lower nest quality at an individual level. Additionally, the deterioration of these self-care behaviours was associated with depression-like behaviours such as less open field activity and increased immobility time during the tail suspension test. These results suggest that chronic corticosterone deteriorates self-care behaviours such as latrine and nesting in mice.

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.

Task-Related c-Fos Expression in the Posterior Parietal Cortex During the "Rubber Tail Task" Is Diminished in Ca2+-Dependent Activator Protein for Secretion 2 (Caps2)-Knockout Mice.

Rubber hand illusion (RHI), a kind of body ownership illusion, is sometimes atypical in individuals with autism spectrum disorder; however, the brain regions associated with the illusion are still unclear. We previously reported that mice responded as if their own tails were being touched when rubber tails were grasped following synchronous stroking to rubber tails and their tails (a "rubber tail illusion", RTI), which is a task based on the human RHI; furthermore, we reported that the RTI response was diminished in Ca2+-dependent activator protein for secretion 2-knockout (Caps2-KO) mice that exhibit autistic-like phenotypes. Importance of the posterior parietal cortex in the formation of illusory perception has previously been reported in human imaging studies. However, the local neural circuits and cell properties associated with this process are not clear. Therefore, we aimed to elucidate the neural basis of the RTI response and its impairment by investigating the c-Fos expression in both wild-type (WT) and Caps2-KO mice during the task since the c-Fos expression occurred soon after the neural activation. Immediately following the delivery of the synchronous stroking to both rubber tails and actual tails, the mice were perfused. Subsequently, whole brains were cryo-sectioned, and each section was immunostained with anti-c-Fos antibody; finally, c-Fos positive cell densities among the groups were compared. The c-Fos expression in the posterior parietal cortex was significantly lower in the Caps2-KO mice than in the WT mice. Additionally, we compared the c-Fos expression in the WT mice between synchronous and asynchronous conditions and found that the c-Fos-positive cell densities were significantly higher in the claustrum and primary somatosensory cortex of the WT mice exposed to the synchronous condition than those exposed to the asynchronous condition. Hence, the results suggest that decreased c-Fos expression in the posterior parietal cortex may be related to impaired multisensory integrations in Caps2-KO mice.

Attention-dependent switching between intrinsic-muscle and extrinsic-visual coordinates during bimanual movements.

Inter-limb coordination is achieved through multiple levels of motor control based on intrinsic-muscle and extrinsic-visual coordinates. Online visual feedback affects which of these coordinates is dominant, and visual perception is involved in the switching of motor coordination across the two hands; however, it remains unclear whether there is any role for attention in inter-limb coordination. Therefore, we evaluated the effects of attention on the dominance of intrinsic-muscle and extrinsic-visual coordinates by investigating inter-limb interference in the right or left hand during bimanual reaching movements, as induced by visual perturbations. We first showed an effect of differences in online visual feedback on bimanual coordination (Experiment 1). We then revealed that attention to visual cursors that directly affected the hand movement led to the dominance of the intrinsic-muscle coordinates, which synchronized homologous muscle activities. In contrast, attention to an integrated visual object controlled by bilateral hand movements was associated with a preference for extrinsic-visual coordinates to synchronize bilateral movement directions (Experiment 2). Thus, attention-dependent switching between intrinsic-muscle and extrinsic-visual coordinates was observed during bimanual movements; extrinsic-visual coordinates may enable goal-directed bimanual movements at least for particular task requirements.

[Manipulation of Human Brain Oscillation to Control Neuron Network Dynamics and its Clinical Application].

Electroencephalographic recordings of human brain oscillations have been performed over approximately a century. Noninvasive methods for manipulation of brain oscillations are currently available. Reportedly, the manipulation of brain oscillations alters human behavior and cognition and is also used for "oscillotherapy" to treat many neurological diseases. In this review, we summarize the physiological mechanisms of brain oscillations, human behavioral and cognitive changes, and oscillotherapy; we have focused on our recent findings of the manipulation of human brain oscillations during bipedal walking and gait disorder recovery.

Self-reorganization of neuronal activation patterns in the cortex under brain-machine interface and neural operant conditioning.

