Orofacial Movements Research Articles

Higher or lower? Interpersonal behavioral and neural synchronization of movement imitation in autistic children.

How well autistic children can imitate movements and how their brain activity synchronizes with the person they are imitating have been understudied. The current study adopted functional near-infrared spectroscopy (fNIRS) hyperscanning and employed a task involving real interactions involving meaningful and meaningless movement imitation to explore the fundamental nature of imitation as a dynamic and interactive process. Experiment 1 explored meaningful and meaningless gesture imitation. The results revealed that autistic children exhibited lower imitation accuracy and behavioral synchrony than non-autistic children when imitating both meaningful and meaningless gestures. Specifically, compared to non-autistic children, autistic children displayed significantly higher interpersonal neural synchronization (INS) in the right inferior parietal lobule (r-IPL) (channel 12) when imitating meaningful gestures but lower INS when imitating meaningless gestures. Experiment 2 further investigated the imitation of four types of meaningless movements (orofacial movements, transitive movements, limb movements, and gestures). The results revealed that across all four movement types, autistic children exhibited significantly lower imitation accuracy, behavioral synchrony, and INS in the r-IPL (channel 12) than non-autistic children. This study is the first to identify INS as a biomarker of movement imitation difficulties in autistic individuals. Furthermore, an intra- and interindividual imitation mechanism model was proposed to explain the underlying causes of movement imitation difficulties in autistic individuals.

Optogenetics in oral and craniofacial research.

Optogenetics combines optics and genetic engineering to control specific gene expression and biological functions and has the advantages of precise spatiotemporal control, noninvasiveness, and high efficiency. Genetically modified photosensory sensors are engineered into proteins to modulate conformational changes with light stimulation. Therefore, optogenetic techniques can provide new insights into oral biological processes at different levels, ranging from the subcellular and cellular levels to neural circuits and behavioral models. Here, we introduce the origins of optogenetics and highlight the recent progress of optogenetic approaches in oral and craniofacial research, focusing on the ability to apply optogenetics to the study of basic scientific neural mechanisms and to establish different oral behavioral test models in vivo (orofacial movement, licking, eating, and drinking), such as channelrhodopsin (ChR), archaerhodopsin (Arch), and halorhodopsin from Natronomonas pharaonis (NpHR). We also review the synergic and antagonistic effects of optogenetics in preclinical studies of trigeminal neuralgia and maxillofacial cellulitis. In addition, optogenetic tools have been used to control the neurogenic differentiation of dental pulp stem cells in translational studies. Although the scope of optogenetic tools is increasing, there are limited large animal experiments and clinical studies in dental research. Potential future directions include exploring therapeutic strategies for addressing loss of taste in patients with coronavirus disease 2019 (COVID-19), studying oral bacterial biofilms, enhancing craniomaxillofacial and periodontal tissue regeneration, and elucidating the possible pathogenesis of dry sockets, xerostomia, and burning mouth syndrome.

Multimodal Technologies for Remote Assessment of Neurological and Mental Health.

Automated remote assessment and monitoring of patients' neurological and mental health is increasingly becoming an essential component of the digital clinic and telehealth ecosystem, especially after the COVID-19 pandemic. This review article reviews various modalities of health information that are useful for developing such remote clinical assessments in the real world at scale. We first present an overview of the various modalities of health information-speech acoustics, natural language, conversational dynamics, orofacial or full body movement, eye gaze, respiration, cardiopulmonary, and neural-which can each be extracted from various signal sources-audio, video, text, or sensors. We further motivate their clinical utility with examples of how information from each modality can help us characterize how different disorders affect different aspects of patients' spoken communication. We then elucidate the advantages of combining one or more of these modalities toward a more holistic, informative, and robust assessment. We find that combining multiple modalities of health information allows for improved scientific interpretability, improved performance on downstream health applications such as early detection and progress monitoring, improved technological robustness, and improved user experience. We illustrate how these principles can be leveraged for remote clinical assessment at scale using a real-world case study of the Modality assessment platform. This review article motivates the combination of human-centric information from multiple modalities to measure various aspects of patients' health, arguing that remote clinical assessment that integrates this complementary information can be more effective and lead to better clinical outcomes than using any one data stream in isolation.

