Resting-State Network Changes Following Transcranial Magnetic Stimulation in Patients With Aphasia-A Randomized Controlled Study.

BACKGROUND: Although repetitive transcranial magnetic stimulation (rTMS) has exhibited promising efficacy in treating stroke-related aphasia, changes in neuroimaging in response to this therapy remain unclear. MATERIALS AND METHODS: By using resting-state functional magnetic resonance imaging (rsfMRI), we examined brain activations associated with language recovery in patients with poststroke nonfluent aphasia during an rTMS intervention. Twenty-six stroke patients with nonfluent aphasia were recruited in this randomized double-blinded study. The patients received real (n = 13) or sham (n = 13) 1-Hz inhibitory rTMS to the right pars triangularis (PTr) for ten consecutive weekdays. They underwent rsfMRI and completed the Concise Chinese Aphasia Test (CCAT) before and after the rTMS intervention. RESULT: The fractional amplitude of low-frequency fluctuation (fALFF) was calculated to investigate spontaneous neural activity in the brain. After treatment, the language function in the experimental group was higher than that in the sham group in terms of total CCAT score (p = 0.014) and the CCAT subscores of conversation (p = 0.012), description (p = 0.006), and expression (p = 0.003). Postintervention intergroup comparisons revealed that fALFF was significantly increased in the right superior temporal gyrus, right dorsolateral prefrontal gyrus, insular cortex, and caudate nucleus. Clusters in the right thalamus exhibited suppressed fALFF. The enhanced clusters in the frontotemporal region were significantly correlated with CCAT score improvements. CONCLUSIONS: Our findings provide empirical evidence for the vital role of the right frontotemporal and subcortical regions in language recovery after rTMS interventions in patients with aphasia. Inhibitory rTMS may improve language expression by promoting involvement of the right frontotemporal region. The results can be further used to refine rTMS protocols and optimize brain stimulation treatments. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03059225.

Speech and Language Presentations of FTLD-TDP Type B Neuropathology.

Four right-handed patients who presented with an isolated impairment of speech or language had transactive response DNA-binding protein of 43 kDa (TDP-43) type B pathology. Comportment and pyramidal motor function were preserved at presentation. Three of the cases developed axial rigidity and oculomotor findings late in their course with no additional pyramidal or lower motor neuron impairments. However, in all 4 cases, postmortem examination disclosed some degree of upper and lower motor neuron disease (MND) pathology in motor cortex, brainstem, and spinal cord. Although TDP-43 type B pathology is commonly associated with MND and behavioral variant frontotemporal dementia, it is less recognized as a pathologic correlate of primary progressive aphasia and/or apraxia of speech as the presenting syndrome. These cases, taken together, contribute to the growing heterogeneity in clinical presentations associated with TDP pathology. Additionally, 2 cases demonstrated left anterior temporal lobe atrophy but without word comprehension impairments, shedding light on the relevance of the left temporal tip for single-word comprehension.

Sentence production in Parkinson's disease.

While growing evidence reports changes in language use in non-demented individuals with Parkinson's disease (PD), the presence and nature of the deficits remain largely unclear. Researchers have proposed that dysfunctioning fronto-basal ganglia circuit results in impaired grammatical processes, predicting qualitatively similar language impairments between individuals with PD and agrammatic Broca's aphasia, whereas others suggest that PD is not associated with language-specific grammatical impairment. In addition, there is a paucity of research examining syntactic production in PD at the sentence-level. This study examined sentence production of individuals with PD, healthy older adults, and individuals with agrammatic Broca's aphasia. In Experiment 1, using a Cinderella story-telling task, proportion of grammatical sentences, number of embedded clauses and production of verb arguments in sentences were examined. In Experiment 2, a structured sentence elicitation task was used in which syntactic complexity of sentences (canonical vs. non-canonical word order) was systematically manipulated while minimizing demands for non-syntactic processing. Only the participants with agrammatic Broca's aphasia showed significantly impaired syntactic production in both experiments. Participants with PD did not show impaired syntactic production in either task, despite impairments in lexical retrieval, repetition of words and sentences, and speech production. These findings suggest that impaired syntactic processing may not be a core deficit underlying the changes in language use in non-demented PD. Changes in language use in PD are qualitatively different from language deficits in aphasia.

