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S Zola-Morgan

Publications and source records attributed to S Zola-Morgan.

16 recordsLinked to original sources
PubMed1992

Impairment of long-term memory and sparing of short-term memory in monkeys with medial temporal lobe lesions: a response to Ringo.

During the last decade, an animal model of human amnesia was developed in the monkey. Studies using this model have identified structures in the medial temporal lobe that are essential for forming long-term memory (i.e. the hippocampus and the entorhinal, perirhinal and parahippocampal cortices). Recently, an important aspect of these studies was questioned by Ringo (Behav. Brain Res., 42 (1991) 123-134). He suggested that the data from the delayed non-matching-to-sample task, which has been extensively used in these studies, have been analyzed in a potentially misleading way. He reanalyzed the data from several laboratories by transforming percent correct data to a discriminability (d') measure based on signal detection theory. In monkeys with lesions, performance appeared to be equivalently impaired at short and long retention delays. He concluded that the data do not support the idea that medial temporal lobe damage produces an impairment in long-term memory, but not short-term memory. However, most of the studies he analyzed were not designed to address the distinction between short-term and long-term memory. We show here that, in studies designed to compare short-term and long-term memory directly, medial temporal lobe lesions impair long-term memory while leaving short-term memory intact. This result is obtained whether the data are analyzed using a percent correct measure, the d' measure, or an arcsine transform.

Animals↗
PubMed1992

Enduring memory impairment in monkeys after ischemic damage to the hippocampus.

Patient RB became amnesic following an episode of global ischemia that resulted in a bilateral lesion of the CA1 field of the hippocampus. This finding suggested that damage restricted to the hippocampus is sufficient to produce clinically significant memory impairment. To evaluate further the effect of ischemic brain damage on memory, we have developed an animal model of cerebral ischemia in the monkey. Monkeys were subjected to 15 min of reversible ischemia, using a noninvasive technique involving carotid occlusion and pharmacologically induced hypotension. These monkeys sustained significant loss of pyramidal cells in the CA1 and CA2 fields of the hippocampus, as well as loss of somatostatin-immunoreactive cells in the hilar region of the dentate gyrus. Cell loss occurred bilaterally throughout the rostrocaudal extent of the hippocampus but was greater in the caudal portion. Except for patchy loss of cerebellar Purkinje cells, significant damage was not detected in areas outside the hippocampus, including adjacent cortical regions, that is, entorhinal, perirhinal, and parahippocampal cortex, and other regions that have been implicated in memory function. On behavioral tests, the ischemic monkeys exhibited significant and enduring memory impairment. On the delayed nonmatching to sample task, the ischemic monkeys were as impaired as monkeys with lesions of the hippocampal formation and adjacent parahippocampal cortex (the H+ lesion). On two other memory tasks, the ischemic monkeys were less impaired than monkeys with the H+ lesion. In neuropathological evaluations, it has always been difficult to rule out the possibility that significant areas of neuronal dysfunction have gone undetected. The finding that ischemic lesions produced overall less memory impairment than H+ lesions indicates that the ischemic monkeys (and by extension, patient RB) are unlikely to have widespread neuronal dysfunction affecting memory that was undetected by histological examination. These results provide additional evidence that the hippocampus is a focal site of pathological change in cerebral ischemia, and that damage limited to the hippocampus is sufficient to impair memory.

Amnesia↗
PubMed1991

The medial temporal lobe memory system.

Studies of human amnesia and studies of an animal model of human amnesia in the monkey have identified the anatomical components of the brain system for memory in the medial temporal lobe and have illuminated its function. This neural system consists of the hippocampus and adjacent, anatomically related cortex, including entorhinal, perirhinal, and parahippocampal cortices. These structures, presumably by virtue of their widespread and reciprocal connections with neocortex, are essential for establishing long-term memory for facts and events (declarative memory). The medial temporal lobe memory system is needed to bind together the distributed storage sites in neocortex that represent a whole memory. However, the role of this system is only temporary. As time passes after learning, memory stored in neocortex gradually becomes independent of medial temporal lobe structures.

Amnesia↗
PubMed1991

Independence of memory functions and emotional behavior: separate contributions of the hippocampal formation and the amygdala.

