Continuous theta burst stimulation over right pars triangularis facilitates naming abilities in chronic post-stroke aphasia by enhancing phonological access
Introduction
Aphasia, the acquired inability to produce and/or comprehend language, is a common cognitive impairment following left hemisphere stroke, affecting more than one million individuals in the United States alone. Aphasia has a profound impact on the affected individuals and their families, often resulting in decreased independence in daily activities and overall perceptions of quality of life (Cruice et al., 2003, Tennant et al., 1997). Currently, speech-language therapy (SLT) is the most commonly employed treatment for aphasia. Although intensive SLT can improve some aspects of language and functional communication (Brady, Kelly, Godwin, Enderby, & Campbell, 2016), its effects on long-term outcomes are only modestly beneficial, leaving many aphasic individuals with life-long communication difficulties. The emergence of noninvasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (rTMS), as focal interventions that can potentially facilitate recovery from chronic post-stroke aphasia provides a promising avenue for language rehabilitation (for reviews, see Chrysikou and Hamilton, 2011, Coslett, 2016, Hamilton et al., 2011, Shah et al., 2013, Torres et al., 2013, Turkeltaub, 2015). However, little is known about which specific aspects of language difficulties NIBS techniques target (cf. Medina et al., 2012), rendering it difficult to advance more tailored approaches that involve specific and efficacious treatment protocols. Here, we explored the characteristics of language impairment that improve following rTMS to better understand how this treatment approach enhances naming abilities in aphasia, and in turn, for whom rTMS therapy is most likely to have the greatest benefit.
The ability to communicate depends largely on successful word retrieval, the loss of which is a ubiquitous problem in aphasia. Even in single-word production tasks, such as picture naming, people with aphasia are often unable to reliably retrieve the names of common objects. By most accounts, producing a word proceeds in two stages: first the translation of a meaning to its word form (i.e., semantic-to-lexical mapping), followed by the translation of the word to its sound form (i.e., lexical-to-phonological mapping; e.g., Dell et al., 1997, Levelt et al., 1999). Because the remediation of word retrieval failures can confer improvements in connected speech (e.g., Hickin, Herbert, Best, Howard, & Osborne, 2002), improving naming abilities is often a focus of aphasia rehabilitation (e.g., Nickels, 2002).
In recent years, a growing body of evidence has shown that rTMS has the potential to enhance naming abilities in chronic post-stroke aphasia (e.g., Barwood et al., 2011, Barwood et al., 2012, Hamilton et al., 2010, Harvey et al., 2017, Naeser et al., 2005a, Naeser et al., 2005b). Typically, researchers administer inhibitory rTMS to a region within the right hemisphere homologue of Broca’s area, the right pars triangularis (rPTr). For many investigators, this approach is motivated by the view that right hemisphere recruitment in language tasks is maladaptive (e.g., Postman-Caucheteux et al., 2010, Saur et al., 2006; but see e.g., Harvey et al., 2017, Turkeltaub et al., 2012), occurring only as a consequence of an imbalance in transcallosal inhibition between the two hemispheres following damage to the language-dominant hemisphere. According to this interhemispheric inhibition hypothesis, left hemisphere damage releases the right hemisphere from transcallosal inhibition, allowing the overactive right hemisphere to suppress recruitment of the already damaged language-dominant hemisphere (Fregni & Pascual-Leone, 2007). Broadly consistent with this hypothesis, inhibitory rTMS to the rPTr or excitatory rTMS to perilesional left hemisphere regions has been shown to increase behaviorally beneficial recruitment of left hemispheric regions during language tasks (e.g., Griffis et al., 2016, Szaflarski et al., 2011). However, it is worth noting that other studies suggest that this may be an oversimplified view of the right hemisphere’s role in aphasia recovery (for reviews, see Hamilton et al., 2010, Torres et al., 2013), suggesting instead that in some cases right hemisphere recruitment for language may be compensatory (Chieffo et al., 2014, Turkeltaub et al., 2011, Turkeltaub et al., 2012, Winhuisen et al., 2005, Winhuisen et al., 2007). Nevertheless, most accounts agree that rTMS facilitates language recovery by prompting neuroplastic changes in the bilateral neural network recruited for language (e.g., Harvey et al., 2017).
However, due to the relative infancy of rTMS as a treatment for aphasia, the field has yet to establish criteria for determining who is a good candidate for this treatment approach. Prior work has emphasized the highly variable nature of rTMS-induced naming improvements across individuals (e.g., Naeser et al., 2005a; see also Martin et al., 2009), but the reasons are not well understood. Some studies have demonstrated that, compared to persons with mild aphasia, individuals with moderate-to-severe aphasia exhibit larger gains following rTMS when administered at both the subacute (Seniów et al., 2013) and chronic phases (Barwood et al., 2012, Naeser et al., 2005a; but see Martin et al., 2009 for evidence of no TMS response in a case of global aphasia). Yet, others have found no such relationship between severity and rTMS response (Kindler et al., 2012, Tsai et al., 2014).
