Less is more: neural mechanisms underlying anomia treatment in chronic aphasic patients.

See Thompson and Woollams (doi:10.1093/brain/awx264) for a scientific commentary on this article. Previous research with aphasic patients has shown that picture naming can be facilitated by concurrent phonemic cueing [e.g. initial phoneme(s) of the word that the patient is trying to retrieve], both as an immediate word retrieval technique, and when practiced repeatedly over time as a long-term anomia treatment. Here, to investigate the neural mechanisms supporting word retrieval, we adopted­for the first time­a functional magnetic resonance imaging task using the same naming procedure as it occurs during the anomia treatment process. Before and directly after a 6-week anomia treatment programme, 18 chronic aphasic stroke patients completed our functional magnetic resonance imaging protocol­a picture naming task aided by three different types of phonemic cues (whole words, initial phonemes, final phonemes) and a noise-control condition. Patients completed a naming task based on the training materials, and a more general comprehensive battery of language tests both before and after the anomia treatment, to determine the effectiveness and specificity of the therapy. Our results demonstrate that the anomia treatment was effective and specific to speech production, significantly improving both patients' naming accuracy and reaction time immediately post-treatment (unstandardized effect size: 29% and 17%, respectively; Cohen's d: 3.45 and 1.83). Longer term gains in naming were maintained 3 months later. Functional imaging results showed that both immediate and long-term facilitation of naming involved a largely overlapping bilateral frontal network including the right anterior insula, inferior frontal and dorsal anterior cingulate cortices, and the left premotor cortex. These areas were associated with a neural priming effect (i.e. reduced blood oxygen level-dependent signal) during both immediate (phonemically-cued versus control-cue conditions), and long-term facilitation of naming (i.e. treated versus untreated items). Of note is that different brain regions were sensitive to different phonemic cue types. Processing of whole word cues was associated with increased activity in the right angular gyrus; whereas partial word cues (initial and final phonemes) recruited the left supplementary motor area, and right anterior insula, inferior frontal cortex, and basal ganglia. The recruitment of multiple and bilateral areas may help explain why phonemic cueing is such a successful behavioural facilitation tool for anomia treatment. Our results have important implications for optimizing current anomia treatment approaches, developing new treatments, and improving speech outcome for aphasic patients.

The Neural and Behavioral Correlates of Anomia Recovery following Personalized Observation, Execution, and Mental Imagery Therapy: A Proof of Concept.

The impact of sensorimotor strategies on aphasia recovery has rarely been explored. This paper reports on the efficacy of personalized observation, execution, and mental imagery (POEM) therapy, a new approach designed to integrate sensorimotor and language-based strategies to treat verb anomia, a frequent aphasia sign. Two participants with verb anomia were followed up in a pre-/posttherapy fMRI study. POEM was administered in a massed stimulation schedule, with personalized stimuli, resulting in significant improvement in both participants, with both trained and untrained items. Given that the latter finding is rarely reported in the literature, the evidence suggests that POEM favors the implementation of a word retrieval strategy that can be integrated and generalized. Changes in fMRI patterns following POEM reflect a reduction in the number of recruited areas supporting naming and the recruitment of brain areas that belong to the language and mirror neuron systems. The data provide evidence on the efficacy of POEM for verb anomia, while pointing to the added value of combined language and sensorimotor strategies for recovery from verb anomia, contributing to the consolidation of a word retrieval strategy that can be better generalized to untrained words. Future studies with a larger sample of participants are required to further explore this avenue.

Baseline structural imaging correlates of treatment outcomes in semantic variant primary progressive aphasia.

