Language supplementary motor area syndrome correlated with dynamic changes in perioperative task-based functional MRI activations: case report.

Supplementary motor area (SMA) syndrome is well known; however, the mechanism underlying recovery from language SMA syndrome is unclear. Herein the authors report the case of a right-handed woman with speech aphasia following resection of an oligodendroglioma located in the anterior aspect of the left superior frontal gyrus. The patient exhibited language SMA syndrome, and functional MRI (fMRI) findings 12 days postoperatively demonstrated a complete shift of blood oxygen level-dependent (BOLD) activation to the contralateral right language SMA/pre-SMA as well as coequal activation and an increased volume of activation in the left Broca's area and the right Broca's homolog. The authors provide, to the best of their knowledge, the first description of dynamic changes in task-based hemispheric language BOLD fMRI activations across the preoperative, immediate postoperative, and more distant postoperative settings associated with the development and subsequent complete resolution of the clinical language SMA syndrome.

18F-FDG PET/CT Brain in a Case of Agrammatic/Nonfluent Variant of Primary Progressive Aphasia (Broca's Aphasia).

Primary progressive aphasia is a neurodegenerative variant of frontotemporal lobe degeneration presenting with isolated selective impairment of language domain, not secondarily due to stroke. We present a case of middle-aged female patient who underwent F-FDG PET of the brain for evaluating progressively declining speaking ability associated with altered fluency of speech and occasional mutism. F-FDG PET revealed asymmetric hypometabolism involving the left inferior frontal gyrus along with left anterior cingulate gyrus suggestive of Broca's aphasia.

Self-regulation of language areas using real-time functional MRI in stroke patients with expressive aphasia.

The objectives of this study were to test (i) If stroke patients with expressive Aphasia could learn to up-regulate the Blood Oxygenation Level Dependent (BOLD) signal in language areas of the brain, namely Inferior Frontal Gyrus (Broca's area) and Superior Temporal Gyrus (Wernicke's area), with real-time fMRI based neurofeedback of the BOLD activation and functional connectivity between the language areas; and (ii) acquired up-regulation could lead to an improvement in expression of language. The study was performed on three groups: Group 1 (n = 4) of Test patients and group 2 (n = 4) of healthy volunteers underwent the neurofeedback training, whereas group 3 (n = 4) of Control patients underwent treatment as usual. Language performance and recovery were assessed using western aphasia battery and picture naming tasks, before and after the neurofeedback training. Results show that the Test group had significant increase in activation of the Broca's area and its right homologue, while the Normal group achieved the greatest activation during neurofeedback. For the Test group both perilesional and contralateral activations were observed. The improvement in language ability of the test patients was not significantly greater than that of the control patients. Neurofeedback training in Aphasia patients induced significant activation of the Broca's area, Wernicke's area and their right homologues, although healthy individuals achieved greater activations in these regions than the patient groups. Training also activated perilesional areas of Rolandic operculum, precentral gyrus and postcentral gyrus for the Test patients significantly. However, lack of behavioral and symptom modifications in the Test group calls for improvements in the efficacy of the approach.

One novel GRN null mutation, two different aphasia phenotypes.

Progranulin gene (GRN) mutations are among the leading causes of frontotemporal lobar degeneration, a group of neurodegenerative diseases characterized by remarkable clinical heterogeneity. In this article, we report the new GRN 708+4A>T splicing mutation, identified in 2 siblings of a family with several members affected by cognitive, behavioral, and motor disorders. Plasma progranulin dosage and GRN expression analysis, together with in silico prediction studies, supported the pathogenicity of the mutation. Both the patients displayed a clinical syndrome in which language impairment was largely predominant. However, motor speech deficits were the major feature in one case, diagnosed as progressive nonfluent aphasia, whereas marked semantic alterations were present in the other, whose clinical phenotype was in favor of a mixed aphasia. The profile of neuroanatomical alterations from imaging studies was in line with the clinical phenotypes. Therefore, also this novel GRN mutation is associated with haploinsufficiency and phenotypic heterogeneity, which are both typical features of progranulinopathies.

Differences in neuroimaging features of early- versus late-onset nonfluent/agrammatic primary progressive aphasia.

This study investigated distinct neuroimaging features measured by cortical thickness and subcortical structural shape abnormality in early-onset (EO, onset age <65 years) and late-onset (LO, onset age ≥65 years) nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) patients. Cortical thickness and subcortical structural shape analyses were performed using a surface-based method from 38 patients with nfvPPA and 76 cognitively normal individuals. To minimize the effects of physiological aging, we used W-scores in comparisons between the groups. The EO-nfvPPA group exhibited more extensive cortical thickness reductions predominantly in the left perisylvian, lateral and medial prefrontal, temporal, posterior cingulate, and precuneus regions than the LO-nfvPPA group. The EO-nfvPPA group also exhibited significantly greater subcortical structural shape abnormality than the LO-nfvPPA group, mainly in the left striatum, hippocampus, and amygdala. Our findings suggested that there were differences in neuroimaging features between these groups by the age of symptom onset, which might be explained by underlying heterogeneous neuropathological differences or the age-related brain reserve hypothesis.

