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L Stefanacci

Publications and source records attributed to L Stefanacci.

12 recordsLinked to original sources

Profound amnesia after damage to the medial temporal lobe: A neuroanatomical and neuropsychological profile of patient E. P.

E. P. became profoundly amnesic in 1992 after viral encephalitis, which damaged his medial temporal lobe bilaterally. Because of the rarity of such patients, we have performed a detailed neuroanatomical analysis of E. P.'s lesion using magnetic resonance imaging, and we have assessed his cognitive abilities with a wide range of neuropsychological tests. Finally, we have compared and contrasted the findings for E. P. with the noted amnesic patient H.M, whose surgical lesion is strikingly similar to E. P.'s lesion.

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Topographic organization of cortical inputs to the lateral nucleus of the macaque monkey amygdala: a retrograde tracing study.

The objective of this study was to identify cortical areas that project to the lateral nucleus of the macaque monkey amygdaloid complex. Discrete injections of the fluorescent retrograde tracers Fast blue and Diamidino yellow were placed into different locations within the lateral nucleus. Retrogradely labeled cells were mapped using a computer-aided digitizing system. In the frontal cortex, low numbers of retrogradely labeled cells were observed in medial and orbitofrontal regions (areas 10, 11, 12, 13, 13a, and 14). In the anterior cingulate cortex, low to moderate numbers of retrogradely labeled cells were located in areas 25, 24, and 32. In the insula, there were moderate to high numbers of retrogradely labeled cells in agranular and dysgranular regions. The parainsula cortex also demonstrated a moderate to high number of retrogradely labeled cells. In the temporal lobe, retrogradely labeled cells were most numerous in the rostral (polar) portion of the perirhinal cortex. Large numbers of labeled cells were also located throughout more caudal portions of the perirhinal regions as well as in the entorhinal cortex, area TE, and the superior temporal gyrus. Fewer retrogradely labeled cells were observed in the cortex along the dorsal bank of the superior temporal sulcus, in the parahippocampal cortex, and in area TEO. Although retrograde tracers can provide only limited evidence for topography, we nonetheless noted that the density of retrogradely labeled cells in a cortical area reliably depended on the location of the tracer injection in the lateral nucleus.

Amygdala↗

Contrasting effects on discrimination learning after hippocampal lesions and conjoint hippocampal-caudate lesions in monkeys.

Eighteen monkeys with lesions of the hippocampal region (the hippocampus proper, the dentate gyrus, and the subiculum) made by an ischemic procedure, radio frequency, or ibotenic acid were tested on a simple, two-choice object discrimination learning task that has been shown to be sensitive to large lesions of the medial temporal lobe. The monkeys were also tested on two other discrimination tasks (pattern discrimination and eight-pair concurrent discrimination) that can be learned normally by monkeys with large medial temporal lobe lesions. All of the lesion groups were impaired at learning the simple object discrimination task. Seven of the monkeys who had sustained damage to the hippocampal region also sustained damage to the tail of the caudate nucleus. These seven monkeys, but not the other 11 monkeys with hippocampal lesions, were impaired on pattern discrimination and concurrent discrimination learning. The results suggest that the hippocampal region is important for learning easy, two-choice discriminations, whereas the caudate nucleus is necessary for the normal learning of more difficult, gradually acquired discrimination tasks. The findings support the distinction between declarative memory, which depends on the hippocampus and related medial temporal lobe structures, and habit learning, which depends on the caudate nucleus.

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Impaired recognition memory in monkeys after damage limited to the hippocampal region.

Monkeys with lesions limited to the hippocampal region (the hippocampus proper, the dentate gyrus, and the subiculum) were impaired on two tasks of recognition memory: delayed nonmatching to sample and the visual paired-comparison task. Recognition memory was impaired in five different groups of monkeys, whether the lesions were made by an ischemic procedure, by radio frequency, or by ibotenic acid. The finding that the hippocampal region is essential for normal recognition memory performance is considered in the context of current ideas about the role of the hippocampus in declarative memory.

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Detection and explanation of sentence ambiguity are unaffected by hippocampal lesions but are impaired by larger temporal lobe lesions.