Semantic variant primary progressive aphasia (svPPA) is a neurodegenerative disorder characterized by a loss of semantic knowledge in the context of anterior temporal lobe atrophy (left > right). Core features of svPPA include anomia and single-word comprehension impairment. Despite growing evidence supporting treatment for anomia in svPPA, there is a paucity of research investigating neural mechanisms supporting treatment-induced gains and generalization to untrained items. In the current study, we examined the relation between the structural integrity of brain parenchyma (tissue inclusive of gray and white matter) at pre-treatment and treatment outcomes for trained and untrained items in a group of 19 individuals with svPPA who completed lexical retrieval treatment. Two structural neuroimaging approaches were used: an exploratory, whole-brain, voxel-wise approach and an a priori region of interest (ROI) approach. Based on previous research, bilateral temporal (inferior, middle, and superior temporal gyri), parietal (supramarginal and angular gyri), frontal (inferior and middle frontal gyri) and medial temporal (hippocampus and parahippocampal gyri) ROIs were selected from the Automated Anatomical Labeling (AAL) atlas. Analyses revealed improved naming of trained items and generalization to untrained items following treatment, providing converging evidence that individuals with svPPA can benefit from treatment for anomia. Better post-treatment naming accuracy was associated with the structural integrity of inferior parietal cortex and the hippocampus. Specifically, improved naming of trained items was related to the left supramarginal (phonological processing) and angular gyri (phonological and semantic processing), and improved naming of trained and untrained items was related to the left hippocampus (episodic, context-based memory). Future research should examine treatment outcomes in relation to pre-treatment functional and structural connectivity as well as changes in network dynamics following speech-language intervention to further elucidate the neural mechanisms underlying treatment response in svPPA and related disorders.

Treatment-induced neuroplasticity after anomia therapy in post-stroke aphasia: A systematic review of neuroimaging studies.

We systematically reviewed the literature on neural changes following anomia treatment post-stroke. We conducted electronic searches of CINAHL, Cochrane Trials, Embase, Ovid MEDLINE, MEDLINE-in-Process and PsycINFO databases; two independent raters assessed all abstracts and full texts. Accepted studies reported original data on adults with post-stroke aphasia, who received behavioural treatment for anomia, and magnetic resonance brain imaging (MRI) pre- and post-treatment. Search results yielded 2481 citations; 33 studies were accepted. Most studies employed functional MRI and the quality of reporting neuroimaging methodology was variable, particularly for pre-processing steps and statistical analyses. The most methodologically robust data were synthesized, focusing on pre- versus post-treatment contrasts. Studies more commonly reported increases (versus decreases) in activation following naming therapy, primarily in the left supramarginal gyrus, and left/bilateral precunei. Our findings highlight the methodological heterogeneity across MRI studies, and the paucity of robust evidence demonstrating direct links between brain and behaviour in anomia rehabilitation.

Effects of concurrent action and object naming treatment on naming skills and functional brain activation patterns in primary progressive aphasia: An fMRI study with a case-series design.

Individuals with primary progressive aphasia (PPA) exhibit differential impairment patterns in noun and verb naming, but it remains unclear whether anomia treatment results in similar improvements in noun and verb naming. Therefore, we examined the immediate and long-term (3-months post-treatment) behavioral and neural effects of an anomia treatment on object and action naming skills in PPA. A case-series design was utilized involving two individuals with PPA. Object and action words were trained concurrently and probed regularly using word lists matched on a number of lexical characteristics. One participant showed improvements in all word categories with different effect sizes whereas the other participant demonstrated improved naming only on trained object words. Treatment-induced fMRI changes were found in both hemispheres, with distinct patterns observed across participants. Further research is needed to better understand the effects of residual language and cognitive skills on behavioral and neurophysiological outcomes following anomia treatment for PPA.

Prosodic changes in aphasic speech: timing.

Controversy remains about the impairment of prosody in aphasia, particularly with regard to speech timing. This paper addresses this topic through an analysis of timing in four sets of a common morphological paradigm. The paradigm consisted of a basic form (stem) and two longer derived forms (e.g. zip, zipper, zippering). Normally, vowel durations are shorter in longer derived forms (e.g. zippering) than in the stem (e.g. zip), due to a process called 'initial shortening'. Twelve patients with aphasia (four each Broca, Wernicke, and Anomic), and 11 age-matched healthy adults were assessed. Structural (CT) and functional brain imaging (PET) were available for all patients. While all groups showed initial shortening between the stem and the derived forms, the patients with Broca's aphasia presented an inverse pattern between the two derived forms (longer initial vowel in 'zippering' than 'zipper'), and the patients with Wernicke's aphasia produced significantly longer vowel durations overall than the healthy participants. The results are related to radiological information regarding the location of structural and functional brain damage and relative preservation and loss of prosodic features in cerebral damage.