Artificial grammar learning in vascular and progressive non-fluent aphasias.

Patients with non-fluent aphasias display impairments of expressive and receptive grammar. This has been attributed to deficits in processing configurational and hierarchical sequencing relationships. This hypothesis had not been formally tested. It was also controversial whether impairments are specific to language, or reflect domain general deficits in processing structured auditory sequences. Here we used an artificial grammar learning paradigm to compare the abilities of controls to participants with agrammatic aphasia of two different aetiologies: stroke and frontotemporal dementia. Ten patients with non-fluent variant primary progressive aphasia (nfvPPA), 12 with non-fluent aphasia due to stroke, and 11 controls implicitly learned a novel mixed-complexity artificial grammar designed to assess processing of increasingly complex sequencing relationships. We compared response profiles for otherwise identical sequences of speech tokens (nonsense words) and tone sweeps. In all three groups the ability to detect grammatical violations varied with sequence complexity, with performance improving over time and being better for adjacent than non-adjacent relationships. Patients performed less well than controls overall, and this was related more strongly to aphasia severity than to aetiology. All groups improved with practice and performed well at a control task of detecting oddball nonwords. Crucially, group differences did not interact with sequence complexity, demonstrating that aphasic patients were not disproportionately impaired on complex structures. Hierarchical cluster analysis revealed that response patterns were very similar across all three groups, but very different between the nonsense word and tone tasks, despite identical artificial grammar structures. Overall, we demonstrate that agrammatic aphasics of two different aetiologies are not disproportionately impaired on complex sequencing relationships, and that the learning of phonological and non-linguistic sequences occurs independently. The similarity of profiles of discriminatory abilities and rule learning across groups suggests that insights from previous studies of implicit sequence learning in vascular aphasia are likely to prove applicable in nfvPPA.

Acquired dyslexia in Serbian speakers with Broca's and Wernicke's aphasia.

This study examined patterns of acquired dyslexia in Serbian aphasic speakers, comparing profiles of groups with Broca's versus Wernicke's aphasia. The study also looked at the relationship of reading and auditory comprehension and between reading comprehension and reading aloud in these groups. Participants were 20 people with Broca's and 20 with Wernicke's aphasia. They were asked to read aloud and to understand written material from the Serbian adaptation of the Boston Diagnostic Aphasia Examination. A Serbian Word Reading Aloud Test was also used. The people with Broca's aphasia achieved better results in reading aloud and in reading comprehension than those with Wernicke's aphasia. Those with Wernicke's aphasia showed significantly more semantic errors than those with Broca's aphasia who had significantly more morphological and phonological errors. From the data we inferred that lesion sites accorded with previous work on networks associated with Broca's and Wernicke's aphasia and with a posterior-anterior axis for reading processes centred on (left) parietal-temporal-frontal lobes.

A stroke patient with impairment of auditory sensory (echoic) memory.

A 42-year-old man suffered damage to the left supra-sylvian areas due to a stroke and presented with verbal short-term memory (STM) deficits. He occasionally could not recall even a single syllable that he had heard one second before. A study of mismatch negativity using magnetoencephalography suggested that the duration of auditory sensory (echoic) memory traces was reduced on the affected side of the brain. His maximum digit span was four with auditory presentation (equivalent to the 1st percentile for normal subjects), whereas it was up to six with visual presentation (almost within the normal range). He simply showed partial recall in the digit span task, and there was no self correction or incorrect reproduction. From these findings, reduced echoic memory was thought to have affected his verbal short-term retention. Thus, the impairment of verbal short-term memory observed in this patient was "pure auditory" unlike previously reported patients with deficits of the phonological short-term store (STS), which is the next higher-order memory system. We report this case to present physiological and behavioral data suggesting impaired short-term storage of verbal information, and to demonstrate the influence of deterioration of echoic memory on verbal STM.

A novel frontal pathway underlies verbal fluency in primary progressive aphasia.

