Journal of Neurolinguistics: Elissa-Marie Cocquyt, Lisa de Ley, Patrick Santens, John Van Borsel, Miet de Letter

Journal of Neurolinguistics 44 (2017) 68e90
Contents lists available at ScienceDirect
Journal of Neurolinguistics
journal homepage: www.elsevier.com/locate/jneuroling
The role of the right hemisphere in the recovery of

stroke-related aphasia: A systematic review
Elissa-Marie Cocquyt a, Lisa De Ley a, Patrick Santens b, John Van Borsel a,
Miet De Letter a, *
a
Department of Speech, Language and Hearing Sciences, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium
b
Department of Neurology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium
a r t i c l e i n f o a b s t r a c t
Article history: Stroke in the language dominant hemisphere is the most frequent cause of aphasia. In the
Received 30 October 2016 course of post-stroke aphasia different mechanisms can contribute to the recovery of
Received in revised form 16 March 2017 language: recovery from ischemia, compensatory rerouting of language modalities and
Accepted 21 March 2017
neuroplasticity occur at different time scales after the initial injury. These mechanisms
Available online 31 March 2017
may occur spontaneously or may be induced or influenced by various therapeutic in-
terventions. This report contains a systematic review of the literature concerning the
Keywords:
debated role of the right hemisphere in the recovery from stroke-related aphasia. The
Aphasia
Stroke
existing literature was approached using the PICOS principle and well-established inclu-
Language recovery sion and exclusion criteria. Although many gaps remain in the knowledge on the role of
Neuroplasticity the right hemisphere, there is some evidence of a facilitation of spontaneous language
Therapy recovery in the acute and subacute phase. In the subacute and chronic phase, the right
Right hemisphere hemisphere homologous language areas, along with memory and attention-related areas,
facilitate treatment related improvement. In contrast, in therapy-free periods in the
chronic stage, the right hemisphere no longer contributes to language recovery or may
even be inhibitory. Injury-, language- and therapy-related variables impact on the role of
the right hemisphere in aphasia recovery.
© 2017 Elsevier Ltd. All rights reserved.
Contents
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
1.1. The recovery of aphasia: general considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
1.2. The right hemisphere in aphasia recovery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
1.3. Variables affecting aphasia recovery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
2. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
3.1. Research design and -quality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
3.2. The role of the right hemisphere in aphasia recovery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
3.2.1. The role of the right hemisphere in spontaneous aphasia recovery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
3.2.2. The role of the right hemisphere in therapy-related aphasia recovery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
3.3. Variables with an influence on the role of the right hemisphere in spontaneous and therapy-related recovery . . . . . . . . . . . 78
* Corresponding author.
E-mail address: miet.deletter@ugent.be (M. De Letter).
http://dx.doi.org/10.1016/j.jneuroling.2017.03.004
0911-6044/© 2017 Elsevier Ltd. All rights reserved.
E.-M. Cocquyt et al. / Journal of Neurolinguistics 44 (2017) 68e90 69
4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
4.1. The role of the right hemisphere in spontaneous and therapy-related aphasia recovery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
4.2. Variables with an influence on the role of the right hemisphere in aphasia recovery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
Search terms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
References reviewed articles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
The scoring system used for evaluating methodological quality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
Methodological quality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
1. Introduction
1.1. The recovery of aphasia: general considerations
Aphasia is a language disorder due to an acquired brain injury, acute or degenerative, in individuals who have had a normal
language development (van Borsel, 2008). In about 70% of the cases the lesion is located in the left hemisphere (Hoffmann &
Chen, 2013). Aphasia is characterized by one or more affected language modalities. Comprehension and production problems
can occur both in spoken and written language. The severity of these disorders varies individually and can range from mild to
very severe, resulting in impaired communication, participation and quality of life. In about 85% the cause of aphasia is a
stroke (Peters et al., 2014), which leads to loss of neurons with disruption of network functions and results in language
dysfunction (Kuks, 2007). In the majority of patients the language problem becomes chronic (Laska, Hellblom, Murray, Kahan,
& Von Arbin, 2001; Maas et al., 2012.)
After a stroke, people with aphasia may exhibit a degree of spontaneous recovery, which is most noticeable during the first
weeks or months post stroke onset. In addition, language therapy can be beneficial for further recovery (Aerts, van Mierlo,
Hartsuiker, Santens, & De Letter, 2014; Nickels, 2002; Pulvermuller et al., 2001; Robey, Schultz, Crawford, & Sinner, 1999).
Several physiological mechanisms underly spontaneous or therapy-related aphasia recovery. Based on the underlying
physiological mechanisms aphasia recovery is divided into the acute, subacute, and chronic phase. The clinical progress in the
acute phase, the first three weeks after a stroke (Bartha & Benke, 2003; Kiran, 2012), depends on the extent to which (a part
of) the perfusion can be restored. If a successful reperfusion and a restoration of a normal glucose metabolism is realized, this
may have a positive impact on the recovery of language functions (Heiss, Kessler, Karbe, Fink, & Pawlik, 1993; Hillis et al.,
2001. Kiran, 2012). The decrease of cerebral edema and the disappearance of local inflammations may further contribute
to recovery (Baldwin & McCoy, 2010). In this phase, the so-called “penumbra” plays a crucial role. This is the zone around an
irreversibly damaged core infarction. Penumbra tissue is able to survive but is dysfunctional as a consequence of inadequate
oxygen supply (Astrup, Siesjo, & Symon, 1981). If the local perfusion does not improve, spontaneously or by therapeutic
intervention, neuronal loss will occur (D. W. Heiss et al., 1992). The recovery of the penumbra is a predictor of clinical progress
(Baron, 1999).
In the subacute phase, up to six months after a stroke (Kiran, 2012), recovery of language functions can occur as a function
of plastic changes in the brain or due to restoration of diaschisis. Neuroplasticity refers to the ability of the brain to form new
neural connections or to repair damaged connections. Neuroplasticity is characterized by two phenomena namely sprouting,
the growth of new dendrites at the level of the axons (Carmichael, 2006), and the activation of silent synapses (Bach-y-Rita,
1990). In addition the restoration of diaschisis may contribute to language recovery in this stage. Diaschisis is the occurrence
of functional defects in an intact part of the nervous system as a result of a lesion at a distance that is structurally connected to
it (von Monakow, 1914). There is a positive correlation between the decrease in diaschisis and recovery of language functions
in the subacute phase (Cappa et al., 1997; Jarso et al., 2013.).
Aphasia recovery in the chronic phase, after six months (Hillis, 2005), is mainly therapy-related as spontaneous recovery
and restoration of diaschisis are minimal at this stage (Hillis & Heidler, 2002; Robey, 1998). Consequently it can be concluded
with more certainty that the measured neuroplasticity after a therapy is the direct result of the therapeutic intervention, in
contrast to the acute and subacute phase where a possible degree of spontaneous recovery should be taken into account.
1.2. The right hemisphere in aphasia recovery
Within studies where spontaneous or therapy-related recovery is examined, the laterality plays an important role
(Barbancho et al., 2015 .; Crosson et al., 2009; Pulvermüller, Hauk, Zohsel, Neininger, & Mohr, 2005; Saur et al., 2006). The
central question is whether a transfer of language functions occurs to the perilesional areas, the right hemisphere or a
combination of both (Turkeltaub, Messing, Norise, & Hamilton, 2011). Especially the role of the right hemisphere in language
reorganization after stroke is a matter of debate.
During the development of the brain and the acquisition of language, one hemisphere becomes dominant for language
functions. Most of the time, the primary language areas are situated in the left hemisphere (Knecht et al., 2000), resulting in
70 E.-M. Cocquyt et al. / Journal of Neurolinguistics 44 (2017) 68e90
limited linguistic abilities of the right hemisphere. The most important linguistic characteristics attributed to the right
hemisphere are: the lexical-semantic processing of high frequent and short words (Bub & Lewine, 1988), processing the
meaning of ambiguous words (Burgess & Simpson, 1988), comprehension and production of the macro structure of written
texts and conversations (Mitchell & Crow, 2005), pragmatic skills (Mitchell & Crow, 2005) and identifying and expressing
emotional prosody (Mitchell & Crow, 2005).
Primary language areas inhibit secondary areas that are usually not activated during language tasks. It concerns areas in
the ipsilateral hemisphere (collateral inhibition) as well as areas in the contralateral hemisphere (transcallosal inhibition)
(Selnes, 2000). In this way a lesion located in a primary language area can lead to disinhibition of secondary areas resulting in
an increased activity in these regions. Multiple studies on aphasia indeed show a relative increase of activity in the right
hemisphere in terms of electrophysiological (Papanicolaou, Moore, Deutsch, Levin, & Eisenberg, 1988; Papanicolaou, Moore,
Levin, & Eisenberg, 1987), metabolic (Karbe et al., 1998) and hemodynamic response. There is no consensus regarding the
consequences of this change in activation (facilitating or inhibiting).
In general three reorganization patterns of language functions are distinguished. These patterns were described by
Hamilton, Chrysikou, and Coslett (2011) in people with chronic aphasia namely 1) functional activation of perilesional areas or
areas in the left hemisphere that also support language functions and are called redundant areas (Marshall, 1984) 2) func-
tional activation of homotopic areas in the right hemisphere and 3) dysfunctional activation of homotopic areas in the right
hemisphere. Several studies show that a better recovery of language skills occurs when perilesional and redundant areas are
activated in the left hemisphere (Szaflarski, Allendorfer, Banks, Vannest, & Holland, 2013; Zahn et al., 2004). On the other
hand the role of the right hemisphere in the recovery of aphasia is disputed. Some have advocated a facilitatory effect of right
hemisphere activity on aphasia recovery, while others have argued against this. A facilitatory effect is suggested by studies
where a second lesion in the right hemisphere, acquired after a lesion in the left hemisphere, leads to a deterioration of
(partly) recovered language functions (Basso, Gardelli, Grassi, & Mariotti, 1989; Gainotti, 1993). Also the observation that adult
patients show no further deterioration of language functions after a left hemispherectomy supports the view that the right
hemisphere has the potential to process linguistic information, even without a functioning left hemisphere (Schramm, Delev,
Wagner, Elger, & von Lehe, 2012). In contrast, several studies suggest a rather inhibitory effect of the right hemisphere, by
showing that the increased activity in the right hemisphere is not related to the clinical progress (Naeser et al., 2002; Rosen
et al., 2000). This view is further supported by positive effects on language recovery after inhibition of the right hemisphere
(Barwood et al., 2011a,b . Naeser et al., 2005; Turkeltaub et al., 2012.). This supports the hypothesis that activity in the right
hemisphere is a reflection of inefficient or maladaptive neuroplasticity. The increased activity would in turn result in
abnormally adverse transcallosal inhibition of the already damaged left hemisphere and in this way it would obstruct aphasia
recovery (Hamilton et al., 2011).
The intriguing report by Turkeltaub et al. (2012) reports on a single case with evidence speaking in favour of both
inhibitory and facilitatory activity of the right hemisphere, with a beneficial effect of inhibitory neurostimulation to the pars
triangularis on the one hand, but on the other hand a deterioration of language after a subsequent right hemispheric stroke.
This suggests that facilitatory and inhibitory effects are dependent on different locations within the right hemisphere, which
