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Biomedical subjects

L Weiskrantz

Publications and source records attributed to L Weiskrantz.

At least 19 recordsLinked to original sources

MK-801 can facilitate passive avoidance memory when retention is not present in control animals, and can fail to facilitate when it is present.

The results confirm that NMDA receptor blockade can result in improved retention performance of mice in step-down passive avoidance. A series of behavioural variations and analyses revealed that memory in the task depended mainly on the appearance of the grid that had been associated with shock, rather than on the execution of an instrumental response or on the spatial locus of the punishment. When the grid was made invisible during retest, retention was never found. However, MK-801 did not facilitate retention based on the appearance of the grid. In contrast, conditions were found in which, even though control animals showed no learning, MK 801 given after the learning trial facilitated retention. Thus, the dominant mode of learning and memory in the step-down task is insensitive to the drug, whereas the drug raises a weaker or alternative mode to above threshold levels.

Animals

Factors affecting visual sensitivity in a hemianopic subject.

A well-studied subject with visual cortex damage (G.Y.) was tested in his hemianopic field with temporally modulated sinusoidal and square-wave gratings. The purpose was to use an extended range of parameters to obtain a detailed spatiotemporal specification of his residual vision and to try to resolve the discrepancy between negative findings of Hess and Pointer (1989) and previous positive claims. Both the spatial and temporal parameters could be Gaussian-weighted. Detection as a function of spatial frequency, contrast, temporal modulation frequency, stimulus size, and slope of the temporal and spatial Gaussian functions was investigated using a two-alternative forced-choice procedure. The most important parameters for this subject were found to be the slope of the temporal Gaussian function and the size and contrast of gratings. With optimum parameters he could reliably achieve a score of 95-100% correct in his 'blind' field. The results are consistent with earlier studies of this subject, especially his ability to respond to moving stimuli, and also may account for why negative results had been reported for him when particular fixed parameters were used.

Contrast Sensitivity

Problems of learning and memory: one or multiple memory systems?

Learning, and hence memory, is ubiquitous not only throughout the animal kingdom, but apparently throughout many regions of the brain. Is all learning reducible to a single common form? Neuropsychological dissociations suggest that the mammalian brain possesses a number of different and potentially independent memory systems, with different mechanisms and anatomical dispositions, some of which are neurally widely dispersed and others of which are narrowly organized. Among the types considered are: (i) short-term memory; (ii) knowledge and skills; (iii) stable associative memory; (iv) event memory; and (v) priming. As double or multiple dissociations do not lead to logically inevitable conclusions, it has been argued that an alternative to multiple memory systems is variable modes of processing. But these, too, would be dissociable on the same lines of evidence. Dissociations, if strong and absolute, have strong pragmatic power when they are combined with evolutionary and neuroscientific evidence. Multiple memory systems may possibly share some common cellular mechanisms, but such mechanisms do not define the separate properties at the systems level.

Amnesia

The Ferrier lecture, 1989. Outlooks for blindsight: explicit methodologies for implicit processes.

In primates the retina is connected with different targets in the brain via several parallel pathways, the largest of which is that going to the lateral geniculate nucleus of the thalamus and thence to the striate cortex, the geniculo-striate pathway. When this route is damaged in man, apparent blindness in a corresponding part of the visual field occurs, despite the integrity of the other parallel pathways. In animals, it has been demonstrated by conventional behavioural forced-choice techniques that extrastriate routes can sustain a variety of visual discriminations. Comparable discriminations are also possible in some human subjects with geniculo-striate damage when forced-choice 'guessing' techniques are used. 'Blind-sight' refers to those subjects who state that they are unaware of the visual stimuli, even when performing discriminations at high levels of proficiency. Extensions of this approach are reviewed, especially to spectral sensitivity and movement discrimination. But residual capacities can also be assessed without requiring guessing responses, thereby avoiding issues of differential response criteria and other practical difficulties. Effects of 'unseen' stimuli in the cortically blind field on the visible perception of concurrent stimuli in the intact field can be measured. Also, positive reactions of the autonomic nervous system, such as the galvanic skin response, can be recorded to visual stimuli presented in the blind field. Recent evidence demonstrates that the pupil in normal adult subjects is systematically sensitive to structural and chromatic features of visual stimuli. Pupillometry reveals specific changes and residual capacities in visual-field defects of adult patients with striate cortical damage. Thus non-verbal and sensitive methods are available that permit the comparative study of normal and residual visual capacity in human infants, adults and infra-human animals.

Animals

The effects of fornix transection and combined fornix transection, mammillary body lesions and hippocampal ablations on object-pair association memory in the rhesus monkey.