Functional and Effective Connectivity Underlying Semantic Verbal Fluency.

Semantic verbal fluency (SVF) impairment is present in several neurological disorders. Although activation in SVF-related areas has been reported, how these regions are connected and their functional roles in the network remain divergent. We assessed SVF static and dynamic functional connectivity (FC) and effective connectivity in healthy participants using functional magnetic resonance imaging. We observed activation in the inferior frontal (IFG), middle temporal (pMTG) and angular gyri (AG), anterior cingulate (AC), insular cortex, and regions of the superior, middle, and medial frontal gyri (SFG, MFG, MidFG). Our static FC analysis showed a highly interconnected task and resting state network. Increased connectivity of AC with the pMTG and AG was observed for the task. The dynamic FC analysis provided circuits with connections similarly modulated across time and regions related to category identification, language comprehension, word selection and recovery, word generation, inhibition of speaking, speech planning, and articulatory planning of orofacial movements. Finally, the effective connectivity analysis provided a network that best explained our data, starting at the AG and going to the pMTG, from which there was a division between the ventral and dorsal streams. The SFG and MFG regions were connected and modulated by the MidFG, while the inferior regions formed the ventral stream. Therefore, we successfully assessed the SVF network, exploring regions associated with the entire processing, from category identification to word generation. The methodological approach can be helpful for further investigation of the SVF network in neurological disorders.

The COMBO window: A chronic cranial implant for multiscale circuit interrogation in mice.

Neuroscientists studying the neural correlates of mouse behavior often lack access to the brain-wide activity patterns elicited during a specific task of interest. Fortunately, large-scale imaging is becoming increasingly accessible thanks to modalities such as Ca2+ imaging and functional ultrasound (fUS). However, these and other techniques often involve challenging cranial window procedures and are difficult to combine with other neuroscience tools. We address this need with an open-source 3D-printable cranial implant-the COMBO (ChrOnic Multimodal imaging and Behavioral Observation) window. The COMBO window enables chronic imaging of large portions of the brain in head-fixed mice while preserving orofacial movements. We validate the COMBO window stability using both brain-wide fUS and multisite two-photon imaging. Moreover, we demonstrate how the COMBO window facilitates the combination of optogenetics, fUS, and electrophysiology in the same animals to study the effects of circuit perturbations at both the brain-wide and single-neuron level. Overall, the COMBO window provides a versatile solution for performing multimodal brain recordings in head-fixed mice.

Cortical Networks Relating to Arousal Are Differentially Coupled to Neural Activity and Hemodynamics.

Even in the absence of specific sensory input or a behavioral task, the brain produces structured patterns of activity. This organized activity is modulated by changes in arousal. Here, we use wide-field voltage imaging to establish how arousal relates to cortical network voltage and hemodynamic activity in spontaneously behaving head-fixed male and female mice expressing the voltage-sensitive fluorescent FRET sensor Butterfly 1.2. We find that global voltage and hemodynamic signals are both positively correlated with changes in arousal with a maximum correlation of 0.5 and 0.25, respectively, at a time lag of 0 s. We next show that arousal influences distinct cortical regions for both voltage and hemodynamic signals. These include a broad positive correlation across most sensory-motor cortices extending posteriorly to the primary visual cortex observed in both signals. In contrast, activity in the prefrontal cortex is positively correlated to changes in arousal for the voltage signal while it is a slight net negative correlation observed in the hemodynamic signal. Additionally, we show that coherence between voltage and hemodynamic signals relative to arousal is strongest for slow frequencies below 0.15 Hz and is near zero for frequencies >1 Hz. We finally show that coupling patterns are dependent on the behavioral state of the animal with correlations being driven by periods of increased orofacial movement. Our results indicate that while hemodynamic signals show strong relations to behavior and arousal, these relations are distinct from those observed by voltage activity.

