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Background: Letter-by-letter readers identify each letter of the word they are reading serially in left to right order before recognising the word. When their letter naming is also impaired, letter-by-letter reading is inaccurate and can render even single word reading very poor. Tactile and/or kinaesthetic strategies have been reported to improve reading in these patients, but only under certain conditions or for a limited set of stimuli. Aims: The primary aim of the current study was to determine whether a tactile/kinaesthetic treatment could significantly improve reading specifically under normal reading conditions, i.e., reading untrained words presented in free vision and read without overt use of the strategy. Methods & Procedures: Three chronic letter-by-letter readers participated in a tactile/kinaesthetic treatment aimed at first improving letter-naming accuracy (phase 1) and then letter-by-letter reading speed (phase 2). In a multiple case series design, accuracy and speed of reading untrained words without overt use of the trained tactile/kinaesthetic strategy was assessed before phase 1, after phase 1, and again after phase 2. Outcomes & Results: All three patients significantly improved both their speed and accuracy in reading untrained words without overt use of the trained tactile/kinaesthetic strategy. All three patients required the additional practice in phase 2 to achieve significant improvement. Treatment did not target sentence-level reading, yet two of the three patients became so adept that they could read entire sentences. Conclusions: This study replicates previous findings on the efficacy of tactile/kinaesthetic treatment for letter-by-letter readers with poor letter naming. It further demonstrates that this treatment can alter cognitive processing such that words never specifically trained can be read in free vision without overtly using the trained strategy. The data suggest that an important element in achieving this level of generalisation is continuing training beyond the point of initial mastery (i.e., accurate letter naming). [ABSTRACT FROM AUTHOR]

We evaluated the efficacy and cost savings of the pneumococcal pneumonia vaccine in a retrospective cohort study of 762 vaccinated and 1161 randomly selected unvaccinated age-sex matched persons in Blue Cross/Blue Shield of Minnesota using medical and pharmaceutical claims. The pneumonia incidence and the ratio of incidence in the postvaccination to prevaccination periods (rate ratio) were examined in the vaccine group by sex and risk factors. Vaccination significantly reduced pneumonia incidence, with overall efficacy of 69% and higher efficacy in women (86%) than in men (33%). We assigned persons to risk categories based on disease conditions as recorded in the claims by the ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) diagnostic codes. In the risk categories, efficacy varied from 50% to 75% and was confounded by sex. Immunocompromised and immunocompetent women had high efficacy (83% to 88%), while immunocompetent and immunocompromised men had lower efficacy (33%). Persons with a precondition of pneumonia exhibited similar vaccine efficacy to the overall cohort relative to the comparison group. Projected costs of pneumonia cases are 3.6 times the observed costs of vaccination and postvaccination pneumonia costs. We conclude that the pneumococcal pneumonia vaccine is efficacious in persons having had pneumonia, persons "at risk" of developing pneumonia, or persons over 50 years of age, and it corresponds to overall savings of $141 per person. [ABSTRACT FROM AUTHOR]

Background: An individual's diagnostic subtype may fail to predict the efficacy of a given type of treatment for anomia. Classification by conceptual-semantic impairment may be more informative., Aims: This study examined the effects of conceptual-semantic impairment and diagnostic subtype on anomia treatment effects in primary progressive aphasia (PPA) and Alzheimer's disease (AD)., Methods & Procedures: At baseline, the picture and word versions of the Pyramids and Palm Trees and Kissing and Dancing tests were used to measure conceptual-semantic processing. Based on norming that was conducted with unimpaired older adults, participants were classified as being impaired on both the picture and word versions (i.e., modality-general conceptual-semantic impairment), the picture version (Objects or Actions) only (i.e., visual-conceptual impairment), the word version (Nouns or Verbs) only (i.e., lexical-semantic impairment), or neither the picture nor the word version (i.e., no impairment). Following baseline testing, a lexical treatment and a semantic treatment were administered to all participants. The treatment stimuli consisted of nouns and verbs that were consistently named correctly at baseline (Prophylaxis items) and/or nouns and verbs that were consistently named incorrectly at baseline (Remediation items). Naming accuracy was measured at baseline, and it was measured at three, seven, eleven, fourteen, eighteen, and twenty-one months., Outcomes & Results: Compared to baseline naming performance, lexical and semantic treatments both improved naming accuracy for treated Remediation nouns and verbs. For Prophylaxis items, lexical treatment was effective for both nouns and verbs, and semantic treatment was effective for verbs, but the pattern of results was different for nouns -- the effect of semantic treatment was initially nonsignificant or marginally significant, but it was significant beginning at 11 Months, suggesting that the effects of prophylactic semantic treatment may become more apparent as the disorder progresses. Furthermore, the interaction between baseline Conceptual-Semantic Impairment and the Treatment Condition (Lexical vs. Semantic) was significant for verb Prophylaxis items at 3 and 18 Months, and it was significant for noun Prophylaxis items at 14 and 18 Months., Conclusions: The pattern of results suggested that individuals who have modality-general conceptual-semantic impairment at baseline are more likely to benefit from lexical treatment, while individuals who have unimpaired conceptual-semantic processing at baseline are more likely to benefit from semantic treatment as the disorder progresses. In contrast to conceptual-semantic impairment, diagnostic subtype did not typically predict the treatment effects., Competing Interests: The authors report no conflicts of interest.

