Tue Hvass Petersen

Premotor cortex modulates somatosensory cortex during voluntary movements without proprioceptive feedback

Movement perception relies on sensory feedback, but the involvement of efference copies remains unclear. We investigated movements without proprioceptive feedback using ischemic nerve block during fMRI in healthy humans, and found preserved activation of the primary somatosensory cortex. This activation was associated with increased interaction with premotor cortex during voluntary movements, which demonstrates that perception of movements relies in part on predictions of sensory consequences of voluntary movements that are mediated by the premotor cortex.

Individualized, home-based interactive training of cerebral palsy children delivered through the Internet

BackgroundThe available health resources limit the amount of therapy that may be offered to children with cerebral palsy and the amount of training in each session may be insufficient to drive the neuroplastic changes, which are necessary for functional improvements to take place. The aim of this pilot study was to provide proof of concept that individualized and supervised interactive home-based training delivered through the internet may provide an efficient way of maintaining intensive training of children with cerebral palsy over prolonged periods.Methods9 children (aged 9-13 years) with cerebral palsy were included in the study. Motor, perceptual and cognitive abilities were evaluated before and after 20 weeks of home-based training delivered through the internet.ResultsThe children and their families reported great enthusiasm with the training system and all experienced subjective improvements in motor abilities and self-esteem. The children on average trained for 74 hours during a 20 week period equalling just over 30 minutes per day. Significant improvements in functional muscle strength measured as the frontal and lateral step-up and sit-to-stand tests were observed. Assessment of Motor and processing skills also showed significant increases. Endurance measured as the Bruce test showed a significant improvement, whereas there was no significant change in the 6 min walking test. Balance (Romberg) was unchanged. Visual perceptual abilities increased significantly.ConclusionsWe conclude that it is feasible to deliver interactive training of children with cerebral palsy at home through the internet and thereby ensure more intensive and longer lasting training than what is normally offered to this group.

Childhood development of common drive to a human leg muscle during ankle dorsiflexion and gait

Corticospinal drive has been shown to contribute significantly to the control of walking in adult human subjects. It is unknown to what extent functional change in this drive is important for maturation of gait in children. In adults, populations of motor units within a muscle show synchronized discharges during walking with pronounced coherence in the 15–50 Hz frequency band. This coherence has been shown to depend on cortical drive. Here, we investigated how this coherence changes with development. Forty‐four healthy children aged 4–15 years participated in the study. Electromyographic activity (EMG) was recorded from pairs of electrodes placed over the right tibialis anterior (TA) muscle during static dorsiflexion and during walking on a treadmill (speed from 1.8 to 4.8 km h−1). A significant increase of coherence with increasing age was found in the 30–45 Hz frequency band (gamma) during walking and during static ankle dorsiflexion. A significant correlation with age was also found in the 15–25 Hz frequency band (beta) during static foot dorsiflexion. χ2 analysis of differences of coherence between different age groups of children (4–6, 7–9, 10–12 and 13–15 years of age) revealed a significantly lower coherence in the gamma band for recordings during walking in children aged 4–6 years as compared to older children. Recordings during static dorsiflexion revealed significant differences in both the beta and gamma bands for children in the 4–6 and 7–9 years age groups as compared to the older age groups. A significant age‐related decrease in step‐to‐step variability of toe position during the swing phase of walking was observed. This reduction in the step‐to‐step variability of gait was correlated with increased gamma band coherence during walking. We argue that this may reflect an increased ability to precisely control the ankle joint position with age, which may be contingent on maturation of corticospinal control of the foot dorsiflexor muscles.

The SafeBoosC II randomized trial : Treatment guided by near-infrared spectroscopy reduces cerebral hypoxia without changing early biomarkers of brain injury

Background:The SafeBoosC phase II multicentre randomized clinical trial investigated the benefits and harms of monitoring cerebral oxygenation by near-infrared spectroscopy (NIRS) combined with an evidence-based treatment guideline vs. no NIRS data and treatment as usual in the control group during the first 72 h of life. The trial demonstrated a significant reduction in the burden of cerebral hypoxia in the experimental group. We now report the blindly assessed and analyzed treatment effects on electroencephalographic (EEG) outcomes (burst rate and spectral edge frequency 95% (SEF95)) and blood biomarkers of brain injury (S100β, brain fatty acid-binding protein, and neuroketal).Methods:One hundred and sixty-six extremely preterm infants were randomized to either experimental or control group. EEG was recorded at 64 h of age and blood samples were collected at 6 and 64 h of age.Results:One hundred and thirty-three EEGs were evaluated. The two groups did not differ regarding burst rates (experimental 7.2 vs. control 7.7 burst/min) or SEF95 (experimental 18.1 vs. control 18.0 Hz). The two groups did not differ regarding blood S100β, brain fatty acid-binding protein, and neuroketal concentrations at 6 and 64 h (n = 123 participants).Conclusion:Treatment guided by NIRS reduced the cerebral burden of hypoxia without affecting EEG or the selected blood biomarkers.

