Showing papers in "Brain in 1978"

Long latency event-related components of the auditory evoked potential in dementia

Abstract: Long-latency auditory evoked potentials were recorded from two groups of patients, with and without dementia, and were compared with those from a population of normal subjects ranging in age from 15 to 76 years. A sequence of tones of two different frequencies (1000 Hz and 2000 Hz) was presented and each patient was asked to count the occurrences of the rare (P = 0.15) tones in the sequence. Evoked potential waveforms were averaged separately for the rare and frequent tone. Of the various evoked potential components elicited by the tones, the P3 component (latency 300-500 ms) was found to be the most sensitive to aging in normal subjects. It was also the only component which could be used to differentiate between the demented patients and the normal subjects or non-demented patients. The non-demented patients did not differ from normal in any waveform measure. The magnitude of the latency change of the P3 component in dementia relative to normal was sufficiently large that it may provide a practical and objective measure of dementia in a clinical setting.

The neuroanatomy of amnesia. A critique of the hippocampal memory hypothesis.

Abstract: The discovery that medial temporal lobe lesions produce amnesia in humans if the lesion extends sufficiently far posteriorly to include the hippocampus forms the keystone of the hippocampal memory hypothesis. Strong supporting evidence comes from the occurrence of mammillary body disease in Korsakoff's psychosis. Disease of the posterior cerebral artery confirmed the observations on the medial temporal lobectomies by showing that pathology in the ventromedial quadrant of the temporal lobe produces amnesia. The occasional piece of contradictory evidence was sufficiently ambiguous to be dismissed or re-interpreted. Although the contradictory evidence that emerged from animal research created severe difficulties, opinion had crystallized on the matter to the degree that the data were unable to force rejection of the hippocampal memory hypothesis. This necessarily led to the conclusion that the animal model is a poor one: either the human hippocampus is unique with respect to memory or the tests which are used in animals do not tap the same mnemonic processes that are impaired by the human lesions. Both these arguments are nearly impossible to refute. The brain of every species is different and there is no way in which monkeys and humans can be tested under identical conditions. There has never been much enthusiasm for the suggestion that the human hippocampus is so different from other animals that this uniqueness could account for the apparent differences between the behavioural effects of human and animal hippocampal lesions. However, many experimenters have devised clever tests of the possibility that the problem is in the animal behavioural measures. Given sufficient circularity of reasoning, the project must necessarily eventually be successful. The argument is that if the usual tests of learning and memory that are used with animals are not disrupted by hippocampal lesions, then these are not tests of the kinds of learning and memory defects displayed by human amnestics. One has only to search for tasks that are disrupted by hippocampal lesions in animals, and these then must tap the same memory processes that are disrupted by the human lesions. The possibility has rarely been seriously considered that it might be damage to some structure in the ventromedial quadrant of the temporal lobe other than the hippocampus that is responsible for the amnesia. The amygdala and entorhinal area have been ruled out by both the human and animal data. However, the temporal stem is a likely possibility. Its position makes it vulnerable to the surgical approach which was used in human medial temporal lobectomies, and its damage in animals produces deficits in learning and retention. When medial temporal lesions were made in monkeys in the same way that they were made in humans, inadvertent damage to the temporal stem occurred along with the intended amygdaloid and hippocampal injury. Symptoms characteristic of damage to the temporal cortex resulted from these lesions and they were probably caused by the damage to the stem...

Measurements of Visual Evoked Potentials in Parkinson's Disease

Abstract: Visual evoked potentials elicited by reversing grating patterns were recorded in 35 patients with Parkinson's disease and in 26 controls. The average latency of evoked potentials in patients with Parkinson's disease exceeded by two standard deviations the average of the age-matched control group of other neurological patients. Over two-thirds of all patients with Parkinson's disease had abnormal latency. In these patients latency did not correlate with age. In 5 patients the latency became less prolonged on levodopa therapy, suggesting that catecholaminergic pathways have either indirect or direct effects on the generation of visual evoked potentials. Extrapyramidal connections of the visual cortex, as well as retinal dopaminergic neurons, require further study in Parkinson's disease.

Epileptic brain damage: the role of systemic factors that modify cerebral energy metabolism.