Despite the many mistakes we make while speaking, people can effectively communicate because we monitor our speech errors. However, the cognitive abilities and brain structures that support speech error monitoring are unclear. There may be different abilities and brain regions that support monitoring phonological speech errors versus monitoring semantic speech errors. We investigated speech, language, and cognitive control abilities that relate to detecting phonological and semantic speech errors in 41 individuals with aphasia who underwent detailed cognitive testing. Then, we used support vector regression lesion symptom mapping to identify brain regions supporting detection of phonological versus semantic errors in a group of 76 individuals with aphasia. The results revealed that motor speech deficits as well as lesions to the ventral motor cortex were related to reduced detection of phonological errors relative to semantic errors. Detection of semantic errors selectively related to auditory word comprehension deficits. Across all error types, poor cognitive control related to reduced detection. We conclude that monitoring of phonological and semantic errors relies on distinct cognitive abilities and brain regions. Furthermore, we identified cognitive control as a shared cognitive basis for monitoring all types of speech errors. These findings refine and expand our understanding of the neurocognitive basis of speech error monitoring., (© 2023 Massachusetts Institute of Technology.)

Alexia is common in the context of aphasia. It is widely agreed that damage to phonological and semantic systems not specific to reading causes co-morbid alexia and aphasia. Studies of alexia to date have only examined phonology and semantics as singular processes or axes of impairment, typically in the context of stereotyped alexia syndromes. However, phonology, in particular, is known to rely on subprocesses, including sensory-phonological processing, motor-phonological processing, and sensory-motor integration. Moreover, many people with stroke aphasia demonstrate mild or mixed patterns of reading impairment that do not fit neatly with one syndrome. This cross-sectional study tested whether the hallmark symptom of phonological reading impairment, the lexicality effect, emerges from damage to a specific subprocess of phonology in stroke patients not selected for alexia syndromes. Participants were 30 subjects with left-hemispheric stroke and 37 age- and education-matched controls. A logistic mixed-effects model tested whether post-stroke impairments in sensory phonology, motor phonology, or sensory-motor integration modulated the effect of item lexicality on patient accuracy in reading aloud. Support vector regression voxel-based lesion-symptom mapping localized brain regions necessary for reading and non-orthographic phonological processing. Additionally, a novel support vector regression structural connectome-symptom mapping method identified the contribution of both lesioned and spared but disconnected, brain regions to reading accuracy and non-orthographic phonological processing. Specifically, we derived whole-brain structural connectomes using constrained spherical deconvolution-based probabilistic tractography and identified lesioned connections based on comparisons between patients and controls. Logistic mixed-effects regression revealed that only greater motor-phonological impairment related to lower accuracy reading aloud pseudowords versus words. Impaired sensory-motor integration was related to lower overall accuracy in reading aloud. No relationship was identified between sensory-phonological impairment and reading accuracy. Voxel-based and structural connectome lesion-symptom mapping revealed that lesioned and disconnected left ventral precentral gyrus related to both greater motor-phonological impairment and lower sublexical reading accuracy. In contrast, lesioned and disconnected left temporoparietal cortex is related to both impaired sensory-motor integration and reduced overall reading accuracy. These results clarify that at least two dissociable phonological processes contribute to the pattern of reading impairment in aphasia. First, impaired sensory-motor integration, caused by lesions disrupting the left temporoparietal cortex and its structural connections, non-selectively reduces accuracy in reading aloud. Second, impaired motor-phonological processing, caused at least partially by lesions disrupting left ventral premotor cortex and structural connections, selectively reduces sublexical reading accuracy. These results motivate a revised cognitive model of reading aloud that incorporates a sensory-motor phonological circuit., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Findings from several studies have indicated that participants with nfvPPA and participants with svPPA exhibit different patterns on action and object naming tasks, while other recent studies have found that neither participants with nfvPPA nor participants with svPPA show a significant difference in accuracy between object naming and action naming., Aims: The goal of this study was to test the hypothesis that relative action naming impairment is associated with grammatical ability in PPA, rather than a specific subtype of PPA., Methods & Procedures: Thirty-four participants with PPA completed the Boston Naming Test, the Action Naming