Neurocase, 2013 Vol. 19, No. 4, 401–407, http://dx.doi.org/10.1080/13554794.2012.690424
Dissociation of explicit and implicit long-term memory consolidation in semantic dementia: A case study S. Tu1 , E. Mioshi1,2 , S. Savage1,2 , J. R. Hodges1,2 , and M. Hornberger1,2 1
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2
Neuroscience Research Australia, Sydney, Australia School of Medical Sciences, University of New South Wales, Sydney, Australia
We report a case study of a semantic dementia patient, whose episodic memory consolidation was tested over a 2-month period. The results reveal that despite early retention of information, the patient lost all explicit information of the newly learnt material after 2 weeks. By contrast, he retained implicit word information even after a 4-week delay. These findings highlight the critical time window of 2–4 weeks in which newly learnt information should be re-encoded in rehabilitations studies. The results also indicate that learnt information can be still accessed with implicit retrieval strategies when explicit retrieval fails. Keywords: Semantic dementia; Memory; Consolidation; Neuroimaging; Voxel-based morphometry.
Semantic dementia (SD) is a neurodegenerative disease characterized by a progressive and selective loss of multi-modal conceptual knowledge of the world (Hodges & Patterson, 2007). Atrophy in SD is typically asymmetrical, involving the anterior temporal lobe with a variable atrophy in the hippocampus (Davies, Graham, Xuereb, Williams, & Hodges, 2004; Galton et al., 2001). In contrast to their profound semantic deficits, patients with SD show relatively intact episodic memory, particularly for visual material (e.g., Lee, Rahman, Hodges, Sahakian, & Graham, 2003; Simons, Graham, Galton, Patterson, & Hodges, 2001). Moreover, their day-to-day memory is well preserved with good episodic memory performance even after a 24-hour delay (Adlam, Patterson, & Hodges, 2009). Attempts have been made to utilize their intact episodic memory to re-learn lost word or object information, with variable success (Dewar,
Patterson, Wilson, & Graham, 2009; Graham, Patterson, Pratt, & Hodges, 1999; Murray, Koenig, Antani, McCawley, & Grossman, 2007; Snowden & Neary, 2002). One potential reason for these mixed results is that memory consolidation processes may be affected thus hindering the long-term retention of new information. A critical factor for word relearning rehabilitation studies in SD is the time after which newly learnt information deteriorates or is forgotten. Graham et al. (1999) demonstrated that daily rehearsal of word lists over 2 weeks could improve performance on category fluency tasks, however, once daily practice ceased, performance declined to 60% within 6 weeks. Similarly, Snowden and Neary (2002) taught two SD patients the names of a set of line drawn stimulus. One patient (C.R.) was given a booklet that provided a descriptive and contextual meaning for each item studied. The other
This work was supported by an Australian Research Council Federation Fellowship (FF0776229) to JRH. MH is supported by an Australian Research Council Research Fellowship (DP110104202); JRH is supported by an Australian Research Council Federation Fellowship (FF0776229). The authors report no conflicts of interest or disclosures. Address correspondence to Dr Michael Hornberger, Neuroscience Research Australia, PO Box 1165, Sydney, Australia. (E-mail:
[email protected]).
c 2013 Taylor & Francis
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patient (K.B.) showed poor retention of names after a 2-week delay, while C.R. performed at ceiling level 6 months post-training when aided by the trained contextual cue. Two more recent studies (Dewar et al., 2009; Jokel, Rochon, & Leonard, 2006) have replicated these findings in SD cases, indicating that newly learnt information rapidly declines within weeks when no maintenance of the knowledge is provided. It becomes clear that learning mechanisms can be intact in SD, but the durability of newly learnt information is still unclear. In particular, the status of implicit memory has not been explored. It is possible that although newly learnt information cannot be recalled explicitly, implicit memory may be demonstrable. We employed a well established long-term anterograde episodic memory paradigm (Schott, Richardson-Klavehn, Heinze, & Duzel, 2002) with repeated recall of information over a 2-month period. This paradigm allows evaluation of explicit and implicit memory for the same items. We hypothesized that the initial and short-delay episodic explicit retrieval would be good, followed by a deterioration over longer delays. We further assumed that despite an impaired explicit memory performance, some memory information would be intact on an implicit level even after a long delay, as recall of this information should not rely on medial temporal lobe structures, known to be affected in SD.
