Plastic changes following imitation-based speech and language therapy for aphasia: A high-density sleep EEG study

Simone Sarasso; Sara Määttä; Fabio Ferrarelli; Rositsa Poryazova; Giulio Tononi; Steven L. Small

doi:10.1177/1545968313498651

Plastic changes following imitation-based speech and language therapy for aphasia: A high-density sleep EEG study

Simone Sarasso, Sara Määttä, Fabio Ferrarelli, Rositsa Poryazova, Giulio Tononi, Steven L. Small

Research output: Contribution to journal › Article › peer-review

51 Scopus citations

Abstract

Background. Objective measurement of plastic brain changes induced by a novel rehabilitative approach is a key requirement for validating its biological rationale linking the potential therapeutic gains to the changes in brain physiology. Objective. Based on an emerging notion linking cortical plastic changes to EEG sleep slow-wave activity (SWA) regulation, we aimed to assess the acute plastic changes induced by an imitation-based speech therapy in individuals with aphasia by comparing sleep SWA changes before and after therapy. Methods. A total of 13 left-hemispheric stroke patients underwent language assessment with the Western Aphasia Battery (WAB) before and after 2 consecutive high-density (hd) EEG sleep recordings interleaved by a daytime session of imitation-based speech therapy (Intensive Mouth Imitation and Talking for Aphasia Therapeutic Effects [IMITATE]). This protocol is thought to stimulate bilateral connections between the inferior parietal lobule and the ventral premotor areas. Results. A single exposure to IMITATE resulted in increases in local EEG SWA during subsequent sleep over the same regions predicted by the therapeutic rationale, particularly over the right hemisphere (unaffected by the lesion). Furthermore, changes in SWA over the left-precentral areas predicted changes in WAB repetition scores in our group, supporting the role of perilesional areas in predicting positive functional responses. Conclusions. Our results suggest that SWA changes occurring in brain areas activated during imitation-based aphasia therapy may reflect the acute plastic changes induced by this intervention. Further testing will be needed to evaluate SWA as a non-invasive assessment of changes induced by the therapy and as a predictor of positive long-term clinical outcome.

Original language	English (US)
Pages (from-to)	129-138
Number of pages	10
Journal	Neurorehabilitation and Neural Repair
Volume	28
Issue number	2
DOIs	https://doi.org/10.1177/1545968313498651
State	Published - Feb 2014
Externally published	Yes

Keywords

EEG
SWA
aphasia
sleep
stroke

ASJC Scopus subject areas

Rehabilitation
Neurology
Clinical Neurology

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10.1177/1545968313498651

Cite this

@article{5922e6fd545f46d6853cd1572de8f698,

title = "Plastic changes following imitation-based speech and language therapy for aphasia: A high-density sleep EEG study",

abstract = "Background. Objective measurement of plastic brain changes induced by a novel rehabilitative approach is a key requirement for validating its biological rationale linking the potential therapeutic gains to the changes in brain physiology. Objective. Based on an emerging notion linking cortical plastic changes to EEG sleep slow-wave activity (SWA) regulation, we aimed to assess the acute plastic changes induced by an imitation-based speech therapy in individuals with aphasia by comparing sleep SWA changes before and after therapy. Methods. A total of 13 left-hemispheric stroke patients underwent language assessment with the Western Aphasia Battery (WAB) before and after 2 consecutive high-density (hd) EEG sleep recordings interleaved by a daytime session of imitation-based speech therapy (Intensive Mouth Imitation and Talking for Aphasia Therapeutic Effects [IMITATE]). This protocol is thought to stimulate bilateral connections between the inferior parietal lobule and the ventral premotor areas. Results. A single exposure to IMITATE resulted in increases in local EEG SWA during subsequent sleep over the same regions predicted by the therapeutic rationale, particularly over the right hemisphere (unaffected by the lesion). Furthermore, changes in SWA over the left-precentral areas predicted changes in WAB repetition scores in our group, supporting the role of perilesional areas in predicting positive functional responses. Conclusions. Our results suggest that SWA changes occurring in brain areas activated during imitation-based aphasia therapy may reflect the acute plastic changes induced by this intervention. Further testing will be needed to evaluate SWA as a non-invasive assessment of changes induced by the therapy and as a predictor of positive long-term clinical outcome.",

