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Hyperactive tendon reflexes in spastic multiple sclerosis: measures and mechanisms of action.

OBJECTIVE: To develop new measures of tendon reflexes and evaluate hyperactive reflexes in patients with spastic multiple sclerosis (MS). DESIGN: With the subject relaxed, a hand-held instrumented hammer was used to tap the patellar tendon and record the tapping force, while knee extension torque and quadriceps EMG were recorded isometrically as measures of the reflex response. SETTING: Research laboratory in a rehabilitation hospital. SUBJECTS: Ten spastic MS and 14 healthy subjects. MAIN OUTCOME MEASURES: Tendon tapping force (designated as system input), reflex torque (as output), their dynamic relationship (characterized as system parameters tendon reflex gain, contraction rate, and reflex loop delay), Ashworth scale, and tendon reflex scale. RESULTS: The system parameters provide more repeatable measures than do input or output parameters alone because they quantify the input and output simultaneously and dynamically. Compared with control subjects, MS patients had a significantly lower threshold in tapping force (p = .026), yet their evoked reflex torque was significantly higher (p = .033). Despite significant quadriceps weakness (p < .0001), MS patients had a significantly higher reflex gain (p = .0002) and contraction rate (p = .0002), and shorter reflex loop delay (p = .0046), indicating hyperexcitability of motoneurons and peripheral receptors, and indicating that relatively more of the muscle was activated reflexively, with greater recruitment of larger fast-twitch fibers. Both the reflex gain and rate measures correlated more closely with the Ashworth scale and tendon reflex scale than did the output measures, indicating their potential clinical value. CONCLUSIONS: With appropriate simplification, the method may be used in clinical practice to quantify more precisely the tendon jerk than is currently feasible with standard clinical tests.

Adult↗

Electrophysiologic evidence for an intersegmental reflex pathway between lumbar paraspinal tissues.

STUDY DESIGN: Electrophysiologic recordings were obtained from a lumbar paraspinal nerve or muscle in the anesthetized cat while electrically stimulating a paraspinal nerve or facet capsule in an adjacent lumbar segment. A variety of approaches were used to demonstrate the reflex nature of both the nerve and the muscle response. OBJECTIVE: The primary purpose of this study was to seek electrophysiologic evidence for the presence of intersegmental reflexes between adjacent lumbar vertebral segments. A second purpose of this study was to confirm a previous procedure used to evoke paraspinal reflexes. This previous work had shown that electrical stimulation of the L1-L2 facet joint capsule elicits electromyographic activity from multifidus muscle one to two vertebral segments caudal to the stimulated facet in a porcine preparation. SUMMARY OF BACKGROUND DATA: Biomechanical approaches have stressed the need for spinal stability to avoid conditions that could give rise to low back dysfunction. It seems reasonable to believe that reflex interactions between vertebral segments contribute to the sensorimotor integration of lumbar paraspinal tissues. It also seems reasonable to believe that alterations or abnormal elicitation of these reflexes could contribute to biomechanical changes associated with low back pain and paraspinal muscle spasm. METHODS: Experiments were performed on 23 alpha-chloralose anesthetized adult cats. In eight cats the L3, L4, and L5 medial branch from each dorsal ramus was exposed and placed on a bipolar hook electrode. In six cats the L4 medial branch was stimulated and a compound action potential was recorded from the L3 medial branch. In three of the six cats the L5 medial branch was stimulated and a compound action potential was recorded from the L3 medial branch. In one cat the L4 medial branch was stimulated and a compound action potential was recorded from the L5 medial branch. In one cat the L3 medial branch was stimulated and a compound action potential was recorded from the L5 medial branch. At the end of each protocol the medial branch was cut just proximal to the stimulating electrode to confirm that the compound action potential was reflexive in nature and not initiated by volume conduction. In 15 cats three approaches were used to confirm that multifidus electromyographic activity evoked by electrical stimulation of a lumbar facet capsule was reflexive in nature: 1) by anesthetizing the site of the sensory endings, i.e., the facet capsule, 2) by injecting lidocaine intrathecally to block neural conduction centrally, i.e., within the spinal canal, or 3) by cutting the afferent pathway, i.e., the medial branch of the dorsal ramus. RESULTS: Electrical stimulation of the medial branch of the dorsal ramus innervating the medial-most lumbar paraspinal tissues evoked a compound action potential in the medial branch innervating the medial-most paraspinal tissues one and two segments away. Stimulating voltages between 2 and 70 V were necessary to evoke the compound action potential. Each compound action potential was reflexive in nature because cutting the lumbar medial branch proximal to its contact with the stimulating electrode abolished each compound action potential. The conduction velocity of the reflex ranged from 3.5 to 6.1 m/sec. Electrical stimulation of a lumbar facet capsule evoked lumbar multifidus muscle electromyographic activity. However, injecting lidocaine intrathecally or transecting the medial branch of the dorsal ramus had no effect on electromyographic activity. Injecting lidocaine into the facet or into the multifidus muscle around the facet joint (near the stimulating electrode) significantly decreased the magnitude of the multifidus electromyography. CONCLUSION: These results indicate that afferent impulses conveyed by the medial branch of the dorsal ramus reflexly altered efferent activity to an adjacent lumbar segment. This intersegmental paraspinal reflex may span at least one or two vertebral segments. The data suggest that electrical stimulation of the facet joint capsule may not have reflexly elicited multifidus activity because neither chemical interruption (intrathecal lidocaine) nor physical interruption (nerve transection) of the presumed reflex pathway diminished or abolished the electromyographic response. Volume conduction of the stimulating currents likely elicited multifidus activity during electrical stimulation of the facet capsule. When using electrical stimulation of neural paraspinal tissues to evoke reflex muscle activity, appropriate control experiments must be performed to clearly demonstrate the reflexive nature of the response.

