Language improvements after TMS plus modified CILT: Pilot, open-protocol study with two, chronic nonfluent aphasia cases

1.1. Transcranial magnetic stimulation Transcranial magnetic stimulation (TMS) has been applied to promote poststroke recovery in the domains of 1) motor deficits (Fregni et al., 2006); 2) visuospatial neglect following right hemisphere (RH) stroke (Brighina et al., 2003; Koch et al., 2008); and 3) aphasia following left hemisphere (LH) stroke (Barwood et al., 2010; Hamilton et al., 2010; Martin et al., 2009a; Medina et al., 2012; Naeser et al., 2010a, 2005a, 2005b; Turkeltaub et al., 2012; Weiduschat et al., 2011). One principle supporting these improvements poststroke is that TMS may be used to modulate abnormal interhemispheric inhibition in chronic stroke, where increased excitability in parts of the undamaged hemisphere is present due to release of inhibition from the damaged hemisphere (Thiel et al., 2006). Slow, 1Hz repetitive TMS (rTMS) may be used to suppress the hyper-excitability of parts of the undamaged hemisphere in patients who have suffered a stroke, in turn promoting better modulation of both hemispheres. In patients with aphasia due to stroke, better modulation has been observed to promote improved language behavior including naming and phrase length at 2 months or longer, following suppression of one specific, target area (1 cm square) in the RH, usually the R pars triangular is (PTr) (Barwood et al., 2010; Hamilton et al., 2010; Medina et al., 2012; Naeser et al., 2010a, 2005a, 2005b; Turkeltaub et al., 2012; Weiduschat et al., 2011). Functional MRI scans during overt naming of pictures in a patient with chronic, nonfluent aphasia obtained pre- and post- a two-week series of TMS treatments to suppress the R PTr have shown improved naming to be associated with increased activation in parts of the LH, lasting up to 4 years post- TMS (Martin et al., 2009a). Weiduschat et al. (2011) used activation positron emission tomography (PET) scans pre- and post- a two-week series of rTMS treatments (real rTMS to the R PTr versus control-real rTMS to the vertex of the head) plus 45 minutes of individualized speech therapy in a heterogeneous group of patients with subacute aphasia (<4 months poststroke onset). In that study, significant improvement in the overall Aachen Aphasia Test (AAT) score and in the subtest of naming was observed only in the real rTMS group where 1Hz rTMS was used to suppress the R PTr. There was no significant improvement in the overall AAT score or naming in the control rTMS group. In addition, those patients who received real rTMS to suppress the R PTr no longer retained an increased right-laterality index for increased activation for the inferior frontal gyrus/Broca’s area (Weiduschat et al., 2011). These results suggest that rTMS to suppress RPTr, combined with speech therapy can prevent retention of RH lateralization in patients with subacute aphasia; this may in turn, promote better recovery. A subsequent study by this group (with a larger number of patients) replicated these findings (Thiel et al., 2013). Cotelli et al. (2011) has applied high frequency rTMS to the L dorsolateral prefrontal cortex, followed immediately by 25 minutes of speech therapy (anomia treatment), where improved object naming was observed. Long-term TMS effects are believed to engage mechanisms of neural plasticity, thus likely rendering this technique especially suitable for improving poststroke behavior when combined with appropriate behavioral intervention (Rossi and Rossini, 2004; Talelli and Rothwell, 2006).