Effects of repetitive TMS on visually evoked potentials and EEG in the anaesthetized cat: dependence on stimulus frequency and train duration

Repetitive transcranial magnetic stimulation (rTMS) has been shown to alter cortical excitability that lasts beyond the duration of rTMS application itself. High-frequency rTMS leads primarily to facilitation, whereas low-frequency rTMS leads to inhibition of the treated cortex. However, the contribution of rTMS train duration is less clear. In this study, we investigated the effects of nine different rTMS protocols, including low and high frequencies, as well as short and long applications (1, 3 and 10 Hz applied for 1, 5 and 20 min), on visual cortex excitability in anaesthetized and paralysed cats by means of visual evoked potential (VEP) and electroencephalography (EEG) recordings. Our results show that 10 Hz rTMS applied for 1 and 5 min significantly enhanced early VEP amplitudes, while 1 and 3 Hz rTMS applied for 5 and 20 min significantly reduced them. No significant changes were found after 1 and 3 Hz rTMS applied for only 1 min, and 10 Hz rTMS applied for 20 min. EEG activity was only transiently (<20 s) affected, with increased delta activity after 1 and 3 Hz rTMS applied for 1 or 5 min. These findings indicate that the effects of rTMS on cortical excitability depend on the combination of stimulus frequency and duration (or total number of stimuli): short high-frequency trains seem to be more effective than longer trains, and low-frequency rTMS requires longer applications. Changes in the spectral composition of the EEG were not correlated to changes in VEP size.     

Application of extracorporeal shock-waves in the treatment of pseudarthrosis of the lower extremity

Between January 1991 and January 1996, pseudarthroses of the legs were treated prospectively in 48 patients by application of high-energy extracorporeal shock waves with an experimental device. The mean duration of pseudarthrosis was 12 months. On average, 2.4 surgical interventions had previously been performed. A total of 3000 impulses with an energy density of 0.6 mJ/mm² was applied to the pseudarthrosis. Bony union was achieved in 60.4% of our patients after an average of 3.4 months. Failures were found especially in the atrophic types of pseudarthrosis as well as in congenital bone disorders like fibrous dysplasia or osteogenesis imperfecta. No serious complications were observed. Even after numerous surgical interventions high-energy extracorporeal shock-wave therapy showed a fair success rate. A higher success rate of this non-invasive method for the treatment of bony non-unions may be expected by applying strict selection criteria.     

Das traumatisch bedingte Kompartmentsyndrom des Unterschenkels

Zusammenfassung Um den Stellenwert der Sonographie als Methode der Diagnostik von Sp?tsch?den der Muskulatur nach operativ behandeltem Kompartmentsyndrom zu prüfen, wurden 27 Patienten (sechs Frauen, 21 M?nner) der Abteilung für Unfallchirurgie des Universit?tsklinikums Essen am ventralen Unterschenkel nach durchschnittlich 98 Monaten (43 bis 154 Monate) nach dem Trauma standardisiert untersucht und ein Vergleich mit der gesunden Gegenseite durchgeführt. Bei 15 Patienten war die Dermatofasziotomie wegen eines drohenden und bei zw?lf Patienten wegen eines manifesten Kompartmentsyndroms erfolgt. Im Vergleich zur gesunden Gegenseite konnte eine qualitative Gradeinteilung (0 bis 3) der Ver?nderungen erstellt werden, die das Ausma? der Echogenit?tsvermehrung sowie des Verlustes der muskeltypischen Textur wiedergibt. Grauwerthistogramme konnten die qualitative Einteilung best?tigen. Die Gruppe mit manifestem Kompartmentsyndrom zeigte ausschlie?lich deutliche und massive Ver?nderungen (Grad 2 und 3). Bei drohendem Kompartmentsyndrome fand sich zweimal Grad 2 und 13mal Grad 0 oder 1. Die sonographischen Ver?nderungen sind erkl?rbar durch die bekannten pathomorphologischen Zust?nde nach Kompartmentsyndrom der Muskulatur (Denervierung, Vernarbung). Die Sonographie eignet sich zur Beurteilung der Weichteile nach Kompartmentsyndrom. Die Ergebnisse unterstützen die Forderung nach einer frühzeitigen Fasziotomie bei drohendem Kompartmentsyndrom zur Pr?vention vor Muskel- und Nervensch?digungen.

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Traumatic compartment syndrome of the lower limb: Significance of ultrasonography in evaluating long-term damage of muscle after dermatofasciotomy

To determine the significance of sonography in evaluating long-term damage of muscle surgically treated for compartment syndrome 27 patients of the Department for Trauma Surgery, University Clinic Essen, Germany, were examined on their anterior lower limb after an average of 98 (43 to 154) months after trauma. They had had a fasciotomy for imminent (n=15) or manifest (n=12) compartment syndrome. Comparing the healthy side a qualitative grading (0 to 3) of the changes could be introduced reflecting the extent of the increase in echogenicity and the loss of the typical muscle texture. Gray scale histograms confirmed the qualitative grading. Patients with manifest compartment syndrome showed severe changes (grade 2 and 3). In imminent compartment syndrome 2 patients with grade 2 and 13 patients with grade 0 or 1 were found. The sonographical changes can be explained by the known pathomorphological changes after compartment syndrome (denervation, scarification). Sonography is useful in the evaluation of soft tissue after compartment syndrome. The results underline the demands of early fasciotomy in imminent compartment syndrome for prevention of damage of muscle and nerve.