subtest of the Boston Diagnostic Aphasia Examination, and the Northwestern Anagram Test, which was used to measure grammatical ability. Z -scores for the two naming tasks were calculated based on normative data from unimpaired controls. For each participant with PPA, the relative action naming impairment was calculated by subtracting the object naming z -score from the action naming z -score. Linear regression analysis was then used to evaluate the role of grammatical ability as a predictor of relative action naming impairment, while controlling for age, education, cognitive ability (as measured by the Montreal Cognitive Assessment), and semantic ability (as measured by the Pyramids and Palm Trees test). The interaction between grammatical ability and each control variable was also examined., Outcomes & Results: The main effect of grammatical ability was a significant predictor of relative action naming impairment, while none of the control variables was a significant predictor. However, the interaction between grammatical ability and semantic ability was also significant., Conclusions: Individuals who have both grammatical impairment and semantic impairment have the largest relative action naming impairment. These individuals may benefit from a treatment that focuses on the retrieval of verbs and their arguments.

This study examined the maintenance of anomia treatment effects in primary progressive aphasia (PPA). Following baseline testing, a phonological treatment and an orthographic treatment were administered over the course of six months. The treatment stimuli consisted of nouns that were consistently named correctly at baseline (Prophylaxis items) and/or nouns that were consistently named incorrectly at baseline (Remediation items). Naming accuracy was measured at baseline, and it was measured at 1 month, 8 months, and 15 months post-treatment. The change in naming accuracy from baseline to each post-treatment evaluation was calculated within each treatment condition, and within a matched untrained condition. The change in naming accuracy was then compared between the three conditions. The results of these analyses indicate that phonological and orthographic treatments are both effective in the Prophylaxis and Remediation of anomia in all three variants of PPA. For Prophylaxis items, some of the effects of each treatment can persist for as long as 15 months post-treatment. These long-term treatment effects were more robust in the orthographic treatment condition and for participants with the semantic variant of PPA.

Reading involves the rapid extraction of sound and meaning from print through a cooperative division of labor between phonological and lexical-semantic processes. Whereas lesion studies of patients with stereotyped acquired reading deficits contributed to the notion of a dissociation between phonological and lexical-semantic reading, the neuroanatomical basis for effects of lexicality (word vs pseudoword), orthographic regularity (regular vs irregular spelling-sound correspondences), and concreteness (concrete vs abstract meaning) on reading is underspecified, particularly outside the context of strong behavioral dissociations. Support vector regression lesion-symptom mapping (LSM) of 73 left hemisphere stroke survivors (male and female human subjects) not preselected for stereotyped dissociations revealed the differential contributions of specific cortical regions to reading pseudowords (ventral precentral gyrus), regular words (planum temporale, supramarginal gyrus, ventral precentral and postcentral gyrus, and insula), and concrete words (pars orbitalis and pars triangularis). Consistent with the primary systems view of reading being parasitic on language-general circuitry, our multivariate LSM analyses revealed that phonological decoding depends on perisylvian areas subserving sound-motor integration and that semantic effects on reading depend on frontal cortex subserving control over concrete semantic representations that aid phonological access from print. As the first study to localize the differential cortical contributions to reading pseudowords, regular words, and concrete words in stroke survivors with variable reading abilities, our results provide important information on the neurobiological basis of reading and highlight the insights attainable through multivariate, process-based approaches to alexia. SIGNIFICANCE STATEMENT Whereas fMRI evidence for neuroanatomical dissociations between phonological and lexical-semantic reading is abundant, evidence from modern lesion studies establishing the differential contributions of specific brain regions to specific reading processes is lacking. Our application of multivariate lesion-symptom mapping revealed that effects of lexicality, orthographic regularity, and concreteness on reading differentially depend on areas subserving auditory-motor integration and semantic control. Phonological decoding of print relies on a dorsal perisylvian network supporting auditory and articulatory representations, with unfamiliar words relying especially on articulatory mapping. In tandem with this dorsal decoding system, anterior inferior frontal gyrus may coordinate control over concrete semantic representations that support mapping of print to sound, which is a novel potential mechanism for semantic influences on reading., (Copyright © 2019 the authors.)

