Differential Effects of Early Hippocampal Pathology on Episodic and Semantic Memory
Tóm tắt
Global anterograde amnesia is described in three patients with brain injuries that occurred in one case at birth, in another by age 4, and in the third at age 9. Magnetic resonance techniques revealed bilateral hippocampal pathology in all three cases. Remarkably, despite their pronounced amnesia for the episodes of everyday life, all three patients attended mainstream schools and attained levels of speech and language competence, literacy, and factual knowledge that are within the low average to average range. The findings provide support for the view that the episodic and semantic components of cognitive memory are partly dissociable, with only the episodic component being fully dependent on the hippocampus.
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Tài liệu tham khảo
L. R. Squire and B. J. Knowlton in The Cognitive Neurosciences M. S. Gazzaniga Ed. (MIT Press Cambridge MA 1995) pp. 825–837;
F. Wood V. Ebert M. Kinsbourne in Human Memory and Amnesia L. S. Cermak Ed. (Erlbaum Hillsdale NJ 1982) pp. 167–193.
E. Tulving in The Cognitive Neurosciences M. S. Gazzaniga Ed. (MIT Press Cambridge MA 1995) pp. 839–847.
The youngest ages of amnesia-inducing injuries reported previously were 9 [F. B. Wood I. S. Brown R. H. Felton Brain Cognit. 10 76 (1989)] and 10 [
An alternative possibility had been that very early medial temporal damage might fail to produce amnesia because of the reorganizational capacity of the immature brain. Indeed unimpaired memory has been reported in cases of bilateral dysgenesis of the temporal lobes [
Lang C., Lehrl S., Huk W., ibid. 44, 626 (1981);
]. The present findings which indicate that amnesia results from bilateral hippocampal pathology however early such damage occurs (from at least birth onward) rule out this possibility as well.
Informed consent was obtained from all three patients after they had been given a description of the studies to be carried out.
J. L. Talley Children's Auditory Verbal Learning Test (Psychological Assessment Research Odessa FL 1993).
A. Sunderland J. E. Harris A. D. Baddeley J. Verb. Learn. Verb. Behav. 22 341 (1983). The questionnaire asked the parents to rate how often their child forgets each of 29 prototypical daily events on a scale ranging from A (has not occurred in the past 3 months) to I (occurs more than once a day). The vast majority of the ratings by all three sets of parents were either G (more than once a week) H (about once a day) or I (more than once a day).
B. Wilson J. Cockburn A. Baddeley Rivermead Behavioural Memory Test (Thames Valley Test Co. Reading UK 1985).
Magnetic resonance imaging (MRI) and MRS studies were carried out on a 1.5 T Siemens system with a standard quadrature head coil. Structural MRI investigations included 3D data acquisition with the T1-weighted magnetization prepared rapid acquisition gradient echo sequence [
] with the following parameters: repetition time 10 ms; echo time 4 ms; inversion time 200 ms; flip angle 12°; matrix size 256 by 256; field of view 250 mm; partition thickness 1.25 mm; 128 sagittal partitions in the third dimension; acquisition time 8.3 min. For the measurements of hippocampal volumes the data sets were reformatted into 1-mm-thick contiguous slices in a tilted coronal plane that was perpendicular to the long axis of the hippocampus. We measured hippocampal cross-sectional areas along the entire length of the hippocampi using every third slice as described previously (14). We calculated the volumes by summing the cross-sectional areas and then multiplying them by the distance between the measured slices (that is 3 mm). A correction was then made for intracranial volume and the hippocampal volumes are presented here in this corrected form. Hippocampal water T2 values were obtained from T2 maps constructed from a 16-echo sequence as previously described (14 15). The cross section from which the hippocampal T2 values were taken was oriented in a tilted coronal plane along the anterior border of the brain stem perpendicular to and at the level of the body of the hippocampus. We measured T2 values by placing a region of interest in the largest possible circular area within the hippocampus while avoiding boundaries at which partial volume effects with cerebrospinal fluid may occur. For the assessment of more diffuse or widespread pathology we obtained 1 H MRS data from 2 by 2 by 2 cm cubes centered on the medial portions of the right and left temporal lobes using a 90°-180°-180° spin-echo technique (TR 1600 ms; TE 135 ms) as described previously (16). Signal intensities at 2.0 parts per million (ppm) [primarily N-acetylaspartate (NAA)] 3.0 ppm [creatine + phosphocreatine (Cr)] and 3.2 ppm [choline-containing compounds (Cho)] were measured from the peak areas by integration and corrected for differences in radio-frequency coil loading among the different individuals. The data are presented in the form of the signal-intensity ratio NAA/(Cho + Cr) which provides a simple index of spectral abnormality with values below 0.72 (the lower limit of the 95% reference range) being indicative of neuronal loss or damage or astrocytosis or both (16);
]. The positioning and volume of the selected regions are such that the hippocampi in the amnesic subjects make only a minor contribution to the observed signal intensities.
