Stuart Zola-Morgan

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.

The Neuropsychology of Memory

Neuropsychology aims to describe how the brain accomplishes learning and memory, in a way that speaks both to cognitive psychology and neuroscience. This paper presents a summary of presently available information about the neuropsychology of human memory, emphasizing three ideas: a) The neural substrate of memory continues to change for a long time after initial learning. This change (memory consolidation) is distinct from the changes underlying forgetting and involves the medial temporal region of the brain. b) The nervous system honors the distinction between two kinds of learning and memory (procedural vs. declarative). The former is spared in amnesia and does not depend on the integrity of the particular brain regions that when damaged cause amnesia. c) Animal models of human amnesia in the monkey are now available. These models should permit those brain regions damaged in amnesia to be identified and should lead to more detailed neurobiological study of these regions.

Medial temporal lesions in monkeys impair memory on a variety of tasks sensitive to human amnesia.

Monkeys with conjoint bilateral lesions of the hippocampus and amygdala were impaired on four different tests of memory (delayed retention of object discriminations, concurrent discrimination, delayed response, and delayed nonmatching to sample). Because tests involving delays and distractions are known to be especially sensitive to human amnesia, in three of the tasks relatively long delay intervals between training and test trials were used, and in two tasks distraction was introduced during the delay intervals. The severity of the impairment increased with the length of the delay, and distraction markedly increased the memory impairment. For one task given on two occasions (delayed nonmatching to sample), the severity of the impairment was unchanged over a period of 1.5 years. Taken together with previous findings that skill learning is unimpaired in the same operated monkeys, the results of the present study strengthen the conclusion that monkeys with medial temporal lesions constitute an animal model of human amnesia. In addition, the four tasks used here appear to constitute a sensitive and appropriate battery that could be used in other studies of the neuroanatomy of memory functions in the monkey.

Memory impairment in monkeys following lesions limited to the hippocampus.

This study addressed the question of how severe a memory impairment is produced by a lesion limited to the hippocampus. Monkeys with circumscribed hippocampal lesions were tested on the delayed-nonmatching-to-sample task, a test of recognition memory that is sensitive to amnesia in humans. Monkeys were given no preoperative training and were given no postoperative experience prior to training on the delayed-nonmatching-to-sample task. A marked deficit was observed. The results, taken together with those from previous studies, also provided information about the role of several factors that could potentially influence the level of memory impairment following hippocampal lesions. The level of impairment does not appear to be due to any of the following factors: time of testing after surgery, prior postoperative testing, surgical techniques, species differences, or behavioral training methods. However, preoperative training experience does appear to reduce the severity of the impairment, and this factor may account for the observation that the memory impairment associated with hippocampal lesions is sometimes very mild. Finally, a recent case of human amnesia studied in this laboratory is discussed in which a bilateral lesion limited to a portion of the hippocampus produced a well-documented memory deficit.

Memory: brain systems and behavior

Abstract Certain questions about memory address a relatively global, structural level of analysis. Is there one kind of memory or many? What brain structures or systems are involved in memory and what jobs do they do? One useful approach to such questions has focused on studies of neurological patients with memory impairment and parallel studies with animal models.

Damage limited to the hippocampal region produces long-lasting memory impairment in monkeys

Research in humans and monkeys has demonstrated a system of anatomically related structures in the medial temporal lobe that is important for memory function. This system is comprised of the hippocampal region (i.e., the dentate gyrus, hippocampus proper and subicular complex) and the entorhinal, perirhinal, and parahippocampal cortices. While the hippocampal region has long been thought to be important in memory, there are few systematic studies in primates of the effects on memory of damage limited to the hippocampal region. We have used magnetic resonance imaging techniques, together with a stereotaxic approach, to produce bilateral lesions limited to the hippocampal region (the H lesion). Damage to the adjacent perirhinal, entorhinal, and parahippocampal cortex was minimal. Monkeys with the H lesion exhibited significant and long-lasting impairment on the delayed non-matching to sample task. At the same time, on this and other amnesia-sensitive tasks, monkeys with the H lesion performed better overall than monkeys with lesions of the hippocampal region that also included damage to the adjacent entorhinal and parahippocampal cortices (the H+ lesion). These findings show that, first, the hippocampal region itself is essential for normal memory function; and second, the adjacent entorhinal and parahippocampal cortices, either alone or in combination, are also an essential component of the medial temporal lobe memory system.

Recall of remote episodic memory in amnesia

Recall of remote episodic memory was assessed in three types of amnesic patient whose remote semantic memory had been evaluated previously. Patients with Korsakoffs syndrome, case N.A. and patients receiving electroconvulsive therapy all succeeded in recalling specific autobiographical episodes in response to single-word cues, and in many conditions performed as well as control subjects. Their pattern of performance generally paralleled that obtained in previous tests of remote semantic memory. These results argue against a view that amnesia reflects a selective deficit of episodic memory and suggest that the semantic-episodic distinction cannot illuminate the fundamental deficit in amnesia. Nor can the facts of amnesia confirm or deny the validity of this distinction in normal memory.

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.

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.

Comparative neuropsychology and Korsakoff's syndrome. I—Spatial and visual reversal learning

Abstract Alcoholic Korsakoffs disease is associated with widespread cerebral damage. Damage to the hippocampus and its major connections has been linked directly to the severe anterograde amnesia observed in Korsakoff patients. However, since other brain regions also are destroyed with chronic alcoholism, a thorough description of any additional behavioral abnormalities is essential to understanding the alcoholic Korsakoff syndrome. Using spatial and visual reversal-learning paradigms popular in comparative and physiological psychology, we have observed profound defects in the formation of stimulus-reinforcement associations by a group of 12 Korsakoffs in comparison to 13 alcoholic and 11 aphasic control subjects. A group of 15 patients with Huntingtons disease showed severe deficits on visual but not spatial reversals, and their poor visually-based performance was qualitatively different from that of the Korsakoff patients.