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Biomedical subjects

M Mishkin

Publications and source records attributed to M Mishkin.

At least 19 recordsLinked to original sources
PubMed1996

Effects of hemispheric side of injury, age at injury, and presence of seizure disorder on functional ear and hand asymmetries in hemiplegic children.

Dichotic listening, manual functions, and IQ were measured in a large group of hemiplegic children with unilateral hemispheric damage. In the children without a history of seizure disorder, only manual functions were impaired, but in those with such a history (and hence a regime of anticonvulsant medication), all measures were affected. Some children with congenital left hemisphere lesions (with and without siezure disorder) showed a left ear advantage for dichotic digits as well as greater impairment in right hand function than those who showed the usual right ear advantage. The latter result suggests that the hemipheric damage in the subgroup with altered ear asymmetry was greater than in the others and extensive enough to encroach on language areas, shifting language representation to the right.

Adolescent↗
PubMed1995

Protein kinase C in the hippocampus is altered by spatial but not cued discriminations: a component task analysis.

The exact role of the mammalian hippocampus in memory formation remains essentially as an unanswered question for cognitive neuroscience. Experiments with humans and with animals indicate that some types of mnemonic associative processes involve hippocampal function while others do not. Support for the spatial processing hypothesis of hippocampal function has stemmed from the impaired performance of rats with hippocampal lesions in tasks that require spatial discriminations, but not cued discriminations. Previous procedures, however, have confounded the interpretation of spatial versus cued discrimination learning with the number and kinds of irrelevant stimuli present in the discrimination. An empirical set of data describing a role of protein kinase C (PKC) in different mnemonic processes is similarly being developed. Recent work has implicated the activation of this serine-threonine kinase in a variety of learning paradigms, as well as long-term potentiation (LTP), a model system for synaptic plasticity which may subserve some types of learning. The present study employs the principles of component task analysis to examine the role of membrane-associated PKC (mPKC) in hippocampal-dependent memory when all factors other than the type of learning were equivalent. The results indicate that hippocampal mPKC is altered by performance in hippocampally-dependent spatial discriminations, but not hippocampally-independent cued discriminations and provide a general experimental procedure to relate neural changes to specific behavioral changes.

Animals↗
PubMed1995

Long-term effects of selective neonatal temporal lobe lesions on learning and memory in monkeys.

Rhesus monkeys with neonatal damage to either the medial temporal lobe or the inferior temporal cortical area TE, and their normal controls, were reassessed in visual habit formation (24-hour intertrial interval task) and visual recognition (delayed nonmatching to sample; DNMS) at 4-5 years of age and then tested on tactile and spatial DNMS. Results on the two visual tasks were the same as those obtained when the monkeys were under 1 year of age. Specifically, early medial temporal lesions, like late lesions, left habit formation intact but severely impaired recognition memory. Furthermore, the memory deficit extended to the tactile and spatial modalities. By contrast, early damage to TE, unlike late damage to it, yielded only mild deficits on both visual tasks and had no effect on tactile or spatial DNMS. Compensatory mechanisms that promote substantial and permanent recovery thus appear to be available after neonatal TE lesions but not after neonatal medial temporal lesions.

Animals↗
PubMed1995

Responses of cells in the tail of the caudate nucleus during visual discrimination learning.

