Mortality after hospital admission for trauma in Norway: A retrospective observational national cohort study.

BACKGROUND: National quality data for trauma care in Norway have not previously been reported. We have therefore assessed crude and risk-adjusted 30-day mortality in trauma cases after primary hospital admission on national and regional levels for 36 acute care hospitals and four regional trauma centres. METHODS: All patients in the Norwegian Trauma Registry in 2015-2018 were included. Crude and risk-adjusted 30-day mortality was assessed for the total cohort and for severe injuries (Injury Severity Score ≥16), and individual and combined effects of health region, hospital level, and hospital size were studied. RESULTS: 28,415 trauma cases were included. Crude mortality was 3.1% for the total cohort and 14.5% for severe injuries, with no statistically significant difference between regions. Risk-adjusted survival was lower in acute care hospitals than in trauma centres (0.48 fewer excess survivors per 100 patients, P<0.0001), amongst severely injured patients in the Northern health region (4.80 fewer excess survivors per 100 patients, P = 0.004), and in hospitals with <100 trauma admissions per year (0.65 fewer excess survivors than in hospitals with ≥100 admissions, P = 0.01). However, the only statistically significant effects in a multivariable logistic case mix-adjusted descriptive model were hospital level and health region. Case-mix adjusted odds ratio for survival for severely injured patients directly admitted to a trauma centre vs. an acute care hospital was 2.04 (95% CI 1.04-4.00, P = 0.04), and if admitted in the Northern health region vs. all other health regions was 0.47 (95% CI 0.27-0.84, P = 0.01). The proportion of cases admitted directly to the regional trauma centre in the sparsely populated Northern health region was half of that in the other regions (18.4% vs. 37.6%, P<0.0001). CONCLUSION: Differences in risk-adjusted survival for severe injuries can to a large extent be attributed to whether patients are directly admitted to a trauma centre. This should have implications for planning of transport capacity in remote areas.

Validation of the Norwegian survival prediction model in trauma (NORMIT) in Swedish trauma populations.

BACKGROUND: Trauma survival prediction models can be used for quality assessment in trauma populations. The Norwegian survival prediction model in trauma (NORMIT) has been updated recently and validated internally (NORMIT 2). The aim of this observational study was to compare the accuracy of NORMIT 1 and 2 in two Swedish trauma populations. METHODS: Adult patients registered in the national trauma registry during 2014-2016 were eligible for inclusion. The study populations comprised the total national trauma (NT) population, and a subpopulation of patients admitted to a single level I trauma centre (TC). The primary outcome was 30-day mortality. Model validation included receiver operating characteristic (ROC) curve analysis and GiViTI calibration belts. The calibration was also assessed in subgroups of severely injured patients (New Injury Severity Score (NISS) over 15). RESULTS: A total of 26 504 patients were included. Some 18·7 per cent of patients in the NT population and 2·6 per cent in the TC subpopulation were excluded owing to missing data, leaving 21 554 and 3972 respectively for analysis. NORMIT 1 and 2 showed excellent ability to distinguish between survivors and non-survivors in both populations, but poor agreement between predicted and observed outcome in the NT population with overestimation of survival, including in the subgroup with NISS over 15. In the TC subpopulation, NORMIT 1 underestimated survival irrespective of injury severity, but NORMIT 2 showed good calibration both in the total subpopulation and the subgroup with NISS over 15. CONCLUSION: NORMIT 2 is well suited to predict survival in a Swedish trauma centre population, irrespective of injury severity. Both NORMIT 1 and 2 performed poorly in a more heterogeneous national population of injured patients.

