Spinal Reflex Mechanisms Research Articles

Menthol-induced activation of TRPM8 receptors increases cutaneous blood flow across the dermatome.

Topical menthol-based analgesics increase skin blood flow (SkBF) through transient receptor potential melastatin 8 (TRPM8) receptor-dependent activation of sensory nerves and endothelium-derived hyperpolarization factors. It is unclear if menthol-induced TRPM8 activation mediates a reflex change in SkBF across the dermatome in an area not directly treated with menthol. The purpose of this study was to determine the effects of localized topical menthol application on SkBF across a common dermatome. We hypothesized that SkBF would be increased with menthol at the site of application and across the dermatome (contralateral limb) through a spinal reflex mechanism. In a double blind, placebo controlled, cross-over design, 15 healthy participants (7 men; age=22±1yrs) were treated with direct application (3ml over 8×13cm) of 5% menthol gel (Biofreeze™) or placebo gel on the L4 dermatome, separated by 48h. Red blood cell flux was measured using laser Doppler flowmetry over the area of application, on the contralateral leg of the same dermatome, and in a separate dermatome (L5/S1) to serve as control. Cutaneous vascular conductance was calculated for each measurement site (CVC=flux/MAP). At baseline there were no differences in CVC between menthol and placebo gels, or among sites (all p>0.05). After 30±6min, CVC increased at the treated site with menthol (0.12±0.02 vs. 1.36±0.19flux/mmHg, p<0.01) but not the placebo (0.10±0.01 vs. 0.18±0.04flux/mmHg, p=0.91). There was a modest increase in CVC at the contralateral L4 dermatome with menthol gel (0.16±0.04 vs. 0.29±0.06flux/mmHg, p<0.01), but not placebo (0.11±0.02 vs. 0.15±0.03flux/mmHg, p=0.41). There was no effect on SkBF from either treatments at the L5/S1 control dermatome (both, p>0.05), suggesting the lack of a systemic response. In conclusion, menthol containing topical analgesic gels increased SkBF at the treated site, and modestly throughout the dermatome. These data suggest menthol-induced activation of the TRPM8 receptors induces an increase in SkBF across the area of common innervation through a localized spinal reflex mechanism.

An Improved Modeling of Parkinson’s Tremor and Investigation of Some Approaches to Remove this Symptom

In this research, an improved model of Parkinsonian tremor is presented by using a mathematical and computational approach. In Parkinson’s disease (PD), an abnormal signal is produced by basal ganglia (BG). This signal goes to the thalamus, then enters cortex and after interaction with peripheral system goes to muscle and finally appears as tremor. In the presented model, all of the mentioned process are simulated. Also, the skeletal muscle model as well as the central nervous system (basal ganglia, thalamus, cortex and supplementary motor area) and peripheral nervous system (spinal reflex) mechanisms are considered. In addition, two methods for tremor suppression are applied in this paper, 1) deep brain stimulation (DBS) which affects dopamine level in BG and 2) a mechanical method which is based on a negative feedback. The accuracy and efficiency of the presented simulation are demonstrated by comparison of the obtained results with those obtained by clinical tests.

Bilateral and asymmetrical contributions of passive and active ankle plantar flexors stiffness to spasticity in humans with spinal cord injury.

Spasticity is one of the most common symptoms present in humans with spinal cord injury (SCI); however, its clinical assessment remains underdeveloped. The purpose of the study was to examine the contribution of passive muscle stiffness and active spinal reflex mechanisms to clinical outcomes of spasticity after SCI. It is important that passive and active contributions to increased muscle stiffness are distinguished to make appropriate decisions about antispastic treatments and to monitor its effectiveness. To address this question, we combined biomechanical and electrophysiological assessments of ankle plantarflexor muscles bilaterally in individuals with and without chronic SCI. Spasticity was assessed using the Modified Ashworth Scale (MAS) and a self-reported questionnaire. We performed slow and fast dorsiflexion stretches of the ankle joint to measure passive muscle stiffness and reflex-induced torque using a dynamometer and the soleus H reflex using electrical stimulation over the posterior tibial nerve. All SCI participants reported the presence of spasticity. While 96% of them reported higher spasticity on one side compared with the other, the MAS detected differences across sides in only 25% of the them. Passive muscle stiffness and the reflex-induced torque were larger in SCI compared with controls more on one side compared with the other. The soleus stretch reflex, but not the H reflex, was larger in SCI compared with controls and showed differences across sides, with a larger reflex in the side showing a higher reflex-induced torque. MAS scores were not correlated with biomechanical and electrophysiological outcomes. These findings provide evidence for bilateral and asymmetric contributions of passive and active ankle plantar flexors stiffness to spasticity in humans with chronic SCI and highlight a poor agreement between a self-reported questionnaire and the MAS for detecting asymmetries in spasticity across sides.NEW & NOTEWORTHY Spasticity affects a number of people with spinal cord injury (SCI). Using biomechanical, electrophysiological, and clinical assessments, we found that passive muscle properties and active spinal reflex mechanisms contribute bilaterally and asymmetrically to spasticity in ankle plantarflexor muscles in humans with chronic SCI. A self-reported questionnaire had poor agreement with the Modified Ashworth Scale in detecting asymmetries in spasticity. The nature of these changes might contribute to the poor sensitivity of clinical exams.

