Electrophysiological analysis of the vestibulospinal reflex pathway of rabbit. II. Synaptic actions upon spinal neurones.
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Functional and developmental analysis of a visual corticopretectal pathway in the cat: a neuroanatomical and electrophysiological study.
The sensory corticopretectal projection in the cat and in its postnatal development were investigated combining neuroanatomical and electrophysiological techniques. The anatomical pattern of fiber termination was studied in relation to age using the anterograde HRP tracing method. Large injections were made in areas 17 and 18 of one or both hemispheres in 1-13 week old kittens and cats. Terminal label in the ipsilateral pretectum was seen only after the fourth week of life. Electrical stimulation in the same cortical areas evoked postsynaptic orthodromic excitation in 9-18% of cells at 4 weeks increasing to about 60% in the adult. In cats, but not in kittens, successful stimulation depended on the retinotopic matching of stimulation and recording sites. In adult cats a high incidence of direction and velocity tuning and a high degree of binocularity were seen in cells driven by the cortex as opposed to cells not so driven. Cortex driven cells in cats and kittens received convergent retinal input mainly via direct W-fibers, whereas cells not driven from cortex shock mainly received delayed W-fiber input. In kittens visual responses lacked sensitivity for direction and high movement velocity of patterns until 6 weeks postnatally, whereas ocular dominance distribution was not age-dependent.
Animals↗
Contribution of tactile afferent information to the control of isometric finger forces.
The ability to match the voluntary isometric force output of the right and left index fingers when the contact surfaces differ in shape was examined. Before the experiment, subjects were trained to produce both a "low" force level (50 +/- 25 g) and a "high" force level (200 +/- 50 g) with the right and left index finger, separately. Following the training session, subjects were instructed to match the forces of both fingers simultaneously within the required range (either low or high) so that the forces were perceived to be identical. One of the index fingers pushed against a conical contact pad, while the other pushed against a flat contact pad. Midway through the experiment, the two contact pads were reversed. Subjects consistently produced less force with the finger pressing against the conical pad. This asymmetry could already be seen during the beginning of the ramp increase in force and continued throughout the trial, independent of the target force levels (low or high). These findings suggest tactile afferent information at the finger-tip is important for determining the voluntary force exerted by the finger. It must be properly integrated with other peripheral information as well as with the central motor command, otherwise the perception of force is distorted. Furthermore, the perception of the force produced seemingly is dependent on the extent to which the skin of the fingertip is indented rather than the local pressure exerted at the skin.
Adult↗
The role of sensory information in the production of periodic finger-tapping sequences.
A subject lacking proprioceptive and tactile sensibility below the neck and a group of control subjects performed sequences of periodic finger taps involving a pattern of accentuation. The required intertap interval was 700 ms. In some situations, the taps were synchronized with the clicks of a metronome. Feedback conditions were manipulated by either allowing or not allowing the subjects to hear the taps and see their finger movements. We recorded the trajectory of the subjects' finger displacement in the vertical plane, and the force and moment of contact of the finger with the response key. The control subjects achieved precise timing of the finger taps by trading off downstroke onset for movement duration, e.g., they initiated shorter-duration tapping movements with a delay. This strategy did not vary depending on task demands (e.g., synchronization) or feedback conditions. The deafferented patient produced intertap intervals on average close to the required value. However, his tap timing was characterized by increased variability and severe distortion (lengthening) after the accentuated tap, regardless of feedback conditions. He did not manifest the compensatory strategy whereby, in control subjects, movement onset was adjusted to movement duration. Thus, such a strategy in controls seems to depend on intact proprioceptive and/or tactile information from the moving limb. Upon withdrawal of visual and acoustic feedback, the deafferented subject increased the force of the taps and the amplitude of tapping movements; his mean synchronization error with the metronome also increased. However, he did not lose correct phasing between the taps and the clicks of the metronome. These findings suggest that, under normal circumstances, sequential movements are timed by an internal timekeeper which paces sensory consequences relating to the occurrence of behaviorally important events (e.g., finger taps), and not the onset of the movements eliciting those events. In the synchronization task, the timekeeper may be phase locked to the periodic acoustic stimuli by direct entrainment. Feedback information may be needed, however, for keeping any synchronization error as small as possible.
Acoustic Stimulation↗
Nondigital afferent input in reactive control of fingertip forces during precision grip.