1. The tail of the caudate nucleus and adjacent ventral putamen (ventrocaudal neostriatum) are major projection sites of the extrastriate visual cortex. Visual information is then relayed, directly or indirectly, to a variety of structures with motor functions. To test for a role of the ventrocaudal neostriatum in stimulus-response association learning, or habit formation, neuronal responses were recorded while monkeys performed a visual discrimination task. Additional data were collected from cells in cortical area TF, which serve as a comparison and control for the caudate data. 2. Two monkeys were trained to perform an asymmetrically reinforced go-no go visual discrimination. The stimuli were complex colored patterns, randomly assigned to be either positive or negative. The monkey was rewarded with juice for releasing a bar when a positive stimulus was presented, whereas a negative stimulus signaled that no reward was available and that the monkey should withhold its response. Neuronal responses were recorded both while the monkey performed the task with previously learned stimuli and while it learned the task with new stimuli. In some cases, responses were recorded during reversal learning. 3. There was no evidence that cells in the ventrocaudal neostriatum were influenced by the reward contingencies of the task. Cells did not fire preferentially to the onset of either positive or negative stimuli; neither did cells fire in response to the reward itself or in association with the motor response of the monkey. Only visual responses were apparent. 4. The visual properties of cells in these structures resembled those of cells in some of the cortical areas projecting to them. Most cells responded selectively to different visual stimuli. The degree of stimulus selectivity was assessed with discriminant analysis and was found to be quantitatively similar to that of inferior temporal cells tested with similar stimuli. Likewise, like inferior temporal cells, many cells in the ventrocaudal neostriatum had large, bilateral receptive fields. Some cells had "doughnut"-shaped receptive fields, with stronger responses in the periphery of both visual fields than at the fovea, similar to the fields of some cells in the superior temporal polysensory area. Although the absence of task-specific responses argues that ventrocaudal neostriatal cells are not themselves the mediators of visual learning in the task employed, their cortical-like visual properties suggest that they might relay visual information important for visuomotor plasticity in other structures. (ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Verbal memory impairment after right temporal lobe surgery: role of contralateral damage as revealed by 1H magnetic resonance spectroscopy and T2 relaxometry.

We assessed performance on selected tests of verbal memory in 48 patients who had undergone either anterior temporal lobectomy or selective amygdalo-hippocampectomy for the relief of pharmacologically intractable epilepsy. We related performance both to the side of surgical excision and to the presence or absence of abnormalities in the contralateral, unoperated, temporal lobe, as revealed by proton magnetic resonance spectroscopy (1H MRS) or T2 relaxometry. There were abnormalities on the unoperated side detected by 1H MRS in 50% of the 34 patients who successfully underwent spectroscopy, and by T2 relaxometry in 33% of the complete series of 48 patients. There was no systematic relationship between seizure outcome and the presence or absence of abnormalities on the unoperated side. Verbal memory deficits were present in patients with left-sided excision, regardless of whether there were abnormalities on the unoperated side. The patients with right-sided excision also had verbal memory deficits, but only in the group with magnetic resonance abnormalities on the contralateral (ie, left) side and only on delayed recall. The study extends previous findings on the role of the temporal lobes in memory and highlights the role of these new magnetic resonance techniques in relating cognitive processes to brain structures.

Adult↗
PubMed1994

Stimulus recognition.

This review covers recent research on the neural process through which a novel stimulus becomes familiar. Lesion and recording studies have provided data sufficient to outline a tentative stimulus-recognition circuit and to suggest how the circuit might operate to form the new and relatively lasting stimulus traces that must underlie delayed stimulus recognition. The research has reached a stage where further progress could well be hastened by interaction between experiment and the formal, neurobiologically constrained models that are beginning to appear.

Animals↗
PubMed1994

Agnosia, alexia and a remarkable form of amnesia in an adolescent boy.

Childhood cases of global anterograde amnesia, visual agnosia or alexia without agraphia, either alone or in any combination, are extremely rare. Here we report the case of a male adolescent, Neil (a pseudonym), who consequent to a pineal tumour began to exhibit all three disorders in the presence of normal verbal intelligence. The most surprising aspect of Neil's case, however, is his ability to retrieve postmorbid memories through the act of writing without being able to provide any oral account of the content of his written reports. His memory retrieval thus has some of the character of 'automatic writing'. This evidence pointing to Neil's possession of a dissociated form of episodic memory presents a new challenge to our understanding of the organization of memory and of the cerebral systems underlying it.

Adolescent↗
PubMed1994

Effects of selective neonatal temporal lobe lesions on visual recognition memory in rhesus monkeys.