keywords = "EEG, SWA, aphasia, sleep, stroke",

author = "Simone Sarasso and Sara M{\"a}{\"a}tt{\"a} and Fabio Ferrarelli and Rositsa Poryazova and Giulio Tononi and Small, {Steven L.}",

note = "Funding Information: In the present study, we used whole-night sleep hd-EEG recordings to investigate the effects of a single intensive exposure to speech-language therapy on brain plasticity. We focused on an imitation-based, computer-assisted rehabilitative protocol for aphasia treatment aimed at brain remodeling in the parietal-frontal motor pathway known to be important in action observation and imitation. During NREM sleep following the IMITATE protocol—practiced for 3.5 hours during a single day—we found a local increase in EEG SWA in a group of individuals with ischemic stroke and accompanying aphasia. This local increase in SWA was found over a set of cortical areas shown to be particularly active during both speech observation and imitation in healthy individuals. 5 , 10 , 26 Results derived from activation networks based on structural equation modeling of fMRI series during observation and imitation of syllables showed that bilateral connections between the inferior parietal lobule and premotor ventral areas are involved in both observation and imitation, pointing to the notion that observation and imitation of speech engage a frontal-parietal network with significant homologies to the “mirror neuron” circuit in macaques. 11 - It is well established that sleep slow waves can be regulated at a local level based on prior waking activity. 27 31 Many recent studies, however, have also shown that changes in NREM SWA reflect the occurrence of changes in synaptic strength in local networks, consistent with the idea that neuronal plasticity and sleep need are linked. 16 , 32 In humans, a 5-Hz potentiation protocol using repetitive transcranial magnetic stimulation results in local potentiation of cortical responses, consistent with synaptic strengthening followed by a local increase in sleep SWA. 33 , 34 Similarly, paired-associative stimulation protocols involving induction of either cortical potentiation or depression results in local NREM SWA increases and decreases, respectively. 35 Finally, in both humans and rats, learning a motor task increases NREM SWA specifically in the trained cortical area. 12 , 36 Thus, it is likely that the increase in sleep SWA over the right hemisphere observed in the present study may underlie a change in synaptic strength in those cortical circuits engaged by the IMITATE protocol during the day. It is worth reporting that NREM sleep EEG spectral features 37 and topographies 38 have been previously shown to be very stable within individuals across different nights even after massive global behavioral and pharmacological manipulations such as total sleep deprivation 39 and the administration of GABAergic agents. 40 This sleep EEG power “fingerprint” may reflect individual peculiarities of brain functional anatomy, which are known to be determined by genetic factors. It is therefore likely that the local topographical SWA changes found here are reflective of genuine effects induced by the behavioral intervention occurring between the 2 nights (see similar effects reported in Huber et al 24 ). These changes were found during the course of the entire night ( Figure 3 ). As previously discussed in M{\"a}{\"a}tt{\"a} et al, 25 plastic events occurring closer to sleep time may have a larger influence on NREM EEG at the beginning of sleep, during the first sleep cycle. By contrast, plastic events occurring at an earlier time during the day may be more detectable at a later time in sleep NREM EEG power. In line with this study, our IMITATE protocol was carried out during the afternoon up until a few hours before the patient{\textquoteright}s bedtime, thereby inducing SWA changes throughout the night. In addition, following therapy, high-frequency EEG activity in the β range was found to be increased over the same area that showed SWA effects. This result is in line with a previous report showing that human sleep slow waves tend to modulate spindle as well as β EEG activity. 41 Thus, increased synchronization leading to larger slow waves (as reflected by increased SWA) may be also associated with more synchronous β frequency modulation and, in turn, to increased β activity. This is the first study in which the link between local sleep SWA and plasticity is investigated in a population presenting with cortical brain lesions. Although observation and imitation of speech is known to involve both hemispheres in healthy individuals, 10 here the relative heterogeneity of cortical lesions over the left hemisphere ( Figure 1 ) characterizing our patients group may explain why the observed changes induced by IMITATE ( Figure 2 ) were most consistently found over the right, healthy hemisphere. Recently, a regional increase in SWA was found to be associated with behavioral improvement in performance on a previously learned task, 12 thus strictly linking synaptic downscaling during sleep with behavioral gains. 