Rhythmic Motor Research Articles

Speaking rhythmically can shape hearing.

Evidence suggests that temporal predictions arising from the motor system can enhance auditory perception. However, in speech perception, we lack evidence of perception being modulated by production. Here we show a behavioural protocol that captures the existence of such auditory-motor interactions. Participants performed a syllable discrimination task immediately after producing periodic syllable sequences. Two speech rates were explored: a 'natural' (individually preferred) and a fixed 'non-natural' (2 Hz) rate. Using a decoding approach, we show that perceptual performance is modulated by the stimulus phase determined by a participant's own motor rhythm. Remarkably, for 'natural' and 'non-natural' rates, this finding is restricted to a subgroup of the population with quantifiable auditory-motor coupling. The observed pattern is compatible with a neural model assuming a bidirectional interaction of auditory and speech motor cortices. Crucially, the model matches the experimental results only if it incorporates individual differences in the strength of the auditory-motor connection.

Photocontrol of Endogenous Glycine Receptors In Vivo

Glycine receptors (GlyRs) are indispensable for maintaining excitatory/inhibitory balance in neuronal circuits that control reflexes and rhythmic motor behaviors. Here we have developed Glyght, a GlyR ligand controlled with light. It is selective over other Cys-loop receptors, is active invivo, and displays an allosteric mechanism of action. The photomanipulation of glycinergic neurotransmission opens new avenues to understanding inhibitory circuits in intact animals and to developing drug-based phototherapies.

Effect of Stress on Autonomic and Cardiovascular Systems in Military Population: A Systematic Review.

Stress is regulated by the autonomous nervous system, increasing the sympathetic modulation when a threat is perceived. A multifactorial response usually leads to significant behavioural modifications and alterations on homeostasis and physical and psychological status. Moreover, stress is an emotional response that can lead to psychosocial and psychophysiological adversity. Regarding military population, military operations and combat exposure are important stressors that influence acute and chronic stress response in soldiers, affecting their performance and health. A bibliographic search was carried out between April and May 2019, focusing on recent studies (2013–2019) that analysed psychophysiological response, stress, stress regulation, heart rate, heart rate variability, and posttraumatic stress disorder in military population. Autonomic and cardiovascular chronic stress seems to be modulated by experience and previous specific training of each military unit. Physical exercise, music embedded with binaural beat technology, bidirectional sensory motor rhythm training, heart rate variability biofeedback, and transcutaneous vagal nerve stimulation are the main techniques applied to balance stress and to recover body homeostasis. Since military population are usually exposed to multiple stressors, knowing previous training and experience, together with developing techniques to balance stress, is the main practical application in this field of study to balance autonomic and cardiovascular systems.

Cerebral Substrates for Controlling Rhythmic Movements.

Our daily lives are filled with rhythmic movements, such as walking, sports, and dancing, but the mechanisms by which the brain controls rhythmic movements are poorly understood. In this review, we examine the literature on neuropsychological studies of patients with focal brain lesions, and functional brain imaging studies primarily using finger-tapping tasks. These studies suggest a close connection between sensory and motor processing of rhythm, with no apparent distinction between the two functions. Thus, we conducted two functional brain imaging studies to survey the rhythm representations relatively independent of sensory and motor functions. First, we determined brain activations related to rhythm processing in a sensory modality-independent manner. Second, we examined body part-independent brain activation related to rhythm reproduction. Based on previous literature, we discuss how brain areas contribute rhythmic motor control. Furthermore, we also discuss the mechanisms by which the brain controls rhythmic movements.

Testing the stability of 'Default' motor and auditory-perceptual rhythms-A replication failure dataset.

