1. Dissociating Semantic and Phonological Processing in the Left Inferior Frontal Gyrus PM Gough, AC Nobre, JT Devlin* Dept. of Experimental Psychology, Uni. Of Oxford, U.K. *Oxford Centre for Functional Magnetic Resonance Imaging of the brain (FMRIB), U.K. Summary: The left inferior frontal gyrus has been implicated in the processing of both semantics and phonology. There is evidence from separate single dissociation studies to suggest that the anterior portion of this region is more important for the processing of semantics than phonology, and that the posterior portion is more important for the processing of phonology. The present study sought to demonstrate a double dissociation of processing semantics and phonology in the anterior (BA 45/47) and posterior (BA 44/6) inferior frontal gyrus using repetitive transcranial magnetic stimulation to interfere temporarily with information processing while participants completed tasks involving semantic and phonological judgements. Semantic judgements involved deciding whether or not two words, one appearing below and one above a fixation point simultaneously, meant the same thing and could be interchanged in a sentence without changing its meaning i.e. were synonyms. Phonological judgements involved presentation of two words as for the semantic task but subjects were required to decide whether or not the words sounded exactly the same i.e. were homophones. Participants also completed a control task where they decided whether or not two letter strings matched. Analysis of reaction times to items in the two tasks with and without TMS at the two sites, indicated an anterior specialisation for processing semantics and a posterior specialisation for processing phonology. Localisation of sites for stimulation: Anatomical Localisation Four of the subjects had structural MRI scans. Frameless stereotaxy was used to position the the TMS coil on the scalp. A Polaris infra-red camera (Northern Digital, Ontario, Canada) tracked the subject’s head while BrainSight software (Rogue Research, Montreal, Canada) registered the head to the MRI scan. The TMS coil was placed at the approximate site of stimulation and its position adjusted until the estimated direction of maximum field intensity intersected the target stimulation site on the MRI scan. This scalp location then was then used as the initial testing site. For subjects without an MRI scan, the initial site was identified using average scalp measurements. The posterior stimulation site was 4.5cm posterior and 6cm superior to the canther-tragus (CT) line while the anterior stimulation site was 2.5cm posterior and 3cm superior. These values were derived from the structural MRI scans of nine volunteers (3 females, 6 males) who did not participate in the main experiment. For these subjects, BrainSight was used to locate the corresponding sites on the scalp and the positions were marked and measured relative to the CT line. Functional Localisation Testing began by using “localiser” tasks to functionally identify the posterior and anterior stimulation sites. For the posterior site, participants decided whether two simultaneously presented words rhymed (e.g. vein – pane) and indicated their response with a key press. For the anterior site, this involved deciding whether the words came from the same category (e.g. potato – turnip). In each case, 30 pairs were presented, ten with TMS (3 pulses at 10Hz delivered 100msec post-stimulus onset) and twenty without TMS. When TMS facilitated responses by shortening the median reaction time (RT) relative to non-TMS trials, the coil was moved approximately 1cm along the scalp and another site was tested. If TMS increased response latencies, then the same location was tested again to verify the effect. When TMS led to a reproducible increase in RTs, that site was marked, measured, and used for the main experiment. 1000ms 500ms 1700ms + knows + nose Tms (40% of trials) 100, 200, 300ms. In the main experiment, all trials began with a 1 sec fixation cross followed by the simultaneous presentation of two words, one above and below the cross, for 500msec. The screen cleared for 1700msec during which time the participant responded with a key press. Response times and accuracies were measured. The experiment consisted of three conditions: the phonological and semantic test conditions and a visual control condition, each containing 50 trials. In the phonological condition the subject decided whether the pair of words were homophones and in the semantic condition they decided whether the pair of words were synonyms. The control task required subjects to decide whether a pair of consonant letter strings matched. Main Tasks Localisation Results Main Task Results Conclusions POp POr 1000ms 500ms 1700ms + vein + pane Tms (1/3 of trials) 100, 200, 300ms. The effects of opercular (POp) and orbital (POr) stimulation on mean reaction times when making A) homophone judgements, B) synonym judgements, and C) visual matching judgements. Trials with TMS are shown in grey while those without TMS are shown in white. Error bars indicate the standard error of the mean. Reaction times were analysed with a 2  2  2 repeated measures analysis of variance (ANOVA). The independent factors were Site (posterior, anterior), Task (phonological, semantic), and Stimulation (yes, no). There was a significant main effect of Task (F1,8=7.3, p<0.001) indicating that on average, participants responded more quickly in the phonological than semantic task (mean RTs = 837 vs. 882msec, respectively). In addition, there was a significant three-way interaction (F1,8=5.5, p<0.05) indicating that posterior stimulation interfered with performance on the phonological, but not semantic, task while the opposite pattern was observed for stimulation of the anterior site. No other main effects or interactions were significant. In the control task, RTs were not significantly affected by stimulation at either location. Subjectpop Xpop YpopZpor Xpor Ypor Z 1-50148-5034-8 2-521812-5240-8 3-501012-5030-6 4-54180-5434-6 Mean-51.5158-51. 534.5-7 Individual and mean standard co-ordinates for pars opercularis (pop) and pars orbitalis (por) for the 4 subjects with MRI scans. The sites are shown on the mean of the 4 standardised brains. Mean RTs for the localiser tasks at pars opercularis and pars orbitalis for the test sites and adjacent sites. TMS trials are shown in grey, and non-TMS trials in white. The use of TMS has allowed us to demonstrate that regions which the imaging literature indicates are involved in phonological and semantic processing, are necessary for these processes. Results from the functional localisation procedure indicate that the regions important for the two types of processing are quite specific as adjacent sites showed the opposite pattern of results from the final test sites. The results show a clear double dissociation for the processing of semantics and phonology in anterior and posterior inferior frontal gyrus.