Sensory inputs from the digits are important in initiating and scaling automatic reactive grip responses that help prevent frictional slips when grasped objects are subjected to destabilizing load forces. In the present study we analyzed the contribution to grip-force control from mechanoreceptors located proximal to the digits when subjects held a small manipulandum between the tips of the thumb and index finger. Loads of various controlled amplitudes and rates were delivered tangential to the grip surfaces at unpredictable times. Grip forces (normal to the grip surfaces) and the position of the manipulandum were recorded. In addition, movements of hand and arm segments were assessed by recording the position of markers placed at critical points. Subjects performed test series during normal digital sensibility and during local anesthesia of the index finger and thumb. To grade the size of movements of tissues proximal to the digits caused by the loadings, three different conditions of arm and hand support were used; (1) in the hand-support condition the subjects used the three ulnar fingers to grasp a vertical dowel support and the forearm was supported in a vacuum cast; (2) in the forearm-support condition only the forearm was supported; finally, (3) in the no-support condition the arm was free. With normal digital sensibility the size of the movements proximal to the digits had small effects on the grip-force control. In contrast, the grip control was markedly influenced by the extent of such movements during digital anesthesia. The poorest control was observed in the hand-support condition, allowing essentially only digital movements. The grip responses were either absent or attenuated, with greatly prolonged onset latencies. In the forearm and no-support conditions, when marked wrist movements took place, both the frequency and the strength of grip-force responses were higher, and the grip response latencies were shorter. However, the performance never approached normal. It is concluded that sensory inputs from the digits are dominant in reactive grip control. However, nondigital sensory input may be used for some grip control during impaired digital sensibility. Furthermore, the quality of the control during impaired sensibility depends on the extent of movements evoked by the load in the distal, unanesthetized parts of the arm. The origin of these useful sensory signals is discussed.
Adult↗
A functional analysis of the collicular output pathways: a dissociation of deficits following lesions of the dorsal tegmental decussation and the ipsilateral collicular efferent bundle in the Mongolian gerbil.
Mongolian gerbils received either lesions of the superior colliculus, small lesions of the uncrossed efferents of the superior colliculus, knifecuts of the dorsal tegmental decussation, or sham operations. The animals were subsequently tested for avoidance of overhead visual threat, orientation and locomotion toward small targets, and negotiation of a large barrier in order to reach a small target. Animals with collicular lesions showed no responses to overhead threat and had severe deficits in orienting to small targets. Animals with lesions of the uncrossed tectal efferents showed diminished responses to overhead threat but had no deficits in orienting to targets. Animals with lesions of the dorsal tegmental decussation showed only slight reductions in responses to overhead threats but clear impairments in the orientation tasks. The impairments in orientation, however, were less severe than those seen in collicular animals. Animals in all groups were able to negotiate barriers efficiently. These results suggest that separate output pathways of the superior colliculus mediate different types of visuomotor behaviours. The results further suggest that visual orientation to small targets does not depend completely on output through the predorsal bundle, but must also involve other collicular outputs.
Animals↗
Innovative approaches in the treatment of emesis.
Over the last 15 years, appreciation of the role of dopaminergic (D2) receptors and serotonergic (5-HT3) receptors has led to the development of a series of highly effective antiemetic agents. However, in spite of the suggestion of additional significant receptors (such as the NK-1 receptor and the opiate mu receptor), recent innovations in antiemetic treatment have concentrated on refinement of schedule, route, and dose. Single-dose regimens and oral formulations improve the convenience of antiemetic administration, while identification of the minimum effective dose has important economic implications. Involvement of experienced supportive care investigators in objective determination of utility scores for various supportive care modalities will be vital for rational inclusion of supportive care in pharmacoeconomic analysis, critical pathways, and clinical guidelines.
Administration, Oral↗
Vagal afferent dysfunction in naturally occurring canine esophageal motility disorder.
Few studies have examined the vagal afferent innervation of the esophagus in naturally occurring esophageal motility disorders. The present study assessed the integrity of distension-sensitive vagal afferents innervating the esophagus in naturally occurring canine megaesophagus. In the dog, esophageal distension induces reflex inhibition of crural diaphragm electromyographic activity that is mediated by vagal afferents innervating esophageal mechanoreceptors. This reflex was measured during stepwise esophageal distension in six dogs with congenital idiopathic megaesophagus, two dogs with megaesophagus secondary to esophageal striated muscle disease, and eight matched controls. In contrast to control dogs, inhibition of crural electromyographic activity was not observed in megaesophagus dogs with esophageal distension within the control volume range. With esophageal distensions far in excess of the control volume range, inhibition of crural electromyographic activity was not observed in five of six dogs with congenital idiopathic megaesophagus, while crural inhibition was observed in the two dogs with secondary megaesophagus. These findings indicate that a defect is present in the vagal afferent innervation to the esophagus in a majority of dogs with congenital idiopathic megaesophagus.
