Functional Connectivity and Speech Entrainment Speech Entrainment Improves Connectivity Between Anterior and Posterior Cortical Speech Areas in Non-fluent Aphasia.

BACKGROUND: Speech entrainment (SE), the online mimicking of an audio-visual speech model, has been shown to increase speech fluency in individuals with non-fluent aphasia. One theory that may explain why SE improves speech output is that it synchronizes functional connectivity between anterior and posterior language regions to be more similar to that of neurotypical speakers. OBJECTIVES: The present study tested this by measuring functional connectivity between 2 regions shown to be necessary for speech production, and their right hemisphere homologues, in 24 persons with aphasia compared to 20 controls during both free (spontaneous) speech and SE. METHODS: Regional functional connectivity in participants with aphasia were normalized to the control data. Two analyses were then carried out: (1) normalized functional connectivity was compared between persons with aphasia and controls during free speech and SE and (2) stepwise linear models with leave-one-out cross-validation including normed functional connectivity during both tasks and proportion damage to the left hemisphere as independent variables were created for each language score. RESULTS: Left anterior-posterior functional connectivity and left posterior to right anterior functional connectivity were significantly more similar to connectivity of the control group during SE compared to free speech. Additionally, connectivity during free speech was more associated with language measures than connectivity during SE. CONCLUSIONS: Overall, these results suggest that SE promotes normalization of functional connectivity (i.e., return to patterns observed in neurotypical controls), which may explain why individuals with non-fluent aphasia produce more fluent speech during SE compared to spontaneous speech.

Effect of High Frequency Transcranial Magnetic Stimulation on Recovery of Chronic Post-Stroke Aphasia.

BACKGROUND: Both hemispheres have role in post-stroke aphasia recovery but better recovery is expected with the restoration of function by the left hemisphere. Transcranial stimulation has been used to favor recruitment of left-hemispheric language networks and increase activity of the left hemisphere, thus helps aphasia recovery . OBJECTIVE: The aim of this study is to evaluate the effect of excitatory repetitive transcranial magnetic stimulation (rTMS) on recovery of post stroke aphasic patients . MATERIALS AND METHODS: Twenty patients with post stroke chronic aphasia were enrolled in the study. Aphasia severity was assessed using Aphasia Severity Rating Scale (ASRS). Linguistic deficits were assessed using Kasr Al-Aini Arabic Aphasia test (KAAT). Real rTMS was applied three for 10 sessions of 10-Hz stimulation, positioned over the left Broca's area of the affected hemisphere. All patients were evaluated before, after the end of treatment sessions and one month later . RESULTS: There was a significant improvement in the mean total score and mean scores of components of KAAT scale before, immediately after and after one month of rTMS (P< 0.05). Moreover, there was a significant improvement in mean scores of ASRS before, immediately after and after one month of rTMS (P= 0.000). There was a significant difference in mean scores of ASRS and KAAT before, immediately after the last session and after one month between small, medium and large brain infarcts. (P< 0.05). CONCLUSION: Excitatory rTMS is a beneficial adjuvant therapy that improves language skills in patients with chronic post-stroke non-fluent aphasia in short and long term. The protocol of this observational study was registered in clinical trial registration: www.ClinicalTrials.gov, identifier: NCT04708197.

Effect of Low-Frequency rTMS and Intensive Speech Therapy Treatment on Patients With Nonfluent Aphasia After Stroke.

BACKGROUND: To observe the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on patients with nonfluent aphasia after stroke. MATERIALS AND METHODS: Thirty patients were divided into control, rTMS, and 2 times a day low-frequency rTMS (2rTMS) groups, and all 3 groups had intensive speech therapy (ST). Patients were assessed by western aphasia battery (WAB) scale. The spontaneous language, listening comprehension, retelling, and naming were scored, respectively. The expression of brain-derived neurotrophic factor (BDNF) in peripheral blood was detected by enzyme-linked immunosorbent assay. RESULTS: There was significant difference in aphasia quotient after treatment in the 3 groups. The values of the 4 dimensions in the WAB score of the rTMS group were higher than those in the control group. The WAB scores in the 2rTMS group were higher than those in the rTMS group. After 2 weeks treatment, the BDNF levels in the rTMS group and the 2rTMS group were significantly higher than those in the control group. Four weeks later, the 2rTMS group was significantly increased compared with the control group and the rTMS group. CONCLUSIONS: Low-frequency rTMS combined with conventional ST treatment can effectively improve the language function of patients with nonfluent aphasia after stroke. Two times a day low-frequency rTMS therapy combined with conventional ST treatment can improve the language function of patients with nonfluent aphasia after stroke more effectively and it also promote the expression of BDNF more effectively, thereby improving nerve repair and protecting brain tissue.

