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Biomedical subjects

M Mishkin

Publications and source records attributed to M Mishkin.

At least 109 records · Page 6Linked to original sources
PubMed1983

Severe tactual memory deficits in monkeys after combined removal of the amygdala and hippocampus.

Monkeys with bilateral removals of both the amygdaloid complex and hippocampal formation were far more severely impaired on a tactual memory task than were monkeys with removal of either structure alone. These data parallel earlier findings on visual memory in monkeys and suggest that: (i) the memory deficit following combined ablations of the amygdala and hippocampus is multimodal; and (ii) the global anterograde amnesia observed in patients with medial temporal-lobe damage is also due to combined damage to these two structures.

Amygdala↗
PubMed1983

Hypnogenic center theory of sleep: no support from metabolic mapping in monkeys.

By comparing rates of glucose utilization in brains of monkeys in non-REM sleep and two types of awake controls, we attempted to reveal cerebral hypnogenic centers that drive organisms to sleep through increases in their neural activity. Instead we found that metabolic activity is reduced in all the putative hypnogenic centers during sleep as compared to wakefulness. The results thus offer no support for the notion of an active center that either maintains or triggers sleep.

Animals↗
PubMed1983

Memory impairments following restricted medial thalamic lesions in monkeys.

Thalamic contributions to memory were assessed in monkeys with lesions placed in the medial portions of either the anterior or posterior thalamus (AMT and PMT, respectively). Both lesions produced a moderate impairment in a test of object recognition memory. Furthermore, all three animals in the PMT group and two out of the three in the AMT group were moderately impaired on a test of object-reward associative memory. Comparison of these results with those of a previous study in which the AMT and PMT regions were removed jointly (Aggleton and Mishkin 1983) suggests that damage in either region can induce a memory loss but that combined damage to both is required to produce a full-blown amnesia.

Alcohol Amnestic Disorder↗
PubMed1983

Visual recognition impairment following medial thalamic lesions in monkeys.

Monkeys with surgical lesions which removed the medial portions of the medial and anterior thalamic nuclei were markedly impaired on a test of object recognition. The same animals were able to learn visual pattern discriminations and a spatial delayed response task at a normal rate. These findings indicate that lesions in the medial thalamus produce a selective impairment in visual recognition memory in monkeys and, consequently, may provide an experimental model for human "diencephalic amnesia".

Animals↗
PubMed1982

The neuroanatomy of amnesia: amygdala-hippocampus versus temporal stem.

Using a task known to be sensitive to human amnesia, we have evaluated two current hypotheses about which brain regions must be damaged to produce the disorder. Monkeys with bilateral transections of the white matter of the temporal stem were unimpaired, but monkeys with conjoint amygdala-hippocampal lesions exhibited a severe memory deficit. The results indicate that the hippocampus, amygdala, or both, but not the temporal stem, are involved in memory in the monkey and suggest that a rapprochement between the findings for the human and the nonhuman primate may be close at hand.

Amnesia↗
PubMed1982

Mapping the primate visual system with [2-14C]deoxyglucose.

The [2-14C]deoxyglucose method was used to identify the cerebral areas related to vision in the rhesus monkey (Macaca mulatta). This was achieved by comparing glucose utilization in a visually stimulated with that in a visually deafferented hemisphere. The cortical areas related to vision included the entire expanse of striate, prestriate, and inferior temporal cortex as far forward as the temporal pole, the posterior part of the inferior parietal lobule, and the prearcuate and inferior prefrontal cortex. Subcortically, in addition to the dorsal lateral geniculate nucleus and superficial layers of the superior colliculus, and structures related to vision included large parts of the pulvinar, caudate, putamen, claustrum, and amygdala. These results, which are consonant with a model of visual function that postulates an occipito-temporo-prefrontal pathway for object vision and an occipito-parieto-prefrontal pathway for spatial vision, reveal the full extent of those pathways and identify their points of contact with limbic, striatal, and diencephalic structures.

Animals↗
PubMed1982

A memory system in the monkey.

A neural model is presented, based largely on evidence from studies in monkeys, postulating that coded representation of stimuli are stored in the higher-order sensory (i.e. association) areas of the cortex whenever stimulus activation of these areas also triggers a cortico-limbo-thalamo-cortical circuit. This circuit, which could act as either an imprinting or rehearsal mechanism, may actually consist of two parallel circuits, one involving the amygdala and the dorsomedial nucleus of the thalamus, and the other the hippocampus and the anterior nuclei. The stimulus representation stored in cortex by action of these circuits is seen as mediating three different memory processes: recognition, which occurs when the stored representation is reactivated via the original sensory pathway; recall, when it is reactivated via any other pathway; and association, when it activates other stored representations (sensory, affective, spatial, motor) via the outputs of the higher-order sensory areas to the relevant structures.