Afferent Pathways↗
Molecular genetic analysis of the calcineurin signaling pathways.
Calcineurin is a Ca2+- and calmodulin-regulated protein phosphatase that is important in Ca2+-mediated signal transduction. Recent application of the powerful techniques of molecular genetics has demonstrated that calcineurin is involved in the regulation of critical biological processes such as T cell activation, muscle hypertrophy, memory development, glucan synthesis, ion homeostasis, and cell cycle control. Notably, specific transcription factors have been shown to play a key role in regulating these functions, and their calcineurin-mediated dephosphorylation and nuclear translocation appear to be a central event in the signal transduction pathways. This review focuses on recent progress in these areas and discusses the evidence for cross-talk between calcineurin and other signaling pathways.
Animals↗
Human intramuscular and cutaneous pain: psychophysical comparisons.
We used psychophysical methods to compare the central processing of nociceptive inputs from skin and muscle in ten normal humans. Both intramuscular electrical and infrared CO2 laser cutaneous stimulation showed increasing but decelerating (downward concave) stimulus-response curves and similar temporal summation characteristics. Intramuscular stimulation was rated significantly more unpleasant than cutaneous stimulation. The results are consistent with a common mode of central nociceptive processing for skin and muscle pain intensity but suggest a relatively larger activation of affective mechanisms by muscle afferents.
Adult↗
Ancient origin of human complement factor H.
We studied the evolutionary history of two homologous proteins of the human complement system, factor H (FH) and the alpha chain of the C4b binding protein (C4bpalpha), and included in this study the related proteins from the barred sand bass (P. nebulifer) and the nematode C. elegans. Phylogenetic trees inferred from individual short consensus repeats (SCRs) and divergence among repeats from different genes suggest that human FH has a much closer evolutionary relationship to putative complement components from P. nebulifer and C. elegans than does the C4bpalpha. This indicates that a member of the alternative pathway of the complement system (FH) has an ancient origin, while a homologous member of the classical pathway (C4bpalpha) appeared later in evolutionary history as a result of gene duplication. The ancient evolutionary position of FH is in agreement with the suggestion that the alternative pathway of the complement system is older than the classical pathway. Phylogenetic analysis also shows that the sand bass cofactor protein SBP1 and cofactor related protein SBCRP-1 have diverged very recently.
Amino Acid Sequence↗
Evidence for an isomeric muconolactone isomerase involved in the metabolism of 4-methylmuconolactone by Alcaligenes eutrophus JMP134.
An enzyme specifically induced during 4-methylmuconolactone metabolism by Alcaligenes eutrophus JMP 134 and that exhibited muconolactone isomerizing activity was purified to homogeneity. The enzyme, involved in the isomerization of 3-methylmuconolactone had a high degree of sequence similarity with muconolactone isomerase of Alcaligenes eutrophus JMP 134 and other previously described muconolactone isomerases of the 3-oxoadipate pathway. Kinetic analysis showed that the enzyme has a substrate spectrum and a reaction mechanism similar to those of the muconolactone isomerase, but that it has distinct kinetic properties.
Alcaligenes↗
Modulation of masseter exteroceptive suppression by non-nociceptive upper limb afferent activation in humans.
The effects induced by non-noxious electrical stimulation of upper limb nerves on exteroceptive suppression (ES) of masseter muscle EMG activity were studied in 15 healthy subjects. EMG activity of masseter muscles was recorded bilaterally and great care was taken to minimise the activation of afferents other than the stimulated ones. Masseter ES was elicited by applying a non-noxious electrical stimulus to the skin above the mental nerve (Mt) of one side, during a voluntary contraction of masseter muscles at a prescribed steady clenching level. Onset and offset latencies and duration of early and late components of masseter ES (ES1 and ES2, respectively) were evaluated in control conditions and compared to those obtained when a non-noxious electrical stimulation was delivered separately to Med or Rad or simultaneously to both nerves (Med-Rad) of one side. Upper limb nerve stimulation could be simultaneous or it could precede or follow Mt stimulation by various time intervals. In control conditions, ES1 latency onset and duration values (mean +/- SD) were 11.3+/-2.9 ms and 16.9+/-2.1 ms, respectively, and ES2 latency onset and duration values were 44.5+/-6.0 ms and 28.6+/-11.1 ms, respectively. No significant differences were observed which were related to the side being recorded. Two types of effects, opposite in nature, were shown on masseter ES, depending on the time intervals between Mt and upper limb nerve stimulation. The first effect, which was facilitatory, consisted of a significant increase in ES1 and ES2 duration. A maximal increase in ES1 duration (134-155% compared to control value) occurred when upper limb nerve stimulation preceded that of Mt by 18-30 ms. Maximal ES2 lengthening (115-145%) was observed when upper limb nerve stimulation followed that of the Mt by 10 ms. The second effect was inhibitory and affected only ES2, which appeared completely eliminated when Med stimulation preceded that of Mt by 40-80 ms. By contrast, ES1 was never suppressed at any interstimulus interval. These data might reflect the different action of the central outflow, following the upper limb-induced effects, on the different neuronal circuits mediating ES1 and ES2.