Structures and connections in the medial temporal lobe of humans and nonhuman primates have long been recognized as important for normal memory and emotional behavior. The present study investigated memory and emotional behavior in normal monkeys and six groups of monkeys with lesions of the medial temporal lobe. Two groups had damage to the hippocampal formation (or adjacent perirhinal and parahippocampal cortex) but not the amygdaloid complex; two groups had either partial or complete damage to the amygdaloid complex but not the hippocampal formation; and two groups had damage to both the hippocampal formation and the amygdaloid complex. Memory was evaluated with three tasks sensitive to human amnesia: (1) delayed nonmatching to sample; (2) retention of object discriminations; and (3) concurrent discrimination learning. Emotional behavior was assessed by measuring the responsiveness of monkeys to 12 different stimulus situations. Damage to the hippocampal formation or anatomically related cortex impaired memory but did not affect emotional behavior. Partial or complete damage to the amygdaloid complex affected emotional behavior but not memory. These findings show that memory impairment and abnormal emotional behavior are anatomically dissociable and independent effects of damage to the medial temporal lobe.

Amygdala↗
PubMed1991

Stereotaxic lesions of the hippocampus in monkeys: determination of surgical coordinates and analysis of lesions using magnetic resonance imaging.

A technique is described for producing accurate stereotaxic lesions of the hippocampus in monkeys. This technique overcomes the problem that the size and shape of the brain can vary considerably from monkey to monkey. Magnetic resonance imaging (MRI) is used to create an individual brain atlas for each monkey. The atlas is then used to derive coordinates for making stereotaxic radio frequency lesions of the hippocampus. There are two key features of this procedure. First, a specially-designed, acrylic, stereotaxic headholder was constructed that could be used safely with the MR magnet. Second, small glass beads, anchored to the skull of the monkey, served as common landmarks from which lesion coordinates were determined in the MR images and then again in neurosurgery. MRI techniques are also described for determining the extent of tissue damage postoperatively. This technique could also prove useful in other areas of neuroscience research that depend on accurate stereotaxic placement of electrodes (e.g., electrophysiological studies and neuroanatomic tracing studies).

Animals↗
PubMed1991

Inhibition of glucocorticoid secretion by the hippocampal formation in the primate.

Inhibition of the adrenocortical axis by glucocorticoids (GCs) occurs at both hypothalamic and suprahypothalamic sites. In the rat, the hippocampus has been shown to be an essential suprahypothalamic site. The present study shows that the hippocampal system serves a similar role in the nonhuman primate. Bilateral lesions that included the hippocampal formation and the parahippocampal cortex; the hippocampal formation, parahippocampal cortex, and the amygdala; or the fornix all produced GC hypersecretion in cynomolgus monkeys. The hypersecretion occurred throughout the day. Moreover, these lesions were also associated with dexamethasone resistance (i.e., GC hypersecretion following administration of the synthetic GC dexamethasone). The hypersecretion could not be attributed to acute surgical trauma, because neither circumscribed lesions of the amygdala nor conjoint lesions of the perirhinal and parahippocampal cortex produced adrenocortical abnormalities. Finally, in agreement with data derived from the rat, the GC hypersecretion following hippocampal lesions was transient. Secretory activity returned to normal levels by 6-15 months in all operated groups. Thus, the primate hippocampal system appears to share some neuroendocrine functions with the rodent.

Animals↗
PubMed1989

Description of brain injury in the amnesic patient N.A. based on magnetic resonance imaging.

