Regular ArticleHomotopic language reorganization in the right hemisphere after early left hemisphere injury
Highlights
► Small, structurally remote lesions can result in considerable neocortical language plasticity. ► Right hemisphere language is mediated by right Broca’s and Wernicke’s homologues. ► These areas thus appear to be uniquely predisposed to mediate language. ► This is true across a range across productive and perceptive language tasks. ► Certain tasks are more sensitive to variations in inter-hemispheric transfer.
Introduction
The earliest and most compelling evidence for brain plasticity comes from patients with early insult to the left hemisphere who nevertheless develop low-normal to normal language. In some cases, this reflects transfer of language representation to the right hemisphere (Basser, 1962). Atypical (RH) language representation occurs in up to 53% of epilepsy patients, usually when epilepsy has a left hemisphere focus and when onset is early in life (Adcock et al., 2003, Brazdil et al., 2003, Goldmann and Golby, 2005, Helmstaedter et al., 2006, Helmstaedter et al., 1997, Janszky et al., 2006, Rasmussen and Milner, 1977, Springer et al., 1999, Woermann et al., 2003). Although this is most commonly observed after large perinatal lesions, transfer can also occur post-natally and may be associated with small epileptogenic lesions in the medial temporal lobe that interfere with, but do not destroy critical language areas (Liegeois et al., 2004). Transfer may also occur in the absence of epilepsy, associated with perinatal stroke of the left middle cerebral artery (Tillema et al., 2008), white matter damage (Lidzba et al., 2008, Staudt et al., 2001, Staudt et al., 2002), and arteriovenous malformation – AVM (Lazar et al., 2000).
The mechanisms by which language reorganizes are still not well understood. One unresolved issue is the topography of the newly developed right hemisphere language network. Recent functional imaging studies of patients with large, perinatal vascular lesions have suggested that the right hemisphere network mirrors that of the normal left hemisphere, both in the classical language areas (Staudt et al., 2002, Tillema et al., 2008) and also in other regions such as the cerebellum (Lidzba et al., 2008). However, other studies have found differences in the topography of the right hemisphere language network as compared to the left (Liegeois et al., 2008, Tillema et al., 2008, Voets et al., 2006).
Differences across studies may reflect true variability in right hemisphere language networks or cross-study differences in the nature or timing of the lesions or in the activation tasks used. How language transfers and where it transfers to may depend in part on the stage of neural development at the time of injury (de Bode & Curtiss, 2000). Different language tasks also produce different activation patterns, even in normal participants (Cabeza & Nyberg, 2000). Specific language processes may also show differential degrees and patterns of reorganization after damage. For example, Staudt et al. (2001) found extensive changes in the cortical representation of language for a production task but not for a perception task.
Inter-hemispheric transfer of language to the right hemisphere historically has been diagnosed using the intracarotid amobarbital procedure (IAP or the ‘Wada test’), during which each hemisphere is independently anesthetized to determine whether it is critical for language function. Language laterality determined by fMRI is typically highly consistent with Wada results (Adcock et al., 2003, Binder et al., 1996, Carpentier et al., 2001, Rutten et al., 2002, Swanson et al., 2007, Woermann et al., 2003). Greater bilateral or right-sided fMRI activation has been associated with left sided seizure onset, early injury, and atypical speech representation on the Wada (Benke et al., 2006, Berl et al., 2005, Brazdil et al., 2003, Janszky et al., 2006, Thivard et al., 2005). However, even among patients found to be left hemisphere dominant by Wada, left-sided epilepsy is associated with more right sided fMRI activation, suggesting that fMRI may be more sensitive than the Wada to variability in inter-hemispheric reorganization of language (Adcock et al., 2003, Backes et al., 2005, Binder, 2011, Koylu et al., 2006). Variation in reorganization of expressive and receptive language processes has been observed (Backes et al., 2005, Lee et al., 2008, Thivard et al., 2005), suggesting a dissociation between reorganization in frontal and temporal networks in some cases. Although these studies have furthered our understanding of the degree and clinical predictors of inter-hemispheric transfer, they have not formally addressed the issue of localization of different language processes after transfer by comparing samples of left- and right-hemisphere language patients, using multiple fMRI language tasks.
Most prior studies have investigated language reorganization after large, perinatal, vascular lesions with or without a history of seizures or in samples with mixed lesion types. We studied this phenomenon in patients who underwent surgery for intractable epilepsy due to circumscribed, medial temporal lobe lesions to determine whether the results from studies of patients with large lesions generalize to patients with smaller, more circumscribed lesions. In the present study, we compared activation patterns in epilepsy patients with right hemisphere (RH) language dominance or left hemisphere (LH) language dominance, as established by pre-surgical Wada testing. In this setting, RH language presumably reflects inter-hemispheric transfer induced by chronic epileptic activity during a critical period of language development. We controlled for any potential effects of cognitive abilities, lesion location and size on localization of activation, by studying patients who all had left medial temporal lobe epilepsy, similar pre-surgical verbal skills, similar pathology restricted to the medial temporal lobe, and similar extent of left temporal resection. We also administered a battery of language tasks in order to examine the consistency of our findings across different language processes and to explore cortical reorganization of different aspects of language processing.
Section snippets
Participants
Patients with right hemisphere (RH) (n = 7) and a matched group with left hemisphere (LH) (n = 10) speech dominance were recruited from a large cohort of medically-intractable temporal lobe epilepsy patients treated at a single center. All patients had had a left anterior temporal lobectomy at least 5 years before the study, were clinically stable and had no contraindications for MRI. Right-handed healthy volunteers (C) (n = 14) served as controls to identify regions normally activated by our tasks,
Task performance
All participants reached an acceptable level of performance on all tasks on pre-scan practice as observed by the trainer. Performance during scanning was only recorded for the semantic decision task. For this task, accuracy on correct task trials (animal names) was ARH = 64.5% (SD = 11.8), ALH = 60.6% (SD = 11.3), AC = 78% (SD = 8.1), and for correct tone discrimination trials ARH = 82.5% (SD = 16.3), ALH = 81.7% (SD = 22), AC = 93.8% (SD = 6.6). There were no significant differences between groups in accuracy for
Findings of the present study
In this study we examined the topography of language reorganization by studying two groups of patients with well matched medical histories and baseline verbal abilities (to control for effects of disease and treatment) and with known speech dominance as determined by pre-surgical Wada testing. Thus, any differences between the two patient groups in hemispheric language organization is likely to reflect the effect of transfer due to the earlier developmental timing of the initial insult and/or
Acknowledgments
This research was supported by the Schmitt Program for Integrative Brain Research, University of Rochester and by NIH Grant DC00167 and NIH training grant T32 MH019942 to ELN. We would like to thank Dr. Tong Zhu for insightful technical suggestions and Galina Badyulina for her contributions.
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2017, Brain and LanguageCitation Excerpt :That many (but not all) patients with left-hemispheric pre-/perinatal pathology may rely on a right-hemispheric language network has repeatedly been demonstrated for patients with and without epilepsy (Liegeois et al., 2004; Rasmussen & Milner, 1977; Tillema et al., 2008). The reorganized, right-hemispheric activation pattern encompasses areas homotopic to those involved in left-hemispheric language organisation, as investigated in patients with congenital white-matter lesions (Staudt et al., 2002), and in patients with left-hemispheric brain damage after epilepsy surgery (Tivarus, Starling, Newport, & Langfitt, 2012). Interhemispheric reorganization seems to affect networks connecting various regions of the brain, including the cerebellum (Lidzba, Wilke, Staudt, Krägeloh-Mann, & Grodd, 2008).
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