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Modelling spinal circuitry involved in locomotor pattern generation: insights from the effects of afferent stimulation.

A computational model of the mammalian spinal cord circuitry incorporating a two-level central pattern generator (CPG) with separate half-centre rhythm generator (RG) and pattern formation (PF) networks has been developed from observations obtained during fictive locomotion in decerebrate cats. Sensory afferents have been incorporated in the model to study the effects of afferent stimulation on locomotor phase switching and step cycle period and on the firing patterns of flexor and extensor motoneurones. Here we show that this CPG structure can be integrated with reflex circuits to reproduce the reorganization of group I reflex pathways occurring during locomotion. During the extensor phase of fictive locomotion, activation of extensor muscle group I afferents increases extensor motoneurone activity and prolongs the extensor phase. This extensor phase prolongation may occur with or without a resetting of the locomotor cycle, which (according to the model) depends on the degree to which sensory input affects the RG and PF circuits, respectively. The same stimulation delivered during flexion produces a temporary resetting to extension without changing the timing of following locomotor cycles. The model reproduces this behaviour by suggesting that this sensory input influences the PF network without affecting the RG. The model also suggests that the different effects of flexor muscle nerve afferent stimulation observed experimentally (phase prolongation versus resetting) result from opposing influences of flexor group I and II afferents on the PF and RG circuits controlling the activity of flexor and extensor motoneurones. The results of modelling provide insights into proprioceptive control of locomotion.

Action Potentials↗

Auditory brainstem response (ABR) peak amplitude variability reflects individual differences in cochlear response times.

Previously, it was shown [Don et al., J. Acoust. Soc. Am. 94, 2135-2148 (1993)] that cochlear response times are gender specific and about 13% shorter in females than in males. It is also suggested that one of the possible reasons click-evoked auditory brainstem response (ABR) waveforms recorded from females are better defined and have larger amplitudes than those of males is due to a sex difference in cochlear response times leading to better synchronization of the cochlear output across the frequency regions. Variability in cochlear response times would also lead to variability in click evoked ABR amplitudes. The high-pass noise masking derived ABR technique was used to investigate the effect of normalizing the individual temporal variability at the neural and cochlear levels. This involved adjusting for differences in neural conduction time (I-V delay) by a compression or expansion of the derived ABR waveforms and by adjusting for differences in cochlear response times by a shift of the derived ABR waveforms. A summation of the compressed and shifted ABRs results in a normalized unmasked ABR waveform that can then be compared for amplitude variability with the unprocessed unmasked ABRs. Compensation for the neutral I-V variability had little effect while compensation for cochlear response times, particularly the delay between the 5.7- and 2.8-kHz regions, greatly affected the amplitude of wave V of the compounded ABR. This work provides a better understanding of the significant relationship between cochlear response times and variability of the ABR peak amplitudes.

Adolescent↗

A model for binaural response properties of inferior colliculus neurons. I. A model with interaural time difference-sensitive excitatory and inhibitory inputs.

A model was developed that simulates the binaural response properties of low-frequency inferior colliculus (IC) neurons in response to several types of stimuli. The model incorporates existing models for auditory-nerve fibers, bushy cells in the cochlear nucleus, and cells in medial superior olive (MSO). The IC model neuron receives two inputs, one excitatory from an ipsilateral MSO model cell and one inhibitory from a contralateral MSO model cell. The membrane potential of the IC model neuron (and the other model neurons) is described by Hodgkin-Huxley type equations. Responses of IC neurons are simulated for pure-tone stimuli, binaural beat stimuli, interaural phase-modulated tones, single binaural clicks, and pairs of binaural clicks. The simulation results show most of the observed properties of IC discharge patterns, including the bimodal and unimodal interaural time difference (ITD) functions, sensitivities to direction and rate of change of ITD, ITD-dependent echo suppression, and early and late inhibitions in response to clicks. This study demonstrates that these response properties can be generated by a simple model incorporating ITD-dependent excitation and inhibition from binaural neurons.

Acoustic Stimulation↗

A model for binaural response properties of inferior colliculus neurons. II. A model with interaural time difference-sensitive excitatory and inhibitory inputs and an adaptation mechanism.

The inferior colliculus (IC) model of Cai et al. [J. Acoust. Soc. Am. 103, 475-493 (1998)] simulated the binaural response properties of low-frequency IC neurons in response to various acoustic stimuli. This model, however, failed to simulate the sensitivities of IC neurons to dynamically changing temporal features, such as the sharpened dynamic interaural phase difference (IPD) functions. In this paper, the Cai et al. (1998) model is modified such that an adaptation mechanism, viz., an additional channel simulating a calcium-activated, voltage-independent potassium channel which is responsible for afterhyperpolarization, is incorporated in the IC membrane model. Simulations were repeated with this modified model, including the responses to pure tones, binaural beat stimuli, interaural phase-modulated stimuli, binaural clicks, and pairs of binaural clicks. The discharge patterns of the model in response to current injection were also studied and compared with physiological data. It was demonstrated that this model showed all the properties that were simulated by the Cai et al. (1998) model. In addition, it showed some properties that were not simulated by that model, such as the sharpened dynamic IPD functions and adapting discharge patterns in response to current injection.