The frontal aslant tract is a direct pathway connecting Broca's region with the anterior cingulate and pre-supplementary motor area. This tract is left lateralized in right-handed subjects, suggesting a possible role in language. However, there are no previous studies that have reported an involvement of this tract in language disorders. In this study we used diffusion tractography to define the anatomy of the frontal aslant tract in relation to verbal fluency and grammar impairment in primary progressive aphasia. Thirty-five patients with primary progressive aphasia and 29 control subjects were recruited. Tractography was used to obtain indirect indices of microstructural organization of the frontal aslant tract. In addition, tractography analysis of the uncinate fasciculus, a tract associated with semantic processing deficits, was performed. Damage to the frontal aslant tract correlated with performance in verbal fluency as assessed by the Cinderella story test. Conversely, damage to the uncinate fasciculus correlated with deficits in semantic processing as assessed by the Peabody Picture Vocabulary Test. Neither tract correlated with grammatical or repetition deficits. Significant group differences were found in the frontal aslant tract of patients with the non-fluent/agrammatic variant and in the uncinate fasciculus of patients with the semantic variant. These findings indicate that degeneration of the frontal aslant tract underlies verbal fluency deficits in primary progressive aphasia and further confirm the role of the uncinate fasciculus in semantic processing. The lack of correlation between damage to the frontal aslant tract and grammar deficits suggests that verbal fluency and grammar processing rely on distinct anatomical networks.

Exaggerated object affordance and absent automatic inhibition in alien hand syndrome.

Patients with alien hand syndrome (AHS) experience making apparently deliberate and purposeful movements with their hand against their will. However, the mechanisms contributing to these involuntary actions remain poorly understood. Here, we describe two experimental investigations in a patient with corticobasal syndrome (CBS) with alien hand behaviour in her right hand. First, we show that responses with the alien hand are made significantly more quickly to images of objects which afford an action with that hand compared to objects which afford an action with the unaffected hand. This finding suggests that involuntary grasping behaviours in AHS might be due to exaggerated, automatic motor activation evoked by objects which afford actions with that limb. Second, using a backwards masked priming task, we found normal automatic inhibition of primed responses in the patient's unaffected hand, but importantly there was no evidence of such suppression in the alien limb. Taken together, these findings suggest that grasping behaviours in AHS may result from exaggerated object affordance effects, which might potentially arise from disrupted inhibition of automatically evoked responses.

Syntactic and morphosyntactic processing in stroke-induced and primary progressive aphasia.

The paper reports findings derived from three experiments examining syntactic and morphosyntactic processing in individuals with agrammatic and logopenic variants of primary progressive aphasia (PPA-G and PPA-L, respectively) and stroke-induced agrammatic and anomic aphasia (StrAg and StrAn, respectively). We examined comprehension and production of canonical and noncanonical sentence structures and production of tensed and nontensed verb forms using constrained tasks in experiments 1 and 2, using the Northwestern Assessment of Verbs and Sentences (NAVS [57]) and the Northwestern Assessment of Verb Inflection (NAVI, Thompson and Lee, experimental version) test batteries, respectively. Experiment 3 examined free narrative samples, focusing on syntactic and morphosyntactic measures, i.e. production of grammatical sentences, noun to verb ratio, open-class to closed-class word production ratio, and the production of correctly inflected verbs. Results indicate that the two agrammatic groups (i.e., PPA-G and StrAg) pattern alike on syntactic and morphosyntactic measures, showing more impaired noncanonical compared to canonical sentence comprehension and production and greater difficulties producing tensed compared to nontensed verb forms. Their spontaneous speech also contained significantly fewer grammatical sentences and correctly inflected verbs, and they produced a greater proportion of nouns compared to verbs, than healthy speakers. In contrast, PPA-L and StrAn individuals did not display these deficits, and performed significantly better than the agrammatic groups on these measures. The findings suggest that agrammatism, whether induced by degenerative disease or stroke, is associated with characteristic deficits in syntactic and morphosyntactic processing. We therefore recommend that linguistically sophisticated tests and narrative analysis procedures be used to systematically evaluate the linguistic ability of individuals with PPA, contributing to our understanding of the language impairments of different PPA variants.

Short-term memory treatment: patterns of learning and generalisation to sentence comprehension in a person with aphasia.

