Perturbation of the left inferior frontal gyrus triggers adaptive plasticity in the right homologous area during speech production

Abstract

The role of the right hemisphere in aphasia recovery after left hemisphere damage remains unclear. Increased activation of the right hemisphere has been observed after left hemisphere damage. This may simply reflect a release from transcallosal inhibition that does not contribute to language functions. Alternatively, the right hemisphere may actively contribute to language functions by supporting disrupted processing in the left hemisphere via interhemispheric connections. To test this hypothesis, we applied off-line continuous theta burst stimulation (cTBS) over the left inferior frontal gyrus (IFG) in healthy volunteers, then used functional MRI to investigate acute changes in effective connectivity between the left and right hemispheres during repetition of auditory and visual words and pseudowords. In separate sessions, we applied cTBS over the left anterior IFG (aIFG) or posterior IFG (pIFG) to test the anatomic specificity of the effects of cTBS on speech processing. Compared with cTBS over the aIFG, cTBS over the pIFG suppressed activity in the left pIFG and increased activity in the right pIFG during pseudoword vs. word repetition in both modalities. This effect was associated with a stronger facilitatory drive from the right pIFG to the left pIFG during pseudoword repetition. Critically, response became faster as the influence of the right pIFG on left pIFG increased, indicating that homologous areas in the right hemisphere actively contribute to language function after a focal left hemisphere lesion. Our findings lend further support to the notion that increased activation of homologous right hemisphere areas supports aphasia recovery after left hemisphere damage.transcranial magnetic stimulation | dynamic causal modeling | virtual lesion | Broca's area N umerous functional imaging studies have reported increased language-related activation of the right inferior frontal gyrus (IFG) in aphasic patients with left hemisphere damage (1-3). However, it is still a matter of debate whether the temporary recruitment of homologous right hemisphere areas after left hemisphere stroke is essential for language performance (i.e., adaptive plasticity) (2-4) or represents "maladaptive" overactivation resulting from interhemispheric disinhibition after left hemisphere infarction (5-7).In the present study, we investigated the adaptive short-term plasticity that supports speech production after disruption to left frontal language areas. We induced neural activity related to phonetic encoding by comparing reading and auditory repetition of pseudowords and familiar words. We expected to see common effects in both visual and auditory modalities at the level of phonetic encoding, but not at the sensory input level (8). We applied transient virtual lesions in healthy volunteers to test whether an up-regulation of right hemisphere homologous language regions after a focal perturbation of left hemisphere language areas reflects reduced transcallosal inhibition from the left hemisphere to the right hemisphere or an active righ...

Modeling the effects of noninvasive transcranial brain stimulation at the biophysical, network, and cognitive Level

“…Moreover, the relationship between rTMS-induced changes in effective connectivity and individual variations in task performance that was observed in both of our previous DCM studies (i.e., Hartwigsen et al, 2013;Herz et al, 2014a) suggests that the respective connectivity changes might mediate the NTBS-induced changes on the behavioral level.…”

“…A number of previous studies combined offline rTMS with subsequent fMRI or PET to map TMS-induced changes in the task-related effective connectivity between different network nodes for cognitive or motor functions (Boudrias et al, 2012;Hartwigsen et al, 2013;Lee et al, 2003;Megumi et al, 2015;Moisa et al, 2012;Ward et al, 2010). These studies will be discussed in detail below.…”

“…This might involve changes in effective interhemispheric corticocortical (Hartwigsen et al, 2013) or intrahemispheric cortico-subcortical connectivity (Herz et al, 2014a).…”

“…For instance, Hartwigsen et al (2013) used DCM to show that a transient perturbation caused by offline rTMS can induce changes in the effective connectivity between homologous speech regions in the healthy language system (Fig. 3).…”

Dominant hemisphere functional networks compensate for structural connectivity loss to preserve phonological retrieval with aging

“…Also, left hemisphere virtual lesions trigger adaptive plasticity in the right hemisphere homologs (Hartwigsen et al. 2013). Our findings suggest that left hemispheric connectivity drives preserved language function with age.…”