Development of a multiple thin-film semimicro DC-probe for intracerebral recordings.

A thin-film multiple-electrode probe for measuring de potentials at eight sites with interdistances of 1 mm was constructed for the investigation of slow potential changes in deep regions of the human brain during surgery. The thin-film electrodes had to be placed on curved cylinder-shaped surgical instruments with dimensions of 2 mm diameter and 33 cm length used with the Freiburg stereotactic equipment. Several novel technological steps had to be introduced for the solution of the encountered problems: 1) Structuring of the metal layers on curved substrates was accomplished by using flexible masks. 2) Special feed-through technologies had to be invented in order to obtain reliable connections between the thin-film sensors and the copper wires inside the stereotactic instrument. 3) Thin-film Ag-AgCl electrodes had to be formed in order to obtain satisfying recordings of slow potential changes below 10 Hz. Slow potential changes were recorded from different depths in interdistances of only 1 mm with these new miniaturized thin film Ag-AgCl electrodes and bipolar recordings with an electrode interdistance of only 3 mm showed clearly the appearance of Bereitschaftspotentials.

High resolution multi-temperature sensors for biomedical application.

A temperature sensor array was designed in order to study local temperature variations and temperature gradients in biological samples. The sensor probe was inserted in the optical cortex of rabbits in order to study temperature changes during normal brain activity as well as under artificial ventilation conditions. Temperature sensitive areas of 0.14 mm x 0.1 mm are arranged in a row with interdistances of 0.4 mm yielding high spatial resolution. A temperature resolution of 0.1 mK and a 90% response time of maximum 3 milliseconds was obtained utilizing the high temperature dependence of 2%/K of the conductivity of vacuum evaporated germanium films. The sensor is passivated by a 1 micron thick PECVD-silicon nitride layer and can be placed on glass-, alumina- and polymer substrates. For brain tissue studies, in order to minimize tissue damage the temperature sensors were placed on a 0.1 mm thick needle-shaped glass substrate. A sensor element mounted on a glass substrate and immersed in water showed a self heating of less than 5 mK due to the applied measurement current of 2.1 microA.

Stimulus-activated changes in brain tissue temperature in the anesthetized rat.

A new thin-film, multisensor probe was used to determine tissue oxygen tension, tissue temperature, and electrical activity at two depths below the brain surface in chloral hydrate- or nitrous oxide/halothane-anesthetized rats. Brain tissue temperature at both depths was found to be lower than core temperature by 1-2 degrees C. Electrical activation, spreading depression, and pentylenetetrazol seizures all resulted in transient increases of brain tissue temperature of a few tenths degree centigrade. Vasodilation, induced by hypercapnia or hypoxia, caused a warming of brain tissue. Near-maximum oxygen metabolism, reached upon reoxygenation after severe hypoxia, was accompanied by tissue temperature rises of greater than 1 degree C. It was concluded that brain tissue temperature in the anesthetized rat is lower than core temperature due to extensive radiative and conductive heat loss to the environment through the head. Transient increases in tissue temperature during activation are caused by vasodilation and increased metabolism.

Multisite recording of brain field potentials and unit activity in freely moving rats.

A technique has been developed to record from 16 different brain sites of the freely moving rat using subminiature MOSFET preamplifiers. The high input impedance, small size, durability and light weight of the amplifiers and connecting cable allows high quality multisite recording of field potentials and unit activity. In addition, a movable headstage for positioning multiple microelectrodes is described. The compact recording system permits one to construct neocortical EEG maps, instant depth profiles of evoked and spontaneous field data, and to study neuronal synchrony of distant cell populations.

Simultaneous recording of local electrical activity, partial oxygen tension and temperature in the rat hippocampus with a chamber-type microelectrode. Effects of anaesthesia, ischemia and epilepsy.