Many individuals with aphasia report the ability to say words in their heads despite spoken naming difficulty. Here, we examined individual differences in the experience of inner speech (IS) in participants with aphasia to test the hypotheses that self-reported IS reflects intact phonological retrieval and that articulatory output processing is not essential to IS. Participants (N = 53) reported their ability to name items correctly internally during a silent picture-naming task. We compared this measure of self-reported IS to spoken picture naming and a battery of tasks measuring the underlying processes required for naming (i.e., phonological retrieval and output processing). Results from three separate analyses of these measures indicate that self-reported IS relates to phonological retrieval and that speech output processes are not a necessary component of IS. We suggest that self-reported IS may be a clinically valuable measure that could assist in clinical decision-making regarding anomia diagnosis and treatment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose Individuals with aphasia often report that they feel able to say words in their heads, regardless of speech output ability. Here, we examine whether these subjective reports of successful "inner speech" (IS) are meaningful and test the hypothesis that they reflect lexical retrieval. Method Participants were 53 individuals with chronic aphasia. During silent picture naming, participants reported whether or not they could say the name of each item inside their heads. Using the same items, they also completed 3 picture-based tasks that required phonological retrieval and 3 matched auditory tasks that did not. We compared participants' performance on these tasks for items they reported being able to say internally versus those they reported being unable to say internally. Then, we examined the relationship of psycholinguistic word features to self-reported IS and spoken naming accuracy. Results Twenty-six participants reported successful IS on nearly all items, so they could not be included in the item-level analyses. These individuals performed correspondingly better than the remaining participants on tasks requiring phonological retrieval, but not on most other language measures. In the remaining group ( n = 27), IS reports related item-wise to performance on tasks requiring phonological retrieval, but not to matched control tasks. Additionally, IS reports were related to 3 word characteristics associated with lexical retrieval, but not to articulatory complexity; spoken naming accuracy related to all 4 word characteristics. Six participants demonstrated evidence of unreliable IS reporting; compared with the group, they also detected fewer errors in their spoken responses and showed more severe language impairments overall. Conclusions Self-reported IS is meaningful in many individuals with aphasia and reflects lexical phonological retrieval. These findings have potential implications for treatment planning in aphasia and for our understanding of IS in the general population.

This study evaluated the efficacy of phonological and orthographic treatments for anomia in the semantic and logopenic variants of primary progressive aphasia (svPPA and lvPPA, respectively). Both treatments were administered for 6 months. The treatment stimuli consisted of nouns that were consistently named correctly at baseline (prophylaxis items) and/or nouns that were consistently named incorrectly at baseline (remediation items). Oral naming accuracy was measured for trained and untrained picture exemplars, as well as matched items from an untrained condition (UC). Written naming and scene description tasks were also conducted. For all tasks, the change in naming accuracy from baseline to 1 month post-treatment was compared between the UC and each treatment condition. These comparisons indicated that both treatments were effective in the remediation and prophylaxis of anomia in both variants. Furthermore, generalisation to untrained exemplars occurred in both subtypes, whereas item generalisation occurred in lvPPA, and task generalisation was present in svPPA.

