Different TMS patterns of intracortical inhibition in early onset Alzheimer dementia and frontotemporal dementia.

OBJECTIVE: To investigate putative changes in cortical excitability of patients affected by early-onset mild dementia by means of transcranial magnetic stimulation (TMS) and to verify whether a peculiar neurophysiological profile may contribute to characterise Alzheimer's disease (AD) vs frontotemporal dementia (FTD). METHODS: Motor threshold and intracortical inhibition (ICI) and facilitation (ICF) after paired-pulse TMS (inter-stimulus intervals from 1 to 20 ms) were studied in two groups of early-onset demented patients with a neuropsychological profile suggestive of AD (n = 12) and FTD (n = 8). Twelve age-matched healthy subjects were considered as control group. In both patient groups, recordings were performed before and after a single oral dose of 4 mg galantamine. RESULTS: No significant difference in motor threshold was observed among the three studied groups. On the contrary, early-onset AD showed a significant reduction of ICI compared to control group, no changes were detected in FTD patients. No significant changes in ICF were found between both patient groups and healthy subjects. The acute administration of galantamine reversed the modified ICI in AD group. CONCLUSIONS: The differential pattern of ICI exhibited by early-onset AD vs FTD in the early stage of disease may represent a non-invasive, reproducible electrophysiological tool, which may contribute to early differential diagnosis and, possibly, to monitor therapeutic effectiveness. SIGNIFICANCE: The present results support the possibility that subtle, early modifications in intracortical circuitry features AD, but not FTD patients.     

The effect of intravascular saline perfusion on the sequelae of transient cerebral ischemia

Summary Transient global ischemia was produced in cats by interrupting the arterial blood supply to the brain under direct observation of the pial vessels. The pial circulation could be restored only for a brief period after ischemia but intravascular rinsing of the brain during ischemia with various saline solutions considerably improved the postischemic circulation.The functional status of neuronal activity was assessed by recording the EEG and the pyramidal response (PR) after electrical stimulation of the motor cortex. Perfused and nonperfused cats were compared with regard to the structure and function of the motor cortex in the early postischemic period. The neurophysiological signals recovered after ischemia of much longer duration in the perfused animals than in the nonperfused cats. Severe structural alterations were seen in capillaries, neurons and glial cells when ischemia was long enough to suppress the PR. In the perfused animals these changes were virtually absent even after ischemia up to 30 min duration.The increased tolerance of the brain to ischemia produced by the intravascular rinsing appears to result from at least two different mechanisms. Elimination of metabolic waste products presumably reduces tissue damage during ischemia and the improved postischemic circulation prevents secondary ischemic lesions.

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Zuammenfassung Passagere Globalischämie wurde an Katzen durch Unterbrechung der Blutversorgung des Gehirns unter direkter Beobachtung der Piagefäße erzeugt. Die piale Zirkulation konnte nur kurzfristig nach der Ischämie wiederhergestellt werden, doch wurde die postischämische Zirkulation durch intravasale Perfusion des Gehirns mittels verschiedener Salzlösungen beträchtlich verbessert.Der Funktionszustand der neuronalen Aktivität wurde mittels EEG und Pyramidenreaktion (PR) nach elektrischer Reizung des motorischen Cortex geprüft. Perfundierte und nichtperfundierte Katzen wurden im Hinblick auf die Struktur und Funktion des motorischen Cortex in der frühen postischämischen Periode verglichen. Bei perfundierten Tieren kamen die neurophysiologischen Signale nach Ischämie von wesentlich längerer Dauer wieder, als ber nichtperfundierten Katzen. Schwere strukturelle Veränderungen fanden sich an Capillaren, Neuronen und Gliazellen, wenn die Ischämie lange genug anhielt, um die PR zu unterdrücken. Bei perfundierten Tieren fehlten solche Veränderungen selbst nach Ischämie bis zu 30 min Dauer.Die gesteigerte Toleranz des Gehirns gegenüber Ischämie infolge intravasaler Durchströmung erscheint durch zumindest zwei verschiedene Mechanismen bedingt. Die Eliminierung metabolischer Schlackenstoffe verringert vermutlich die Gewebsschäden während der Ischämie und die verbesserte postischämische Zirkulation verhindert sekundäre ischämische Schäden.

     

Dorsal-ventral gradient in vulnerability of CA1 hippocampus to ischemia: a combined histological and electrophysiological study

Transverse hippocampal slices were prepared after 7 days survival from rats subjected to 8 min of global incomplete ischemia by temporary occlusion of both carotid arteries and hypotension. The slices demonstrated a dorsal-ventral gradient in the amount of ischemic neuronal necrosis in the CA1 region. Histologically ischemic cell change decreased from 90% dorsoseptally to 10% ventrotemporally. Electrophysiological analysis of the number of slices with viable synaptic transmission in CA1 also revealed a septotemporal gradient in susceptibility to ischemia.     