Amygdala↗
PubMed1982

Equivalence of parieto-preoccipital subareas for visuospatial ability in monkeys.

Parieto-preoccipital lesions in monkeys produce a variety of behavioral deficits, many of which can be classified as either visuospatial or tactual. Since the lesions typically invade a number of cytoarchitectonic areas, the diverse behavioral effects could be a consequence of damage of different functional systems. To determine whether visuospatial ability depends critically on particular parieto-preoccipital -- or on a particular combination of them, monkeys with lesions of one, two, or all three of these sectors were tested both on the "landmark' task, a visual distance discrimination, and, for comparison, on a visual pattern discrimination. Impairment was found only on the landmark task, and the severity of the impairment depended on the number of sectors included in the removal, completely independent of their locus. In an attempt to integrate these results with current neurobiological data, we propose that the parieto-preoccipital region consists of two subdivisions that are organized hierarchically for the mediation of spatial perception. The lower-order subdivision, composed largely of the modality-specific preoccipital area, dorsal OA, is postulated to serve visuospatial processes selectively. The higher-order subdivision, composed mainly of the poly-sensory parietal area, PG, is postulated to serve a supramodal spatial ability to which both the visual and tactual modalities contribute.

Animals↗
PubMed1982

Contribution of striate inputs to the visuospatial functions of parieto-preoccipital cortex in monkeys.

In Experiments 1 and 2, monkeys received 3-stage operations intended to serially disconnect parieto-preoccipital from striate cortex. At each stage (unilateral parieto-preoccipital removal, contralateral striate removal and posterior callosal transection) the monkeys were tested for retention of the landmark task, a visuospatial discrimination sensitive to the effects of bilateral parieto-preoccipital damage. To check the effectiveness of the disconnection, the monkeys were also tested after removal of the remaining parieto-preoccipital cortex. The results demonstrated that corticocortical inputs from striate cortex are crucial for the visuospatial functions of parieto-preoccipital cortex, just as they had been shown earlier to be crucial for the pattern discrimination functions of inferior temporal cortex. Relative to inferior temporal cortex, however, parieto-preoccipital cortex was found to be especially dependent on ipsilateral (as compared with contralateral) striate inputs. In Experiment 3, monkeys received bilateral lesions of either lateral on medial striate cortex and were tested on both a pattern discrimination task, to assess residual inferior temporal function, and the landmark task, to assess residual parieto-preoccipital function. The results indicated that the pattern discrimination functions of inferior temporal cortex are especially dependent on inputs from lateral striate cortex, whereas the visuospatial functions of parieto-preoccipital cortex are equally dependent on inputs from lateral and medial striate cortex. The relatively greater contribution to parieto-preoccipital than to inferior temporal cortex made by ipsilateral and medial striate inputs (representing contralateral and peripheral visual fields, respectively) can also be seen in the receptive field properties of parieto-preoccipital and inferior temporal neurons. The differences in the organization of striate inputs to these two cortical association areas presumably reflect differences in the processing required for spatial vs object vision.

Animals↗
PubMed1982

Light exposure reduces and pinealectomy virtually stops urinary excretion of 6-hydroxymelatonin by rhesus monkeys.

The major metabolite of the pineal hormone melatonin, conjugated 6-hydroxymelatonin, was hydrolyzed, separated from the urine of rhesus monkeys, and assayed mass spectrometrically. The daily excretion pattern reflected pineal melatonin synthetic activity, being 5- to 16-fold higher at night than during the day. Progressive lengthening of the daily photoperiod beyond 12 h decreased the daily excretion of 6-hydroxymelatonin proportional to the increase duration of light exposure. Constant light reduced daily excretion by 90%, and pinealectomy reduced daily excretion by 96%. These results demonstrate the absence of significant extrapineal contributions to the urinary melatonin metabolite and confirm the use of 6-hydroxymelatonin excretion rates as a valid index of pineal gland melatonin synthesis.

Animals↗
PubMed1981

Time discrimination with positional responses after selective prefrontal lesions in monkeys.