METHODS Case description Patient R.W. (b. 1951) presented in June 2008 with anomia and word finding difficulties. A previously avid crossworder he had become aware of progressive difficulty in thinking of word meanings. His wife also reported subtle changes in personality, including socially inappropriate behavior and difficulty with personal boundaries. R.W.’s recall of autobiographical details was good, although frequently interrupted by word finding pauses and anomia. The patient was good at repeating multisyllabic words, such as chrysanthemum and hippopotamus but had no knowledge of their meaning. When given an array of toy animals, he was unable to name any and made errors when asked to point in response to their name. On formal neuropsychological assessments he scored of
26 (out of 30) on the MMSE and a 62 (out of 100) on the ACE-R (Table 1). Tests of verbal and non-verbal anterograde memory (Table 1) showed significant impairment in verbal episodic memory, while non-verbal memory was good, compared to controls. Semantic memory, as expected, was poor with a total of 3 (out of 15) on the Boston Naming task (Table 1). In 2009, follow-up assessments showed R.W.’s anomia and comprehension problems had deteriorated, but his nonverbal memory performance remained on a similar level to controls (Table 1).
Imaging acquisition and Voxel-based morphometry (VBM) analysis R.W. and controls underwent the same imaging protocol with whole-brain T1 and DTI-weighted images using a 3T Philips MRI scanner with standard quadrature head coil (8 channels). The 3D T1-weighted sequences were acquired as follows: coronal orientation, matrix 256 × 256, 200 slices, 1 × 1 mm2 in-plane resolution, slice thickness 1 mm, TE/TR = 2.6/5.8 ms. 3D T1-weighted sequences were analyzed with FSL-VBM, a voxel-based morphometry analysis (Ashburner and Friston, 2000; Good et al., 2001) which is part of the FSL software package http://www.fmrib.ox.ac.uk/fsl/fslvbm/index.html. First, tissue segmentation was carried out using FMRIB’s Automatic Segmentation Tool (FAST) (Zhang et al., 2001) from brain extracted images. The resulting gray matter partial volume maps were then aligned to the Montreal Neurological Institute standard space (MNI152) using the nonlinear registration approach using FNIRT (Andersson et al., 2007), which uses a b-spline representation of the registration warp field (Rueckert et al., 1999). The registered partial volume maps were then modulated (to correct for local expansion or contraction) by dividing them by the Jacobian of the warp field. The modulated images were then smoothed with an isotropic Gaussian kernel with a standard deviation of 3 mm (FWHM: 8 mm). Finally, a voxel-wise general linear model (GLM) was applied and permutation-based non-parametric testing was used to form clusters with the Threshold-Free Cluster Enhancement (TFCE) method (Smith & Nichols, 2009), tested for significance at p < .05, corrected for multiple comparisons via family-wise error (FEW) correction across space.
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TABLE 1 Selected neuropsychological scores for patient R.W. in 2008 and 2009, and normative data
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Test Score (max score)
2008
MMSE (30) ACE-R Memory (26) Total (100) RAVLT Immediate Recall – A6 (15) Delayed Recall – 30 min (15) Recognition (15) Total RCFT Copy (36) Delayed Recall – 30 min (36) Doors & People Part A (15) Part B (15) SYD-BAT Naming (30) Comprehension (30) Repetition (30) Semantic Association (30) Boston Naming Total (15)
2009
Normal Mean (SD)
26
25
29.3 (1)
7 62
6 57 N/D
25.5 (0.6) 96.5 (1.7)
2 2 13 29 32 15
12 (1.2) 11.8 (2.5) 14.5 (1) 57.3 (9.1) 35 23.5 N/D
13 9
34.8 (1.5) 23.4 (3.6) 11.5 (1.7) 11.3 (1.7) N/D
7 29 30 23
5 18 27 25
3
2
N/D
Normative data taken from 4 age-matched controls recruited from our patient database. SD, standard deviation of the mean; N/D represents no data due to task not being administered. MMSE, Mini-mental state examination; ACE-R, Addenbrooke’s cognitive examination; RAVLT, Rey auditory verbal learning test; RCFT, Rey complex figure test and recognition trial.