     

GABA-induced inactivation of functionally characterized sites in cat visual cortex (area 18): effects on orientation tuning.

Microiontophoresis of the inhibitory transmitter GABA was used to reversibly inactivate small sites of defined orientation specificity at a horizontal distance of some 600 microns from single cells recorded in area 18 of cat visual cortex, and the effects on orientation tuning were studied. The receptive fields of cells at the recording and inactivation sites overlapped extensively. During the inactivation of sites where the orientation preference differed by 45 degrees or more from that of a recorded cell ("cross-orientation" sites), 65% of 54 cells tested showed significant broadening of orientation tuning, with a mean increase in tuning width (measured at half the maximum response) of 93%, and an almost fourfold increase in the relative response to the orientation orthogonal to the optimum, compared with the response to the optimum; four cells essentially lost their orientation tuning. Broadening of tuning reflected an increase in response to nonoptimal orientations and was reversible upon termination of GABA application. The effects on orientation tuning typically peaked within 10-15 min of the onset of GABA iontophoresis with 50-100 nA ejecting currents, and could not be replicated by inactivating sites where the orientation preference was similar to that of a recorded cell; when the orientation preference at the inactivation sites was within 22.5 degrees of that of a recorded cell ("iso-orientation" sites), only 3 of 22 cells showed significant broadening of tuning, and in these cases, the effects were relatively weak (mean increase in tuning width of 39% and a negligible change in the relative response to the orientation orthogonal to the optimum). The effect of inactivating "iso-orientation" sites consisted primarily in an increase in response magnitude. The difference in the magnitude of the effects on orientation tuning elicited by inactivating "cross-orientation" and "iso-orientation" sites was highly statistically significant. Additionally, inactivation of "cross-orientation" or "iso-orientation" sites elicited differential effects on orientation tuning in 10 of the 13 cells in which direct comparisons were made. It is argued that the observed broadening of tuning was due to the loss of a "cross-orientation" inhibitory input, which normally sharpens orientation tuning by suppressing responses to nonoptimal orientations.     

Paired-pulse transcranial magnetic stimulation protocol applied to visual cortex of anaesthetized cat: effects on visually evoked single-unit activity

In this study, we tested the paired-pulse transcranial magnetic stimulation (ppTMS) protocol – a conditioning stimulus (CS) given at variable intervals prior to a test stimulus (TS) – for visually evoked single-unit activity in cat primary visual cortex. We defined the TS as being supra-threshold when it caused a significant increase or decrease in the visually evoked activity. By systematically varying the interstimulus interval (ISI) between 2 and 30 ms and the strength of CS within the range 15–130% of TS, we found a clear dependence of the ppTMS effect on CS strength but little relation to ISI. The CS effect was strongest with an ISI of 3 ms and steadily declined for longer ISIs. A switch from enhancement of intracortical inhibition at short ISIs (2–5 ms, SICI) to intracortical facilitation (ICF) at longer ISIs (7–30 ms), as demonstrated for human motor cortex, was not evident. Whether the CS caused facilitation or suppression of the TS effect mainly depended on the strength of CS and the polarity of the TS effect: within a range of 60–130% a positive correlation between ppTMS and TS effect was evident, resulting in a stronger facilitation if the TS caused facilitation of visual activity, and more suppression if the TS was suppressive by itself. The correlation inverted when CS was reduced to 15–30%. The ppTMS effect was not simply the sum of the CS and TS effect, it was much smaller at weak CS strength (15–50%) but stronger than the sum of CS and TS effects at CS strength 60–100%. Differences in the physiological state between sensory and motor cortices and the interactions of paired synaptic inputs are discussed as possible reasons for the partly different effects of ppTMS in cat visual cortex and human motor cortex.     

Spatio-temporal plasticity of cortical receptive fields in response to repetitive visual stimulation in the adult cat