A miniature multiple thin-film recording sensor was used to measure simultaneously the electrical activity, oxygen content and temperature of brain tissue. The chamber-type potential sensor was an Ag/AgCl electrode covered by an Si3N4 (silicon nitride) chamber. The chamber-type oxygen sensor consisted of an Au-Ag/AgCl two-electrode electrochemical cell embedded in an electrolyte-filled Si3N4 chamber. The temperature sensor was a thin-film germanium resistor. The different sensors were spaced 300 microns apart. Anaesthetics (pentobarbital, chloral hydrate, chlornembutal, halothane) were shown to depress electrical activity and to increase local oxygen tension in the hippocampus. Halothane, but not the other anaesthetics, also increased the current output of the oxygen sensor when tested in saline bath, indicating that the apparent increase in measured oxygen levels during halothane anaesthesia was partly due to an electrochemical effect of halothane on the oxygen sensors. The decrease of tissue oxygen consumption produced by the other anaesthetics is likely to be the result of metabolic depression. Cerebral ischemia, evoked by cauterization of the vertebral arteries and occlusion of the carotid arteries for 30 min, resulted in the disappearance of both spontaneous and evoked electrical activity in the hippocampus and a decrease of both local temperature and oxygen tension. There was a marked overshoot of the oxygen tension to above preocclusion level following the release of the carotid arteries. As soon as electrical activity returned, the oxygen tension fell again, often below the lowest level seen during the ischemic period. This secondary decrease of oxygen level could be reversed by administration of supplementary small doses of anaesthetic. The anaesthetic-induced increase in oxygen tension was accompanied by a marked decrease in electroencephalogram amplitude and frequency. During electrically induced seizures a decrease in hippocampal oxygen content occurred and was accompanied by an increase of local temperature. Since the rectal temperature was kept constant, the changes in temperature are likely to reflect changes in blood perfusion of the recorded area. These findings are in agreement with previous observations made with conventional electrodes. In addition, the miniature size of the chamber-type microelectrode assembly allows a correlated monitoring of parallel physiological changes with high spatial and temporal resolution during anaesthesia, ischemia and epilepsy.

Brain tissue temperature: activation-induced changes determined with a new multisensor probe.

Local brain tissue oxygen tension, temperature, and electrical potential were continuously and simultaneously measured at each of two different depths in anesthetized, paralyzed rat brain. Brain tissue temperature increases up to 1 degree C were recorded in response to direct electrical stimulation, spreading depression, PTZ-induced seizures, hypercapnia, and hypoxia. An increase in brain tissue temperature was also recorded during reoxygenation after hypoxia. Thus, we have shown that, in this preparation, increases in either blood flow or oxidative metabolism lead to transient warming of the brain.

Procedure for identification of different stages of EEG background activity and its application to the detection of drug effects.

A procedure for the detection of a change in EEG background activity is introduced. Here the time path of the relative power in the alpha band is modelled by fitting two lines, each corresponding to a different level of background activity. The jumping point between these two lines is estimated and serves as an indicator of drug effects.

Changes in neuronal transmission in the rat hippocampus during behavior.

Rats with implanted stimulating and recording microelectrodes were trained in a straight alley to repeatedly press a bar placed at one end of the alley and to run for water reward available at the other end. Stimulating the commissural input evoked field EPSP and population spike in the CA1 region while no population spike was observed in the dentate area. The amplitude of the CA1 population spike was maximum during running and smallest during drinking. Field potentials in the dentate gyrus changed in an opposite manner (drink greater than groom greater than press greater than run). Perforant path evoked cell discharges in the dentate gyrus which were maximal during drinking and smallest during running. The behavior dependent changes of the evoked potentials covaried with the frequency and power of the simultaneously recorded theta activity. Perforant path stimulation during the negative-going phase of the dentate theta cycle evoked significantly greater granule cell responses than stimuli during the positive-going phase. These observations suggest that the medical septum exerts a potent biasing effect on the efficacy of other afferent to the hippocampus.

Pattern of intracortical potential distribution during focal interictal epileptiform discharges (FIED) and its relation to spinal field potentials in the rat.

The pattern of intracortical potential distribution during focal interictal epileptiform discharges (FIED) was analysed with respect to the occurrence of descending neuronal activity to the spinal cord recorded as spinal field potentials (SFPs). The experiments were performed in rats. Epileptiform activity was elicited by application of penicillin to the motor cortex. The spread of active penicillin was limited by penicillinase in part of the experiments. (1) When penicillinase was applied 10--20 sec before penicillin to the cortical surface typical FIED appeared in the epicortical lead. During well-established focal activity they were accompanied by negative field potentials at a depth of 300 micrometers and 600 micrometers and by positive field potentials in deeper records. This pattern of intracortical potential distribution was not associated with characteristic SFPs. (2) When penicillinase was applied simultaneously with penicillin, the fully developed epicortical FIED were accompanied by negative intracortical field potentials which in this case reached a depth of 900 micrometers. In the layers below predominantly positive potential fluctuations occurred. This pattern of intracortical potential distribution was associated with characteristic SFPs. (3) Intracortical application of penicillin at a depth of 800--900 micrometers led to negative field potentials of large amplitude in all intracortical records, with the concomitant epicortical potentials being positive in polarity. In this case SFPs occurred throughout the interictal activity. Since seizure activity can be restricted to only a few cortical laminae, descending neuronal activity to the spinal cord need not be correlated with definite epicortical potentials. A prerequisite for cortical output is intracortical activity reflected negative potentials at a depth of approx. 900 micrometers.