Ten-month-old infant monkeys that had received neonatal ablations of either inferior temporal cortex (area TE) or the medial temporal region were compared with age-matched normal infant monkeys in visual delayed nonmatching-to-sample with trial-unique objects. Both types of early damage caused impairment in visual recognition, but the degree of deficit after early area TE lesions differed sharply from that after early medial temporal removals. Thus, whereas early medial temporal damage yielded a marked decline in visual recognition when the delays and lists were gradually increased, early area TE damage yielded normal recognition up to a delay of 60 sec and only mild impairment at longer delays and lists. The data indicate that, unlike adult monkeys, which suffer severe and nearly equivalent losses in visual object recognition after both types of ablation, the infant monkeys' recognition ability is largely spared after early damage to area TE but not after early damage to the medial temporal lobe. Together with recent clinical reports of profound memory loss in children with early dysfunction of the medial temporal region, the present findings demonstrate that medial temporal lobe structures operate early to sustain visual recognition memory, and recovery from early damage is limited at best. Early damage to higher-order visual cortex, however, can be largely compensated, presumably by one or more of the visual cortical areas that were left intact.

Animals↗
PubMed1993

A modality-specific somatosensory area within the insula of the rhesus monkey.

Response properties of neurons in the monkey's granular insula (Ig) were examined with somatic, auditory, visual, and gustatory stimuli. Results indicate that a major portion of Ig is a somatic processing area exclusively, with units that have large and often bilateral receptive fields, consistent with the view that this area serves as a higher-order, modality-specific link in the somatosensory-limbic pathway.

Acoustic Stimulation↗
PubMed1993

Scopolamine impairs recall of one-trial stimulus-reward association in monkeys.

Performance of three rhesus monkeys on a test of one-trial stimulus-reward association, in which recall intervals ranged from 0.5 to 6.5 min, was evaluated during nondrug-control conditions and following administration of the muscarinic-receptor blocker scopolamine. During control sessions, performance averaged 78% correct responses. Following administration of 10.0 and 17.8 micrograms/kg of scopolamine, performance fell significantly, to 69% and 63% correct responses, respectively. This dose-dependent impairment in recall was similar to the impairment we reported previously in recognition. Although the results thus failed to support a suggestion derived from behavioral electrophysiological findings that stimulus-reward association might be more vulnerable to scopolamine than stimulus recognition, they provide additional evidence for a cholinergic contribution to cognitive memory.

Animals↗
PubMed1993

Hippocampectomized monkeys can remember one place but not two.

In an earlier study by Parkinson et al. (J. Neurosci. 8, 4159-4167, 1988), hippocampectomized monkeys were found to be impaired on a task in which they were required to remember the spatial positions of trial-unique objects overlying two of the wells in a three-well test tray. There were two types of trial in the task. One type (object-place) required memory for the conjunction of object quality and object location, whereas the other (place only) required memory only for the location of the objects, i.e. independent of object quality. The hippocampectomized monkeys performed at near chance levels on both types of trials. The present study sought to determine whether the poor performance of the hippocampectomized monkeys on the place-only trials, which closely resembled spatial delayed response (an ability that is unaffected by hippocampectomy when similarly short delays are used), could have been due to interference from the simultaneous training they had received on the object-place trials. To this end, we examined the effect of hippocampal removals on performance of the "place-only" trial type when that was the only training given. The hippocampectomized monkeys in the present study were found to be just as severely impaired as those in the earlier study, thus ruling out the possible explanation outlined above. Since performance on this modified version of spatial delayed response, unlike performance on the classical version with the same delay, is critically dependent on the hippocampus, it appears that monkeys with hippocampectomy can remember one place after a short delay but not two.

Animals↗
PubMed1993

Effects on visual recognition of combined and separate ablations of the entorhinal and perirhinal cortex in rhesus monkeys.

