Commentators: Carol Lam Mahmoud Younes Aditya Talwar Patrick Steadman Adam Stevenson

1. A Critical Analysis of:Differential Effects of Early Hippocampal Pathology on Episodic and Semantic Memory Authors: Vargha- Khadem, F. Gadian, D.G. Watkins, K.e. Connelly, A. Van Paesschen, W. Mishkin, M. Commentators: Carol Lam Mahmoud Younes Aditya Talwar Patrick Steadman Adam Stevenson

2. Carol Lam Methodological Issues Does the data presented support the claims of Vargha-Khadem et al.? • The authors of this paper infer correlation between bilateral pathology to the hippocampus and severe episodic memory loss but not semantic memory loss. • They further deduce that such damage spares semantic memory because semantic memory can be largely supported by the underlying cortices .

3. Carol Lam Supporting Evidence • VIQ-MQ discrepancy test • Recall of the WMS stories • Children’s Auditory Verbal Learning Test • Reproduction of the Rey-Osterreith Figure • Rivermead Behavioral Memory Test • Volumetric measurements • T2 relaxometry • Proton magnetic resonance spectroscopy • WORD test • Computerized associative-recognition test

4. Moody Younes VIQ – MQ Discrepancies • MQ - VIQ comparisons are a pretty reliable indicator of amnesia and have been used to progress the field of memory research to where it is today • Comments: • Applying it in these patients especially with the discrepancies of 20 and over (only characteristic of less than 5% of pop) was appropriate (Groth-Marnat, G.) • Resulting gaps in scores were very consistent with the accepted difference between two quotients and the subjective presence of amnesia in the patients

5. Moody Younes W.M.S. Stories • Original W.M.S. test portion used is for logical memory • Results show a substantial difference between normal control and subjects • Comments • A logical test might have some aspects that may also be involved in semantic memory • Therefore it might not have been the best test to isolate episodic memory

6. Moody Younes Auditory Verbal Learning Test • Words read aloud, followed by immediate and delayed recall • Comments • Results show that delayed recall was almost completely impaired for the tested subjects • Inferred general long term memory deficits

7. Aditya Talwar Rivermead Behavioral Memory Test • Specifically designed to asses memory skills. • Aspects of the test include remembering a route, a date, a message, and other day to day tasks. • The test scores were recorded immediately and after a time delay. • Out of a possible score of 12 all three children scored between 2 and 4. The cutoff for impairment is 9. • Resulting scores indicate that all three children have severe memory impairment.

8. Aditya Talwar • Comments • In terms of the study, the test provided stronger evidence that the children had impaired episodic memory. • From subject history and parental questionnaire, it was inferred that the children had episodic memory loss, therefore further tests were redundant. • To improve the experiment, the authors could have done additional experiments to further isolate episodic memory as their only deficit

9. Patrick Steadman Imaging Techniques in assessing Neuropathology • Hippocampal abnormalities were assessed using T2 weighted MR imaging and volumetric measurements • Temporal-lobe abnormalities were assessed using Proton MR spectroscopy, a measure of proton signal intensity (Hydrogen density in molecules other than water) • Comments • It is unclear why the same diagnostic methods were not used for both the hippocampus and temporal-lobe/underlying cortices • Size and density were the only determinants used to establish functionality, other determinants would help to strengthen conclusions (e.g. Blood-oxygen-level dependent fMRI) • Next step is to image an individual with damage to the cortices underlying the Hippocampus only, using same diagnostic criteria to apply double dissociation theory to the article’s conclusion

10. Patrick Steadman Imaging Techniques Continued • How this data supports the authors conclusion • Volume Measurements • T2 weighted water levels • Proton MR spectroscopy signal intensity Vargha-Khadem, F et al, Differential Effects of Early Hippocampal Pathology on Episodic and Semantic Memory, 1997

11. Patrick Steadman Imaging Techniques Continued • Anatomical evidence, collected by imaging techniques, was used primarily to show damage or no damage to areas of interest • Not used to show functionality • Comments • Could have shown functionality using imaging techniques such as Blood-oxygen-level dependent MRI • Used only to show smaller size hippocampus and similar size of surrounding cortices toNC

