Retrograde amnesia after hippocampal damage: recent vs. remote memories in two tasks.

We review evidence from experiments conducted in our laboratory on retrograde amnesia in rats with damage to the hippocampal formation. In a new experiment reported here, we show that N-methyl-D-aspartate (NMDA)-induced hippocampal damage produced retrograde amnesia for both hidden platform and two-choice visible platform discriminations in the Morris water task. For both problems there was a significant trend for longer training-surgery intervals to be associated with worse retention performance. Little support is offered by our work for the concept that there is a process involving hippocampal-dependent consolidation of memories in extrahippocampal permanent storage sites. Long-term memory consolidation may take place within the hippocampus. The hippocampus may be involved permanently in storage and/or retrieval of a variety of relational and nonrelational memories if it was intact at the time of learning, even involving information which is definitely not affected in anterograde amnesia after hippocampal damage.

Retrograde amnesia and selective damage to the hippocampal formation: memory for places and object discriminations.

Using a within-subjects design, rats were trained on two place-memory problems and five object-discrimination problems at different intervals prior to receiving either ibotenate lesions of the hippocampal formation or sham surgery. Places # 1 and 2 were fixed-platform water-maze tasks that were run in different rooms and they were learned during the 14th and 2nd week before surgery, respectively. Object-discrimination problems # 1-5 were learned during the 13th, 10th, 7th, 4th, and 1st week before surgery, respectively. Rats with hippocampal lesions displayed impaired retention of both Place problems with no evidence of a temporal gradient to the impairment. In contrast to their retrograde place-memory deficits, the hippocampal rats displayed normal retention of the five object-discriminations that were learned before surgery. Hippocampal lesions had similar consequences for anterograde learning, as the lesioned rats were impaired in acquisition of a new water-maze problem that was run in a third room (Place #3), whereas they showed normal acquisition of two new object-discriminations. The findings indicate that the hippocampal formation is not required for long-term consolidation of information underlying accurate performance of object-discriminations, and that its critical role in memory for places persists for at least 14 weeks, and probably for as long as those memories exist.

A characterization of performance by men and women in a virtual Morris water task: a large and reliable sex difference.

In many mammalian species, it is known that males and females differ in place learning ability. The performance by men and women is commonly reported to also differ, despite a large amount of variability and ambiguity in measuring spatial abilities. In the non-human literature, the gold standard for measuring place learning ability in mammals is the Morris water task. This task requires subjects to use the spatial arrangement of cues outside of a circular pool to swim to a hidden goal platform located in a fixed location. We used a computerized version of the Morris water task to assess whether this task will generalize into the human domain and to examine whether sex differences exist in this domain of topographical learning and memory. Across three separate experiments, varying in attempts to maximize spatial performance, we consistently found males navigate to the hidden platform better than females across a variety of measures. The effect sizes of these differences are some of the largest ever reported and are robust and replicable across experiments. These results are the first to demonstrate the effectiveness and utility of the virtual Morris water task for humans and show a robust sex difference in virtual place learning.

Nonverbal working memory of humans and monkeys: rehearsal in the sketchpad?

Investigations of working memory tend to focus on the retention of verbal information. The present experiments were designed to characterize the active maintenance rehearsal process used in the retention of visuospatial information. Rhesus monkeys (Macaca mulatta; N = 6) were tested as well as humans (total N = 90) because these nonhuman primates have excellent visual working memory but, unlike humans, cannot verbally recode the stimuli to employ verbal rehearsal mechanisms. A series of experiments was conducted using a distractor-task paradigm, a directed forgetting procedure, and a dual-task paradigm. No evidence was found for an active maintenance process for either species. Rather, it appears that information is maintained in the visuospatial sketchpad without active rehearsal.

Hypoplasia of the cerebellar vermis and cognitive deficits in survivors of childhood leukemia.