Many psychophysical experiments on perceptual learning in humans show increases of performance that are most probably based on functions of early visual cortical areas. Long-term plasticity of the primary visual cortex has so far been shown in vivo with the use of visual stimuli paired with electrical or pharmacological stimulation at the cellular level. Here, we report that plasticity in the adult visual cortex can be achieved by repetitive visual stimulation. First, spatial receptive field profiles of single units (n=38) in area 17 or 18 of the anesthetized cat were determined with optimally oriented flashing light bars. Then a conditioning protocol was applied to induce associative synaptic plasticity. The receptive field center and an unresponsive region just outside the excitatory receptive field were synchronously stimulated ('costimulation', repetition rate 1 Hz; for 10-75 min). After costimulation the receptive field and its adjacent regions were mapped again. We observed specific increases of the receptive field size, changes of the receptive field subfield structure as well as shifts in response latency.In 37% of the cells the receptive field size increased specifically towards the stimulated side but not towards the non-stimulated opposite side of the receptive field. In addition, changes in the relative strength and size of the on and off subfield regions were observed. These specific alterations were dependent on the level of neuronal activity during costimulation. During recovery, the new responses dropped down to 120% of the preconditioning value on average within 103 min; however, the decay times significantly depended on the response magnitude after costimulation. In the temporal domain, the latency of new responses appeared to be strongly influenced by the latency of the response during costimulation.Twenty-nine percent of the units displayed no receptive field enlargement, most likely because the activity during costimulation was significantly lower than in the cases with enlarged receptive fields. An unspecific receptive field enlargement towards both the stimulated and non-stimulated side was observed in 34% of the tested cells. In contrast to the cells with specifically enlarged receptive fields, the unspecific increase of receptive field size was always accompanied by a strong increase of the general activity level.We conclude that the receptive field changes presumably took place by strengthening of synaptic inputs at the recorded cells in a Hebbian way as previously shown in the visual cortex in vitro and in vivo. The observed receptive field changes may be related to preattentive perceptual learning and could represent a basis of the 'filling in' of cortical scotomas obtained with specific training procedures in human patients suffering from visual cortex lesions.     

Enhanced responsiveness of human extravisual areas to photic stimulation in patients with severely reduced vision

Lesions in the primary visual cortex induce severe loss of visual perception. Depending on the size of the lesion, the visual field might be affected by small scotomas, hemianopia, or complete loss of vision (cortical blindness). In many cases, the whole visual field of the patient is affected by the lesion, but diffuse light-dark discrimination remains (residual rudimentary vision, RRV). In other cases, a sparing of a few degrees can be found (severely reduced vision, SRV).In a follow-up study, we mapped visually induced cerebral activation of three subjects with SRV using functional magnetic resonance imaging. We were especially interested in the visual areas that would be activated if subjects could perceive the stimulus consciously although information flow from V1 to higher visual areas was strongly reduced or virtually absent. Because subjects were only able to discriminate strong light from darkness, we used goggles flashing intense red light at a frequency of 3 Hz for full visual field stimulation. Besides reduced activation in V1, we found activation in the parietal cortex, the frontal eye fields (FEF), and the supplementary eye fields (SEF). In all patients, FEF activation was pronounced in the right hemisphere. These patterns were never seen in healthy volunteers. In a patient who recovered completely, we observed that extrastriate activation disappeared in parallel with the visual field restitution. This result suggests that damage to the primary visual cortex changes the responsiveness of parietal and extravisual frontal areas in patients with SRV. This unexpected result might be explained by increased stimulus-related activation of attention-related networks.     

Velocity invariance of preferred axis of motion for single spot stimuli in simple cells of cat striate cortex

In slices from the visual cortex of kittens maintained in vitro, long-term potentiation of synaptic transmission following high frequency stimuli (10 Hz, 2 min) delivered at low to medium stimulus intensities (80 to 200 A), is accompanied by changes of certain electrophysiological measures recorded intracellularly, such as long-lasting depolarization of membrane potential and decreased threshold to elicitation of an action potential. These parameters have never before been shown to be altered following high frequency stimulation in other systems widely used in studying synaptic plasticity, such as in hippocampal neurons. Another important difference between results from these two systems is that the amplitude of the excitatory post-synaptic potential is enhanced after high frequency stimulation in hippocampal neurons, whereas in striate cortex from young kittens, we observed a decrease. We demonstrate here that this decrease can be reversed to show enhancement from the original amplitude, upon clamp of membrane potential back to the voltage observed prior to stimulation. Thus, what appears to be long-term depression of synaptic transmission, as recorded extracellularly and represented by diminished flow of synaptic current, can be reversed by stepping membrane voltage back to the pre-high frequency stimulation level, to produce responses that then become consistent with long-term potentiation.     

NMDA receptor blockade prevents LTD, but not LTP induction by intracellular tetanization

Intracellular tetanization, the activation of a postsynaptic cell without concomitant presynaptic stimulation, was applied to layer II/III pyramidal cells in slices of rat visual cortex. In standard extracellular medium, intracellular tetanization led to LTP (21 of 43 inputs) or LTD (14 of 43 inputs), the direction of the amplitude change depending on initial paired-pulse facilitation (PPF) ratio: inputs with high initial PPF ratio were usually potentiated, and inputs with initially low PPF were most often depressed or did not change. When applied during blockade of NMDA receptors (50 microM APV), intracellular tetanization failed to induce LTD, but was still capable of inducing LTP (14 of 26 inputs). Although LTP could occur in inputs with both, low and high initial PPF ratio, the correlation between the amplitude change and initial PPF ratio remained: potentiation was stronger in inputs with initially higher PPF. These data suggest that intracellular tetanization activated simultaneously NMDA receptor-dependent LTD mechanisms and NMDA receptor-independent LTP mechanisms, the final change of synaptic gain depending on their balance.