HUMAN INTELLIGENCE OPERATED BY INNATE SIGN REFLEX LOGIC OF DICHOTOMY AND DUALISM AND POST-NATALLY ACQUIRED LOGIC OF “GROUP” AND “FORWARD ERROR CORRECTION (FEC)” - DIGITAL LINGUISTICS

It is plausible that language is processed by the innate spinal sign reflex mechanism. Human speech sound contains logical properties of phoneme and mora, which interact with in-brain antigen/antibody molecular structures and networking memories in the postnatally developed logical circuits optimized for signals of syllables, a character set (long lasting syllables) and electronic form (interactive and ubiquitous syllables). For grammatical decoding, sound localization function at the brainstem auditory nuclei is converted to process sound vectors of grammatical syllables. For axiomatic scientific concepts, sign reflex logic of “If A then B” must be upgraded by mathematical group logic to be acquired by learning, so that the results of interdisciplinary conceptual operations should become meaningful and productive. As electronic data is interactive, we can discover as many relevant linguistic information as possible with keyword search on the internet within a few seconds. As a result, we obtain multi-disciplinary and voluminous linguistic information but with uncertain reliability. To inherit collective human intelligence and correct any errors in linguistic information of the past, regenerative reading might be appropriate for individual ontogenesis to repeat intellectual and conceptual phylogeny. Errors cannot be corrected by the original authors posthumously but only by those who are alive now and equipped with error correction techniques for linguistic information.

The Three Stage Digital Evolution of Linguistic Humans

Digital Linguistics (DL) is an interdisciplinary study that identifies human language as a digital evolution of mammal analog vocal sign communications, founded on the vertebrate spinal sign reflex mechanism [Tokumaru 2017 a/b, 2018 a/b/c/d]. Analog signs are unique with their physical sound waveforms but limited in number, whilst human digital word signs are infinite by permutation of their logical property, phonemes. The first digital evolution took place 66,000 years ago with South African Neolithic industries, Howiesons Poort, when linguistic humans acquired a hypertrophied mandibular bone to house a descended larynx for vowel accented syllables containing logical properties of phonemes and morae. Morae made each syllable distinctive in the time axis and enabled grammatical modulation by alternately transmitting conceptual and grammatical syllables. The sign reflex mechanism is an unconscious self-protection and life-support mechanism, operated by immune cell networks inside the ventricle system. DL identified cellular and molecular structures for the sign (=concept) device as a B lymphocyte (or, in other words, Mobile Ad-Hoc Networking Neuron), connects to sensory, conceptual and networking memories, which consist of its meanings [Table 1]. Its antibodies can network with antigens of CSF-Contacting Neurons at the brainstem reticular formation and of Microglia cells at the neocortex [Figure 1]. It is plausible that the 3D structure of the antigen molecule takes the shape of word sound waveform multiplexing intensity and pitch, and that specifically pairing the antibody molecule consists of three CDRs (Complementality Defining Regions) in the Antibody Variable Region network with the logic of dichotomy and dualism. As sign reflex deals with survival issues such as food, safety and reproduction, it is stubborn, passive and inflexible: It does not spontaneously look for something new, and it is not designed to revise itself. These characteristics are not desirable for the development of human intelligence, and thus are to be overcome. All the word, sensory and network memories in the brain must be acquired postnatally through individual learning and thought. The reason and intelligence of humans depend on how correctly and efficiently humans learn new words and acquire appropriate meanings for them.