AMPK-mediated autophagy pathway activation promotes ΔFosB degradation to improve levodopa-induced dyskinesia

BackgroundParkinson's disease patients on chronic levodopa often suffer from motor complications, which tend to reduce their quality of life. Levodopa-induced dyskinesia (LID) is one of the most prevalent motor complications, often characterized by abnormal involuntary movements, and the pathogenesis of LID is still unclear but recent studies have suggested the involvement of autophagy. MethodsThe onset of LID was mimicked by chronic levodopa treatment in a unilateral 6-hydroxydopamine (6-OHDA) -lesion rat model. Overexpression of ΔFosB in HEK293 cells to mimic the state of ΔFosB accumulation. The modulation of the AMP-activated protein kinase (AMPK)-mediated autophagy pathway using by metformin, AICAR (an AMPK activator), Compound C (an AMPK inhibitor) and chloroquine (an autophagy pathway inhibitor). The severity of LID was assessed by axial, limb, and orofacial (ALO) abnormal involuntary movements (AIMs) score and in vivo electrophysiology. The activity of AMPK pathway as well as autophagy markers and FosB-ΔFosB levels were detected by western blotting. RT-qPCR was performed to detect the transcription level of FosB-ΔFosB. The mechanism of autophagy dysfunction was further explored by immunofluorescence and transmission electron microscopy. ResultsIn vivo experiments demonstrated that chronic levodopa treatment reduced AMPK phosphorylation, impaired autophagosome-lysosomal fusion and caused FosB-ΔFosB accumulation in the striatum of PD rats. Long-term metformin intervention improved ALO AIMs scores as well as reduced the mean power of high gamma (hγ) oscillations and the proportion of striatal projection neurons unstable in response to dopamine for LID rats. Moreover, the intervention of metformin promoted AMPK phosphorylation, ameliorated the impairment of autophagosome-lysosomal fusion, thus, promoting FosB-ΔFosB degradation to attenuate its accumulation in the striatum of LID rats. However, the aforementioned roles of metformin were reversed by Compound C and chloroquine. The results of in vitro studies demonstrated the ability of metformin and AICAR to attenuate ΔFosB levels by promoting its degradation, while Compound C and chloroquine could block this effect. ConclusionsIn conclusion, our results suggest that long-term metformin treatment could promote ΔFosB degradation and thus attenuate the development of LID through activating the AMPK-mediated autophagy pathway. Overall, our results support the AMPK-mediated autophagy pathway as a novel therapeutic target for LID and also indicate that metformin is a promising therapeutic candidate for LID.

Triple dissociation of visual, auditory and motor processing in mouse primary visual cortex.

Primary sensory cortices respond to crossmodal stimuli-for example, auditory responses are found in primary visual cortex (V1). However, it remains unclear whether these responses reflect sensory inputs or behavioral modulation through sound-evoked body movement. We address this controversy by showing that sound-evoked activity in V1 of awake mice can be dissociated into auditory and behavioral components with distinct spatiotemporal profiles. The auditory component began at approximately 27 ms, was found in superficial and deep layers and originated from auditory cortex. Sound-evoked orofacial movements correlated with V1 neural activity starting at approximately 80-100 ms and explained auditory frequency tuning. Visual, auditory and motor activity were expressed by different laminar profiles and largely segregated subsets of neuronal populations. During simultaneous audiovisual stimulation, visual representations remained dissociable from auditory-related and motor-related activity. This three-fold dissociability of auditory, motor and visual processing is central to understanding how distinct inputs to visual cortex interact to support vision.

Effects of stepped speech rehabilitation and psychological intervention on speech disorders and cognitive function in Parkinson disease patients

To examine the impact of stepwise speech rehabilitation exercise therapy in the treatment of patients with Parkinson speech problems under psychological intervention on clinical results and cognitive functioning. Parkinson speech disorder patients who met the inclusion criteria were selected and divided into a control group and an observation group for training respectively. The control group used conventional nursing methods, including training in orofacial movement, vocalization, pitch, volume and breath control. The observation group used stepwise speech rehabilitation exercise intervention combined with psychotherapy nursing programme. In the statistical analysis, independent sample t-test and chi-square test were used to test the significance of the data processing methods. In the statistical analysis of baseline functional level (P > .05). The difference was not statistically significant. After 7 weeks of training, the mFDA level and speech intelligibility increased in both the observation and control groups. From the situation analysis of “modified drinking test” and the comparison of UPDRS-I scores, it can be seen that dysphagia and Parkinson dysphasia were reduced in both groups after training. The observation group spontaneous speech dimension was greater than the control group by around 0.07 in the aphasia comparison. Both groups displayed an upward trend in their MMSE and Montreal Cognitive Assessment (MoCA) when measuring cognitive function; the evaluation of P300, constructive function, and quality of life revealed this. The observation group P300 potential score was 0.13 points higher than that of the control group. The therapeutic training of stepped speech rehabilitation exercise care combined with psychological intervention has significant nursing effects on patients with Parkinson disease speech disorders, and the patients’ cognitive functions have been effectively improved.