Another factor that may impact the extent to which individuals respond to rTMS relates to the processes and stages at which word retrieval becomes impaired due to stroke. Little is known about the specific cognitive processes rTMS alters to facilitate naming performance in aphasia (see e.g., Medina et al., 2012; reviewed in Schwartz, Middleton, & Hamilton, 2015). The characteristics of word retrieval failure in aphasia offer a rich source of information about the underlying cause of naming impairment. For instance, naming performance is in some cases inconsistent, meaning that successful word retrieval for a given item is not always predictive of future retrieval success (e.g., Freed, Marshall, & Chuhlantseff, 1996). Computational models of word retrieval failure account for inconsistent performance by assuming that stroke-related damage increases noise in the production system, where the likelihood of retrieval success for a given item depends on the level of noise that occurs when attempting to access that representation (e.g., Dell et al., 1997, Schwartz et al., 2006; also see Warrington & Cipolotti, 1996; cf. Howard, 1995, Jefferies and Lambon Ralph, 2006). Accordingly, successful retrieval of a word for which there is some degree of noise will be unreliable, whereas retrieval success for words with elevated noise levels will be unlikely. In addition, erroneous responses typically share a meaning- and/or sound-based relationship with the target response, which provides insight into the stage of processing at which word retrieval fails. Error responses that are semantically similar to the target (e.g., saying “cat” for the picture DOG) arise due to faulty semantic-to-lexical mapping, whereas error responses that are phonologically similar to the target (e.g., saying “log” for the picture DOG) arise due to faulty lexical-to-phonological mapping (Dell et al., 1997, Schwartz et al., 2006, Schwartz, 2014). Understanding where in the production system rTMS facilitates language improvements in people with aphasia may lead to better stratification of patients into rTMS treatment protocols – potentially by identifying who is a good candidate for this neurorehabilitative approach.
The present research investigated whether a single session of continuous theta burst stimulation (cTBS) delivered to the rPTr vs. a control site (vertex) confers naming improvements in chronic aphasia, and if so, whether responsiveness to this NIBS technique varies as a function of the severity and/or type of naming impairment. CTBS is an inhibitory form of rTMS that induces robust effects on cortical excitability in a fraction of the time (<1 min) required to produce similar effects using low frequency rTMS (e.g., Huang, Edwards, Rounis, Bhatia, & Rothwell, 2005). While rTMS studies of aphasia usually involve many days of stimulation to induce enduring effects, we have demonstrated previously that a single session of stimulation can elicit transient benefits in performance (e.g., Hamilton et al., 2010, Harvey et al., 2017). To better understand for whom this treatment approach is most likely to benefit, and how it may alter cognitive processes to enhance naming abilities, we explored the following three characteristics of aphasic individual’s naming performance: (1) severity of baseline naming impairment; (2) consistency of item-level response accuracy; and (3) the primary locus of naming impairment, as evidenced by the types of errors committed at baseline and their improvement following cTBS. Based on prior work (Barwood et al., 2012, Seniów et al., 2013), we predicted that participants with more severe naming impairments would exhibit larger gains following cTBS of the rPTr vs. vertex when compared to those with less impaired naming abilities. In addition, we hypothesized that items for which retrieval success at baseline was inconsistent would be more likely to improve following cTBS of the rPTr vs. vertex when compared to those that were consistently retrieved unsuccessfully. If true, this would suggest that cTBS enhances naming performance by reducing, rather than eliminating, noise arising during word retrieval.
Lastly, to identify the primary locus of naming failures and the stage at which cTBS enhances performance, we classified all inaccurate responses based on error type. We focused on semantic and phonological errors, as the stages at which these error types arise have been well characterized within cognitive models of word retrieval deficits in aphasia (e.g., Dell et al., 1997, Schwartz et al., 2006). Because the preponderance of NIBS research in aphasia has focused solely on naming accuracy overall, we did not have specific predictions regarding the types of errors this treatment approach targets. If indeed rTMS confers naming improvements by altering specific cognitive processes that underlie successful word retrieval, we speculated that treatment outcomes might differ depending on where in the system word retrieval fails.
Section snippets
Participants
Eleven participants (9 males) with chronic aphasia due to left hemisphere stroke completed the study protocol (age range = 29–79, mean (M) = 56). All participants were pre-morbidly right-handed (Oldfield, 1971), native English speakers who had suffered a single stroke at least 6 months prior to participation (M = 64.6 months; range = 6–173) (see Table 1). No participant had contraindications to structural magnetic resonance imaging (MRI) or TMS. Informed consent was obtained from all
Results
Analyses at the group level (n = 11) revealed that naming accuracy pre- vs. post-cTBS did not differ between rPTr and vertex for either inconsistent or wrong items (p’s > .41; see Table 2). However, as expected, individuals varied considerably in their response to cTBS. For inconsistent items, post- minus pre-cTBS naming accuracy (i.e., stimulation effect) ranged from −23.1 to 23.4% following rPTr stimulation, whereas the rPTr-stimulation effect for wrong items ranged from −25.0 to 41.3%.