Acoustic Stimulation↗

The effects of sensory hearing loss on cochlear filter times estimated from auditory brainstem response latencies.

Derived-band auditory brainstem responses (ABRs) were obtained in 43 normal-hearing and 80 cochlear hearing-impaired individuals using clicks and high-pass noise masking. The response times across the cochlea [the latency difference between wave V's of the 5.7- and 1.4-kHz center frequency (CF) derived bands] were calculated for five levels of click stimulation ranging from 53 to 93 dB p.-p.e. SPL (23 to 63 dB nHL) in 10-dB steps. Cochlear response times appeared to shorten significantly with hearing loss, especially when the average pure tone (1 to 8 kHz) hearing loss exceeded 30 dB. Examination of derived-band latencies indicates that this shortening is due to a dramatic decrease of wave V latency in the lower CF derived band. Estimates of cochlear filter times in terms of the number of periods to maximum response (Nmax) were calculated from derived-band latencies corrected for gender-dependent cochlear transport and neural conduction times. Nmax decreased as a function of hearing loss, especially for the low CF derived bands. The functions were similar for both males and females. These results are consistent with broader cochlear tuning due to peripheral hearing loss. Estimating filter response times from ABR latencies enhances objective noninvasive diagnosis and allows delineation of the differential effects of pathology on the underlying cochlear mechanisms involved in cochlear transport and filter build-up times.

Acoustic Stimulation↗

Motor pattern production in reciprocally inhibitory neurons exhibiting postinhibitory rebound.

Pairs of neurons which inhibit each other can produce regular alternating bursts of impulses if they also exhibit postinhibitory rebound (PIR). Computer studies show that stable patterns occur spontaneously in systems of pacemaker neurons with PIR, and can be triggered in systems of nonpacemakers without requiring tonic excitation. The repetition rates of these patterns are determined largely by the PIR parameters. The patterns resist perturbation by phasic synaptic inputs, but can be modulated or turned off by tonic inputs. One pair of PIR neurons can be entrained by another pair with a different repetition rate to produce more complex firing patterns.

Animals↗

Structural maturation of neural pathways in children and adolescents: in vivo study.

Structural maturation of fiber tracts in the human brain, including an increase in the diameter and myelination of axons, may play a role in cognitive development during childhood and adolescence. A computational analysis of structural magnetic resonance images obtained in 111 children and adolescents revealed age-related increases in white matter density in fiber tracts constituting putative corticospinal and frontotemporal pathways. The maturation of the corticospinal tract was bilateral, whereas that of the frontotemporal pathway was found predominantly in the left (speech-dominant) hemisphere. These findings provide evidence for a gradual maturation, during late childhood and adolescence, of fiber pathways presumably supporting motor and speech functions.

Adolescent↗

Dynamic optimization of odor representations by slow temporal patterning of mitral cell activity.

Mitral cells (MCs) in the olfactory bulb (OB) respond to odors with slow temporal firing patterns. The representation of each odor by activity patterns across the MC population thus changes continuously throughout a stimulus, in an odor-specific manner. In the zebrafish OB, we found that this distributed temporal patterning progressively reduced the similarity between ensemble representations of related odors, thereby making each odor's representation more specific over time. The tuning of individual MCs was not sharpened during this process. Hence, the individual responses of MCs did not become more specific, but the odor-coding MC assemblies changed such that their overlap decreased. This optimization of ensemble representations did not occur among olfactory afferents but resulted from OB circuit dynamics. Time can therefore gradually optimize stimulus representations in a sensory network.

Amino Acids↗

Ponto-geniculo-occipital (PGO) burst neurons: correlative evidence for neuronal generators of PGO waves.

A newly discovered class of neurons, ponto-geniculo-occipital (PGO) burst neurons, has PGO wave relationships of phase-leading, stereotyped discharge bursts, and the highest reported discharge specificity and coherence; these neurons thus fulfill correlative criteria for output generator neurons for PGO waves. The PGO burst neurons are recorded in a discrete dorsal brainstem area in apposition to the brachium conjunctivum.

Action Potentials↗

Renshaw cell activity in man.

The H-reflex elicited in triceps surae by percutaneous stimulation of the posterior tibial nerve was conditioned by stimuli applied through the same electrode. The differential sensitivity of motor and sensory fibres to duration of the stimulus pulse made it possible to condition the H-reflex with either a motor or a sensory stimulus. With both types of conditioning, the H-reflex was inhibited at conditioning-test intervals of 2-3 msec and was then facilitated, the peak of facilitation occurring at 5-8 msec with motor conditioning and 6-10 msec with sensory conditioning. The phase of facilitation was followed by further inhibition. We have concluded (1) that the effects of motor conditioning on the H-reflex result from the discharge of Renshaw cells activated by the antidromic volley in the motor axons, and (2) that the effects of sensory conditioning (at the times used in these experiments) are largely due to the activation of Renshaw cells secondary to the discharge of alpha motoneurones by the conditioning volley.