Several studies have found that the motor rhythms that individuals produce spontaneously, for example during finger tapping, clapping or walking, are also rated perceptually as ‘very comfortable’ to listen to. This motivated proposal of the Preferred Period Hypothesis, suggesting that individuals have a characteristic preferred rhythm, that generalizes across perception and production.However, some of the experimental procedures used previously raise two methodological concerns: First, in many of these studies, the rhythms used for assessment of participants’ Perceptual Preferred Tempo (PPT) were tailored specifically around each participant's personal Spontaneous Motor Tempo (SMT). This may have biased results toward the central rhythm used, artificially increasing the similarity between spontaneous motor and auditory perceptual preferences. Second, a key prediction of the Preferred Period Hypothesis is that the same default rhythms are repeatedly found within-subject. However, measures of consistency are seldom reported, and increased within-subject variability has sometimes been used to exclude participants.The current study was an attempt to replicate reports of a correspondence between motor and perceptual rhythms, and closely followed previous experimental protocols by conducting three tasks: SMT was evaluated by instructing participants to tap ‘at their most comfortable rate’; PPT was assessed by asking participants to rate a 10 different rhythms according to how ‘comfortable’ they were; and motor-replication of rhythms was assessed using a Synchronization-Continuation task, over a wide range of rhythms.However, in contrast to previous studies, for all participants we use the same 10 perceptual rhythms in both the PPT and Synchronization-Continuation task, irrespective of their SMT. Moreover, we assessed and report measures of within- and between-trial consistency, in order to evaluate whether participants gave similar rating and produced similar motor rhythms across multiple sessions throughout the experiment.The data presented here fail to show any correlation between motor and perceptual preferences, nor do they support improved synchronization-continuation performance near an individual's so-called SMT or PPT. Rather, they demonstrate substantial within-subject variability in the spontaneous motor rhythms produced across repeated sessions, as well as their subjective rating of perceived rhythms. This report accompanies our article “Spontaneous and Stimulus-Driven Rhythmic Behaviors in ADHD Adults and Controls”[1], and provided motivation and insight for modifying the procedures used for SMT and PPT evaluation, and their interpretation.

The Role of Motor and Environmental Visual Rhythms in Structuring Auditory Cortical Excitability.

SummaryPrevious studies indicate that motor sampling patterns modulate neuronal excitability in sensory brain regions by entraining brain rhythms, a process termed motor-initiated entrainment. In addition, rhythms of the external environment are also capable of entraining brain rhythms. Our first goal was to investigate the properties of motor-initiated entrainment in the auditory system using a prominent visual motor sampling pattern in primates, saccades. Second, we wanted to determine whether/how motor-initiated entrainment interacts with visual environmental entrainment. We examined laminar profiles of neuronal ensemble activity in primary auditory cortex and found that whereas motor-initiated entrainment has a suppressive effect, visual environmental entrainment has an enhancive effect. We also found that these processes are temporally coupled, and their temporal relationship ensures that their effect on excitability is complementary rather than interfering. Altogether, our results demonstrate that motor and sensory systems continuously interact in orchestrating the brain's context for the optimal sampling of our multisensory environment.

Spontaneous and stimulus-driven rhythmic behaviors in ADHD adults and controls

Many aspects of human behavior are inherently rhythmic, requiring production of rhythmic motor actions as well as synchronizing to rhythms in the environment. It is well-established that individuals with ADHD exhibit deficits in temporal estimation and timing functions, which may impact their ability to accurately produce and interact with rhythmic stimuli. In the current study we seek to understand the specific aspects of rhythmic behavior that are implicated in ADHD. We specifically ask whether they are attributed to imprecision in the internal generation of rhythms or to reduced acuity in rhythm perception. We also test key predictions of the Preferred Period Hypothesis, which suggests that both perceptual and motor rhythmic behaviors are biased towards a specific personal ‘default’ tempo. To this end, we tested several aspects of rhythmic behavior and the correspondence between them, including spontaneous motor tempo (SMT), preferred auditory perceptual tempo (PPT) and synchronization-continuations tapping in a broad range of rhythms, from sub-second to supra-second intervals. Moreover, we evaluate the intra-subject consistency of rhythmic preferences, as a means for testing the reality and reliability of personal ‘default-rhythms’. We used a modified operational definition for assessing SMT and PPT, instructing participants to tap or calibrate the rhythms most comfortable for them to count along with, to avoid subjective interpretations of the task. Our results shed new light on the specific aspect of rhythmic deficits implicated in ADHD adults. We find that individuals with ADHD are primarily challenged in producing and maintaining isochronous self-generated motor rhythms, during both spontaneous and memory-paced tapping. However, they nonetheless exhibit good flexibility for synchronizing to a broad range of external rhythms, suggesting that auditory-motor entrainment for simple rhythms is preserved in ADHD, and that the presence of an external pacer allows overcoming their inherent difficulty in self-generating isochronous motor rhythms. In addition, both groups showed optimal memory-paced tapping for rhythms near their ‘counting-based’ SMT and PPT, which were slightly faster in the ADHD group. This is in line with the predictions of the Preferred Period Hypothesis, indicating that at least for this well-defined rhythmic behavior (i.e., counting), individuals tend to prefer similar time-scales in both motor production and perceptual evaluation.