Action Potentials↗

System identification of tendon reflex dynamics.

Patellar tendon reflexes were evaluated in 12 healthy adult subjects using several measures of the reflex responses and of the system input-output relationship. A hand-held instrumented hammer was used to tap the patellar tendon and to elicit the reflex response. Tendon reflex dynamics were estimated using the recorded tapping force (as input) and the quadriceps muscle electromyogram and knee joint extension torque signals (as output). A dome-shaped rubber pad was mounted onto the most sensitive spot on the patellar tendon, where it served as a tapping target, and helped to reduce the reflex variability significantly (p < 0.01). The input-output properties of the system relating the reflex torque to the tapping force were characterized using several measures: the tendon reflex gain (Gtr), contraction rate (Rc), and half-relaxation rate (Rhr). Reflex loop delay (t(d)) was estimated using the delay from the onset of tapping force to the onset of reflex torque. We determined that these system parameters provided significantly more repeatable and consistent characterization of tendon reflexes than did reflexive torque or EMG signals alone (p < 0.025). The input-output relationship relating the EMG signals of the stretched muscle to the tapping force was also identified to help characterize neuromuscular dynamics of tendon reflexes. The observed sensitivity and consistency of the reflex system measures suggest that with appropriate simplification of the instrumentation, these methods may prove useful in routine clinical practice, and may allow more precise quantification of the tendon jerk than is currently feasible with standard clinical tests.

Adult↗

The C fibre reflex of the cat urinary bladder.

1. Reflexes evoked in bladder parasympathetic neurones by electrical stimulation of bladder C afferent fibres were studied in cats anaesthetized with alpha-chloralose. The responses were compared with the ordinary micturition reflex evoked by low-threshold Adelta afferents from bladder mechanoreceptors and mediated by a spino-ponto-spinal reflex pathway. 2. The bladder was catheterized for fluid instillations and pressure recordings. Efferent reflex discharges were recorded from the cut central end of a small distal bladder branch of the pelvic nerve. The remaining bladder pelvic nerve branches were stimulated electrically close to the bladder. 3. Stimulation at C afferent intensity evoked a late reflex discharge in bladder pelvic efferents in all animals. The response was centrally mediated, had a latency of 150-250 ms, and was much weaker after stimulation on the contralateral nerve. 4. The bladder C fibre reflex differed in several functional aspects from the ordinary Adelta micturition reflex. It could be evoked at a low rate of stimulation, with an empty bladder and no background activity from bladder mechanoreceptors. In this situation, the normal Adelta micturition reflex is not elicited. The C fibre reflex also survived an acute spinalization at a low thoracic level. 5. The C fibre reflex was strongly inhibited by dorsal clitoris or dorsal penis nerve stimulation, an effect that was maintained after spinalization. It was facilitated by bladder or urethra exposure to cold and menthol, stimuli that activate specific cold-sensitive receptors associated with unmyelinated C afferents. 6. It is concluded that the central pathway of the C fibre reflex is spinal and partly separate from that of the ordinary micturition reflex. These observations are in keeping with the clinical finding that a bladder cooling reflex can be elicited in patients with disturbed descending control of the bladder.

Animals↗

Pharmacological analysis of the local and reflex responses to bradykinin on rat urinary bladder motility in vivo.

