Michael Trippel

Gating and reversal of reflexes in ankle muscles during human walking

SummaryPhase-dependent reflex modulation was studied by recording the electromyographic (EMG) responses in ankle flexors (Tibialis Anterior, TA) and extensors (Gastrocnemius Medialis, GM and Soleus, SOL) to a 20 ms train of electrical pulses, applied to the tibial or sural nerve at the ankle, in human volunteers walking on a treadmill at 4 km/h. For low intensity stimuli (i.e. 1.6 times perception threshold), given during the swing phase, the most common response was a suppression of the TA activity with a latency of 67 to 118 ms. With high intensity of stimulation (i.e. 2.8 × T), a facilitatory response appeared in TA with a latency of 74 ms. This latter response was largest during the middle of the swing phase, when it was correlated with exaggerated ankle dorsiflexion. The TA reflex amplitude was not a simple function of the level of spontaneous ongoing activity. During stance, TA responses were small or absent and accompanied by a suppression of the GM activity with a latency ranging from 62 to 101 ms. A few subjects showed an early facilitatory, instead of a suppressive, GM response (88 to 136 ms latency). They showed a phase-dependent reflex reversal from a dominant TA response during swing to a facilitatory GM response with an equivalent latency during stance. The GM facilitation occurred exclusively during the early stance phase and habituated more than the TA responses. It is concluded that phase-dependent gating of reflexes occurs in ankle muscles of man, but only when vigorous extensor reflexes are present. More commonly, a phase-dependent modulation is seen, both of facilitatory and suppressive responses.

Regulation of bipedal stance: dependency on “load” receptors

SummaryAccording to recent observations, influence of body load has to be taken into account for the neuronal control of upright stance in addition to the systems known to be involved in this regulation (e.g. afferent input from vestibular canals, visual and muscle stretch receptors). The modulation of compensatory leg muscle electromyographic (EMG) responses observed during horizontal body posture indicates the existence of a receptor system which responds to loading of the body against the supporting platform. This receptor should be located within the extensor muscles because a compensatory EMG response and a loading effect on this response was only present following translational, but not rotational impulses. As the EMG responses were identical to those obtained during upright stance, it is argued that these load receptors activate postural reflexes. According to recent observations in the spinal cat, this afferent input probably arises from Golgi tendon organs and represents a newly discovered function of these receptors in the regulation of stance and gait.

Selective activation of human soleus or gastrocnemius in reflex responses during walking and running

SummaryPhase-dependent reflex modulation was studied by recording the electromyographic (EMG) responses in soleus (SOL) and gastrocnemius medialis (GM) to a 20 ms train of 5 electrical pulses, applied to the sural or tibial nerve at the ankle, in 14 volunteers walking or running on a treadmill. Although both the spontaneous activity and the reflex responses were usually similar for both muscles, instances were identified in which separate control was evident. During walking (4 km/h), activity in SOL started earlier in the stance phase than GM activity. Correspondingly, the amplitude of the reflex responses was larger in SOL than in GM in early stance, both ipsi- and contralateral to the side of stimulation. In some cases, the same stimulus could elicit contralaterally a suppression of GM in synchrony with a facilitation of SOL. These crossed extensor reflexes had a low threshold (1.2 × T) and a latency ranging from 72 to 105 ms. During running (8 km/h or more), responses were seen selectively in GM instead, without concomitant responses in SOL. Such responses had a latency ranging from 82 to 158 ms and they appeared during the first extension phase, at the end of the swing phase. In addition, selective GM responses, with latencies above 200 ms, were seen near the transition from stance to swing during running. These instances of separate reflex control of SOL and GM were correlated with step cycle periods during which the motoneurones of either one of these muscles received more spontaneous activation than the other. Nevertheless, it is argued that premotoneuronal gating must also be involved since the increased amplitude of the crossed SOL responses (in early stance) and of GM responses (at end swing) was not strictly linked to an elevated amount of spontaneous activity during these parts of the step cycle as compared to other parts.