Cynomolgus monkeys were tested on an associative memory task in which they had to remember object-object pairings. Eight animals (4 unoperated monkeys and 4 monkeys with lesions to components of the 'hippocampal-mammillary' circuit) were trained initially on a conditional object-pair association task that was similar to simple discrimination learning, but which involved presentation of object-pairs instead of single objects. Object-pairs were made up from 4 different objects, each with an identical copy. Animals had to learn which pairings of the 4 objects were rewarded (e.g. AB or CD) and which pairings were not (e.g. AC or BD). Objects appeared as a member of both rewarded and non-rewarded pairs. After several stages of training all monkeys reached a high level of performance making greater than 90% correct choices. In a performance test the monkeys had to discriminate between 3 single objects depending on their past associations with the other objects. Animals had to choose the two objects which in initial training were rewarded as an object pair. Monkeys with the 'hippocampal-mammillary' circuit lesions learned the initial object-pair discriminations at the same rate as control monkeys. In the performance test, however, monkeys with the 'hippocampal-mammillary' circuit lesions performed at chance levels, whereas the control monkeys performed significantly better. The results demonstrate a dissociation between the 'habit' and 'mediational' memory systems for ostensibly the same object-pair associations. They also indicate an important contribution of the 'hippocampal-mammillary' circuit in nonspatial association memory.

Animals

NMDA receptor antagonists can enhance or impair learning performance in animals.

The effects of NMDA receptor antagonism on learning and memory were investigated using competitive (DL-2-amino-7-phosphonoheptanoate, AP7) and non-competitive (MK 801) blockers in three different learning tasks. Administration (i.p.) of drugs prior to training resulted in impaired learning performance in the place-navigation and dark-avoidance paradigms, and improved performance in the step-down passive avoidance task; however, using this treatment protocol, the possibility of drug-induced non-mnemonic effects modifying learning performance could not be excluded. Drug administration immediately post-trial had no effect in the place-navigation paradigm, and improved retention performance in the dark-avoidance and step-down avoidance tasks. The similar results obtained with both types of antagonist indicate that the observed effects are indeed due to NMDA receptor blockade, and hence that such blockade modifies learning in a task-dependent manner. Exclusion of non-mnemonic effects by using the post-trial treatment regime demonstrates that NMDA antagonists facilitate learning of passive avoidance tasks.

2-Amino-5-phosphonovalerate

Residual vision in a scotoma. A follow-up study of 'form' discrimination.

This study is a follow-up of a patient, D.B., who was reported (Weiskrantz et al., 1974) to be able to discriminate between simple visual forms within the scotoma caused by a lesion in calcarine cortex. Among other capacities, he was able to discriminate between lines of different orientation in the frontal plane. Given the reported deficits for form discrimination but a high sensitivity for orientation discrimination in primates without striate cortex, the question arises whether D.B.'s apparent 'form' discrimination arises from an ability to discriminate the orientations of components of the figures. It is shown in the first experiment, by using the optic disc as a control, that his ability to detect stimuli in his scotoma cannot be due to stray light falling upon the intact field. Next, his ability to discriminate orientations is confirmed, and an orientation threshold determined. A range of form discriminations is presented varying in degree of orientation cues of their components. It is confirmed that he can discriminate those forms originally studied, in which such differences are large, but not when orientation cues are small or minimal. Finally, his ability to compare two forms both projected within his scotoma is examined. Even when the components of the two forms have large orientation differences and are highly discriminable when presented successfully, D.B. appears to be unable to make a 'same-different' comparison when both are presented simultaneously. The evidence is interpreted against D.B.'s having a residual capacity for form discrimination.

Follow-Up Studies

Residual tactile sensitivity with self-directed stimulation in hemianaesthesia.

A case of hemianaesthesia caused by right hemisphere stroke was found to have good sensitivity and cutaneous localisation when she touched her impaired hand with her good contralateral hand or with a probe held by that hand. The capacity did not depend solely upon movement or positioning of her right arm, and she could also discriminate whether her own left fingers, as opposed to someone else's inter-digitated fingers, were being touched, but only when she did the touching. Thus, the threshold of the impaired hand appeared to be markedly affected by active involvement of the contralateral limb in delivering the stimulus.

Cerebral Cortex

Neuroanatomy of memory and amnesia: a case for multiple memory systems.

