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Poster D29, Thursday, November 9, 6:15 – 7:30 pm, Harborview and Loch Raven Ballrooms

Implicit verbal structure learning in Developmental Verbal/Orofacial Dyspraxia due to FOXP2 mutation: An fMRI study

Georgios P.D. Argyropoulos1, Mortimer Mishkin2, Faraneh Vargha-Khadem1,3;1UCL Great Ormond Street Institute of Child Health, London, UK, 2National Institutes of Health, Bethesda, Maryland, USA, 3Great Ormond Street Hospital for Children National Health Foundation Trust, London, UK

Introduction: A dominantly inherited speech and language disorder in half the members of the multi-generational ‘KE family’ (Hurst et al., 1990; Vargha-Khadem et al., 1995) is linked to a mutation in the FOXP2 gene (Lai et al., 2001). The neural phenotype of this mutation is primarily characterized by a pronounced volume reduction in the caudate nucleus bilaterally (Vargha-Khadem et al., 1998). Since both speech and grammar involve the implicit acquisition of structured sequences, the developmental verbal/orofacial dyspraxia in the affected KE (aKE) members may extend to impaired grammar learning (Vargha-Khadem et al., 2005). An ideal paradigm to study the implicit acquisition of combinatorial rules is provided by artificial grammar learning (AGL; Reber, 1967). After implicit training with outputs of a grammar, neurotypical adults (CTRs) accurately classify novel outputs according to their well-formedness (viz Grammaticality), without awareness of rule structure. This is consistent with fMRI studies associating Grammaticality with caudate activation (Lieberman et al., 2004). To determine whether the structurally abnormal cortico-striatal circuitry of aKE members is associated with deficits in implicit acquisition of abstract combinatorial rules, we conducted an fMRI study of AGL. We predicted that aKE members would show behavioural/hemodynamic abnormalities related to judgements of Grammaticality. Methods: 20 CTRs and 4 aKE members were implicitly trained on an auditory-verbal version of a finite-state grammar (Lieberman et al., 2004), and made grammatical classifications on new words during (rapid event-related) fMRI. Grammaticality of words and their Similarity to exemplars of the training phase were manipulated in an orthogonal fashion. Results: Behaviour: CTRs performed above chance (t=3.79, p=.001), endorsing grammatical more frequently than ungrammatical words (t=3.65, p=.002), and low-similarity items more frequently than high-similarity ones (t=3.03, p=.007); aKE members performed at chance-level (t=-.9), worse than CTRs (t=2.20, p=.039), showing reduced Grammaticality (Grammaticality*Group: F=4.62, p=.043) but not Similarity (Similarity*Group: F<1) effects on endorsement rates. fMRI: For CTRs, Grammaticality-related activations were found in superior occipital gyri and dorsal striatum; Similarity-related activations were seen in the right supramarginal gyrus and left posterior HVIIa Crus I/II; aKE members showed hypoactivations for Grammaticality-related effects in right superior temporal gyrus, left supplementary motor area, bilateral central operculum/anterior insula, left paravermal HVI/HVIIa Crus I and HVIII; no functional abnormalities were observed for Similarity effects. Activation clusters survived whole-brain FWE-correction (p < .05) at cluster size / voxel peak level over individual voxel threshold of p < .001. Conclusion: aKE members show compromised implicit AGL and associated hypoactivation in structures fundamental to speech processing. Our results support the proposal that the cortico-striatal structural/functional abnormalities of the aKE members give rise to a series of impairments that stem from, but go beyond the acquisition of articulate speech and impede the implicit acquisition of verbal structure (Vargha-Khadem et al., 2005). The combined behavioural-neural phenotype of aKE members is consistent with deficits in the cortico-striatal habit system (Mishkin & Petri, 1984).

Topic Area: Language Disorders

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