Human postural reflexes and gravity — An under water simulation

This study represents the first attempt to investigate the influence of gravity on postural adjustments. Subjects were displaced while standing under water on a movable platform, while the buoyancy of the body was adjusted by using a variety of lead vests. Under water, an approximately linear relationship was found between body weight and impulse directed electromyographic response amplitudes in the leg and thigh muscles. Loading of the subjects out of water resulted in a saturation of the response amplitude. The biomechanical signals recorded during the displacements indicated that neither vestibulospinal nor muscle proprioceptive reflex mechanisms can account for the effect observed under water. It is suggested that the EMG responses are mediated by reflexes which are activated by pressure receptors within the body in order to hold the centre of gravity over the feet.

Phase-dependent reversal of reflexly induced movements during human gait

SummaryTo investigate whether phase-dependent reversals in reflex responses on electromyography (EMG) are accompanied by movement reversals, a series of human volunteers were studied for their behavioural responses to sural nerve stimulation during running or walking on a treadmill. Low-intensity stimulation (< 2.5 x perception threshold, T) of the sural nerve yielded facilitatory responses in the tibialis anterior muscle (TA), correlated with an induced ankle dorsiflexion (mean maximum 4°) in early swing. The same stimuli yielded primarily TA suppression and weak ankle plantar flexion (mean maximum 1°) at end swing. The correlated induced knee angle changes did not precede the ankle changes, and they were relatively small. Mean maximum flexion in early swing was 6.2°, while mean maximum extension was 3.7°. High-intensity stimulation of the sural nerve (> 2.5 x T) always gave rise to suppression of the ongoing activity. This resulted in a second type of movement reversal. During late stance and early swing the responses in TA were suppressive (i.e. below background activity) and related to ankle plantar flexion. In contrast, the responses during early and middle stance consisted of suppression in extensor activity (gastrocnemius medialis and soleus) and ankle dorsiflexion.The data are discussed in terms of a new hypothesis, which states that the responses to electrical stimulation of cutaneous nerves during locomotion do not correspond directly to corrections for stumbling following mechanical perturbations during the step cycle. Instead, the data invite a reinterpretation in terms of the opening and closing of reflex pathways, presumably by a central pattern generator for locomotion.

Neural Activity in Human Hippocampal Formation Reveals the Spatial Context of Retrieved Memories

Remembrance of Places Past The hippocampus has two major roles in cognition. Place-responsive neurons form a context-sensitive cognitive map, firing more strongly when an animal traverses specific regions of its environment. Both humans and animals thus need the hippocampus to learn their way around novel environments. Similarly, the hippocampus is critical for our ability to remember a specific event in space and time. It has thus been suggested that the spatial and memory functions of the hippocampus reflect a common architecture. Recording from neurosurgical patients playing a virtual reality memory game, Miller et al. (p. 1111) found that the recall of events was indeed associated with reinstatement of the place-firing of neurons activated as the subjects navigated through the environment. Place cells in the human brain that fired at an object’s location are reactivated during spontaneous recall. In many species, spatial navigation is supported by a network of place cells that exhibit increased firing whenever an animal is in a certain region of an environment. Does this neural representation of location form part of the spatiotemporal context into which episodic memories are encoded? We recorded medial temporal lobe neuronal activity as epilepsy patients performed a hybrid spatial and episodic memory task. We identified place-responsive cells active during virtual navigation and then asked whether the same cells activated during the subsequent recall of navigation-related memories without actual navigation. Place-responsive cell activity was reinstated during episodic memory retrieval. Neuronal firing during the retrieval of each memory was similar to the activity that represented the locations in the environment where the memory was initially encoded.

Compensation of human stance perturbations: selection of the appropriate electromyographic pattern.

