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Biomedical subjects

M Mishkin

Publications and source records attributed to M Mishkin.

At least 73 records · Page 4Linked to original sources

Picture recognition vs. picture discrimination learning in monkeys with medial temporal removals.

Three monkeys with complete ablations of temporal-lobe limbic structures and three unoperated controls were compared in an automated testing apparatus for their ability to remember pictures presented between 1 and 180 seconds previously, as well as to learn picture discriminations in which successive trials with a given pair were separated by either 20 seconds or 24 hours. The operated animals were not impaired in picture discrimination learning under either condition and they were not impaired in picture recognition memory up to about 10 seconds. At 10 seconds and beyond, however, the operated animals showed rapid deterioration of picture memory. The results demonstrate that the limbic system's selective contribution to learning and retention uncovered initially with objects applies equally to pictures, this contribution being essential for recognition memory but not for discrimination habits. The results demonstrate further that, as in humans, temporal-lobe limbic structures are essential for recognition only when the retention test exceeds the immediate memory span of a few seconds.

Animals↗

Age and sex differences in the effects of selective temporal lobe lesion on the formation of visual discrimination habits in rhesus monkeys (Macaca mulatta).

Three-month-old infant monkeys with neonatal ablations of either cortical area TE or the amygdala and hippocampus and age-matched normal infants were trained in a concurrent object discrimination task with 24-hr intertrial intervals. Neonatal area TE lesions yielded a transient deficit in visual habit formation, present in the female monkeys only, whereas the same lesions in adult monkeys yielded a severe and long-lasting deficit in both males and females. Although pointing to a greater neural compensation for the early loss as compared with the later loss of cortical area TE, the results also corroborate a recent suggestion (Bachevalier, Hagger, & Bercu, 1989) that, at 3 months of age, area TE is more fully functional in females than in males. Neither early nor late amygdalohippocampal lesions impaired the ability to form visual discrimination habits, strengthening the proposal that the habit system uses a corticononlimbic circuit.

Aging↗

ACR survey results: diagnostic imaging scientists and engineers.

The American College of Radiology's Committee on Physics Resources of the Commission on Human Resources conducted a survey of diagnostic imaging scientists and engineers to assess who is providing radiologic physics and related services in diagnostic imaging departments. The survey forms were distributed through the members of the American Healthcare Radiology Administrators. Survey results showed a predominance of M.S. and Ph.D. degrees in physics and medical/radiological physics. Nearly all respondents had their time split between numerous categories of work, such as clinical and research, and between different modalities such as diagnostic x-ray, nuclear medicine and radiation oncology. To enhance physics services in important areas such as CT, which currently receive little time, support is needed for work prioritization, for training, and for positions for physics and physics-support personnel.

Certification↗

Discrimination learning alters the distribution of protein kinase C in the hippocampus of rats.

Protein kinase C (PKC), an enzyme that plays an essential role in eukaryotic cell regulation (Nishizuka, 1988; Huang et al., 1989), is critical to memory storage processes both in the marine snail Hermissenda crassicornis and in the rabbit (Alkon et al., 1988; Bank et al., 1988; Olds et al., 1989). Specifically, activation of PKC mimics neurobiological correlates of classical conditioning in both Hermissenda and the rabbit, and the distribution of the enzyme within the rabbit hippocampus changes after Pavlovian conditioning. Here, we report that the amount of PKC, as assayed by specific binding of 3H-phorbol-12,13-dibutyrate (3H-PDBU), decreased significantly within the hippocampal CA3 cell region in rats trained to solve a water maze task either by cognitive mapping or by visual discrimination strategies, but not in control rats. Furthermore, hippocampal lesions interfered with acquisition of both of these tasks. We interpret these findings to support the conclusion that distributional changes of PKC within the mammalian hippocampus play a crucial role in memory storage processes.

Animals↗

Mnemonic and neuropathological effects of occluding the posterior cerebral artery in Macaca mulatta.