Distribution of scalp somatosensory potentials evoked by stimulation of the tibial nerve in man

The scalp distribution of the response to stimulation of the tibial nerve at the medial malleolus was systematically analysed. The somatosensory evoked potential (SEP) was recorded with electrodes placed in a transversal line over the ipsilateral and contralateral postcentral gyri and in a sagittal line over the longitudinal brain fissure. The SEPs recorded over the ipsilateral hemisphere and along the sagittal line were similar to the F response (the response over the foot primary somatosensory region). Over the contralateral hemisphere the waveform of the responses changed obviously from point F to the point C (contralateral hand primary somatosensory region). The C response started with N37, P40 had a longer latency, N50 was not present and the subsequent waves were also considerably different. Mathematical simulation of the responses recorded from the electrodes between points F and C has shown that they represent an electrical algebraic summation of the activity over points F and C. Although the F and C responses may be 2 potentials arising from the opposite sides of a single dipole generator which is located in the medial fissure, it is more probable that the somatosensory evoked potential on tibial nerve stimulation reflects the activity of 2 separate generators.     

The electrode,the brain and the mind

Conclusion Finally, the brain does function as an integrated whole in one sense. But there are semi-separable mechanisms within that integration. We must continue to study them. This is the way of progress that was begun for us by Fritsch and Hitzig, and Charcot and Jackson.As scientists, we should reserve judgment as to the ultimate nature of things. Meantime we can only use the language of dualism, and speak thus of the mind and the brain. There is no other medium of analytical discussion. The ancient riddle of how brain and mind do interact is still unsolved. But, we begin to understand the brain, if not the mind. The mind receives messages. It seems to direct brain action in the focussing of attention and in voluntary activity.There is a special mechanism for the mind. It can be activated from a distance by an electrode on the interpretive cortex. The mechanism is sometimes arrested by epileptic discharge in centrally placed gray matter. During this activation, consciousness is not lost. During this arrest, consciousness is lost and since other mechanisms continue without control from the mind's mechanism, the individual becomes an automaton.Fritsch and Hitzig had stumbled upon the truth. The brain does function, as they said, by isolated mechanical means. And we can now perceive the outline of a further truth: The mind is matched by a specific corresponding mechanism in the brain. Human behaviour is determined by interaction of brain and mind.The Fritsch and Hitzig Centennial Lecture, Deutsche Gesellschaft für Neurologie and La Société Neurologique de France, München, October 8, 1970.     

Electrophysiological methods for the identification of thalamic nuclei

Summary To increase the precision of the anatomical localization in stereotaxic neurosurgery, three techniques are now in common use to identify the thalamic nuclei: electrophysiological recording, local stimulation, reversible local blockade. A comparison is made between the results obtained by these three methods.Translated from a paper presented at the Joint Meeting of the German and French Neurological Societies, Munich 1970.     

Expressing qualitative biomedical knowledge exactly using the language LESK

A language (LESK) is described which allows one to make mainly qualitative declarations of the essential terminology and facts in some technical subject. LESK is essentially first order predicate calculus, made to look like natural language. A LESK system, now partially implemented in PROLOG, allows one to enter declarations and assertions, check consistency, and deductively answer predominately generic, universally quantified questions.An extensive example is presented in which LESK is used to describe neurophysiological knowledge about the stretch reflex.     

Quantification of synaptic vesicles in hippocampus of aging rats and initial studies of possible relations to neurophysiology

Synaptic vesicle populations were quantified in Schaffer-commissural synapses which terminate on CA1 pyramidal cell apical dendrites, in aging and young-mature rats. Vesicles were found to be reduced with age, and this effect was most pronounced in the oldest animals (e.g., 28 months) within the aged group. Numerical density of synaptic vesicles in aged rat hippocampus was reduced whether expressed as vesicles per terminal, vesicles per μ² of terminal, or vesicles per μ² of terminal corrected for shrinkage or swelling as assessed by mitochondrial cross-sectional diameters. Counted synaptic terminal areas were not significantly different in the aged animals, although a trend toward reduced terminal size with aging was seen. The latter observation apparently rules out increased terminal swelling in aged rat synapses as a basis for reduced vesicle density. In some rats, neurophysiological studies were concomitantly performed. A significant correlation was found between the amplitude of the monosynaptic population spike after 20 min of 4 Hz stimulation of the Schaffer-commissural fibers and synaptic vesicle populations in terminals of these stimulated pathways. However, because of a low n this result must be viewed as preliminary.     

Activation of mossy and climbing fiber pathways to the cerebellar cortex by stimulation of the fornix in the rat

Summary The fornix of the rat was electrically stimulated with bipolar concentric electrodes to determine the properties of single unit responses in Purkinje cells of the cerebellar cortex. Both climbing (CF) and mossy fiber (MF) pathways were activated by fornix stimulation. MF responses were indicated by single or double spike responses appearing at latencies of 5–10 ms. The MF spike responses, as quantified by histogram analysis, were further identified by appearance of graded responses with increasing stimulus strength and by following at frequencies up to and greater than 20/s. CF responses were identified by characteristic complex all-or-none burst responses with latencies usually between 10 and 20 ms and with following frequencies at no faster than 10/s. Experiments which involved movement of the stimulating electrode and production of lesions around it established that the activated fiber system was within the dorsal fornix and not in adjacent areas. The results indicate that hippocampal and other limbic areas can influence the cerebellar cortex by direct mossy and climbing fiber pathways, as has been demonstrated for other afferents. It is further suggested that motor patterns linked to hippocampal activity may be regulated by this system.This work was supported by N.S.F. Grant No. 77-01174 awarded to Dr. Donald J. Woodward, and an award from the Biological Humanics Foundation