In this review, we describe recent experimental observations and model simulations in the research subject of brain-machine interface (BMI). Studies of BMIs have applied decoding models to extract functional characteristics of the recorded neurons, and some of these have more focused on adaptation based on neural operant conditioning. Under a closed loop feedback with the environment through BMIs, neuronal activities are forced to interact directly with the environment. These studies have shown that the neuron ensembles self-reorganized their activity patterns and completed a transition to adaptive state within a short time scale. Based on these observations, we discuss how the brain could identify the target neurons directly interacting with the environment and determine in which direction the activities of those neurons should be changed for adaptation. For adaptation over a short time scale, the changes of neuron ensemble activities seem to be restricted by the intrinsic correlation structure of the neuronal network (intrinsic manifold). On the other hand, for adaptation over a long time scale, modifications to the synaptic connections enable the neuronal network to generate a novel activation pattern required by BMI (extension of the intrinsic manifold). Understanding of the intrinsic constraints in adaptive changes of neuronal activities will provide the basic principles of learning mechanisms in the brain and methodological clues for better performance in engineering and clinical applications of BMI.

Cerebellar transcranial alternating current stimulation modulates human gait rhythm.

Although specific brain regions are important for regularly patterned limb movements, the rhythm generation system that governs bipedal locomotion in humans is not thoroughly understood. We investigated whether rhythmic transcranial brain stimulation over the cerebellum could alter walking rhythm. Fourteen healthy subjects performed over-ground walking for 10 min during which they were given, in a random order, transcranial alternating current stimulation (tACS) over the left cerebellum at the approximated frequency of their gait cycle, tACS over the skin of the scalp, and during sham stimulation. Cerebellar tACS showed a significant entrainment of gait rhythm compared with the control conditions. When the direction of the tACS currents was symmetrically inverted, some subjects showed entrainment at an approximately 180° inverted phase, suggesting that gait modulation is dependent on current orientation. These findings indicate that tACS over cerebellum can modulate gait generation system in cerebellum and become an innovative approach for the recovery of locomotion in patients with gait disturbances caused by CNS disorders.

Gait-Synchronized Rhythmic Brain Stimulation Improves Poststroke Gait Disturbance: A Pilot Study.

Background and Purpose- Gait disturbance is one of serious impairments lowering activity of daily life in poststroke patients. The patients often show reduced hip and knee joint flexion and ankle dorsiflexion of the lower limbs during the swing phase of gait, which is partly controlled by the primary motor cortex (M1). In the present study, we investigated whether gait-synchronized rhythmic brain stimulation targeting swing phase-related M1 activity can improve gait function in poststroke patients. Methods- Eleven poststroke patients in the chronic phase participated in this single-blind crossover study. Each patient received oscillatory transcranial direct current stimulation over the affected M1 foot area and sham stimulation during treadmill gait. The brain stimulation was synchronized with individual gait rhythm, and the electrical current peaks reached immediately before initiation of the swing phase of the paretic lower limb. Ankle dorsiflexion was assisted by electrical neuromuscular stimulation in both real and sham conditions. Results- Regarding the effects of a single intervention, the speed of self-paced gait was significantly increased after oscillatory transcranial direct current stimulation, but not after sham stimulation (paired t test, P=0.009). After we administered the intervention repeatedly, self- and maximally paced gait speed and timed up and go test performance were significantly improved (self-paced: F(1,21)=8.91, P=0.007, maximally paced: F(1,21)=7.09, P=0.015 and timed up and go test: F(1,21)=12.27, P=0.002), along with improved balance function and increased joint flexion of the paretic limbs during gait. Conclusions- These findings suggest that rhythmic brain stimulation synchronized with gait rhythm might be a promising approach to induce gait recovery in poststroke patients. Clinical Trial Registration- URL: https://www.umin.ac.jp/ctr/. Unique identifier: UMIN000013676.

Rubber tail illusion is weakened in Ca2+-dependent activator protein for secretion 2 (Caps2)-knockout mice.

Body ownership is a fundamental aspect of self-consciousness. Illusion of body ownership is caused by updating body representation through multisensory integration. Synchronous visuotactile stimulation of a hand and rubber hand leads to illusory changes in body ownership in humans, but this is impaired in individuals with autism spectrum disorder (ASD). We previously reported that mice also exhibit body ownership illusion. With synchronous stroking of a tail and rubber tail, mice responded as if their own tails were being touched when the rubber tails were grasped ('rubber tail illusion'). However, it remains unknown whether deficits in illusion of body ownership occur in mouse models of autism. Here, we examined whether the 'rubber tail illusion' occurred in Ca2+-dependent activator protein for secretion 2-knockout (Caps2-KO) mice, which exhibit autistic-like phenotypes. During the synchronous stroking, response rates were significantly lower in Caps2-KO mice than in wild-type mice. There were no significant differences between the response rates of wild-type and Caps2-KO mice during the asynchronous stroking. The 'rubber tail illusion' was weak in Caps2-KO mice, suggesting that Caps2-KO mice experienced weaker visuotactile integration during the task. The rubber tail task will be a useful tool in mouse models of autism to evaluate atypical sensory processing.