Adult Onset of Pyruvate Dehydrogenase Deficiency Presenting with Dystonia and Chorea in Female Patient from India - A Very Rare Case

We reported a very rare case of pyruvate dehydrogenase complex E1α (PDHA1) gene deficiency presenting as cervical dystonia and chorea in an adult female patient from India. Patient was presented with a history of involuntary rhythmic repetitive movements of both hands, legs, and head, lips and stammering of speech with tilting of neck to one side along with orofacial dyskinetic movements since past 6 years and gait changes since past 4 years. Her symptoms were progressive in nature. Her physical examination and systemic examinations were normal. Neurological examinations suggestive of cervical dystonia with chorea form movements. Brain MRI investigations revealed marked atrophy of bilateral caudate nuclei and putamina. Patient had a familial history of father and second brother had mild hand tremors. Patient has been referred for whole exome sequencing. The exome data analysis identified a very rare and unusual heterozygous indel variant c.-20_-19delinsCT, (chrX:19344018_19344019delinsCT) in 5’UTR region of PDHA1 gene caused late phenotypic onset of cervical dystonia as major clinical manifestation of PDHA1 deficiency along with chorea form movement disorders at the age of 24 year. In conclusion, to the best of our literature knowledge this is the novel and unusual case of adult female patient wherein we are reporting a novel heterozygous indel variant c.-20_-19delinsCT, (chrX:19344018_19344019delinsCT) in 5’UTR region of PDHA1 gene responsible for PDHA1 deficiency presenting with cervical dystonia and chorea as major clinical manifestations. Hence, dystonia and chorea as major clinical manifestations of PDH deficiency could be considered in adult patients also rather than only in paediatric patients.

Mesotrode chronic simultaneous mesoscale cortical imaging and subcortical or peripheral nerve spiking activity recording in mice.

Brain function originates from hierarchical spatial-temporal neural dynamics distributed across cortical and subcortical networks. However, techniques available to assess large-scale brain network activity with single-neuron resolution in behaving animals remain limited. Here, we present Mesotrode that integrates chronic wide-field mesoscale cortical imaging and compact multi-site cortical/subcortical cellular electrophysiology in head-fixed mice that undergo self-initiated running or orofacial movements. Specifically, we harnessed the flexibility of chronic multi-site tetrode recordings to monitor single-neuron activity in multiple subcortical structures while simultaneously imaging the mesoscale activity of the entire dorsal cortex. A mesoscale spike-triggered averaging procedure allowed the identification of cortical activity motifs preferentially associated with single-neuron spiking. Using this approach, we were able to characterize chronic single-neuron-related functional connectivity maps for up to 60 days post-implantation. Neurons recorded from distinct subcortical structures display diverse but segregated cortical maps, suggesting that neurons of different origins participate in distinct cortico-subcortical pathways. We extended the capability of Mesotrode by implanting the micro-electrode at the facial motor nerve and found that facial nerve spiking is functionally associated with the PTA, RSP, and M2 network, and optogenetic inhibition of the PTA area significantly reduced the facial movement of the mice. These findings demonstrate that Mesotrode can be used to sample different combinations of cortico-subcortical networks over prolonged periods, generating multimodal and multi-scale network activity from a single implant, offering new insights into the neural mechanisms underlying specific behaviors.