Failure of normal development of central drive to ankle dorsiflexors relates to gait deficits in children with cerebral palsy

Neurophysiological markers of the central control of gait in children with cerebral palsy (CP) are used to assess developmental response to therapy. We measured the central common drive to a leg muscle in children with CP. We recorded electromyograms (EMGs) from the tibialis anterior (TA) muscle of 40 children with hemiplegic CP and 42 typically developing age-matched controls during static dorsiflexion of the ankle and during the swing phase of treadmill walking. The common drive to TA motoneurons was identified through time- and frequency-domain cross-correlation methods. In control subjects, the common drive consists of frequencies between 1 and 60 Hz with peaks at beta (15-25 Hz) and gamma (30-45 Hz) frequencies known to be caused by activity within sensorimotor cortex networks: this drive to motoneurons strengthens during childhood. Similar to this drive in control subjects, this drive to the least affected TA in the CP children tended to strengthen with age, although compared with that in the control subjects, it was slightly weaker. For CP subjects of all ages, the most affected TA muscle common drive was markedly reduced compared with that of their least affected muscle as well as that of controls. These differences between the least and most affected TA muscles were unrelated to differences in the magnitude of EMG in the two muscles but positively correlated with ankle dorsiflexion velocity and joint angle during gait. Time- and frequency-domain analysis of ongoing EMG recruited during behaviorally relevant lower limb tasks provides a noninvasive and important measure of the central drive to motoneurons in subjects with CP.

Interference in Ballistic Motor Learning: Specificity and Role of Sensory Error Signals

Humans are capable of learning numerous motor skills, but newly acquired skills may be abolished by subsequent learning. Here we ask what factors determine whether interference occurs in motor learning. We speculated that interference requires competing processes of synaptic plasticity in overlapping circuits and predicted specificity. To test this, subjects learned a ballistic motor task. Interference was observed following subsequent learning of an accuracy-tracking task, but only if the competing task involved the same muscles and movement direction. Interference was not observed from a non-learning task suggesting that interference requires competing learning. Subsequent learning of the competing task 4 h after initial learning did not cause interference suggesting disruption of early motor memory consolidation as one possible mechanism underlying interference. Repeated transcranial magnetic stimulation (rTMS) of corticospinal motor output at intensities below movement threshold did not cause interference, whereas suprathreshold rTMS evoking motor responses and (re)afferent activation did. Finally, the experiments revealed that suprathreshold repetitive electrical stimulation of the agonist (but not antagonist) peripheral nerve caused interference. The present study is, to our knowledge, the first to demonstrate that peripheral nerve stimulation may cause interference. The finding underscores the importance of sensory feedback as error signals in motor learning. We conclude that interference requires competing plasticity in overlapping circuits. Interference is remarkably specific for circuits involved in a specific movement and it may relate to sensory error signals.

Central common drive to antagonistic ankle muscles in relation to short-term cocontraction training in nondancers and professional ballet dancers.

Optimization of cocontraction of antagonistic muscles around the ankle joint has been shown to involve plastic changes in spinal and cortical neural circuitries. Such changes may explain the ability of elite ballet dancers to maintain a steady balance during various ballet postures. Here we investigated whether short-term cocontraction training in ballet dancers and nondancers leads to changes in the coupling between antagonistic ankle motor units. Eleven ballet dancers and 10 nondancers were recruited for the study. Prior to training, ballet dancers and nondancers showed an equal amount of coherence in the 15- to 35-Hz frequency band and short-term synchronization between antagonistic tibialis anterior and soleus motor units. The ballet dancers tended to be better at maintaining a stable cocontraction of the antagonistic muscles, but this difference was not significant (P = 0.09). Following 27 min of cocontraction training, the nondancers improved their performance significantly, whereas no significant improvement was observed for the ballet dancers. The nondancers showed a significant increase in 15- to 35-Hz coherence following the training, whereas the ballet dancers did not show a significant change. A group of control subjects (n = 4), who performed cocontraction of the antagonistic muscles for an equal amount of time, but without any requirement to improve their performance, showed no change in coherence. We suggest that improved ability to maintain a stable cocontraction around the ankle joint is accompanied by short-term plastic changes in the neural drive to the involved muscles, but that such changes are not necessary for maintained high-level performance.

