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Climate change is causing widespread melting of land and sea ice in the Arctic, leading to an increase in freshwater input to the ocean. This may have an impact on ocean circulation, marine ecosystems, and biodiversity in the region. Our findings provide new insights into the summer hydrography conditions at proglacial fjord entrances along large parts of the east coast of Greenland. As most freshwater exits the Arctic Ocean through Fram Strait this study focuses on understanding the origin of spatial distribution of temperature and freshwater in the coastal waters in East Greenland. We find that Polar Water and the Atlantic Water variants (Eurasian Basin Atlantic Water/Subpolar Mode Water) dominate coastal waters north and south of Denmark Strait, respectively, and that coastal waters are influenced by advected meltwater from the Arctic Ocean, glacier meltwater and local precipitation. Combining hydrographic observations, water isotope data, and water source fraction analysis, we show that glacier meltwaters can be detected at fjord entrances and down to approximately 200 m. Integrated over the upper 200 m of the water column, glacial meltwater account for approximately 9%, precipitation for around 8% and Polar Water (including sea ice melt) for approximately 83% of the freshwater observed along the East Greenland coast. Below 200 m, Atlantic Water variants dominate the entire coastal section. The freshwater along East Greenland stays close to the coast and we could not detect any glacier meltwater at the slope. The rapid warming of our planet has increased freshwater input to the Arctic Ocean. A major portion of this freshwater is exiting through Fram Strait. Also, meltwater runoff from tundra lands and glaciers connected to the Greenland ice sheet is an increasingly significant freshwater source to fjords. At present, incomplete observations exist regarding the spatial distribution of freshwater and its origin along East Greenland. Here we present results from a compressed survey of the pan‐East Greenland coastal system from the entrance of fjords. We describe the spatial distribution of water masses and source water fractions along East Greenland and their link to proglacial fjords. Polar Water and Atlantic Water variants dominate East Greenland coastal waters north and south of Denmark Strait, respectivelyGlacier meltwater cannot be detected at the slope and most Polar Water, meteoric water, and glacier meltwater are confined to the coastAlong the coast, glacial meltwater account for ∼9%, precipitation for ∼8% and Polar Water (including sea ice melt) for ∼83% of the freshwater Polar Water and Atlantic Water variants dominate East Greenland coastal waters north and south of Denmark Strait, respectively Glacier meltwater cannot be detected at the slope and most Polar Water, meteoric water, and glacier meltwater are confined to the coast Along the coast, glacial meltwater account for ∼9%, precipitation for ∼8% and Polar Water (including sea ice melt) for ∼83% of the freshwater

La infección por el coronavirus SARS-CoV-2 originada en diciembre de 2019 en la región china de Wuhan ha adquirido proporciones pandémicas. A día de hoy ha ocasionado más de 1,7 millones de contagios y más de 100.000 muertes en todo el mundo. La investigación científica actual se centra en el mejor conocimiento de la infección aguda y de sus estrategias terapéuticas. Dada la magnitud de la epidemia, planteamos una revisión especulativa sobre las posibles consecuencias en patología neurológica a medio/largo plazo, con especial atención a enfermedades neurodegenerativas y neuropsiquiátricas con base neuroinflamatoria, teniendo en cuenta la evidencia directa de afectación neurológica a causa de la infección aguda.

Telemonitoring of home blood pressure measurements (TBPM) is a new and promising supplement to diagnosis, control and treatment of hypertension. We wanted to compare the outcome of antihypertensive treatment based on TBPM and conventional monitoring of blood pressure. Participants were recruited from a prevalence study among citizens aged 55–64 years in the municipality of Holstebro, Denmark. The study was a randomized, controlled, unblinded 3 months’ trial. In the intervention group, antihypertensive treatment was based on TBPM with transmission of the measurements and subsequent communication by telephone or e-mail. In the control group, patients received usual care. Primary outcome was reduction in daytime ambulatory blood pressure measurements (ABPM) from baseline to 3 months’ follow-up. Of 375 participants randomized, primary outcome data were available for 356 (95%). In both groups, daytime ABPM decreased significantly. The decrease in daytime ABPM in the intervention group was systolic/diastolic, −8±12/−4±7 mm Hg. This did not differ significantly from the control group’s −8±13/−4±8 mm Hg. An equal number of participants obtained normal daytime ABPM, in the intervention group 17% (31/175) versus control 21% (37/181), P=0.34. We found that both TBPM patients and controls achieved a significant blood pressure reduction in this randomized, controlled, unblinded 3-month trial. We found no difference in blood pressure reduction or number of patients reaching blood pressure goals. Further information and education of some general practitioners seem to be relevant regarding blood pressure management and control of hypertension.

Parodontal erkrankte Patienten weisen bei der Versorgung mit dentalen Implantaten ein erhöhtes Implantatverlustrisiko und ein erhöhtes Risiko für periimplantären Knochenverlust auf. Anhand des klinischen Fallbeispiels einer parodontal erkrankten Patientin wird im vorliegenden Beitrag ein Konzept zur Risikoreduktion aufgezeigt. Hierbei liegt der Fokus auf den drei Faktoren der parodontalen Vor-/Nachsorge, der Auswahl einer gering-moderat rauen Implantatoberfläche und der Etablierung von befestigter Mukosa. Ziel ist es, dem Leser eine Vorgehensweise an die Hand zu geben, die auf eigene klinische Fälle adaptiert werden kann.

The pathophysiological mechanisms underlying the development of spasticity are not clear, but the excitability of the disynaptic reciprocal inhibitory pathway is affected in many patients with spasticity of different origin. Patients with genetically identified autosomal dominant pure spastic paraparesis (ADPSP) develop spasticity and paresis in the legs, but usually have no symptoms in the arms. Comparison of the spinal and supraspinal control of the legs and arms in these patients may therefore provide valuable information about the pathophysiology of spasticity. In the present study, we tested the hypothesis that one of the pathophysiological mechanisms of spasticity in these patients is abnormal corticospinal transmission and that this may lead to decreased reciprocal inhibition. Ten patients and 15 healthy age-matched control subjects were investigated. The patients were all spastic in the legs (with hyperactive tendon reflexes, increased muscle tone and Babinski sign), but had no neurological symptoms in the arms (except for one patient). Disynaptic reciprocal Ia inhibition of flexor carpi radialis (FCR) and soleus (SOL) motoneurons was measured (as the depression of the background FCR and SOL EMG activity and as the short latency inhibition of the FCR and SOL H-reflex evoked by radial and peroneal nerve stimulation). In addition, the latency of motor evoked potentials (MEPs) in the FCR muscle and the tibialis anterior (TA) muscle was measured. In the patients, the mean reciprocal inhibition was normal in the arms, while it was significantly decreased in the leg compared with the healthy subjects. In the patients, the average latency of MEPs in the FCR muscle was normal, while the latency to the MEP in TA muscle was significantly longer than that found in healthy subjects. Four patients, however, differed from the other patients by having significant reciprocal inhibition in the leg and a significantly shorter latency of TA MEPs than found in the other patients. The six patients without reciprocal inhibition in the leg instead had significant short latency facilitation of the SOL H-reflex and a longer TA MEP latency than seen in the healthy subjects and in the four patients with retained reciprocal inhibition. These findings support the hypothesis that disynaptic reciprocal inhibition and short latency facilitation are involved in the development of spasticity and, furthermore, they suggest a positive correlation between impairment of corticospinal transmission and decrease of reciprocal inhibition/appearance of reciprocal facilitation.