Mesotrode allows chronic simultaneous mesoscale cortical imaging and subcortical or peripheral nerve spiking activity recording in mice

Brain function originates from hierarchical spatial-temporal neural dynamics distributed across cortical and subcortical networks. However, techniques available to assess large-scale brain network activity with single-neuron resolution in behaving animals remain limited. Here, we present Mesotrode that integrates chronic wide-field mesoscale cortical imaging and compact multi-site cortical/subcortical cellular electrophysiology in head-fixed mice that undergo self-initiated running or orofacial movements. Specifically, we harnessed the flexibility of chronic multi-site tetrode recordings to monitor single-neuron activity in multiple subcortical structures while simultaneously imaging the mesoscale activity of the entire dorsal cortex. A mesoscale spike-triggered averaging procedure allowed the identification of cortical activity motifs preferentially associated with single-neuron spiking. Using this approach, we were able to characterize chronic single-neuron-related functional connectivity maps for up to 60 days post-implantation. Neurons recorded from distinct subcortical structures display diverse but segregated cortical maps, suggesting that neurons of different origins participate in distinct cortico-subcortical pathways. We extended the capability of Mesotrode by implanting the micro-electrode at the facial motor nerve and found that facial nerve spiking is functionally associated with the PTA, RSP, and M2 network, and optogenetic inhibition of the PTA area significantly reduced the facial movement of the mice. These findings demonstrate that Mesotrode can be used to sample different combinations of cortico-subcortical networks over prolonged periods, generating multimodal and multi-scale network activity from a single implant, offering new insights into the neural mechanisms underlying specific behaviors.

Layer 5 Intratelencephalic Neurons in the Motor Cortex Stably Encode Skilled Movement.

The primary motor cortex (M1) and the dorsal striatum play a critical role in motor learning and the retention of learned behaviors. Motor representations of corticostriatal ensembles emerge during motor learning. In the coordinated reorganization of M1 and the dorsal striatum for motor learning, layer 5a (L5a) which connects M1 to the ipsilateral and contralateral dorsal striatum, should be a key layer. Although M1 L5a neurons represent movement-related activity in the late stage of learning, it is unclear whether the activity is retained as a memory engram. Here, using Tlx3-Cre male transgenic mice, we conducted two-photon calcium imaging of striatum-projecting L5a intratelencephalic (IT) neurons in forelimb M1 during late sessions of a self-initiated lever-pull task and in sessions after 6 d of nontraining following the late sessions. We found that trained male animals exhibited stable motor performance before and after the nontraining days. At the same time, we found that M1 L5a IT neurons strongly represented the well-learned forelimb movement but not uninstructed orofacial movements. A subset of M1 L5a IT neurons consistently coded the well-learned forelimb movement before and after the nontraining days. Inactivation of M1 IT neurons after learning impaired task performance when the lever was made heavier or when the target range of the pull distance was narrowed. These results suggest that a subset of M1 L5a IT neurons continuously represent skilled movement after learning and serve to fine-tune the kinematics of well-learned movement.SIGNIFICANCE STATEMENT Motor memory persists even when it is not used for a while. IT neurons in L5a of the M1 gradually come to represent skilled forelimb movements during motor learning. However, it remains to be determined whether these changes persist over a long period and how these neurons contribute to skilled movements. Here, we show that a subset of M1 L5a IT neurons retain information for skilled forelimb movements even after nontraining days. Furthermore, suppressing the activity of these neurons during skilled forelimb movements impaired behavioral stability and adaptability. Our results suggest the importance of M1 L5a IT neurons for tuning skilled forelimb movements over a long period.

A high-performance neuroprosthesis for speech decoding and avatar control.

Speech neuroprostheses have the potential to restore communication to people living with paralysis, but naturalistic speed and expressivity are elusive1. Here we use high-density surface recordings of the speech cortex in a clinical-trial participant with severe limb and vocal paralysis to achieve high-performance real-time decoding across three complementary speech-related output modalities: text, speech audio and facial-avatar animation. We trained and evaluated deep-learning models using neural data collected as the participant attempted to silently speak sentences. For text, we demonstrate accurate and rapid large-vocabulary decoding with a median rate of 78 words per minute and median word error rate of 25%. For speech audio, we demonstrate intelligible and rapid speech synthesis andpersonalizationto the participant's pre-injury voice. For facial-avatar animation, we demonstrate the control of virtual orofacial movements for speech and non-speech communicative gestures. The decoders reached high performance with less than two weeks of training. Our findings introduce a multimodal speech-neuroprosthetic approach that has substantial promise to restore full, embodied communication to people living with severe paralysis.