ANTECEDENTES: Los modelos de predicción de supervivencia en los traumatismos pueden ser utilizados para la evaluación de la calidad en las poblaciones con traumatismos. Recientemente, el modelo noruego de predicción de supervivencia en traumatismos (NORMIT) se ha actualizado y validado internamente (NORMIT 2). El objetivo de este estudio observacional fue comparar la precisión de los modelos NORMIT 1 y 2 en dos poblaciones suecas con traumatismos. MÉTODOS: Pacientes adultos registrados en el registro nacional de traumatismos durante 2014-2016 fueron elegibles para el estudio. Las poblaciones de estudio eran: (1) la población total nacional de traumatismos (national trauma, NT) y (2) una subpoblación de pacientes ingresados en un único centro de trauma de nivel I (trauma centre, TC). El resultado primario fue la mortalidad a los 30 días. La validación del modelo incluyó curvas de características operativas del receptor y cinturones GiViTI de calibración. La calibración también se evaluó en subgrupos de pacientes con lesiones graves (New Injury Severity Score, NISS >15). RESULTADOS: Se incluyeron un total de 26.504 pacientes. La exclusión por falta de datos fue del 18,7% en la población NT (n = 21.554) y del 2,6% en la población TC (n = 3.972). Los modelos NORMIT 1 y 2 mostraron una habilidad excelente para distinguir entre supervivientes y no supervivientes en ambas poblaciones, pero con un grado de acuerdo pobre entre el resultado predicho y el observado en la población NT, con sobreestimación de la supervivencia incluido el subgrupo de NISS >15. En la subpoblación TC, NORMIT 1 subestimó la supervivencia independientemente de la gravedad de la lesión, pero NORMIT 2 mostró una buena calibración tanto en la subpoblación total, como en el subgrupo NISS >15. CONCLUSIÓN: El modelo NORMIT 2 es muy apropiado para predecir la supervivencia en la población de un centro de traumatismos sueco independientemente de la gravedad de la lesión. Los modelos tanto NORMIT 1 como NORMIT 2 funcionan mal en una población de traumatismos nacional más heterogenea.

Validating performance of TRISS, TARN and NORMIT survival prediction models in a Norwegian trauma population.

INTRODUCTION: Anatomic injury, physiological derangement, age, injury mechanism and pre-injury comorbidity are well-founded predictors of trauma outcome. Statistical prediction models may have poorer discrimination, calibration and accuracy when applied in new locations. We aimed to compare the TRISS, TARN and NORMIT survival prediction models in a Norwegian trauma population. METHODS: Consecutive patients admitted to Oslo University Hospital Ullevål within 24 h after injury, with Injury Severity Score ≥ 10, proximal penetrating injuries, or received by trauma team, were studied. Original NORMIT coefficients were updated in a derivation dataset (NORMIT 2; n = 5923; 2005-2009). TRISS, TARN and NORMIT prediction models were evaluated in the validation dataset (n = 6348; 2010-2013) using two different AIS editions for injury coding. Exclusion due to missing data was 0.26%. Outcome was 30-day mortality. Validation included AUROC, scaled Brier statistics, and calibration plots. RESULTS: The NORMIT models had significantly better discrimination, calibration, and overall fit than the TRISS 09, TARN 09 and TARN 12 models. The updated NORMIT 2 had higher numerical values of AUROC and scaled Brier than the original NORMIT, but with overlapping 95%CI. Overlapping 95%CI for AUROCs and Discrimination slopes indicated that the TARN and TRISS models performed similarly. Calibration plots showed tight and consistent predictions over all Ps strata for NORMIT 2 run on AIS'98 coded data, and only little deterioration when AIS'08 data was substituted. CONCLUSIONS: In a Norwegian trauma population, the updated Norwegian survival prediction model in trauma (NORMIT 2) performed better than well-established British and US alternatives. External validation of these three models in other Nordic populations is warranted.

Norwegian survival prediction model in trauma: modelling effects of anatomic injury, acute physiology, age, and co-morbidity.

INTRODUCTION: Anatomic injury, physiological derangement, age, and injury mechanism are well-founded predictors of trauma outcome. We aimed to develop and validate the first Scandinavian survival prediction model for trauma. METHODS: Eligible were patients admitted to Oslo University Hospital Ullevål within 24 h after injury with Injury Severity Score ≥ 10, proximal penetrating injuries or received by a trauma team. The derivation dataset comprised 5363 patients (August 2000 to July 2006); the validation dataset comprised 2517 patients (August 2006 to July 2008). Exclusion because of missing data was < 1%. Outcome was 30-day mortality. Logistic regression analysis incorporated fractional polynomial modelling and interaction effects. Model validation included a calibration plot, Hosmer-Lemeshow test and receiver operating characteristic (ROC) curves. RESULTS: The new survival prediction model included the anatomic New Injury Severity Score (NISS), Triage Revised Trauma Score (T-RTS, comprising Glascow Coma Scale score, respiratory rate, and systolic blood pressure), age, pre-injury co-morbidity scored according to the American Society of Anesthesiologists Physical Status Classification System (ASA-PS), and an interaction term. Fractional polynomial analysis supported treating NISS and T-RTS as linear functions and age as cubic. Model discrimination between survivors and non-survivors was excellent. Area (95% confidence interval) under the ROC curve was 0.966 (0.959-0.972) in the derivation and 0.946 (0.930-0.962) in the validation dataset. Overall, low mortality and skewed survival probability distribution invalidated model calibration using the Hosmer-Lemeshow test. CONCLUSIONS: The Norwegian survival prediction model in trauma (NORMIT) is a promising alternative to existing prediction models. External validation of the model in other trauma populations is warranted.