Behavioral task The memory task was an adapted version of the word-stem completion test as described by Schott et al. (2002) previously found this task to be effective in assessing implicit and explicit memory in both healthy participants and amnesic patients (Schott et al., 2006). Briefly, R.W. and an age-matched control were shown a list of 15 high-frequency words (Table 2), on a computer screen and asked to recall (explicitly) the list without delay. Both participants were shown the list until they were able to recall accurately the entire list on two consecutive occasions. At test, 30 three-letter word stems were presented and participants were asked to complete them with a word from the study list, but if they could not, to use the first word that came to mind. Afterwards, they were required to state whether the word they used was part of the study list or not with an old/new response. Critically, of the 30 word stems presented at test, only 15 could be completed with words from the study list. Importantly, R.W.’s comprehension for all words tested was intact. The word stems were selected so that the correct completion could not be
guessed by chance but instead required the implicit retrieval of the encoded information. The order of word stem presentation was pseudo-randomized and 3 test sets (A, B, C) were established (Table 2). Testing occurred immediately following training (A) and after 2- (B), 4- (C), and 8- (A) week delays. Implicit memory was scored as the percentage of correct responses when the study list word was completed but not identified as “old.” Explicit memory was scored as the percentage of correct responses when the study list word was completed and identified as “old.” Therefore, explicit and implicit memory scores were mutually exclusive as the scoring protocol categorizes a correct implicit response as successfully recalling the primed study list word, but not explicitly stating its membership in the study list. RESULTS Voxel-based morphometry Grey matter atrophy patterns of R.W. versus 18 age- and education-matched healthy controls showed greater atrophy for R.W. in left and right
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TU ET AL. TABLE 2 Word study list and word stem test list Word Stem Sets
Word List
(A)
(B)
(C)
BRIDGE
BRI BEA CAP SCO STE BIR CIR DIN BEL FIN MOB PIL OPI REV TAL SMO ENJ FLI WIN SMI OPE MEA LIM SIL FAS ORI SNA VIS GAR BRU
FIN GAR STE MEA ORI ENJ BEA CIR LIM DIN OPE SNA SIL WIN FLI TAL SMO PIL BIR BEL SMI VIS REV OPI FAS CAP BRU BRI SCO MOB
TAL WIN BRI SNA ENJ ORI FIN OPE MEA VIS BRU BEA MOB LIM GAR SCO FLI SMO DIN BEL PIL BIR CAP STE FAS REV OPI SIL SMI CIR
CAPITAL BIRTH CIRCUS BELIEF
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MOBILE REVIEW TALENT ENJOY FLIGHT OPERA SILENCE ORIGIN VISION GARDEN
temporal lobe, as well as left hippocampal and left insula atrophy in comparison to (Figure 1). Atrophy results shown are corrected for FWE rate at p < .05, detailed descriptions of atrophy clusters are reported in Table 3.
Long-term anterograde memory task As evident in Figure 2, R.W. and the control showed similar high levels of performance for explicitly recognition and stem completion at baseline, i.e., immediately after learning the list of words to criterion. After a 2-week delay, R.W. still completed over 70% of word stems correctly and recognized them but after a 4- and 8-week delay none of the word stems were explicitly recognized. By contrast 60 and 40%, respectively, were completed implicitly.
The control subject was able to recognize 90% of the words correctly even after an 8-week delay and showed only minimal need for implicit memory retrieval with only the 4-week delay eliciting approximately 10% correctly completed word stems.