To investigate experimentally the mnemonic and neuropathological effects of blockage of the posterior cerebral arteries (PCA), a cerebrovascular accident that can lead to global anterograde amnesia in humans, we permanently occluded these arteries bilaterally in six monkeys and then evaluated their performance on a visual recognition task, after which we assessed the extent of their ischemic infarcts. The latter showed substantial individual variation, ranging from almost no damage in one case to massive unilateral injury of both the ventromedial o occipitotemporal cortex and hippocampal formation in another. In the four remaining cases, however, the infarcts fell within a narrow range, being confined almost entirely to the hippocampal formation and parahippocampal gyrus, and then only to restricted portions of these structures, unilaterally in one case, and bilaterally in the three others. Performance on the recognition task was related to the presence and bilaterality of the hippocampal injury. Thus, the case without any hippocampal damage performed at a rate equal to that of normal controls; the case with unilateral hippocampal damage was mildly impaired; and the three cases with bilateral infarctions, involving between 20 and 55% of the hippocampal formation, showed substantial impairment, with scores averaging 20% below those of normal controls. The only subfields of the hippocampus damaged in common in these cases were CA1 and CA2. Paradoxically, the memory loss found in these three animals with only partial bilateral hippocampal damage was significantly greater than that found in animals with total bilateral ablation of the hippocampal formation, whose scores averaged only 10% below those of normal controls. Possible explanations for this extremely puzzling outcome are proposed.

Amnesia↗

Improved recognition memory in monkeys following naloxone administration.

The effects of naloxone on visual recognition were evaluated in five macaques trained in delayed nonmatching-to-sample with trial-unique objects. In four of the five monkeys, naloxone yielded an inverted U-shaped dose-effect curve. For each of these four animals, as well as for all five animals as a group, at least one dose within a narrow range (0.32-3.2 mg/kg) produced a significant increase in the number of objects correctly recognized. Lower doses had little effect, while the highest dose (10.0 mg/kg) tended to disrupt performance.

Animals↗

Dissociation of the effects of inferior temporal and limbic lesions on object discrimination learning with 24-h intertrial intervals.

Monkeys with bilateral ablations of the inferior temporal cortical area TE were trained on a visual discrimination task thought to measure non-cognitive habit formation. The task consisted of 20 object discriminations presented concurrently, but at the rate of only one trial on each per day; successive trials on a given discrimination were thus separated by 24-h intertrial intervals. Performance on this task by the animals with TE lesions was compared to that of both normal control monkeys and monkeys that had sustained bilateral removals of the amygdala and hippocampus. In contrast to the latter animals, which learned the 24-h intertrial interval task about as quickly as the normal controls, monkeys with area TE removals were markedly impaired. Taken together with earlier findings demonstrating that ablation of area TE impairs visual recognition memory, the present results suggest that area TE contributes not only, like limbic structures, to a cognitive memory system, but also, unlike limbic structures, to a non-cognitive habit system. Evidence is reviewed suggesting that this latter system may involve a corticostriatal circuit.

Animals↗

Lesion-induced plasticity in the second somatosensory cortex of adult macaques.

We have reported that elimination of the representation of any body part in the primary (i.e., postcentral) somatosensory cortex of the adult macaque selectively eliminates the representation of that same body part in the second somatosensory area SII. We now report that, although removal of the entire postcentral hand representation does indeed leave the SII hand representation unresponsive to somatic stimulation initially, 6-8 weeks later this cortex is no longer silent. Instead, most or all of the region that had been vacated by the hand representation is now found to be occupied by an expanded foot representation. This massive somatotopic reorganization, involving more than half the areal extent of SII, exceeds that previously observed in the postcentral cortex after peripheral nerve damage and may reflect a greater capacity for reorganizational changes in higher order than in primary sensory cortical areas.

Animals↗

A selective mnemonic role for the hippocampus in monkeys: memory for the location of objects.

Monkeys were trained preoperatively on a one-trial learning task in which they were required to associate in memory a novel object and the place in which it had just appeared. After learning the task to a level of 80% correct responses, they received bilateral ablations of either the hippocampal formation or the amygdaloid complex. The monkeys with amygdalectomy showed a small drop in performance initially but then regained their preoperative level. By contrast, the monkeys with hippocampectomy dropped to near-chance levels of performance and remained there throughout postoperative testing. Both groups performed at better than 90% correct responses on a test of recognition memory. These results, taken together with earlier work, suggest that although the hippocampus and amygdala appear to participate equally in object recognition, only the hippocampus is critical for the rapid formation of object-place associations.

Animals↗

Gradients of protein kinase C substrate phosphorylation in primate visual system peak in visual memory storage areas.