further underscores the complex role of the right hemisphere in the recovery of aphasia following left hemispheric lesions.
1.3. Variables affecting aphasia recovery
There is a large interindividual variability in the degree, type and speed of recovery among people with aphasia (Kiran,
2012). This interindividual variability can be explained by multiple variables that influence the recovery of language func-
tions. These variables can be classified into six categories namely 1) time-related 2) task-related 3) injury-related 4) language-
related 5) person-related and 6) therapy-related.
The involvement of the right hemisphere is potentially a dynamic process that changes as a function of time. In a lon-
gitudinal study of Saur et al. (2006) fMRI measurements were made during an auditory comprehension task respectively in
the acute, subacute and chronic phase. In the acute phase almost no activity was observed in both hemispheres, in the
subacute phase a large bilateral activity increase was measured with the largest increase at the homotopic area of Broca's
region in the right hemisphere. In the chronic phase, activity shifted again to the left hemisphere. In addition, the increased
activity in the subacute and chronic phase correlated with the clinical progress (Saur et al., 2006). In the evaluation of lan-
guage recovery and the underlying physiological mechanisms many different language tasks can be used. Increased
involvement of the right hemisphere is not necessarily negative when it comes to language functions that were already
bilaterally organized before the stroke, such as semantics (Tyler, Wright, Randall, Marslen-Wilson, & Stamatakis, 2010). On
the other hand an activity increase in the right hemisphere during phonological and syntactical tasks, which are strongly left
lateralized functions, can indicate a dysfunctional reorganization pattern. The injury that lead to the development of aphasia
has an important influence on the observed recovery process. As to the type of stroke, there is a better language outcome after
a haemorrhage compared to an ischemic insult (Basso, 1992), and this discrepancy is preserved even when language therapy
is combined with transcranial direct current stimulation (Jung, Lim, Kang, Sohn, & Paik, 2011). The severity of stroke also
predicts the language outcome. The more severe the stroke, the less favorable the recovery will be (Maas et al., 2012 .;
Pedersen, Jorgensen, Nakayama, Raaschou, & Olsen, 1995; Pedersen, Vinter, & Olsen, 2004). Research about the relationship
between the localization of the lesion and the language outcome shows the importance of a preserved superior temporal
gyrus (Goldenberg & Spatt, 1994; Kertesz, Harlock, & Coates, 1979; Maas et al., 2012; Selnes, Knopman, Niccum, Rubens, &
Larson, 1983). The preservation of the basal ganglia has a positive impact on the recovery of language functions (Heiss, Thiel,
Kessler, & Herholz, 2003; Henseler, Regenbrecht, & Obrig, 2014). Further, multiple studies show that the size of the injury has
a negative effect on aphasia recovery (Goldenberg & Spatt, 1994; Kertesz & McCabe, 1977; Kertesz, Lau, & Polk, 1993; Maas
et al., 2012) and possibly there's only a significant role for the right hemisphere when the left hemisphere is severely damaged
(Heiss & Thiel, 2006; Marini et al., 2016; Zahn et al., 2004). On the other hand Price, Seghier, and Leff (2010) mention that not
the size of the injury, but rather the integrity of networks subserving a particular language function, determines recovery.
These language routes or networks exceed the vascular regions provided by a certain artery, therefore a distinction has to be
made between injury and language-related factors. There is no consensus in the literature about the relationship between the
type of aphasia and the language outcome (Kertesz & McCabe, 1977; Lazar et al., 2010; Pedersen et al., 2004). Possibly this is a
reflection of the different classification and selection criteria. The progress of certain aspects of language differs depending on
the time post stroke onset. For example there is a better prognosis for language comprehension than language production
during spontaneous recovery (Mazzoni et al., 1992). Language modalities recover at a different time. The recovery of
phonology, semantics and syntax were observed for one year post stroke in 147 aphasic patients using the ScreeLing (Visch-
Brink, Sandt-Koenderman, & Hachioui, 2010). This study shows that the recovery of phonology starts earlier, but takes longer
(El Hachioui et al., 2013). Furthermore, the initial severity of aphasia can only partially predict the language outcome. Studies
investigating this correlation show a high interindividual variability among patients (Kertesz & McCabe, 1977; P.; Pedersen
et al., 2004) although some find a predictable relation between aphasia recovery and initial impairment (Lazar et al.,
2010). Nonetheless, when considered together with the localization of the lesion the severity of aphasia was used as a
contributor to a model that predicts when and to what extent the right hemisphere contributes to aphasia recovery (Anglade,
Thiel, & Ansaldo, 2014). In this model the following estimations are formulated.
o A limited aphasia, with preserved primary language areas (Broca and Wernicke's area), has a full recovery with minimal
involvement of the right hemisphere.
o A moderate aphasia, with an injury partially compromising the primary language areas, has a partial recovery with an
activity increase in the right hemisphere in the subacute phase and a shift to the left hemisphere in the chronic phase.
o A severe aphasia, with an injury totally affecting the primary language areas, has a weak recovery with significant
activation in the right hemisphere in the subacute and chronic phase.
Besides time-, task-, injury- and language-related factors interindividual personal differences have an influence on the
recovery of aphasia. There is only weak evidence that age, sex, handedness and education influence functional recovery
(Connor, Obler, Tocco, Fitzpatrick, & Albert, 2001; Gonza lez-Fernandez et al., 2011; Inatomi et al., 2008; Lazar & Antoniello,
2008; Lazar, Speizer, Festa, Krakauer, & Marshall, 2008; Lecours et al., 1987; Pedersen et al., 2004; Pickersgill & Lincoln, 1983).
Pre-existing cognitive problems have a negative impact on aphasia recovery (Vukovic, Vuksanovic, and Vukovic, 2008),
primarily because they affect the learning ability of the patients during rehabilitation (Rogalski, Altmann, Plummer-D'Amato,
Behrman, & Marsiske, 2010). In contrast, a good insight in the language disorders, support from relatives and friends and a
high motivation have a positive effect on the outcome (Basso, 1992; Koenig-Bruhin, Kolonko, At, Annoni, & Hunziker, 2013).
Finally factors related to therapy have an important influence on the neuroplasticity and the recovery process. Language,
instrumental (Barwood et al., 2011a,b; Barwood et al., 2012; Naeser et al., 2005) and pharmacological (Berthier, Pulvermüller,
Davila, Casares, & Gutie
rrez, 2011; Chen et al., 2010; Kertesz et al., 2008) therapies are possible, as well as a combination of
them (Abo et al., 2012; Berthier et al., 2009). When focused on language therapy, a distinction can be made between therapies
with a focus on the specific linguistic disorder or a focus on participation in daily life. Both types of therapy can have a positive
influence on language outcome (Conklyn, Novak, Boissy, Bethoux, & Chemali, 2012; Li, Kitselman, Dusatko, & Spinelli, 1988;
Marangolo et al., 2010; Marcotte et al., 2012; Pulvermuller et al., 2001; Wambaugh & Ferguson, 2007; Wambaugh, Mauszycki,
Cameron, Wright, & Nessler, 2013). Besides the therapy type, the duration, intensity and an early start of treatment are
considered determining factors for recovery (David, Enderby, and Bainton, 1982). The study by Martins et al. (2013) showed
greater progress in terms of language abilities and functional communication after an intensive boost therapy (two hours/day,
five days/week, 10 weeks) as compared with conventional therapy (two hours/week, 50 weeks) (Martins et al., 2013).
In summary, the recovery of aphasia after a lesion in the left hemisphere is characterized by physiological changes in the
ipsilateral and/or contralateral hemisphere. This process takes place in three phases and recovery is influenced by multiple
variables. The aim of this article is to provide an overview of the role of the right hemisphere in the three phases of spon-
taneous and therapy-related aphasia recovery. Therapy-related recovery only includes recovery as a result of language
therapies, either focused on the language disorder or on participation in daily life. Subsequently this article will provide an
overview of the variables that affect the role of the right hemisphere in aphasia recovery.
2. Methods
A systematic review of the literature on the role of the right hemisphere in aphasia recovery was performed. By using the
PICOS-principle, an acronym standing for Population, Intervention, Control, Outcome and Study Design (Moher, Liberati,
Tetzlaff, Altman, & Group, 2010), the following research questions where formulated: “What is the role of the right hemi-
sphere in the acute, subacute and chronic phase in spontaneous and therapy-related aphasia recovery?” and “Which variables
have an influence on the role of the right hemisphere?”. Combining the key words “aphasia” OR 00 acquired dyslexia/dys-
graphia” AND keywords referring to recovery, neuroplasticity, a language modality, an imaging technique or the right
hemisphere resulted in 60 search terms, which are listed in Appendix A. Using these search terms the electronic literature
databases Pubmed and Web Of Science were screened up to October 2015. Excluding duplicates this search yielded a recall of
1372 abstracts in total. Subsequently in- and exclusion criteria (Table 1) were applied on the abstracts, resulting in a total of
130 abstracts. Full articles were searched for through SFX (UGent-collection) or by contacting the authors. The full version of
16 articles could not be found. After reading the 114 available articles another 63 articles were excluded. Reasons of exclusion
were 1) reviews 2) the absence of baseline measurements or 3) measurements of physiological changes 4) inclusion of
persons with a stroke in the right hemisphere or 5) persons without aphasia 6) the reporting of information exclusively about
changes in the left hemisphere 7) the inclusion of persons with a stroke that was not the first neurological disorder or 8) with
comorbid speech- or language disorders 9) uncertainty about the therapy and 10) the absence of a distinction between
spontaneous and therapy-related recovery. In total 51 articles were included in this review for analysis. The references of the
reviewed articles can be found in Appendix B. The flow chart in Fig. 1 shows the data sampling. In order to secure the validity
of the articles, a scoring system including multiple aspects was used. Each aspect could achieve a maximum score of 1 or 2,
depending on the relative value. The detailed terms and weighted distribution of points for each aspect can be found in
Appendix C. After reading the 51 articles, they were stratified based on the phase of recovery and the language task used
during the measurements. All of the information was processed in a summary table. Afterwards, the role of the right
hemisphere and the influencing variables were tallied through the established frequency tables. The results were shown by
using descriptive statistics.
3. Results
3.1. Research design and -quality
In this systematic review 51 studies were included. In 9.8% (5/51) of the studies there was a description of spontaneous
aphasia recovery and in 94.1% (48/51) of treatment-related aphasia recovery. In two studies, both forms of recovery were
discussed (Breier, Maher, Schmadeke, Hasan, & Papanicolaou, 2007; Mattioli et al., 2013.). In order to discuss compensatory or
neuroplasticit alterations and the role of the right hemisphere in detail, a distinction has to be made depending on the re-
covery phase and the studied language aspects. In the following paragraphs, we provide an overview of the study designs,
recovery phases, tested language aspects and imaging techniques that were used and described in the included articles. The
methodological quality is shown in Appendix D.
Five studies reported spontaneous aphasia recovery, 3/5 (60%) were group studies and 2/5 (40%) were case studies. Within
the group studies 1/3 reported on results in the acute and 2/3 in the subacute phase. In addition to one measurement at rest,
changes in brain activity were measured during auditory comprehension tasks only (Table 2), this mainly by using a neu-
roimaging technique, which yields spatial information (Table 3). Within the two single case studies results were described
once in the subacute and once in the chronic phase. Also in these studies brain activation was only measured during
Table 1
In- and exclusion criteria used for the selection of articles in the systematic review.
Selection Inclusion criteria Exclusion criteria