Auditory-verbal short-term memory deficits (STM) are prevalent in aphasia and can contribute to sentence comprehension deficits. This study investigated the effectiveness of a novel STM treatment in improving STM (measured with span tasks) and sentence comprehension (measured with the Token Test and the Test for the Reception of Grammar, TROG) in a person with severe aphasia (transcortical motor). In particular, the research questions were: (1) Would STM training improve STM? (2) Would improvements from the STM training generalise to improvements in comprehension of sentences? STM was trained using listening span tasks of serial word recognition. No other language or sentence comprehension skills were trained. Following treatment, STM abilities improved (listening span, forward digit span). There was also evidence of generalisation to untreated sentence comprehension (only on the TROG). Backward digit span, phonological processing and single word comprehension did not improve. Improvements in sentence comprehension may have resulted from resilience to rapid decay of linguistic representations within sentences (words and phrases). This in turn facilitated comprehension.

Selective impairment of masculine gender processing: evidence from a German aphasic.

The present single case study describes the performance of the German aphasic E.M. who exhibited a severe impairment of grammatical gender processing in masculine nouns but relatively spared performance regarding feminine and neuter ones. This error pattern was assessed with tests of gender assignment to orally or visually presented words, with oral or written responses, and with tests of gender congruency decision on noun phrases. The pattern occurred across tasks and modalities, thus suggesting a gender-specific impairment at a modality-independent level of processing. It was sensitive to frequency, thus supporting the assumption that access to gender features as part of grammatical processing is frequency sensitive. Besides being the first description of a gender-specific impairment in an aphasic subject, the data therefore have implications regarding the modelling of representation and processing of grammatical gender information within the mental lexicon.

Speaking of events: the case of C.M.

C.M. is an agrammatic patient who on assessment tests shows a disproportionate difficulty when producing verbs compared with nouns. In three experiments, we investigated whether C.M. also has difficulties with nouns referring to events and whether event nouns and verbs show similar patterns of disruption. Experiment 1 suggested that she is sensitive to argument structure complexity and has a greater impairment in the production of event nouns and verbs than object nouns. Experiment 2 revealed that C.M. finds derivationally complex words, such as event nouns, difficult to produce. However, morphological complexity does not completely explain C.M.'s problems with event nouns. In Experiment 3, an assessment of C.M.'s ability to use different aspects of semantic and syntactic knowledge relative to event nouns and verbs showed an almost identical performance with the two types of words. The relevance of the findings with respect to models of word production is considered.

Agrammatism in a case of formal thought disorder: Beyond intellectual decline and working memory deficit.

Previous studies have suggested that naming and syntactic deficits in formal thought disorder may be related to global cognitive decline. This article reports the case of a patient, FM, with formal thought disorder schizophrenia who presents disproportionate deficits in receptive and expressive grammar with respect to his intellectual level of functioning. Syntactic and morphologic components of expressive grammar appeared equally impaired. Deficits in language comprehension were observed independently from working memory limitations. FM showed preserved grammaticality judgment, but defective sentence comprehension where semantic context does not provide heuristics for assigning thematic roles, but syntactic knowledge is essential. These atypical results are discussed within a neurodevelopmental aetiological model of formal thought disorder.

Articulatory agility in cognitive decline.

OBJECTIVE: Motor speech disorders are believed to be uncommon in early Alzheimer's disease (AD). However, data from maximum performance tests of motor speech function in AD and related disorders are virtually nonexistent. The aim of this study was to make such data available. MATERIALS AND METHODS: Sequential speech motion rate was analyzed in 236 memory clinic patients with different levels of cognitive functioning. RESULTS: Sequential speech motion rate was moderately but significantly decreased in mild dementia in AD. About 10% of AD and mild cognitive impairment cases had markedly decreased rates. Rates were strongly reduced in progressive nonfluent aphasia, whereas semantic dementia did not differ from subjective cognitive impairment. Frontotemporal dementia had lower rates than AD. CONCLUSIONS: A proportion of patients with cognitive decline has markedly reduced articulatory agility. The cause of this reduction in some patients with mild cognitive impairment and mild AD is unknown. Semantic dementia is not associated with impaired articulatory agility.

Effect of propranolol on naming in chronic Broca's aphasia with anomia.