A 16-fold semi-microelectrode for intracortical recording of field potentials.

A 16-fold semi-microelectrode with 10 x 10 sq. microns contacts at distances of 150 microns, produced by means of thin-film technology, is described. These small dimensions are required to study the laminar electrophysiological differences within the cerebral cortex.

[Local pO2 measurements in the cochlear perilymph of guinea pigs in oxygen and oxygen/carbon dioxide breathing (author's transl)]. / Lokale pO2-Messungen in der Perilymphe der Meerschweinchenkochlea bei Sauerstoff- und Sauerstoff-/Kohlendioxyd-Inhalationen.

After breathing a mix of 10% CO2 and 90% O2 or hyperbaric O2 (2 bar absolute) an appreciable rise of pO2 can be demonstrated by D.C. polarography in the scala tympani of the guinea pig chochlea. When test animals are made to breathe 100% pure O2 at normal pressure the rise of pO2 is significantly less pronounced. The observations made in these animal experiments suggest that the inhalation of CO2O2 currently constitutes the only valid inhalation treatment in acute inner ear deafness. Further compression of hyperbaric O2 is associated with a clear-cut rise of pO2. It should, however, be remembered that hyperbaric oxygen may produce toxic effects in various body tissues.

[The phenomenon of synchronization in the status epilepticus produced by penicillin and its changes after Clonazepam (author's transl)]. / Das Phänomen der Synchronisierung im Penicillinstatus und dessen Veränderung unter Clonazepam

The purpose of this series of experiments was to understand how Clonazepam changes the mechanisms of synchronization in seizures. Penicillin was applied to the rabbits cortex. Interictal spikes and seizures were recorded with multiple electrodes from both the cortical surface and intracortically. The spatio-temporal relationships during these electrical events were studied by topographical methods. Moreover, power spectrum and coherence estimates were performed. A most characteristic feature seen with low doses of Clonazepam is a regularization of the spatio-temporal behaviour of both spikes and seizures. The number of tonic phases considerably increases at the cost of clonic phases. The seizures take more time to become generalized. The generator-zones become larger. This is explained by a decrease of the number of neurones--by Clonazepam--which are still left to produce "paroxysmal depolarization shifts". The findings confirm the increase of postsynaptic cortical inhibition under Clonazepam, as demonstrated by various authors.

[Intracortical electrogenesis: spontaneous activity, sleep and epileptic seizure (author's transl)]. / Zur intrakortikalen Elektrogenese: spontantätigkeit, Schlaf und epileptischer Anfall

Various electrical activities were recorded in rabbits from within the cortex by means of a multielectrode carrying, on a glass needle, 8 Ag-AgCl contacts (50X50 micronm) at 300 micronm distances. The records were stored on tape and analyzed (power spectrum, coherence and phase). Generally, the relatively uniform pattern of the cortical surface is paralleled by a spatio-temporally very complex intracortical activity. In all activities a zone of minimum activity ("zero zone") was found between roughly 500 and 800 micronm below surface. Beyond this zone, activities often appear like a mirrorimage of the surface activities although true phase-reversals never occur. In spontaneous activities this zone remains constant, during seizures it may shift and broaden. The maximum power is usually found below this zone. The transcortical power profile often changes during seizures. Tonic patterns, although fairly uniform in the ECoG from the surface of the cortex, turn out to be composed of several components when studied intracortically. The "generator zones" of the various intracortically identifiable graphoelements have various vertical position and extension. These findings demonstrate that a certain neuronal circuitry may be responsible for the shape of the potential recorded. This circuitry is far from rigid but may change in different stages of synchronization. For a better spatio-temporal resolution of intracortical activities, the interelectrode distance has still to be reduced.