criteria
Population - Adults (18 years) - Children (18 years)
- Men and women - No exclusion
- Language dominance in the left hemisphere - Crossed aphasia
- Aphasia due to a stroke in the left hemisphere - Other causes (traumatic brain injuries, in-
- Aphasia as a primary neurological disease fections, etc.) or a stroke in the right
- Isolated aphasia hemisphere
- Aphasia as a secondary/tertiary/ … neurolog-
ical disease
- Aphasia with comorbid speech- or language
disorders (dysarthria/apraxia of speech)
Intervention - None (spontaneous recovery) Instrumental or pharmacological therapies
- Language therapy
Study Measurements of neuro-plasticity and the functional repercussion in spontaneous and No measurements of neuroplasticity
parameters therapy-related aphasia recovery
Imaging fMRI, PET, SPECT, DTI, EEG (ERP), MEG No exclusion
techniques
Publication A1-publications Books, posters, editorial letters
type
Language Dutch and English Other languages
Publication All publication years No exclusion
year
Study design Pro- or retrospective case- or group studies with or without a control group No exclusion
Fig. 1. Overview of the data collection process.
Table 2
Overview of the tested language aspects in each recovery phase in the five articles on spontaneous recovery.
Spontaneous recovery (n ¼ 5)
Group studies (n ¼ 3) Ratio (%) Case studies (n ¼ 2) Ratio (%)

Acute (n ¼ 1) Acute (n ¼ 0)
Auditory sentence comprehension 1 (100) / /
Subacute (n ¼ 2) Subacute (n ¼ 1)
Auditory word comprehension 1 (50) Reading comprehension (sentences) 1 (100)
Measurement at rest 1 (50)
Chronic (n ¼ 0) Chronic (n ¼ 1)
/ / Auditory word comprehension 1 (100)
Table 3
Overview of the instrumental techniques used in the five studies on spontaneous recovery.
Spatial Temporal Temporo-spatial
Ratio (%)
Acute Group studies (n ¼ 1) 1 (100)
Case studies (n ¼ 0) / / /
Subacute Group studies (n ¼ 2) 1 (50) 1 (50)
Case studies (n ¼ 1) 1 (100)
Chronic Group studies (n ¼ 0) / / /
comprehension tasks (auditory or reading) by using a functional neuro-imaging technique or magneto-encephalography

technique (which can be considered as yielding temporo-spatial information). In terms of the methodological quality, the
median of the total scores of the group studies (median 15.5, range: 12.5e15.5) is higher than the median of the case studies
(median 12.75, range 12.5e13). This is in part due to the fact that no standardized language battery was used in one case study
to show the clinical progress. On the other hand the case studies evidently lost one point on the aspect “group study”
(Appendix D, Table 3).
Forty-seven the 48 therapy-related studies (97.9%) reported results after a therapy focused on the language disorders and
only 1 after a therapy focused on participation in daily life. The treatment effects in these studies were examined by using a
withdrawal ABA design. In one of the 47 articles, with results after a therapy focused on the language disorders, there was no
measurement of brain activation, but lateralization was assessed and estimated by using a visual lexical decision task. There
was a follow-up from the subacute to the chronic phase. The remaining 46 articles existed of 20 group studies (43.5%) and 26
case studies (56.5%). Within the group studies, results were almost exclusively (19/20, 95%) reported in the chronic phase,
namely in of the studies. One single study mentioned results in the acute phase. Language-evoked brain activity was
measured during comprehension and production tasks, with approximately an equal distribution. To a lesser extent brain
activation was studied during reading tasks and at rest (Table 4). The 26 case studies (16 single and 10 multiple cases)
described the results of 46 persons in total. Also in these studies results were mostly described in the chronic phase (23/26,
88.5%). In contrast to the group studies brain activity was measured mainly during production tasks. Comprehension tasks,
repeating and measurements at rest were only used to a limited extent. The other three studies reported results in the
subacute phase, where mainly auditory comprehension tasks were used (Table 4). Throughout these studies mainly func-
tional neuroimaging was used. Only in the 3 studies on the subacute phase, electrophysiology was used in 2/3 (Table 5). In the
only case study with a therapy focused on participation neuroplasticity was measured during a verbal production task in the
chronic phase by using a spatial neuroimaging technique (Tables 4 and 5). In terms of the methodological quality of the
therapy-related studies, the median of the total scores of the group studies (median: 15.25, range: 11.5e18) was slightly
higher than the median of the case studies (median: 14.25, range 11e17). On the one hand because of the limited use of a
control group in the case studies, namely in 28.5% (8/28) compared to 55% (11/20) in the group studies. On the other hand
only 50% (14/28) of the case studies used a standardized language battery to report the clinical progress, compared to 65% (12/
20) in the group studies (Appendix D, Tables 1 and 2).
3.2. The role of the right hemisphere in aphasia recovery
In the following paragraphs, the role of the right hemisphere (facilitating/inhibiting) will be reported both in spontaneous
and therapy-related aphasia recovery. In most of the studies they used fMRI to measure neuroplasticity. If another imaging
technique was used, this is explicitly mentioned. In this review only neuroplasticity in the right hemisphere is reported, but
it's important to remember that neuroplasticity is a continuous process in both hemispheres. It is the reorganization of
language in both hemispheres that leads to the inhibition or facilitation of aphasia recovery (Saur & Hartwigsen, 2012).
Finally, also the variables with an influence on spontaneous and therapy-related neuroplasticity and more specifically on the
role of the right hemisphere will be discussed.
3.2.1. The role of the right hemisphere in spontaneous aphasia recovery
3.2.1.1. Acute phase. The role of the right hemisphere is reported to be facilitating in the single study in this phase, which
focussed on auditory comprehension. Mattioli et al. (2013) investigated the fMRI-correlates of an early initiated therapy as
well as of spontaneous aphasia recovery. The spontaneous recovery group showed an inferior frontal activity increase during
Table 4
Overview of the tested language aspects in each recovery phase in the 47 treatment-related recovery studies using an imaging technique.
Therapy-related recovery e focus on language disorders (n ¼ 46)
Acute (n ¼ 1) Acute (n ¼ 0)
Auditory sentence comprehension 1 (100) / /
Subacute (n ¼ 0) Subacute (n ¼ 3; 5 measurementsa)