Abstract: The possible role of systemic physiological changes (occurring secondarily during status epilepticus) in the causation of epileptic brain damage has been evaluated in rats. Animals were anaesthetized, paralysed and mechanically ventilated; sustained electrocortical seizure discharges were induced by the intravenous injection of bicuculline, 1.2 mg/kg. After two hours of seizure activity brains were fixed by perfusion for histology. Physiological variables were maintained within certain limits from the end of the initial seizure phase (approximate duration twenty minutes) until two hours after onset of seizure to provide six groups: (1) Standard: mean arterial pressure above 120 mmHg, no hypoxia or hypoglycaemia, rectal temperature close to 37 degrees C. (2) Moderate Hypotension: mean arterial pressure at 70-75 mmHg. (3) Severe Hypotension: mean arterial pressure at 50 mmHg. (4) Hypoxia: arterial oxygen tension at 50 mmHg. (5) Hypoglycaemia: non-fed animals, with blood glucose close to 3.0 mumol/g. (6) Hyperthermia: rectal temperature at 40 degrees C. Microvacuolation and ischaemic cell change were identified by light microscopy in scattered neurons in the cortex (principally in the outer layers) in animals in three groups (Standard, Severe Hypotension and Hyperthermia). Similar neuronal changes were seen in the hippocampus (predominantly in the h1 or Sommer sector) in the Standard and Hyperthermia Groups. It is tentatively proposed that neuronal damage in animals with unrestricted cerebral oxygen and glucose availability is due to oxidative mechanisms in cells with excessively enhanced neuronal activity and that lesions caused by failing energy production do not appear until severe degrees of hypoxia are reached.

Electroencephalographic studies myoclonus.

Abstract: Electroencephalographic studies were carried out in 30 patients with various kinds of myoclonus. It was confirmed that the technique of jerk-locked averaging with a backward averaging program was useful for detecting cortical spikes in association with the spontaneously occurring myoclonus, which are not recognized on the convential polygraph, and for evaluating the temporal and topographical relationship between the spike and the myoclonus. By this technique, cortical spikes were shown to precede the myoclonus of a contralateral upper extremity muscle by 7 to 15 ms ith progressive myoclonic epilepsy showed a high amplitude somatosensory evoked potential (SEP) in response to electrical stimulation of the median nerve. The N33 component of this high amplitude SEP was found to be similar to the myoclonus-related cortical spike in their wave form, time relationship and topographical distribution, suggesting an involvement of similar physiological mechanisms in the genesis of both phenomena. Myoclonus in these patients is compatible with "pyramidal" or "cortical loop reflex" type.

The role of frontal and parietal cortex in cognitive processing: tests of spatial and sequence functions.

Abstract: Normal monkeys and monkeys with resection of anterior frontal or posterior parietal cortex were trained to press a panel next to a green panel as a test of extrapersonal spatial orientation and to press a panel next to their own prior press as a test of personal spatial orientation. All monkeys also learned two sets of sequence problems in which the solutions were made independent of spatial location by randomly shifting the locations of the stimuli after each response within a trial. The Parietal Group was significantly impaired on the extrapersonal 'next-to' task but not the more difficult personal 'next-to' task. The Frontal Group was impaired on both the personal and the extrapersonal 'next-to' tasks but only when the relevant cues shifted spatial locations from trial to trial. The performance of the Parietal Group completely overlapped that of the Normal Group on the sequence problems regardless of the level of testing sophistication the monkeys had attained. In contrast, the Frontal Group demonstrated a significant impairment in learning sequences but only when the monkeys were naive. Once they became sophisticated they learned each sequence at a normal rate. Their poor performance was attributed to the lack of stability in the spatial location of the stimuli. The data support the view that a distinction between personal and extrapersonal spatial orientation is relevant to posterior parietal function but indicate that neither sequencing per se nor personal spatial orientation or spatial memory per se is dependent on intact frontal functioning. Rather, the frontal cortex is involved with a higher-order control essential to allow the monkey to perceive the reliable aspects of stimuli contained in a stimulus context full of unreliable noise and to further allow for flexible response pattern appropriate to the demands of a variable context.

Sensory action potentials and biopsy of the sural nerve in neuropathy

Abstract: In 167 consecutive patients with various types of neuropathy, the amplitude of the sensory potential and the maximum conduction velocity along the sural nerve were compared with conduction in other sensory nerves, and were related to structural changes revealed by nerve biopsy. Electrophysiological findings in the sural nerve were similar to those in the superficial peroneal and the median nerve, though the distal segment of the median nerve was normal in 20 per cent of the patients when it was abnormal in the sural nerve. Quantitation of histological findings was a more sensitive method than the electrophysiological study in that two-thirds of 33 patients with normal electrophysiology in the sural nerve showed mild loss of fibres or signs of remyelination in teased fibres. The amplitude of the sensory potential was grossly related to the number of large myelinated fibres (more than 7 micrometer in diameter). Considering the 95 nerves from which teased fibres were obtained, maximum conduction velocity was abnormal in half. In 18 of these nerves, slowing in conduction was due to axonal degeneration: the velocity was as to be expected from the diameter of the largest fibres in the biopsy ("proportionate slowing"). In 9 nerves slowing was severe and more marked than to be expected from loss of the largest fibres ("disproportionate slowing"); these nerves showed paranodal or segmental demyelination in more than 30 per cent of the fibres. In 16 nerves from patients with neuropathy of different aetiology neither loss of fibres nor demyelination could explain the moderate slowing. The cause of slowing in these nerves is unknown; other conditions are referred to in which slowing in conduction cannot be attributed to morphological changes. Finally, electrophysiological and histological findings are reported in some patients with neuropathy associated with malignant neoplasm, with rheumatoid arthritis, with polyarteritis nodosa, with acute intermittent porphyria and with cirrhosis of the liver.