Perturbations of stance evoke purposive EMG patterns which are directed to hold the bodys centre of gravity over the feet. Dorsiflexing rotation of the feet is followed by a monosynaptic stretch reflex response in the gastrocnemius muscle, succeeded by a late compensatory tibialis anterior activation. Backward translation of the feet elicits only a compensatory polysynaptic EMG response in the gastrocnemius muscle, while an early gastrocnemius response is absent. The amplitude modulation of the gastrocnemius H-reflex has been investigated during the early part of the two modes of perturbation. Only during translational perturbation a progressive decrease in gastrocnemius H-reflex amplitude started within 5 ms after onset of displacement. The degree of the reduction in amplitude in the former perturbation was dependent on the displacement velocity. Only the contact forces (torques) differed between the two modes of perturbations within the first 10 ms after onset of perturbations. It is suggested that signals from pressure receptors within the body are responsible for the early change in H-reflex amplitude during translational perturbations and it is concluded that the simplest spinal reflex is under very rapid and powerful moment-to-moment control by changes in peripheral feedback. In view of a strong reciprocal modulation of monosynaptic and polysynaptic reflex responses, the later purposive EMG responses may be determined by early changes in presynaptic inhibition of group I afferents.

Amplitude modulation of the human quadriceps tendon jerk reflex during gait

SummaryAmplitude modulation of the quadriceps tendon jerk reflex was investigated during the step cycle in normal human subjects. Reflex amplitude was compared with that obtained during a control stance condition, with “equivalent” levels of EMG activity and limb position. During gait there was a progressive decrease in the reflex amplitude early in the stance phase, i.e. during yielding of the knee, and it remained reduced throughout the step cycle. This pattern of changes in reflex amplitude correlated with neither the quadriceps EMG activity nor with the knee joint movements. The behavior of the tendon reflex was similar to that described for the modulation of the quadriceps H-reflex during the early stages of the stance phase of gait. In the latter study it was argued that changes in presynaptic inhibition of quadriceps la terminals could account for the amplitude modulation. We conclude that there is no dramatic change in the gamma drive to quadriceps muscle spindles: tendon reflexes are modulated during the step cycle in much the same way as H-reflexes, in spite of the peripheral and central differences between them. Similar behavior has been described for the soleus H-reflex and Achilles tendon reflex during gait although the modulation of these reflexes followed a different pattern than that seen in the quadriceps.

BCNU for recurrent glioblastoma multiforme: efficacy, toxicity and prognostic factors

BackgroundThe prognosis for patients with recurrent glioblastoma is still poor with a median survival between 3 and 6 months. Reports about the application of carmustine (BCNU), one of the standard chemotherapeutic drugs in the treatment of newly diagnosed glioblastoma, in the recurrent situation are rare.MethodsWe performed a retrospective analysis of 35 patients with recurrent or progressive glioblastoma treated with 80 mg/m2 BCNU on days 1 on 3 intravenously at our department for efficacy, toxicity and prognostic factors. Progression free survival and overall survival were estimated by the Kaplan-Meier method. The influence of age, Karnofsky performance status (KPS), tumor burden, pretreatment with temozolomide (TMZ), type of surgery for initial diagnosis and number of previous relapses on outcome was analyzed in a proportional hazards regression model.ResultsThe median age of the group was 53 years, median KPS was 70. Median progression free survival was 11 weeks (95% confidence interval [CI]: 8-15), median overall survival 22 weeks (95% CI: 18-27). The rate of adverse events, especially hematological toxicity, is relatively high, and in 3 patients treatment had to be terminated due to adverse events (one pulmonary embolism, one pulmonary fibrosis, and one severe bone marrow suppression). No influence of age, KPS, tumor burden, pre-treatment with TMZ and number of previous relapses on outcome could be demonstrated, while gross total resection prior to recurrence showed a borderline statistically significant negative impact on PFS and OS. These data compare well with historical survival figures. However prospective randomized studies are needed to evaluate BCNU efficacy against newer drugs like bevacizumab or the intensified temozolomide regime (one week on/one week off).ConclusionIn summary, BCNU treatment appears to be a valuable therapeutic option for recurrent glioblastomas, where no other validated radio- and/or chemotherapy are available.

Interstitial radiosurgery in the treatment of gelastic epilepsy due to hypothalamic hamartomas

The authors evaluated a new stereotactic radiosurgical approach in seven patients with gelastic epilepsy due to hypothalamic hamartomas. Stereotactic implantation of 125I-seeds into the hamartoma was feasible in six patients. At follow-up at least 1 year after interstitial radiotherapy, two patients had become seizure-free within 2 months, and two others had only persisting auras. There were no major perioperative or postoperative side effects.