12. Adam Stevenson Tests of Semantic Memory • WORD (Wechsler Objective Reading Dimensions) test • Test of competence in speech and language • Comprehension not requiring long-term memory system (all information available during the test) • Normal mean 100 +/- 15 • WISC-III/WAIS-R (Wechsler Intelligence scale measured for adults/children respectively) • “Most commonly used, individually administered test of general intelligence” (Nielson et. al., 1990) • Comprising of 11 subtests, 6 verbal, 5 non-verbal • Measures a subject’s VIQ, PIQ, and FSIQ (Nielson et. al., 1990) • Normal mean 10 +/- 3

13. Adam Stevenson W.O.R.D. • Used to test a subjects reading spelling and reading comprehension capabilities • Used by the researchers to establish that language (a function of semantic memory) was intact in the subjects • Comments: • Language acquisition occurs and develops rapidly between the ages of 6 months to 3 years in humans, an age where our episodic memory is still grossly underdeveloped (Kuhl) • Produced speculation of deeper seated mechanisms which assist in the acquisition of language (Kuhl) • Intact language areas do not necessarily indicate that semantic memory is equally untouched with damage localized to the hippocampus • Structures such as Wernicke’s and Broca’s areas being responsible for speech specific functions indicates that language may belong to a separate system (Zurif et. al.)

14. Adam Stevenson WISC-III/WAIS-R • These tests were chosen to identify the subjects VIQ (verbal intelligence quotients) as supplementary to their aptitude on the WORD test Comments: • Perhaps the researchers would have improved their results by including numbers on the other forms of intelligence • The relevance of language and verbal intelligence to semantic memory has not, in the article been properly identified. • This would greater support their conclusion of a distinction between the plasticity of the two memory systems.

15. Carol Lam Conclusion • It is important to remember that Vargha- Khadem et al. does notinfer causation between pathologies of the hippocampus and episodic memory loss, thus the supporting evidence is sufficient to support this inference • Further studies that would likely help the authors’ make a stronger claim would be to use double dissociative methods of experiment i.e. Study patients that only have damage to the underlying cortices to determine semantic memory loss

16. Carol Lam Improvements to be made • Improved identification of intact semantic memory of the subjects • BOLD MRI, studies to further indicate functionality of hippocampus in episodic and semantic memory tests

17. References Groth-Marnat, G. (2003). Handbook of Psychological Assessment: Wiley Kuhl, P.K. (2004). EARLY LANGUAGE ACQUISITION:craking the speech code.Neuroscience, 5, Retrieved September 22, 2008, from http://biology.kenyon.edu/courses/biol358/Butcher/Early%20Language%20Kuhl.pdf Nielson , W.A., Gelb, A.W., Penny, F.J., Merchant, R.N., Casey, J.E. & Manninen, P.H. (1990). Long-term Cognitive and Social Sequelae of general versus regional Anesthesia during Arthroplasty in the Elderly. Anesthesiology, 73, Retrieved September 22, 2008, from http://scholar.google.ca/scholar?hl=en&lr=&q=info:sjpafeLQtGEJ:scholar.google.com/&output=viewport&pg=1.

18. Vargha-Khadem, F. (1997).Differential effects of early hippocampal pathology on episodic and semantic memory. Science. 277 Wilson, Barbra, Ph.D. RBMT - Rivermead Behavioral Memory Test. Retrieved September 22, 2008, from RBMT - Rivermead Behavioral Memory Test Web site from http://www.nss-nrs.com/cgi-bin/WebObjects/NSS.woa/wa/Products/detail?id=1000073 Zurif, E., Swinney, D., Prather, P., Solomon, J., & C. Bushell. (1993). An On-Line Analysis of Syntactic Processing in Broca's and Wernicke's Aphasia. Brain and Language, 45, Retrieved September 22, 2008, from http://lcnl.ucsd.edu/LCNL_main_page/Publications_PDF/1993_Zurif_Swinney_Prather_Solomon_Bushell.pdf