Background: Individuals with primary progressive aphasia (PPA) and their caregivers want to know what to expect so that they can plan support appropriately. The ability to predict decline in naming and semantic knowledge, and advise individuals with PPA and their caregivers regarding future planning, would be invaluable clinically., Aims: The aims of this study were to investigate patterns of decline in naming and semantic knowledge in each of the clinical variants of PPA (logopenic variant PPA, lvPPA; nonfluent agrammatic PPA, nfaPPA; and semantic variant PPA, svPPA) and to examine the effects of other variables on rate of decline. We hypothesized that speech-language rehabilitation, higher education, and higher baseline test scores would be associated with slower decline, and older age with faster decline., Methods and Procedures: A total of ninety-four participants with PPA underwent language testing, including thirty six participants with lvPPA, thirty-one participants with nfaPPA, and twenty-seven participants with svPPA. All participant groups were similar in age and education. We focused on decline on three tests: the short form of the Boston Naming Test (BNT), the Hopkins Assessment of Naming Actions (HANA), and the short form of the Pyramids and Palm Trees Test (PPTT)., Outcome and Results: Across language tests, the most precipitous rates of decline (loss of points per month) occurred in nfaPPA, followed by svPPA, then lvPPA. Female sex, longer symptom duration, higher baseline test score, and speech-language rehabilitation were associated with slower decline., Conclusions: PPA variants were distinguishable by rapidity of decline, with nfaPPA having the most precipitous decline. As hypothesized, higher baseline test scores and speech-language rehabilitation were associated with slower decline. Surprisingly, age and education were not important prognostically for individuals in this study. Further study of prognostically-relevant variables in PPA is indicated in this population.

Objective: An important aspect of the rehabilitation of cognitive and linguistic function subsequent to brain injury is the maintenance of learning beyond the time of initial treatment. Such maintenance is often not satisfactorily achieved. Additional practice, or overtraining, may play a key role in long-term maintenance. In particular, the literature on learning in cognitively intact persons has suggested that it is testing, and not studying, that contributes to maintenance of learning. The present study investigates the hypothesis that continuing to test relearned words in persons with anomia will lead to significantly greater maintenance compared with continuing to study relearned words., Method: The current study combines overtraining with the variable of test versus study in examining the effects of overtesting and overstudying on maintenance of word finding in 3 persons with aphasia. First, treatment successfully reestablished the connections between known items and their names. Once the connections were reestablished (i.e., items could be named successfully), each item was placed into 1 of 4 overtraining conditions: test and study, only test, only study, or no longer test or study. Maintenance was probed at 1 month and 4 months following the end of overtraining., Results: The results are consistent with an advantage of testing compared with studying. All 3 participants showed significantly greater maintenance for words that were overtested than for words that were overstudied. This testing benefit persisted at 1 month and 4 months after completion of the treatment. In fact, there was no clear evidence for any benefit of overstudying., Conclusions: The present study demonstrates that overtesting, but not overstudying, leads to lasting maintenance of language rehabilitation gains in patients with anomia. The implications for the design of other treatment protocols are immense. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Many individuals with aphasia describe anomia with comments like "I know it but I can't say it." The exact meaning of such phrases is unclear. We hypothesize that at least two discrete experiences exist: the sense of (1) knowing a concept, but failing to find the right word, and (2) saying the correct word internally but not aloud (successful inner speech, sIS). We propose that sIS reflects successful lexical access; subsequent overt anomia indicates post-lexical output deficits. In this pilot study, we probed the subjective experience of anomia in 37 persons with aphasia. Self-reported sIS related to aphasia severity and phonological output deficits. In multivariate lesion-symptom mapping, sIS was associated with dorsal stream lesions, particularly in ventral sensorimotor cortex. These preliminary results suggest that people with aphasia can often provide meaningful insights about their experience of anomia and that reports of sIS relate to specific lesion locations and language deficits., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Structural imaging has not been used previously to predict the effect of treatment in primary progressive aphasia (PPA)., Aims: This study examined relationships between baseline brain volume and the effects of phonological and orthographic treatments for anomia in PPA. It was predicted that lower baseline volume would be associated with lower post-treatment naming accuracy for treated items and smaller generalization effects., Methods & Procedures: Twenty-one individuals with PPA participated. The treatment stimuli consisted of nouns that were consistently named correctly at baseline (Prophylaxis items) and/or nouns that were consistently named incorrectly at baseline (Remediation items). All 21 participants had Prophylaxis items, while 10 participants had Remediation items. Naming accuracy for untrained and trained items (Exemplar set 1) was measured. In addition, stimulus generalization was examined by having participants name an alternative exemplar of each untrained and trained item (Exemplar set 2). Correlational analyses focused on the relationships between naming accuracy and volume of regions previously identified as having a role in naming and semantic processing., Outcomes & Results: Unexpectedly, there were no significant correlations between baseline volume and post-treatment accuracy for treated items. However, baseline volume within the left temporal pole was positively correlated with post-treatment accuracy for Untrained Exemplar set 2 Prophylaxis items, while baseline volume in the left inferior temporal gyrus was positively correlated with post-treatment accuracy for Untrained Exemplar set 1 Remediation items., Conclusions: These findings suggest that lower volume in the left temporal pole is associated with decline for Untrained items, while lower volume in the left inferior temporal gyrus is associated with a lack of improvement for Untrained items. Possible explanations for the different patterns observed across Exemplar sets are discussed.

