Neuroplasticity of language networks in aphasia: advances, updates, and future challenges

Researchers have sought to understand how language is processed in the brain, how brain damage affects language abilities, and what can be expected during the recovery period since the early 19th century. In this review, we first discuss mechanisms of damage and plasticity in the post-stroke brain, both in the acute and the chronic phase of recovery. We then review factors that are associated with recovery. First, we review organism intrinsic variables such as age, lesion volume and location and structural integrity that influence language recovery. Next, we review organism extrinsic factors such as treatment that influence language recovery. Here, we discuss recent advances in our understanding of language recovery and highlight recent work that emphasizes a network perspective of language recovery. Finally, we propose our interpretation of the principles of neuroplasticity, originally proposed by Kleim and Jones (1) in the context of extant literature in aphasia recovery and rehabilitation. Ultimately, we encourage researchers to propose sophisticated intervention studies that bring us closer to the goal of providing precision treatment for patients with aphasia and a better understanding of the neural mechanisms that underlie successful neuroplasticity.P50 DC012283 - NIDCD NIH HHSPublished versio

Magnetoencephalography in Stroke Recovery and Rehabilitation

Magnetoencephalography (MEG) is a non-invasive neurophysiological technique used to study the cerebral cortex. Currently, MEG is mainly used clinically to localize epileptic foci and eloquent brain areas in order to avoid damage during neurosurgery. MEG might, however, also be of help in monitoring stroke recovery and rehabilitation. This review focuses on experimental use of MEG in neurorehabilitation. MEG has been employed to detect early modifications in neuroplasticity and connectivity, but there is insufficient evidence as to whether these methods are sensitive enough to be used as a clinical diagnostic test. MEG has also been exploited to derive the relationship between brain activity and movement kinematics for a motor-based brain-computer interface. In the current body of experimental research, MEG appears to be a powerful tool in neurorehabilitation, but it is necessary to produce new data to confirm its clinical utility

fMRI evidence from auditory semantic processing

The role of the two hemispheres in the neurorehabilitation of language is still under dispute. This study explored the changes in language-evoked brain activation over a 2-week treatment interval with intensive constraint induced aphasia therapy (CIAT), which is also called intensive language action therapy (ILAT). Functional magnetic resonance imaging (fMRI) was used to assess brain activation in perilesional left hemispheric and in homotopic right hemispheric areas during passive listening to high and low-ambiguity sentences and non- speech control stimuli in chronic non-fluent aphasia patients. All patients demonstrated significant clinical improvements of language functions after therapy. In an event-related fMRI experiment, a significant increase of BOLD signal was manifest in right inferior frontal and temporal areas. This activation increase was stronger for highly ambiguous sentences than for unambiguous ones. These results suggest that the known language improvements brought about by intensive constraint-induced language action therapy at least in part relies on circuits within the right-hemispheric homologs of left- perisylvian language areas, which are most strongly activated in the processing of semantically complex language

Changes of right-hemispheric activation after constraint-induced, intensive language action therapy in chronic aphasia: fMRI evidence from auditory semantic processing

The role of the two hemispheres in the neurorehabilitation of language is still under dispute. This study explored the changes in language-evoked brain activation over a 2-week treatment interval with intensive constraint induced aphasia therapy (CIAT), which is also called intensive language action therapy (ILAT). Functional magnetic resonance imaging (fMRI) was used to assess brain activation in perilesional left hemispheric and in homotopic right hemispheric areas during passive listening to high and low-ambiguity sentences and non-speech control stimuli in chronic non-fluent aphasia patients. All patients demonstrated significant clinical improvements of language functions after therapy. In an event-related fMRI experiment, a significant increase of BOLD signal was manifest in right inferior frontal and temporal areas. This activation increase was stronger for highly ambiguous sentences than for unambiguous ones. These results suggest that the known language improvements brought about by intensive constraint-induced language action therapy at least in part relies on circuits within the right-hemispheric homologs of left-perisylvian language areas, which are most strongly activated in the processing of semantically complex language

A Mismatch Negativity Study of (A)Grammatical and Meaningful/less Mini- Constructions