1. The topical application of bradykinin (BK) (0.05-5000 pmol/rat) onto the serosal surface of the urinary bladder in urethane-anaesthetized rats, evoked low amplitude tonic contractions (not exceeding 25 mmHg) or high amplitude (about 50 mmHg), phasic reflex contractions (chemoceptive micturition reflex) which were abolished by bilateral ablation of the pelvic ganglia. In ganglionectomized rats, BK induced only a local, tonic-type contraction. 2. Systemic capsaicin pretreatment (164 mumol kg-1, 4 days before) reduced the incidence of chemoceptive reflex induced by BK (500 pmol/rat) but had no effect on the magnitude of the tonic-type contraction elicited by BK in ganglionectomized rats. Indomethacin (11 mumol kg-1, 20 min before) reduced the incidence but not the amplitude of the reflex contractions induced by topical application of BK (500 pmol/rat). In ganglionectomized rats, indomethacin (11 mumol kg-1, 20 min before) decreased the amplitude of the tonic contraction evoked by BK. Indomethacin did not affect the chemoceptive reflex induced by topical application of capsaicin (15 nmol/rat) onto the bladder. 3. Intrathecal administration of the tachykinin NK1 receptor antagonists, RP 67,580 (10 nmol/rat) or SR 140,333 (10 nmol/rat), abolished the chemoceptive reflex induced by BK without modifying the magnitude of the tonic contraction. SR 140,333 (10 nmol/rat) also abolished the occurrence of the chemoceptive reflex induced by capsaicin. 4. Intravenous administration of the B2 receptor antagonist, Hoe 140 (35 nmol kg-1, 10 min before) abolished the reflex and local effects induced by BK on bladder motility but failed to modify the chemoceptive reflex induced by topical application of capsaicin (15 nmol/rat). 5. Intrathecal administration of Hoe 140 (10 nmol/rat) reduced the incidence of the chemoceptive reflex induced by BK but had no effect on the amplitude of the local motor response. Likewise, Hoe 140(10 nmol/rat, i.t.) reduced the incidence of reflex bladder contractions induced by topical application of capsaicin (15 nmol/rat) without affecting the magnitude of the tonic-type contraction.6. These findings indicate that BK stimulates motility through B2 receptors in the rat urinary bladder.BK activates the reflex response by stimulating capsaicin-sensitive afferent nerves with a contribution from prostanoids. At the spinal cord level, tachykinin NK1 and BK B2 receptors could also be involved in the chemoceptive reflex induced by BK or capsaicin.

Adrenergic beta-Antagonists↗

Analysis of contributions of acetylcholine and tachykinins to neuro-neuronal transmission in motility reflexes in the guinea-pig ileum.

1. The roles of acetylcholine (ACh) and tachykinins in neuro-neuronal transmission during ascending excitatory and descending inhibitory reflexes were studied by recording intracellular reflex responses of the circular muscle to physiological stimuli. Experiments were carried out in opened segments of guinea pig ileum in an organ bath that was partitioned so that three regions could be independently exposed to drugs. 2. Ascending excitatory reflexes evoked by either distension from the serosal side or compression of the mucosa were depressed by 55% and 85%, respectively, in the presence of hexamethonium (200 microM) and by 30% and 45%, respectively, by a desensitizing concentration of the selective NK3 receptor agonist, senktide (1 microM), in the chamber in which reflexes were initiated. Together, hexamethonium and senktide abolished responses to compression. A residual response to distension persisted. This was abolished by hyoscine (1 microM). 3. Hexamethonium (200 microM) abolished ascending reflexes when applied to the region between the stimulus and the recording sites, or to the recording chamber. 4. Descending reflex responses were reduced by 35% by synaptic blockade in the stimulus chamber with physiological saline containing 0.1 mM Ca2+ plus 10 mM Mg2+. Senktide (1 microM) in the stimulus chamber reduced distension reflexes to the same extent as synaptic blockade, whereas hexamethonium (200 microM) and hyoscine (1 microM) depressed responses by less than 20%. Responses to compression were reduced by 40% by senktide alone, while senktide and hexamethonium together reduced responses by 60%, an effect similar to synaptic blockade. Under these conditions, hyoscine in the stimulus chamber restored reflexes evoked by distension, but did not alter those evoked by mucosal compression. 5. Total synaptic blockade in the intermediate chamber, between stimulus and recording sites, reduced descending reflex responses by more than 90%. In contrast, hexamethonium (200 microM) had no effect and hyoscine (1 microM) reduced only the responses to distension (by 30%). Senktide (1 microM) depressed responses to both stimuli by approximately 80%. 6. Application of hexamethonium (200 microM) to the recording chamber depressed descending reflex responses to distension applied in the near stimulation chamber by 15%, but had no effect on responses to compression in the near chamber or to either stimulus applied in the far chamber. 7. Descending reflexes evoked by near chamber stimuli were unaffected by hyoscine (1 microM) or senktide (1 microM) applied to the recording chamber; hyoscine enhanced reflexes evoked by compression in the far chamber by 50%. 8. For the ascending excitatory reflex pathway, it is concluded that transmission from sensory neurones is mediated by ACh acting via both nicotinic and muscarinic receptors, and by tachykinins acting at NK3 receptors. Transmission from ascending interneurones appears to be predominantly via nicotinic receptors. The descending inhibitory pathways are more complex, and while transmission from sensory neurones involves nicotinic, muscarinic and NK3 receptor-dependent components, transmission from descending interneurones to inhibitory motor neurones is neither cholinergic nor due to tachykinins acting via NK3 receptors.