Cognitive and Social Rehabilitation in Schizophrenia-From Neurophysiology to Neuromodulation. Pilot Study.

The aim of this pilot study was to analyse the influence of Galvanic Skin Response (GSR) Biofeedback training in a group of 18 men with schizophrenia at the remission stage. The results were verified according to: Positive and Negative Syndrome Scale (PANSS), Acceptance of Illness Scale (AIS), Self-efficacy Scale (GSES), Beck Cognitive Insight Scale (BCIS) scales, Colour Trial Test (CTT-1, CTT-2), d2 psychological tests, Quantitative Electroencephalogram (QEEG) Biofeedback, auditory event-related potentials (ERPs), and serum levels of brain-derived neurotrophic factor (BDNF). The results were compared in the same patients after 3 months. Statistically significant changes were noted in results for the variables on the PANSS scale. For the BDNF variable, a statistically significant increase occurred, indicating that GSR Biofeedback training may influence serum levels of the neurotrophic factor. Statistically significant changes were noted in results for the variables on the BCIS, AIS, and GSES indicating an improvement in the cognitive and social functioning. Changes were noted for results for theta/beta and theta/Sensory Motor Rhythm (SMR) ratios, which indicate an improvement in concentration and attention. Changes were noted for the N1 wave amplitude in the frontal brain region (F-z), and for the P2 wave latency in the central brain region (C-z), which indicates an improvement in the initial perceptual analysis. The use of GSR Biofeedback in a group of patients with schizophrenia gives interesting results, but requires further in-depth research.

Reduce brain computer interface inefficiency by combining sensory motor rhythm and movement-related cortical potential features

Objective. Brain Computer Interface (BCI) inefficiency indicates that there would be 10% to 50% of users are unable to operate Motor-Imagery-based BCI systems. Importantly, the almost all previous studieds on BCI inefficiency were based on tests of Sensory Motor Rhythm (SMR) feature. In this work, we assessed the occurrence of BCI inefficiency with SMR and Movement-Related Cortical Potential (MRCP) features. Approach. A pool of datasets of resting state and movements related EEG signals was recorded with 93 subjects during 2 sessions in separated days. Two methods, Common Spatial Pattern (CSP) and template matching, were used for SMR and MRCP feature extraction, and a winner-take-all strategy was applied to assess pattern recognition with posterior probabilities from Linear Discriminant Analysis to combine SMR and MRCP features. Main results. The results showed that the two types of features showed high complementarity, in line with their weak intercorrelation. In the subject group with poor accuracies (< 70%) by SMR feature in the two-class problem (right foot vs. right hand), the combination of SMR and MRCP features improved the averaged accuracy from 62% to 79%. Importantly, accuracies obtained by feature combination exceeded the inefficiency threshold. Significance. The feature combination of SMR and MRCP is not new in BCI decoding, but the large scale and repeatable study on BCI inefficiency assessment by using SMR and MRCP features is novel. MRCP feature provides the similar classification accuracies on the two subject groups with poor (< 70%) and good (> 90%) accuracies by SMR feature. These results suggest that the combination of SMR and MRCP features may be a practical approach to reduce BCI inefficiency. While, ‘BCI inefficiency’ might be more aptly called ‘SMR inefficiency’ after this study.