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.

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.

Correlación neurorradiológica de las afasias. Mapa cortico-subcortical del lenguaje / Neuroradiologic correlation with aphasias. Cortico-subcortical map of language

La afasia es una alteración adquirida del lenguaje debida a una lesión cerebral, que se caracteriza por errores en la producción, la denominación o la comprensión del lenguaje. Aunque la mayoría de las afasias suelen ser mixtas, desde un punto de vista práctico se clasifican en diferentes tipos según sus rasgos clínicos principales: afasia de Broca, afasia de Wernicke, afasia de conducción, afasia transcortical y alexia con o sin agrafia. Presentamos los hallazgos clínicos de los principales subtipos representándolos con casos radiológicos, y proporcionamos una revisión actualizada de la red del lenguaje con imágenes de resonancia funcional y de tractografía

Aphasia is an acquired language disorder due to a cerebral lesion; it is characterized by errors in production, denomination, or comprehension of language. Although most aphasias are mixed, from a practical point of view they are classified into different types according to their main clinical features: Broca's aphasia, Wernicke's aphasia, conduction aphasia, transcortical aphasia, and alexia with or without agraphia. We present the clinical findings for the main subtypes of aphasia, illustrating them with imaging cases, and we provide an up-to-date review of the language network with images from functional magnetic resonance imaging and tractography

Malignant atrophic papulosis with motor aphasia and intestinal perforation: A case report and review of published works.

Malignant atrophic papulosis (MAP) is a rare type of obliterating vasculopathy that can present as pure cutaneous lesions or a systemic entity affecting multiple organs. Systemic disease, such as gastrointestinal or central nervous system involvement, may predispose the patients to poorer or even fatal outcomes. We present a 30-year-old female patient with systemic manifestation of MAP 10 days after delivery of a full-term pregnancy who subsequently developed motor aphasia and intestinal perforation. The patient was administrated empirical treatment with an antiplatelet, anticoagulant, methylprednisolone sodium succinate and alprostadil. Antibiotics were administrated due to intestinal perforation and secondary sepsis. Despite all treatment, the patient died a week later. We summarized all the previous reports of MAP based on thorough review of previous published work. Overall, this is the first patient with MAP combined with motor aphasia and intestinal perforation and may provide insights for future studies on the treatment of this disease.

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.

Advantages of Staged Angioplasty in a Patient with Internal Carotid Artery Pseudo-Occlusion Besides Prevention of Cerebral Hyperperfusion Syndrome.

BACKGROUND: Staged angioplasty for carotid artery stenosis has been reported to be effective in preventing postoperative cerebral hyperperfusion syndrome (CHS) in patients with severe carotid stenosis; thus, it is also recommended for patients with internal carotid artery (ICA) pseudo-occlusion, the treatment strategy for which is controversial. CASE DESCRIPTION: This study reports the case of an Asian man in his 50s who had motor aphasia and right-side weakness caused by pseudo-occlusion of the left ICA. After medical treatment, he underwent a staged angioplasty. After the first stage of percutaneous transluminal angioplasty, anterograde blood flow to the left ICA increased but the distal ICA remained partially collapsed. Initially, the second stage of carotid artery stenting (CAS) was planned for 2 weeks after the first stage; however, hemorrhagic infarction was observed the day before the CAS, and it was postponed by 2 weeks, after adjustment of antiplatelet therapy. At the time of the CAS, the diameter of the initially collapsed left distal ICA was remodeled and it was fully dilated; thus, we used a balloon-type embolic protection device and conducted CAS successfully without apparent embolic complications. The postoperative course was uneventful. The patient did not develop CHS. CONCLUSIONS: Besides preventing CHS, staged angioplasty has advantages when used for treating patients with ICA pseudo-occlusions in that the extent of dilation of the distal ICA after percutaneous transluminal angioplasty can be confirmed and the development of a possible hemorrhagic infarction can be assessed before stent placement.

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.

Preserved processing of musical structure in a person with agrammatic aphasia.

Evidence for shared processing of structure (or syntax) in language and in music conflicts with neuropsychological dissociations between the two. However, while harmonic structural processing can be impaired in patients with spared linguistic syntactic abilities (Peretz, I. (1993). Auditory atonalia for melodies. Cognitive Neuropsychology, 10, 21-56. doi:10.1080/02643299308253455), evidence for the opposite dissociation-preserved harmonic processing despite agrammatism-is largely lacking. Here, we report one such case: HV, a former musician with Broca's aphasia and agrammatic speech, was impaired in making linguistic, but not musical, acceptability judgments. Similarly, she showed no sensitivity to linguistic structure, but normal sensitivity to musical structure, in implicit priming tasks. To our knowledge, this is the first non-anecdotal report of a patient with agrammatic aphasia demonstrating preserved harmonic processing abilities, supporting claims that aspects of musical and linguistic structure rely on distinct neural mechanisms.