16 Here we observed a correlation between the SWA changes and the improvement in WAB Repetition subscale scores after IMITATE in a cluster of electrodes located over the left hemisphere and overlapping with the areas predicted by the therapeutic rationale. These preliminary observations, although limited by the single exposure to speech therapy and by the small sample size, seem to suggest that the effects of IMITATE over perilesional left-hemispheric regions might be predictive of functional outcome. Supporting this view, previous preliminary work based on fMRI data from a single aphasic patient reported long-term reorganization of a left-hemispheric functional network toward the normative model 10 after the administration of the full 6-week IMITATE therapy. 42 This is consistent with recent 43 and earlier imaging studies 44 of aphasia recovery. - Any intense behavioral manipulation involving experience-dependent plasticity exerts its effect over widespread areas of the cortex involved in the task execution. Our data are in line with previous human and animal models of stroke recovery, revealing functional and structural neural plasticity occurring both in perilesional areas and in brain regions distant from the lesion site 45 48 and further imply a dynamic process for aphasia recovery. The observed changes in SWA after IMITATE over the right hemisphere (here not predictive of functional outcome) may thus reflect functional reorganization induced by the therapy possibly related to the specific task execution per se rather than linked to speech function recovery. - Although the role of the left versus the right hemisphere in facilitating recovery from aphasia has been a highly debated issue in clinical research, 49 it is becoming increasingly accepted that perilesional left-hemisphere activity in aphasia poststroke predicts the best language outcomes. Of course, such activity—and the concomitant outcome—largely depends on the left-hemispheric lesion extent. Usually, patients with small lesions of the left hemisphere tend to recruit left-perilesional areas with variable involvement of right-hemispheric structures. 44 , 50 , 51 Conversely, in patients with relatively large lesions in the left hemisphere, the only path to recovery may be through the recruitment of homologous language and speech-motor regions in the right hemisphere. 50 54 Thus, in order to shed light on which path to recovery IMITATE protocol is more actively stimulating, future studies should apply the standard 6-week IMITATE protocol on patients affected by small left-hemispheric lesions versus patients with lesions involving large portions of the left hemisphere. In addition, in order to test the reliability of the changes in sleep SWA in predicting positive long-term clinical outcomes, patients{\textquoteright} sleep as well as speech assessment should be reassessed both after the first exposure to IMITATE and at the end of the full therapeutic regimen, therefore also excluding potential learning effects resulting from repeated exposure to the WAB items. To test for the specificity of the observed local changes, in future studies, it would also be important to compare the effects on sleep SWA following IMITATE with those obtained by applying other intensive speech therapeutic interventions not specifically targeting the imitation domain. Altogether, these findings suggest that plastic changes occur in areas activated during the execution of IMITATE, possibly reflecting the effectiveness of such intervention, therefore providing evidence for the neurobiological rationale of the therapy. Furthermore, these results support the notion that sleep hd-EEG and the topographical analysis of SWA are well suited to investigating local brain plastic changes underpinning functional recovery in neurological populations, allowing for a noninvasive and repeatable assessment of such changes. Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The work described here has been supported by the National Institute of Deafness and other Communication Disorders of the National Institutes of Health of the United States of America under grant R01-DC-0007488 (Dr Small) and by the James S. McDonnell Foundation grant to the Brain Network Recovery Group and The Virtual Brain project (Drs Small and Tononi) as well as by the support of “Dote ricerca”: FSE, Regione Lombardia (Dr Sarasso). The aphasia testing described here was performed by speech-language pathologists in the laboratory of Dr Leora Cherney at the Rehabilitation Institute of Chicago, including Edie Babbitt, Robert Rosalind Hurwitz, and Jaime Lee. In addition, both Blythe Buchholz and Rob Fowler provided critical technical support at The University of Chicago and Susan Duncan helped significantly at the University of California, Irvine. The support of our funding agencies and these supporting personnel is gratefully acknowledged. ",