Several different dissociable memory systems are considered in terms of their known or putative sites of pathology. In man, short-term memory can be selectively impaired by left hemisphere lesions near the acoustic projection area. There may be other modality-specific deficits. Long-term memory is considered in terms of a) knowledge systems, b) stable associative memory; c) priming, and d) event memory, with special reference to the amnesic syndrome. For each of these categories, clinical neuropathological and relevant animal evidence is reviewed. It is concluded that "memory" is not holistic, and the anatomical bases must be considered independently for each of the several dissociable (but normally interacting) systems. Some are likely to involve virtually all levels of the nervous system, while others are highly specific.

Amnesia

Introduction: categorization, cleverness and consciousness.

Various recurring themes in the history of the subject are reviewed. In the context of adaptation to a complex environment, one precondition for survival must be a capacity for object identity, which may be the most basic form of categorization. Evidence will be presented that suggests that the capacity is not learned. In considering learned associations among categorized items, a distinction is made between reflexive and reflective processes: that is between those associations in which a cue or signal provides an unambiguous route to the response, no matter how complex that route may be, in contrast to those in which learned information must be ordered and reordered 'in thought'. An example of one experimental approach to the latter is provided. Finally, the problem of conscious awareness is considered in terms of stored categorical knowledge and associations, on the one hand, and a system that monitors them, on the other. Neurological evidence of disconnections between these different levels is reviewed.

Animals

Memory disorder in Korsakoff's psychosis: a neuropathological and neuropsychological investigation of two cases.

Neuropathological findings in the brains of two alcoholic patients with Korsakoff's psychosis are reported. Their memory defects had been studied in detail quantitatively over a period of nine years in one case and three years in the other, relevant details of which are presented. Both patients had had a relatively pure long-term memory impairment in the absence of other cognitive deficits and in the absence of a short-term memory impairment. Their retrograde amnesia for public events and famous faces had been measured and found to have extended backwards over at least twenty-five years. There was severe impairment in anterograde recognition memory for both verbal and non-verbal material. On a newly prepared memory quotient battery both patients had scored well below the bottom of the normal scale (less than 60, where 100 is the mean with a standard deviation of +/- 15). Both patients had also shown the characteristic differential improvement in retention when tested by cued recall and also the characteristic 'prior learning effect', i.e. normal retention of one list of words when tested by cued recall but impaired retention of a second list sharing the same cues as the first list. There had been a slight but significant deterioration in intelligence in one of the patients in the two years prior to his death, although his IQ still fell within the normal range. The other patient remained undeteriorated until his death, and his IQ also was close to an estimated measure of his premorbid IQ. In the brains of both patients there was marked gliosis, shrinkage and discolouration bilaterally in the medial nuclei of the mammillary bodies. In addition there was a thin band of gliosis bilaterally between the wall of the third ventricle and the medial dorsal nucleus, the rostral limit lying anterior to the medial dorsal nucleus. In the patient with no intellectual deterioration these were the only pathological changes that were seen. In neither patient was there evident local loss of nerve cells, gliosis or any other qualitative evidence of abnormality in the hippocampi, the white matter of the temporal lobes or the greater part of the medial dorsal nuclei, although it is difficult to be certain whether there was any overlap between the band of gliosis and the most medial region of the medial dorsal nueleus and other adjacent thalamic nuclei. In the other patient there was also a small zone of softening in the cerebellum and an increase in astrocytes in other regions of the cerebral hemispheres, including the basal ganglia, amygdala, and brain-stem, but without noticeable loss of cells. The question of the minimal lesion for the alcoholic Korsakoff amnesic state, and some aspects of the related anatomy, is discussed in the context of other reports in the literature which are, however, difficult to assess in the absence of details of the specificity, severity and character of the memory disorders.

Aged

A comparison of hippocampal pathology in man and other animals.

Bilateral damage to the medial temporal lobe, including the hippocampus, in man is associated with a severe amnesic syndrome. It is still not clear whether the hippocampus (or its output pathways and related target projection sites) is the critical structure in producing this syndrome, especially as more severe learning deficits in animals are found with lesions in the anterior inferotemporal cortex than with hippocampal lesions per se. But the problem of trying to relate memory deficits in man and animals depends on the characterization of the amnesic syndrome itself. It was originally thought to be a failure of input into long-term memory store or a failure of consolidation. Medial temporal and hippocampal lesions in animals do not produce results that fit such a characterization. On re-examination of the human syndrome, however, for which some of the evidence is reviewed, it appears that the amnesic patients can learn and remember over long intervals if certain testing paradigms are used. The results are more readily matched to some of the results of hippocampal lesion studies in animals. Two main classes of current theories of the amnesic syndrome are discussed. A somewhat different approach is suggested here, based on the dissociation between human amnesic subjects' commentaries and their objective performance, which suggests a dissociation between levels of processing rather than a failure on any particular level.

Alcohol Amnestic Disorder