Adult↗
Short-latency afferent inhibition during selective finger movement.
During individual finger movement, two opposite phenomena occur at the level of the central nervous system that could affect other intrinsic hand muscle representations, unintentional co-activation, and surround inhibition (SI). At rest, excitability in the motor cortex (M1) is inhibited at about 20 ms after electric stimulation of a peripheral nerve [short-latency afferent inhibition (SAI)]. We sought to determine whether SAI changes during selective index finger movement. Effects were measured by the response to transcranial magnetic stimulation in two functionally distinct target muscles of the hand [abductor digiti minimi muscle (ADM), first dorsal interosseus muscle (FDI)]. An increase in SAI in the ADM during index finger movement compared to at rest could help explain the genesis of SI. Electrical stimulation was applied to either the little finger (homotopic for ADM, heterotopic for FDI) or the index finger (heterotopic for ADM, homotopic for FDI). During index finger movement, homotopic SAI was present only in the ADM, and the effect of peripheral stimulation was greater when there was less co-activation. Heterotopic SAI found at rest disappeared with movement. We conclude that during movement, homotopic SAI on the muscle in the surround of the intended movement may contribute to SI.
Adult↗
Centrifugal regulation of task-relevant somatosensory signals to trigger a voluntary movement.
Many previous papers have reported the modulation of somatosensory evoked potentials (SEPs) during voluntary movement, but the locus and mechanism underlying the movement-induced centrifugal modulation of the SEPs elicited by a task-relevant somatosensory stimulus still remain unclear. We investigated the centrifugal modulation of the SEPs elicited by a task-relevant somatosensory stimulus which triggers a voluntary movement in a forewarned reaction time task. A pair of warning (S1: auditory) and imperative stimuli (S2: somatosensory) was presented with a 1 s interstimulus interval. Subjects were instructed to respond by moving the hand ipsilateral or contralateral to the somatosensory stimulation which elicits the SEPs. In four experiments, the locus and selectivity of the SEPs' modulation, the contribution of cutaneous afferents and the effect of contraction magnitude were examined, respectively. A control condition where subjects had no task to perform was compared to several task conditions. The amplitude of the frontal N30, parietal P30, and central P25 was decreased and that of the long latency P80 and N140 was increased when the somatosensory stimuli triggered a voluntary movement of the stimulated finger compared to the control condition. The N60 decreased with the movement of any finger. These results were considered to be caused by the centrifugal influence of neuronal activity which occurs before a somatosensory imperative stimulus. The present findings did not support the hypothesis that the inhibition of afferent inputs by descending motor commands can occur at subcortical levels. A higher contraction magnitude produced a further attenuation of the amplitude of the frontal N30, while it decreased the enhancement of the P80. Moreover, the modulation of neuronal responses seems to result mainly from the modulation of cutaneous afferents, especially from the moved body parts. In conclusion, the short- and long-latency somatosensory neuronal activities evoked by task-relevant ascending afferents from the moved body parts are regulated differently by motor-related neuronal activities before those afferent inputs. The latter activities may be associated with sensory gain regulation related to directing attention to body parts involved in the action.
Acoustic Stimulation↗
Entrainment to extinction of physiological tremor by spindle afferent input.
In this study the systematic modulation of wrist flexor muscle activity by imposed joint movement was examined. Ten subjects maintained a constant contraction level (25% of the maximum; trial duration: 20 s) in flexor carpi radialis while their wrists were perturbed with 50 different quasi-sinusoidal signals (frequency range: 0.5-9.5 Hz; amplitude: 0.3-4.2 degrees ). The frequency spectra of wrist position and the rectified and filtered electromyogram (EMG) were determined. The muscle activity was only weakly entrained to imposed movements of small amplitude and low frequency, as shown by a small peak in the EMG spectrum at the frequency of movement, while the most prominent peak in the spectrum was between 9 and 15 Hz, corresponding to the frequency range of physiological tremor. The entrainment of muscle activity increased markedly as the amplitude and frequency of the imposed movement increased, to the point of saturation of modulation and harmonic peaks in the spectrum. In parallel with this increase in entrainment, the 9-15 Hz tremor peak was progressively extinguished. The results are consistent with a coupled oscillator model in which the central oscillatory source(s) of tremor became fully entrained to the imposed movement at the highest amplitudes and frequencies. Such coupling depends on communication between the external forcing oscillator and the central oscillator(s), the I (a) afferent signal from the imposed movement being the most likely candidate to provide the entraining signal for the central oscillator(s).