Pulmonary surfactant lowers the surface tension of the lung air−liquid interface to prevent alveolar collapse. It is composed mainly of saturated and unsaturated phosphatidylcholines and phosphatidylglycerols. Solvent-spread films of a pulmonary surfactant, bovine lipid extract surfactant (BLES), form liquid condensed and liquid expanded phases with changing surface pressures, as seen by fluorescence and atomic force microscopy. Time-of-flight secondary ion mass spectrometry conducted in an imaging mode below the static limit provides a novel means of mapping the identities of the molecular species present in each phase. Images can be obtained for cations, like calcium and sodium, as well as for phospholipid parent and fragment ions. The phospholipids identified include dipalmitoyl- and palmitoyloleoylphosphatidylcholine as positive ions and dipalmitoyl- and palmitoyloleoylphosphatidylglycerol as negative ions. We observe good miscibility of phospholipids with similar chain lengths but different headgroups. At higher surface pressures, dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylglycerol cocrystallize in the liquid condensed (LC) phase. As well, there is evidence of an intermediate phase, within the LC region. The results indicate that the details of phospholipid mixing and reorganization in surfactant films can be determined by static secondary ion mass spectrometry imaging at high resolution, thus providing insight into the relationship between composition and structure in surfactant films at the air−aqueous interface.

Time- and frequency-domain analysis of the coupling between pairs of electromyograms (EMG) recorded from leg muscles was investigated during walking in healthy human subjects. For two independent surface EMG signals from the tibialis anterior (TA) muscle, coupling estimated from coherence measurements was observed at frequencies ≤50 Hz, with identifiable peaks occurring in two frequency bands ranging approximately from 8 to 15 and 15 to 20 Hz. The coherence between TA recordings was greatest toward the end of swing, reduced in early swing, and largely absent in midswing. In time-domain estimates constructed from paired TA EMG recordings, a short-lasting central peak indicative of motor-unit synchronization was observed. This feature of motor-unit coupling was also reduced in mid swing. In paired recordings made among triceps surae, quadriceps, and hamstring muscles, a similar pattern of correlation to that for paired TA recordings was observed. However, no significant coupling was observed in recordings for which one EMG recording was made from an ankle flexor/extensor muscle and the other from a knee extensor/flexor muscle. These results demonstrate that for TA a modulation exists in the functional coupling of motor units recruited during swing. The data also indicate that human motoneurons belonging to different muscles are only weakly coupled during walking. This absence of widespread short-term synchronization between the activities of muscles of the leg may provide a basis for the highly adaptive nature of human gait patterns.

Normal coordinated movement requires that the activity of antagonistic motoneurones may be depressed at appropriate times during the movement. Both glycinergic and GABAergic inhibitory mechanisms participate in this control. Patients with the major form of hyperekplexia (hereditary startle disease) have impaired inhibition of spinal motoneurones from local glycinergic interneurones and represent an ideal opportunity for studying the role of glycinergic inhibition in the control of antagonistic muscles. In the present study we investigated whether impaired glycinergic inhibition affects the corticospinal control of antagonistic spinal motoneurones in 10 patients with hyperekplexia and whether there are mechanisms that may compensate for the lack of glycinergic inhibition. In healthy subjects transcranial magnetic stimulation (TMS) produced a short‐latency inhibition of the soleus H‐reflex at rest and during tonic dorsiflexion. This inhibition, which has been shown to be mediated by spinal (glycinergic) inhibitory interneurones, was absent in all four patients in whom this experiment was performed. This confirms that glycinergic transmission is impaired in the patients. During voluntary dorsiflexion subthreshold TMS produced a depression of the ongoing EMG activity in the tibialis anterior (TA) muscle in both healthy subjects and all of the six tested patients. This is consistent with the idea that this EMG depression is caused by activation of cortical (GABAergic) inhibitory interneurones. Cross‐correlation analysis revealed normal short‐term synchronization of TA motor units accompanied by coherence in the 8‐12 Hz and 18‐35 Hz frequency bands in the 10 patients. As in healthy subjects, 8‐12 Hz coherence accompanied by decreased tendency to discharge synchronously (de‐synchronization) was found in recordings from the antagonistic TA and soleus muscles in 2 of the 10 patients. This suggests that glycinergic inhibition is not responsible for de‐synchronization of antagonistic motor units, but that other GABAergic‐inhibitory mechanisms must be involved. We propose that such mechanisms may compensate for the lack of glycinergic reciprocal inhibition in the hyperekplectic patients and explain why voluntary movements are not more severely affected.

It has been demonstrated in man that the H-reflex is more depressed by presynaptic inhibition than the stretch reflex. Here we investigated this finding further in the alpha-chloralose-anesthetized cat. Soleus monosynaptic reflexes were evoked by electrical stimulation of the tibial nerve or by stretch of the triceps surae muscle. Conditioning stimulation of the posterior biceps and semitendinosus nerve (PBSt) produced a significantly stronger depression of the electrically than the mechanically evoked reflexes. The depression of the reflexes has been shown to be caused by presynaptic inhibition of triceps surae Ia afferents. We investigated the hypothesis that repetitive activation of peripheral afferents may reduce their sensitivity to presynaptic inhibition. In triceps surae motoneurones, we measured the effect of presynaptic inhibition on excitatory postsynaptic potentials (EPSPs) produced by repetitive activation of the peripheral afferents or by fast and slow muscle stretch. EPSPs evoked by single electrical stimulation of the tibial nerve or by fast muscle stretch were significantly depressed by PBSt stimulation. However, the last EPSP in a series of EPSPs evoked by a train of electrical stimuli (5–6 shocks, 150–200 Hz) was significantly less depressed by the conditioning stimulation than the first EPSP. In addition, the last part of the long-lasting EPSPs evoked by a slow muscle stretch was also less depressed than the first part. A single EPSP evoked by stimulation of the medial gastrocnemius nerve was less depressed when preceded by a train of stimuli applied to the same nerve than when the same train of stimuli was applied to a synergistic nerve. The decreased sensitivity of the test EPSP to presynaptic inhibition was maximal when it was evoked within 20 ms after the train of EPSPs. It was not observed at intervals longer than 30 ms. These findings suggest that afferent activity may decrease the efficiency of presynaptic inhibition. We propose that the described interaction between afferent nerve activity and presynaptic inhibition may partly explain why electrically and mechanically evoked reflexes are differently sensitive to presynaptic inhibition.