year = "2014",

month = feb,

doi = "10.1177/1545968313498651",

language = "English (US)",

volume = "28",

pages = "129--138",

journal = "Neurorehabilitation and Neural Repair",

issn = "1545-9683",

publisher = "Sage Science Press",

number = "2",

}

TY - JOUR

T1 - Plastic changes following imitation-based speech and language therapy for aphasia

T2 - A high-density sleep EEG study

AU - Sarasso, Simone

AU - Määttä, Sara

AU - Ferrarelli, Fabio

AU - Poryazova, Rositsa

AU - Tononi, Giulio

AU - Small, Steven L.

N1 - Funding Information: In the present study, we used whole-night sleep hd-EEG recordings to investigate the effects of a single intensive exposure to speech-language therapy on brain plasticity. We focused on an imitation-based, computer-assisted rehabilitative protocol for aphasia treatment aimed at brain remodeling in the parietal-frontal motor pathway known to be important in action observation and imitation. During NREM sleep following the IMITATE protocol—practiced for 3.5 hours during a single day—we found a local increase in EEG SWA in a group of individuals with ischemic stroke and accompanying aphasia. This local increase in SWA was found over a set of cortical areas shown to be particularly active during both speech observation and imitation in healthy individuals. 5 , 10 , 26 Results derived from activation networks based on structural equation modeling of fMRI series during observation and imitation of syllables showed that bilateral connections between the inferior parietal lobule and premotor ventral areas are involved in both observation and imitation, pointing to the notion that observation and imitation of speech engage a frontal-parietal network with significant homologies to the “mirror neuron” circuit in macaques. 11 - It is well established that sleep slow waves can be regulated at a local level based on prior waking activity. 27 31 Many recent studies, however, have also shown that changes in NREM SWA reflect the occurrence of changes in synaptic strength in local networks, consistent with the idea that neuronal plasticity and sleep need are linked. 16 , 32 In humans, a 5-Hz potentiation protocol using repetitive transcranial magnetic stimulation results in local potentiation of cortical responses, consistent with synaptic strengthening followed by a local increase in sleep SWA. 33 , 34 Similarly, paired-associative stimulation protocols involving induction of either cortical potentiation or depression results in local NREM SWA increases and decreases, respectively. 35 Finally, in both humans and rats, learning a motor task increases NREM SWA specifically in the trained cortical area. 12 , 36 Thus, it is likely that the increase in sleep SWA over the right hemisphere observed in the present study may underlie a change in synaptic strength in those cortical circuits engaged by the IMITATE protocol during the day. It is worth reporting that NREM sleep EEG spectral features 37 and topographies 38 have been previously shown to be very stable within individuals across different nights even after massive global behavioral and pharmacological manipulations such as total sleep deprivation 39 and the administration of GABAergic agents. 40 This sleep EEG power “fingerprint” may reflect individual peculiarities of brain functional anatomy, which are known to be determined by genetic factors. It is therefore likely that the local topographical SWA changes found here are reflective of genuine effects induced by the behavioral intervention occurring between the 2 nights (see similar effects reported in Huber et al 24 ). These changes were found during the course of the entire night ( Figure 3 ). As previously discussed in Määttä et al, 25 plastic events occurring closer to sleep time may have a larger influence on NREM EEG at the beginning of sleep, during the first sleep cycle. By contrast, plastic events occurring at an earlier time during the day may be more detectable at a later time in sleep NREM EEG power. In line with this study, our IMITATE protocol was carried out during the afternoon up until a few hours before the patient’s bedtime, thereby inducing SWA changes throughout the night. In addition, following therapy, high-frequency EEG activity in the β range was found to be increased over the same area that showed SWA effects. This result is in line with a previous report showing that human sleep slow waves tend to modulate spindle as well as β EEG activity. 41 Thus, increased synchronization leading to larger slow waves (as reflected by increased SWA) may be also associated with more synchronous β frequency modulation and, in turn, to increased β activity. This is the first study in which the link between local sleep SWA and plasticity is investigated in a population presenting with cortical brain lesions. Although observation and imitation of speech is known to involve both hemispheres in healthy individuals, 10 here the relative heterogeneity of cortical lesions over the left hemisphere ( Figure 1 ) characterizing our patients group may explain why the observed changes induced by IMITATE ( Figure 2 ) were most consistently found over the right, healthy hemisphere. Recently, a regional increase in SWA was found to be associated with behavioral improvement in performance on a previously learned task, 12 thus strictly linking synaptic downscaling during sleep with behavioral gains. 