Previous research suggests that the noradrenergic system modulates flexibility of access to the lexical-semantic network, with propranolol benefiting normal subjects in lexical-semantic problem solving tasks. Patients with Broca's aphasia with anomia have impaired ability to access appropriate verbal output for a given visual stimulus in a naming task. Therefore, we tested naming in a pilot study of chronic Broca's aphasia patients with anomia after propranolol and after placebo in a double-blinded crossover manner. Naming was better after propranolol than after placebo, suggesting a potential benefit from propranolol in chronic Broca's aphasia with anomia. Larger follow-up studies are necessary to further investigate this effect.

Motor neuron disease associated with non-fluent rapidly progressive aphasia: case report and review of the literature.

The superimposed clinical features of motor neuron disease (MND) and frontotemporal lobar degeneration (FTLD) comprise a rare neurological overlap syndrome that represents a diagnostic challenge to neurologists. Currently, FTLD-MND is considered a distinct entity and its clinicopathological basis has recently been reviewed. Our aim is to present a patient with MND and non-fluent rapidly progressive aphasia with clinical, imaging and histopathological correlation, as well as a brief review of the literature. We demonstrated the selective corticospinal tract (CST) and temporal lobe involvement using T1 spin-echo with an additional magnetization transfer contrast pulse on resonance (T1 SE/MTC) and FLAIR MR sequences in our patient, with further clinical and histopathological correlation. To the best of our knowledge, there is no description about the use of these particular MR sequences in the evaluation of FTLD-MND patients.

An EMA analysis of the effect of increasing word length on consonant production in apraxia of speech: a case study.

The effect of increasing word length on the articulatory dynamics (i.e. duration, distance, maximum acceleration, maximum deceleration, and maximum velocity) of consonant production in acquired apraxia of speech was investigated using electromagnetic articulography (EMA). Tongue-tip and tongue-back movement of one apraxic patient was recorded using the AG-200 EMA system during word-initial consonant productions in one, two, and three syllable words. Significantly deviant articulatory parameters were recorded for each of the target consonants during one, two, and three syllables words. Word length effects were most evident during the release phase of target consonant productions. The results are discussed with respect to theories of speech motor control as they relate to AOS.

The Marc Dax (1770-1837)/Paul Broca (1824-1880) controversy over priority in science: left hemisphere specificity for seat of articulate language and for lesions that cause aphemia.

One of the most fascinating and frustrating issues in the priority of discovery in science is over just who, for the first time, went on record in the public forum, either orally at a conference or through a published communication, proclaiming that the faculty of articulate human speech was located in the left, not the right, cortical hemisphere. The disputed paper was purportedly written in 1836 by Marc Dax, who died subsequently in 1837. He was a physician in southern France in the city of Montpellier--far from the medical center of Paris. Little note was made of the presumed paper until the early and mid-1860s, when the issue of language localization in the human brain took on increased activity, as the clinico-pathological method of explanation continued to flourish in the "Art of Physick." Marc Dax's son, Gustave, happened to be studying medicine in Paris in the 1860s, and, as most of the neuroscientific and anthropological researchers, came to know of Broca's published work, which in 1861, agreed with phrenological theory that this faculty was, indeed, in the anterior lobes, but further claimed, de novo, that the region in the anterior lobe was more precisely focused at the foot of the 3rd frontal convolution in that lobe, still assuming with phrenological theory and the "Law of Symmetry" that the faculty was bilaterally located. It was not until 1865 that Broca clearly, non-hesitatingly, and unambiguously claimed that the faculty was in the left hemisphere. As it turned out, Gustave, six weeks before Broca's paper appeared, had published the paper he said his father had written in 1836. In 1863, in fact, Gustave had submitted his (Gustave's) long monograph on aphemia, integrating what he claimed to be his father's 1836 pronouncement along with his own data. He sent this communication to the French Academy of Sciences and to the French Academy of Medicine; he heard nothing back from either academy. After waiting two years, he managed to publish his material. Gustave's valiant move to promote his father's priority for one of the most significant conclusions in the history of the neurosciences is a lesson in frustration. Broca's attitude towards Gustave's case was disarmingly nonchalant; the issue deserves further historical inquiry.