/ / Auditory word comprehension 2 (40)
Auditory sentence comprehension 1 (20)
Verbal word production 2 (40)
Chronic (n ¼ 19; 21 measurementsb) Chronic (n ¼ 23; 24 measurementsc)

Auditory word comprehension 3 (14,3) Auditory word comprehension 2 (8,3)
Auditory sentence comprehension 2 (9,5) Auditory sentence comprehension 2 (8,3)
Reading comprehension (sentences) 1 (4,8) Reading comprehension (sentences) 1 (4,2)
Reading 4 (19) Reading 3 (12,5)
Verbal word production 6 (28,6) Verbal word production 14 (58,3)
Measurement at rest 5 (23,8) Verbal sentence production 1 (4,2)
Measurement at rest 1 (4,2)
Therapy-related recovery e focus on participation in daily life (n ¼ 1)
/ / Chronic (n ¼ 1)
Verbal word production 1 (100)
a
Davis and Harrington, 2006 & Aerts et al. (2014) did two measurements.
b
Richter et al. (2008) did two measurements.
c
Cherney and Small, 2006 did two measurements.
Table 5
Overview of the instrumental techniques used in the 47 studies on therapy-related recovery.
Therapy-related recovery e focus on language disorders (n ¼ 46)
Ratio (%)
Acute Group studies (n ¼ 1) 1 (100)
Case studies (n ¼ 0) / / /
Subacute Group studies (n ¼ 0) / / /

Case studies (n ¼ 3) 1 (33,3) 2 (66,7)
Chronic Group studies (n ¼ 19) 13 (68,4) 3 (15,8) 3 (15,8)

Case studies (n ¼ 23) 18 (78,3) 1 (4,3) 4 (17,4)
Therapy-related recovery e focus on participation in daily life (n ¼ 1)
Ratio (%)
Chronic Group studies (n ¼ 0) / / /
an auditory sentence comprehension task that correlated with the clinical progress of naming. This clinical improvement was
maintained until the follow-up assessment about six months post stroke onset, where a bilateral increase of activity was
measured, but mainly in the left hemisphere.
3.2.1.2. Subacute phase. The role of the right hemisphere was found to be facilitating in the single study on auditory
comprehension. Ilvonen et al. (2003) reported spontaneous recovery of auditory discrimination skills by using mismatch
negativity measurements (MMN). For stimuli presented to the left ear (processed in the right hemisphere) there was a
significant amplitude increase in the frontal regions for stimuli deviating in terms of frequency (not in terms of duration). In
terms of latency, no significant changes were measured. The facilitating effect was concluded from a progressive improve-
ment of language comprehension.
In a single study on reading comprehension, the role of the right hemisphere was described as facilitating. During a
sentence reading comprehension task, a strong left hemisphere lateralization of the Wernicke area and an increase of the
right hemisphere lateralization of the Broca area led to a positive recovery in which the person evolved from an aphasia of
Broca to mild word finding difficulties (Thulborn, Carpenter, & Just, 1999).
In one study using SPECT-measurement of cerebral bloodflow during the resting state there was no difference in the right
hemisphere, between the group with a good recovery and the group with a weak recovery (Vallar et al., 1988).
Therefore in the subacute phase there is an overall idea of a facilitation of spontaneous recovery by right hemispheric
activity, although not all studies are equally convincing.
3.2.1.3. Chronic phase. In Breier, Maher, Schmadeke, Hasan, and Papanicolaou (2007) spontaneous evolution of language has
been described in a case by using MEG measurements. During the active auditory word recognition task a decrease of cerebral
activity was measured at the level of the right supramarginal gyrus and the superior temporal gyrus. The person showed, as
expected in the chronic phase, minimal clinical progress. Unfortunately, the role of the right hemisphere was not discussed.
3.2.2. The role of the right hemisphere in therapy-related aphasia recovery