Recovery of language function in Korean-Japanese crossed bilingual aphasia following right basal ganglia hemorrhage.

Few studies have investigated language recovery patterns and the mechanisms of crossed bilingual aphasia following a subcortical stroke. In particular, Korean-Japanese crossed bilingual aphasia has not been reported. A 47-year-old, right-handed man was diagnosed with an extensive right basal ganglia hemorrhage. He was bilingual, fluent in both Korean and Japanese. After his stroke, the patient presented with crossed aphasia. We investigated changes in the Korean (L1) and Japanese (L2) language recovery patterns. Both Korean and Japanese versions of the Western Aphasia Battery (WAB) were completed one month after the stroke, and functional magnetic resonance imaging (fMRI) was performed using picture-naming tasks. The WAB showed a paradoxical pattern of bilingual aphasia, with an aphasia quotient (AQ) of 32 for Korean and 50.6 for Japanese, with Broca's aphasia. The patient scored better in the Japanese version of all domains of the tests. The fMRI study showed left lateralized activation in both language tasks, especially in the inferior frontal gyrus. After six months of language therapy targeting L1, the Korean-WAB score improved significantly, while the Japanese-WAB score showed slight improvement. In this case, the subcortical lesion contributed to crossed bilingual aphasia more highly affecting L1 due to loss of the cortico-subcortical control mechanism in the dominant hemisphere. The paradoxical pattern of bilingual aphasia disappeared after lengthy language therapy targeting L1, and the therapy effect did not transfer to L2. Language recovery in L1 might have been accomplished by reintegrating language networks, including the contralesional language homologue area in the left hemisphere.

Based on the Network Degeneration Hypothesis: Separating Individual Patients with Different Neurodegenerative Syndromes in a Preliminary Hybrid PET/MR Study.

UNLABELLED: The network degeneration hypothesis (NDH) of neurodegenerative syndromes suggests that pathologic brain changes distribute primarily along distinct brain networks, which are characteristic for different syndromes. Brain changes of neurodegenerative syndromes can be characterized in vivo by different imaging modalities. Our aim was to test the hypothesis whether multimodal imaging based on the NDH separates individual patients with different neurodegenerative syndromes. METHODS: Twenty patients with Alzheimer disease (AD) and 20 patients with frontotemporal lobar degeneration (behavioral variant frontotemporal dementia [bvFTD, n = 11], semantic dementia [SD, n = 4], or progressive nonfluent aphasia [PNFA, n = 5]) underwent simultaneous MRI and (18)F-FDG PET in a hybrid PET/MR scanner. The 3 outcome measures were voxelwise values of degree centrality as a surrogate for regional functional connectivity, glucose metabolism as a surrogate for regional metabolism, and volumetric-based morphometry as a surrogate for regional gray matter volume. Outcome measures were derived from predefined core regions of 4 intrinsic networks based on the NDH, which have been demonstrated to be characteristic for AD, bvFTD, SD, and PNFA, respectively. Subsequently, we applied support vector machine to classify individual patients via combined imaging measures, and results were evaluated by leave-one-out cross-validation. RESULTS: On the basis of multimodal voxelwise regional patterns, classification accuracies for separating patients with different neurodegenerative syndromes were 77.5% for AD versus others, 82.5% for bvFTD versus others, 97.5% for SD versus others, and 87.5% for PNFA versus others. Multimodal classification results were significantly superior to unimodal approaches. CONCLUSION: Our finding provides initial evidence that the combination of regional metabolism, functional connectivity, and gray matter volume, which were derived from disease characteristic networks, separates individual patients with different neurodegenerative syndromes. Preliminary results suggest that employing multimodal imaging guided by the NDH may generate promising biomarkers of neurodegenerative syndromes.

Language specificity of lexical-phonological therapy in bilingual aphasia: A clinical and electrophysiological study.

Based on findings for overlapping representations of bilingual people's first (L1) and second (L2) languages, unilingual therapies of bilingual aphasia have been proposed to benefit the untrained language. However, the generalisation patterns of intra- and cross-language and phonological therapy and their neural bases remain unclear. We tested whether the effects of an intensive lexical-phonological training (LPT) in L2 transferred to L1 word production in a Persian-French bilingual stroke patient with Broca's aphasia. Language performance was assessed using the Bilingual Aphasia Test, a 144-item picture naming (PN) task and a word-picture verification (WPV) task. Electroencephalography (EEG) was recorded during PN and WPV in both languages before and after an LPT in French on a wordlist from the PN task. After the therapy, naming improved only for the treated L2 items. The naming performance improved neither in the untrained L2 items nor in the corresponding items in L1. EEG analyses revealed a Language x Session topographic interaction at 540 ms post-stimulus, driven by a modification of the electrophysiological response to the treated L2 but not L1 items. These results indicate that LPT modified the brain networks engaged in the phonological-phonetic processing during naming only in the trained language for the trained items.