Long-term use of a neural prosthesis in progressive paralysis.

Brain-computer interfaces (BCIs) enable communication with others and allow machines or computers to be controlled in the absence of motor activity. Clinical studies evaluating neural prostheses in amyotrophic lateral sclerosis (ALS) patients have been performed; however, to date, no study has reported that ALS patients who progressed from locked-in syndrome (LIS), which has very limited voluntary movement, to a completely locked-in state (CLIS), characterized by complete loss of voluntary movements, were able to continue controlling neural prostheses. To clarify this, we used a BCI system to evaluate three late-stage ALS patients over 27 months. We employed steady-state visual evoked brain potentials elicited by flickering green and blue light-emitting diodes to control the BCI system. All participants reliably controlled the system throughout the entire period (median accuracy: 83.3%). One patient who progressed to CLIS was able to continue operating the system with high accuracy. Furthermore, this patient successfully used the system to respond to yes/no questions. Thus, this CLIS patient was able to operate a neuroprosthetic device, suggesting that the BCI system confers advantages for patients with severe paralysis, including those exhibiting complete loss of muscle movement.

Body ownership and agency altered by an electromyographically controlled robotic arm.

Understanding how we consciously experience our bodies is a fundamental issue in cognitive neuroscience. Two fundamental components of this are the sense of body ownership (the experience of the body as one's own) and the sense of agency (the feeling of control over one's bodily actions). These constructs have been used to investigate the incorporation of prostheses. To date, however, no evidence has been provided showing whether representations of ownership and agency in amputees are altered when operating a robotic prosthesis. Here we investigated a robotic arm using myoelectric control, for which the user varied the joint position continuously, in a rubber hand illusion task. Fifteen able-bodied participants and three trans-radial amputees were instructed to contract their wrist flexors/extensors alternately, and to watch the robotic arm move. The sense of ownership in both groups was extended to the robotic arm when the wrists of the real and robotic arm were flexed/extended synchronously, with the effect being smaller when they moved in opposite directions. Both groups also experienced a sense of agency over the robotic arm. These results suggest that these experimental settings induced successful incorporation of the prosthesis, at least for the amputees who took part in the present study.

Comparison of Four Control Methods for a Five-Choice Assistive Technology.

Severe motor impairments can affect the ability to communicate. The ability to see has a decisive influence on the augmentative and alternative communication (AAC) systems available to the user. To better understand the initial impressions users have of AAC systems we asked naïve healthy participants to compare two visual (a visual P300 brain-computer interface (BCI) and an eye-tracker) and two non-visual systems (an auditory and a tactile P300 BCI). Eleven healthy participants performed 20 selections in a five choice task with each system. The visual P300 BCI used face stimuli, the auditory P300 BCI used Japanese Hiragana syllables and the tactile P300 BCI used a stimulator on the small left finger, middle left finger, right thumb, middle right finger and small right finger. The eye-tracker required a dwell time of 3 s on the target for selection. We calculated accuracies and information-transfer rates (ITRs) for each control method using the selection time that yielded the highest ITR and an accuracy above 70% for each system. Accuracies of 88% were achieved with the visual P300 BCI (4.8 s selection time, 20.9 bits/min), of 70% with the auditory BCI (19.9 s, 3.3 bits/min), of 71% with the tactile BCI (18 s, 3.4 bits/min) and of 100% with the eye-tracker (5.1 s, 28.2 bits/min). Performance between eye-tracker and visual BCI correlated strongly, correlation between tactile and auditory BCI performance was lower. Our data showed no advantage for either non-visual system in terms of ITR but a lower correlation of performance which suggests that choosing the system which suits a particular user is of higher importance for non-visual systems than visual systems.

Operation of a P300-based brain-computer interface in patients with Duchenne muscular dystrophy.

A brain-computer interface (BCI) or brain-machine interface is a technology that enables the control of a computer and other external devices using signals from the brain. This technology has been tested in paralysed patients, such as those with cervical spinal cord injuries or amyotrophic lateral sclerosis, but it has not been tested systematically in Duchenne muscular dystrophy (DMD), which is a severe type of muscular dystrophy due to the loss of dystrophin and is often accompanied by progressive muscle weakness and wasting. Here, we investigated the efficacy of a P300-based BCI for patients with DMD. Eight bedridden patients with DMD and eight age- and gender-matched able-bodied controls were instructed to input hiragana characters. We used a region-based, two-step P300-based BCI with green/blue flicker stimuli. EEG data were recorded, and a linear discriminant analysis distinguished the target from other non-targets. The mean online accuracy of inputted characters (accuracy for the two-step procedure) was 71.6% for patients with DMD and 80.6% for controls, with no significant difference between the patients and controls. The P300-based BCI was operated successfully by individuals with DMD in an advanced stage and these findings suggest that this technology may be beneficial for patients with this disease.