Presynaptic inhibition in restless legs syndrome

Introduction: Restless legs syndrome (RLS) is a condition that particularly urges at night in resting and causes the need to move the legs. Although the pathophysiology has not yet been clarified, dopamine and iron metabolism and spinal cord pathologies are blamed for causing the condition. There are few studies on spinal reflex mechanisms on RLS. In the present study, we aimed to investigate the role of presynaptic inhibition (PreI) in the spinal cord in RLS.Methods: Fourteen patients with RLS and 14 controls with similar demographic characteristics were included in the study. Soleus muscle H-reflex (Ht) investigation was performed for subjects whose electrophysiologic investigation was normal. The Ht response was conditioned to the stimulation of the common peroneal nerve (CPN) (Hc). The test and conditioned stimulation intervals were kept between 10 ms, 20 ms, 30 ms, 40 ms, 50 ms, 75 ms, 100 ms, 150 ms and 200 ms. In each inter-stimulus interval, nonparametric repeat measurement evaluations were conducted with the percentage value of Hc/Ht. The Hc/Ht values of the study and control groups in the same intervals were compared separately.Results: A significant decrease was detected in Hc values in the control group in the repeat measurement values at 20 ms and 100 ms inter-stimulus intervals; however, there was not decrease in any intervals in the patient’s group.Conclusion: The absence of any decrease in Hc reflexes for 20–100 ms intervals revealed that discernible PreI was vanished in RLS patients.

An Information Theory of Language (Digital Linguistics)

Digital Linguistics (DL) is an interdisciplinary study that identifies human language as a digital evolution of mammal analog vocal sign communications, founded on the vertebrate spinal sign reflex mechanism. The author identifies the birth of linguistic humans at the time of the laryngeal descent, which provided vowel accented syllables containing logical properties of phonemes and morae. A character set and literacy is the second evolution. Written text is long lasting syllables in the brain of literate persons, and a civilization started as a linguistic phenomenon. At the end of their biological life, they can write their accumulated knowledge with a character set, so that subsequent generations can share their thoughts and experiences to develop further. In the 21st century, text is available in electronic form, which is interactive against keyword searches. It is time for linguistic humans to integrate disciplinary sciences and correct any errors to establish collective human intelligence. Piaget indicated that concepts can be manipulated correctly based on a group theory, which seems to be a base logic for intellectual evolution of linguistic humans as well as a tool for respectful and productive interdisciplinary discussions. [1][2]

A Mobile Hypothesis of Neural Networks for Spinal Reflex and Linguistic Processing (Digital Linguistics)

Digital Linguistics (DL) is an interdisciplinary study that identifies human language as a digital evolution of mammal analog vocal sign communications, founded on the vertebrate spinal sign reflex mechanism. The evolutionary process of linguistic humans and the in-brain mechanism for linguistic phenomena are the biggest enigma in human history. There is not a single hypothesis with a detailed location/timing or cellular/molecular level explanation. A comprehensive academic boycott against South Africa (1960s-1990s) gave rise to international academics overlooking a plethora of modern human archaeological sites and artefacts in that country, and the sensor-motor synaptic connection hypothesis on the neocortex for linguistic circuit hides the true mechanism. Pavlov [1927] had observed counter-evidence for the cortical synaptic connection hypothesis for conditioned reflexes. Although he did not report it like that in his lectures, he expressed his expectation to be corrected by subsequent generations. DL hypothesized inside the ventricular system immune cell networks for linguistic processing and mechanism of meaning. There are B-lymphocytes floating inside Cerebrospinal Fluid (CSF), which function as conceptual devices and network with epitope terminals of CSF-contacting neurons (CSF-CN) on the ventricle wall and of Microglia on the neocortex. Lymphocytes are evolved neurons which do not require fixed synaptic connections for networking, but they network in a mobile-ad-hoc manner with antigen/antibody terminals on the membrane surface. A mobile hypothesis of distributed and autonomous mobile neural networks fulfills the requirements for linguistic processing and intelligence. As sign reflex is involuntary and an ego-centric reflex mechanism, linguistic humans have to overcome its restrictions to enhance our linguistic ability and intelligence.