People with aphasia frequently report being able to say a word correctly in their heads, even if they are unable to say that word aloud. It is difficult to know what is meant by these reports of "successful inner speech". We probe the experience of successful inner speech in two people with aphasia. We show that these reports are associated with correct overt speech and phonologically related nonword errors, that they relate to word characteristics associated with ease of lexical access but not ease of production, and that they predict whether or not individual words are relearned during anomia treatment. These findings suggest that reports of successful inner speech are meaningful and may be useful to study self-monitoring in aphasia, to better understand anomia, and to predict treatment outcomes. Ultimately, the study of inner speech in people with aphasia could provide critical insights that inform our understanding of normal language.

Background: The efficacy of telerehabilitation-based treatment for anomia has been demonstrated in post-stroke aphasia, but the efficacy of this method of anomia treatment delivery has not been established within the context of degenerative illness., Aims: The current study evaluated the feasibility and efficacy of a telerehabilitation-based approach to anomia treatment within the three subtypes of primary progressive aphasia (PPA)., Methods & Procedures: Each of the three telerehabilitation participants represented a distinct subtype of PPA. Following a baseline evaluation of language and cognition, a phonological treatment and an orthographic treatment were administered to all participants over the course of six months. One month after the end of treatment, a post-treatment evaluation began. All treatment sessions and the majority of the evaluation sessions were administered via telerehabilitation. Treatment effects were examined within each subject, and treatment effects were also compared between each telerehabilitation participant and a group of in-person participants who had the same subtype of PPA., Outcomes & Results: All three telerehabilitation participants exhibited positive treatment effects. CGR (nonfluent/agrammatic variant PPA) and WCH (logopenic variant PPA) showed maintenance of naming for prophylaxis items in both treatment conditions, while ACR (semantic variant PPA) demonstrated increased naming of remediation items in the phonological treatment condition. Compared to in-person participants with the same subtype of PPA, each of the telerehabilitation participants typically showed effects that were either within the expected range or larger than expected., Conclusions: Telerehabilitation-based anomia treatment is feasible and effective in all three subtypes of PPA.