How 'visual' is the visual cortex? The interactions between the visual cortex and other sensory, motivational and motor systems as enabling factors for visual perception.

The definition of the visual cortex is primarily based on the evidence that lesions of this area impair visual perception. However, this does not exclude that the visual cortex may process more information than of retinal origin alone, or that other brain structures contribute to vision. Indeed, research across the past decades has shown that non-visual information, such as neural activity related to reward expectation and value, locomotion, working memory and other sensory modalities, can modulate primary visual cortical responses to retinal inputs. Nevertheless, the function of this non-visual information is poorly understood. Here we review recent evidence, coming primarily from studies in rodents, arguing that non-visual and motor effects in visual cortex play a role in visual processing itself, for instance disentangling direct auditory effects on visual cortex from effects of sound-evoked orofacial movement. These findings are placed in a broader framework casting vision in terms of predictive processing under control of frontal, reward- and motor-related systems. In contrast to the prevalent notion that vision is exclusively constructed by the visual cortical system, we propose that visual percepts are generated by a larger network-the extended visual system-spanning other sensory cortices, supramodal areas and frontal systems. This article is part of the theme issue 'Decision and control processes in multisensory perception'.

Neural mechanisms underlying uninstructed orofacial movements during reward-based learning behaviors

During reward-based learning tasks, animals make orofacial movements that globally influence brain activity at the timings of reward expectation and acquisition. These orofacial movements are not explicitly instructed and typically appear along with goal-directed behaviors. Here, we show that reinforcing optogenetic stimulation of dopamine neurons in the ventral tegmental area (oDAS) in mice is sufficient to induce orofacial movements in the whiskers and nose without accompanying goal-directed behaviors. Pavlovian conditioning with a sensory cue and oDAS elicited cue-locked and oDAS-aligned orofacial movements, which were distinguishable by a machine-learning model. Inhibition or knockout of dopamine D1 receptors in the nucleus accumbens inhibited oDAS-induced motion but spared cue-locked motion, suggesting differential regulation of these two types of orofacial motions. In contrast, inactivation of the whisker primary motor cortex (wM1) abolished both types of orofacial movements. We found specific neuronal populations in wM1 representing either oDAS-aligned or cue-locked whisker movements. Notably, optogenetic stimulation of wM1 neurons successfully replicated these two types of movements. Our results thus suggest that accumbal D1-receptor-dependent and -independent neuronal signals converge in the wM1 for facilitating distinct uninstructed orofacial movements during a reward-based learning task.

Disentangling Effects of Memory Storage and Inter-articulator Coordination on Generalization in Speech Motor Sequence Learning.

Generalization in motor control is the extent to which motor learning affects movements in situations different than those in which it originally occurred. Recent data on orofacial speech movements indicates that motor sequence learning generalizes to novel syllable sequences containing phonotactically illegal, but previously practiced, consonant clusters. Practicing an entire syllable, however, results in even larger performance gains compared to practicing just its clusters. These patterns of generalization could reflect language-general changes in phonological memory storage and/or inter-articulator coordination during motor sequence learning. To disentangle these factors, we conducted two experiments in which talkers intensively practiced producing novel syllables containing illegal onset and coda clusters over two consecutive days. During the practice phases of both experiments, we observed that, through repetition, talkers gradually produced the syllables with fewer errors, indicative of learning. After learning, talkers were tested for generalization to single syllables (Experiment 1) or syllable pairs (Experiment 2) that overlapped to varying degrees with the practiced syllables. Across both experiments, we found that performance improvements from practicing syllables with illegal clusters partially generalized to novel syllables that contained those clusters, but performance was more error prone if the clusters occurred in a different syllable position (onset versus coda) as in practice, demonstrating that inter-articulator coordination is contextually sensitive. Furthermore, changing the position of a cluster was found to be more deleterious to motor performance during the production of the second syllables in syllable pairs, which required talkers to store more phonological material in memory prior to articulation, compared to single syllables. This interaction effect reveals a complex interplay between memory storage and inter-articulator coordination on generalization in speech motor sequence learning.

Behavioral assessment scale of consciousness for nonhuman primates: A Delphi study.