The Grasp Reflex and Moro Reflex in Infants: Hierarchy of Primitive Reflex Responses

The plantar grasp reflex is of great clinical significance, especially in terms of the detection of spasticity. The palmar grasp reflex also has diagnostic significance. This grasp reflex of the hands and feet is mediated by a spinal reflex mechanism, which appears to be under the regulatory control of nonprimary motor areas through the spinal interneurons. This reflex in human infants can be regarded as a rudiment of phylogenetic function. The absence of the Moro reflex during the neonatal period and early infancy is highly diagnostic, indicating a variety of compromised conditions. The center of the reflex is probably in the lower region of the pons to the medulla. The phylogenetic meaning of the reflex remains unclear. However, the hierarchical interrelation among these primitive reflexes seems to be essential for the arboreal life of monkey newborns, and the possible role of the Moro reflex in these newborns was discussed in relation to the interrelationship.

Neural Mechanism and Clinical Significance of the Plantar Grasp Reflex in Infants

The plantar grasp reflex can be elicited in all normal infants from 25 weeks of postconceptional age until the end of 6 months of corrected age according to the expected birth date. This reflex in human infants can be regarded as a rudiment of responses that were once essential for ape infants in arboreal life. The spinal center for this reflex is probably located at the L(5)-S(2) levels, which, however, are controlled by higher brain structures. Nonprimary motor areas may exert regulatory control of the spinal reflex mechanism through interneurons. In infants, this reflex can be elicited as the result of insufficient control of the spinal mechanism by the immature brain. In adults, lesions in nonprimary motor areas may cause a release of inhibitory control by spinal interneurons, leading to a reappearance of the reflex. The plantar grasp reflex in infants is of high clinical significance. A negative or diminished reflex during early infancy is often a sensitive indicator of spasticity. Infants with athetoid type cerebral palsy exhibit an extremely strong retention of the reflex, and infants with mental retardation also exhibit a tendency toward prolonged retention of the reflex.

Body surface stimulation and rectal motility

The effects of mechanical stimulation on various skin areas on rectal motility were examined in anesthetized rats as a model of human. The rectal motility was measured by the balloon method at a position about 4–6 cm from the anus. Mechanical stimulation of the perineum induced a characteristic contraction of the rectum. Stimulation of the other skin areas did not produce any responses in the rectal motility. After the spinal transection at the 1st to 2nd cervical level, stimulation on the hindpaw and lower abdomen as well as the perineum induced the characteristic contraction of the rectum. These responses were abolished by severance of the pelvic nerves. After the severance of the sympathetic nerves innervating the rectum, the rectal motility increased its frequency, behind which the stimulation-induced responses were hidden and could not be observed. These results indicate that rectal motility was modulated by cutaneous mechanical stimulation through a segmental spinal reflex mechanism in anesthetized rats.

Pressor effect of water drinking in tetraplegic patients may be a spinal reflex.

Water drinking elicits a profound sympathetically mediated pressor response in patients with autonomic failure. To further elucidate the mechanism of the response, we assessed the acute effect of drinking water on supine blood pressure and heart rate in 13 tetraplegic patients (12 men, 1 woman; 39+/-4 years of age; body mass index, 25+/-1 kg/m2) with complete spinal cord injury (C2 to C7). Heart rate and finger blood pressure were recorded continuously. Brachial blood pressure was measured every 5 minutes. Baroreflex sensitivity was assessed by the sequence method. Stroke volume was calculated by use of transthoracic bioimpedance. Patients were placed in the supine position with the upper body elevated by 15 degrees. After 30 minutes, supine patients ingested 500 mL of water and the following 60 minutes were monitored. Finger blood pressure at baseline was 123+/-8/65+/-4 mm Hg. Water drinking elicited a pressor response that was apparent within 5 minutes and reached a maximum of 138+/-8/73+/-4 mm Hg after 35 to 40 minutes (P<0.05). Heart rate decreased from 64+/-2 bpm at baseline to 60+/-2 bpm (P<0.001). The mean area under the curve for brachial systolic blood pressure changes differed significantly from zero (364+/-151 mm Hg/min). Total peripheral resistance increased by 15+/-4% (P<0.05). Baroreflex sensitivity increased from 18+/-5 ms/mm Hg at baseline to 23+/-6 ms/mm Hg at 35 minutes after water drinking (P<0.01). Water drinking elicits a pressor response even if the direct connection between brain stem cardiovascular centers and spinal sympathetic neurons is interrupted. This observation might suggest that water drinking activates postganglionic sympathetic neurons either directly or through a spinal reflex mechanism.

Influence of postoperative epidural analgesia with bupivacaine on intestinal motility, transit time, and anastomotic healing.