DISCUSSION Our findings show that long-term consolidation of episodic memory in SD is particularly vulnerable after a 2-week delay of encoding new information. More specifically, patient R.W. showed intact recognition of word list items after immediate and a 2-week delay but he could not explicitly recognize any of the words after 4 and 8 weeks post-encoding. By contrast, he still was able to complete a high percentage of word stems even after 4 and 8 weeks, despite not being able to recognize them as having been learnt before. These findings have implications for rehabilitation programs in SD based on word training. There is debate in the literature concerning the best time frame for patients to relearn words and at what time interval these need to be re-activated. In most previous SD case re-learning studies (Dewar et al., 2009; Graham et al., 1999; Jokel et al., 2006; Snowden & Neary, 2002) daily rehearsal of stimuli lists significantly improved patient performance. This approach does not, however, always result in a beneficial effect as the daily repetition of items can cause an increased stress in the patient (Graham et al., 1999). Continued rehearsal also had a negative effect on his state of mind, as it was a constant reminder of his disease progression. Our results suggest unequivocally that SD patients need to reactivate the newly learnt material after a 2-week period to increase the chance of retaining this information. It is not clear, however, if a re-activation of those memories would increase the time these memories are kept, which would be interesting to explore in future studies. Furthermore, our findings suggest that implicit memory techniques in SD might help or even facilitate the retrieval of newly learnt information, which could benefit the patient’s everyday functioning. Indeed, a previous study employing an implicit lexical acquisition task in SD has showed good retention after a 1-week delay (Murray et al., 2007). Such implicit techniques appear therefore beneficial in that patients might be able to utilize
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Figure 1. VBM results showing brain atrophy of R.W. in comparison to age- and education-matched controls (n = 18). Clusters are overlaid on the MNI standard brain (t > 2.09). Colored voxels show regions which were significant in the analyses for p < .05 corrected for FWE rate. [To view this figure in color, please see the online version of this journal]. TABLE 3 Voxel-based morphometry (VBM) results showing regions of significant grey matter intensity decrease for RW in comparison to Controls MNI coordinates Regions RW vs. Controls Inferior temporal cortex, Temporal pole, Hippocampus, Insula Inferior temporal cortex Temporal pole Planum temporal Orbitofrontal cortex
Hemisphere (L/R/B)
X
Y
Z
Number of voxels
T-score
L
−34
−14
−42
2185
0.998
R R R L
28 28 46 −20
4 20 10 26
−48 −38 −16 −22
267 212 76 47
0.998 0.998 0.996 0.992
All results corrected for multiple comparison (FWE) at p < .05.
implicitly learnt information more efficiently than when it is learnt explicitly. On an anatomical level, it is interesting that our patient was able to learn and retain new verbal information over a 2-week period, despite having quite extensive left hippocampal damage. Still, the residual left hippocampal volume as well
as right hippocampus and other related memory structures might have compensated for the left hippocampal atrophy (Maguire, Kumaran, Hassabis, & Kopelman, 2010). Nevertheless, this needs to be further investigated, which might also shed light on competing theories of long-term memory consolidation (Squire & Alvarez, 1995; Winocur,
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Figure 2. Implicit and explicit memory task performance of R.W. and age-matched control immediately (baseline), and 2, 4, and 8 weeks after training. Performance is shown as the percentage of total correct response.
Moscovitch, & Bontempi, 2010), which both state that an intact hippocampus is necessary to retain in the short term. Our results are at odds with this notion as we show that storage of the actual information was only partly affected by the atrophy in the medial temporal lobe, because R.W. was able to implicitly complete a percentage of word stems. In conclusion, the findings indicate that although recent anterograde episodic memory is preserved in SD, the durability of the memory is relatively short. This finding has implications for rehabilitation programs in SD. Original manuscript received 29 June 2011 Revised manuscript accepted 28 March 2012 First published online 11 July 2012
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