Transcranial magnetic stimulation activates corticospinal neurones directly and transsynaptically and hence, activates motoneurones and results in a response in the muscle. Transmastoid stimulation results in a similar muscle response through activation of axons in the spinal cord. This study was designed to determine whether the two stimuli activate the same descending axons. Responses to transcranial magnetic stimuli paired with electrical transmastoid stimuli were examined in biceps brachii in human subjects. Twelve interstimulus intervals (ISIs) from −6 ms (magnet before transmastoid) to 5 ms were investigated. When responses to the individual stimuli were set at 10‐15 % of the maximal M‐wave, responses to the paired stimuli were larger than expected at ISIs of −6 and −5 ms but were reduced in size at ISIs of −2 to 1 ms and at 3 to 5 ms. With individual responses of 3‐5 % of maximal M‐wave, facilitation still occurred at ISIs of −6 and −5 ms and depression of the paired response at ISIs of 0, 1, 4 and 5 ms. The interaction of the response to transmastoid stimulation with the multiple descending volleys elicited by magnetic stimulation of the cortex is complex. However, depression of the response to the paired stimuli at short ISIs is consistent with an occlusive interaction in which an antidromic volley evoked by the transmastoid stimulus collides with and annihilates descending action potentials evoked by the transcranial magnetic stimulus. Thus, it is consistent with the two stimuli activating some of the same corticospinal axons.

Secondary ion mass spectrometry (SIMS) image depth profiles have been made through grain structures on nickel alloy material that had displayed differing levels of intergranular stress corrosion cracking. The distributions of trace impurities, both within and outside the grain boundaries, are documented qualitatively through three‐dimensional imaging, and quantitatively through the use of cross‐correlation spectroscopy. Copyright © 2002 John Wiley & Sons, Ltd.

Synchronization of motor unit activity was investigated during treadmill walking (speed: 3–4 km/h) in 25 healthy human subjects. Recordings were made by pairs of wire electrodes inserted into the tibialis anterior (TA) muscle and by pairs of surface electrodes placed over this muscle and a number of other lower limb muscles (soleus, gastrocnemius lateralis, gastrocnemius medialis, biceps femoris, vastus lateralis, and vastus medialis). Short-lasting synchronization (average duration: 9.6 ± 1.1 ms) was observed between spike trains generated from multiunit electromyographic (EMG) signals recorded by the wire electrodes in TA in eight of nine subjects. Synchronization with a slightly longer duration (12.8 ± 1.2 ms) was also found in 13 of 14 subjects for paired TA surface EMG recordings. The duration and size of this synchronization was within the same range as that observed during tonic dorsiflexion in sitting subjects. There was no relationship between the amount of synchronization and the speed of walking. Synchronization was also observed for pairs of surface EMG recordings from different ankle plantarflexors (soleus, medial gastrocnemius, and lateral gastrocnemius) and knee extensors (vastus lateralis and medialis of quadriceps), but not or rarely for paired recordings from ankle and knee muscles. The data demonstrate that human motor units within a muscle as well as synergistic muscles acting on the same joint receive a common synaptic drive during human gait. It is speculated that the common drive responsible for the motor unit synchronization during gait may be similar to that responsible for short-term synchronization during tonic voluntary contraction.

The aim of the study was to investigate whether impaired control of transmission in spinal inhibitory pathways contributes to the functional disability of patients with spasticity. To this end, transmission in the pathways mediating disynaptic reciprocal Ia inhibition and presynaptic inhibition was investigated in 23 healthy subjects and 20 patients with spastic multiple sclerosis during ankle dorsiflexion and plantar flexion. In healthy subjects, but not in spastic patients, the soleus H reflex was depressed at the onset of dorsiflexion (300 ms rise time, 20% of maximal voluntary effort). At the onset of plantar flexion, the soleus H reflex was more facilitated in the healthy subjects than in the patients. The H reflex increased more with increasing level of tonic plantar flexion and decreased more with dorsiflexion in the healthy subjects than in the spastic patients. Transmission in the disynaptic Ia reciprocal inhibitory pathway from ankle dorsiflexors to plantar flexors was investigated by conditioning the soleus H reflex by previous stimulation of the common peroneal nerve (conditioning-test interval 2-3 ms; stimulation intensity 1.05 times the motor response threshold). At the onset of dorsiflexion, stimulation of the common peroneal nerve evoked a significantly larger inhibition than at rest in the healthy subjects but not in the spastic patients. At the onset of plantar flexion the inhibition decreased in the healthy subjects, but because only weak inhibition was observed at rest in the patients it was not possible to determine whether a similar decrease occurred in this group. There were no differences in the modulation of inhibition during tonic plantar flexion and dorsiflexion in the two populations. Presynaptic inhibition of Ia afferents terminating on soleus motor neurones was evaluated from the monosynaptic Ia facilitation of the soleus H reflex evoked by femoral nerve stimulation. Femoral nerve facilitation was decreased at the onset of dorsiflexion and increased at the onset of plantar flexion in the healthy subjects and patients, but the changes were significantly greater in the healthy subjects. There was no difference between the two populations in the modulation of presynaptic inhibition during tonic plantar flexion and dorsiflexion. It is suggested that the abnormal regulation of disynaptic reciprocal inhibition and presynaptic inhibition in patients with spasticity is responsible for the abnormal modulation of stretch reflexes in relation to voluntary movement in these patients. Lack of an increase in reciprocal inhibition and presynaptic inhibition at the onset of dorsiflexion may be responsible for the tendency to elicitation of unwanted stretch reflex activity and co-contraction of antagonistic muscles in patients with spasticity.

The aim of the study was to investigate whether impaired control of transmission in spinal inhibitory pathways contributes to the functional disability of patients with spasticity. To this end, transmission in the pathways mediating disynaptic reciprocal Ia inhibition and presynaptic inhibition was investigated in 23 healthy subjects and 20 patients with spastic multiple sclerosis during ankle dorsiflexion and plantar flexion. In healthy subjects, but not in spastic patients, the soleus H reflex was depressed at the onset of dorsiflexion (300 ms rise time, 20% of maximal voluntary effort). At the onset of plantar flexion, the soleus H reflex was more facilitated in the healthy subjects than in the patients. The H reflex increased more with increasing level of tonic plantar flexion and decreased more with dorsiflexion in the healthy subjects than in the spastic patients. Transmission in the disynaptic Ia reciprocal inhibitory pathway from ankle dorsiflexors to plantar flexors was investigated by conditioning the soleus H reflex by previous stimulation of the common peroneal nerve (conditioning-test interval 2–3 ms; stimulation intensity 1.05 times the motor response threshold). At the onset of dorsiflexion, stimulation of the common peroneal nerve evoked a significantly larger inhibition than at rest in the healthy subjects but not in the spastic patients. At the onset of plantar flexion the inhibition decreased in the healthy subjects, but because only weak inhibition was observed at rest in the patients it was not possible to determine whether a similar decrease occurred in this group. There were no differences in the modulation of inhibition during tonic plantar flexion and dorsiflexion in the two populations. Presynaptic inhibition of Ia afferents terminating on soleus motor neurones was evaluated from the monosynaptic Ia facilitation of the soleus H reflex evoked by femoral nerve stimulation. Femoral nerve facilitation was decreased at the onset of dorsiflexion and increased at the onset of plantar flexion in the healthy subjects and patients, but the changes were significantly greater in the healthy subjects. There was no difference between the two populations in the modulation of presynaptic inhibition during tonic plantar flexion and dorsiflexion. It is suggested that the abnormal regulation of disynaptic reciprocal inhibition and presynaptic inhibition in patients with spasticity is responsible for the abnormal modulation of stretch reflexes in relation to voluntary movement in these patients. Lack of an increase in reciprocal inhibition and presynaptic inhibition at the onset of dorsiflexion may be responsible for the tendency to elicitation of unwanted stretch reflex activity and co-contraction of antagonistic muscles in patients with spasticity.