BACKGROUND: Neurodevelopmental evidence of the cerebellum's protracted course of postnatal development suggests that it is particularly sensitive to early toxic insult from cancer therapy. If this is the case, one would expect that there is a relationship between the pattern of neuropsychological and magnetic resonance imaging deficits and that both may indicate cerebellar abnormalities. OBJECTIVE: To investigate the profiles of neuropsychological functions and the morphologic features of the cerebellum, using in vivo magnetic resonance imaging planimetry in survivors of acute lymphoblastic leukemia (ALL) treated with radiation and chemotherapy. DESIGN: Thirteen survivors of childhood ALL with onset at age 2 to 5 years and a uniform protocol of treatment involving cranial radiation of 24 Gy and five doses of intrathecal methotrexate sodium participated in the study. Ten controls matched the patients in age and socioeconomic status. Each child was assessed with a comprehensive battery of neuropsychological tests and with magnetic resonance imaging of the brain. MEASUREMENTS: The neuropsychological scores were transformed into z scores and clustered into right and left hemisphere measures. Planimetric measures of the cerebellar vermis and pons were collected in the midsagittal plane. RESULTS: Consistently observed in survivors of ALL were the following: (1) significant cognitive deficits in visual-spatial-motor coordination and figural memory, functions commonly related to the right side of the brain; and (2) hypoplasia of the cerebellar vermis, lobuli I through V and particularly VI to VII. Lateralization of the neurobehavioral deficits was not reflected in structural brain abnormalities. CONCLUSIONS: Coexistence of the cerebellar hypoplasia and visual-motor coordination and memory deficits supports the neurodevelopmental approach to brain sequelae in survivors of ALL; it also suggests significance of the cerebellum for both motor and complex nonmotor cognitive processing.

Role of the forebrain commissures in bihemispheric mnemonic integration in macaques.

A serial probe recognition task was used to examine the interhemispheric exchange of visual data in macaques. Each block of trials began with the memorization of one to six visual target images. The monkeys then had to determine, in tests that followed immediately, whether probe images were or were not members of the learned target set. Previous work with both humans and macaques has shown that the time required for the evaluation of probes generally increases, while response accuracy decreases, as a function of the number of targets, the "memory load". By testing animals with bisected optic chiasm, it was possible to direct visual information to only one hemisphere at a time, simply by occluding the opposite eye. In this fashion, the quality of intrahemispheric evaluations (in which a monocular probe was a match for a target previously viewed through the same eye) was compared with that of interhemispheric evaluations (in which a probe was a match for a target previously designated through the opposite eye). A key question was whether division of the target list between the hemispheres modified the relationships between reaction time, response accuracy, and memory load. Provided that either the anterior commissure or the splenium of the corpus callosum was intact, interhemispheric processing was only subtly less efficient than intrahemispheric processing. The ability to perform interhemispheric evaluations was selectively and completely disrupted if all forebrain commissural fibers were transected. In this latter split-brain condition, the time required for probe evaluations was, as expected, determined solely by the number of target items memorized by the probed hemisphere. Accuracy, however, was always a function of the total memory load, regardless of the distribution of targets between the hemispheres. This implies, first, that accuracy and latency do not reflect identical mnemonic factors, as frequently held, and second, that in mnemonic processing, the two hemispheres draw upon a unified, shared resource, probably allocated by the intact brainstem.

Cortical organization in adulthood is modified by neonatal infarct: a case study.

PURPOSE: To assess anomalous cortical organization of somatosensory function in a 23-year-old man who had had a neonatal infarct involving the left middle cerebral artery. MATERIALS AND METHODS: The infarct destroyed the primary and secondary somatosensory areas of the subject's left hemisphere but caused only mild perturbation of somatosensation on the right side of his body. With magnetic source imaging, the authors integrated magnetoencephalographic data with magnetic resonance imaging data to create magnetic source localization images that showed the mapping between brain function and structure. RESULTS: Electrical stimulation of the right median nerve evoked activity in two nontraditional areas: (a) an intact region of the left inferior temporal gyrus and (b) the ipsilateral right medial parietal cortex. CONCLUSION: These data suggest that bilateral neural reorganization can be induced by unilateral neonatal damage.