Physiologic, demographic and mechanistic factors predicting New Injury Severity Score (NISS) in motor vehicle accident victims.

BACKGROUND: Current literature on motor vehicle accidents (MVAs) has few reports regarding field factors that predict the degree of injury. Also, studies of mechanistic factors rarely consider concurrent predictive effects of on-scene patient physiology. The New Injury Severity Score (NISS) has previously been found to correlate with mortality, need for ICU admission, length of hospital stay, and functional recovery after trauma. To potentially increase future precision of trauma triage, we assessed how the NISS is associated with physiologic, demographic and mechanistic variables from the accident site. METHODS: Using mixed-model linear regression analyses, we explored the association between NISS and pre-hospital Glasgow Coma Scale (GCS) score, Revised Trauma Score (RTS) categories of respiratory rate (RR) and systolic blood pressure (SBP), gender, age, subject position in the vehicle, seatbelt use, airbag deployment, and the estimated squared change in vehicle velocity on impact ((Δv)(2)). Missing values were handled with multiple imputation. RESULTS: We included 190 accidents with 353 dead or injured subjects (mean NISS 17, median NISS 8, IQR 1-27). For the 307 subjects in front-impact MVAs, the mean increase in NISS was -2.58 per GCS point, -2.52 per RR category level, -2.77 per SBP category level, -1.08 for male gender, 0.18 per year of age, 4.98 for driver vs. rear passengers, 4.83 for no seatbelt use, 13.52 for indeterminable seatbelt use, 5.07 for no airbag deployment, and 0.0003 per (km/h)(2) velocity change (all p<0.002). CONCLUSION: This study in victims of MVAs demonstrated that injury severity (NISS) was concurrently and independently predicted by poor pre-hospital physiologic status, increasing age and female gender, and several mechanistic measures of localised and generalised trauma energy. Our findings underscore the need for precise information from the site of trauma, to reduce undertriage, target diagnostic efforts, and anticipate need for high-level care and rehabilitative resources.

Efficacy of a two-tiered trauma team activation protocol in a Norwegian trauma centre.

BACKGROUND: A registry-based analysis revealed imprecise informal one-tiered trauma team activation (TTA) in a primary trauma centre. A two-tiered TTA protocol was introduced and analysed to examine its impact on triage precision and resource utilization. METHODS: Interhospital transfers and patients admitted by non-healthcare personnel were excluded. Undertriage was defined as the fraction of major trauma victims (New Injury Severity Score over 15) admitted without TTA. Overtriage was the fraction of TTA without major trauma. RESULTS: Of 1812 patients, 768 had major trauma. Overall undertriage was reduced from 28·4 to 19·1 per cent (P < 0·001) after system revision. Overall overtriage increased from 61·5 to 71·6 per cent, whereas the mean number of skilled hours spent per overtriaged patient was reduced from 6·5 to 3·5 (P < 0·001) and the number of skilled hours spent per major trauma victim was reduced from 7·4 to 7·1 (P < 0·001). Increasing age increased risk for undertriage and decreased risk for overtriage. Falls increased risk for undertriage and decreased risk for overtriage, whereas motor vehicle-related accidents showed the opposite effects. Patients triaged to a prehospital response involving an anaesthetist had less chance of both undertriage and overtriage. CONCLUSION: A two-tiered TTA protocol was associated with reduced undertriage and increased overtriage, while trauma team resource consumption was reduced. REGISTRATION NUMBER: NCT00876564 (http://www.clinicaltrials.gov).

Activity of hindlimb motor units during locomotion in the conscious rat.