Early biomarkers of brain injury and cerebral hypo- and hyperoxia in the SafeBoosC II trial

Background The randomized clinical trial, SafeBoosC II, examined the effect of monitoring of cerebral oxygenation by near-infrared spectroscopy combined with a guideline on treatment when cerebral oxygenation was out of the target range. Data on cerebral oxygenation was collected in both the intervention and the control group. The primary outcome was the reduction in the burden of cerebral hypo- and hyperoxia between the two groups. In this study we describe the associations between the burden of cerebral hypo- and hyperoxia, regardless of allocation to intervention or control group, and the biomarkers of brain injury from birth till term equivalent age that was collected as secondary and explorative outcomes in the SafeBoosC II trial. Methods Cerebral oxygenation was continuously monitored during the first 72h of life in 166 extremely preterm infants. Cranial ultrasound was performed at day 1,4,7,14, and 35 and at term. Electroencephalogram (EEG) was recorded at 64h. Blood-samples taken at 6 and 64 hours were analysed for the brain injury biomarkers; S100beta, brain-fatty-acid-binding-protein, and neuroketal. All analyses were conducted post hoc. Results Significantly more infants with a cerebral burden of hypoxia within the 4th quartile versus infants within quartile 1–3 were diagnosed with severe intracranial haemorrhage (11/39 versus 11/117, p = 0.003), had low burst rate on EEG (12/28 versus 21/103, p = 0.015), or died (14/41 versus 18/123, p = 0.006), whereas none of these events were significantly associated with cerebral hyperoxia. The blood biomarkers were not significantly associated with the burden of cerebral hypo- or hyperoxia. Conclusions The explorative analysis showed that early burden of cerebral hypoxia, but not hyperoxia was significantly associated with low brain electrical activity and severe intracranial haemorrhage while none of the three blood biomarkers were associated with the burden of either cerebral hypo- or hyperoxia.

Impaired Cerebral Autoregulation during Head Up Tilt in Patients with Severe Brain Injury

Early mobilization is of importance for improving long-term outcome for patients after severe acquired brain injury. A limiting factor for early mobilization by head-up tilt is orthostatic intolerance. The purpose of the present study was to examine cerebral autoregulation in patients with severe acquired brain injury and a low level of consciousness. Fourteen patients with severe acquired brain injury and orthostatic intolerance and fifteen healthy volunteers were enrolled. Blood pressure was evaluated by pulse contour analysis, heart rate and RR-intervals were determined by electrocardiography, middle cerebral artery velocity was evaluated by transcranial Doppler, and near-infrared spectroscopy determined frontal lobe oxygenation in the supine position and during head-up tilt. Cerebral autoregulation was evaluated as the mean flow index calculated as the ratio between middle cerebral artery mean velocity and estimated cerebral perfusion pressure. Patients with acquired brain injury presented an increase in mean flow index during head-up tilt indicating impaired autoregulation (P < 0.001). Spectral analysis of heart rate variability in the frequency domain revealed lower magnitudes of ~0.1 Hz spectral power in patients compared to healthy controls suggesting baroreflex dysfunction. In conclusion, patients with severe acquired brain injury and orthostatic intolerance during head-up tilt have impaired cerebral autoregulation more than one month after brain injury.

Intravenous saline administration in patients with severe acquired brain injury and orthostatic intolerance for tilt-table mobilization

ABSTRACT Primary objective: This study aimed to investigate the effect of intravenous saline administration on orthostatic hypotension (OH) during head up tilt (HUT) and the change in the renin–angiotensin–aldosterone system before and after HUT in patients with severe acquired brain injury (ABI). Research design: The study is designed as an observational study. Methods and procedures: Fourteen patients with ABI, low level of consciousness and OH were monitored before, during and after HUT with non-invasive beat-to-beat blood pressure measurement, and transcranial Doppler determination of middle cerebral artery blood flow velocity. Blood samples were collected before and after two HUT sessions separated by 1 hour and saline was administered in between. Main outcomes and results: Patients’ ability to stand upright did not change after saline administration due to OH. The patients showed signs of reduced cerebral autoregulation at both HUT sessions. The patients had a significant lower level of renin and angiotensin II but not aldosterone. Conclusions: Patients with severe ABI and OH demonstrate no improvement in standing time with reduced plasma renin and angiotensin II after two HUT sessions and 1 hour fluid administration. Research focusing on the ability to retain fluid after bed rest is warranted.