Adult↗

Cutaneous reflexes in small muscles of the hand.

A study has been made of the responses of motoneurones innervating small muscles of the hand to electrical and mechanical stimulation of the skin. Both excitatory and inhibitory effects could be observed in the same muscle after a single stimulus to a given area of skin. The earliest excitatory and inhibitory responses are probably mediated by group III and the smaller group II afferent nerve fibres. A later inhibition results from activity in the larger group II fibres which are connected to cutaneous mechanoreceptors, especially those in the tips of the fingers and thumb. This late inhibitory reflex may operate through the fusimotor system. The possible roles of these reflexes are discussed in relation to previous investigations in man and the cat.

Action Potentials↗

Effect of white matter disease on functional connections in the aging brain.

Periventricular white matter hyperintensities (PVHs) seen on T2 weighted MRI studies are common in elderly people and often represent demyelination of fibres. Damage to these fibres could lead to functional disconnection between brain regions. Electroencephalographic coherence, a measure of shared electrical activity between regions, was examined to determine if there was evidence for such disconnection. Twenty two subjects with clinically diagnosed dementia of the Alzheimer's type, 16 with multi-infarct dementia, and 18 normal controls were studied. It was hypothesised that coherence between areas presumably linked by fibres that traverse the periventricular region would be decreased in subjects with PVHs, and that PVHs would have a stronger association with decreased coherence than clinical diagnosis. It was also hypothesised that coherence between areas presumably connected by long corticocortical tracts that are neuroanatomically separated from the ventricles would be low in patients with Alzheimer's disease because of pyramidal cell death in this group, but would not be affected by the presence of PVHs. Patients with PVHs in fact had lower coherence than those without PVHs in the pre-Rolandic and post-Rolandic areas, where connecting fibres traverse the periventricular region. There was no effect of PVHs, however, on coherence between areas separated by the Rolandic fissure that were connected by long corticocortical tracts; this coherence was lowest among the patients with Alzheimer's disease. These patterns of association suggest that coherence may detect different types of neurophysiological "disconnection," and may be sensitive to selective damage to different fibre pathways.

Aged↗

Somatosensory evoked blink response: findings in patients with Miller Fisher syndrome and in normal subjects.

Reflex blinking was elicited by the electrical stimulation of peripheral nerves and various parts of the body of seven of 11 patients with Miller Fisher syndrome. This reflex blinking disappeared during recovery. Reflex blinking was elicited in normal subjects only with specific stimulation of the peripheral nerves of their upper extremities. This response may be due to a release phenomenon transmitted via the brainstem reticular formation and may be useful in detecting latent CNS involvement in patients with Miller Fisher syndrome.

Adult↗

Focal hand dystonia in a patient with thoracic outlet syndrome.

A patient affected by thoracic outlet syndrome, with an involvement of the left lower primary trunk due to a rudimentary cervical rib, developed a severe hand dystonia on the same side. The dystonic posture was characterised by a flexion of the wrist with the fingers curled into the palm. Polygraphic recordings performed on the left flexor digitorum superficialis (FDS4) and extensor digitorum superficialis (EDC4) muscles, during a repetitive tapping task of the fourth digit, showed a loss of well formed bursts without a clear silent period along with long duration bursts of cocontraction in antagonistic muscles. The study of reciprocal inhibition between forearm flexor and extensor muscles showed a reduced amount of inhibition in both the disynaptic and the later presynaptic phase of inhibition. The patient underwent an operation with resection of the cervical rib. Twelve hours after the operation the patient experienced a significant improvement of the hand dystonia; the distonia had disappeared completely by two months with a progressive normalisation of reciprocal inhibition.

Adult↗

Isolated dysarthria due to extracerebellar lacunar stroke: a central monoparesis of the tongue.

OBJECTIVES: The pathophysiology of dysarthria can preferentially be studied in patients with the rare lacunar stroke syndrome of "isolated dysarthria". METHODS: A single study was carried out on seven consecutive patients with sudden onset of isolated dysarthria due to single ischaemic lesion. The localisation of the lesion was identified using MRI. The corticolingual, cortico-orofacial, and corticospinal tract functions were investigated using transcranial magnetic stimulation. Corticopontocerebellar tract function was assessed using 99mTc hexamethylpropylene amine oxime-single photon emission computerised tomography (HMPAO-SPECT) in six patients. Sensory functions were evaluated clinically and by somatosensory evoked potentials. RESULTS: Brain MRI showed the lesions to be located in the corona radiata (n=4) and the internal capsule (n=2). No morphological lesion was identified in one patient. Corticolingual tract function was impaired in all patients. In four patients with additional cortico-orofacial tract dysfunction, dysarthria did not differ from that in patients with isolated corticolingual tract dysfunction. Corticospinal tract functions were normal in all patients. HMPAO-SPECT showed no cerebellar diaschisis, suggesting unimpaired corticopontocerebellar tract function. Sensory functions were not affected. CONCLUSION: Interruption of the corticolingual pathways to the tongue is crucial in the pathogenesis of isolated dysarthria after extracerebellar lacunar stroke.

Cerebellum↗