This paper compares the activity of hindlimb motor units from muscles mainly composed of fast-twitch muscle fibers (medial and lateral gastrocnemius: MG/LG, tibialis anterior: TA) to motor units from a muscle mainly composed of slow-twitch muscle fibers (soleus: SOL) during unrestrained walking in the conscious rat. Several differences in the activation profiles of motor units from these two groups of muscles were observed. For example, motor units from fast muscles (e.g., MG/LG and TA) fired at very high mean frequencies of discharge, ranging from 60 to 100 Hz, and almost always were recruited with initial doublets or triplets, i.e., initial frequencies >/=100 Hz. In contrast, the majority of SOL units fired at much lower mean rates of discharge, approximately 30 Hz, and had initial frequencies of only 30-60 Hz (i.e., there were no initial doublets/triplets >/=100 Hz). Thus the presence of initial doublet or triplets was dependent on the intrinsic properties of the motor unit, i.e., faster units were recruited with a doublet/triplet more often than slower units. Moreover, in contrast to units from the slow SOL muscle, the activity of single motor units from the fast MG/LG muscle, especially units recruited midway or near the end of a locomotor burst, was unrelated to the activity of the remainder of the motoneuron pool, as measured by the corresponding gross-electromyographic (EMG) signal. This dissociation of activity was suggested to arise from a compartmentalized recruitment of the MG/LG motoneuron pool by the rhythm-generating networks of the spinal cord. In contrast, when comparing the rate modulation of simultaneously recorded motor units within a single LG muscle compartment, the frequency profiles of unit pairs were modulated in a parallel fashion. This suggested that the parent motoneurons were responsive to changes in synaptic inputs during unrestrained walking, unlike the poor rate modulation that occurs during locomotion induced from brain stem stimulation. In summary, data from this study provide evidence that the firing behavior of motor units during unrestrained walking is influenced by both the intrinsic properties of the parent motoneuron and by synaptic inputs from the locomotor networks of the spinal cord. In addition, it also provides the first extensive description of motor-unit activity from different muscles during unrestrained walking in the conscious rat.

Hypoplasia of the sphenoid sinuses as a diagnostic tool in cystic fibrosis.

PURPOSE: To measure and compare the size of the sphenoid sinuses in patients with cystic fibrosis (CF) to patients with inflammatory sinonasal disease, and to correlate the size with number of CF mutations in each patient. MATERIAL AND METHODS: Ninety-six CF patients aged 5-47 years (median 19 years) and 130 control patients aged 7-51 years (median 32 years) were examined using coronal CT of the paranasal sinuses. In each patient, the CT image with the largest coronal area of the sphenoid sinuses was scanned into a Macintosh computer with image processing and analysis software. Largest coronal area and largest circumference of the right and left sphenoid sinuses were automatically measured. Additionally, antero-posterior extension of the sphenoid sinuses was calculated from the lateral scanograms. CF patients were grouped according to number of confirmed mutations (CF-0, CF-1, or CF-2). RESULTS: CF patients generally had small sphenoid sinuses. The largest differences for all parameters were observed between the CF-2 and the control groups (p<0.0001). No CF-2 patient had pneumatization beyond the presphenoid. The CF-0 and CF-1 groups consisted of two populations, one overlapping the CF-2 group and another overlapping the control group. CONCLUSION: Hypoplasia of the sphenoid sinuses is a characteristic finding in CF patients. When pneumatization of the basisphenoid is present, the existing CF diagnosis should be questioned.

Activation patterns of hindlimb motor units in the awake rat and their relation to motoneuron intrinsic properties.

The activity of hindlimb motor units from the lateral gastrocnemius and tibialis anterior muscles in the awake rat was compared during locomotion and during slow, sinusoidal muscle stretch. The majority of units were activated with high initial frequencies and often commenced firing with an initial doublet or triplet, even when activated by slow muscle stretch. The high firing rates at recruitment occurred without jumps in the firing rates of other concurrently activated units, the firing rate profiles of which were used as a measure of the net synaptic drive onto the motoneuronal pool. This suggested that the sharp recruitment jumps were not due to an abrupt increase in synaptic drive but rather due to intrinsic properties of the motoneuron. In addition, motor units that were activated phasically by the muscle stretch fired more action potentials during muscle shortening than during muscle lengthening, resulting in rightwardly skewed, asymmetrical firing profiles. In contrast, when the same units fired tonically during the imposed muscle stretch, the frequency profiles were modulated symmetrically and no nonlinearities were observed. Tonically firing units were modulated symmetrically throughout a wide range of firing frequencies, and discrete jumps in rate (i.e., bistable firing) were not observed. The sharp recruitment jumps during locomotion and muscle stretch are proposed to have resulted from the additional depolarization produced by the activation of plateau potentials at recruitment. Likewise, the sustained activation of plateaus subsequent to recruitment may have produced the prolonged firing of the motor units during sinusoidal muscle stretch.