Connelly A., Jackson G. D., Duncan J. S., King M. D., Gadian D. G., ibid. 44, 1411 (1994).
Although our MRS findings suggest that the bilateral temporal-lobe pathology is focal rather than widespread the low spatial resolution of the technique does not preclude the possibility that the pathology extended into the underlying perirhinal and entorhinal cortices an area known to be critical for many types of memory formation in monkeys [
Spiegler B. J., Mishkin M., Soc. Neurosci. Abstr. 5, 323 (1979);
Murray E. A., Gaffan D., ibid. 19, 438 (1993);
; S. Goulet and E. A. Murray ibid. 21 1446 (1995)]. We therefore carefully examined the MRI 3D data sets for any evidence of structural abnormality in this specific region as well as in other regions throughout the brain. Although the possibility of undetected damage in the perirhinal and entorhinal regions or elsewhere in the three patients cannot be excluded the only visible abnormalities noted outside the hippocampal formation were in Beth's scans in which there was an increase in T2-weighted signal intensity in the periventricular and particularly peritrigonal white matter accompanied by a marked loss of white matter bulk and thinning of the corpus callosum. These extrahippocampal abnormalities could well be the cause of Beth's impaired intellectual development described earlier. No extrahippocampal abnormalities were detectable in the other two patients. Thus as far as we could determine from the magnetic resonance findings the only abnormality common to all three patients was bilateral pathology of the hippocampal formation.
J. Rust S. Golombok G. Trickey Wechsler Objective Reading Dimensions Test (Psychological Corporation Sidcup UK 1993).
Like the tests used in monkeys (18) the tests for humans were designed with memory loads (that is number of items and length of delays) that exceeded online working memory capacity so as to tap memory storage ability. It should be emphasized that these tests are not considered to be selective measures of either episodic or semantic learning [see (28)].
Photos of 20 different female faces were presented in succession on the computer monitor with each one paired with a recording of that person's voice uttering the phrase “I am sorry I am not able to meet you but I hope you will remember me.” After presentation of the 20 face-voice pairs one of the recorded voices uttering the same phrase was repeated while two faces were presented on the monitor: the correct face for that particular voice together with an incorrect one associated with a different voice. The individual responded by touching one of the faces which produced an indication of “correct” or “incorrect” on the screen depending on the choice. Such choice tests for all 20 face-voice pairs completed a trial and the trials were repeated until the individual achieved at least 18 correct responses in one trial or had received a maximum of 10 trials. Each of the normal control individuals learned these associations rapidly (mean 1.8 trials; range 1 to 5 trials) and accumulated very few errors (mean 5.8 errors; range 1 to 23 errors). By contrast among the amnesic patients only Jon performed as well as the poorest control individual requiring five trials to learn and making 20 errors; Kate learned the associations in six trials (31 errors) and Beth was unable to reach the criterion in the 10-trial limit making 57 errors. The group difference was significant at P < 0.05 for both trials and errors.
Pictures of 20 different objects were presented in succession on the right side of the computer monitor with each object paired with a different circle in an irregular array of 40 circles located in the center of the monitor; the paired circle was illuminated and the object then appeared within it. After presentation of the 20 object-place pairs one of the previously lit circles was relit while two objects were presented on the right: the correct object for that particular circle in the array together with an incorrect one associated with a different circle. The individual responded by touching one of the objects which produced a voice-recorded “correct” or “incorrect ” depending on the choice. Such choice tests for all 20 object-place pairs completed a trial and the trials were repeated until the individual achieved at least 18 correct responses in one trial or had received a maximum of 10 trials. Each of the normal individuals learned these object-place associations rapidly (mean 1.7 trials; range 1 to 5 trials) and accumulated very few errors (mean 4.2 errors; range 0 to 19 errors). By contrast none of the amnesic patients learned within the 10-trial limit each one barely exceeding chance performance (Beth 86 errors in 200 responses; Jon 75 errors; Kate 95 errors). The group differences in trials and errors were each significant at P < 0.01.
. How spatial memory and episodic memory are related to each other in humans and nonhuman primates remains a high-priority issue for research.
Murray E. A., Mishkin M., Soc. Neurosci. Abstr. 22, 281 (1996).
This proposal does not imply that the computerized recognition tasks are tests of semantic learning; however neither are they tests of episodic learning. The distinction between the two forms of cognitive memory applies not to the moment that memories are first acquired but rather to their long-term content. At the moment that attended sensory information is encoded for initial storage the information is necessarily in the form of an unfolding event or episode replete with context including time place surroundings and persons; how much of the information in that episode is retained in long-term memory is what determines whether the memory is properly classified as episodic or semantic.
Rempel-Clower N. L., Zola-Morgan S., Squire L. R., Soc. Neurosci. Abstr. 20, 1075 (1994).
We thank A. Incisa della Rocchetta for setting up the computerized tests A. Incisa della Rocchetta and M.-C. Jones for testing some of the control individuals and K. Pettigrew for statistical advice. Supported by the Wellcome Trust and Action Research.