The role of semantic transparency in processing compound nouns: evidence from people with Broca's Aphasia.

This article investigated the role of semantic transparency in processing root compound nouns in Persian individuals with Broca's aphasia through picture confrontation naming and repetition tasks. The relationship between semantic transparency and affected constituents of nouns showed that semantic transparency had no role in processing compound nouns. The results showed that transparent, opaque and partially transparent compound nouns were processed by dual-routes (holistic and decomposing). Frequency of errors also revealed dissociation of naming and repetition processes as well as simple and compound nouns. The comparison of errors and their types in confrontation naming and repetition tasks indicated that naming was relatively more complex than repetition.

Neural structures supporting spontaneous and assisted (entrained) speech fluency.

Non-fluent speech is one of the most common impairments in post-stroke aphasia. The rehabilitation of non-fluent speech in aphasia is particularly challenging as patients are rarely able to produce and practice fluent speech production. Speech entrainment is a behavioural technique that enables patients with non-fluent aphasia to speak fluently. However, its mechanisms are not well understood and the level of improved fluency with speech entrainment varies among individuals with non-fluent aphasia. In this study, we evaluated the behavioural and neuroanatomical factors associated with better speech fluency with the aid of speech entrainment during the training phase of speech entrainment. We used a lesion-symptom mapping approach to define the relationship between chronic stroke location on MRI and the number of different words per second produced during speech entrainment versus picture description spontaneous speech. The behavioural variable of interest was the speech entrainment/picture description ratio, which, if ≥1, indicated an increase in speech output during speech entrainment compared to picture description. We used machine learning (shallow neural network) to assess the statistical significance and out-of-sample predictive accuracy of the neuroanatomical model, and its regional contributors. We observed that better assisted speech (higher speech entrainment/picture description ratio) was achieved by individuals who had preservation of the posterior middle temporal gyrus, inferior fronto-occipital fasciculus and uncinate fasciculus, while exhibiting lesions in areas typically associated with non-fluent aphasia, such as the superior longitudinal fasciculus, precentral, inferior frontal, supramarginal and insular cortices. Our findings suggest that individuals with dorsal stream damage but preservation of ventral stream structures are more likely to achieve more fluent speech with the aid of speech entrainment compared to spontaneous speech. This observation provides insight into the mechanisms of non-fluent speech in aphasia and has potential implications for future research using speech entrainment for rehabilitation of non-fluent aphasia.

In search for common patterns in aphasia: The case of Spanish wh-dependencies.

BACKGROUND: Research on comprehension of wh-dependencies in Broca's aphasia has resulted in discrepant findings, suggesting that structurally different languages may involve different comprehension patterns. AIMS: In the present study, we investigated whether Spanish speakers with Broca's aphasia rely on a language-specific cue that might facilitate comprehension of object wh-dependencies - the preposition a. Since the preposition a in Spanish indicates animate objects, reliance on this cue would facilitate comprehension of more demanding object wh-dependencies, cancelling out processing differences between structures with subject and object extractions. METHODS: We studied comprehension of subject vs. object quién ("who") and qué ("which") direct and embedded questions, and relative clauses introduced by que in seven speakers with aphasia (SWA): six with Broca's and one with mixed aphasia. Control data were obtained from ten neurologically intact elderly Spanish speakers. RESULTS: Mann-Whitney test revealed that compared to healthy controls, SWA had preserved comprehension of both subject and object who direct questions, object which direct questions, and object relative clauses. However, they exhibited considerably worse comprehension of subject which direct questions, all embedded questions regardless of the extraction site (subject, object) or type of wh-word (who, which), and subject relative clauses. Individual comprehension profiles obtained in a modified t-test and revised standardized difference test, while containing some variability, largely support lack of subject-object asymmetry and objects-better patterns. Furthermore, in direct questions, comprehension of who questions was better than the comprehension of which questions, while the opposite was found in embedded questions. CONCLUSIONS: The lack of significant subject-object asymmetry in most conditions, together with better comprehension of object than subject extractions in direct questions, indicates that Spanish SWA rely on the preposition a in the comprehension of object wh-dependencies. However, this strategy fails in more complex conditions (embedded questions), because the processing costs outweigh the facilitating effects of this cue, unless additional cues to the object are present (object relatives). The present findings have implications for the accounts of wh-dependencies in Broca's aphasia involving Discourse-linking, the Intervener hypothesis, and the Competition model.