Performance on visual delayed nonmatching-to-sample was assessed in rhesus monkeys with combined and separate ablations of the perirhinal and entorhinal cortex, as well as in unoperated controls. Combined (i.e., rhinal cortex) lesions yielded a striking impairment on this task, one almost as severe as that seen after combined amygdalohippocampal removals that included some of this subjacent cortex (Mishkin, 1978; Murray and Mishkin, 1984). Ablations of the perirhinal cortex alone produced a deficit nearly as severe as that found after rhinal cortex lesions, whereas ablations of the entorhinal cortex alone produced only a mild deficit. Contrary to the conclusion from an earlier study (Murray and Mishkin, 1986), the present results demonstrate not only that damage limited to the rhinal cortex is sufficient to produce a severe loss in visual recognition, but also that such damage leads to a far greater loss than damage to any other single structure in the medial part of the temporal lobe.

Animals↗
PubMed1993

Visually guided reaching with the forelimb contralateral to a "blind" hemisphere: a metabolic mapping study in monkeys.

The 2-14C-deoxyglucose method was used to map local cerebral metabolic activity in monkeys performing a unimanual task requiring visually guided arm reaching and key pressing. The study was carried out with monkeys that either had intact brains or had one hemisphere deprived of visual input by unilateral optic tract section combined in some cases with forebrain commissurotomy. The metabolic mapping revealed activation of sensorimotor cortex only in the hemisphere contralateral to the moving forelimb, irrespective of whether this hemisphere was intact or visually deafferented. These results suggest that visually guided reaching with the forelimb contralateral to the "blind" hemisphere is subserved by that hemisphere's sensorimotor cortex and not by the cortex of the ipsilateral, "seeing" hemisphere. Other areas that were more active metabolically in the "blind" than in the "seeing" hemisphere included the supplementary motor, the secondary somatosensory, and certain posterior parietal cortical areas, intraparietal lateral 5 (lateral 5-ip), 7a, and intraparietal 7 (7-ip). It is suggested that the "blind" hemisphere utilizes at least two distinct pieces of information to guide forelimb movements to visual targets: (1) information about the location of the visual target derived from head and eye movements made to this target and mediated via the inferior parietal cortical areas 7a and 7-ip, and (2) information about the instantaneous upper extremity position derived from forelimb proprioceptive mechanisms and mediated via the somatosensory cortex and thereafter via the superior parietal cortical area, lateral 5-ip.

Animals↗
PubMed1993

Neural substrates of visual stimulus-stimulus association in rhesus monkeys.

Rhesus monkeys learned 10 visual stimulus-stimulus association, or paired associates. They then received bilateral removals of either the amygdaloid complex and underlying cortex, the hippocampal formation and underlying cortex, or both combined, or they were retained as unoperated controls. After surgery or rest, the monkeys were tested for their retention of the preoperatively learned set of paired associates, as well as for their ability to learn new associations of the same type. Both unoperated controls and hippocampectomized monkeys relearned the preoperatively trained set of paired associates almost immediately. By contrast, monkeys with amygdala removals were moderately retarded in relearning, and monkeys with combined amygdala and hippocampal ablations were severely retarded. When confronted with new sets of visual stimuli, monkeys with amygdala removals or hippocampal removals learned new sets of paired associates at the same rate as the controls, whereas monkeys with the combined ablation were again profoundly retarded. Only one monkey with the combined lesion was able to learn new stimulus-stimulus associations to criterion, and then only after extensive training, despite the ability of all three animals in this group to perform delayed matching-to-sample with the same stimuli and the same intraatrial delays as those used in the paired associate task. At the end of the main experiment, two of the unoperated controls received bilateral ablations of the rhinal cortex. These monkeys showed the same level of difficulty in learning new paired associates as the animals in the main experiment that had received the combined amygdala plus hippocampal ablations. The results implicate the medial temporal lobe, and particularly the rhinal cortex, in the formation of stimulus-stimulus associative memories.