Spontaneous electromyographic activity in adult rat soleus muscle.

Single-motor-unit and gross electromyograms (EMG) were recorded from the soleus muscle in six unrestrained rats. The median firing frequencies of nine motor units were in the 16-25 Hz range, in agreement with previous studies. One additional motor unit had a median firing frequency of 47 Hz. This unit and one of the lower-frequency units regularly fired doublets. Motor-unit firing frequency was well correlated to whole-muscle EMG during locomotion. Integrated rectified gross EMG revealed periods of continuous modulation, phasic high-amplitude events, and tonic low-amplitude segments. The tonic segments typically were caused by a small number of motor units firing at stable high frequencies (20-30 Hz) for extended periods of time without detectable activity in other units. This long-lasting firing in single motor units typically was initiated by transient mass activity, which recruited many units. However, only one or a few units continued firing at a stable high frequency. The tonic firing terminated spontaneously or in conjunction with an episode of mass activity. Different units were active in different tonic segments. Thus there was an apparent dissociation between activity in different single motor units and consequently between single-motor-unit activity and whole-muscle EMG. It is proposed that the maintained tonic motor-unit activity is caused by intrinsic motoneuron properties in the form of depolarizing plateau potentials.

Functional role of plateau potentials in vertebrate motor neurons.

The expression of plateau potentials in spinal motor neurons is regulated by neuromodulatory substances. Recent experiments have shed new light on this regulation at the cellular level. It is now possible to evaluate the existence of plateau potentials in intact organisms, including humans, and to address the functional role of plateau potentials in motor control, as well as in information transfer in the brain.

Prolonged firing in motor units: evidence of plateau potentials in human motoneurons?

Serotonin (5-HT) and norepinephrine-dependent plateau potentials are found in spinal motoneurons in reduced turtle and cat preparations. Triggering the plateau potential by short-lasting synaptic excitation causes a prolonged self-sustained firing, which can be terminated by short-lasting synaptic inhibition. The presence of plateau potentials can also allow neurons to fire in a bistable manner, i.e., shifting between stable low and high firing frequencies. Such a bistable firing behavior has been found in soleus motor units in unrestrained rats. In the present study single motor-unit activity was recorded from low-threshold units in human soleus and tibialis anterior muscles to evaluate whether a bistable firing behavior and/or prolonged firing could be evoked. Vibration of the homonymous muscle tendon (30-100 Hz, 2-10 s) was used as excitatory input to the motoneuron pool. Brief excitation while the muscle was electrically silent induced firing during the vibration and sometimes recruited units into prolonged stable firing outlasting the vibratory stimulus. However, a bistable firing behavior, i.e., vibration-induced maintained shifts between two stable levels of firing, could not be convincingly demonstrated. The reason for this was twofold. First, low-threshold human motor units tended to jump to a "preferred firing range" shortly after voluntary recruitment. This firing range was the same as when units were recruited from silence into prolonged firing by vibration. Below the preferred firing range, maintained firing was unstable and usually only possible when subjects were listening to the spike potentials or had visual force-feedback. Second, vibration when units were firing in the preferred firing range caused a transient increase in firing frequency but no maintained frequency shifts. Recordings from pairs of motor units showed that short-lasting vibration could recruit one unit into prolonged firing, while a second unit, which already fired in its preferred firing range, only transiently increased its firing rate during the vibration. This suggests that the prolonged firing was not the result of an increase in the common synaptic drive to the motoneuron pool. We conclude that a bistable firing behavior as seen in intact rats is probably absent in human low-threshold motor units, but that prolonged firing could be seen in response to short-lasting excitation. This latter phenomenon is compatible with the existence of plateau potentials, which have to have a threshold close to the threshold for sodium spike generation.

Selective depletion of spinal monoamines changes the rat soleus EMG from a tonic to a more phasic pattern.