CPG Control for Harmonic Motion of Assistive Robot With Human Motor Control Identification

Various movements in human life, such as walking, bicycling, cleaning, chewing, swimming, and so on, are periodic or repetitive. This paper proposes a method for designing a feedback controller for a robotic system to help a human with periodic (harmonic, in particular) motion tasks. The control objective is to stabilize a human-intended oscillatory movement while reducing the required human effort. For the control architecture, we adopt the central pattern generator (CPG), which is a neuronal circuit for rhythmic motor pattern. Animal locomotions under CPG control are capable of complying with various environment dynamics to yield different oscillatory movements. We take advantage of this adaptation property of the CPG controller that acts as a nonlinear damping compensator and removes part of the resistive forces in the system, thereby reducing the human effort without interfering with the human intention. It is shown that the resulting human-intended oscillation is a locally stable harmonic solution of the closed-loop human-robot CPG system, assuming a simple model of the human motor control. The proposed control method is experimentally validated for a simple robotic arm, with a system identification of the human motor control.

Co‐modulation of the Na+/K+ pump and hyperpolarization‐activated currents as a mechanism for robust neuromodulation

Specialized oscillatory circuits, central pattern generators (CPGs), control rhythmic motor behaviors such as locomotion and breathing. To accommodate a motor pattern to environmental changes and behavioral goals, neuromodulators adjust the dynamics of CPGs by orchestrating changes in various ionic currents in a wide range of their biophysical parameters to expand temporal characteristics of the functional pattern. Recent studies provide evidence that the Na+/K+ pump contributes to the dynamics of CPGs and is controlled by neuromodulation [1– 4]. In the leech heartbeat CPG, the neuropeptide myomodulin reduces the period of bursting activity by increasing the hyperpolarization‐activated (h)‐current and decreasing the Na+/K+ pump current [4]. The application of myomodulin reduces the period of oscillatory activity by 17%. Application of Cs+, which is an h‐current blocker, increases the period of bursting by 24% relative to control. The application of myomodulin along with Cs+ decreases the period by 12% relative to treatment with Cs+ [4]. Here we investigate how the period of a bursting can be controlled in a wide range while functional bursting is maintained with a focus on the role of the Na+/K+ pump. We also investigate the risk associated with multistability in neuronal dynamics.We optimized a model of the leech heart interneuron (HN), which includes the Na+/K+ pump current and intracellular Na+ dynamics [1] and investigated the activity regimes of pairs of mutually inhibitory coupled HNs forming half‐center oscillators (HCOs). HCOs form the kernel of the leech heartbeat CPG. We investigated eight model variants representing combinations of three experimental treatments: the blockade of chemical synapses representing the application of bicuculline, the blockade of h‐current representing the application of Cs+, and the enhancement of the h‐current and inhibition of the Na+/K+ pump current representing the application of myomodulin. The model captures the qualitative trends in change of cycle period observed in experiments with myomodulin and Cs+. We found ranges of parameters where neurons showed functional bursting. The coordinated changes of maximal conductance of h‐current (Gh) and maximal pump activity (IPumpMax) increases the range of period of functional bursting as well as the range of parameters Gh and IPumpMax. We hypothesize that myomodulin co‐modulates h‐ and pump currents to expand the domain of the functional activity.Support or Funding InformationSupported by NINDS 1 R01 NS085006 to RLC and 1 R21 NS111355 to RLC and GSC.

The Role of Chloride in the Breathing‐related Response to Central Acidosis in Developing Birds