In the following sections the role of the right hemisphere in each recovery phase is described, as evidenced by functional
activity measurements that took place immediately after ending the therapy period. Follow-up measurements of neuro-
plasticity and language skills, after therapy-free months, only occurred in a limited number of studies. If available, these
results are mentioned separately.
3.2.2.1. Acute phase. In a group study by Mattioli et al. (2013) there was no change in activity during auditory comprehension
in the right hemisphere related to the effects of therapy, which started already two days after the stroke. Therapy-specific
effects which correlated with recovery were only observed in the left inferior frontal gyrus. In comparison to the sponta-
neous recovery group (cfr. supra), the recovery in the treatment group was better. This was evidenced by the significantly
higher score for naming and writing at the Aachen Aphasia Test immediately after treatment and at the follow-up assessment
six months later.
3.2.2.2. Subacute phase. In a single case design Ansaldo, Arguin, and Lecours (2002) examined the effect of therapy on the
lateralization in the subacute and chronic phase. In the subacute phase there was an increase of the right hemisphere
lateralization as evidenced by a reduction in error rate and response time for (pseudo) words presented in the left visual field
during a visual lexical decision task. Along with this increase a significant recovery of language comprehension was measured.
Studies using auditory comprehension showed ambiguous results. Aerts, van Mierlo, Hartsuiker, Santens, and De Letter
(2014) investigated the effect of 90 h of therapy, starting ten days after stroke (three weeks boost therapy, seven weeks
conventional therapy, three weeks boost therapy) by using two neurophysiological tasks: auditory discrimination and word
recognition. There was an amplitude increase of the MMN for tones deviating in the manner of articulation in right lateralized
frontotemporal regions (auditory discrimination) as well as a significant increase for the N400 for pseudowords in bilateral
anterior frontal and right posterior frontoparietal regions (word recognition). This reorganization pattern facilitated the
recovery process as shown by the clinical progress on several language tests. The behavioral results were maintained after a
treatment-free period of six months, measured one year post onset (chronic phase). This contrasted with a decrease of the
neurophysiological responses described above. During an auditory sentence comprehension task in the study by Davis and
Harrington (2006) the meaning of the decrease of the strong right hemisphere lateralization (inferior frontal and superior
temporal gyrus) after an intense semantic therapy was unclear.
Similar ambiguity on the role of right hemisphere activation was described when studying verbal production. In the study
of Laganaro, Morand, Schwitter, Zimmermann, and Schnider (2008) ERP measurements during a verbal word production task
showed in 2/3 cases an increase of amplitude after a computer assisted anomia therapy. This pattern persisted until the
follow-up measurement in the chronic phase for P1 and appeared at this later stage for P2. This neuroplasticity in the right
hemisphere was seen as a facilitator for recovery. The case in Davis and Harrington (2006) showed an increase of inferior
temporal activity (covert naming task) after a semantic therapy, but its impact was considered unclear.
As such a tendency for a facilitatory role of the right hemisphere in treatment-related recovery in the subacute stage can be
retained.s
3.2.2.3. Chronic phase. In one study using a visual lexical decision task, a decrease of right hemisphere lateralization was
measured along with a progress of language production. Nevertheless, the role of right hemisphere was not clear, only the
role of the left hemisphere was discussed (Ansaldo et al., 2002).
Investigation of neuroplastic changes have been described by using MEG or ERP measurements of auditory compre-
hension after Constraint Induced Aphasia Therapy (CIAT) or Intensive Language Action Therapy (ILAT) (Pulvermuller et al.,
2001). A facilitating influence of the right hemisphere was described in a group study of Pulvermüller et al. (2005) where
aphasic patients showed a significant amplitude increase in the time window 250e300 msec for existing words in the
different regions of interest, including the right frontal cortex. This activation increase was positively correlated with the
progress on the Token Test. The case study of Breier et al. (2007) however showed an activity increase in the superior temporal
and the supramarginal gyrus. During the follow-up assessment three months after ending the therapy, a mesial temporal
activity increase was measured in both hemispheres, but there was no more significant activation of the supramarginal gyrus.
The clinical progress on several language batteries remained. In another study of Breier et al. (2009), there was no clear
association between the clinical progress and the changes in activity after CILT. But on the other hand, the pre-CILT activity in
the right hemisphere predicted clinical progress immediately after treatment, but not at follow-up. After a three-month
therapy-free period an inhibitory role of the right hemisphere was shown as the strongest right hemisphere lateralization
(frontotemporoparietal) was measured in the “lost-responders”. In MacGregor, Difrancesco, Pulvermüller, Shtyrov, and Mohr
(2015) no role of the right hemisphere was found. This was confirmed in Breier, Juranek, and Papanicolaou (2011), where no
neuroplastic changes in the right hemisphere were detected immediately after the CILT-therapy. However, the follow-up
assessment, three months after the therapy, pointed to an inhibitory role of the diffuse activity increase because most of
the clinical progress had disappeared.
A facilitating role was shown during auditory sentence comprehension tasks in the PET-study of Musso et al. (1999) where
an increase of posterior superior temporal activity correlated with the progress of language comprehension after an intense
auditory comprehension training. The case in Cherney and Small (2006) showed a similar activity increase after twelve weeks
of classical language therapy as well as the group in Mohr, Difrancesco, Harrington, Evans, and Pulvermüller (2014) after ILAT,
but here mainly at ambiguous sentences. The case in Chouinard, Cummine, and Kim (2012) also showed this pattern at
ambiguous sentences, but in this study the role of the right hemisphere was not discussed.
In two reports brain activity was studied during reading comprehension. The importance of the right inferior frontal gyrus
was reported in three of the five aphasic patients in Kiran, Meier, Kapse, and Glynn (2015). They showed a significant
modulation of the connection MFG-IFG and IFG-MTG after a semantic anomia therapy. A significant progress for the trained
items was measured. In contrast, the case described by Small, Flores, and Noll (1998) showed a mesial temporal activity
decline, but the role of the right hemisphere was not discussed.
Six studies reported on brain activation during reading. During the silent reading of content words Richter, Miltner, and
Straube (2008) referred to the importance of right inferior frontal and insular activity pre-CIAT, as there was a positive
correlation with therapy success. Further, no effect on neuroplasticity was measured as a result of the therapy. A facilitating
influence on the other hand was described in the ERP-study by Barbancho et al. (2015). The global progress after CIAT in
combination with memantine occurred after an amplitude increase of the P100, equally strong in the left and right hemi-
sphere, as measured at the vertex. This amplitude increase correlated with the clinical progress. Also after an effective reading
therapy a facilitating role of the right hemisphere was shown. An increase of inferior frontal and posterior superior temporal
activity was measured during the silent reading of pseudo-words (Adair et al., 2000). This contradicted findings in a group
where the role of the decrease of the right hemisphere lateralization, during the reading of words and pseudowords, was
unclear (Meinzer, Paul, Wienbruch, Djundja, & Rockstroh, 2009). During the reading aloud of content words, the case in
Cherney and Small (2006) showed a decrease in inferior frontal activity after phonological therapy. This person made
progress in terms of discourse production. However, the role of the RH here is unclear since it was not further discussed. A
facilitating effect on the other hand was reported in the case study by Kurland et al. (2008). After an effective reading therapy
an increase of inferior frontal and parietal activity was measured during the reading aloud of abstract words and function
words.
A fair group of 22 studies were selected that reported on brain activity during verbal production. Most of these studies (14)
suggested a facilitatory influence of right hemispheric activity, but 2 were rather indicative of an inhibitory influence, while 3
indicated no role and in 3 the effects were unclear. The single-case studies by Meinzer et al. (2006, 2007) showed a facilitating
role of the right hemisphere after an effective CIAT-therapy. During a naming task an inferior frontal activity increase
appeared as the semantic relationship between response and target word became bigger, with the highest activity when the
answer was correct. Furthermore, subcortical activity (putamen and thalamus) and activity of the cingulate gyrus was
detected (Meinzer et al., 2006). In addition to the cingulate activity an increase of superior and medial frontal activity was
measured in a bilingual case, but only in the German language (Meinzer, Obleser, Flaisch, Eulitz, & Rockstroh, 2007). “Anomia
intention therapy” was developed, based on the opinion that the right hemisphere has a facilitating role in aphasia recovery
(Richards, Singletary, Rothi, Koehler, & Crosson, 2002). The purpose of therapy, namely moving the intention mechanisms to
the right hemisphere, was achieved as evidenced by an activity shift to the right pre-SMA and lateral frontal lobe (Crosson
et al., 2005, 2009) or the preservation of the this lateralization (Crosson et al., 2005). Not only a shift to the right hemi-
sphere, but also a faster response from certain areas after this therapy type was measured. Peck et al. (2004) observed in 1/2
cases a decrease of the response time which correlated with a decrease in the hemodynamic “time to peak activation” in the
right area of Broca, motor cortex and pre-SMA.
Another therapy relying on skills of the right hemisphere is Melodic Intonation Therapy. After this therapy an activity
increase occurred in the inferior frontal, posterior superior temporal and premotor cortex. The language outcome exceeded
the outcome of a control subject (who received classical language therapy) without neuroplastic changes in the right
hemisphere (Schlaug, Marchina, & Norton, 2008). However, a positive influence of the right hemisphere was not confirmed in
the MEG-study by Breier, Randle, Maher, and Papanicolaou (2010), where a decrease of temporofrontal activity was required
in order to observe clinical progress. Breier et al. reported an inhibitory role of the right hemisphere (covert naming task).
Also after anomia therapies with a semantic and/or phonological focus, neuroplasticity was described. After a phonological
anomia therapy in Italian, a parallel recovery in both languages (Dutch and Italian) occurred in a bilingual patient. An activity
increase was measured at the pre- and post-central gyrus and the superior temporal gyrus. Marangolo, Rizzi, Peran, Piras, and
Sabatini (2009) supported the vision of a facilitating role. The same view was supported by Vitali et al. (2007), but another
reorganization pattern occurred in his patient. It was the activity increase at the area of Broca, precuneus and cingulate cortex
that was associated with the clinical progress. Still, the facilitating effect must be put into perspective because more anomic
moments were observed. An increase of activity at the precuneus was confirmed in several studies (Fridriksson et al., 2007;
van Hees, McMahon, Angwin, de Zubicaray, & Copland, 2014.). van Hees et al. (2014) even described a correlation between
this activity increase and the clinical progress of naming.
After a semantic anomia therapy, the results regarding the role of the right hemisphere are discrepant. A facilitating role
was described in the group study by Kiran et al. (2015), where the most consistently modulated connection was IFG-MFG,
what was linked to the clinical progress of naming. On the other hand Marcotte et al. (2012) mentioned a negative role of
the right hemisphere since the two individuals with a weak recovery showed an increase in right hemisphere areas in
contrast to the patients with a good recovery and no increase of activity in the right hemisphere. Cornelissen et al. (2003)
reported no influence.
After computer-assisted anomia therapies (combination of semantic and phonological cuing techniques) a facilitating role
of the right hemisphere was shown. In every study a correlation was found between the activity increase and the clinical
progress. Raboyeau et al. (2008) found an increase at the inferior frontal (BA 45), insular and cingulate gyrus. The cingulate
activity was also measured in the study by Menke et al. (2009) and was, together with the temporoparietal activity (fusiform
gyrus, precuneus, hippocampus), associated with short-term therapy success (immediately after therapy). Long-term success,
eight months after ending the therapy, was determined by the level of activity in the right homologue of Wernicke's area.
Within all the therapy-related articles only one study mentioned results after a therapy with the focus on participation in
daily life, namely PACE. Immediately after this therapy functional imaging during naming demonstrated a recruitment of left
frontal networks. However, the results at follow-up suggested an inhibitory role of the right hemisphere as an activity in-
crease at Wernicke's homologous area, cingulate and fusiform gyrus was measured during the production of incorrect re-
sponses (Kurland, Baldwin, & Tauer, 2010).
After an effective grammatical therapy Thompson, Riley, den Ouden, Meltzer-Asscher, and Lukic (2013) described a
facilitating role of the right hemisphere. The increase of activity at the sensorimotor cortex and superior temporal gyrus
contributed to the restoration of a normal activation pattern. During a sentence generation task (covert task) on the other
hand, no neuroplasticity was measured in both patients in the study by Wierenga et al. (2006).
Finally, a number of studies mentioned activity changes during verbal production in the right hemisphere but their role
was not discussed and thus remains unclear (Meinzer et al., 2008; Fridriksson, Morrow-Odom, Moser, Fridriksson, & Baylis,
2006; Abutalebi, Della Rosa, Tettamanti, Green, & Cappa, 2009).
The role of the right hemisphere is found to be facilitating in half of the 6 studies on resting state measurements. Sarraso
et al. (2010, 2014) investigated, in a case and a group study respectively, the effect of IMITATE-therapy after one day with
seven therapy sessions of 30 min each. The aphasic patients showed minimal progress on the WAB subtest ‘repeating’.
Therapy-effects were measured by using a sleep EEG. The focus was on slow-wave activity. However, the role of the activity
increase in right frontal (Sarasso et al., 2010), superior temporal and parietal areas (Sarasso et al., 2014) was unclear. A
facilitating role was shown by van Hees et al. (2014) who examined the effect of anomia therapy alternately with a
phonological and semantic focus. Over the entire treatment period, an increase of connectivity was measured between the
right inferior temporal and frontal gyrus as well as the right inferior frontal and left supramarginal gyrus. Inferior frontal
activity in the right hemisphere was important because there was a significant positive correlation with the clinical progress
of naming items trained during the phonological therapy. No correlations were found for the semantic therapy, which was
less effective. In an additional study the integrity of the arcuate (AF) and uncinate fasciculus (UF) were examined, but no
significant changes were measured in the right hemisphere (van Hees et al., 2014).