Correlates of anomia in non-semantic variants of primary progressive aphasia converge over time.

To track neural correlates of naming performance with disease progression, we estimated key areas affected in nonfluent/agrammatic (nfvPPA) and logopenic (lvPPA) primary progressive aphasia variants over time and changes in naming correlates over time. Twenty-nine non-semantic PPA participants (17 nfvPPA and 12 lvPPA) were selected based upon current diagnostic criteria and PiB-PET status and conducted a confrontation-naming task and a structural MRI. Linear mixed-effect models implemented in FreeSurfer were used for tracking cortical thickness and epicenters of atrophy over time. Using averaged cortical thickness of epicenters and naming performance as variables of interest, two sets of multivariate analyses were conducted to compare atrophy progression and naming correlates across groups. While all PPA participants demonstrated naming deterioration and progressive cortical thinning in the left temporal lobe and the left inferior frontal gyrus, the lvPPA cohort showed greater naming deterioration and thinning in the left posterior inferior parietal cortex over time than it did the nfvPPA cohort. The multivariate analyses confirmed a widespread cortical thinning in lvPPA over time, but a more rapid thinning in the right superior frontal gyrus of nfvPPA participants. Impaired naming correlated with common cortical regions in both groups. These regions included the left anterior superior temporal gyrus and the posterior middle temporal gyrus, which was primarily affected in lvPPA. Non-semantic PPA variants initially present with separate epicenters of atrophy and different spatial-temporal patterns of neurodegeneration over time, but the common involvement in key cortical regions of the left temporal lobe accounts for naming deterioration in both groups.

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.

Common and divergent neural correlates of anomia in amnestic and logopenic presentations of Alzheimer's disease.

The majority of logopenic variant primary progressive aphasia (lv-PPA) cases harbour Alzheimer pathology, suggesting that lv-PPA constitutes an atypical presentation of Alzheimer's disease (AD). However, even if caused by Alzheimer pathology, the clinical manifestations of lv-PPA differ from those observed in the typical or amnestic AD presentation: in lv-PPA, aphasia is the main feature while amnestic AD is characterised by impaired episodic memory. Anomia or impaired naming, however, is present in both AD presentations. Whether these presentations share anatomical and mechanistic processes of anomia has not been fully investigated. Accordingly, we studied naming performance and its relationship with regions of brain atrophy in 23 amnestic AD and 22 lv-PPA cases with presumed underlying Alzheimer pathology. Both AD groups displayed some degree of anomia and impaired word comprehension but these were particularly severe in lv-PPA and accompanied by a range of linguistic deficits, comprising phonological substitutions, superordinate semantic paraphasias and abnormal single-word repetition. Analysis of cortical thickness revealed that anomia was correlated with thinning in left superior temporal gyrus in both groups. In amnestic AD, however, anomia was also associated with thinning in right inferior temporal regions. Single-word comprehension (SWC), by contrast, was associated with cortical thinning involving bilateral fusiform gyri in both groups. These findings suggest that anomia in both amnestic AD and lv-PPA results from the involvement at multiple steps of word processing, in particular, semantic and lexical retrieval; in addition lv-PPA patients display a more marked involvement of phonological processing.

Visual anomia: a unidirectional disconnection.

A right-handed patient with a complete right homonymous hemianopia could not name objects seen in her left hemifield but could always select an object from an assortment when the object was named. If the right hemisphere was devoid of auditory language function, we must postulate separate transcallosal pathways from visual to verbal and from auditory language to visual information. Because only the former pathway was interrupted, our patient exhibited a "unidirectional" disconnection.

Naming deficit for non-living items: neuropsychological and PET study.