Rhythmic spontaneous neural activity (rSNA) is thought to contribute to the organization and development of motor circuits. In spinal motor networks, rSNA has a role in synapse refinement, axon trajectory, and the formation of neuromuscular junctions. In the zebra finch embryo, extracellular recordings of hindbrain breathing‐related motor activity also show that rSNA burst pattern, shape, and neurotransmitter signaling change in an age‐dependent manner. Further, the role of chloride‐mediated neurotransmission exhibits a switch in polarity such that GABAergic and glycinergic signaling transitions from excitatory to inhibitory over the course of 24–48 hours. Despite recognizing these ontogenetic changes in hindbrain rSNA, we are just beginning to explore whether the changing physiochemical environment within the eggshell shapes rhythmic motor activity. As a bird embryo grows within the egg, it experiences progressive alterations in respiratory gases (↓PO2, ↑PCO2), an emerging acidosis, as well as modifications to the anatomical structures that facilitate gas exchange. Data show that lowering and raising the pH of the superfusate bathing the isolated avian hindbrain influences breathing‐linked rSNA as a function of age. Embryos employing diffusive gas exchange within the egg show a decreased rate of rSNA, while freely breathing birds employing pulmonary gas exchange show an increased rate of cranial nerve motor output. Given these findings, our objective here was to test mechanisms contributing to this pH response. We speculate that chloride is an important player as a result of three observations: 1) chloride‐mediated neurotransmission shifts in polarity at nearly the same embryonic age as the switch in the rSNA response to low pH; 2) chloride transport is involved in pH homeostasis; 3) GABAA receptors conduct both chloride and hydrogen carbonate, which are tied to pH regulation. To explore the first point, we recorded rSNA and breathing‐related motor rhythms while lowering pH under chloride free conditions. Results show that the removal of chloride eliminates rSNA in embryonic days (E) 4–6 embryos. On E7‐10, chloride removal decreases the rate of motor output compared with low pH alone. Related to the second point, we treated the hindbrain with low pH and bumetanide, an antagonist for the transmembrane sodium‐potassium‐chloride cotransporter (NKCC1). Data show that, compared to controls, the instantaneous frequency increases in E7‐10 birds. To address the third point, we applied the GABAA receptor antagonist picrotoxin (PTX) during low pH treatments. Results show that PTX and low pH treatment decreases rSNA frequency to 49 ± 11% of control in &lt;E11 birds and increases frequency to 129 ± 20% of control at &gt;E11. Together, our results suggest that interfering with chloride gradients and blocking GABAA receptor activity during low pH treatment has consequences for rSNA that are similar to lowering pH alone. In contrast, the inhibition of NKCC1 with bumetanide seems to disrupt the rhythmic response to central acidosis in the zebra finch hindbrain, at least prior to the onset of breathing.Support or Funding InformationIdaho IDeA Network of Biomedical Research and Excellence Program Grant # P20 GM103408 and the National Institute of Neurological Disorders and Stroke via the AREA Program Grant # 1R15NS087521‐01A1.

Neuromodulatory Selection of Motor Neuron Recruitment Patterns in a Visuomotor Behavior Increases Speed.

Animals generate locomotion at different speeds to suit their behavioral needs. Spinal circuits generate locomotion at these varying speeds by sequential activation of different spinal interneurons and motor neurons. Larval zebrafish can generate slow swims for prey capture and exploration by activation of secondary motor neurons and much faster and vigorous swims during escape and struggle via additional activation of primary motor neurons. Neuromodulators are known to alter the motor output of spinal circuits, but their precise role in speed regulation is not wellunderstood. Here, in the context of optomotor response (OMR), an innate evoked locomotor behavior, we show that dopamine (DA) provides an additional layer to regulation of swim speed in larval zebrafish. Activation of D1-like receptors increases swim speed during OMR in free-swimming larvae. By analyzing tail bend kinematics in head-restrained larvae, we show that the increase in speed is actuated by larger tail bends. Whole-cell patch-clamp recordings from motor neurons reveal that, during OMR, typically only secondary motor neurons are active, whereas primary motor neurons are quiescent. Activation of D1-like receptors increases intrinsic excitability and excitatory synaptic drive in primary and secondary motor neurons. These actions result in greater recruitment of motor neurons during OMR. Our findings provide an example of neuromodulatory reconfiguration of spinal motor neuron speed modules where members are selectively recruited and motor drive is increased to effect changes in locomotor speed. VIDEO ABSTRACT.

Relationships Between Distention-, Butyrate- and Pellet-Induced Stimulation of Peristalsis in the Mouse Colon.

