Background and Purpose-Functional neuroimaging studies have demonstrated right inferior frontal gyrus (IFG) activation in poststroke aphasia. It remains unclear whether this activation is essential for language performance. We tested this hypothesis in a positron emission tomography (PET) activation study during a semantic task with repetitive transcranial magnetic stimulation (rTMS) on right-handed patients experiencing poststroke aphasia and examined whether rTMS stimulation over the right and left IFG would interfere with language performance. Methods-Eleven patients with left-sided middle cerebral arterial infarction, 50 to 75 years of age, were tested with the Aachen Aphasia Test Battery and underwent 15 O-H 2 O PET activation during a semantic task within 2 weeks after stroke. PET activation images were coregistered to T1-weighted MRIs. Stimulation sites were determined on renderings of head and brain over the maximum activation within left and right IFG. rTMS was performed with 20% maximum output (2.1 T), 10-s train duration, at 4Hz frequency. A positive rTMS effect was defined as an increased reaction time latency or error rate in the semantic task. Results-PET activations of the IFG were observed on the left (3 patients) and bilaterally (8 patients). Right IFG stimulation was positive in 5 patients with right IFG activation, indicating essential language function. In a verbal fluency task, these patients had a lower performance than patients without right-sided TMS effect. Conclusions-In some poststroke aphasics, right IFG activation is essential for residual language function. However, its compensatory potential seems to be less effective than in patients who recover left IFG function. These results suggest a hierarchy in recovery from poststroke aphasia and a (limited) compensatory potential of the nondominant hemisphere.

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Background and Purpose-Recently, a combined repetitive transcranial magnetic stimulation (rTMS) and activation positron emission tomography (PET) study showed essential language function of the right inferior frontal gyrus (IFG) in some right-handed acute poststroke aphasics. We reexamined these patients in the chronic phase to test whether the right IFG remained essential for language performance. Methods-We reexamined 9 male right-handed patients, age 41 to 75 years, with aphasia 8 weeks after left hemispheric stroke. rTMS was performed over the maximum activation within the left and right IFG as defined by 15 [O]water PET to interfere with language function. A positive rTMS effect was defined as increased reaction time latency or error rate in the semantic task relative to no stimulation. Results-PET activations of the IFG were observed on the left (2 patients) and bilaterally (7). During rTMS interference over the left IFG, all patients had positive TMS effects, indicating that the left IFG remained essential. Stimulation over the right IFG yielded positive rTMS effects in 2 patients with persisting right IFG activation. Two patients with positive rTMS effects over the right side in the initial study did not show these effects at follow-up. Language performance improved in all patients. Conclusions-Successful regeneration from poststroke aphasia seems to depend more on the integration of available language-related brain regions than on recruiting new brain regions during the rehabilitation process. Restoration of the left hemisphere network seems to be more effective, although in some cases, right hemisphere areas are integrated successfully.

Neuroimaging studies of language networks in patients with brain lesions of the left language-dominant hemisphere have shown activation in the right inferior frontal gyrus (IFG). We tested the functional relevance of right IFG activation using neuroimaging-guided repetitive transcranial magnetic stimulation (rTMS) to disturb language function over bilateral IFG in right-handed patients with brain tumors and controls. All subjects were susceptible to TMS over the left IFG. In patients, this susceptibility correlated with left-sided the degree of language lateralization to the left. Those patients with lowest dominance were also susceptible to right-sided TMS proving relevant language function of the right IFG. Neurol 2005;57:128 -131 Activations of the right hemisphere homolog structures of classic language areas have been described repeatedly in neuroimaging studies of patients with focal brain lesions. [1][2][3][4] In the largest activation study to date in patients with brain tumors of the left hemisphere, 5 right inferior frontal activations were reported in 60% of patients. Although there is no question that language paradigms can induce task-related activity in right-sided homologous language areas, there is considerable debate about the functional relevance of this contralateral activity. 2-4,6 -8 In patients with brain tumors, no significant difference in language performance between patients with and without right inferior frontal gyrus (IFG) activation could be detected. Ann5 Because neuroimaging studies can only demonstrate which brain regions are involved but can never prove whether a brain region is essential for a task, 9 we combined a positron emission tomography (PET) activation study during verb generation in right-handed patients with suspected gliomas of the left hemisphere and normal controls with repetitive transcranial magnetic stimulation (rTMS) to interfere with left and right IFG activation. We hypothesized that if the right IFG activation in patients was essential for language function, rTMS should induce longer verb-generation latencies or verbgeneration errors during stimulation not only over the left but also over the right IFG. Subjects and MethodsWe examined 5 male volunteers without previous history of neurological or psychiatric disease and 14 patients with known or suspected gliomas (Table).At the time of the study, all patients were free of seizures for at least 2 weeks under antiepileptic medication, with plasma drug levels within the recommended therapeutic range and without epileptic activity in surface electroencephalogram. At the time TMS was performed, none of the patients had signs of increased intracranial pressure. Patients were formally tested for symptoms of aphasia when entering the study using the Aachen Aphasia Test Battery.10 Written informed consent was obtained from all patients and normal subjects, and the study was approved by the local ethics committee.PET scans were performed on a CTI/Siemens (Knoxville, TN) ECAT EXACT HR scanner using an overt verbgener...