We report a patient with progressive left hemisphere atrophy who presented a lexical retrieval deficit more pronounced in naming non-living items than in naming living items. Word frequency and familiarity strongly influenced the performance, but the dissociation persisted when the items were controlled for these factors. In addition, the prevalent deficit for non-living items in respect to living items could be confirmed in tasks where other patients presented the opposite pattern. A PET study showed a significant hypometabolism in the left hemisphere regions suggesting that, at variance with living deficit which is observed in patients with bilateral lesions, non-living deficit is produced by unilateral left hemispheric lesions. This patient confirms that living and non-living categories may dissociate and that distinct neural systems subsume their knowledge.

Right temporal compensatory mechanisms in a deep dysphasic patient: a case report with activation study by SPECT.

A brain activation study using SPECT and 133Xe in a deep dysphasic patient with left temporal lesion is presented. The activation paradigm consisted of a passive listening to foreign language as baseline, a phoneme monitoring condition and a semantic word monitoring condition. The specific activation of the right middle temporal cortex observed in the semantic condition is congruent with the hypothesis of a compensatory role of the right hemisphere in processing concrete words. This case illustrates the interest of functional imaging for a better understanding of neural mechanisms of functional recovery after brain injury.

Frontotemporal decreases in rCBF correlate with degree of dysnomia in primary progressive aphasia.

UNLABELLED: Primary progressive aphasia (PPA) is an uncommon degenerative dementia characterized by gradual impairment of language function with initial sparing of the memory domain. Using semiquantitative 99mTc-hexamethyl propyleneamine oxime (HMPAO) brain SPECT as a measure of regional cerebral blood flow (rCBF), we investigated the relationship between reduced 99mTc-HMPAO uptake and the severity of dysnomia in PPA. METHODS: Seven right-handed patients with PPA had their dysnomia assessed by the Boston Naming Test (BNT), a subtest of the Boston Diagnostic Aphasia Examination. Neuroimaging studies, including 99mTc-HMPAO brain SPECT, CT, and MRI, were performed. Correlational analysis between reduced rCBF and BNT was performed. RESULTS: Brain SPECT showed a reduction in 99mTc-HMPAO uptake involving the frontal and temporal lobes in all 7 patients. CT and MRI showed mild to moderate cerebral atrophy in 4 patients. Low scores on the BNT correlated with low frontotemporal 99mTc-HMPAO (Spearman r = 0.97, P = 0.004) in the 5 patients with left-hemisphere involvement. CONCLUSION: Decreased rCBF to the frontotemporal region characterized the cerebral abnormalities associated with PPA. The finding of focal rCBF abnormalities in the right hemisphere of 2 right-handed women corroborates that PPA symptoms may arise from a "non-left-dominant"-hemisphere degenerative process. Our results support the usefulness of rCBF SPECT imaging as a diagnostic aid in PPA.

Associative anomia: dissociating words and their definitions.

A 60-year-old woman, in whom magnetic resonance imaging and single photon emission computed tomography confirmed the presence of chronic damage to the left temporal lobe, had pure anomia with sparing of other language and cognitive functions. She could independently access lexical knowledge (words) and semantic knowledge (word definitions). We postulate that her anomia was due to a failure to associate lexical and semantic knowledge.

Localisation of lesions in aphasia: clinical-CT scan correlations in stroke patients.

Ninety right-handed patients with present or past evidence of aphasia following a stroke were given a standard language battery and a CT scan examination. Presence and type of aphasia were correlated with the location and extent of the CT scan lesion. Most of the findings were compatible with the traditional views about the localisation of lesions in aphasia (e.g., anterior lesions in nonfluent aphasias with good comprehension, posterior lesions in fluent aphasia, etc.). The possible explanations for some unexpected findings (e.g., purely anterior lesions in global aphasia, or purely deep lesions in Broca's aphasia) are discussed. It is stressed that in establishing clinico-CT scan correlation, careful consideration must be given to the fact that both aphasia and the underlying lesion evolve with time.

