Elsevier

Cortex

Volume 48, Issue 9, October 2012, Pages 1179-1186
Cortex

Research report
The right hemisphere is not unitary in its role in aphasia recovery

https://doi.org/10.1016/j.cortex.2011.06.010Get rights and content

Abstract

Neurologists and aphasiologists have debated for over a century whether right hemisphere recruitment facilitates or impedes recovery from aphasia. Here we present a well-characterized patient with sequential left and right hemisphere strokes whose case substantially informs this debate. A 72-year-old woman with chronic nonfluent aphasia was enrolled in a trial of transcranial magnetic stimulation (TMS). She underwent 10 daily sessions of inhibitory TMS to the right pars triangularis. Brain activity was measured during picture naming using functional magnetic resonance imaging (fMRI) prior to TMS exposure and before and after TMS on the first day of treatment. Language and cognition were tested behaviorally three times prior to treatment, and at 2 and 6 months afterward. Inhibitory TMS to the right pars triangularis induced immediate improvement in naming, which was sustained 2 months later. fMRI confirmed a local reduction in activity at the TMS target, without expected increased activity in corresponding left hemisphere areas. Three months after TMS, the patient suffered a right hemisphere ischemic stroke, resulting in worsening of aphasia without other clinical deficits. Behavioral testing 3 months later confirmed that language function was impacted more than other cognitive domains. The paradoxical effects of inhibitory TMS and the stroke to the right hemisphere demonstrate that even within a single patient, involvement of some right hemisphere areas may support recovery, while others interfere. The behavioral evidence confirms that compensatory reorganization occurred within the right hemisphere after the original stroke. No support is found for interhemispheric inhibition, the theoretical framework on which most therapeutic brain stimulation protocols for aphasia are based.

Highlights

► We report a patient with aphasia who received TMS, then had a right hemisphere stroke. ► Inhibition of right pars triangularis using TMS improved word retrieval. ► fMRI data did not support a release of transcallosal inhibition as a mechanism of TMS. ► A subsequent right hemisphere stroke specifically worsened language function. ► The right hemisphere supports aphasia recovery, but the pars triangularis interferes.

Introduction

In 1877, Barlow described a boy who developed aphasia after a stroke involving Broca’s area, recovered significantly, but then worsened after a symmetric stroke in the right hemisphere (RH) (Barlow, 1877). This case was taken as evidence that the RH can reorganize in order to assume functions of the left hemisphere (LH) in aphasia, and launched a debate regarding the role of the RH in aphasia recovery that continues today. Only a few similar cases have followed (Basso et al., 1989), and the validity of the original case has recently been subject to debate (Hellal and Lorch, 2007). Behavioral studies demonstrating a left visual field or left ear advantage for verbal stimuli, Wada studies demonstrating worsening with right carotid injection, and cases of language recovery after left hemispherectomy supported RH involvement in aphasia recovery [see Basso et al. (1989) for review]. However, as research tools have become more precise, the role of the RH has become less clear. Some functional imaging studies have supported compensatory RH recruitment (Blasi et al., 2002, Leff et al., 2002, Musso et al., 1999, Ohyama et al., 1996, Saur et al., 2006), although the RH is thought to be computationally less efficient in its language processing than native LH areas (Heiss et al., 1999, Heiss et al., 2003, Winhuisen et al., 2005). Others have concluded that RH activity is “ineffective” (Postman-Caucheteux et al., 2010, Richter et al., 2008) or is associated with nonlinguistic processes like executive control that are called upon nonspecifically when processing load is high (van Oers et al., 2010).

Another hypothesis is that the RH is aberrantly recruited after a LH stroke due to a release of left-to-right transcallosal inhibition. Over-activity in RH areas then putatively inhibits recovery of LH perilesional cortex, limiting recovery from aphasia. This “theory of interhemispheric inhibition” has motivated several studies attempting to use inhibitory RH transcranial magnetic stimulation (TMS) as a treatment to improve aphasia (Barwood et al., 2011, Naeser et al., 2005). Responses to local inhibition of the RH using TMS have varied between patients (Winhuisen et al., 2007), and between stimulation targets (Hamilton et al., 2010), but the most consistent effect of RH TMS has been sustained improvement in speech production after inhibition of the right pars triangularis (Barwood et al., 2011, Hamilton et al., 2010, Martin et al., 2009b, Naeser et al., 2005). This beneficial effect of inhibitory RH TMS on aphasia recovery has been taken as evidence that RH recruitment is detrimental to recovery.

Variation between patients in the role of the RH in aphasia recovery may explain some of the inconsistencies in the literature, but it is equally plausible that different areas within the RH play competing roles in aphasia recovery even within a single patient. Reorganization after LH injury may result in compensatory recruitment of some RH areas, while others interfere with recovery. Here we present a patient whose aphasia improved after TMS-induced inhibition of the right pars triangularis, but then worsened after a distant RH stroke. Specific patterns in performance demonstrate unequivocally that the initial LH stroke induced compensatory reorganization within RH networks supporting language. The dissociation between the effects of TMS and the RH stroke provides clear evidence that different areas of the RH can have opposing effects on aphasia recovery in a single patient, and raises questions regarding the proposed mechanism of therapeutic TMS.

Section snippets

Clinical trial and neuropsychology methods

The patient was enrolled in a randomized subject-blinded sham-controlled partial crossover trial of TMS for chronic nonfluent aphasia (clinicaltrials.gov ID: NCT00608582). Procedures were approved by the University of Pennsylvania IRB. Written informed consent was obtained from the subject. The trial protocol has been described in detail previously (Martin et al., 2009b). The subject underwent three sessions of neuropsychological testing to establish a stable baseline measurement of language

Case description

A 67-year-old female retired school counselor was found down at home with global aphasia and right hemiplegia. She was diagnosed with a left middle cerebral artery (MCA) ischemic stroke (Fig. 1A); no thrombolytic agents were administered. She was discharged to an inpatient rehabilitation hospital 3 weeks later, where she remained for 1 month. She received speech therapy 3 days per week for approximately 2 years. Four years after the stroke, she enrolled in a clinical trial of TMS as detailed

Discussion

This case demonstrates seemingly paradoxical effects from two modes of RH disruption in the same aphasic patient: first, inhibiting the right pars triangularis using TMS improved aspects of aphasia both in the short and long-term, and second, a RH stroke worsened aphasia, even in comparison to its impact on other cognitive domains. Together, these findings demonstrate that the RH is not unitary in its role in aphasia recovery. Even within a single patient, involvement of some RH areas may

Acknowledgments

This work was supported by the American Academy of Neurology Foundation (Clinical Research Training Fellowship to P.E.T), and the NIH (K01NS060995 to R.H.H and RO1 DC05672). We thank the patient and her family for their participation in this research.

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