Functional Connectivity of Language Regions of Stroke Patients with Expressive Aphasia During Real-Time Functional Magnetic Resonance Imaging Based Neurofeedback.

Stroke lesions in the language centers of the brain impair the language areas and their connectivity. This article describes the dynamics of functional connectivity (FC) of language areas (FCL) during real-time functional magnetic resonance imaging (RT-fMRI)-based neurofeedback training for poststroke patients with expressive aphasia. The hypothesis is that FCL increases during the upregulation of language areas during neurofeedback training and that the training improves FCL with an increasing number of sessions and restores it toward normalcy. Four test and four control patients with expressive aphasia were recruited for the study along with four healthy volunteers termed as the normal group. The test and normal groups were administered four neurofeedback training sessions in between two test sessions, whereas the control group underwent only the two test sessions. The training session requires the subject to exercise language activity covertly so that it upregulates the feedback signal obtained from the Broca's area (in left inferior frontal gyrus) and amplifies the feedback when it is correlated with the Wernicke's area (in left superior temporal gyrus) using RT-fMRI. FC was measured by Pearson's correlation coefficient. The results indicate that the FC of the test group was weaker in the left hemisphere than that of the normal group, and post-training the connections have strengthened (correlation coefficient increases) in the left hemisphere when compared with the control group. The connections of language areas strengthened in both hemispheres during neurofeedback-based upregulation, and multiple training sessions strengthened new pathways and restored left hemispheric connections toward normalcy.

Progressive agrammatic aphasia without apraxia of speech as a distinct syndrome.

Agrammatic aphasia affects grammatical language production and can result from a neurodegenerative disease. Although it typically presents with concomitant apraxia of speech, this is not always the case. Little is known about the clinical course and imaging features of patients that present with agrammatism in the absence of apraxia of speech, which we will refer to as progressive agrammatic aphasia. We aimed to make a detailed description of the longitudinal clinical, linguistic, and neuroimaging features of a cohort of 11 patients with progressive agrammatic aphasia to provide a complete picture of this syndrome. All patients underwent detailed speech and language, neurological and neuropsychological assessments, 3 T structural and diffusion tensor imaging MRI, 18F-fluorodeoxyglucose and Pittsburgh compound B PET. The 11 patients were matched by age and gender to 22 patients who had mixed apraxia of speech and agrammatism. The progressive agrammatic aphasia patients performed abnormally on tests of language, general cognition, executive function, and functional ability at baseline and declined in these measures over time. Only two patients eventually developed apraxia of speech, while parkinsonism was absent-to-mild throughout all visits for all patients. When compared to the patients with mixed apraxia of speech and agrammatism, the patients with progressive agrammatic aphasia performed better on tests of motor speech and parkinsonism but more poorly, and declined faster over time, on tests of general aphasia severity, agrammatism, and naming. The patients with progressive agrammatic aphasia also showed different neuroimaging abnormalities, with greater atrophy, hypometabolism and white matter tract degeneration in the prefrontal and anterior temporal lobes compared to patients with mixed apraxia of speech and agrammatism. These differences were more pronounced as the disease progressed. These results demonstrate that progressive agrammatic aphasia has a different clinical disease course and different underlying neuroanatomical abnormalities than patients with the more common syndrome of mixed agrammatism and apraxia of speech. This supports the distinction of progressive agrammatic aphasia and has implications for the classification of patients with agrammatic aphasia.