Monkeys with ablations of the cortex in the principal sulcus who were impaired on a spatial delayed reaction test were unimpaired on a time discrimination test in which length of time since the last trial signalled the spatial position of the correct foodwell. The finding undermines the view that the classical delayed reaction deficit after lateral prefrontal lesions reflects the loss of temporal structuring of the stream of sensory input. The result is consistent instead with the alternative view that the classical deficit reflects a spatial memory disorder. Monkeys with inferior prefrontal ablations were impaired on both spatial tasks, and on object discrimination reversal as well; analysis of their deficits indicated that they were instances of perseverative interference. Finally, monkeys with ablations of the cortex in the arcuate sulcus were not consistently impaired on any of the tasks. There is no evidence from these results that prefrontal cortex plays any role in time perception.

Animals↗
PubMed1981

Opiate receptor gradients in monkey cerebral cortex: correspondence with sensory processing hierarchies.

In order to obtain information on the possible functions of endogenous opiates in the primate cerebral cortex, we assessed the distribution of mu-like opiate receptors (which selectively bind 3H-labeled naloxone) and delta-like opiate receptors (which selectively bind 3H-labeled D-Ala2, D-Leu5-enkephalin) throughout the cerebral cortex of the rhesus monkey. Stereospecific [3H]naloxone binding sites increased in a gradient along hierarchically organized cortical systems that sequentially process modality-specific sensory information of a progressively more complex nature. Specific [3H]enkephalin binding sites, in contrast, were relatively evenly distributed throughout the cerebral cortex. These results, in combination with electrophysiological studies of monkeys and humans, suggest that mu-like opiate receptors may play a role in the affective filtering of sensory stimuli at the cortical level, that is, in emotion-induced selective attention.

Animals↗
PubMed1981

Evidence for the sequential participation of inferior temporal cortex and amygdala in the acquisition of stimulus-reward associations.

On a test of one-trial learning of object-reward associations, monkeys showed marked impairment after lesions of either the anterior part of inferior temporal cortex (area TE) or the amygdala (A). By contrast, little or no loss followed lesions of either the posterior part of inferior temporal cortex (area TEO) or the fusiform-hippocampal gyrus and hippocampus (FHH). The finding of impairment after either the area TE or A lesions fits the view [11] that stimulus-reward learning in vision is mediated by a functional chain connecting the visual system to the limbic system through relays in the inferior temporal cortex and the amygdala. Area TE is considered to be the last purely visual link in this pathway. A previous study [19] showed that damage to area TE, but not to other temporal lobe structures (TEO, A or FHH), severely impairs performance on a one-trial-learning test of object recognition as distinguished from object-reward association. Presumably, the impairment after TE lesions in the present study was due to this same basic recognition disorder. The impairment after amygdalectomy, however, not being attributable to a recognition disorder, appears to reflect instead a disorder in object-reward association learning. Together, these results provide evidence that the formation of object-reward associations in vision involves the sequential participation of a recognition mechanism dependent on the inferior temporal cortex and an associative process dependent on the amygdala.

Amygdala↗
PubMed1981

Effects of damage to the suprachiasmatic area of the anterior hypothalamus on the daily melatonin and cortisol rhythms in the rhesus monkey.

The effects of lesions of the suprachiasmatic nucleus (SCN) on the circadian rhythms in melatonin and cortisol were examined in the rhesus monkey. The concentrations of the two hormones were monitored in cerebrospinal fluid (CSF) withdrawn from two sham-operated animals, two animals with complete bilateral SCN lesions, and two animals with partial SCN damage at 4 and 8 months after surgery. In the sham-operated animals, as in the intact animal, the daily melatonin rhythm was entrained to the daily light-dark cycle, was suppressed in constant light, and persisted in constant darkness. In contrast, neither animal with complete SCN ablation exhibited a daily pattern of CSF melatonin in diurnal lighting at 4 months after surgery nor were their melatonin levels at constant low values. Furthermore, CSF melatonin concentrations were not suppressed in either animal by constant light. Surprisingly, at 8 months after surgery, spectral analysis revealed a 24-hr component to the melatonin patterns for each animal with complete SCN ablation in both diurnal lighting and constant darkness. The two animals with partial SCN damage exhibited a daily melatonin rhythm in diurnal lighting, but constant light did not suppress CSF melatonin concentrations consistently. Daily rhythms persisted in both for a 6 1/2-d period of study in constant darkness. In contrast to the alterations in the melatonin rhythm after SCN damage, there was no apparent effect of either partial or complete SCN ablation on the daily CSF cortisol rhythm. These data indicate that, in the rhesus monkey, the SCN is important for the generation, photic entrainment, and photic suppression of the melatonin rhythm. However, circadian oscillators located outside of the SCN region may control the normal daily cortisol rhythm and perhaps the melatonin rhythm in the absence of the SCN.

Amino Acids↗