Language-activated single-photon emission tomography imaging in the evaluation of language lateralization--evidence from a case of crossed aphasia: case report.

We report a right-handed patient who developed a nonfluent aphasia after surgery for a right parietal arteriovenous malformation. Resting brain single-photon emission tomography displayed decreased regional cerebral blood flow only in the right hemisphere, with spared regional cerebral blood flow in the left hemisphere. Single-photon emission tomography performed after a language activation task (Boston Naming Task) showed a consistent area of increased regional cerebral blood flow in the right inferior and posterior frontal lobe, supporting a right hemisphere dominance for language. These results suggest a potential role for this noninvasive study in the evaluation of language lateralization.

Acute computerized tomographic scans: their value in the localization of lesions and as prognostic indicators in aphasia.

Twenty three patients with past or present evidence of aphasia following either stroke (n = 19) or head trauma (n = 4) were given the Boston Diagnostic Aphasia Examination in order to classify their aphasia type and determine their language deficit at least three months postonset of their neurological disorder. The location and extent of brain lesions identified from computerized tomographic (C.T.) scans taken in the acute stage and, wherever possible, in the chronic stage (n = 7) were correlated with the type of aphasia. Lesions associated with global, Wernicke's, Broca's, conduction, and anomic aphasia are described and discussed in relation to the findings of previously reported clinico-C.T. scan correlation studies. The value of the acute stage C.T. scan as a predictor of long-term language deficits is discussed.

[Progressive aphasia without dementia]. / Afasia progresiva sin demencia.

INTRODUCTION: Slowly progressive aphasia without generalized dementia is considered as a degenerative disorder that can be differentiated of others well-known neurodegenerative disorders. CLINICAL CASE: We present a case report of a patient with slowly progressive aphasia, characterized by a progressive anomia and without generalized dementia. The patient was evaluated in the last four years: a neuropsychological assessment, a neurological exploration and structural (MRI) and functional (SPECT) neuroimaging were performed. CONCLUSION: This case is interesting on account of a selective implication of the left temporal hemisphere is showed in the pathogenesis of this disorder.

[Localization of lesions in aphasia: clinical-CT scan correlations (Part 1)].

Using a microcomputer, the locus and extent of the lesions, as demonstrated by computed tomography for 127 cases with various types of aphasia were superimposed onto standardized matrices. The relationship between the foci of the lesions and the types of aphasia was investigated. Broca ++aphasics (n = 39): Since the accumulated site of the lesions highly involved the deep structures of the lower part of the precentral gyrus as well as the insula and lenticular nucleus, only 60% of the Broca aphasics had lesions on these areas. This finding has proved to have little localizing value. Wernicke aphasics (n = 23): The size of the lesion was significantly smaller than Broca's aphasia. At least 70% of the patients had the superior temporal lesions involving Wernicke's area and subcortical lesions of the superior and middle temporal gyri. The site of lesion corresponded roughly to the previous clinico-pathological reports but located a little deep. Amnestic aphasics (n = 18): The size of the lesion was smaller than any other types. While there was some concentration of the lesions (maximum 40%) in the area of the subcortical region of the anterior temporal gyrus adjacent to Wernicke's area and the lenticular nucleus, the lesions were distributed throughout the left hemisphere. Amnestic aphasia was thought to be the least localizable. Conduction aphasics (n = 11): The lesions were relatively small in size. Many patients had posterior speech area lesions involving at least partially Wernicke's area. In particular, more than 80% of the conduction aphasics had lesions of the supramarginal gyrus and it's adjacent deep structures. Global aphasics (n = 36): In general, the size of the lesion was very large and 70% of the global aphasics had extensive lesions involving both Broca's and Wernicke's areas. However, there were observations showing that the lesions can be small and confined. Because of the large variability in lesion patterns and speech disturbances, it is necessary to expand the number of cases for relate detailed neuropsychological examinations with morphological CT-findings. Our method permits it easily to process and to analyze a large number of cases. By studying larger series, the better definition in the relationship between anatomic lesion location and aphasia type, even for less common aphasia syndromes could be obtained.