Clinical language performance and neurophysiological correlates of language processing were measured before and after intensive language therapy in patients with chronic (time post stroke >1 year) post stroke aphasia (PSA). As event-related potential (ERP) measure, the mismatch negativity (MMN) was recorded in a distracted oddball paradigm to short spoken sentences. Critical ‘deviant’ sentence stimuli where either well-formed and meaningful, or syntactically, or lexico-semantically incorrect. After 4 weeks of speech- language therapy (SLT) delivered with high intensity (10.5 h per week), clinical language assessment with the Aachen Aphasia Test battery demonstrated significant linguistic improvements, which were accompanied by enhanced MMN responses. More specifically, MMN amplitudes to grammatically correct and meaningful mini-constructions and to ‘jabberwocky’ sentences containing a pseudoword significantly increased after therapy. However, no therapy-related changes in MMN responses to syntactically incorrect strings including agreement violations were observed. While MMN increases to well-formed meaningful strings can be explained both at the word and construction levels, the neuroplastic change seen for ‘jabberwocky’ sentences suggests an explanation in terms of constructions. The results confirm previous reports that intensive SLT leads to improvements of linguistic skills in chronic aphasia patients and now demonstrate that this clinical improvement is associated with enhanced automatic brain indexes of construction processing, although no comparable change is present for ungrammatical strings. Furthermore, the data confirm that the language-induced MMN is a useful tool to map functional language recovery in PSA

Melodic Intonation Therapy in Post-Stroke Non-Fluent Aphasia and Its Effects on Brain Plasticity

Melodic Intonation Therapy (MIT) is one of the most well-known therapies for the rehabilitation of speech in patients with non-fluent aphasia and which is thought to promote right-hemisphere involvement in language processing. This review focuses on the study of language lateralization and/or neuroplastic reorganization with neuroimaging and/or neurophysiological techniques in non-fluent aphasic patients post-stroke during or after MIT. A systematic search was carried out according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) in databases (PubMed, Scopus, EMBASE, Dialnet, Web of Science, Cochrane) with the keywords melodic intonation therapy, neuroimaging, functional magnetic resonance, and positron emission tomography and the boolean operators AND and OR. Articles including patients of all ages and either sex with any type of aphasia post-stroke and in any language, which studied language lateralization and/or neuroplastic reorganization after or during MIT were included. Articles which did not achieve the objectives, revisions and conferences were excluded. Different results were obtained from the 16 studies included in the review: predominantly greater activation of the right hemisphere but also of the left hemisphere or both. MIT is an effective therapy to rehabilitate non-fluent aphasic patients post-stroke. It involves different neurobiological mechanisms and depends on multiple individual factors. Studies with larger samples are necessary.Open access funding provided by University of Málaga and PAIDI Group CTS 159

Change in Right Inferior Longitudinal Fasciculus Integrity Is Associated With Naming Recovery in Subacute Poststroke Aphasia

Background. Despite progress made in understanding functional reorganization patterns underlying recovery in subacute aphasia, the relation between recovery and changes in white matter structure remains unclear. Objective. To investigate changes in dorsal and ventral language white matter tract integrity in relation to naming recovery in subacute poststroke aphasia. Methods. Ten participants with aphasia after left-hemisphere stroke underwent language testing and diffusion tensor imaging twice within 3 months post onset, with a 1-month interval between sessions. Deterministic tractography was used to bilaterally reconstruct the superior longitudinal fasciculus (SLF), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), middle longitudinal fasciculus (MdLF), and uncinate fasciculus (UF). Per tract, the mean fractional anisotropy (FA) was extracted as a measure of microstructural integrity. Naming accuracy was assessed with the Boston Naming Test (BNT). Correlational analyses were performed to investigate the relationship between changes in FA values and change in BNT score. Results. A strong positive correlation was found between FA change in the right ILF within the ventral stream and change on the BNT (r = 0.91, P <.001). An increase in FA in the right ILF was associated with considerable improvement of naming accuracy (range BNT change score: 12-14), a reduction with limited improvement or slight deterioration. No significant correlations were found between change in naming accuracy and FA change in any of the other right or left ventral and dorsal language tracts. Conclusions. Naming recovery in subacute aphasia is associated with change in the integrity of the right ILF