1In cat lumbar motoneurones, disynaptic inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of antagonist motor nerves were depressed for at least 150 ms following conditioning stimulation of flexor (1.7‐2 times threshold (T)) and ankle extensor (5T) nerves. The aim of the present study was to investigate the possibility that this depression is caused by presynaptic inhibitory mechanisms acting at the terminals of group I afferent fibres projecting to the Ia inhibitory interneurones and/or the terminals of these interneurones to the target motoneurones.2Conditioning stimulation of flexor, but not ankle extensor, nerves evoked a depression of the monosynaptic Ia excitatory postsynaptic potentials (EPSPs) recorded intracellularly in Ia inhibitory interneurones. This depression lasted between 200 and 700 ms and was not accompanied by a depression of the monosynaptic EPSPs evoked by stimulation of descending pathways. These results suggest that flexor, but not ankle extensor, group I afferent fibres can modulate sensory transmission at the synapse between Ia afferent fibres and Ia inhibitory interneurones.3Conditioning stimulation of flexor muscle nerves, extensor muscle nerves and cutaneous nerves produced a long‐lasting increase in excitability of the terminals of the Ia inhibitory interneurones. The increase in the excitability of the terminals was not secondary to an electrotonic spread of synaptic excitation at the soma. Indeed, concomitant with the excitability increase of the terminals there were signs of synaptic inhibition in the soma.4The unitary IPSPs induced in target motoneurones following the spike activity of single Ia inhibitory interneurones were depressed by conditioning stimulation of muscle and cutaneous nerves. Since the conditioning stimulation also evoked compound IPSPs in those motoneurones, a firm conclusion as to whether unitary IPSP depression involved presynaptic inhibitory mechanism of the terminals of the interneurones could not be reached.5The possibility that the changes in excitability of the Ia interneuronal terminals reflect the presence of a presynaptic inhibitory mechanism similar to that operating at the terminals of the afferent fibres (presynaptic inhibition) is discussed.1. In cat lumbar motoneurones, disynaptic inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of antagonist motor nerves were depressed for at least 150 ms following conditioning stimulation of flexor (1.7‐2 times threshold (T)) and ankle extensor (5T) nerves. The aim of the present study was to investigate the possibility that this depression is caused by presynaptic inhibitory mechanisms acting at the terminals of group I afferent fibres projecting to the Ia inhibitory interneurones and/or the terminals of these interneurones to the target motoneurones.

Objectives: To measure the effect of baclofen on the transmission in different spinal pathways to soleus motoneurones in spastic multiple sclerosis patients.

1Motor unit firing rates and voluntary activation of muscle decline during sustained isometric contractions. After exercise, the responses to motor cortical and corticospinal stimulation are reduced. These changes may reflect motoneuronal inhibition mediated by group III and IV muscle afferents. To determine whether the post‐contraction depression of the responses to corticospinal or motor cortical stimulation could be maintained by continued firing of ischaemically sensitive group III and IV muscle afferents, we examined responses in muscles that were held ischaemic after exercise.2Following a sustained maximal voluntary contraction (MVC) of the elbow flexors lasting 2 min, the response to stimulation of the corticospinal tract was reduced but the usual recovery (over ∼2 min) was not delayed when the muscles were maintained ischaemic for 2 min after the contraction.3Following a sustained MVC, the time course of the reduction in the response to motor cortical stimulation (a gradual decrease over ∼2 min, maintained for > 10 min) was also not altered if the muscle was held ischaemic.4Mean arterial blood pressure rose to 155 ± 12 mmHg during the 2 min MVC, declined to 125 ± 9 mmHg immediately after it, but remained at this level without returning to pre‐exercise levels (102 ± 10 mmHg) until circulation to the arm was restored. This confirms that the sustained MVC activated a reflex dependent on group III and IV muscle afferents.5This study shows that ischaemically sensitive group III and IV muscle afferents do not mediate depression of responses to motor cortical or corticospinal stimulation after fatiguing exercise. It also suggests that firing of such afferents does not directly inhibit motoneurones or motor cortical output cells.

Abstract: The responses of 34 extensor-carpi-radialis motor units to graded transcranial magnetic stimulation (TMS) and electrical stimulation of the radial nerve were investigated in six human subjects. Simultaneously with the recording of the single motor-unit discharges, motor-evoked potentials (MEPs) and H-reflexes evoked by the two types of stimulation were recorded by surface electrodes and expressed as a percentage of the maximal motor response (Mmax). Ten motor units were activated in the H-reflex when it was less than 5% of Mmax, but not in the MEP even when it was 15% of Mmax. The opposite was observed for three motor units. Eleven motor units were recruited by both stimuli, but with significantly different recruitment thresholds. Only ten motor units had a threshold similar to TMS and radial nerve stimulation. From these observations, we suggest that caution should be taken when making conclusions regarding motor cortical excitability based on changes in the size of MEPs, even when it is ensured that there are no similar changes in background EMG-activity or H-reflexes.

The forked protein is an actin binding protein involved in the formation of large actin fiber bundles in developing Drosophila bristles. These are the largest example of a type of actin bundle characterized by parallel, hexagonally packed actin fibers, also found in intestinal microvilli, kidney proximal tubule microvilli, and stereocilia in the ear. Understanding how these structures are constructed and how that construction is regulated is an important question in cell and developmental biology. Because the timing of forked gene expression coincides with the formation of the actin fiber bundles, and since the forked protein is localized at the site of initiation of these bundles before they form, it has been proposed that the forked protein is an initiator of actin bundle formation. In this paper we show that the forked protein can induce the formation of bundles and increase actin polymerization in vertebrate cells. We use this system to identify regions of the forked protein which are essential for bundle formation and actin co-localization.

An improved protocol for site-directed mutagenesis based on the two-step polymerase chain reaction (PCR) megaprimer method is described. Compared to previously published protocols, the protocol described in this article ensures consistently a success rate of at least 85% with essentially no introduction of unwanted secondary mutations. The essential features of this protocol include an optimization of the template-primer amounts and ratio that allows the use of a reduced number of PCR cycles and the use of proof-reading thermostable DNA polymerases.