However, Schlaug, Marchina, and Norton (2009) found a significant increase in the number of AF fibers and the AF volume
after MIT. There was a trend toward a correlation between clinical progress in terms of correct information units/min (CIU's/
min) and the increasing number of AF fibers in the right hemisphere. Also Wan, Zheng, Marchina, Norton, and Schlaug (2014)
described the facilitating role of the right hemisphere after MIT. There was a significant inverse correlation between the
decrease in fractional anisotropy (FA) (Sen & Basser, 2005) at the inferior frontal white matter (BA 44) and the clinical
progress of CIU's/min. The FA decline indicated more branches within the right hemisphere. In both MIT studies the
involvement of the right hemisphere was interpreted as facilitating.
From these data a clear and unambiguous picture of the role of right hemispheric activity in treatment-related aphasia
recovery in the chronic stage does not emerge, although it seems that the largest number of studies suggests a facilitatory
influence. Multiple variables may be of influence, including, among others, the type of rehabilitation.
3.3. Variables with an influence on the role of the right hemisphere in spontaneous and therapy-related recovery
Eleven studies mentioned variables that influence changes in the activity of the right hemisphere. Five of them were
injury-related variables, another 5 concerned therapy-related variables and one reported on the influence of language
variables.
During spontaneous recovery, the influence of the localization of the lesion as an injury-related variable, was reported by
Vallar et al. (1988) in a study using resting state measurements. All aphasic patients had a subcortical injury and showed no
activity changes in the right hemisphere. The authors mentioned the importance of the regression of perilesional diaschisis
for subcortical lesions during spontaneous recovery, but reported a more complex reorganization pattern for cortical lesions.
Also, in therapy-related recovery the localization of the lesion was found to have an influence on the role of the right
hemisphere. Meinzer et al. (2006) and Crosson et al. (2005) reported the importance of intact left basal ganglia for a facili-
tating effect of the right hemisphere. An increase of right hemisphere activity during a naming task facilitated the recovery
process, but only when the left basal ganglia were intact. Injury to the inferior frontal gyrus (containing Broca's area) is
determining for a switch of activity to the right hemisphere. An activity increase in the right homologous area contributed to a
positive, but not optimal recovery (Vitali et al., 2007). In contrast, in another study a temporoparietal injury predicted
involvement of the right hemisphere in recovery during an auditory sentence comprehension task, but the specific influence
of the localization of the injury on the role of the right hemisphere remained unclear (Cherney & Small, 2006).
Crosson et al. (2009) reported on the influence of a language-related variable namely the severity of aphasia. A greater
severity prevented the facilitating effect of the right hemisphere after an anomia intention therapy. A facilitating increase of
the right hemisphere lateral frontal activity was only observed in patients with a mild to moderate aphasia. Severely aphasic
patients did not benefit from the therapy and showed no activity changes in the right hemisphere.
The impact of early start of therapy, therapy intensity and content was described as examples of therapy-related variables.
Mattioli et al. (2013) reported the importance of an early start of therapy (two days after stroke) for a favorable reorganization
pattern not involving the right hemisphere. In addition to an early start of therapy, therapy intensity affected the role of the
right hemisphere. The patient described in Aerts et al. (2014) showed an amplitude increase of the N400 for pseudowords in
bilateral anterior frontal and right posterior frontoparietal regions after intensive therapy while a decrease of this activity
occurred after the conventional therapy. The neurophysiological results reflected the results of behavioral tests with pseudo
words (PALPA 1-5-8): there was an improvement after each intensive therapy and a stagnation after the conventional therapy.
Thus after intensive therapy in the subacute phase a facilitating contribution of the right hemisphere, as measured imme-
diately after the therapy period, could be found. The role after a six months therapy-free period is unclear due to a mismatch
between the behavioral and neurophysiological responses, since the behavioral results were unchanged and neurophysio-
logical responses seemed to deteriorate. Finally, the therapy content, was described as having an impact during naming tasks
in the chronic phase. Fridriksson et al. (2006) & van Hees et al. (2014) showed different neural correlates after a phonological
and a semantic anomia therapy. Only after the phonological therapy a facilitating effect of the right precuneus was described.
As last Schlaug et al. (2008) mentioned the importance of the unique MIT components since the role of the right hemisphere
was only facilitating when these components were integrated into the therapy.
4. Discussion
4.1. The role of the right hemisphere in spontaneous and therapy-related aphasia recovery
The aim of this article was to provide an overview of the role of the right hemisphere in the three stages of spontaneous
and therapy-related aphasia recovery after a first stroke in the left hemisphere. Furthermore, the aim was to provide an
overview of the variables that have an influence on the role of the right hemisphere. The current knowledge on this topic has
been inventoried by means of a systematic review. Two electronic databases were screened followed by applying the in- and
exclusion criteria.
A facilitating role of the right hemisphere was described in spontaneous aphasia recovery. During comprehension tasks
(auditory and reading) the inferior frontal gyrus was the most important region both in the acute and subacute phase. The fact
that spontaneous recovery only occurred in the acute and subacute phase is in accordance with the results of a meta-analysis
about the clinical outcome in patients with aphasia (Robey, 1998). The role of the right hemisphere was only described during
comprehension tasks. This may reflect the faster spontaneous recovery of language comprehension compared to language
production (Mazzoni et al., 1992). Unfortunately, due to the limited number of studies about the neural correlates of spon-
taneous aphasia recovery (n ¼ 5), these results should be interpreted with caution and cannot be generalized.
Studies about the neural correlates of therapy-related aphasia recovery mainly mentioned results after a therapy focused
on the language disorder(s). In the acute phase, no indices of activity changes were found in the right hemisphere during an
auditory sentence comprehension task (Mattioli et al., 2013). This finding is not in accordance with the results of Saur et al.
(2006) where a peak activation was observed in the right hemispheric equivalent of Broca's area 12 days post stroke onset.
This contrasting result is possibly due to therapy differences (type/duration/intensity) as these were not specified by Saur
et al.
In the subacute phase only limited research was performed, but a facilitating role of right hemispheric activity was re-
ported in the majority of reports, as measured immediately after ending the therapy. An amplitude increase of the MMN
(manner of articulation) in right lateralized frontotemporal areas was measured during an auditory discrimination task (Aerts
et al., 2014) and a temporal activity increase during a naming task (Laganaro et al., 2008). In addition a visual lexical decision
task showed the importance of the right hemisphere for the recovery of language comprehension (Ansaldo et al., 2002). This
finding corroborates the model on aphasia recovery proposed by Saur et al. (2006) where an increased involvement of ho-
mologous language areas in the right hemisphere accompanies clinical progress.
Regarding the role of the right hemisphere months after ending the therapy in the subacute phase, further research is
required. Aerts et al. (2014) described a dichotomy between the behavioral and neurophysiological results one year post
stroke onset (six months after ending the therapy in the subacute phase). A longer follow-up in the future may possibly
identify the neurophysiological evolution and its relationship with the clinical outcome.
An important aspect to take into account when measuring therapy effects in the first months after stroke is the possible
occurrence of spontaneous recovery. It is therefore impossible to tell with any certainty whether the observed neurophysi-
ological and behavioral changes are the result of the therapeutic intervention, of spontaneous recovery or a combination of
both (R. M. Lazar et al., 2008 . Pulvermüller & Berthier, 2008).
The majority of studies described a facilitating role of the right hemisphere in the chronic phase, as measured during
auditory comprehension tasks immediately after therapy. Activation of homologous language areas in the right hemisphere
was measured and frontal and superior temporal activity correlated with the clinical progress in language comprehension
(Musso et al., 1999; Pulvermüller et al., 2005). The superior temporal activity was particularly related to ambiguous sentences.
This shows the importance of an intact right hemisphere for semantic language processing. This finding has already been
reported in patients after a hemisperectomy (Zaidel, 1976) and can be explained by the bilateral representation of the ventral
pathway (Hickok & Poeppel, 2007).
Two studies reported results of a follow-up assessment (auditory word comprehension), which took place months after
ending the therapy. In both studies, a facilitating role of the right hemisphere was denied, as a strong right hemisphere
lateralization was associated with the loss of clinical progress (Breier et al., 2007, 2009 .). There is no clear explanation as to
why these reports contradict the results of the abovementioned studies in chronic aphasia.
During verbal word production mainly a facilitating role of the right hemisphere was described, again measured imme-
diately after therapy. An activity increase in homologous language areas as well as non-language-related areas (hippocampal
gyrus, cingulate gyrus and precuneus) was found in various studies. Specific correlations were found between clinical
progress and activity increase at the inferior frontal gyrus and insula as well as the right cingulate gyrus, precuneus and
hippocampal gyrus. The activation of homologous language areas is in line with the results described above. Activation of the
cingulate gyrus, precuneus and hippocampal gyrus is not. It involves areas related to attention (Price & Devlin, 2003) and
(episodic) memory (Cavanna, 2007). A role for areas related to memory has previously been described in healthy subjects who
learn new words. This indicates a similarity between neural mechanisms in the acquisition of language and the recovery from
aphasia after stroke (Rijntjes, 2006). Still the facilitating role of the right hemisphere should be interpreted with caution
because next to clinical improvement an increase of anomic moments was observed (Vitali et al., 2007). Furthermore, two
studies clearly indicate a contradictory inhibitory role (Breier et al., 2010 . Marcotte et al., 2012.).
A clear statement about the role of the right hemisphere in the longer term, being months after ending the therapy, cannot
be formulated. The one study with results after a therapy focused on participation in daily life showed an activity increase at
the right homologue of Wernicke's area was measured during incorrect responses (Kurland et al., 2010). Although this could
be considered as a demonstration of maladaptive plasticity involving the right hemisphere, there might be alternative in-
terpretations. On the other hand long-term success, eight months after an anomia therapy, was linked to this activity increase
(Menke et al., 2009). These contrasting results are possibly due to the different approaches in the therapy (participation
versus language disorders), but further research is required to confirm this.
Studies in which sentence reading comprehension tasks, reading tasks and measurements at rest were used to describe
neuroplasticity are scarce and results of the role of the right hemisphere are diverse. More research is required to yield a
clearer picture about this topic.
4.2. Variables with an influence on the role of the right hemisphere in aphasia recovery
Localization was mentioned as an injury-related variable in studies about spontaneous and therapy-related recovery.
Spontaneous recovery after a subcortical injury would only be based on regression of perilesional diaschisis with no role for
the right hemisphere (Vallar et al., 1988). In therapy-related recovery the importance of intact basal ganglia was emphasized
for a facilitating role of the right hemisphere (Meinzer et al., 2006; Crosson et al., 2005). A lesion including Broca's area was
suggested to be required for an activation of the right hemisphere. Its role is considered to be facilitating, but not optimal
(Vitali et al., 2007). The importance of a preserved superior temporal gyrus for a favorable language outcome has been
described previously (Goldenberg & Spatt, 1994; Kertesz et al., 1979; Maas et al., 2012 .; Selnes et al., 1983), but the effect of
this variable on the role of the right hemisphere is not clear from the included studies.
The impact of language-related variables such as the severity of aphasia was described after anomia intention therapy.
Only in patients with a mild to moderate aphasia improved from the treatment while the right hemisphere exhibited a
facilitating role. Severely aphasic patients showed no beneficial effects from the therapy and did not show the facilitating
right hemisphere lateralization of activity in the lateral frontal regions (Crosson et al., 2005).
Finally three treatment-related variables were described: an early start, the therapy intensity and therapy content. An
early start of therapy resulted in a more favorable outcome without an involvement of the right hemisphere (Mattioli et al.,
2013). In addition, intensive and conventional therapies were characterized by different neural correlates. As described in the
study by Aerts et al. (2014), a bilateral anterior frontal and right posterior frontoparietal amplitude increase of the N400 for
pseudowords occurred after intensive therapy, but a decrease after conventional therapy. Therapy content additionally
affected changes of activity in the right hemisphere. Only after a phonological therapy the facilitating role of the right pre-
cuneus (Fridriksson et al., 2006; van Hees et al., 2014) was shown. Furthermore, the unique MIT components resulted in a
facilitating contribution of the right hemisphere (Schlaug et al., 2008).
Results on the variables affecting the role of the right hemisphere in spontaneous and therapy-related aphasia recovery are
scarce. Only 11 of the 51 included articles made mention of this. Based on this limited information a conclusive answer to the
research question cannot be formulated. These primary results can be seen as a basis for further research.
5. Conclusion
This systematic review gives an overview of the current knowledge about the role of the right hemisphere in the three
stages of spontaneous and therapy-related aphasia recovery. The literature on the neural correlates of spontaneous and
therapy-related aphasia recovery in the acute and subacute phase is still too scarce to clearly define the role of the right
hemisphere. In contrast, more research has been done in the chronic phase and a facilitating role of right hemispheric activity
during comprehension and production tasks can be described in the period following language therapy. However, there is a
need for a systematic follow-up of neuroplastic changes and behavioral language skills to obtain a clearer picture of the role of
the right hemisphere in the longer term. Finally, further research on variables affecting the role of the right hemisphere in
aphasia recovery is required to fill the gaps in the current knowledge.
Appendix A. Search terms
“Aphasia þ brain plasticity”