Augmented Dyadic Therapy Boosts Recovery of Language Function in Patients With Nonfluent Aphasia.

Background and Purpose- Evidence suggests that therapy can be effective in recovering from aphasia, provided that it consists of socially embedded, intensive training of behaviorally relevant tasks. However, the resources of healthcare systems are often too limited to provide such treatment at sufficient dosage. Hence, there is a need for evidence-based, cost-effective rehabilitation methods. Here, we asked whether virtual reality-based treatment grounded in the principles of use-dependent learning, behavioral relevance, and intensity positively impacts recovery from nonfluent aphasia. Methods- Seventeen patients with chronic nonfluent aphasia underwent intensive therapy in a randomized, controlled, parallel-group trial. Participants were assigned to the control group (N=8) receiving standard treatment or to the experimental group (N=9) receiving augmented embodied therapy with the Rehabilitation Gaming System for aphasia. All Rehabilitation Gaming System for aphasia sessions were supervised by an assistant who monitored the patients but did not offer any elements of standard therapy. Both interventions were matched for intensity and materials. Results- Our results revealed that at the end of the treatment both groups significantly improved on the primary outcome measure (Boston Diagnostic Aphasia Examination: control group, P=0.04; experimental group, P=0.01), and the secondary outcome measure (lexical access-vocabulary test: control group, P=0.01; experimental group, P=0.007). However, only the Rehabilitation Gaming System for aphasia group improved on the Communicative Aphasia Log ( P=0.01). The follow-up assessment (week 16) demonstrated that while both groups retained vocabulary-related changes (control group, P=0.01; experimental group, P=0.007), only the Rehabilitation Gaming System for aphasia group showed therapy-induced improvements in language ( P=0.01) and communication ( P=0.05). Conclusions- Our results demonstrate the effectiveness of Rehabilitation Gaming System for aphasia for improving language and communication in patients with chronic aphasia suggesting that current challenges faced by the healthcare system in the treatment of stroke might be effectively addressed by augmenting traditional therapy with computer-based methods. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02928822.

Fundamental or forgotten? Is Pierre Paul Broca still relevant in modern neuroscience?

The ability to speak is a unique human capacity, but where is it located in our brains? This question is closely connected to the pioneering work of Pierre Paul Broca in the 1860s. Based on post-mortem observations of aphasic patients' brains, Broca located language production in the 3rd convolution of the left frontal lobe and thus reinitiated the localizationist view of brain functions. However, contemporary neuroscience has partially rejected this view in favor of a network-based perspective. This leads to the question, whether Broca's findings are still relevant today. In this mini-review, we discuss current and historical implications of Broca's work by focusing on his original contribution and contrasting it with contemporary knowledge. Borrowing from Broca's famous quote, our review shows that humans indeed "speak with the left hemisphere"- but Broca's area is not the sole "seat of articulatory language".

Primary Progressive Aphasia and Stroke Aphasia.

PURPOSE OF REVIEW: This article summarizes the clinical and anatomic features of the three named variants of primary progressive aphasia (PPA): semantic variant PPA, nonfluent/agrammatic variant PPA, and logopenic variant PPA. Three stroke aphasia syndromes that resemble the PPA variants (Broca aphasia, Wernicke aphasia, and conduction aphasia) are also presented. RECENT FINDINGS: Semantic variant PPA and Wernicke aphasia are characterized by fluent speech with naming and comprehension difficulty; these syndromes are associated with disease in different portions of the left temporal lobe. Patients with nonfluent/agrammatic variant PPA or Broca aphasia have nonfluent speech with grammatical difficulty; these syndromes are associated with disease centered in the left inferior frontal lobe. Patients with logopenic variant PPA or conduction aphasia have difficulty with repetition and word finding in conversational speech; these syndromes are associated with disease in the left inferior parietal lobe. While PPA and stroke aphasias resemble one another, this article also presents their distinguishing features. SUMMARY: Primary progressive and stroke aphasia syndromes interrupt the left perisylvian language network, resulting in identifiable aphasic syndromes.