Abstract: Stimulation of cutaneous foot afferents has been shown to evoke a facilitation of the tibialis anterior (TA) EMG-activity at a latency of 70–95 ms in the early and middle swing phase of human walking. The present study investigated the underlying mechanism for this facilitation. In those subjects in whom it was possible to elicit a reflex during tonic dorsiflexion while seated (6 out of 17 tested), the facilitation in the TA EMG evoked by stimulation of the sural nerve (3 shocks, 3-ms interval, 2.0–2.5 perception threshold) was found to have the same latency in the swing phase of walking. The facilitation observed during tonic dorsiflexion has been suggested to be – at least partly – mediated by a transcortical pathway. To investigate whether a similar mechanism contributes to the facilitation observed during walking, magnetic stimulation of the motor cortex (1.2 motor threshold) was applied in the early swing phase at different intervals in relation to the cutaneous stimulation in 17 subjects. In 13 of the subjects, the motor potentials evoked by the magnetic stimulation (MEPs) were more facilitated by prior sural-nerve stimulation (conditioning-test intervals of 50–80 ms) than the algebraic sum of the control MEP and the cutaneous facilitation in the EMG when evoked separately. In four of these subjects, a tibialis anterior H-reflex could also be evoked during walking. In none of the subjects was an increase of the H-reflex similar to that for the MEP observed. In five experiments on four subjects, MEPs evoked by magnetic and electrical cortical stimulation were compared. In four of these experiments, only the magnetically induced MEPs were facilitated by prior stimulation of the sural nerve. We suggest that a transcortical pathway may also contribute to late cutaneous reflexes during walking.

1Activation of descending corticospinal tracts with transmastoid electrical stimuli has been used to assess changes in the behaviour of motoneurones after voluntary contractions. Stimuli were delivered before and after maximal voluntary isometric contractions (MVCs) of the elbow flexor muscles.2Following a sustained MVC of the elbow flexors lasting 5–120 s there was an immediate reduction of the response to transmastoid stimulation to about half of the control value. The response recovered to control levels after about 2 min. This was evident even when the size of the responses was adjusted to accommodate changes in the maximal muscle action potential (assessed with supramaximal stimuli at the brachial plexus).3To determine whether the post‐contraction depression required activity in descending motor paths, motoneurones were activated by supramaximal tetanic stimulation of the musculocutaneous nerve for 10 s. This did not depress the response to transmastoid stimulation.4Following a sustained MVC of 120 s duration, the response to transcranial magnetic stimulation of the motor cortex gradually declined to a minimal level by about 2 min and remained depressed for more than 10 min.5Additional studies were performed to check that the activation of descending tracts by transmastoid stimulation was likely to involve excitation of direct corticospinal paths. When magnetic cortical stimuli and transmastoid stimuli were timed appropriately, the response to magnetic cortical stimulation could be largely occluded.6This study describes a novel depression of effectiveness of corticospinal actions on human motoneurones. This depression may involve the corticomotoneuronal synapse.

The fluorescence characteristics of the polyene antibiotic Nystatin have been studied by measurements of quantum yields, lifetimes, and anisotropies in a model bilayer membrane. These measurements have been performed as a function of temperature and fluorophore-to-phospholipid molar ratio. Comparisons with data available for the parinaric acids demonstrate that the photophysics of the two polyene chromophores is similar. The quantum yield decreases at increasing Nystatin densities while the lifetimes are constant. These observations combined with quantitative comparisons with calculations of the density dependence of dynamic quenching in two-dimensional systems show that Nystatin fluorescence is quenched in bilayer membranes by a static process. This is likely due to the formation of complexes within the bilayer. The quenching is equally efficient in both the gel and liquid crystalline phases of the bilayer which suggests that the formation of the complexes occurs at all temperatures. At high Nystatin densities, there is also a quenching of the polarization, but the mechanism whereby this occurs is not clear. The limiting anisotropy at low concentrations is between 0.33 and 0.35 at all temperatures, suggesting that the Nystatin monomer is highly restricted in its reorientational motion in both gel and liquid crystalline phases.

1. The effect of magnetic stimulation of the human motor cortex on the excitability of soleus, tibialis anterior and flexor carpi radialis motoneurones was investigated by H reflex testing in ten healthy subjects. 2. At rest, an early facilitation of the flexor capri radialis and tibialis anterior H reflexes was always seen, whereas a similar early facilitation of the soleus H reflex was seen in only two out of seven subjects. For all three motoneuronal pools the facilitation was curtailed 1‐5 ms later by an inhibition which lasted for another 3‐4 ms. In five subjects an inhibition without any evidence of an earlier facilitation was seen for the soleus H reflex. 3. The intensity of the magnetic stimulation was subsequently decreased so that it had no effect on the H reflex at rest. When the subject then performed a voluntary agonist contraction a facilitatory effect with an early onset and a duration of 20‐25 ms was observed for all three muscles. When the subject performed a voluntary antagonist contraction an inhibition was seen for the soleus H reflex with an onset 1‐3 ms later than the facilitation. This is interpreted as resulting from the excitation by the magnetic stimulus of corticospinal neurones voluntarily activated in relation to the given motor task. 4. The initial part of the facilitation was significantly smaller during co‐contraction of both agonists and antagonists than during isolated agonist contraction. 5. Whereas the early part of the facilitation always occurred during plantarflexion when the H reflex was conditioned by magnetic stimulation, this was never the case when it was conditioned by electrical stimulation of the cortex with the stimulus regimes used in these experiments. 6. It is suggested that the early part of the facilitation observed during agonist contraction is caused by activation of cortico‐motoneuronal cells projecting to the agonist motoneuronal pool and that the inhibition observed during antagonist contraction is caused by activation of corticospinal cells projecting both to the antagonist motoneuronal pool and Ia inhibitory interneurones to the agonist motoneuronal pool. The smaller size of the earliest part of the facilitation observed during co‐contraction in relation to agonist contraction suggests a different cortical control of the two tasks.

1. The soleus (Sol) H reflex was conditioned by magnetic stimulation of the contralateral motor cortex at rest and during voluntary contraction in healthy human subjects. The intensity of the magnetic stimulus was adjusted so as to have no effect on the H reflex at rest. During tonic voluntary contraction the same magnetic stimulus produced a facilitation with a short latency and a long duration, thus reflecting an increased excitation of Sol motoneurones by the magnetic stimulus during voluntary contraction. 2. The amount of reflex facilitation produced by brain stimulation within the initial 0.5‐1 ms after its onset was investigated at different times during dynamic ramp‐and‐hold plantar flexion. The facilitation was largest at the onset of voluntary activity in the Sol muscle. It then decreased abruptly within 100 ms after the onset of the voluntary contraction. Neither the voluntary Sol activity nor the control H reflex decreased at this time. 3. Electrical stimulation of the brain with the anode placed lateral to the vertex produced a facilitation of the H reflex, which preceded the facilitation evoked by magnetic stimulation by 1‐2 ms. The facilitation produced by the magnetic stimulus occurred or increased at the onset of contraction in relation to rest in all experiments. However, this was the case in only two out of eight experiments, when the brain was stimulated electrically. 4. The size of the reflex facilitation measured at the onset of contraction was larger the faster the contraction. Positive correlations were found between the size of the facilitation and the peak of the first and second derivative of the torque and the peak Sol EMG activity. 5. It is suggested that the observed changes in the size of the short‐latency reflex facilitation produced by magnetic brain stimulation mainly reflects changes in the excitability of corticospinal cells, since similar changes were not observed in the size of the unconditioned Sol H reflex or in the short‐latency reflex facilitation produced by electrical brain stimulation. The data support the hypothesis that fast conducting corticospinal fibres with monosynaptic projections to spinal motoneurones are involved in the initiation of voluntary movement in man.