16 Here we observed a correlation between the SWA changes and the improvement in WAB Repetition subscale scores after IMITATE in a cluster of electrodes located over the left hemisphere and overlapping with the areas predicted by the therapeutic rationale. These preliminary observations, although limited by the single exposure to speech therapy and by the small sample size, seem to suggest that the effects of IMITATE over perilesional left-hemispheric regions might be predictive of functional outcome. Supporting this view, previous preliminary work based on fMRI data from a single aphasic patient reported long-term reorganization of a left-hemispheric functional network toward the normative model 10 after the administration of the full 6-week IMITATE therapy. 42 This is consistent with recent 43 and earlier imaging studies 44 of aphasia recovery. - Any intense behavioral manipulation involving experience-dependent plasticity exerts its effect over widespread areas of the cortex involved in the task execution. Our data are in line with previous human and animal models of stroke recovery, revealing functional and structural neural plasticity occurring both in perilesional areas and in brain regions distant from the lesion site 45 48 and further imply a dynamic process for aphasia recovery. The observed changes in SWA after IMITATE over the right hemisphere (here not predictive of functional outcome) may thus reflect functional reorganization induced by the therapy possibly related to the specific task execution per se rather than linked to speech function recovery. - Although the role of the left versus the right hemisphere in facilitating recovery from aphasia has been a highly debated issue in clinical research, 49 it is becoming increasingly accepted that perilesional left-hemisphere activity in aphasia poststroke predicts the best language outcomes. Of course, such activity—and the concomitant outcome—largely depends on the left-hemispheric lesion extent. Usually, patients with small lesions of the left hemisphere tend to recruit left-perilesional areas with variable involvement of right-hemispheric structures. 44 , 50 , 51 Conversely, in patients with relatively large lesions in the left hemisphere, the only path to recovery may be through the recruitment of homologous language and speech-motor regions in the right hemisphere. 50 54 Thus, in order to shed light on which path to recovery IMITATE protocol is more actively stimulating, future studies should apply the standard 6-week IMITATE protocol on patients affected by small left-hemispheric lesions versus patients with lesions involving large portions of the left hemisphere. In addition, in order to test the reliability of the changes in sleep SWA in predicting positive long-term clinical outcomes, patients’ sleep as well as speech assessment should be reassessed both after the first exposure to IMITATE and at the end of the full therapeutic regimen, therefore also excluding potential learning effects resulting from repeated exposure to the WAB items. To test for the specificity of the observed local changes, in future studies, it would also be important to compare the effects on sleep SWA following IMITATE with those obtained by applying other intensive speech therapeutic interventions not specifically targeting the imitation domain. Altogether, these findings suggest that plastic changes occur in areas activated during the execution of IMITATE, possibly reflecting the effectiveness of such intervention, therefore providing evidence for the neurobiological rationale of the therapy. Furthermore, these results support the notion that sleep hd-EEG and the topographical analysis of SWA are well suited to investigating local brain plastic changes underpinning functional recovery in neurological populations, allowing for a noninvasive and repeatable assessment of such changes. Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The work described here has been supported by the National Institute of Deafness and other Communication Disorders of the National Institutes of Health of the United States of America under grant R01-DC-0007488 (Dr Small) and by the James S. McDonnell Foundation grant to the Brain Network Recovery Group and The Virtual Brain project (Drs Small and Tononi) as well as by the support of “Dote ricerca”: FSE, Regione Lombardia (Dr Sarasso). The aphasia testing described here was performed by speech-language pathologists in the laboratory of Dr Leora Cherney at the Rehabilitation Institute of Chicago, including Edie Babbitt, Robert Rosalind Hurwitz, and Jaime Lee. In addition, both Blythe Buchholz and Rob Fowler provided critical technical support at The University of Chicago and Susan Duncan helped significantly at the University of California, Irvine. The support of our funding agencies and these supporting personnel is gratefully acknowledged.