Amygdala↗
PubMed1992

Serial and parallel processing of tactual information in somatosensory cortex of rhesus monkeys.

1. Selective ablations of the hand representations in postcentral cortical areas 3a, 3b, 1, and 2 were made in different combinations to determine each area's contribution to the responsivity and modality properties of neurons in the hand representation in SII. 2. Ablations that left intact only the postcentral areas that process predominantly cutaneous inputs (i.e., areas 3b and 1) yielded SII recording sites responsive to cutaneous stimulation and none driven exclusively by high-intensity or "deep" stimulation. Conversely, ablations that left intact only the postcentral areas that process predominantly deep receptor inputs (i.e., areas 3a and 2) yielded mostly SII recording sites that responded exclusively to deep stimulation. 3. Ablations that left intact only area 3a or only area 2 yielded substantial and roughly equal reductions in the number of deep receptive fields in SII. By contrast, ablations that left intact only area 3b or only area 1 yielded unequal reductions in the number of cutaneous receptive fields in SII: a small reduction when area 3b alone was intact but a somewhat larger one when only area 1 was intact. 4. Finally, when the hand representation in area 3b was ablated, leaving areas 3a, 1, and 2 fully intact, there was again a substantial reduction in the encounter rate of cutaneous receptive fields. 5. The partial ablations often led to unresponsive sites in the SII hand representation. In SII representations other than of the hand no such unresponsive sites were found and there were no substantial changes in the ratio of cutaneous to deep receptive fields, indicating that the foregoing results were not due to long-lasting postsurgical depression or effects of anesthesia. 6. The findings indicate that modality-specific information is relayed from postcentral cortical areas to SII along parallel channels, with cutaneous inputs transmitted via areas 3b and 1, and deep inputs via areas 3a and 2. Further, area 3b provides the major source of cutaneous input to SII, directly and perhaps also via area 1. 7. The results are in line with accumulating anatomic and electrophysiologic evidence pointing to an evolutionary shift in the organization of the somatosensory system from the general mammalian plan, in which tactile information is processed in parallel in SI and SII, to a new organization in higher primates in which the processing of tactile information proceeds serially from SI to SII. The presumed functional advantages of this evolutionary shift are unknown.

Animals↗
PubMed1991

Massive cortical reorganization after sensory deafferentation in adult macaques.

After limited sensory deafferentations in adult primates, somatosensory cortical maps reorganize over a distance of 1 to 2 millimeters mediolaterally, that is, in the dimension along which different body parts are represented. This amount of reorganization was considered to be an upper limit imposed by the size of the projection zones of individual thalamocortical axons, which typically also extend a mediolateral distance of 1 to 2 millimeters. However, after extensive long-term deafferentations in adult primates, changes in cortical maps were found to be an order of magnitude greater than those previously described. These results show the need for a reevaluation of both the upper limit of cortical reorganization in adult primates and the mechanisms responsible for it.

Afferent Pathways↗
PubMed1991

Dissociation of object and spatial visual processing pathways in human extrastriate cortex.

The existence and neuroanatomical locations of separate extrastriate visual pathways for object recognition and spatial localization were investigated in healthy young men. Regional cerebral blood flow was measured by positron emission tomography and bolus injections of H2(15)O, while subjects performed face matching, dot-location matching, or sensorimotor control tasks. Both visual matching tasks activated lateral occipital cortex. Face discrimination alone activated a region of occipitotemporal cortex that was anterior and inferior to the occipital area activated by both tasks. The spatial location task alone activated a region of lateral superior parietal cortex. Perisylvian and anterior temporal cortices were not activated by either task. These results demonstrate the existence of three functionally dissociable regions of human visual extrastriate cortex. The ventral and dorsal locations of the regions specialized for object recognition and spatial localization, respectively, suggest some homology between human and nonhuman primate extrastriate cortex, with displacement in human brain, possibly related to the evolution of phylogenetically newer cortical areas.

Adult↗