“Aphasia þ epilepsy þ right hemisphere”
“Aphasia þ language recovery”
“Aphasia þ language reorganization”
“Aphasia þ language reorganization þ brain plasticity”
“Aphasia þ language reorganization þ stroke”
“Aphasia þ neuroplasticity”
“Aphasia þ neuroplasticity þ right hemisphere”

“Aphasic patients þ brain plasticity”
“Aphasia þ phonological encoding disorder”
“Aphasia þ post stroke þ contralesional regions”
“Aphasia þ post stroke þ language þ right frontal regions”
“Aphasia þ recovery grammar”
“Aphasia þ recovery þ language lateralization”
“Aphasia þ recovery þ language outcome”
“Aphasia þ recovery þ language reorganization”
“Aphasia þ recovery þ neurophysiology”
“Aphasia þ recovery þ neuroplasticity”
“Aphasia þ recovery phonology”
“Aphasia þ recovery pragmatics”
“Aphasia þ recovery þ reorganization patterns”
“Aphasia þ recovery þ right frontal regions”
“Aphasia þ recovery þ right hemisphere”
“Aphasia þ recovery þ right hemisphere þ neuroplasticity”
“Aphasia þ recovery semantics”
“Aphasia þ recovery þ stroke þ right hemisphere”
“Aphasia þ recovery syntax”
“Aphasia þ rehabilitation þ right hemisphere”
“Aphasia þ rehabilitation þ outcome”
“Aphasia þ right hemisphere compensation”
“Aphasia þ right hemisphere involvement”
“Aphasia þ right hemisphere þ neural activity”
“Aphasia þ right hemisphere þ phoneme perception”
“Aphasia þ right hemisphere þ phonological”
“Aphasia þ right hemisphere þ phonological network”
“Aphasia þ right hemisphere þ phonology”
“Aphasia þ right hemisphere þ semantics”
“Aphasia þ right hemisphere þ syntax”
“Aphasia þ spontaneous recovery”
“Aphasia þ spontaneous recovery þ fMRI”
“Aphasia þ spontaneous recovery þ MEG”
“Aphasia þ spontaneous recovery þ PET”
“Aphasia þ spontaneous recovery þ SPECT”
“Aphasia þ spontaneous recovery þ ERP”
“Aphasia þ spontaneous recovery þ neural substrates”
“Aphasia þ therapy þ functional magnetic resonance imaging”
“Aphasia þ therapy þ magnetoencephalography”
“Aphasia þ therapy þ event related potentials”
“Aphasia þ therapy þ PET”
“Aphasia þ therapy þ SPECT”
“Acquired dyslexia þ therapy þ fMRI”
“Acquired dyslexia þ therapy þ MEG”
“Acquired dyslexia þ therapy þ PET”
“Acquired dyslexia þ therapy þ ERP”
“Acquired dyslexia þ therapy þ SPECT”
“Acquired dysgraphia þ therapy þ fMRI”
“Acquired dysgraphia þ therapy þ PET”
“Acquired dysgraphia þ therapy þ SPECT”
“Acquired dysgraphia þ therapy þ MEG”
“Acquired dysgraphia þ therapy þ ERP”
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Sarasso, S., Ma €a
€tta
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Appendix C. The scoring system used for evaluating methodological quality
Table 1
The detailed scoring system for the methodological quality of the study design
Item Maximum score (4) Distribution of points

Study design
Prospective study 1 0/1: retrospective study 1/1: prospective study
Group study 1 0/1: case study 1/1: group study
Control group 2 0/2: no control group 2/2: control group
Table 2
The detailed scoring system for the methodological quality of the study content (items marked with * were not scored for studies that described spontaneous
recovery)
Item Maximum score Distribution of points

