Functional Reorganization of Right Prefrontal Cortex Underlies Sustained Naming Improvements in Chronic Aphasia via Repetitive Transcranial Magnetic Stimulation

Abstract

Background and objective: While noninvasive brain stimulation techniques show promise for language recovery after stroke, the underlying mechanisms remain unclear. We applied inhibitory repetitive transcranial magnetic stimulation (rTMS) to regions of interest in the right inferior frontal gyrus of patients with chronic poststroke aphasia and examined changes in picture naming performance and cortical activation.

Methods: Nine patients received 10 days of 1-Hz rTMS (Monday through Friday for 2 weeks). We assessed naming performance before and immediately after stimulation on the first and last days of rTMS therapy, and then again at 2 and 6 months post-rTMS. A subset of six of these patients underwent functional magnetic resonance imaging pre-rTMS (baseline) and at 2 and 6 months post-rTMS.

Results: Naming accuracy increased from pre- to post-rTMS on both the first and last days of treatment. We also found naming improvements long after rTMS, with the greatest improvements at 6 months post-rTMS. Long-lasting effects were associated with a posterior shift in the recruitment of the right inferior frontal gyrus: from the more anterior Brodmann area 45 to the more posterior Brodmann areas 6, 44, and 46. The number of left hemispheric regions recruited for naming also increased.

Conclusions: This study found that rTMS to the right hemisphere Broca area homologue confers long-lasting improvements in picture naming performance. The mechanism involves dynamic bilateral neural network changes in language processing, which take place within the right prefrontal cortex and the left hemisphere more generally.

Clinical trial registration: ClinicalTrials.gov (Identifier NCT00608582).

Figure 1

Structural T1-weighted axial slices depicting lesion location and size in the six patients who participated in the fMRI portion of the study.

Figure 2

Schematic example of the fMRI study using a block design.

Figure 3

Behavioral results showing the immediate effects of rTMS therapy. A: Mean percent correct (collapsed across repeated and novel items) and associated within-subjects 95% confidence intervals for pre-rTMS and post-rTMS performance on the first and last days of treatment. B: Mean stimulation effect (difference between post-rTMS and pre-rTMS mean naming accuracy) and associated within-subjects 95% confidence intervals for repeated and novel items on the first and last days of treatment.

Figure 4

Behavioral results showing long-term effects of rTMS therapy. A: Boston Diagnostic Aphasia Examination naming performance and associated within-subjects 95% confidence intervals at baseline and 2 and 6 months post-rTMS for all patients (n = 9). B: Results for the subset of patients who participated in the fMRI portion of the study (n = 6).

Figure 5

Neuroimaging results. Regions significantly more active for picture naming than for pattern viewing at baseline (8 images on the left) and 6 months post-rTMS (8 images on the right) found in the group analyses of the subset of patients who participated in the fMRI portion of the study (n = 6). Color maps correspond to the t values reflecting the picture naming versus pattern viewing contrast at each time point after thresholding at a voxel-wise level of P < 0.001 (uncorrected) and cluster level of P < 0.05 (family-wise error). Brighter colors represent higher t values.