Factors influencing the risk of multiple sclerosis developing in patients with optic neuritis

Abstract: One-hundred and forty-six patients who had presented with optic neuritis but without evidence of demyelination elsewhere in the nervous system, and in whom no specific cause could be identified, were reassessed clinically between one month and twenty-three years after the onset. Fifty-eight patients (40 per cent) had developed MS. All 146 patients were HLA-typed. Three factors were identified which were significantly associated with the development of MS: positive typing for the HLA antigen BT 101, winter onset of the initial attack of optic neuritis in BT 101-positive patients only, and recurrent attacks of optic neuritis. The application of these results to the individual patient is of limited use. However, recurrent attacks of optic neuritis should be given the same significance in the clinical classification of MS as episodes of demyelination occurring elsewhere in the central nervous system in a patient with a previous attack of optic neuritis. The results suggest that optic neuritis is caused by two different environmental agents or groups of agents and that the agent which is most common in the winter leads to the development of MS in the genetically susceptible individual. The agent more common in the summer is much less likely to cause MS in either suscetible or non-susceptible individuals. The biological role of the HLA system in the handling of foreign antigens is discussed and it is suggested that the presence of the HLA antigens associated with MS confers a specific disadvantage on individuals in the ability to handle infection by the MS causative agent and that this allows damaging immunological processes to develop.

Acetylcholine receptors and end-plate electrophysiology in myasthenia gravis

Abstract: and 'Immunological associations of acquired neuromyotonia (Isaacs' syndrome). Report of five cases and literature review'. John Newsom-Davis published 12 original articles in Brain. Many dealt with autoimmunity in disorders of the neuromuscular junction or peripheral nerve. Together this work provided a foundation for knowledge on disorders resulting from autoantibodies directed at the acetylcholine receptor, pre-synaptic calcium channels, and peripheral nerve potassium channels. In 1978, Newsom-Davis and colleagues ask: is the defect in myasthenia gravis pre-or post-synaptic? Previous recordings of miniature end-plate potentials and the response to repetitive firing suggest reduced amounts of pre-synaptic acetylcholine released in individual quanta; but, conversely, studies using radioactively labelled-bungarotoxin indicate fewer functional post-synaptic acetylcholine receptors. This ambiguity needs to be resolved. But one thing is clear. Myasthenia gravis is an autoimmune disease: patients have antibody directed against the acetylcholine receptor; and passive transfer of their serum induces a transient defect of neuromuscular transmission in mice. Now John Newsom-Davis and colleagues report their findings on pre-and post-synaptic function in intercostal muscle removed at thymectomy from 20 patients with myasthenia gravis. The diagnosis is established clinically; and by both a positive response to intravenous edrophonium and the presence, in 13 of 14 patients tested, of anti-acetylcholine receptor antibody. Clinical severity varies amongst the patients; and seven are known to have a thymoma. No patient has taken anti-cholinesterases in the preoperative period; but four are on low-dose alternate day prednisolone. Control muscle is taken from patients undergoing thoracotomy for a variety of reasons. Ricardo Miledi has already confirmed that exposure to-bungaratoxin leads to rapid and irreversible decline in muscle twitch tension and size, but not frequency , of the miniature end-plate potential. Taken with retained sensitivity of the muscle to direct electrical stimulation, the evidence favours an effect of-bungaratoxin on acetylcholine receptors. But is the small size of the miniature end-plate potential due to fewer ion channels opening in response to binding of acetylcholine with its receptor or an alteration in amplitude of the elementary event that follows the opening of each individual channel? With Sir Bernard Katz a normal value for the elementary event of 0.3–0.4 mV at 25 C has previously been established; myasthenic end-plates are less sensitive but, once induced, have an equivalent amplitude and time-course of the elementary event (Fig. 1). I 125-bungaratoxin binding is confounded by non-specific decoration of elements other than the end-plate—tendons and muscle fibres themselves—making it necessary to dissect out …