[Jose Ingenieros and the amusias: the beginning of the neuropsychology in Argentina]. / Jose Ingenieros y las amusias, sobre los origenes de la neuropsicologia argentina.

The Argentine neuropsychological school is born of the hand of the European school and is part of the beginning of the Experimental Psychology. In 1896 Horacio Pinero creates the first Department of Psychology at the University of Buenos Aires and in 1898 the first laboratory of Experimental Psychology is annexed. Jose Ingeniero, psychiatrist, neurologist, politician and above all sociologist publishes in France his work about the musical aphasia, the first neuropsychological work with international significance. In the same redeems to Charcot instead of to Knoblauch like the first one to describe the amusias, it speaks of an intelligence instead of a musical language and proposes a new classification and a methodology of assessment with a neurological-psychiatric integrative perspective. This article gave rise to this book in French on the musical language and its hysterical alterations awarded by the Academy of Medicine of Paris.

TITLE: Jose Ingenieros y las amusias, sobre los origenes de la neuropsicologia argentina.La escuela neuropsicologica argentina nace de la mano de la escuela europea y forma parte del inicio de la psicologia experimental. En 1896, Horacio Pinero crea la primera catedra de psicologia de la Universidad de Buenos Aires, y en 1898 se anexa el primer laboratorio de psicologia experimental. Jose Ingenieros, psiquiatra, neurologo, politico y, sobre todo, sociologo publica en Francia su trabajo sobre afasias musicales, el primer estudio neuropsicologico argentino con trascendencia internacional. En el redime a Charcot y no a Knoblauch como el primero en describir la amusia, habla de una inteligencia y no de un lenguaje musical, y propone una clasificacion y una metodologia de evaluacion con una perspectiva integradora neurologica-psiquiatrica. Este articulo dio origen a su libro en frances sobre el lenguaje musical y sus alteraciones histericas, premiado por la Academia de Medicina de Paris.

Sentence composition ability in two patients with non-fluent/agrammatic variant primary progressive aphasia.

Agrammatism is one of the core clinical features of non-fluent/agrammatic variant primary progressive aphasia, and it has traditionally been considered the hallmark of non-fluent aphasia in Western countries. However, agrammatic speech may remain undetected in Japanese patients because of the agglutinative structure of the language and high flexibility in word order. In the present study, we aimed to analyze agrammatism in the speech production of Japanese patients with aphasia due to neurodegenerative disease using an anagram test generated by our laboratory. Four patients were recruited from the dementia clinic at Tohoku University Hospital between December 2014 and August 2015: two patients with non-fluent/agrammatic variant primary progressive aphasia, one with semantic variant primary progressive aphasia, and one with probable Alzheimer's disease experiencing episodic memory impairment accompanied by transcortical sensory aphasia. All patients underwent thorough neurological and neuropsychological testing before performing a Japanese anagram task based on the Northwestern Anagram Test. Our findings indicated that the two patients with non-fluent/agrammatic variant primary progressive aphasia exhibited poorer performance on the anagram task than the remaining two patients. Therefore, the anagram test used in the present study may aid in detecting output aspects of agrammatism in Japanese patients with aphasia, although future studies are required to develop a standardized version of test.

Phonotactic processing deficit following left-hemisphere stroke.

The neural basis of speech processing is still a matter of great debate. Phonotactic knowledge-knowledge of the allowable sound combinations in a language-remains particularly understudied. The purpose of this study was to investigate the brain regions crucial to phonotactic knowledge in left-hemisphere stroke survivors. Results were compared to areas in which gray matter anatomy related to phonotactic knowledge in healthy controls. 44 patients with chronic left-hemisphere stroke, and 32 controls performed an English-likeness rating task on 60 auditory non-words of varying phonotactic regularities. They were asked to rate on a 1-5 scale, how close each non-word sounded to English. Patients' performance was compared to that of healthy controls, using mixed effects modeling. Multivariate lesion-symptom mapping and voxel-based morphometry were used to find the brain regions important for phonotactic processing in patients and controls respectively. The results showed that compared to controls, stroke survivors were less sensitive to phonotactic regularity differences. Lesion-symptom mapping demonstrated that a loss of sensitivity to phonotactic regularities was associated with lesions in left angular gyrus and posterior middle temporal gyrus. Voxel-based morphometry also revealed a positive correlation between gray matter density in left angular gyrus and sensitivity to phonotactic regularities in controls. We suggest that the angular gyrus is used to compare the incoming speech stream to internal predictions based on the frequency of sound sequences in the language derived from stored lexical representations in the posterior middle temporal gyrus.