1. To assess the role of descending monoaminergic pathways for motor activity long-lasting EMG recordings were performed from the adult soleus muscle before and after selective depletion of spinal monoamines. 2. Rats were chronically implanted with an intrathecal catheter placed in the lumbar subarachnoid space and gross-EMG recording electrodes in the soleus muscle. EMG recordings were performed in control conditions and at different times after intrathecal administration of either 40-55 micrograms 5,6-dihydroxytryptamine (5,6-DHT) and 40-55 micrograms 6-hydroxydopamine (6-OHDA) or 80 micrograms 5,7-dihydroxytryptamine (5,7-DHT) alone. The depletions were evaluated biochemically in brains and spinal cords after recordings. 3. In agreement with previous studies the intrathecal administration of neurotoxins caused a reduction of the noradrenaline (NA) and serotonin (5-HT) content of the lumbar spinal cord to about 2-3% of control, with little or no changes in the monoamine content of the cortex. 4. In non-treated chronically catheterized rats the integrated rectified gross EMG displayed long-lasting EMG episodes composed of phasic high-amplitude events and tonic segments of varying duration and amplitude. 5. After intrathecal administration of neurotoxins the number of long-lasting gross-EMG episodes, the mean episode duration, and the total EMG activity per 24 h, were reduced. These changes were accompanied by a simultaneous increase both in the number of short-lasting EMG episodes and the total number of EMG episodes per 24 h period. The changes were apparent 5-6 days after drug administration and fully developed after 2-3 weeks. 6. No changes in general movement ability were observed, except that the denervated animals had a tendency to a less errect posture. 7. These results indicate that descending monoaminergic pathways are important for the maintained motor output in tonic hindlimb muscles.

Activity of single motor units in attention-demanding tasks: firing pattern in the human trapezius muscle.

Activity of single motor units in relation to surface electromyography (EMG) was studied in 11 subjects in attention-demanding work tasks with minimal requirement of movement. In 53 verified firing periods, single motor units fired continuously from 30 s to 10 min (duration of the experiment work task) with a stable median firing rate in the range of 8-13 Hz. When the integrated surface EMG were stable, the motor units identified as a rule were continuously active with only small modulations of firing rate corresponding to low-amplitude fluctuations in surface EMG. Marked changes in the surface EMG, either sudden or gradual, were caused by recruitment or derecruitment of motor units, and not by modulations of the motor unit firing rate. Motor unit firing periods (duration 10 s-35 s) in low-level voluntary contractions (approximately 1%-5% EMGmax) performed by the same subjects showed median firing rates (7-12 Hz) similar to the observations in attention-related activation.

The importance of frequency and amount of electrical stimulation for contractile properties of denervated rat muscles.

Soleus (SOL) and extensor digitorum longus (EDL) muscles were denervated and directly stimulated for 23-69 days through implanted electrodes employing three different patterns. The stimulation was delivered in impulse trains where the pulse frequency differed (20, 75, and 150 Hz), while the train duration (0.3 s) and train repetition rate (1 min-1) were identical. Consequently, the number of pulses varied such that higher frequency was combined with a higher amount of stimulation. In both SOL and EDL the high-frequency pattern resulted in shorter twitch time-to-peak, greater post-tetanic potentiation, and greater tetanic force than the low frequency. Isotonic shortening velocity was increased to the same extent by all the patterns in SOL whereas in EDL fast intrinsic shortening velocity was maintained by the low-frequency pattern while it was decreased by the high-frequency pattern. We attribute this unexpected effect on the EDL to the larger number of pulses in the high-frequency pattern. By combining the present findings with previous data on directly stimulated rat muscles we conclude: in SOL the twitch duration is influenced by both the frequency and the amount of impulse activity, higher frequencies and smaller amounts leading to faster twitches. The EDL twitch duration is similarly dependent on the amount of activity, but the role of frequency is more unclear. In both SOL and EDL the isotonic shortening velocity is reduced by increasing amounts of activity and there is no evidence that impulse frequency plays a role. In EDL force output is strongly influenced by the impulse frequency, low frequencies resulting in low force outputs irrespective of the amount of activity.

Bistable firing properties of soleus motor units in unrestrained rats.

EMG recordings from single motor units in the soleus muscle were performed in alert unrestrained rats. A cuff electrode around the tibial nerve and subcutaneously placed electrodes in the foot permitted stimulation of afferent fibres. The movements of the rat and the simultaneous EMG activity were displayed together on a video monitor. Most motor units were tonically active for extended periods during quiet standing. During tonic discharge, maintained shifts between stable low (8-12 Hz; quartiles) and high (16-22.8 Hz) frequency ranges were initiated by short-lasting synaptic excitation of the motoneuron pool by stimulation of Ia afferents, or inhibition by stimulation of skin afferents. The shifts were not related to gross limb movements. This phenomenon is referred to as a bistable firing pattern. Bistable firing also occurred spontaneously during quiet standing. Typically the firing frequency shifted between a low (9-12.5 Hz) and a high (20-24.5 Hz) mode. During recordings of simultaneous activity in two units, spontaneous and stimulus-induced frequency jumps causing maintained changes in firing frequency were regularly seen to occur in one unit, while the frequency in the second unit was unchanged or only phasically influenced. These results demonstrate for the first time a bistable firing pattern during postural activity in the intact animal. The firing pattern closely resembles the bistable behaviour described in spinal motoneurons in reduced preparations, where it is due to the presence of a plateau potential. This suggests that the bistable firing is unexplained by plateau potentials also in the intact animal.