Nonhuman primates (NHPs) are suitable for being model animals in the study of consciousness and loss of consciousness (LoC) with a similar brain structure and function to humans. However, there is no effective consciousness assessment scale for them. This study aimed to develop a behavioral assessment scale of consciousness for NHPs. We constructed an initial indicator framework based on the clinical consciousness disorder assessment scales and the physiological characteristics, consciousness, and arousal behavior of NHPs. A two-round online Delphi method was conducted by a multidisciplinary expert panel to construct a behavioral assessment scale of consciousness for NHPs. The indicators and descriptions were revised according to the experts' feedback and then sent out for repeated consultations along with a summary of the results of the previous round of consultations. The accepted competencies of indicators were established with mean scores in two scoring criteria (importance and feasibility) ≥4.0, agreement rate with a rating of importance or essential ≥70.0%, and a coefficient of variation ≤0.25, as well as discussions of the research group. Consensus was achieved after the second round of consultations, which was completed by 28 experts who specialized in rehabilitation, neuroscience, psychology, neurosurgery, and neurology. A new behavioral assessment scale of consciousness for NHPs, including 37 items organized hierarchically within seven dimensions including visual function, auditory function, motor function, orofacial movements, arousal, brainstem reflexes, and respiration, was developed in this study. This study has successfully developed a behavioral assessment scale for measuring the conscious state of NHPs or NHP models with LoC. This tool is expected to facilitate future research into the underlying mechanisms of consciousness by providing a detailed and comprehensive means of measurement.

Modulation of reflex responses of the anterior and posterior bellies of the digastric muscle in freely moving rats.

Chewing and licking are primarily activated by central pattern generator (CPG) neuronal circuits in the brainstem and when activated trigger repetitive rhythmic orofacial movements such as chewing, licking and swallowing. These CPGs are reported to modulate orofacial reflex responses in functions such as chewing. This study explored the modulation of reflex responses in the anterior and posterior bellies (ant-Dig and post-Dig, respectively) of the digastric muscle evoked by low-intensity trigeminal stimulation in conscious rats. The ant-Dig and post-Dig reflexes were evoked by using low-intensity electrical stimulation applied to either the right or left inferior alveolar nerve. Peak-to-peak amplitudes and onset latencies were measured. No difference was observed between threshold and onset latency for evoking ant-Dig and post-Dig reflexes, suggesting that the latter was also evoked disynaptically. The peak-to-peak amplitude of both reflexes was significantly reduced during chewing, licking and swallowing as compared to resting period and was lowest during the jaw-closing phase of chewing and licking. Onset latency was significantly largest during the jaw-closing phase. Inhibitory level was similar between the ant-Dig and post-Dig reflex responses and between the ipsilateral and contralateral sides. These results suggest that both the ant-Dig and post-Dig reflex responses were significantly inhibited, probably due to CPG activation during feeding behaviours to maintain coordination of jaw and hyoid movements and hence ensure smooth feeding mechanics.

Dystonia as Presenting Feature of Compound Heterozygous PMPCA Gene Variants.

Video 1. This video shows the patient at 24 years. Dystonia is generalized, particularly severe at cranio-cervical level, but also involving the upper limbs. Speech is severely impaired. The clip shows involuntary orofacial movements, jaw-opening and tongue protrusion dystonia. At cervical level, there are abnormal postures and torsional movements relieved by a sensory trick (touching the chin with the left hand). Upper limb involvement is prevalent in the right arm with writer's cramp and evidence of mirror dystonia. Gait is broad-based with evident right foot dystonia accentuated by walking. Video 2. Video taken at home at age 29, three months after bilateral GPi implant. Dystonia has progressed. Facial grimaces are continuous, there is constantly flexed neck posture with head tilt to the right and rotational movements. Speech is not intelligible. Dystonic slowing is evident upon repetitive finger and foot tapping. There is bilateral dysmetria in the upper limbs. Sensory tricks (touching of eyelids) provides inconstant relief. The patient is unable to write. Diffuse muscle atrophy is evident, with normal strength. Deep tendon reflexes are brisk bilaterally. The patient is able to stand-up unassisted and uses a walker due to severe gait ataxia. Standing posture is characterized by severe neck and trunk flexion. Gait is wide-based with cock-walk appearance. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.