We address the recent suggestion that the "hippocampal system" is important for understanding ambiguities in language (MacKay et al., J Cogn Neurosci 1998;10:377-394). Seven amnesic patients and 11 controls first decided whether a sentence was ambiguous and then tried to explain the ambiguity. Three amnesic patients with damage limited to the hippocampal formation and one amnesic patient with primarily diencephalic damage performed like the controls in all respects. Thus, the ability to comprehend ambiguity is independent of the hippocampal formation. By contrast, three patients with larger temporal lobe lesions, which extended beyond the medial temporal lobe, were impaired to about the same degree as the noted amnesic patient H.M. (as reported by Lackner, Neuropsychologia 1974;12:199-207; MacKay et al., J Cogn Neurosci 1998;10:377-394). Patient H.M., like our 3 impaired patients, has some damage outside the medial temporal lobe. However, patient H.M. also had additional difficulties on these and other language tests that the patients with larger temporal lobe lesions did not exhibit. Accordingly, it is possible that H.M.'s impairment has a different basis.

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fMRI of monkey visual cortex.

While functional magnetic resonance imaging (fMRI) is now used widely for demonstrating neural activity-related signals associated with perceptual, motor, and cognitive processes in humans, to date this technique has not been developed for use with nonhuman primates. fMRI in monkeys offers a potentially valuable experimental approach for investigating brain function, which will complement and aid existing techniques such as electrophysiology and the behavioral analysis of the effects of brain lesions. There are, however, a number of significant technical challenges involved in using fMRI with monkeys. Here, we describe the procedures by which we have overcome these challenges to carry out successful fMRI experiments in an alert monkey, and we present the first evidence of activity-related fMRI signals from monkey cerebral cortex.

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A reexamination of the concurrent discrimination learning task: the importance of anterior inferotemporal cortex, area TE.

For 30 years, the concurrent discrimination learning task has figured prominently in studies used to determine the effects of medial temporal lobe damage in monkeys. However, the findings from these studies have been contradictory. We explored the contribution to concurrent discrimination performance of inadvertent damage to area TE by reexamining the behavioral data and histological material from monkeys with medial temporal lobe lesions previously tested in our laboratory. The amount of inadvertent damage to area TE was more predictive of impaired performance on the concurrent discrimination learning task than was the amount of damage to any medial temporal lobe structure, including the perirhinal cortex. These findings resolve earlier inconsistent findings regarding the concurrent discrimination learning task by demonstrating that performance on this task depends on area TE and not on perirhinal cortex or other medial temporal lobe structures.

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When amnesic patients perform well on recognition memory tests.

Extended exposure to study material can markedly improve subsequent recognition memory performance in amnesic patients, even the densely amnesic patient H.M. To understand this phenomenon, the severely amnesic patient E.P., 3 other amnesic patients, and controls studied pictorial material and then were given either a yes-no (Experiment 1) or a 2-alternative, forced-choice (Experiment 2) recognition test. The amnesic patients and controls benefited substantially from extended exposure, but patient E.P. consistently performed at chance. Furthermore, confidence ratings corresponded to recognition accuracy. The results do not support the idea that the benefit of extended study time is due to some kind of familiarity process made available through nondeclarative memory. It is likely that amnesic patients benefit from extended study time to the extent that they have residual capacity for declarative memory.

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Organization of connections between the amygdaloid complex and the perirhinal and parahippocampal cortices in macaque monkeys.

