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

Action Semantic Deficits and Impaired Motor Skills in Autistic Adults Without Intellectual Impairment

Several studies indicate the functional importance of the motor cortex for higher cognition, language and semantic processing, and place the neural substrate of these processes in sensorimotor action-perception circuits linking motor, sensory and perisylvian language regions. Interestingly, in individuals with autism spectrum disorder (ASD), semantic processing of action and emotion words seems to be impaired and is associated with hypoactivity of the motor cortex during semantic processing. In this study, the relationship between semantic processing, fine motor skills and clinical symptoms was investigated in 19 individuals with ASD and 22 typically-developing matched controls. Participants completed two semantic decision tasks involving words from different semantic categories, a test of alexithymia (the Toronto Alexithymia Scale), and a test of fine motor skills (the Purdue Pegboard Test). A significant Group × Word Category interaction in accuracy (p < 0.05) demonstrated impaired semantic processing for action words, but not object words in the autistic group. There was no significant group difference when processing abstract emotional words or abstract neutral words. Moreover, our study revealed deficits in fine motor skills as well as evidence for alexithymia in the ASD group, but not in neurotypical controls. However, these motor deficits did not correlate significantly with impairments in action-semantic processing. We interpret the data in terms of an underlying dysfunction of the action-perception system in ASD and its specific impact on semantic language processing

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

Lost for emotion words: what motor and limbic brain activity reveals about autism and semantic theory.

Autism spectrum conditions (ASC) are characterised by deficits in understanding and expressing emotions and are frequently accompanied by alexithymia, a difficulty in understanding and expressing emotion words. Words are differentially represented in the brain according to their semantic category and these difficulties in ASC predict reduced activation to emotion-related words in limbic structures crucial for affective processing. Semantic theories view 'emotion actions' as critical for learning the semantic relationship between a word and the emotion it describes, such that emotion words typically activate the cortical motor systems involved in expressing emotion actions such as facial expressions. As ASC are also characterised by motor deficits and atypical brain structure and function in these regions, motor structures would also be expected to show reduced activation during emotion-semantic processing. Here we used event-related fMRI to compare passive processing of emotion words in comparison to abstract verbs and animal names in typically-developing controls and individuals with ASC. Relatively reduced brain activation in ASC for emotion words, but not matched control words, was found in motor areas and cingulate cortex specifically. The degree of activation evoked by emotion words in the motor system was also associated with the extent of autistic traits as revealed by the Autism Spectrum Quotient. We suggest that hypoactivation of motor and limbic regions for emotion word processing may underlie difficulties in processing emotional language in ASC. The role that sensorimotor systems and their connections might play in the affective and social-communication difficulties in ASC is discussed.This work was supported by the Medical Research Council (MRC) (MC_US_A060_0034, U1055.04.003.00001.01 to F.P., MC_US_A060_0043, MC-A060-5PQ90 to Y. S., MRC studentship to R.M.).The is the final published paper originally published in NeuroImage under a CC-BY licence (RL Moseley, Y Shtyrov, B Mohr, MV Lombardo, S Baron-Cohen, F Pulvermüller, NeuroImage 2015, 104, 413-422

Increased recruitment of domain general neural networks in language processing following Intensive Language-Action Therapy – fMRI evidence from people with chronic aphasia.

Purpose: The present study aimed to provide novel insights into the neural correlates of language improvement following Intensive Language Action Therapy (ILAT; also known as Constraint Induced Aphasia Therapy, CIAT). Method: Sixteen people with chronic aphasia underwent clinical aphasia assessment (Aachen Aphasia Test, AAT), as well as functional magnetic resonance imaging (fMRI), both administered before (T1) and after ILAT (T2). The fMRI task included passive reading of single written words, with hashmark strings as visual baseline. Results: Behavioral results indicated significant improvements of AAT scores across therapy and fMRI results showed T2−T1 blood oxygenation level dependent (BOLD) signal change in the left precuneus to be modulated by the degree of AAT score increase. Subsequent region-of-interest (ROI) analysis of this precuneus cluster confirmed a positive correlation of T2−T1 BOLD signal change and improvement on the clinical aphasia test. Similarly, the entire default mode network (DMN) revealed a positive correlation between T2−T1 BOLD signal change and clinical language improvement. Conclusion: These results are consistent with a more efficient recruitment of domain general neural networks in language processing, including those involved in attentional control, following aphasia therapy with ILAT.This work was supported by the Deutsche Forschungsgemeinschaft (pu 97/15-1 and 97/15-2 awarded to F. P.), the Deutsche Akademische Austauschdienst (fellowship to G. L.), and the Einstein Center for Neuroscience Berlin (fellowship awarded to L. D.