Acetylcholine↗

Excitability of the soleus H reflex during graded walking in humans.

The excitability of the soleus Hoffmann (H) reflex was measured in five healthy male subjects during graded treadmill walking. Uphill and downhill walking at an 8% grade as well as level walking were used to vary the demands for lengthening and shortening contractions of the soleus muscle. These changes were assumed to cause differences in control of the afferent input in the spinal cord and the voluntary output to the soleus muscle. The H reflex was strongly modulated in all three walking conditions, high during the stance phase and low or absent during the swing phase. The shape of the modulations was, however, different. At uphill walking the reflex increased gradually during the whole stance phase and seemed to follow the soleus electromyogram (EMG) pattern closely. In the downhill condition the reflex excitability increased rapidly at heel strike like the soleus EMG and co-contraction of the anterior tibial muscle was observed. At level walking a fast rise in reflex excitability was seen just after heel strike with low or absent soleus EMG. Mean soleus EMG was lower during downhill than during uphill or level walking, but the mean H reflex amplitude was similar in all three conditions. However, when the H reflex was related directly to the EMG activity by linear regression the reflex gain was lower during uphill walking than in the two other conditions. Furthermore, the ratio between H reflex and EMG amplitude was high during the first half of the stance phase at level walking indicating an elevated reflex excitability independent of the voluntary motor output. It is therefore concluded that the modulation of reflexes during walking cannot be interpreted in terms of the idea of automatic gain compensation. The reflexes must be controlled specifically and independently during the different phases of the motor output to meet the mechanical requirements of the movement task. Most explicitly this was seen during downhill walking, where an elevated reflex excitability together with co-contraction at the ankle joint seem to provide increased joint stiffness and security, when the kinetic energy of the body has to be brought under control at heel strike.

Adult↗

Specific patterns of neuronal connexions involved in the control of the rabbit's vestibulo-ocular reflexes by the cerebellar flocculus.

1. In anaesthetized albino rabbits, the occurrence of Purkinje cell inhibition on canal-ocular reflexes was surveyed with a reflex testing method. 2. Test reflexes were elicited by electrical stimulation of the semicircular canals. The results were appaised by recording potentials and tension from extraocular muscles. Twelve reflexes were defined in terms of the receptor canal and the effector muscle. 3. Conditioning electrical stimuli were applied to the flocculus, the inferior olive, and optic pathways at the retinae, optic chiasm, pretectal area and upper medulla. 4. The conditioning stimulation at the ipsilateral flocculus induced depression in six of the twelve canal-ocular reflexes; four of the six arose from the anterior canal and the remaining two from the horizontal canal. 5. The effect of stimulation of the contralateral inferior olive was similar to that of the ipsilateral flocculus, though less clear in two of the four reflexes from the anterior canal because of a contaminating effect. 6. The two reflexes from the horizontal canal were depressed by stimulation of the ipsilateral optic pathway which reached the ipsilateral flocculus via the contralateral pretectal area and inferior olive. 7. The four reflexes from the anterior canal were affected by stimulation of optic pathways in a different manner from each other. One was depressed from the contralateral retina via the ipsilateral pretectal area, while another was depressed from the ipsilateral retina via the contralateral pretectal area, though only occasionally. The third reflex was depressed from the ipsilateral pretectal area but not from the retina. The fourth was affected from neither the retina nor the pretectal area. 8. On the basis of latency measurements, it was concluded that the depression of canal-ocular reflexes was due to inhibition of relay neurones of the testing reflexes by flocculus Purkinje cells which were activated either directly, or indirectly through olivocerebellar climbing fibre afferents. 9. The above conclusion was supported by the observation that the depression induced by stimulation of the inferior olive and optic pathways was abolished by acute destruction of the ipsilateral flocculus. 10. The possible functional significance of the specific patterns of connexions from flocculus Purkinje cells to canal-ocular reflex pathways is discussed, and specialization among flocculus Purkinje cells in relationship with vestibulo-ocular reflexes is postulated.