Background/AimsLuminal factors such as short-chain fatty acids are increasingly recognized for playing a regulatory role in peristaltic activity. Our objective was to understand the roles of butyrate and propionate in regulating peristaltic activity in relation to distention-induced activities.MethodsButyrate and propionate were perfused intraluminally under varying intraluminal pressures in murine colons bathed in Krebs solution. We used video recording and spatiotemporal maps to examine peristalsis induced by the intrinsic rhythmic colonic motor complex (CMC) as well as pellet-induced peristaltic reflex movements.ResultsThe CMC showed several configurations at different levels of excitation, culminating in long distance contractions (LDCs) which possess a triangular shape in murine colon spatiotemporal maps. Butyrate increased the frequency of CMCs but was a much weaker stimulus than distention and only contributed to significant changes under low distention. Propionate inhibited CMCs by decreasing either their amplitudes or frequencies, but only in low distention conditions. Butyrate did not consistently counteract propionate-induced inhibition likely due to the multiple and distinct mechanisms of action for these signaling molecules in the lumen. Pellet movement occurred through ongoing CMCs as well as pellet induced peristaltic reflex movements and butyrate augmented both types of peristaltic motor patterns to decrease the amount of time required to expel each pellet.ConclusionsButyrate is effective in promoting peristalsis, but only when the level of colonic activity is low such as under conditions of low intraluminal pressure. This suggests that it may play a significant role in patients with poor fiber intake, where there is low mechanical stimulation in the lumen.

Identification of putative neuropeptidergic signaling systems in the spiny lobster, Panulirus argus.

Members of the decapod infraorder Achelata, specifically species from the genus Panulirus, have storied histories as models for investigating the basic principles governing the generation, maintenance, and modulation of rhythmic motor behavior, including modulation by locally released and circulating peptides. Despite their contributions to our understanding of peptidergic neuromodulation, little is known about the identity of the native neuropeptides and neuronal peptide receptors present in these crustaceans. Here, a Panulirus argus nervous system-specific transcriptome was used to help fill this void, providing insight into the neuropeptidome and neuronal peptide receptome of this species. A neuropeptidome consisting of 266 distinct peptides was predicted using the P. argus assembly, 128 having structures placing them into a generally recognized arthropod peptide family: agatoxin-like peptide, allatostatin A (AST-A), allatostatin B, allatostatin C, bursicon, CCHamide, crustacean cardioactive peptide, crustacean hyperglycemic hormone/molt-inhibiting hormone, diuretic hormone 31 (DH31), ecdysis-triggering hormone (ETH), FMRFamide-like peptide (FLP), glycoprotein hormone (GPH), GSEFLamide, inotocin, leucokinin, myosuppressin, natalisin, neuroparsin, neuropeptide F, orcokinin, orcomyotropin, periviscerokinin, pigment-dispersing hormone, pyrokinin, red pigment-concentrating hormone, RYamide, short neuropeptide F (sNPF), SIFamide, sulfakinin, tachykinin-related peptide (TRP), and trissin. Twenty-five putative neuronal receptors, encompassing 15 peptide groups, were also identified from the P. argus transcriptome: AST-A, bursicon, CCHamide, DH31, diuretic hormone 44, ETH, FLP, GPH, inotocin, insulin-like peptide, myosuppressin, natalisin, periviscerokinin, sNPF, and TRP. Collectively, the reported data provide a powerful resource for expanding studies of neuropeptidergic control of physiology and behavior in members of the genus Panulirus specifically, and decapods generally.

Phase-Specific Motor Efference during a Rhythmic Motor Pattern.