Possible functions of transmitter-controlled plateau potentials in alpha motoneurones.

An increasing number of vertebrate central neurones has been shown to possess complex membrane properties. However, the functional significance of such properties is unclear. The aim of the present paper is to review some old and new findings in this field from this laboratory. First, a bistability in alpha motoneurones in reduced preparations is described. Thereafter we present some new data on a bistable behaviour in motor units in unrestrained intact animals during posture. Finally, the possible role of motoneuronal bistability in locomotion and in spasticity is discussed. Recently a bistable firing behaviour in motoneurones was described in the unanaesthetized decerebrate cat. This behaviour is generated by a plateau potential, which causes long-lasting excitability increase and can be initiated and terminated by short-lasting synaptic excitation and inhibition respectively, and is contingent upon activity in descending noradrenergic and serotonergic systems. In an in vitro preparation of the turtle spinal cord the plateau potential was shown to be serotonin dependent and generated by a voltage-dependent non-inactivating calcium conductance. In order to elucidate possible functional consequences of a bistable firing behaviour in the intact animal, the firing pattern of individual soleus motor units was studied by means of chronic EMG registration in awake unrestrained rats during quiet standing. Implanted electrodes allowed the delivery of excitatory and inhibitory stimulus trains to the motoneurones. It was found that short-lasting synaptic stimulation could induce maintained shifts between two stable levels of motoneurone firing frequencies, as in the decerebrate cat. Spontaneous shifts between the same two levels were also present. It seems most likely that plateau potentials are responsible for this bistable firing property in intact animals. The role of plateau potentials in locomotion is difficult to study. At present there are no clear indications of the utilization of plateau potentials in locomotion in intact animals. However, "clamped frequency" bursts which are observed in fictive locomotion in spinal cats might be explained by plateaus. The existence of plateau potentials in motoneurones may also be of importance in spasticity. Therefore, the development of spasticity in two spinalized cats was followed for 3 weeks. Acute experiments demonstrated plateau potentials in some motoneurones in this preparation.

Electrical stimulation resembling normal motor-unit activity: effects on denervated fast and slow rat muscles.

1. The slow-twitch soleus muscle and the fast-twitch extensor digitorum longus muscle (EDL) were denervated and stimulated directly with implanted electrodes for 33-82 days. Four different stimulation patterns were used in order to mimic important characteristics of the natural motor-unit activity in these muscles. In addition, to compare the effects of direct stimulation to other experimental models, some EDLs were stimulated through the nerve or cross-innervated by soleus axons. 2. After 33-82 days of stimulation the contractile properties were measured under isometric and isotonic conditions. 3. 'Native' stimulation patterns could maintain normal contractile speed in both EDL and soleus. In the EDL, normal isotonic shortening velocity was maintained only by a stimulation pattern consisting of very brief trains with an initial short interspike interval (doublet), and not by the other 'native' high-frequency patterns. 4. The contractile properties of both EDL and soleus muscles receiving a 'foreign' stimulation pattern were transformed in the direction of the muscle normally receiving that type of activity. The transformations were not complete, and soleus and EDL muscles stimulated with the same stimulation pattern remained different. This suggests that adult muscle fibres in rat EDL and soleus are irreversibly differentiated into different fibre types earlier in development. 5. The three high-frequency stimulation patterns used differed in their ability to change or maintain various contractile properties in the soleus and the EDL. The results indicate that the following qualities of a stimulation pattern might be of importance for the control of contractile properties: instantaneous frequency, total amount of stimulation, train length, interval between trains and presence of an initial doublet. 6. With the exception of the EDL shortening velocity, changes in contractile speed induced by a 'foreign' stimulation pattern were quantitatively similar to the effects of cross-innervation both in the EDL and the soleus. We thus suggest that the change in activity pattern is the mechanism behind most of the changes induced by cross-innervation.