1. The latency of effects in the tibialis anterior (TA) and soleus (Sol) muscles evoked by electrical and magnetic stimulation of the motor cortex was evaluated in human subjects by H reflex testing. Post‐stimulus time histograms (PSTHs) were established for the discharge of single voluntarily activated motor units and motor‐evoked potentials (MEPs) in the surface electromyogram. 2. At rest both electrical and magnetic stimulation evoked an inhibition of the Sol H reflex at the lowest intensities of stimulation. In some subjects a facilitation with an earlier onset was seen when increasing the stimulation strength. When the anode for the electrical stimulation was placed at the vertex directly above the leg motor area, the inhibition or facilitation often had the same latency as when evoked by magnetic stimulation. However, when the anode was placed 2‐3 cm lateral to the vertex, effects evoked by the electrical stimulus often occurred 1‐2 ms earlier. 3. Short‐latency peaks in the PSTH of the discharges of single TA motor units also tended to occur earlier when evoked by electrical stimulation with the anode lateral to the vertex than when evoked by magnetic stimulation or electrical stimulation with the anode at the vertex. 4. In one subject, near‐maximal electrical stimulation evoked MEPs with a latency corresponding to that seen following stimulation of the brainstem by electrodes placed bilaterally over the mastoid processes approximately 16 cm more distal. Maximal magnetic stimulation, in contrast, never resulted in responses with a latency shorter than that seen with the weakest electrical stimuli at the vertex. 5. The initial facilitation of the Sol H reflex evoked by magnetic stimulation and by electrical anodal stimulation at the vertex increased when the subject performed a voluntary plantarflexion. In contrast, the earlier facilitation evoked by electrical anodal stimulation 2‐3 cm lateral to the vertex had the same size both at rest and during contraction. 6. We suggest that magnetic stimulation and electrical anodal stimulation at the vertex may preferentially activate descending cortical cells at, or close to, the cell soma. The initial responses evoked by these two stimuli may therefore be influenced by the excitability of the cortical cells. On the other hand, electrical stimulation with the anode 2‐3 cm lateral to the vertex seems to often activate the axons at a deeper level. The initial responses evoked by this type of stimulation may therefore not be influenced by the excitability of the cortical cells.

1. In resting subjects low‐intensity magnetic stimulation of the brain evoked an inhibition of the soleus H reflex at short latency (conditioning‐test interval, ‐2 to +1 ms) followed approximately 10 ms later by a period of facilitation. During voluntary dynamic or tonic plantar flexion the same stimulus evoked a facilitation with a shorter latency than the inhibition (conditioning‐test interval, ‐5 to ‐1 ms). 2. At the onset of ramp‐and‐hold plantar flexion the short‐latency facilitation was seen at lower intensities of stimulation than the long‐latency facilitation in six of seven subjects. At rest and/or during tonic plantar flexion the opposite was observed in four of the subjects, whereas the two facilitations had approximately the same threshold in the remaining subjects. 3. The short‐latency facilitation decreased approximately 100 ms after the onset of ramp‐and‐hold plantar flexion in all of eight subjects. The long‐latency facilitation, in contrast, either had the same size throughout the ramp phase or even increased around the end of the ramp phase. 4. The short‐latency facilitation of the reflex was significantly larger at the onset of a fast ramp‐and‐hold plantar flexion (10 N m (150 ms)‐1) than at the onset of a slow contraction (10 N m (600 ms)‐1), whereas the opposite was the case for the long‐latency facilitation. 5. As the short‐ and long‐latency facilitations had different thresholds and were differently regulated during voluntary movement, it is suggested that they are caused by activation of different descending pathways by the magnetic stimulus.

The size of the soleus H-reflex was measured after a slow (17 deg/s) passive stretch of ankle plantarflex ors and compared to its control size without muscle stretch in ten neurologically healthy subjects and in six spastic spinal-cord-injured patients. Two seconds after the end of the stretch, the size of the H-reflex was reduced to about 30% of its pre-stretch size in the healthy sub jects. The depression remained for 10–15 s. In the spastic, spinal-cord-injured patients, stretch caused significantly less reduction in the size of the H-reflex. The H-reflex also regained its pre-stretch size much faster than in healthy subjects. We suggest that the smaller depression of the H-reflex observed in spastic patients may be involved in the pathophysiology of spasticity.

The investigated material comprises rocks of the Palaeozoic ophiolitic assemblage exposed around the Sowie Góry Mountains Massif in the Sudetes in the form of the three units: Ślȩża, Ząbkowice and Nowa Ruda. The radiometric age (U-Pb) of the rocks, stated as 420 ∓ 20 Ma, places them in the Silurian. A palaeomagnetic study reveals the presence of four groups of palaeomagnetic poles. One of these is derived from an isolated component representing Permian overprinting. The second remanence component fits with the Silurian results from Baltica and may therefore be regarded as being of Silurian age. According to this interpretation, the ophiolitic complex would not have been involved in tectonic action after Silurian times. On the other hand, this component does not agree with the results of the neighbouring Bohemian Massif but is consistent with Late Carboniferous data of the European Variscans. In this case the other two components should be interpreted as Early- to Mid-Carboniferous overprints. This interpretation implies important strike-slip movements. In order to exclude one of these hypotheses, more data are still needed.

Scattering at random inhomogeneities in a gradient medium results in systematic deviations of the rays and travel times of refracted body waves from those corresponding to the deterministic velocity component. The character of the difference depends on the parameters of the deterministic and random velocity component. However, at great distances to the source, independently of the velocity parameters (weakly or strongly inhomogeneous medium), the most probable depth of the ray turning point is smaller than that corresponding to the deterministic velocity component, the most probable travel times also being lower. The relative uncertainty in the deterministic velocity component, derived from the mean travel times using methods developed for laterally homogeneous media (for instance, the Herglotz-Wiechert method), is systematic in character, but does not exceed the contrast of velocity inhomogeneities by magnitude. The gradient of the deterministic velocity component has a significant effect on the travel-time fluctuations. The variance at great distances to the source is mainly controlled by shallow inhomogeneities. The travel-time flucutations are studied only for weakly inhomogeneous media.