Neuronal circuits that control motor behaviors orchestrate multiple tasks, including the inhibition of self-generated sensory signals. In the hermaphroditic leech, T and P mechanosensory neurons respond to light touch and pressure on the skin, respectively. We show that the low threshold T cells were also sensitive to topological changes of the animal surface, caused by contraction of the muscles that erect the skin annuli. P cells were unresponsive to this movement. Annuli erection is part of the contraction phase of crawling, a leech locomotive behavior. In isolated ganglia, T cells showed phase-dependent IPSPs during dopamine-induced fictive crawling, whereas P cells were unaffected. The timing and magnitude of the T-IPSPs were highly correlated with the activity of the motoneurons excited during the contraction phase. Together, the results suggest that the central network responsible for crawling sends a reafferent signal onto the T cells, concomitant with the signal to the motoneurons. This reafference is specifically targeted at the sensory neurons that are affected by the movements; and it is behaviorally relevant as excitation of T cells affected the rhythmic motor pattern, probably acting upon the rhythmogenic circuit. Corollary discharge is a highly conserved function of motor systems throughout evolution, and we provide clear evidence of the specificity of its targets and timing and of the benefit of counteracting self-generated sensory input.SIGNIFICANCE STATEMENT Neuronal circuits that control motor behaviors orchestrate multiple tasks, including inhibition of sensory signals originated by the animal movement, a phenomenon known as corollary discharge. Leeches crawl on solid surfaces through a sequence of elongation and contraction movements. During the contraction, the skin topology changes, affecting a subpopulation of mechanosensory receptors, T (touch) neurons, but not P (pressure) sensory neurons. In the isolated nervous system, T neurons were inhibited during the contraction but not during the elongation phase, whereas P cells were unaffected throughout crawling. Excitation of T cells during the contraction phase temporarily disrupted the rhythmic pattern. Thus, corollary discharge was target (T vs P) and phase (contraction vs elongation) specific, and prevented self-generated signals to perturb motor behaviors.

P057 WIRELESS ELECTRODE PATCHES SHOW INTRAPATIENT REPRODUCIBILITY IN A LONGITUDINAL STUDY OF PATIENTS WITH CROHN’S DISEASE IN REMISSION

Abstract Background Crohn’s disease (CD) patients would benefit from a non-invasive indicator of gut function to better predict changes in disease state, such as the onset of flare. A study of CD patients using non-invasive wireless electrode patches (G-Tech Medical, Mountain View, CA) that read myoelectric signals from the gut over 3 days is underway at Stanford University’s IBD center. The study will include 40 patients presenting in flare and 30 in remission to be tested at t=0, 1, 3 and 6 months. In addition, one-time tests will be performed on 20 healthy controls. Aims Herein, we report on the first 6 CD patients tested at t=0 and 1 month while in remission. Methods Each patient wore 3 abdominal patches (each 2.7” diameter) for 3 consecutive days while pursuing regular daily activities and meals (Figure 1). Each patch recorded 4 channels of myoelectric activity from the stomach, small intestine and colon, and transmitted the raw data to an iPod Touch, which relayed the data to a secure cloud server. Data were later downloaded and processed to remove artifacts, create frequency spectra, and search them for peaks representing rhythmic motor activity. We find that, nominally, stomach activity appears at 3 cycles/minute (cpm), small intestine at 6–12 cpm, and colon at 12–25 cpm. Results Figure 2 shows peak spectra for the 6 patients at t=0 and 1 month. Individual peaks represent motor activity at a specific frequency associated with the stomach, small intestine, or colon. Each patient has a unique overall pattern, or GutPrint, reflecting the frequencies and levels of activity of their GI motility. The GutPrint for each individual reproduces well at the second test and is easily recognizable for each subject. Although the peak amplitudes may vary, virtually all of the peaks that appear at specific frequencies at t=0 are also present at 1 month representing a quantifiable signature that reflects each patient’s unique motility. Conclusion The G-Tech patch system provides a practical and noninvasive, physiologic means of measuring motor activity of the gut over multiple days. Its intra-patient reproducibility allows for the possibility of measuring changes to gut performance over time, whether naturally- or drug-induced, showing promise in CD monitoring.

