Using transcranial magnetic stimulation of the undamaged brain to identify lesion sites that predict language outcome...

Transcranial magnetic stimulation focused on either the left anterior supramarginal gyrus or opercular part of the left inferior frontal gyrus has been reported to transiently impair the ability to perform phonological more than semantic tasks. Here we tested whether phonological processing abilities were also impaired following lesions to these regions in right-handed, English speaking adults, who were investigated at least 1 year after a left-hemisphere stroke. When our regions of interest were limited to 0.5 cm3 of grey matter centred around sites that had been identified with transcranial magnetic stimulation-based functional localization, phonological impairments were observed in 74% (40/54) of patients with damage to the regions and 21% (21/100) of patients sparing these regions. This classification accuracy was better than that observed when using regions of interest centred on activation sites in previous functional magnetic resonance imaging studies of phonological processing, or transcranial magnetic stimulation sites that did not use functional localization. New regions of interest were generated by redefining the borders of each of the transcranial magnetic stimulation sites to include areas that were consistently damaged in the patients with phonological impairments. This increased the incidence of phonological impairments in the presence of damage to 85% (46/54) and also reduced the incidence of phonological impairments in the absence of damage to 15% (15/100). The difference in phonological processing abilities between those with and without damage to these 'transcranial magnetic stimulation-guided' regions remained highly significant even after controlling for the effect of lesion size. The classification accuracy of the transcranial magnetic stimulation-guided regions was validated in a second sample of 108 patients and found to be better than that for (i) functional magnetic resonance imaging-guided regions; (ii) a region identified from an unguided lesion overlap map; and (iii) a region identified from voxel-based lesion-symptom mapping. Finally, consistent with prior findings from functional imaging and transcranial magnetic stimulation in healthy participants, we show how damage to our transcranial magnetic stimulation-guided regions affected performance on phonologically more than semantically demanding tasks. The observation that phonological processing abilities were impaired years after the stroke, suggests that other brain regions were not able to fully compensate for the contribution that the transcranial magnetic stimulation-guided regions make to language tasks. More generally, our novel transcranial magnetic stimulation-guided lesion-deficit mapping approach shows how non-invasive stimulation of the healthy brain can be used to guide the identification of regions where brain damage is likely to cause persistent behavioural effects.