PY - 2014/2

Y1 - 2014/2

N2 - Background. Objective measurement of plastic brain changes induced by a novel rehabilitative approach is a key requirement for validating its biological rationale linking the potential therapeutic gains to the changes in brain physiology. Objective. Based on an emerging notion linking cortical plastic changes to EEG sleep slow-wave activity (SWA) regulation, we aimed to assess the acute plastic changes induced by an imitation-based speech therapy in individuals with aphasia by comparing sleep SWA changes before and after therapy. Methods. A total of 13 left-hemispheric stroke patients underwent language assessment with the Western Aphasia Battery (WAB) before and after 2 consecutive high-density (hd) EEG sleep recordings interleaved by a daytime session of imitation-based speech therapy (Intensive Mouth Imitation and Talking for Aphasia Therapeutic Effects [IMITATE]). This protocol is thought to stimulate bilateral connections between the inferior parietal lobule and the ventral premotor areas. Results. A single exposure to IMITATE resulted in increases in local EEG SWA during subsequent sleep over the same regions predicted by the therapeutic rationale, particularly over the right hemisphere (unaffected by the lesion). Furthermore, changes in SWA over the left-precentral areas predicted changes in WAB repetition scores in our group, supporting the role of perilesional areas in predicting positive functional responses. Conclusions. Our results suggest that SWA changes occurring in brain areas activated during imitation-based aphasia therapy may reflect the acute plastic changes induced by this intervention. Further testing will be needed to evaluate SWA as a non-invasive assessment of changes induced by the therapy and as a predictor of positive long-term clinical outcome.

AB - Background. Objective measurement of plastic brain changes induced by a novel rehabilitative approach is a key requirement for validating its biological rationale linking the potential therapeutic gains to the changes in brain physiology. Objective. Based on an emerging notion linking cortical plastic changes to EEG sleep slow-wave activity (SWA) regulation, we aimed to assess the acute plastic changes induced by an imitation-based speech therapy in individuals with aphasia by comparing sleep SWA changes before and after therapy. Methods. A total of 13 left-hemispheric stroke patients underwent language assessment with the Western Aphasia Battery (WAB) before and after 2 consecutive high-density (hd) EEG sleep recordings interleaved by a daytime session of imitation-based speech therapy (Intensive Mouth Imitation and Talking for Aphasia Therapeutic Effects [IMITATE]). This protocol is thought to stimulate bilateral connections between the inferior parietal lobule and the ventral premotor areas. Results. A single exposure to IMITATE resulted in increases in local EEG SWA during subsequent sleep over the same regions predicted by the therapeutic rationale, particularly over the right hemisphere (unaffected by the lesion). Furthermore, changes in SWA over the left-precentral areas predicted changes in WAB repetition scores in our group, supporting the role of perilesional areas in predicting positive functional responses. Conclusions. Our results suggest that SWA changes occurring in brain areas activated during imitation-based aphasia therapy may reflect the acute plastic changes induced by this intervention. Further testing will be needed to evaluate SWA as a non-invasive assessment of changes induced by the therapy and as a predictor of positive long-term clinical outcome.

KW - EEG

KW - SWA

KW - aphasia

KW - sleep

KW - stroke

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Plastic changes following imitation-based speech and language therapy for aphasia: A high-density sleep EEG study

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