The iming of acivaion in synesthesia: a magnetoencephalography study D Brang, EM Hubbard, S Coulson, M Huang & VS Ramachandran University of CA, San Diego dbrang@ucsd.edu Introducion In synesthesia, simulaion of one processing stream (e.g. hearing) elicits concur- rent experiences in a second, unsimulated stream (e.g. visual colors). For ex- ample, to synesthete JC the number 2 always appears green (2), irrespecive of its actual color. Although psychophysical experiments have demonstrated the reality of synestheic experiences, the neural mechanisms underlying this phenomenon remain a mater of contenion. Two main theories have been proposed to account for synestheic experiences. The cross-acivaion model suggests that the experience of colored leters in syn- esthesia reflects hyperconnecivity between posterior fusiform areas involved in grapheme processing and adjacent color area V4¹. In contrast, the disinhibited feedback theory proposes a disinhibiion of pre-exising, 'latent' feedback con- necions among areas in the hierarchy of visual processing²; the two models thus make different predicions about the ime course of neural acivity in color area V4 (early vs. late). In order to resolve this debate, we used magnetoencephalog- raphy (MEG) to test whether V4 and grapheme regions acivate nearly simultane- ously, as predicted by the cross-acivaion theory, or whether V4 acivaion occurs only ater the iniial stages of grapheme processing, as predicted by the disinhib- ited feedback theory. Methods Discussion References 1. Ramachandran, V.S. & Hubbard, E.M. (2001). Proc Royal Soc Lond B 268, 979-983. 2. Grossenbacher, P.G. & Lovelace, C.T. (2001). Trends in Cogniive Sciences 5, 36-41. 3. Huang, M., Dale, A.M., Song, T., Halgren, E., Harrington, D.L., Podgorny, I., Canive, J.M., Lewis, S., Lee, R.R. (2006). NeuroImage. 31(3):1025-1037 4. Hubbard, E.M., Arman, A.C., Ramachandran, V.S. & Boynton, G.M. (2005). Neuron 45, 975-985. 5. Peseni, M., Thioux, M., Seron, X., and De Volder, A. (2000). J. Cogn. Neurosci. 12, 461–479. 6. Rouw, R. & Scholte, H.S. (2007). Nature Neuroscience 10, 792-797. 4 grapheme-color synesthetes (projectors) and 4 age- and handedness-matched controls. Data collected with a whole-head Elekta Neuromag 306-channel system in an enhanced muli-layer magneically shielded room. Data analyzed using an L1-norm (VESTAL) approach³. Timing of acivity within V4 and Grapheme ROIs Grapheme Task V4 Reinotopy Task In order to funcionally localize V4 within each subject, square blocks were presented randomly in one of four visual quadrants, in order to elicit reinotopy in visual area V4; while idenical simuli were presented in each quadrant, blocks are displayed here in different colors for presentaion. Simuli and Procedure Red blocks subtending 3.1 degrees of the visual field 200 trials per visual quadrant 200ms presentaion with ISI ranging 200-248ms V4 localized within posterior temporal lobe areas showing reinotopy V4 Reinotopy Inflated Ventral View Ventral View MEG acivaion between 120-200ms 0 0.02 0.04 0.06 0.08 0.1 0.12 0.14 10 40 70 100 130 160 190 220 250 280 310 340 370 400 nanoAmperes x mm^2 Time (ms) A c Upright vs. italic detecion task 2.2° tall white leters, numbers, and non-linguisic characters⁵ Approximately 100 targets per condiion 500ms presentaion with 1000ms ISI Using methods similar to those of Hubbard and colleagues⁴, synesthetes and con- trols were presented with graphemes and non-graphemic simuli in a randomly intermixed presentaion format. Grapheme ROIs created from a separate run. Whereas controls show only significant acivaion within grapheme regions in the posterior temporal lobe (light blue), synesthetes showed significant co-acivaion of both grapheme and V4 color ROIs (dark blue). Significant acivaions from the Grapheme Task localized to the posterior temporal lobe. Data is overlaid on sub- jects’ inflated corical reconstrucions, viewed ventrally. Grapheme ROI V4 ROI Let hemisphere Right hemisphere Grapheme ROI V4 ROI Let hemisphere Right hemisphere Average acivity in synesthetes’ and controls’ V4 ROIs Average acivity in synesthetes’ and controls’ grapheme ROIs -0.005 0 0.005 0.01 0.015 0.02 0.025 0.03 0.035 0.04 10 40 70 100 130 160 190 220 250 280 310 340 370 400 nanoAmperes x mm^2 Time (ms) 10 40 70 100 130 160 190 220 250 280 310 340 370 400 Synesthetes Controls -0.04 -0.02 0 0.02 0.04 0.06 0.08 0.1 0.12 0.14 10 40 70 100 130 160 190 220 250 280 310 340 370 400 nanoAmperes x mm^2 Time (ms) 10 40 70 100 130 160 190 220 250 280 310 340 370 400 Achromaic leters and numbers evoked significantly more acivity in synesthetes compared to controls between 141-160ms in V4 t(6) = 3.09, p<.05, but not in the Grapheme Area t(6) = 0.06, p=.95. Color area V4 Grapheme ROI Synesthetes Controls Acivity in synesthetes’ Grapheme and V4 ROIs Acivity in synesthetes’ grapheme ROI reached significance between 135 and 139ms t(3) = 3.14, p=.05, with acivity in the V4 ROI reaching signifi- cance between 140 and 144ms t(3) = 3.61, p<.05, suggesing V4 engagement occurs near simultaneously with processing of graphemes. These data provide the strongest evidence to date that grapheme-color syn- esthesia involves direct communicaion between V4 and grapheme process- ing areas in the posterior temporal lobe (PTGA). The near simultaneous aci- vaion of color area V4 and PTGA between 135-145ms argues strongly against the corical disinhibited feedback model of synesthesia which pre- dicts acivaion of V4 only ater substanial processing has occurred. The similar onset latencies we observed for increased acivity in synesthetes' grapheme (135-139ms) and color (140-144ms) ROIs suggest the rapid ex- change of informaion between these areas, in keeping with the report of in- creased connecivity between V4 and the posterior fusiform in synesthetes⁶. Italic leter Italic non-linguisic Control subject Synestheic subject