Action Potentials↗

Lung C-fibre receptor activation and defensive reflexes in anaesthetized cats.

1. With pentobarbitone-anaesthetized cats we have elicited cough reflexes from the tracheobronchial tree and the larynx, and the aspiration and sneeze reflexes from the nasopharynx and the nose respectively. The reflexes were induced by mechanical stimulation of the mucosa, before and during activation of pulmonary C-fibre receptors by intravenous injections of capsaicin or phenylbiguanide. 2. During the 20-30 s apnoea due to C-fibre stimulation, the cough reflex from both sites and the sneeze reflex were completely abolished, whereas the aspiration reflex response was approximately halved. Reflex contractions of genioglossus muscle still occurred at this time, but were far weaker than in the control state. 3. During the rapid shallow breathing that immediately followed apnoea due to C-fibre receptor stimulation, the defensive reflexes recovered: the aspiration and sneeze reflexes fully and the cough reflexes to about half of the control response. 4. Acute hypotension due to haemorrhage, of a size considerably greater than that due to stimulation of the pulmonary C-fibre receptors, caused no significant inhibition of the cough reflex from the tracheobronchial tree. 5. We conclude that the pulmonary C-fibre reflex powerfully inhibits airway defensive reflexes, and that its activation is unlikely to contribute positively to coughing induced by aerosols of capsaicin and similar agents.

Action Potentials↗

A bladder-to-bladder cooling reflex in the cat.

1. Reflex effects of cold stimulation of the lower urinary tract were studied in cats anaesthetized with alpha-chloralose. The bladder and the urethra were catheterized for separate fluid instillations and the bladder pressure was monitored together with the evoked efferent nerve responses in pelvic nerve filaments. 2. A bladder cooling reflex could be evoked from both the bladder and the urethra. The response was an efferent discharge in preganglionic pelvic motor fibres to the bladder. 3. Bladder mechanoreceptors that drive the normal micturition reflex were not directly involved in the cooling reflex. Their tension sensitivity was decreased by cooling and the efferent reflex response typically occurred before any activation of these receptors. The efferent activity of the cooling reflex also survived an intentional unloading of the mechanoreceptors, a manipulation that abolishes the normal micturition reflex. 4. The dynamic threshold temperature of the cooling reflex was about 30-32 degrees C, which was at the thermal neutral point of the bladder in our experimental situation. 5. The bladder-evoked component of the reflex was greatly reduced or abolished by an intravesical infusion of the local anaesthetic Xylocaine. It was also abolished by total bladder denervation. 6. The vesical component of the reflex was unchanged by bilateral transections of the hypogastric nerves but abolished by pelvic nerve transection. The cooling reflex from the distal urethra was abolished by transection of the pudendal nerves. 7. It was proposed that the cooling reflex originates from cold receptors in the bladder and urethral walls and that the responsible afferent fibres are unmyelinated C fibres. The function of the reflex may be to rid the body of a thermal ballast when under cooling stress.

Action Potentials↗

Organisation of sensitisation of hind limb withdrawal reflexes from acute noxious stimuli in the rabbit.