Adult↗
Altered cortical integration of dual somatosensory input following the cessation of a 20 min period of repetitive muscle activity.
The adult human central nervous system (CNS) retains its ability to reorganize itself in response to altered afferent input. Intracortical inhibition is thought to play an important role in central motor reorganization. However, the mechanisms responsible for altered cortical sensory maps remain more elusive. The aim of the current study was to investigate changes in the intrinsic inhibitory interactions within the somatosensory system subsequent to a period of repetitive contractions. To achieve this, the dual peripheral nerve stimulation somatosensory evoked potential (SEP) ratio technique was utilized in 14 subjects. SEPs were recorded following median and ulnar nerve stimulation at the wrist (1 ms square wave pulse, 2.47 Hz, 1x motor threshold). SEP ratios were calculated for the N9, N11, N13, P14-18, N20-P25 and P22-N30 peak complexes from SEP amplitudes obtained from simultaneous median and ulnar (MU) stimulation divided by the arithmetic sum of SEPs obtained from individual stimulation of the median (M) and ulnar (U) nerves. There was a significant increase in the MU/M + U ratio for both cortical SEP components following the 20 min repetitive contraction task, i.e. the N20-P25 complex, and the P22-N30 SEP complex. These cortical ratio changes appear to be due to a reduced ability to suppress the dual input, as there was also a significant increase in the amplitude of the MU recordings for the same two cortical SEP peaks (N20-P25 and P22-N30) following the typing task. No changes were observed following a control intervention. The N20 (S1) changes may reflect the mechanism responsible for altering the boundaries of cortical sensory maps, changing the way the CNS perceives and processes information from adjacent body parts. The N30 changes may be related to the intracortical inhibitory changes shown previously with both single and paired pulse TMS. These findings may have implications for understanding the role of the cortex in the initiation of overuse injuries.
Adult↗
Inhibition versus facilitation of the reflex responsiveness of identified wrist extensor motor units by antagonist flexor afferent inputs in humans.
The question of whether Ia reciprocal inhibition might depend on the motor task and on the type of motor unit activated was investigated in the human extensor carpi radialis muscles. Ia reciprocal inhibition induced by stimulating the median nerve (conditioning stimulation) was estimated by measuring the changes in the firing probability of 37 extensor motor units in response to the radial nerve stimulation (100 test stimuli) delivered 1 ms after the conditioning stimulation. Six subjects were asked to perform a task consisting of either selectively contracting their wrist extensor muscles or co-activating their wrist and finger antagonist muscles by clenching their hand around a manipulandum. In the control recordings (test stimulation alone), the mean response probability of the 37 motor units was found to be greater during hand clenching. The motor units were identified on the basis of their force thresholds, their macro-potentials, and their twitch contraction times. The data obtained in the control recordings were consistent with the size principle. In the recordings where the responses were conditioned by applying median nerve stimulation, the response probability of the motor units with low force thresholds, small macro-potential areas, and long twitch contraction times tended to decrease, in line with the presence of Ia reciprocal inhibition, whereas the response probability of the motor units with higher force thresholds, larger macro-potential areas, and shorter twitch contraction times tended to increase. The median nerve stimulation may therefore have altered the efficiency with which the extensor Ia inputs recruited the homonymous motoneurones in the pool. The flexor group I afferents activated while the median nerve was stimulated had inhibitory effects on the slow contracting motor units, and facilitatory effects mainly on the fast contracting motor units. Both of these effects were stronger during hand clenching, in which the numerous cutaneous receptors of the palm and fingertips are liable to be activated. Besides their own effects on the excitability of the various types of motor units, cutaneous inputs are known to potentiate the Ib interneurones. In addition, the effects of the conditioning stimulation were superimposed on the tonic activity of the Ia and Ib afferents from the flexor wrist and finger muscles. This may explain why both the inhibitory and facilitatory effects of the median nerve stimulation were enhanced during hand clenching.
Action Potentials↗