The effects of silent visuomotor cueing on word retrieval in Broca's aphasies: A pilot study.

About a quarter of stroke patients worldwide suffer serious language disorders such as aphasias. Most common symptoms of Broca's aphasia are word naming disorders which highly impact verbal communication and the quality of life of aphasic patients. In order to recover disturbances in word retrieval, several cueing methods (i.e. phonemic and semantic) have been established to improve lexical access establishing effective language rehabilitation techniques. Based on recent evidence from action-perception theories, which postulate that neural circuits for speech perception and articulation are tightly coupled, in the present work, we propose and investigate an alternative type of cueing using silent articulation-related visual stimuli. We hypothesize that providing patients with primes in the form of silent videos showing lip motions representative of correct pronunciation of target words, will result in faster word retrieval than when no such cue is provided. To test our prediction, we realize a longitudinal clinical virtual reality-based trial with four post-stroke Broca's patients and compare the interaction times between the two conditions over the eight weeks of the therapy. Our results suggest that silent visuomotor cues indeed facilitate word retrieval and verbal execution, and might be beneficial in lexical relearning in chronic Broca's patients.

Overcoming discourse-linking difficulties in aphasia: The case of clitic pronouns.

The present study aims to contribute to the ongoing discussion about the impact of discourse-linking deficits on the performance of individuals with aphasia by providing new data from a set of rarely investigated constructions: sentences in which a clitic pronoun coexists alongside with the full DP it agrees with. To do so, we use data of individuals with non-fluent aphasias who need to overcome the difficulties in direct object (accusative) clitic production. This results in overproduction of non-target clitic right dislocations (RDs) and clitic doubling (CD). Data from 15 individual's native speakers of Spanish and Catalan are discussed. Data complement the results of previous investigations on discourse-linking effects in these languages, allowing the interpretation of results across constructions.

Recovery of injured Broca's portion of arcuate fasciculus in the dominant hemisphere in a patient with traumatic brain injury.

RATIONALE: Recovery of injured AF in patients with traumatic brain injury (TBI) has not been reported. In this study, we report on a patient with TBI who recovered from an injury to Broca's portion of AF in the dominant hemisphere, diagnosed by diffusion tensor tractography (DTT). PATIENT CONCERNS: A 28-year-old right-handed male patient suffered head trauma resulting from sliding while riding a motorcycle. DIAGNOSES: He was diagnosed with a traumatic contusional hemorrhage in the left frontal lobe, subarachnoid hemorrhage, and subdural hemorrhage in the left fronto-temporal lobe. INTERVENTIONS: He underwent craniectomy on the left fronto-temporal area, and hematoma removal for the subdural hemorrhage in the neurosurgery department of a university hospital. Two weeks after the injury, he was transferred to the rehabilitation department of another university hospital. He showed severe aphasia and brain MRI showed leukomalactic lesion in the left frontal lobe. OUTCOMES: The result WAB for the patient showed severe aphasia, with an aphasia quotient of 45.3 percentile. However, his aphasia improved rapidly by 9 months with an aphasia quotient at the 100.0 percentile. 2-week DTT detected discontinuity in the subcortical white matter at the branch to Broca's area of left AF. By contrast, on 9-month DTT, the discontinued portion of left AF was elongated to the left Broca's area. LESSONS: Recovery of injured Broca's portion of AF in the dominant hemisphere along with excellent improvement of aphasia was demonstrated in a patient with TBI. This study has important implications in brain rehabilitation because the mechanism of recovery from aphasia following TBI has not been elucidated.