Epidural application of bupivacaine has been suggested to have a sympatholytic effect on spinal reflex mechanisms that shortens postoperative paralysis and leads to an improved transit time. The influence on anastomitic healing remains controversial. Laparotomy was performed in eight dogs. A short segment of the distal colon was resected and five electrodes were fixed on the serosa to measure the myoelectric activity (e.g., Migrating Myoelectric Complex--MMC). After operation a peridural catheter was placed between L7 and the sacral crest. One milliliter of bupivacaine 0.25% for each 3 kg of body weight was injected every 4 hours. Barium pellets coated in wax were placed into the stomach to allow radiographic representation of transit time. After 5 days the colon anastomosis was resected to measure the bursting pressure. In the peridural analgesia group (PDA) we found one small bowel intussusception and one covered anastomotic leakage. Postoperative PDA led to early and severe myoelectric activity but did not influence the time until the first MMC occurred (44 +/- 0.8 h, PDA; 44.6 +/- 1.5 h,control). Neither the transit time to the colon (50.2 +/- 1.9h, PDA; 51.7 +/- 5.5 h, control) nor the anastomotic healing was influenced (bursting pressure: 176 +/- 21.1 mmHg, PDA; 152 +/- 27.7 mmHg, control). Postoperative epidural analgesia with bupivacaine shortens intestinal paralysis. Early myoelectric activity with a lack of propulsive activity can cause complications like small bowel intussusception. Hence early postoperative enteral nutrition after epidural analgesia is risky. Because the influence of epidural analgesia on propulsive motility remains unclear, it seems reasonable to recommend its limited use in colon surgery.

Relations between the directions of vibration-induced kinesthetic illusions and the pattern of activation of antagonist muscles

In humans, tendon vibration evokes illusory sensations of movement that are usually associated with an excitatory tonic response in muscles antagonistic to those vibrated (antagonist vibratory response, AVR), i.e., in the muscle groups normally contracted if the illusory movement had been performed. The aim of the present study was to investigate the relation between the parameters of the illusory sensation of movement and those of the AVR and to determine whether vectorial models could account for the integration of proprioceptive inputs from several muscles, as well as for the organization of the elementary motor commands leading to one unified motor response. For that purpose, we analyzed the relations between the anatomical site of the tendon vibration, the direction of the illusory movement, the muscles in which the AVR develops, and the characteristics of the AVR (surface EMG, motor unit types, firing rates, and activation latencies). This study confirmed the close relationship between the parameters of an AVR and those of the kinesthetic illusion. It showed that, during illusions of movements in different directions, motor units are activated according to a specific pattern correlated with their type, with the direction of the illusory movement and with the biomechanical properties of their bearing muscles. Finally, kinesthetic illusions and AVRs can be effectively represented using similar vectorial computations. These strong relations between the perceptual and motor effects of tendon vibration once again suggest that the AVR may result from a perceptual-to-motor transformation of proprioceptive information, rather than from spinal reflex mechanisms.

Weight support and balance during perturbed stance in the chronic spinal cat.

The intact cat maintains balance during unexpected disturbances of stance through automatic postural responses that are stereotyped and rapid. The extent to which the chronic spinal cat can maintain balance during stance is unclear, and there have been no quantitative studies that examined this question directly. This study examined whether the isolated lumbosacral cord of the chronic spinal cat can generate automatic postural responses in the hindlimbs during translation of the support surface. Responses to 16 directions of linear translation in the horizontal plane were quantified before and after spinalization at the T(6) level in terms of forces exerted by each paw against the support, motion of the body segments (kinematics), and electromyographic (EMG) activity. After spinalization, the cats were trained on a daily basis to stand on the force platform, and all four cats were able to support their full body weight. The cats usually required assistance for balance or stability in the horizontal plane, which was provided by an experimenter exerting gentle lateral force at the level of the hips. Three of the four animals could maintain independent stance for a brief period (10 s) after the experimenter stabilized them. The fourth cat maintained weight support but always required assistance with balance. Perturbations were delivered during the periods of independent stance in three cats and during assisted stance in the fourth. A response to translation in the spinal cats was observed only in those muscles that were tonically active to maintain stance and never in the flexors. Moreover, latencies were increased and amplitudes of activation were diminished compared with control. Nevertheless, flexors and extensors were recruited easily during behaviors such as paw shake and stepping. It is concluded that centers above the lumbosacral cord are required for the full elaboration of automatic postural responses. Although the spinal cat can achieve good weight support, it cannot maintain balance during stance except for brief periods and within narrow limits. This limited stability is probably achieved through spinal reflex mechanisms and the stiffness characteristics of the tonically active extensors.