Bilateral tactile aphasia: a tacto-verbal dysfunction

Abstract: Bilateral tactile aphasia was exhibited by a patient who was operated upon for a left parieto-occipital haematoma. Neuropsychological investigation established the following points: (1) the patient, in whom no expressive or receptive dysphasia could be found, misnamed objects when they were presented to him tactually, whereas he almost always gave the correct name when they were presented visually or auditorily; (2) the naming disturbance was identical when the object was presented to the left hand or to the right hand; (3) not only did the patient have no sensory deficit, but he could give unquestionable proof of correct tactile identification by using the objects presented to him tactually; (4) the defect appeared in the verbo-tactile as well as in the tacto-verbal direction; (5) it was not restricted to the name of the object since the patient was unable to describe, without making dysphasic errors, the morphology or usage of objects presented to him tactually; (6) the tacto-verbal dysfunction did not result from a tacto-visual impairment. Computerized tomography scans showed that: (1) there was no evidence suggesting a lesion of the right hemisphere, nor of the corpus callosum; (2) the left lesion involved the angular gyrus, the posterior part of the second temporal convolution, the inferior longitudinal fasciculus, the geniculostriate fibres and some fibres of the tapetum.

The intrinsic connections of the cortex of area 4 of the monkey

Abstract: The intrinsic connections of area 4 of the monkey have been investigated with axonal degeneration methods after the placement of microelectrode lesions within the cortex. The fibre degeneration is restricted to within a few millimetres of the damage and is asymmetrically distributed in the form of an ellipse with its long axis anteroposteriorly. The same pattern is found in all topographic subdivisions of the motor cortex. There are two distinct zones of degeneration, dense fine terminal degeneration for 200 to 300 micrometer all around the lesion, and a moderate degree of fibre terminal degeneration for a further 2 to 3 mm. The intrinsic connections are disposed predominantly in a horizontal or oblique direction and within the laminae of origin, but there are fibres passing between adjoining laminae and between layers III and V and VI. Two horizontal plexuses of degenerating fibres are present, at the boundary layers II and III and at the level of the Betz cells, and these fibres arise within the cortex. The afferent and efferent fibres of the cortex are arranged strictly perpendicular to the surface. The extent and pattern of the intrinsic connections of area 4 are very similar to those of area 17 of the visual cortex.

A clinical and genetic study of spinal muscular atrophy of adult onset: the autosomal recessive form as a discrete disease entity.

Abstract: A clinical and genetic study of spinal muscular atrophy (SMA) of adult onset is reported. A genetic analysis of all cases of SMA occurring over a ten-year period in North-east England (48 index cases) has shown that chronic proximal SMA of adult onset is a distinct clinical and genetic entity, and is not a variant of the more common and relatively benign late juvenile cases. Nine cases of SMA of adult onset have been studied, occurring in 6 families. The median age of clinical onset was 35 years and the mean age at initial medical presentation was 37 years. The sex ratio was 5:4 (males:females). The condition is relatively benign and there is no evidence to date that life expectancy is shortened; there is usually no premonitory evidence of muscular weakness in early adult life. The muscular involvement is relatively symmetrical and the distal musculature is well preserved; clinical progression of the disease is interrupted by periods of apparent arrest. No patient was able to walk completely unaided twenty years after the initial clinical onset; the median age of patients in the study was 61 years but only one was confined to a wheelchair. In the early stages the recessive form of familial motor neuron disease must be excluded. A segregation analysis of sibs born after index cases was undertaken (segregation ratio of 0.20). This finding is consistent with autosomal recessive inheritance with an extended period during which the disease might initially present. The presence of new dominant mutations cannot be excluded, but is unlikely to account for more than 10% of cases. The carrier rate in the English population is estimated to be 1 in 300, with a gene frequency q = 0.00165. Prevalence is 0.32 per 100,000 in the general population. Empirical risks for genetic counselling are presented.

An electron microscopic study of the termination of intracortical axons upon Betz cells in area 4 of the monkey.

Abstract: After small lesions within the cortex of area 4 of the monkey degenerating axon terminals have been seen with the electron microscopy to contact the cell bodies, proximal parts of the apical dendrites and initial segments of Betz cells 0.5 to 2.5 mm from the damage. The degenerating axon terminals make symmetrical synapses which are presumed to be inhibitory in function. The degenerating terminals are probably from the axons of the basket cells described in Golgi-impregnated material, and which correspond to the large stellate cell recognized in electron microscopic studies.