Discussion
We investigated the cognitive mechanism(s) by which rTMS enhances naming abilities in individuals with chronic post-stroke aphasia by exploring whether the degree and/or primary source of naming impairment was associated with individuals’ responsiveness to this treatment approach. Our findings indicate that cTBS of the rPTr enhances naming abilities for individuals with more severe baseline naming impairment when naming objects for which they could retrieve successfully – albeit inconsistently
Conclusion
To our knowledge, this is the first study to examine the characteristics of naming impairment in aphasia as it relates to variable rTMS treatment outcomes. The findings from this research not only lay the groundwork for incorporating cognitive models of word retrieval failure in future studies of rTMS in aphasia, but they also have the potential to inform the stratification of patients into effective rTMS protocols. In the current study, we provide evidence that individuals with word retrieval
Statement of significance
This research points to phonological processing as a specific cognitive-linguistic ability that is enhanced in persons with chronic post-stroke aphasia who undergo TMS therapy. By clarifying which aspects of word retrieval improve following TMS, this work has the potential to inform optimal stratification of patients in TMS treatment protocols.
Acknowledgements
We thank Adelyn Brecher and Hannah Juhel for assistance in coding data for this study.
Funding
This work was supported by the National Institutes of Health [grant number R01 DC012780] and the Dana Foundation Brain and Immunoimaging Award, New York, NY awarded to R.H.H. D.Y.H was supported by the National Institutes of Health [grant number T32 HD071844].
Disclosure
The authors report no potential conflicts of interest.
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2022, Clinical NeurophysiologyCitation Excerpt :More complex rTMS protocols, including excitatory intermittent theta burst stimulation (iTBS) and the inhibitory continuous theta burst stimulation (cTBS) can produce more stable and longer-lasting changes in cortical excitability compared to standard rTMS protocols (Cárdenas-Morales et al., 2010; Goldsworthy et al., 2012; Hsu et al., 2011; Huang et al., 2005). Studies that use rTMS for therapeutic purposes suggest that changes in neuronal responsiveness induced by rTMS can be observed beyond the actual period of stimulation and can persist for days or weeks after multiple stimulation sessions (Barwood et al., 2013; Harvey et al., 2019; Hu et al., 2018; Kindler et al., 2012; Seniów et al., 2013; Tsai et al., 2014; Versace et al., 2020; Waldowski et al., 2012). Because rTMS allows for noninvasive manipulation of cortical excitability in the targeted brain regions, it can provide a way to induce cortical plasticity in people with post-stroke aphasia.
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2022, Handbook of Clinical NeurologyCitation Excerpt :Future research is needed to understand the various factors at play that influence the spontaneous reorganization of the language system, and in turn the best approach for administering NIBS for treating aphasia. The vast majority of research utilizing NIBS for the treatment of poststroke aphasia has investigated its potential to facilitate aphasia recovery by assessing changes in spoken word production via confrontation naming tasks (see e.g., Naeser et al., 2005a,b, 2011; Martin et al., 2009; Cotelli et al., 2011; Harvey et al., 2017, 2019 for rTMS evidence; see e.g., Monti et al., 2008; Fridriksson et al., 2018b; Elsner et al., 2020 for tDCS evidence). There are at least two factors that contribute to the emergence of naming as the principal outcome measure in NIBS studies of poststroke aphasia: (1) impairments in word retrieval are a ubiquitous problem in PWA, as patients often report word-finding difficulties regardless of the degree of language impairment severity or aphasia classification type; and (2) changes in naming performance are easily quantifiable when compared to other, less constrained measures of language abilities (e.g., narrative discourse production, grammatic accuracy, etc.).
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2021, Neuroscience and Biobehavioral ReviewsCitation Excerpt :To restore the balance between the hemispheres and enhance language production, 34 studies inhibited the rIFG, corresponding to the homolog of Broca’s area (Tables 1 and 2). Most of these studies used LF stimulation (1 Hz) to suppress the right PTr, although some studies also used continuous (c)TBS (Georgiou et al., 2019; Harvey et al., 2019; Kindler et al., 2012; Vuksanović et al., 2015). In addition, four studies (Dammekens et al., 2012; Griffis et al., 2016; Szaflarski et al., 2011, 2018) used HF iTBS to stimulate the left inferior frontal gyrus (lIFG), corresponding to Broca’s area.
- 1
Present address: Sidney Kimmel Medical College, Thomas Jefferson University, 1025 Walnut Street, Philadelphia, PA 19107, USA.
- 2
Present address: Rotman Research Institute, Baycrest Health Sciences Centre, Toronto, ON, Canada.