Vesicoanal, urethroanal, and urethrovesical reflexes initiated by lower urinary tract irritation in the rat.

Irritation of the urinary bladder causes activation of normally "silent" nociceptive primary afferent fibers. In the present study, it is reported that irritation of the urinary bladder or urethra with infusion of 0.5% acetic acid robustly activates motoneurons that innervate the striated muscle of the external anal sphincter via spinal reflex mechanisms. The activation of anal motoneurons following irritation of the bladder and urethra are termed vesicoanal and urethroanal reflexes, respectively. The reflexes can be mimicked by acute application of capsaicin to the bladder and urethra, and they show desensitization following prolonged topical application of capsaicin or following chronic systemic pretreatment with capsaicin. The reflexes can be demonstrated in chronic spinal cord-transected animals, indicating that the reflex pathways are organized within the spinal cord. The urethroanal reflex is also physiologically activated by urethral distension and/or increases in intraluminal pressure. In addition to activation of anal sphincter activity, slight distension, pressure increases, or instillation of 0.5% acetic acid into the urethra inhibited bladder contractions through activation of an inhibitory urethrovesical reflex. These reflexes are discussed in terms of clinical characteristics of urethritis and prostatitis. Anecdotally, it was discovered that the bladder can buffer acetic acid.

Antagonist motor responses correlate with kinesthetic illusions induced by tendon vibration.

In humans, vibration applied to muscle tendons evokes illusory sensations of movement that are usually associated with an excitatory tonic response in muscles antagonistic to those vibrated (antagonist vibratory response or AVR). The aim of the present study was to investigate the neurophysiological mechanisms underlying such a motor response. For that purpose, we analyzed the relationships between the parameters of the tendon vibration (anatomical site and frequency) and those of the illusory movement perceived (direction and velocity), as well as the temporal, spatial, and quantitative characteristics of the corresponding AVRs (i.e., surface EMG, motor unit firing rates and activation latencies). Analogies were supposed between the characteristics of AVRs and voluntary contractions. The parameters of the AVR were thus compared with those of a voluntary contraction with similar temporal and mechanical characteristics, involving the same muscle groups as those activated by vibration. Wrist flexor muscles were vibrated either separately or simultaneously with wrist extensor muscles at frequencies between 30 and 80 Hz. The illusory movement sensations were quantified through contralateral hand-tracking movements. Electromyographic activity from the extensor carpi radialis muscles was recorded with surface and intramuscular microelectrodes. The results showed that vibration of the wrist flexor muscle group induced both a kinesthetic illusion of wrist extension and a motor response in the extensor carpi radialis muscles. Combined vibration of the two antagonistic muscle groups at the same frequency evoked neither kinesthetic illusion nor motor activity. In addition, vibrating the same two antagonistic muscle groups at different frequencies induced both a kinesthetic illusion and a motor response in the muscle vibrated at the lowest frequency. The surface EMG amplitude of the extensor carpi radialis as well as the motor unit activation latency and discharge frequency were clearly correlated to the parameters of the illusory movement evoked by the vibration. Indeed, the faster the illusory sensation of movement, the greater the surface EMG in these muscles during the AVRs and the sooner and the more intense the activation of the motor units of the wrist extensor muscles. Moreover, comparison of the AVR with voluntary contraction showed that all parameters were highly similar. Mainly slow motor units were recruited during the AVR and during its voluntary reproduction. That the AVR is observed only when a kinesthetic illusion is evoked, together with the similarities between voluntary contractions and AVRs, suggests that this vibration-induced motor response may result from a perceptual-to-motor transformation of proprioceptive information, rather than from spinal reflex mechanisms.

Uterine contractility and blood flow are reflexively regulated by cutaneous afferent stimulation in anesthetized rats

The effects of cutaneous mechanical afferent stimulation of various skin areas on uterine contractility and blood flow were examined in anesthetized non-pregnant rats. The contractility of the uterus was measured by the balloon method in the uterus. The uterine blood flow was measured by laser Doppler flowmetry. Noxious pinching stimulation of the perineum for 1 min induced an abrupt contraction of the uterus during stimulation. Pinching of a hindpaw or perineum and innocuous brushing of the perineum for 1 min increased uterine blood flow. Stimulation of other skin areas produced no changes in uterine contractility or blood flow. Most uterine responses were abolished by severance of the pelvic nerves, which innervated the uterus. The activity of pelvic parasympathetic efferent nerves to the uterus increased following perineal pinching. All these cutaneous stimulation-induced responses of uterine contractility, blood flow and pelvic efferent nerve activity still existed, and were even augmented, after acute spinalization. These results indicate that cutaneous mechanical sensory stimulation can regulate uterine contractility and blood flow by a segmental spinal reflex mechanism via uterine parasympathetic efferent nerves.