Neuroanatomical studies in macaque monkeys have demonstrated that the perirhinal and parahippocampal (PRPH) cortices are strongly interconnected with the hippocampal formation. Recent behavioral evidence indicates that these cortical regions are importantly involved in normal recognition memory function. The PRPH cortices are also interconnected with the amygdaloid complex, although comparatively little is known about the precise topography of these connections. We investigated the topographic organization of reciprocal connections between the amygdala and the PRPH cortices by placing anterograde and retrograde tracers throughout these three regions. We found that there was an organized arrangement of connections between the amygdala and the PRPH cortices and that the deep (lateral, basal, and accessory basal) nuclei of the amygdaloid complex were the source of most connections between the amygdala and the PRPH cortices. The temporal polar regions of the perirhinal cortex had the strongest and most widespread interconnections with the amygdala. Connections from more caudal levels of the perirhinal cortex had a more discrete pattern of termination. Perirhinal inputs to the amygdala terminated primarily in the lateral nucleus, the magnocellular and parvicellular divisions of the basal nucleus, and the magnocellular division of the accessory basal nucleus. Return projections originated predominately in the lateral nucleus, the intermediate and parvicellular divisions of the basal nucleus, and the magnocellular division of the accessory basal nucleus. The interconnections between the amygdala and the parahippocampal cortex were substantially less robust than those with the perirhinal cortex and mainly involved the basal nucleus. Area TF was more strongly interconnected with the amygdala than was area TH. Input from the parahippocampal cortex terminated predominantly in the lateral half of the parvicellular division of the basal nucleus but also to a lesser extent in the magnocellular division of the basal nucleus and the lateral nucleus. Return projections originated predominantly in the magnocellular division of the basal nucleus and were directed almost exclusively to area TF.

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Intrinsic connections of the rat amygdaloid complex: projections originating in the lateral nucleus.

The amygdaloid complex receives sensory information from a variety of sources. A widely held view is that the amygdaloid complex utilizes this information to orchestrate appropriate species-specific behaviors to ongoing experiences. Relatively little is known, however, about the circuitry through which information is processed within the amygdaloid complex. The lateral nucleus is the major recipient of extrinsic sensory information and is the origin of many intra-amygdaloid projections. In this study, we reinvestigated the organization of intra-amygdaloid projections originating from the lateral nucleus using the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L). The lateral nucleus has highly organized intranuclear connections. Dense projections interconnect rostral and caudal levels of the lateral and the medial divisions of the nucleus, and the lateral and medial divisions of the lateral nucleus are also interconnected. The major extranuclear projections of the lateral nucleus are (in descending order of magnitude) to the accessory basal nucleus, the basal nucleus, the periamygdaloid cortex, the dorsal portion of the central division of the medial nucleus, the posterior cortical nucleus, the capsular division of the central nucleus, and the lateral division of the amygdalohippocampal area. The pattern of extranuclear projections varied depending on the rostrocaudal or mediolateral location of the injection site within the lateral nucleus. These findings indicate that intra-amygdaloid projections originating in the lateral nucleus are both more widespread and more topographically organized than was previously appreciated.

Amygdala↗

Projections from the lateral nucleus to the basal nucleus of the amygdala: a light and electron microscopic PHA-L study in the rat.

A recent study, carried out in the monkey brain demonstrated a hitherto undescribed projection from the lateral to the basal nucleus of the amygdaloid complex. In the present study, we used light and electron microscopic techniques to determine whether a similar connection exists in the rat brain and to define what type(s) of synaptic contacts are produced by fibers of this projection. Injections of the lectin tracer Phaseolus vulgaris leucoagglutinin (PHA-L) were placed into several levels of the lateral nucleus and the distribution of fibers in the basal (basolateral) nucleus was evaluated. All lateral nucleus injections resulted in labeled fibers in the basal nucleus, though the density and distribution of labeled fibers depended on the position of the injection site within the lateral nucleus. In general, the heaviest labeling of the basal nucleus was observed after injections at midrostrocaudal levels of the lateral nucleus, especially when the injection was located ventrally. Fibers originating from cells labeled by these injections were observed throughout much of the rostrocaudal extent of the basal nucleus. Rostrally situated injections resulted in substantially lower levels of labeled fibers in the basal nucleus. Injections placed caudally in the lateral nucleus resulted in light to medium levels of labeled fibers in the basal nucleus; the terminal field in these cases did not extend as far rostrally as after the rostral and midlevel injections. Electron microscopic analysis of PHA-L labeled fibers revealed that they contributed synapses to the basal nucleus. The majority of PHA-L labeled terminals formed asymmetric contacts on dendritic spines or shafts; a smaller number of PHA-L labeled terminals formed symmetrical synapses.

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