N.A. has been amnesic since 1960 when at the age of 22 years he sustained a penetrating brain injury with a miniature fencing foil. The amnesia primarily affects verbal material and occurs in the absence of other detectable cognitive deficits. Previous CT scans demonstrated a lucency in the region of the left mediodorsal thalamic nucleus, but no additional damage was revealed. Beginning in 1986 when he was 48 years old, N.A. was evaluated with a series of magnetic resonance imaging (MR) studies. Three major areas of damage were identified. In the left thalamus there is a prominent 3- to 4-mm-wide linear lesion that approximates the position and orientation of the internal medullary lamina. The defect extends for approximately 20 mm anteroposteriorly and likely involves the rostral group of intralaminar nuclei (central medial, paracentral, central lateral, rhomboid, and reuniens nuclei), the caudal group of intralaminar nuclei (centrum medianum and parafascicular nuclei), the ventral aspect of the mediodorsal nucleus, and the ventral lateral and ventral anterior nuclei. It also likely interrupts the trajectories of the mammillothalamic tract and postcommissural fornix. The posterior hypothalamus is markedly disrupted and the mammillary nuclei appear to be missing bilaterally. Finally, the right anterior temporal lobe is damaged for a distance of about 3.5 cm from the pole to midway through the amygdaloid complex. This damage probably occurred during exploratory neurosurgery done at the time of N.A.'s injury. The hippocampal formation appears intact on both sides. A comparison of these findings with those from other patients with diencephalic amnesia suggests that amnesia can result when several diencephalic structures are damaged conjointly, including the internal medullary lamina, the intralaminar nuclei, the mediodorsal nucleus, and the mammillothalamic tract. Whether amnesia as severe as N.A.'s would result from selective damage to any one of these structures remains to be determined.

Adult↗
PubMed1989

Successful performance by monkeys with lesions of the hippocampal formation on AB and object retrieval, two tasks that mark developmental changes in human infants.

In this study, (a) what determines success or failure on the AB and object retrieval tasks and (b) the relation between brain maturation and cognitive development as indexed by these tasks were examined. Specifically, does improved performance on these tasks with age reflect maturation of memory functions dependent on the medial temporal lobe? In AB, the S watches a reward being hidden in 1 of 2 wells; after a brief delay S reaches for that reward. The AB error consists of the S continuing to reach to the first location (A) when side of hiding is shifted to the second location (B). In object retrieval, a reward is placed in a transparent box open on 1 side. Although the reward is visible through all sides of the box, it can only be retrieved through the 1 open side. Intact cynomolgus monkeys and those with bilateral lesions of the hippocampal formation (H+) were tested. Although H+ monkeys exhibited impaired memory by performing poorly on the delayed nonmatching to sample taks, they performed well on AB at delays of 2-15 s. Performance declined as delays increased to 30 s, but H+ monkeys never showed the AB error pattern. On object retrieval, H+ monkeys succeeded quickly and efficiently, even when required to detour to the box opening. This reseach demonstrates that memory impairment alone cannot account for deficits on AB or on object retrieval and strengthens the conclusion (Diamond, 1988a, 1988b, in press) that improved performance on AB and object retrieval during infancy reflects maturation of dorsolateral prefrontal cortex.

Aging↗
PubMed1989

Lesions of the hippocampal formation but not lesions of the fornix or the mammillary nuclei produce long-lasting memory impairment in monkeys.

A group of tasks sensitive to human amnesia were used to characterize the severity and duration of memory impairment in monkeys following bilateral damage to the hippocampal formation, fornix, or mammillary nuclei. Monkeys with hippocampal formation lesions (which included the hippocampus proper, dentate gyrus, subiculum, posterior entorhinal cortex, and much of the parahippocampal gyrus) exhibited a substantial and lasting memory impairment. Monkeys with fornix transection or bilateral damage to the mammillary nuclei were impaired on the first task administered after surgery (delayed nonmatching to sample). However, they performed all the other tasks normally and were unimpaired when the delayed nonmatching to sample task was re-administered 18 months after surgery. The findings are consistent with reports that damage limited to the human hippocampus can produce a clinically significant and permanent amnesia. Because fornix transection or mammillary lesions produced only transient memory impairment, it seems unlikely that similar damage in humans can cause a severe or permanent amnesia.

Animals↗
PubMed1989

Lesions of perirhinal and parahippocampal cortex that spare the amygdala and hippocampal formation produce severe memory impairment.