Facilitation of microglial motility by thyroid hormones requires the presence of neurons in cell culture: A distinctive feature of the brainstem versus the cortex

Microglia are critical for the refinement of neural networks that takes place during the perinatal period. Their phenotype and actions are guided by the signals produced by neighbouring cells and hormones present in their surrounding milieu. Cell populations and the signals they produce differ between regions. The fact that thyroid hormones (THs) promote the growth and morphological differentiation of microglia within the cortex contributes to the TH’s powerful actions on the developing brain. The brainstem is especially active during early life owing to its role in generation of the rhythmic respiratory motor command. Despite evidences indicating that THs are necessary to proper development of the neural networks regulating this vital homeostatic function, their actions on microglia originating from the brainstem remain unknown. Using primary cultured microglia from newborn mice (C57BL/6J), we first report that regulation of microglial motility by THs is different between cortex and brainstem. Microglial motility (μm traveled over 3 h) was monitored with or without triiodothyronine (T3, 1μM). Exposure to T3 did not stimulate microglial motility from brainstem, but significantly stimulated (316 %) when they were co-cultured with neurons. Motility of cortex microglia was stimulated to the similar extent either with or without neurons. These data suggest that the microglial function in different regions of the brain is determined by the surrounding environment.

PECULIARITIES OF MOTOR AND SPEECH RHYTHMIC PROCESSES FORMATION IN CHILDREN OF SENIOR PRESCHOOL AGE WITH STUTTERING BY MEANS OF LOGORHYTHMIC EXERCISES

The scientific article proves that the functional aspects of motor-speech development in senior preschool children with stuttering are closely related to the basic morphofunctional provision of motor skills and speech, which involves activating the cerebral cortex, improving blood supply to the brain, restoring motor and articulatory innervation. By applying a multidisciplinary approach philosophical, psychophysiological, neurobiological, psychological and linguistic aspects of the nature of rhythm were highlighted. Comparative indicators of the level of motor and speech rhythm development were determined before and after performing logarithmic exercises. Theoretical and methodological analysis of the problem of motor and speech rhythms development in children of senior preschool age with stuttering confirmed the assumption about delayed rhythm development in children of this nosological group. The need for a comprehensive study of this issue was the driving force for carrying out the observational experiment, whose purpose was to study the peculiarities of the development of motor and speech rhythms in older preschool children with stuttering. In the process of analyzing the comparative characteristics of the levels of motor and verbal response in senior preschool children with stuttering, it was proved that these two processes develop simultaneously and are interdependent. The retardation of one process leads to the retardation of the other one, which affects the development of children's motor and verbal (speech) rhythm. Comparative characteristics of the formation levels of motor and verbal rhythms in senior preschool children with stuttering before and after correctional and developmental classes show that after performing correctional and developmental exercises there are no children with zero and low levels of reproduction, while medium and sufficient levels of motor reproduction and speech response prevail. This fact experimentally confirmed that the selected correctional and developmental work, conducting of speech therapy and logorhythmic classes aimed at the development of motor and verbal rhythms contributed to a significant improvement in the children’s results.

Orexins modulate membrane excitability in rat trigeminal motoneurons.

Orexins (Oxs) are multifunctional neuropeptides, secreted from the lateral hypothalamus, that stimulate feeding behavior and energy expenditure. In this study, the direct effects of Oxs on the membrane properties of trigeminal motoneurons (TMNs) were examined, which critically participate in the genesis of rhythmical oral motor activities underlying suckling and mastication. Sprague-Dawley rats (3-6 day-old) were used to obtain whole-cell patch-clamp recordings from TMNs. Bath application of Ox-A depolarized the membrane potential and induced inward current, wherein Na+ and Ca2+ were charge carriers. Transient receptor potential channel activation potentially contributed to current and voltage responses by way of Ox-A. Ox-A increased the peak amplitude and duration at half-amplitude of the medium-duration after hyperpolarization following the action potential. The interspike frequency of steady-state firings during repetitive discharge was increased, along with a shift in the frequency-current relationship occurring toward the left. Extracellular and intracellular Ca2+ were involved in regulating modulatory effects, but a requisite level of intracellular Ca2+ was not essential for Ox-induced upregulation of the interspike frequency. Ox-A also enhanced conditional bursting induced by N-methyl-d-aspartate and 5-HT, suggesting it participates in modulating TMNs' discharge patterns during various oral motor activities.