New Face-Name Paradigm for Patients with Mild Alzheimer’s Disease Lab Meeting 7th March 2007 Jackie O’Brien & Maija Pihlajamäki

Summary of the new paradigm SCAN: Encoding Repeated x 3 Recognition with Confidence Rating POSTSCAN: Cued Recall

Subjects Older Controls (OC) Subjects with Mild Cognitive Impairment (MCI) Patients with Alzheimer’s disease (AD) Use in clinical trials, for example Therefore, the new paradigm should also be feasible to more impaired AD patients as their disease may have progressed during the time between baseline and follow-up examinations.

Objectives: Increase accuracy for ADs Look at effects of repetitive encoding e.g., Rand-Giovanetti et al. (2006) Look at MTL and posterior cortical activation during recognition

Background I: Initial Encoding QUESTION: Whether the MTL activation and posterior cortical deactivation are greater during initial encoding of novel associations which are later remembered vs forgotten? SOME RELEVANT FINDINGS IN PREVIOUS STUDIES: AD patients, compared to OC, demonstrated hippocampal hypoactivation during encoding of FN pairs that were later correctly recognized versus incorrectly recognized pairs. Pariente J et al. Ann Neurol 2005; 58: 870-9. Elderly controls and AD patients, no MCI; fMRI deactivations not reported. Young adults demonstrated greater deactivation in posterior cortical regions during successful compared to failed encoding, whereas older adults did not demonstrate a differential pattern of deactivation. The failure of deactivation was most evident in older adults who performed poorly on the memory task. Miller et al., submitted. Young and elderly controls. SlowER task is challenging for AD patients. The balance of MTL activation and posterior cortical deactivation during successful vs failed initial encoding in MCI and AD remains to be investigated.

Backgrounds II: Repetition Suppression QUESTION: Whether suppression of the MTL activation and posterior cortical deactivation responses to repeated encoding is stronger for novel associations which are later remembered vs forgotten? SOME RELEVANT FINDINGS IN PREVIOUS STUDIES: Reduced MTL activity through repetition suppression is correlated with stronger recognition of items. Gonsalves BD et al. Neuron 2005; 47: 751-61. Young subjects; fMRI deactivations not reported. Hippocampus was activated during the first encoding trials of FN pairs that were subsequently remembered correctly, but there was no hippocampal response during the second and third encoding trials. Rand-Giovannetti E et al. Neurobiol Aging 2006; 27: 173-82. Young and elderly controls ; fMRI deactivations not reported. The suppression of MTL activation, and posterior cortical deactivation responses in particular, in MCI and AD remains to be investigated.

Backgrounds III: Recognition QUESTION: Whether the MTL and posterior cortical activation is greater during correct recognition with high confidence than incorrect recognition? SOME RELEVANT FINDINGS IN PREVIOUS STUDIES: The comparison of confidence assessment to recognition showed greater relative activation during confidence assessment in posterior cortical regions. Chua EF et al. Neuroimage 2006; 29: 1150-60. Young subjects. MCI participants showed posterior cortical activation during self-assessment, but not during episodic retrieval. This result suggests that the posterior cortices show functional degradation during episodic retrieval; however, their role in retrieval and evaluation of semantic autobiographical information is more well-preserved. Ries ML et al. Neuroimage 2006; 29: 485-92. Elderly controls and MCI subjects. Episodic retrieval confidence not assessed. The MTL and posterior cortical correlates of recognition with high confidence in OC, MCI and AD remain to be investigated.

Overview of the Runs 1) Encoding 1, EN1 (20 faces) 3) Forced-choice Recognition with Confidence Rating, RC12 (40 faces, from EN1 & EN2) 4) Encoding 3, EN3 (20 faces) 5) Encoding 4, EN4 (20 faces) 6) Forced-choice Recognition with Confidence Rating, RC34 (40 faces, from EN3 & EN4)

Encoding: 20 faces per run 4 encoding runs = 80 faces total stimulus duration = 2.75s see each face 3x

Encoding Order 1) ”Mini-blocks” of four FN-pairs (pairs 1-4, 5-8, etc) 2) Two consecutive presentations of each mini-block (A1A2, B1B2,… 3) Pseudorandom order of FN-pairs within the mini-blocks 4) Third presentation of the mini-blocks (A3, B3, …) at the end of each encoding run as a reminder For faces 1-20: 1 2 3 4 2 1 4 3 5 6 7 8 6 8 5 7 . . . . . . . . . . . . . 17 18 19 20 19 20 17 18 1 2 3 4 5 6 7 8 . . . . . A1 A2 B1 B2 … C1C2 D1D2 A3 B3 …C3 D3

Forced-choice Recognition 2 choice forced recognition, followed by confidence rating Includes faces from two previous encoding runs (40 faces)

Post Scan Give phonemic cue: “starts with an ‘A’. ” Outside of scanner self paced? Time limit? Format of slides?

Encoding alternatives Three consecutive repetitions For faces 1-20: 1 2 3 4 4 2 1 3 2 4 3 1 5 6 7 8 7 5 6 8 6 8 5 7 . . . . . . . . . . 17 18 19 20 18 19 20 17 20 18 19 17 A1A2 A3 B1B2 B3 ……. C1C2 C3 D1D2 D3

First Idea: Chunked: *Repeat 5 times so subject learns 20 faces “remember” “learn” 4 faces 4 faces 4 faces *Repeat 5 times so subject learns 20 faces

Sequential: 1 face 1 face 1 face *repeat 20 times Problem: lots of task switching

Retrieval Version B: 3 choice forced recognition 1 correct name, one familiar name, one new name Includes faces from two previous encoding runs (40)