Two protein kinase C (PKC) substrates of 50 and 81 kDa display topographical gradients in 32P-incorporation along the occipitotemporal visual processing pathway in rhesus monkey cerebral cortex. The 50 kDa protein appears to be homologous to protein F1 from rat (47 kDa) on the basis of isoelectric point, two-dimensional phosphopeptide maps, and kinase specificity, while the 81 kDa protein is probably the same as a previously described PKC substrate. The phosphorylation of protein F1 and 81 kDa was significantly higher in temporal regions of the occipitotemporal pathway, which have been implicated in the storage of visual representations, than in occipital regions, which appear to be less important for visual memory functions. These results suggest that the PKC phosphorylation system, which has been related previously to changes in neural plasticity, plays a progressively greater role in later stages of visual processing, and that this role may involve the storage of visual information in inferotemporal cortical areas.

Animals↗

Physiological evidence for serial processing in somatosensory cortex.

Removal of the representation of a specific body part in the postcentral cortex of the macaque resulted in the somatic deactivation of the corresponding body part in the second somatosensory area. In contrast, removal of the entire second somatosensory area had no grossly detectable effect on the somatic responsivity of neurons in the postcentral cortex. This direct electrophysiological evidence for serial cortical processing in somesthesia is similar to that found earlier for vision and, taken together with recent anatomical evidence, suggests that there is a common cortical plan for the processing of sensory information in the various sensory modalities.

Animals↗

Effects of scopolamine and physostigmine on recognition memory in monkeys with ibotenic-acid lesions of the nucleus basalis of Meynert.

Monkeys with bilateral ibotenic-acid lesions of the nucleus basalis of Meynert, an area rich in cholinergic neurons that innervate the cerebral cortex, were compared with unoperated control monkeys on a recognition memory task. Although animals with large lesions had substantial reductions of cortical choline acetyltransferase activity, none showed impairment in the task. Lesion effects were observed, however, when performance was assessed following administration of a muscarinic receptor blocker (scopolamine) or a cholinesterase inhibitor (physostigmine). Although scopolamine produced dose-related impairments in both groups, this effect was greater in the experimental animals. Conversely, whereas physostigmine produced modest improvement in performance in the control group, no such improvement was observed in the experimental animals. The altered sensitivity to the mnemonic effects of cholinergic agents in the experimental group suggests that the cholinergic neurons of the nucleus basalis of Meynert contribute to recognition memory.

Acetylcholinesterase↗

A comparison between the connections of the amygdala and hippocampus with the basal forebrain in the macaque.

Autoradiographic experiments indicated that the amygdala projects to division Ch3 and Ch4 of the basal forebrain (nomenclature from Mesulam et al. 1983) and the olfactory tubercle. The heaviest of these amygdaloid outputs arose from the lateral basal, accessory basal, central, and medial amygdaloid nuclei, each with a slightly different pattern of distribution from that of the other. Injections of the retrograde tracer horseradish peroxidase (HRP) into the amygdala revealed dense reciprocal projections arising from region Ch4, especially from subdivisions Ch4al, Ch4iv, and Ch4p. The other basal forebrain regions, by contrast, provided very little input to the amygdala. Hippocampal efferents terminated densely in the medial (Ch1), lateral and dorsal septum, and in region Ch2. Hippocampal efferents terminated less densely in restricted portions of the olfactory tubercle and in Ch4. Experiments in which the fornix was transected showed that all of these hippocampal projections to the basal forebrain ran through the fornix. The hippocampal output to the septum, which was the heaviest projection of those examined, appears to have a crude topographic arrangement. Little overlap was observed between the terminal zones of the amygdaloid and hippocampal projections to the basal forebrain, indicating yet again the independence of the amygdaloid and hippocampal systems that has been demonstrated in other regions of the forebrain, such as the thalamus and cerebral cortex.

Amygdala↗

The role of striate cortex in the guidance of eye movements in the monkey.