It has been argued that individuals with logopenic variant primary progressive aphasia (lvPPA) have an impairment of the phonological loop, which is a component of the short-term memory (STM) system. In contrast, this type of impairment is not thought to be present in mild typical Alzheimer's disease (AD). Thus, one would predict that people with lvPPA would score significantly lower than a matched AD group on tasks that require phonological STM. In the current study, an lvPPA group was compared with a mild AD group that was matched on age, education, and general cognitive functioning. For a subset of the tasks that involved pseudowords, the AD and lvPPA groups were compared to a healthy control group that was matched on age and education. The lvPPA group was more impaired than the AD group on all of the tasks that required phonological STM, including the pseudoword tasks, but there were no significant differences between these groups on tasks that required visuospatial STM. Compared to the healthy controls, the lvPPA group performed significantly worse on the repetition and reading of pseudowords, while the AD group did not differ significantly from the controls on these tasks. These findings are consistent with the hypothesis that phonological STM is impaired in lvPPA., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Treatment studies for anomia in PPA have rarely compared multiple treatments in the same individual, and few anomia treatment studies have included participants with the logopenic variant of PPA (lvPPA)., Aims: The goals of this study were to evaluate two types of treatment for anomia in a bilingual participant (ND) with lvPPA, and to examine possible cross-language transfer of treatment effects., Methods & Procedures: ND is a Norwegian-English bilingual woman with lvPPA who began this study at the age of 69. In the phonological treatment, ND listened to a word while viewing a corresponding picture, and she repeated the word. In the orthographic treatment, ND read a word out loud while viewing the corresponding picture, and she then copied the word. Both treatments were conducted in English, and accuracy for three tasks (oral naming, written naming, and naming to definition) was assessed in English and Norwegian. The treatment occurred over a one-year period, with eight sessions at the laboratory during the first month, followed by monthly laboratory sessions and thrice-weekly home practice sessions during the subsequent 11 months. Post-treatment assessments were conducted at 1 week, 8 months, 1 year, 20 months, and 3 years., Outcomes & Results: Compared to untrained items, the orthographic treatment resulted in greater English written naming accuracy. This treatment also resulted in cross-language transfer: greater Norwegian oral naming and naming to definition accuracy. The phonological treatment resulted in marginally greater English oral naming accuracy, but it did not have a significant effect on naming accuracy in Norwegian., Conclusions: These findings suggest that the orthographic treatment was effective in strengthening the orthographic representations of the treated items, which facilitated ND's written naming performance. The pattern of cross-language transfer suggests that the orthographic treatment also strengthened the language-independent semantic representations of the treated items, thereby facilitating access to their Norwegian phonological representations.

Anterior and posterior brain areas are involved in the storage and retrieval of semantic representations, but it is not known how these areas dynamically interact during semantic processing. We hypothesized that long-range theta-band coherence would reflect coupling of these areas and examined the oscillatory dynamics of lexical-semantic processing using a semantic priming paradigm with a delayed letter-search task while recording subjects' EEG. Time-frequency analysis revealed facilitation of semantic processing for Related compared to Unrelated conditions, which resulted in a reduced N400 and reduced gamma power from 150 to 450ms. Moreover, we observed greater anterior-posterior theta coherence for Unrelated compared to Related conditions over the time windows 150-425ms and 600-900ms. We suggest that while gamma power reflects activation of local functional networks supporting semantic representations, theta coherence indicates dynamic coupling of anterior and posterior areas for retrieval and post-retrieval processing and possibly an interaction between semantic relatedness and working memory., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Differences in the oscillatory EEG dynamics of reading open class (OC) and closed class (CC) words have previously been found (Bastiaansen et al., 2005) and are thought to reflect differences in lexical-semantic content between these word classes. In particular, the theta-band (4-7 Hz) seems to play a prominent role in lexical-semantic retrieval. We tested whether this theta effect is robust in an older population of subjects. Additionally, we examined how the context of a word can modulate the oscillatory dynamics underlying retrieval for the two different classes of words. Older participants (mean age 55) read words presented in either syntactically correct sentences or in a scrambled order ("scrambled sentence") while their EEG was recorded. We performed time-frequency analysis to examine how power varied based on the context or class of the word. We observed larger power decreases in the alpha (8-12 Hz) band between 200-700 ms for the OC compared to CC words, but this was true only for the scrambled sentence context. We did not observe differences in theta power between these conditions. Context exerted an effect on the alpha and low beta (13-18 Hz) bands between 0 and 700 ms. These results suggest that the previously observed word class effects on theta power changes in a younger participant sample do not seem to be a robust effect in this older population. Though this is an indirect comparison between studies, it may suggest the existence of aging effects on word retrieval dynamics for different populations. Additionally, the interaction between word class and context suggests that word retrieval mechanisms interact with sentence-level comprehension mechanisms in the alpha-band.