Spatial aspects of central sensitisation were investigated by studying the effects on three hind limb withdrawal reflexes of an acute noxious stimulus (20 % mustard oil) applied to a number of locations around the body in decerebrate and in anaesthetised rabbits. Reflex responses to electrical stimulation of the toes were recorded from the ankle flexor tibialis anterior (TA) and the knee flexor semitendinosus (ST), whereas responses to stimulation of the heel were recorded from the ankle extensor medial gastrocnemius (MG). In non-spinalised, decerebrated, pentobarbitone-sedated preparations, flexor reflexes were facilitated significantly from sites on the plantar surface of the ipsilateral foot but were either inhibited or unaffected by stimulation of sites away from this location. The heel-MG reflex was facilitated from the ipsilateral heel and was inhibited from a number of ipsilateral, contralateral and off-limb sites. In decerebrated, spinalised, pentobarbitone-sedated animals, mustard oil applied to any site on the ipsilateral hind limb enhanced both flexor reflexes, whereas the MG reflex was enhanced only after stimulation at the ipsilateral heel and was inhibited after stimulation of the toe tips or TA muscle. Mustard oil on the contralateral limb had no effect on any reflex. In rabbits anaesthetised with pentobarbitone and prepared with minimal surgical interference, the sensitisation fields for the heel-MG and toes-TA reflexes were very similar to those in non-spinal decerebrates whereas that for toes-ST was more like the pattern observed in spinalised animals. In no preparation was sensitisation or inhibition of reflexes related to the degree of motoneurone activity generated in direct response to the sensitising stimulus. This study provides for the first time a complete description of the sensitisation fields for reflexes to individual muscles. Descending controls had a marked effect on the area from which sensitisation of flexor reflexes could be obtained, as the sensitisation fields for the flexor reflexes evoked from the toes were larger in spinalised compared to decerebrated, non-spinalised animals. The intermediate sizes of sensitisation fields in anaesthetised animals suggests that the area of these fields can be dynamically controlled from the brain. On the other hand, the sensitisation field for the heel-MG reflex varied little between preparations and appears to be a function of spinal neurones.

Animals↗

Quadriceps H-reflex modulation during pedaling.

The main aims of this study were 1) to investigate possible phase-, speed-, and task-dependent changes in the quadriceps H-reflex during pedaling, and to achieve this, 2) to develop an optimized H-reflex recording and processing procedure for recording of quadriceps H-reflexes during movement. It was hypothesized that the behavior of the quadriceps H-reflex concerning phase, speed, and task dependency corresponds to the behavior of the soleus H-reflex during rhythmical leg movements. The applied H-reflex procedure appeared to be reliable for obtaining the quadriceps H-reflex modulation during leg movement. The vastus lateralis (VL) and rectus femoris (RF) H-reflexes showed a phase-dependent modulation during pedaling at a frequency of 80 rpm with almost parallel changes in the reflex amplitude and motor recruitment level. However, when the speed of movement was reduced from 80 to 40 revolutions per minute (rpm) and crank load simultaneously increased (i.e., a halving of the movement speed with a constant motor recruitment level), the quadriceps H-reflex modulation pattern changed significantly in relation to the pattern of motor recruitment, i.e., at 40 rpm, the reflex excitability remained high during a gradual derecruitment during power generation in downstroke. Comparison of the "operationally defined H-reflex gain function" obtained during 1) pedaling at 80 rpm and 2) isometric quadriceps contractions in sitting position showed no significant task-dependent changes in the quadriceps H-reflex. Consequently, the hypothesis was only partly corroborated, and the findings indicate differences in the neural control of the soleus and the quadriceps muscle during rhythmical movements.

Adult↗

Improvement in linearity and regulation of stiffness that results from actions of stretch reflex.

We studied stretch reflexes of soleus muscles of intercollicularly decerebrated cats using a new technique for estimating the component of a stretch reflex that results from the purely mechanical properties of the active muscle (mechanical response). The difference between a net stretch reflex and its underlying mechanical response provided a direct measure of reflex action. 1. The relative contributions of reflex action and the mechanical response are different for stretch and release. With stretch, reflex action is generally large and the mechanical response small. The opposite is true with release. The property that remains relatively constant, when stretch and release are compared, is the net stiffness in opposition to length change. We concluded that reflex action compensates for variations in the inherent stiffness of the muscle. 2. Compensation is effective over a range of intermediate values of initial force, but it fails whenever the reflex force approaches zero or the maximal force at that length. 3. Reflex action is capable of modifying muscular force within 22 ms of the onset of length change. This indicates that even during a fast gallop, there is sufficient time for reflex action. 4. The mechanical properties of the active soleus muscle are highly nonlinear; e.g., muscular stiffness becomes negative transiently during stretch. In stable decerebrate preparations we found that reflex action resulted in a considerable improvement in linearity. 5. Our results support two complementary hypotheses: a) stiffness may be the regulated property of the stretch reflex, and b) the main function of autogenetic reflexes may be to conpensate for variations in the properties of skeletal muscle rather than to oppose changes in load.

Animals↗

Modulation of spontaneous and reflex activity of crayfish leg motor neurons by octopamine and serotonin.

