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Science 18 July 1997:
Vol. 277. no. 5324, pp. 376 - 380
DOI: 10.1126/science.277.5324.376
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Reports

Differential Effects of Early Hippocampal Pathology on Episodic and Semantic Memory

F. Vargha-Khadem, * D. G. Gadian, K. E. Watkins, A. Connelly, W. Van Paesschen, M. Mishkin

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.

F. Vargha-Khadem and K. E. Watkins, Cognitive Neuroscience Unit, Institute of Child Health, University College London Medical School, Wolfson Centre, Mecklenburgh Square, London WC1N 2AP, UK.
D. G. Gadian and A. Connelly, Radiology and Physics Unit, Institute of Child Health, University College London Medical School, 30 Guilford Street, London WC1N 1EH, UK.
W. Van Paesschen, Radiology and Physics Unit, Institute of Child Health, University College London Medical School, 30 Guilford Street, London WC1N 1EH, UK, and Institute of Neurology, Queen Square, London WC1N 3BG, UK.
M. Mishkin, Laboratory of Neuropsychology, National Institutes of Mental Health, 49 Convent Drive, Bethesda, MD 20892-4415, USA.
*   To whom correspondence should be addressed. E-mail: fkhadem{at}ich.ucl.ac.uk

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
Autism and visual agnosia in a child with right occipital lobectomy.
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   Abstract »    Full Text »
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