A neurologic basis for the overactive bladder

Objectives The functions of the lower urinary tract (LUT) to store and periodically release urine are dependent on neural circuits in the brain and spinal cord. This paper reviews the central neural control of micturition and how disruption of this control can lead to bladder overactivity and incontinence. Methods Neuroanatomic, electrophysiologic, and pharmacologic techniques have provided information about the neural circuitry and the neurotransmitters involved in the central nervous control of voiding. Experimental models of neural injury, including spinal cord transection, cerebral infarction, and localized brain lesions, have been studied to identify the mechanisms contributing to the neurogenic overactive bladder. Results Normal storage of urine is dependent on 1) spinal reflex mechanisms that activate sympathetic and somatic pathways to the urethral outlet and 2) tonic inhibitory systems in the brain that suppress the parasympathetic excitatory outflow to the urinary bladder. Voiding is mediated by inhibition of sympatheticsomatic pathways and activation of a spinobulbospinal parasympathetic reflex pathway passing through a micturition center in the rostral pons. Damage to the brain can induce bladder overactivity by reducing suprapontine inhibition. Damage to axonal pathways in the spinal cord leads to the emergence of primitive spinal bladder reflexes triggered by C-fiber bladder afferent neurons. The C-fiber afferent neurotoxin capsaicin, administered intravesically, has been useful in treating certain types of neurogenic bladder overactivity. Conclusions The central nervous mechanisms controlling the LUT are organized in the brain and spinal cord as simple on-off switching circuits that are under voluntary control. Damage to central inhibitory pathways or sensitization of peripheral afferent terminals in the bladder can unmask primitive voiding reflexes that trigger bladder overactivity.

Role of the cerebellum and motor cortex in the regulation of visually controlled locomotion

An account is given of the current state of knowledge of the contributions of the cerebellum and the forelimb motor cortex (MC) to the neural control of walking movements in the cat. The main emphasis is on information obtained by recording from single MC and cerebellar neurones in chronically instrumented cats engaged in walking on the rungs of a horizontal ladder, a form of locomotion that is heavily dependent on visual input and for which the integrity of MC is essential. Evidence from the authors' laboratory and from other studies is presented which establishes that MC neurones, including pyramidal tract neurones, show higher levels of activity during ladder walking than during overground walking (i.e., when less constraint exists over the locus of footfall) and that this increase is greatest in late swing-early stance in the contralateral forelimb, consistent with one role of MC being to help determine the locus of footfall. However, many MC neurones develop peak activity at other times in the step cycle, and a comparison with recordings during treadmill walking suggests MC may also help regulate stance duration when walking speed is an important performance variable. Recordings from Purkinje cells and cerebellar nuclear neurones show that during ladder walking step-related activity is widespread in the vermal, paravermal, and crural regions of cortex and in the interposed and dentate nuclei. Nuclear cell activity is so timed that it could be contributing to producing the locomotor rhythms evident in MC cells, although this is not yet proven. Results are also presented and discussed relating to MC and cerebellar neuronal responses that occur when a step onto an unstable rung results in an unexpected external perturbation of the forelimb step cycle. MC responses begin with onset latency as short as 20 ms so that MC may assist spinal reflex mechanisms to produce a post hoc compensatory change in motor output. However, work in progress suggests that corresponding responses in paravermal cerebellum are weak and infrequent, so provisionally it seems that the MC responses are initiated via pathways that do not pass through the cerebellum. By contrast, current work involving a paradigm in which a ladder rung is motor driven to a new position as the animal approaches (thereby providing a visual cue that an adaptive change in gait will soon be required) is revealing in lateral cerebellar neurones, including dentate neurones, changes in discharge that are time locked to the execution of an adapted pace. In addition, there are prominent earlier responses, which begin at short latency after the onset of rung movement. These apparently visual responses have characteristics that encourage the speculation that they may represent a cerebellar signal that "primes for action" other more directly motor regions of the central nervous system.