1. We compared the effects of octopamine and serotonin on the activity of crayfish leg motor neurons in an isolated preparation of the 4th thoracic ganglion. Spontaneous activity of leg promotor (swing phase in a forward walking crayfish) and remotor (stance phase) motor neurons consisted either of continuous promotor activity (with the remotor nerve silent) or alternating bursts of promotor and remotor activity. Octopamine and serotonin, at high concentrations (< or = 100 and < or = 20 microM, respectively), abolished spontaneous promotor activity and rhythmic bursting (if ongoing). Both amines induced tonic remotor nerve activity, but each amine activated different identified remotor motor neurons. 2. Reflex responses of remotor motor neurons to stimulation of thoracocoxal (TC) joint proprioceptors were modulated by octopamine and serotonin in characteristic ways. The muscle receptor (TCMRO) that signals joint remotion excited a subset of remotor motor neurons in an assistance reflex. The chordotonal organ (TCCO) that signals joint promotion excited different remotor motor neurons in a resistance reflex. Octopamine abolished assistance reflexes and facilitated resistance reflexes. One assistance group unit was inhibited, whereas reflex reversal was induced in another: this unit was now excited in a resistance reflex, rather than in an assistance reflex. The responses of resistance group remotor units were enhanced. Serotonin had the opposite effect on assistance group remotors: one unit was excited and generated a stronger assistance reflex. The effect of serotonin on resistance group remotor units was similar (but quantitatively different) to that of octopamine. 3. Both octopamine and serotonin modulated spontaneous motor output at concentrations below those required to inhibit promotor nerve activity. Rhythmic promotor and remotor bursting was abolished, and replaced with continuous promotor activity, by serotonin at 1 microM and octopamine at 1-10 microM. In nonbursting preparations, promotor activity could be excited (instead of inhibited) by either amine at lower concentrations. 4. Octopaminergic inhibition of spontaneous promotor activity was antagonized by mianserin (10 microM). Phentolamine at the same concentration was less effective as an antagonist. Serotonergic inhibition of promotor activity was not blocked by mianserin. Mianserin also antagonized inhibitory, but not excitatory, effects of octopamine on remotor reflex responses. Serotonergic modulation of these reflexes was not affected. 5. An intersegmental difference was found in aminergic inhibition of promotor nerve activity. Whereas the effect (at the higher concentrations used) was inhibition of promotor activity from T4, simultaneous recordings from promotor nerves of the more rostral ganglia T3 and T2 showed either promotor excitation, or inhibition that was significantly weaker than in T4. This may relate to the known postural effects of these amines in intact crayfish and lobsters. 6. We conclude that octopamine and serotonin are modulators of segmental reflexes in the crayfish walking system. Each amine "assembles" a unique remotor nerve reflex response from different combinations of remotor units. In the case of octopamine, inhibitory effects are mediated by a mianserin-sensitive receptor, whereas excitatory effects are mediated by a mianserin-insensitive receptor.

Animals↗

Modulation of stretch reflexes during imposed walking movements of the human ankle.

Our overall objectives were to examine the role of peripheral afferents from the ankle in modulating stretch reflexes during imposed walking movements and to assess the mechanical consequences of this reflex activity. Specifically we sought to define the changes in the electromyographic (EMG) and mechanical responses to a stretch as a function of the phase of the step cycle. We recorded the ankle position of a normal subject walking on a treadmill at 3 km/h and used a hydraulic actuator to impose the same movements on supine subjects generating a constant level of ankle torque. Small pulse displacements, superimposed on the simulated walking movement, evoked stretch reflexes at different phases of the cycle. Three major findings resulted: 1) soleus reflex EMG responses were influenced strongly by imposed walking movements. The response amplitude was substantially smaller than that observed during steady-state conditions and was modulated throughout the step cycle. This modulation was qualitatively similar to that observed during active walking. Because central factors were held constant during the imposed walking experiments, we conclude that peripheral mechanisms were capable of both reducing the amplitude of the reflex EMG and producing its modulation throughout the movement. 2) Pulse disturbances applied from early to midstance of the imposed walking cycle generated large reflex torques, suggesting that the stretch reflex could help to resist unexpected perturbations during this phase of walking. In contrast, pulses applied during late stance and swing phase generated little reflex torque. 3) Reflex EMG and reflex torque were modulated differently throughout the imposed walking cycle. In fact, at the time when the reflex EMG response was largest, the corresponding reflex torque was negligible. Thus movement not only changes the reflex EMG but greatly modifies the mechanical output that results.

Adult↗

Pharyngoglottal closure reflex: characterization in healthy young, elderly and dysphagic patients with predeglutitive aspiration.