We studied the effect of unilateral striate cortical ablations on smooth pursuit and saccadic eye movements in the monkey. The monkeys made quite accurate saccades to stationary stimuli in the field contralateral to the lesion, and they readily pursued foveal targets moving in all directions. However, when visual stimuli were stepped into the field contralateral to the lesion and then began to move, thus insuring that the moving stimulus was confined to the impaired visual hemifield, several oculomotor abnormalities emerged. Saccades to moving stimuli presented in the impaired field consistently undershot targets that moved away from the central fixation point after the step, and overshot targets that moved back towards the central fixation point. There was little or no smooth pursuit eye velocity generated in any direction to moving stimuli in the impaired field, and the monkeys could not generate smooth pursuit to stimuli maintained a few degrees from the fovea in the impaired field, although they were able to pursue such stimuli held in the normal field. Ablation of striate cortex also affected the latencies of saccades. When step-ramp stimuli were presented in the normal field, the monkeys delayed the initiation of saccades to targets moving towards the central fixation point, and hastened the initiation of saccades to targets moving away from the central fixation point. By contrast, changes in the direction of target movement did not affect the latencies of saccades into the impaired field. The deficits seemed permanent, lasting as long as the monkeys were tested--over 2 years in one case--but they were not total. Each monkey could use stimuli moving into the affected field to develop some eye velocity, although this residual ability had a much longer latency and lower gain than that provided by the intact visual system. These results show that striate cortex is intimately involved in the estimation of stimulus velocity critical to the genesis of smooth pursuit and saccadic eye movements.

Animals↗

Cortical connections of the somatosensory fields of the lateral sulcus of macaques: evidence for a corticolimbic pathway for touch.

The ipsilateral corticocortical connections of the somatosensory fields of the lateral sulcus of macaques were examined with both anterograde and retrograde axonal transport methods. In most cases, the field of interest was identified prior to the injection of the tracer substance by recording neuronal responses to somatic stimulation. The results show that the second somatosensory area (S2) is reciprocally connected with the retroinsular area (Ri), area 7b, and the granular (Ig) and dysgranular (Id) insular fields. Ri is also reciprocally connected with Ig. Previously reported connections were confirmed between S2 and areas 3a, 3b, 1, and 2 and between area 5 and both area 7 and Ri. Moreover, the portions of Ig and Id that receive somatic inputs were shown to project to the amygdaloid complex. Id projects, in addition, to the perirhinal cortex, which supplies input to the hippocampal formation. The corticocortical projections were found to have two distinct laminar patterns of termination. One is characterized by heavy terminations in layers IV and IIIb and the other by heavy terminations in layer I, but no terminations in layers IV and IIIb. These two patterns were typically found to be reciprocally related. The results suggest that somatosensory information is processed by a series of cortical fields, including areas 3a, 3b, 1, 2, 5, 7b, S2, Ig, and Id. These fields have access to the amygdaloid complex and the hippocampal formation. Thus, a ventrally directed tactile processing pathway can be followed from S1 to the temporal lobe limbic structures via relays in S2 and the insula; this corticolimbic pathway may subserve tactile learning and memory.

Animals↗

The origin, course, and termination of the hippocampothalamic projections in the macaque.

The projections from the hippocampal formation to the thalamus were investigated with both anterograde and retrograde tracers. Horseradish peroxidase was injected into medial and midline thalamic sites in six cases, and tritiated amino acids were injected into the hippocampal formation in nine others, five of which had prior transections of the fornix. Only the subicular and entorhinal cortices were found to project to the thalamus. From the subicular cortex, dense bilateral projections were traced through the fornix to the anterior nuclei, while lighter fornical projections terminated in other rostral midline sites, including the nuclei reuniens, centralis latocellularis, and paraventricularis. These projections arose predominantly from the polymorphic cells which are located in the deepest cellular layers of the subiculum and prosubiculum. In addition, the subicular cortex was found to project to the nucleus lateralis dorsalis. The latter projection, which showed evidence of a crude topographic organization, ran either through the fornix or, unlike the other subicular efferents, through the sublenticular limb of the internal capsule to form part of the temporopulvinar bundle of Arnold. The nonfornical projection to the nucleus lateralis dorsalis passed through the medial pulvinar, where there was some additional termination. Few, if any, projections from the entorhinal cortex to the thalamus travelled in the fornix. Rather, the entorhinal efferents were carried in the inferior thalamic peduncle to the magnocellular portion of the nucleus medialis dorsalis, and in the internal capsule and bundle of Arnold to the medial pulvinar and the nucleus lateralis dorsalis.

Afferent Pathways↗