Clathrin associated adaptor protein is involved in endocytosis at the plasma membrane (AP-2) and protein sorting at the Golgi membrane (AP-1). There is a great deal of information available on the structure, function and binding characteristics of AP-2, however, there is little quantitative data on the AP-2 distribution at the membrane. Image correlation spectroscopy is a technique which yields number counts from an autocorrelation analysis of intensity fluctuations within confocal microscopy images. Image correlation spectroscopy analysis of the indirect immunofluorescence from AP-2 at the plasma membrane of CV-1 cells shows that AP-2 is in a bimodal distribution consisting of large coated pit associated aggregates of approximately 60 AP-2 molecules, and smaller aggregates containing approximately 20 AP-2 molecules, which we propose are coated pit nucleation sites. Following hypertonic treatment 25% of the AP-2 molecules dissociate from the large AP-2 aggregates and form AP-2 dimers, leaving the remaining AP-2 as large aggregates with approximately 45 molecules. The smaller AP-2 aggregates completely dissociate forming AP-2 dimers. Dispersion of AP-2 with hypertonic treatment is not seen qualitatively because the number of large AP-2 aggregates is unchanged, the aggregates are just 25% smaller. Change in temperature from 37 degrees C to 4 degrees C has no affect on the number of AP-2 aggregates or the AP-2 distribution between the two populations. These data and estimates of the coated pit size suggest that coated pits cover approximately 0.9% of the cell membrane. Combination of image correlation spectroscopy analysis and measurements of the CV-1 cell surface area show that there are approximately 6x10(5) AP-2 molecules per CV-1 cell with approximately 2x10(5) AP-2 molecules within coated pit structures.

Abstract: The existence of a spinal network capable of generating rhythmic alternating activity resembling locomotion still has not been firmly established in primates, including man, although evidence for one is accumulating. The present study investigated whether it is possible to activate such a network by administration of a variety of pharmacological agents to acutely spinalized marmoset monkeys (Callithrix jacchus) in the absence of phasic afferent input to the spinal cord. Fourteen marmoset monkeys were decerebrated, spinalized, and paralyzed. The nerves supplying both hindlimbs were cut and recorded from. In 5 monkeys the effect of electrical stimulation of the brainstem was investigated before spinalization. In 3 of these monkeys, rhythmic activity alternating between extensors and flexor nerves was seen. In the 2 other monkeys only synchronized activity was elicited. In acutely spinalized monkeys, administration of l-3,4-dihydroxyphenylalanine (l-dopa; 3–4 h after treatment with nialamide) failed to evoke any rhythmic alternating activity. In contrast, administration of clonidine elicited alternating activity in all of 8 monkeys tested. In 4 of these monkeys, the activity was restricted to alternation between ipsilateral and contralateral flexor nerves, whereas alternating activity between ipsilateral flexors and extensors was also seen in the other 4 monkeys. Administration of excitatory amino acids (NMDA or NMA) also elicited rhythmic alternating activity in 7 of 10 spinalized monkeys. In 4, rhythmic alternating activity was seen between extensors and flexors on one limb as well as between ipsilateral and contralateral flexors. In 3 monkeys NMDA/NMA produced alternation between extensors and flexors of one limb without alternation between the ipsilateral and contralateral sides. Administration of noradrenaline failed to elicit any rhythmic activity, but rather completely depressed already existing activity. Administration of serotonin (5-HT) was ineffective in facilitating alternating activity in 6 of 8 monkeys and was facilitatory to rhythmic activity in the other 2. We suggest that these data provide further evidence of a network capable of eliciting rhythmic alternating activity resembling locomotion in the primate spinal cord. The network, however, seems to be more difficult to activate pharmacologically in those conditions than in other mammals. This may especially be the case in higher primates, including man.

A mild heat shock at 35 degrees C, which induces heat shock gene expression, greatly enhances survival and the recovery of protein synthesis in Drosophila cells after a higher temperature heat shock. The 35 degrees C treatment is also effective in preventing heat-induced developmental defects in pupae. We show here that the major larval mRNAs are present in approximately normal (25 degrees C) concentrations after a 40.1 degrees C heat shock whether or not the animals receive a pretreatment. This indicates that the pretreatment affects translation directly rather than messenger concentration. We also observe selective translation of heat shock messages and some 25 degrees C messages during recovery from heat shock.

Familial hypercholesterolaemia (FH) is an autosomal dominant hereditary disease of lipid metabolism that in most families is caused by mutations in the low density lipoprotein receptor (LDLR) gene. Though more than 150 mutations are known, the clinical picture associated with most of these is not known. Genetic FH diagnosis may soon become routine in the setting of genetic counselling, and therefore thorough information on the phenotype——genotype relationship of different mutations is now important. In this study, index patients from each of 14 Danish FH families were screened for mutations in exon 2 of the LDLR gene using a denaturing gradient gel electrophoresis (DGGE)-based mutation screening assay. A deviating DGGE pattern identified two index patients, where subsequent sequencing revealed heterozygosity for the FH Cincinnati type 5 Trp23-to-Stop LDLR mutation. Data from three generations of the families allowed the first clinical and biochemical description of this mutation. Evidence that genetic analysis adds independent diagnostic information compared to traditional clinical/biochemical FH diagnosis was documented by demonstrating the presence of the FH Cincinnati mutation in a family member with a completely normal lipid profile. By comparison to non-FH family members, it was documented that carrier status for the FH Cincinnati mutation is associated with a significant risk of cardiovascular disease. Thus, genetic analysis may improve diagnostic precision and help to define more precisely which of the members of FH families are in need of preventive interventions and may aid in establishing phenotype——genotype relationships allowing more refined genetic counselling in FH.

Internalization of membrane proteins involves their recruitment into plasma membrane clathrin-coated pits, with which they are thought to interact by binding to AP-2 adaptor protein complexes. To investigate the interactions of membrane proteins with coated pits at the cell surface, we applied image correlation spectroscopy to measure directly and quantitatively the clustering of influenza hemagglutinin (HA) protein mutants carrying specific cytoplasmic internalization signals. The HA system enables direct comparison between isolated internalization signals, because HA itself is excluded from coated pits. The studies presented here provide, for the first time, a direct quantitative measure for the degree of clustering of membrane proteins in coated pits at the cell surface. The degree of clustering depended on the strength of the internalization signal and on the integrity of the clathrin lattices and correlated with the internalization rates of the mutants. The clustering of the HA mutants fully correlated with their ability to co-precipitate alpha-adaptin from whole cells, the first such demonstration for a membrane protein that is not a member of the epidermal growth factor receptor family. Furthermore, both the clustering in coated pits and the co-precipitation with alpha-adaptin were dramatically reduced in the cold, suggesting that low temperature can interfere with the sorting of proteins into coated pits. In addition to the specific results reported here, the general applicability of the image correlation spectroscopy approach to study any process involving the clustering or oligomerization of membrane receptors at the cell surface is discussed.