Ultra-rapid access to words in chronic aphasia: the effects of intensive language action therapy (ILAT).

Effects of intensive language action therapy (ILAT) on automatic language processing were assessed using Magnetoencephalography (MEG). Auditory magnetic mismatch negativity (MMNm) responses to words and pseudowords were recorded in twelve patients with chronic aphasia before and immediately after two weeks of ILAT. Following therapy, Patients showed significant clinical improvements of auditory comprehension as measured by the Token Test and in word retrieval and naming as measured by the Boston Naming Test. Neuromagnetic responses dissociated between meaningful words and meaningless word-like stimuli ultra-rapidly, approximately 50 ms after acoustic information first allowed for stimulus identification. Over treatment, there was a significant increase in the left-lateralisation of this early word-elicited activation, observed in perilesional fronto-temporal regions. No comparable change was seen for pseudowords. The results may reflect successful, therapy-induced, language restitution in the left hemisphere

Hemispheric contributions to language reorganisation: An MEG study of neuroplasticity in chronic post stroke aphasia.

Previous studies have demonstrated that efficient neurorehabilitation in post stroke aphasia leads to clinical language improvements and promotes neuroplasticity. Brain areas frequently implicated in functional restitution of language after stroke comprise perilesional sites in the left hemisphere and homotopic regions in the right hemisphere. However, the neuronal mechanisms underlying therapy-induced language restitution are still largely unclear. In this study, magnetoencephalography was used to investigate neurophysiological changes in a group of chronic aphasia patients who underwent intensive language action therapy (ILAT), also known as constraint-induced aphasia therapy (CIAT). Before and immediately after ILAT, patients' language and communication skills were assessed and their brain responses were recorded during a lexical magnetic mismatch negativity (MMNm) paradigm, presenting familiar spoken words and meaningless pseudowords. After the two-week therapy interval, patients showed significant clinical improvements of language and communication skills. Spatio-temporal dynamics of neuronal changes revealed a significant increase in word-specific neuro-magnetic MMNm activation around 200ms after stimulus identification points. This enhanced brain response occurred specifically for words and was most pronounced over perilesional areas in the left hemisphere. Therapy-related changes in neuromagnetic activation for words in both hemispheres significantly correlated with performance on a clinical language test. The findings indicate that functional recovery of language in chronic post stroke aphasia is associated with neuroplastic changes in both cerebral hemispheres, with stronger left-hemispheric contribution during automatic stages of language processing

Donepezil alone and combined with intensive language-action therapy on depression and apathy in chronic post-stroke aphasia: A feasibility study

This study explored the feasibility and effectiveness of a short-term (10-week) intervention trial using Donepezil administered alone and combined with intensive language action therapy (ILAT) for the treatment of apathy and depression in ten people with chronic post-stroke aphasia. Outcome measures were the Western Aphasia Battery and the Stroke Aphasia Depression Questionnaire-21. Structural magnetic resonance imaging and 18fluorodeoxyglucose positron emission tomography were acquired at baseline and after two endpoints (Donepezil alone and Donepezil-ILAT). The intervention was found to be feasible to implement. Large treatment effects were found. Donepezil alone and combined with ILAT reduced aphasia severity, while apathy and depression only improved with Donepezil-ILAT. Structural and functional neuroimaging data did not show conclusive results but provide hints for future research. Given these overall positive findings on feasibility, language and behavioral benefits, further studies in larger sample sizes and including a placebo-control group are indicated