In monkeys, bilateral damage to the medial temporal region produces severe memory impairment. This lesion, which includes the hippocampal formation, amygdala, and adjacent cortex, including the parahippocampal gyrus (the H+A+ lesion), appears to constitute an animal model of human medial temporal lobe amnesia. Reexamination of histological material from previously studied monkeys with H+A+ lesions indicated that the perirhinal cortex had also sustained significant damage. Furthermore, recent neuroanatomical studies show that the perirhinal cortex and the closely associated parahippocampal cortex provide the major source of cortical input to the hippocampal formation. Based on these 2 findings, we evaluated the severity of memory impairment in a group of monkeys that received bilateral lesions limited to the perirhinal cortex and parahippocampal gyrus (the PRPH lesion). The performance of the PRPH group was compared with that of monkeys with H+A+ lesions, who had been studied previously, and with a group of normal monkeys. Monkeys with PRPH lesions were severely impaired on 3 amnesia-sensitive tasks: delayed nonmatching to sample, object retention, and 8-pair concurrent discrimination. On pattern discrimination, a task analogous to ones that amnesic patients perform well, monkeys in the PRPH group performed normally. Overall, monkeys with PRPH lesions were as impaired or more impaired than the comparison group of monkeys with H+A+ lesions. These and other recent findings (Zola-Morgan et al., 1989b) suggest that the severe memory impairment in monkeys and humans associated with bilateral medial temporal lesions results from damage to the hippocampal formation and adjacent, anatomically related cortex, not from conjoint hippocampus-amygdala damage.

Amygdala↗
PubMed1989

Lesions of the amygdala that spare adjacent cortical regions do not impair memory or exacerbate the impairment following lesions of the hippocampal formation.

Monkeys with stereotaxic lesions of the amygdaloid complex that spared the surrounding cortex (i.e., the periamygdaloid, entorhinal, and perirhinal cortices) performed normally on the delayed nonmatching to sample task, as well as on 3 other memory tasks (object retention, concurrent discrimination, and delayed response) administered during the 1 1/2 years after surgery. These animals also performed normally on pattern discrimination and motor-skill learning, 2 tasks analogous to ones amnesic patients perform well. A second group of monkeys with conjoint lesions that included both the amygdaloid complex, as just described, and the hippocampal formation were impaired on the same 4 memory tasks. However, the severity of impairment in this group was no greater than in monkeys with lesions of the hippocampal formation alone. Thus, circumscribed bilateral lesions of the amygdala did not impair performance on 4 different memory tasks, nor did they exacerbate the memory impairment that followed hippocampal formation lesions alone. These findings suggest that one must look to structures other than the amygdala to account for the severe memory impairment that follows large lesions of the medial temporal region. One possibility is that damage to the cortical regions that surround the amygdala contributes to memory impairment.

Amygdala↗
PubMed1988

Human amnesia and animal models of amnesia: performance of amnesic patients on tests designed for the monkey.

The performance of amnesic patients was assessed on five tasks, which have figured prominently in the development of animal models of human amnesia in the monkey. The amnesic patients were impaired on four of these tasks (delayed nonmatching to sample, object-reward association, 8-pair concurrent discrimination learning, and an object discrimination task), in correspondence with previous findings for monkeys with bilateral medial temporal or diencephalic lesions. Moreover, performance of the amnesic patients correlated with the ability to verbalize the principle underlying the tasks and with the ability to describe and recognize the stimulus materials. These tasks therefore seem to be sensitive to the memory functions that are affected in human amnesia, and they can provide valid measures of memory impairment in studies with monkeys. For the fifth task (24-hour concurrent discrimination learning), the findings for the amnesic patients did not correspond to previous findings for operated monkeys. Whereas monkeys with medial temporal lesions reportedly learn this task at a normal rate, the amnesic patients were markedly impaired. Monkeys may learn this task differently than humans.

Alcohol Amnestic Disorder↗
PubMed1988

P3-like brain waves in normal monkeys and in monkeys with medial temporal lesions.

The human brain produces a characteristic electrical response to relevant events that occur unexpectedly. Recent reports have suggested that a prominent part of this event-related brain potential--the P3 wave--may be related to memory functions and may arise from activity within the medial temporal lobe, especially the hippocampus. The latter idea was tested by means of epidural recordings of brain waves in monkeys. Responses to deviant auditory stimuli bore a close resemblance to P3 waves recorded from human subjects under comparable conditions. Monkeys with bilateral lesions of the medial temporal lobe still produced P3-like brain waves, which indicates that medial temporal brain structures are not critical for their generation.

Acoustic Stimulation↗