1In human subjects, stretch applied to ankle dorsiflexors elicited three bursts of reflex activity in the tibialis anterior (TA) muscle (labelled M1, M2 and M3) at mean onset latencies of 44, 69 and 95 ms, respectively. The possibility that the later of these reflex bursts is mediated by a transcortical pathway was investigated.2The stretch evoked a cerebral potential recorded from the somatosensory cortex at a mean onset latency of 47 ms in nine subjects. In the same subjects a compound motor‐evoked potential (MEP) in the TA muscle, evoked by magnetic stimulation of the motor cortex, had a mean onset latency of 32 ms. The M1 and the M2 reflexes thus had too short a latency to be caused by a transcortical pathway (minimum latency, 79 ms (47 + 32)), whereas the later part of the M2 and all of the M3 reflex had a sufficiently long latency.3When the transcranial magnetic stimulation was timed so that the MEP arrived in the TA muscle at the same time as the M1 or M2 reflexes, no extra increase in the potential was observed. However, when the MEP arrived at the same time as the M3 reflex a significant (P< 0.01) extra‐facilitation was observed in all twelve subjects investigated.4Peaks evoked by transcranial magnetic stimulation in the post‐stimulus time histogram of the discharge probability of single TA motor units (n= 28) were strongly facilitated when they occurred at the same time as the M3 response. This was not the case for the first peaks evoked by electrical transcranial stimulation in any of nine units investigated.5We suggest that these findings are explained by an increased cortical excitability following TA stretch and that this supports the hypothesis that the M3 response in the TA muscle is ‐ at least partly ‐ mediated by a transcortical reflex.

1Stimulation of the superficial peroneal or the sural nerve (3 shocks, 3 ms interval, 1 ms duration, 2.5 × perception threshold) evoked a reflex activation of the tibialis anterior muscle at a latency of approximately 70–95 ms in all of nine healthy human subjects. Stimulation of the medial plantar nerve only rarely produced similar effects. The possibility that a transcortical pathway contributes to these late reflex responses was investigated by combining the cutaneous stimulations and a transcranial magnetic stimulation of the contralateral motor cortex.2A significant facilitation of short‐latency peaks in the post‐stimulus time histogram of single tibialis anterior motor units evoked by the transcortical magnetic stimulation was observed in eight out of nine subjects following stimulation of the superficial peroneal or sural nerves at the latency of the long‐latency reflex. In contrast such a facilitation was only rarely seen when the medial plantar nerve was stimulated.3With the same timing for the stimuli, the superficial peroneal and sural nerve stimulations also produced a significant increase in the short‐latency, presumed monosynaptic, facilitation of the tibialis anterior H reflex produced by the brain stimulation.4Similar facilitatory effects of the cutaneous stimuli could not be demonstrated when the magnetic stimulation of the cortex was replaced with electrical stimulation, implying that cortical excitability is affected by a conditioning cutaneous stimulation.5It is suggested that the long‐latency reflexes in the tibialis anterior muscle evoked by activation of cutaneous afferents from the human foot are, at least partly, mediated by a transcortical pathway.

Abstract:  The generation of locomotor-like spinal rhythms has been proposed to involve two neural centres with mutual reciprocal inhibition (Graham Brown’s ”half-centre” hypothesis). Much later a particular set of segmental flexor reflex pathways were described as being organized in accordance with this half-centre hypothesis. As these pathways became operative following injection of monoaminoxidase inhibitors and l-3,4-dihydroxyphenylalanine (l-dopa), i.e. under the same conditions under which a spontaneous locomotor activity may develop, it was assumed that these particular pathways and spinal rhythm generators involve the same neuronal networks. In order to give further evidence to this hypothesis, we investigated whether short trains to ”flexor reflex afferents” (FRA) reset the spinal locomotor rhythm, i.e. shorten or lengthen the stimulated cycle after which the regular rhythm is resumed with step cycles of the original duration. The experiments were performed in anaemically decapitated, high-spinal curarized cats. A steady locomotor rhythm was induced by injection of nialamide and l-dopa and the influence of electrical stimulation (trains of 50–1000 ms) of FRA (joint, cutaneous, and group II and III muscle afferents) onto this rhythm was tested. Stimulation of FRA induced a clear resetting of the locomotor rhythm, which was mainly characterized by a flexion reflex pattern: during the extension phase the extensor activity was interrupted and a flexion phase was initiated; during the late flexion phase mainly a prolongation of that phase with a variable change of the following extension phase was induced. In addition to this prevailing pattern, stimulation of some nerves (in particular nerves to more distal extensors and the sural nerve) could often prolong extension, when stimulated during the late extension, or terminate the flexor burst and initiate a new extension phase, when stimulated during the late flexion phase. This pattern is probably due to the concomitant stimulation of group I afferents in the case of the muscle nerves and to separate non-FRA pathways in the case of the sural nerve. The results demonstrate that the interneurones of the FRA pathways, which are operative during l-dopa-induced locomotion in spinal animals, can be considered as neuronal elements of the rhythm-generating network for locomotion.

Morita, H., N. Petersen, L.O.D. Christensen, T. Sinkjær, and J. Nielsen.Sensitivity of H-reflexes and stretch reflexes to presynaptic inhibition in humans. J. Neurophysiol.80: 610–620, 1998. The sensitivity of soleus H-reflexes, T-reflexes, and short-latency stretch reflexes (M1) to presynaptic inhibition evoked by a weak tap applied to the biceps femoris tendon or stimulation of the common peroneal nerve (CPN) was compared in 17 healthy human subjects. The H-reflex was strongly depressed for a period lasting up to 300–400 ms (depression to 48 ± 23%, mean ± SD, of control at a conditioning test interval of 70 ms) by the biceps femoris tendon tap. In contrast, the short-latency soleus stretch reflex elicited by a quick passive dorsiflexion of the ankle joint was not depressed. The soleus T-reflex elicited by an Achilles tendon tap was only weakly depressed (92 ± 8%). The H-reflex was also significantly more depressed than the T-reflex at long intervals (>15 ms) after stimulation of CPN (H-reflex 63 ± 14%, T-reflex 91 ± 13%; P< 0.01). However, the short-latency (2 ms) disynaptic reciprocal Ia inhibition evoked by stimulation of CPN was equally strong for H- and T-reflexes (H-reflex 72 ± 10%, T-reflex 67 ± 13%; P= 0.07). Peaks in the poststimulus time histogram (PSTH) of the discharge probability of single soleus motor units (n= 53) elicited by an Achilles tendon tap had a longer duration than peaks evoked by electrical stimulation of the tibial nerve (on average 5.0 ms as compared with 2.7 ms). All parts of the electrically evoked peaks were depressed by the conditioning biceps femoris tendon tap (average depression to 55 ± 27% of control; P< 0.001). A similar depression was observed for the initial 2 ms of the peaks evoked by the Achilles tendon tap (69 ± 48%; P< 0.001), but the last 2 ms were not depressed. Conditioning stimulation of the CPN at long intervals (>15 ms) also depressed all parts of the electrically evoked PSTH peaks (n= 34; average 65%; P< 0.001) but had only a significant effect on the initial 2 ms of the peaks evoked by the Achilles tendon tap (85%; P< 0.001). We suggest that the different sensitivity of mechanically and electrically evoked reflexes to presynaptic inhibition is caused by a difference in the shape and composition of the excitatory postsynaptic potentials underlying the two reflexes. This difference may be explained by a different composition and/or temporal dispersion of the afferent volleys evoked by electrical and mechanical stimuli. We conclude that it is not straightforward to predict the modulation of stretch reflexes based on observations of H-reflex modulation.