(15)
Study content
Phase of recovery 2 0/2: not mentioned
2/2: clearly mentioned
Cause of aphasia 1 0/1: not mentioned
0,5/1: only “stroke” is mentioned
1/1: the type of stroke (ischemic ischemia hemorraghe) is mentioned
Type of aphasia 1 0/1: not mentioned
0,5/1: only “fluent/nonfluent” is mentioned 1/1: the type of aphasia is clearly mentioned
Localization of the injury 2 0/2: not mentioned
1/2: the localization is mentioned in terms of the vascular areas 2/2: a specific description of the
localization is mentioned
Activity on T1 1 0/1: not mentioned
Activity on T2 1 0/1: not mentioned
Follow-up* 1 0/1: none
0,5/1: follow-up of the language skills OR neural activity
1/1: follow-up of the language skills AND neural activity
Objective imaging 2 0/2: no use of an objective imaging technique AND no clarification of the examined language aspect
technique 1/2: no use of an objective imaging technique OR no clarification of the examined language aspect
2/2: use of an objective imaging technique and a clarification of the examined language aspect
Standardized language 2 0/2: the clinical progress was not described by using a standardized language battery
battery 2/2: the clinical progress was described by using a standardized language battery
Information about 2 0/2: no information about the content, duration, frequency and intensity of the therapy
therapy* 2/2: no information about the content(0.5), duration (0.5), frequency (0.5) and intensity (0.5) of the
therapy
Appendix D. Methodological quality
Table 1
Methodological quality of the reviewed articles (therapy-related recovery, group studies)
N Author Published Prospective study (1) Group study (1) Control group (2) Recovery phase (2) Cause (1) Type of aphasia (1)
1 Musso et al. 1999 1 1 0 2 0,5 1
2 F. Pulvermüller et al. 2005 1 1 0 2 0,5 1
3 M. Meinzer et al. 2008 1 1 0 2 1 1
4 G. Raboyeau et al. 2008 1 1 0 2 0,5 1
5 M. Richter et al. 2008 1 1 2 2 0,5 1
6 B. Crosson et al. 2009 1 1 2 2 1 1
7 J. Breier et al. 2009 1 1 0 2 1 0
8 G. Schlaug et al. 2009 1 1 0 2 0,5 1
9 R. Menke et al. 2009 1 1 2 2 1 1
10 M. Meinzer et al. 2009 1 1 2 2 1 1
11 F. Mattioli 2013 1 1 2 2 0,5 1
12 S. Van Hees 2014 1 1 2 2 0,5 1
13 S. Van Hees 2014 1 1 2 2 0,5 1
14 S. Van Hees 2014 1 1 2 2 0,5 1
15 C. Wan et al. 2014 1 1 2 2 1 1
16 S. Sarasso et al. 2014 1 1 0 2 1 1
17 B. Mohr et al. 2014 1 1 0 2 1 0,5
18 L.J. MacGregor et al. 2014 1 1 0 2 1 0,5
19 M. Barbancho et al. 2015 1 1 2 2 1 1
20 S. Kiran et al. 2015 1 1 2 2 0,5 0
N Injury Activity before therapy Activity after therapy Follow-up Objective imaging Standardized language Therapy Total
(2) (1) (1) (1) technique (2) battery (2) (2) (19)
1 2 0 1 0 2 0 2 12,5
2 2 1 1 0 2 2 2 15,5
3 1 0,5 0,5 0 2 2 2 14
4 2 0 1 0 2 0 2 12,5
5 2 1 1 0 2 2 2 17,5
6 2 1 1 0 2 2 1,5 17,5
7 1 1 1 0,5 2 2 2 14,5
Table 1 (continued )
N Injury Activity before therapy Activity after therapy Follow-up Objective imaging Standardized language Therapy Total
(2) (1) (1) (1) technique (2) battery (2) (2) (19)
8 0 1 1 0 1 2 2 12,5
9 1 1 1 1 2 0 2 16
10 0 1 1 0 2 2 2 16
11 2 1 1 1 2 2 1,5 18
12 2 1 1 0 2 0 1,5 15
13 2 1 1 0 1 0 1,5 14
14 2 1 1 0 1 0 1,5 14
15 1 1 1 0 1 2 2 16
16 2 1 1 0 1 2 2 15
17 2 1 1 0 2 2 2 15,5
18 2 1 1 0 2 2 2 15,5
19 1 1 1 1 2 2 2 18
20 1 0 1 0 2 0 1 11,5
Table 2
Methodological quality of the reviewed articles (therapy-related recovery, case studies, * no measurement of neuroplasticity, ** therapy focused on
participation)
1 S. Small 1998 1 0 0 2 1 0
2 Adair et al. 2000 1 0 0 2 1 1
3* Ansaldo et al. 2002 1 0 0 2 1 0
4 Cornelissen et al.
2002 1 0 0 2 1 1
5 Peck et al. 2004 1 0 2 2 0,5 0,5
6 B. Crosson et al.
2005 1 0 0 2 1 0,5
7 M. Meinzer et al.
2006 1 0 2 2 1 1
8 L. Cherney et al.
2006 1 0 2 2 1 1
9 J. Fridriksson 2006 1 0 2 2 1 1
10 C. Davis et al. 2006 1 0 0 2 1 1
11 C. Wierenga et al.
2006 1 0 0 2 1 1
12 P. Vitali et al.2007 1 0 0 2 1 1
13 J. Fridriksson et al.
2007 1 0 2 2 1 1
14 J. Breier et al.2007 1 0 2 2 1 0
15 M. Meinzer et al.
2007 1 0 0 2 1 1
16 G. Schlaug et al.
2008 1 0 0 2 1 1
17 J. Kurland et al.
2008 1 0 0 2 0,5 0,5
18 M. Laganaro et al.
2008
P1 1 0 2 2 1 1
P2 1 0 2 2 1 1
P3 1 0 2 2 1 0,5
19 P. Marangolo et al. 2009 1 0 0 2 1 0
20 J. Abutalebi 2009 1 0 0 2 1 0,5
21** J. Kurland et al. 2010 1 0 0 2 0,5 1
22 S. Sarasso 2010 1 0 0 2 1 0,5
23 J. Breier et al. 2010 1 0 0 2 1 0,5
24 J. Breier et al. 2011 1 0 0 2 0,5 0
25 B. Chouinard et al. 2012 1 0 0 2 0,5 1
26 K. Marcotte et al. 2012 1 0 0 2 0,5 1
27 C. Thompson 2013 1 0 2 2 0,5 0,5
28 A. Aerts et al. 2015 1 0 0 2 1 1
N Injury Activity before Activity after therapy Follow-up Objective imaging Standardized language Therapy Total
(2) therapy (1) (1) (1) technique (2) battery (2) (2) (19)
1 2 1 1 0 2 0 1 11
2 2 1 1 0 2 0 1 12
3* 2 1 1 0 1 2 2 13
4 2 1 1 0 2 2 2 15
5 2 1 1 0 2 0 1,5 13,5
6 2 1 1 0 2 0 1,5 12
7 2 1 1 0 2 2 2 17
8 2 1 1 0 2 2 2 17
9 2 1 1 0 2 0 2 15
10 2 1 1 0 2 2 2 15
11 2 1 1 0 2 2 2 15
(continued on next page)
Table 2 (continued )
N Injury Activity before Activity after therapy Follow-up Objective imaging Standardized language Therapy Total
(2) therapy (1) (1) (1) technique (2) battery (2) (2) (19)
12 2 1 1 0 2 0 2 13
13 2 1 1 0 2 2 2 17
14 2 1 1 1 2 2 2 17
15 2 1 1 0 2 1 2 14
16 2 1 1 0 2 2 2 15
17 2 1 1 0 2 0 2 12
18 15
2 1 1 1 2 0 1,5 15,5
2 1 1 1 2 0 1,5 15,5
2 1 1 0 2 0 1,5 14
19 2 1 1 0 2 0 2 12
20 2 1 1 0 2 2 2 14,5
21** 2 1 1 1 2 0 2 13,5
22 0 1 1 0 1 2 2 11,5
23 2 1 1 0 2 2 2 14,5
24 2 1 1 1 2 2 2 14,5
25 2 0 1 0 2 0 2 11,5
26 2 1 1 0 2 0 2 11,5
27 2 1 1 0 2 0 2 14
28 2 1 1 1 2 2 2 16
Table 3
Methodological quality of the reviewed articles (spontaneous recovery)
1 Giuseppe Vallar et al. 1988 1 1 0 2 1 0,5
2 Keith R. Thulborn et al. 1999 1 0 2 2 1 0,5
3 Ilvonen et al. 2003 1 1 2 2 0,5 1
4 J. Breier et al. 2007 1 0 2 2 1 0
5 Mattioli et al. 2013 1 1 2 2 0,5 1
N Injury (2) Activity on T1 (1) Activity on T2 (1) Objective imaging technique (2) Standardized language battery (2) Total (16)
1 2 1 1 1 2 12,5
2 2 1 1 2 0 12,5
3 2 1 1 2 2 15,5
4 1 1 1 2 2 13
5 2 1 1 2 2 15,5
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Journal of Neurolinguistics: Elissa-Marie Cocquyt, Lisa de Ley, Patrick Santens, John Van Borsel, Miet de Letter

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Journal of Neurolinguistics 44 (2017) 68e90

Contents lists available at ScienceDirect

The role of the right hemisphere in the recovery of

1.1. The recovery of aphasia: general considerations

1.2. The right hemisphere in aphasia recovery

1.3. Variables affecting aphasia recovery

3.1. Research design and -quality

Selection Inclusion criteria Exclusion criteria

Fig. 1. Overview of the data collection process.

Group studies (n ¼ 3) Ratio (%) Case studies (n ¼ 2) Ratio (%)

Spatial Temporal Temporo-spatial

comprehension tasks (auditory or reading) by using a functional neuro-imaging technique or magneto-encephalography

3.2. The role of the right hemisphere in aphasia recovery

3.2.1. The role of the right hemisphere in spontaneous aphasia recovery

Therapy-related recovery e focus on language disorders (n ¼ 46)

Subacute (n ¼ 0) Subacute (n ¼ 3; 5 measurementsa)

Chronic (n ¼ 19; 21 measurementsb) Chronic (n ¼ 23; 24 measurementsc)

Therapy-related recovery e focus on language disorders (n ¼ 46)

Spatial Temporal Temporo-spatial

Subacute Group studies (n ¼ 0) / / /

Chronic Group studies (n ¼ 19) 13 (68,4) 3 (15,8) 3 (15,8)

3.2.2. The role of the right hemisphere in therapy-related aphasia recovery

Appendix A. Search terms

“Aphasia þ brain plasticity”

“Aphasia þ neuroplasticity þ right hemisphere”

Appendix B. References reviewed articles

Appendix C. The scoring system used for evaluating methodological quality

Item Maximum score (4) Distribution of points

Item Maximum score Distribution of points

Appendix D. Methodological quality

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