Incorporation of prosthetic limbs into the body representation of amputees: Evidence from the crossed hands temporal order illusion.

Understanding how we consciously experience our bodies is a fundamental issue in both psychology and neuroscience. To date, the incorporation of nonbody objects into the body representation has been investigated extensively, and the incorporation of prosthetic arms in amputees has been demonstrated using the rubber hand illusion. In this study, we investigated the incorporation of prosthetic arms in amputees using the crossed hands illusion, in which successive somatosensory stimuli are delivered, one to each arm, at intervals of 300ms or less, and where arm crossing often causes inversion of perceived tactile temporal order. The induced reversal illusion was greater with a prosthetic limb than without in three amputees. With a shorter prosthetic arm (i.e., one that did not reach the contralateral limb), the illusion induced by vision of the short prosthetic arm was significantly reduced as compared to that seen when the long prosthetic arm crossed over the other arm. These results therefore suggest that the somatosensory signals were referred to the spatial location of the tips of the prosthetic arm, which was incorporated into the body representation by the amputees.

Affective Stimuli for an Auditory P300 Brain-Computer Interface.

Gaze-independent brain computer interfaces (BCIs) are a potential communication tool for persons with paralysis. This study applies affective auditory stimuli to investigate their effects using a P300 BCI. Fifteen able-bodied participants operated the P300 BCI, with positive and negative affective sounds (PA: a meowing cat sound, NA: a screaming cat sound). Permuted stimuli of the positive and negative affective sounds (permuted-PA, permuted-NA) were also used for comparison. Electroencephalography data was collected, and offline classification accuracies were compared. We used a visual analog scale (VAS) to measure positive and negative affective feelings in the participants. The mean classification accuracies were 84.7% for PA and 67.3% for permuted-PA, while the VAS scores were 58.5 for PA and -12.1 for permuted-PA. The positive affective stimulus showed significantly higher accuracy and VAS scores than the negative affective stimulus. In contrast, mean classification accuracies were 77.3% for NA and 76.0% for permuted-NA, while the VAS scores were -50.0 for NA and -39.2 for permuted NA, which are not significantly different. We determined that a positive affective stimulus with accompanying positive affective feelings significantly improved BCI accuracy. Additionally, an ALS patient achieved 90% online classification accuracy. These results suggest that affective stimuli may be useful for preparing a practical auditory BCI system for patients with disabilities.

A hybrid BMI-based exoskeleton for paresis: EMG control for assisting arm movements.

OBJECTIVE: Brain-machine interface (BMI) technologies have succeeded in controlling robotic exoskeletons, enabling some paralyzed people to control their own arms and hands. We have developed an exoskeleton asynchronously controlled by EEG signals. In this study, to enable real-time control of the exoskeleton for paresis, we developed a hybrid system with EEG and EMG signals, and the EMG signals were used to estimate its joint angles. APPROACH: Eleven able-bodied subjects and two patients with upper cervical spinal cord injuries (SCIs) performed hand and arm movements, and the angles of the metacarpophalangeal (MP) joint of the index finger, wrist, and elbow were estimated from EMG signals using a formula that we derived to calculate joint angles from EMG signals, based on a musculoskeletal model. The formula was exploited to control the elbow of the exoskeleton after automatic adjustments. Four able-bodied subjects and a patient with upper cervical SCI wore an exoskeleton controlled using EMG signals and were required to perform hand and arm movements to carry and release a ball. MAIN RESULTS: Estimated angles of the MP joints of index fingers, wrists, and elbows were correlated well with the measured angles in 11 able-bodied subjects (correlation coefficients were 0.81 ± 0.09, 0.85 ± 0.09, and 0.76 ± 0.13, respectively) and the patients (e.g. 0.91 ± 0.01 in the elbow of a patient). Four able-bodied subjects successfully positioned their arms to adequate angles by extending their elbows and a joint of the exoskeleton, with root-mean-square errors <6°. An upper cervical SCI patient, empowered by the exoskeleton, successfully carried a ball to a goal in all 10 trials. SIGNIFICANCE: A BMI-based exoskeleton for paralyzed arms and hands using real-time control was realized by designing a new method to estimate joint angles based on EMG signals, and these may be useful for practical rehabilitation and the support of daily actions.