F048 Semantic processing deficits in manifest Huntington’s disease

<h3>Background</h3> In Huntington’s disease (HD), language disturbances have traditionally focused on motor, syntactic and speech organization defects, but little is known about semantic processing integrity. We aimed to explore semantic processing in manifest HD by means of neurophysiological indexes and its association with other parameters derived from language assessment. <h3>Methods</h3> We recruited a sample of n=31 HD and n=21 controls. We designed a high congruent (HC) vs high incongruent (HI) final sentence task performed during EEG acquisition aimed to elicit the semantic-related N400. In parallel, an in-depth language assessment was also done. <h3>Results</h3> A significant effect was found for the mean amplitude of the N400 between HC and HI [F(1,51) = 17.139; p&lt;0.0001] consistent with an increased negative deflection around frontal-central sites in HI words. Repeated measures ANOVA showed a main interaction between the factors ‘group’ (controls vs HD) and ‘condition’ (HC vs HI) [F(1,50)=3.7; p&lt;0.05], driven by a dramatic reduction of the N400 in HD [t(52)=2.206; p=0.032], and a significantly increased latency (control=410ms vs HD=547ms; p&lt;0.0001). Regression analysis showed significant associations between the amplitude of the N400 and measures of semantic association (r=-0.444; p=0.001), fluency (r=-0.490; &lt;0.0001), speech production (r=-0.402; p=0.003) and comprehension (r=-0.281; p=0.04). Increased latency was associated with the same components and with reading abilities (r=-0.402; p=0.002), phonology (r=-0.454; p=0.001) and syntax (r=-0.580; p&lt;0.0001) figure 1. <h3>Conclusion</h3> Semantic processing is compromised in manifest HD. The N400 is dramatically disrupted in amplitude and delayed latency, which in turns translates into several linguistic deficits in speech, comprehension, phonology and syntax.