BACKGROUND: Mechanism(s) of aspiration, a common complication of oropharyngeal dysphagia, is not completely elucidated. Since the pharyngoglottal closure reflex induces vocal cord adduction in healthy young humans, it may help prevent aspiration during premature spill of oral content. OBJECTIVE: The objective of this study was to characterize this reflex in normal young and elderly humans and dysphagic patients with predeglutitive aspiration; a potential group for developing abnormalities of this reflex. METHODS: We used a concurrent video endoscopic and manometric technique for recording of the vocal cords' response to pharyngeal water stimulation. We first studied 9 young (26 +/- 2 years) and 9 elderly (77 +/- 14 years) healthy volunteers to characterize and determine the effect of aging on the pharyngoglottal closure reflex. Subsequently, we studied 8 patients (65 +/- 16 years) with predeglutitive aspiration and 7 age-matched controls to characterize this reflex among patients with compromised airway safety during swallowing. RESULTS: The threshold volume of water for triggering both glottal closure and reflexive pharyngeal swallow in the elderly volunteers for rapid pulse injection was significantly larger than that for the young (p < 0.05). Neither glottal closure reflex nor pharyngeal reflexive swallow could be induced in any of the dysphagic patients with volumes of injected water as large as 1 ml. In contrast, in all age-matched controls, both the pharyngoglottal reflex and reflexive pharyngeal swallow were stimulated with threshold volumes of 0.3 +/- 0.07 and 0.6 +/- 0.05 ml, respectively. CONCLUSIONS: Pharyngeal stimulation by water induces vocal cord adduction in humans; the pharyngoglottal closure reflex. Although preserved, a significantly larger volume of water is required to stimulate this reflex by rapid pulse injection in the elderly, suggesting some deterioration in this age group. The pharyngoglottal closure reflex induced by rapid pulse injection is absent in dysphagic patients with predeglutitive aspiration, suggesting its contribution to airway protection against aspiration.

Adult↗

The role of cardiac receptor and arterial baroreceptor reflexes in control of the circulation during acute change of blood volume in the conscious rabbit.

We have studied overall reflex control of the circulation by the arterial baroreceptors and cardiac receptors during acute change of blood volume in seven conscious rabbits. A factorial experimental design allowed analysis of the direction, magnitude, and significance of the reflex effects of independent input from each set of receptors, and the reflex interactions when the inputs were combined. Right atrial pressure, arterial pressure, systemic vascular resistance, cardiac output, and heart rate were measured during acute, graded, isohemic change of blood volume over the range +/- 27%. This was done with both reflexes present, only the arterial baroreceptor reflex present (intrapericardial 2% procaine), only the cardiac receptor reflex present (surgical baroreceptor denervation), and with both reflexes absent. As blood volume was depleted, the arterial baroreceptor reflex independently increased systemic vascular resistance and sustained arterial pressure, but the cardiac receptor reflex had no significant independent or interactive effects. As blood volume was expanded, each reflex had an independent effect in decreasing systemic vascular resistance and preventing arterial pressure from rising, the cardiac receptor reflex being the more powerful. Their effect in combination on systemic vascular resistance and arterial pressure was only two-fifths of the sum of their independent effects, so that they interacted negatively. In combination, the reflexes supported right atrial pressure during blood loss, despite their negative interaction, but did not significantly affect the relation of cardiac output to blood volume change in either direction. Thus both reflexes have important actions in moderating the overall effects of acute blood volume changes in conscious rabbits, but these are markedly diminished by their interactions.

Afferent Pathways↗

Transcranial magnetic stimulation over sensorimotor cortex disrupts anticipatory reflex gain modulation for skilled action.

Skilled interactions with new environments require flexible changes to the transformation from somatosensory signals to motor outputs. Transcortical reflex gains are known to be modulated according to task and environmental dynamics, but the mechanism of this modulation remains unclear. We examined reflex organization in the sensorimotor cortex. Subjects performed point-to-point arm movements into predictable force fields. When a small perturbation was applied just before the arm encountered the force field, reflex responses in the shoulder muscles changed according to the upcoming force field direction, indicating anticipatory reflex gain modulation. However, when a transcranial magnetic stimulation (TMS) was applied before the reflex response to such perturbations so that the silent period caused by TMS overlapped the reflex processing period, this modulation was abolished, while the reflex itself remained. Loss of reflex gain modulation could not be explained by reduced reflex amplitudes nor by peripheral effects of TMS on the muscles themselves. Instead, we suggest that TMS disrupted interneuronal networks in the sensorimotor cortex, which contribute to reflex gain modulation rather than reflex generation. We suggest that these networks normally provide the adaptability of rapid sensorimotor reflex responses by regulating reflex gains according to the current dynamical environment.

Adult↗