BACKGROUND: Letter-by-letter readers identify each letter of the word they are reading serially in left to right order before recognizing the word. When their letter naming is also impaired, letter-by-letter reading is inaccurate and can render even single word reading very poor. Tactile and/or kinesthetic strategies have been reported to improve reading in these patients, but only under certain conditions or for a limited set of stimuli. AIMS: The primary aim of the current study was to determine whether a tactile/kinesthetic treatment could significantly improve reading specifically under normal reading conditions, i.e. reading untrained words presented in free vision and read without overt use of the strategy. METHODS #ENTITYSTARTX00026; PROCEDURES: Three chronic letter-by-letter readers participated in a tactile/kinesthetic treatment aimed at first improving letter naming accuracy (phase 1) and then letter-by-letter reading speed (phase 2). In a multiple case series design, accuracy and speed of reading untrained words without overt use of the trained tactile/kinesthetic strategy was assessed before phase 1, after phase 1 and again after phase 2. OUTCOMES #ENTITYSTARTX00026; RESULTS: All three patients significantly improved both their speed and accuracy reading untrained words without overt use of the trained tactile/kinesthetic strategy. All three patients required the additional practice in phase 2 to achieve significant improvement. Treatment did not target sentence level reading, yet two of the three patients became so adept that they could read entire sentences. CONCLUSIONS: This study replicates previous findings on the efficacy of tactile/kinesthetic treatment for letter-by-letter readers with poor letter naming. It further demonstrates that this treatment can alter cognitive processing such that words never specifically trained can be read in free vision without overtly using the trained strategy. The data suggest that an important element in achieving this level of generalization is continuing training beyond the point of initial mastery (i.e. accurate letter naming).

This study examines the reasons for the success of Multiple Oral Re-reading (MOR; Moyer, 1979), a non-invasive, easily administered alexia treatment that has been reported in the literature and is currently in clinical use. The treatment consists of reading text passages aloud multiple times a day. Findings that MOR improves reading speed on practised as well as novel text have been inconsistent, making MOR's role in the rehabilitation of alexia unclear. We hypothesised that MOR's treatment mechanism works through repetition of high frequency words (i.e., bottom-up processing). We designed and controlled our text passages to test the hypothesis that participants would not improve on all novel text but would improve on text that includes a critical mass of the words contained in the passages they were re-reading. We further hypothesised that the improvement would be at the level of their specific alexic deficit. We tested four participants with phonological alexia and two with pure alexia during 8 weeks of MOR treatment. Contrary to the conclusions of previous studies, our results indicate that improvements in top-down processing cannot explain generalisation in MOR and that much of the improvement in reading is through repetition of the practised words. However, most patients also showed improvement when specific phrases were re-used in novel passages, indicating that practice of difficult words in context may be crucial to reading improvement.

BACKGROUND: Phonologic text alexia (PhTA) is a reading disorder in which reading of pseudowords is impaired, but reading of real words is impaired only when reading text. Oral reading accuracy remains well preserved when words are presented individually, but when presented in text the part-of-speech effect that is often seen in phonologic alexia (PhA) emerges. AIMS: To determine whether repetition priming could strengthen and/or maintain the activation of words during text reading. METHODS #ENTITYSTARTX00026; PROCEDURES: We trained NYR, a patient with PhTA, to use a strategy, Sentence Building, designed to improve accuracy of reading words in text. The strategy required NYR to first read the initial word, and then build up the sentence by adding on sequential words, in a step-wise manner, utilizing the benefits of repetition priming to enhance accuracy. OUTCOMES #ENTITYSTARTX00026; RESULTS: When using the strategy, NYR displayed improved accuracy not only for sentences she practiced using the strategy, but unpracticed sentences as well. Additionally, NYR performed better on a test of comprehension when using the strategy, as compared to without the strategy. CONCLUSIONS: In light of research linking repetition priming to increased neural processing efficiency, our results suggest that use of this compensatory strategy improves reading accuracy and comprehension by temporarily boosting phonologic activation levels.

We constrain parity-violating interactions to the surface of last scattering using spectra from the QUaD experiment's second and third seasons of observations by searching for a possible systematic rotation of the polarization directions of cosmic microwave background photons. We measure the rotation angle due to such a possible "cosmological birefringence" to be 0.55 degrees +/-0.82 degrees (random) +/-0.5 degrees (systematic) using QUaD's 100 and 150 GHz temperature-curl and gradient-curl spectra over the spectra over the multipole range 200

Patients with phonologic alexia can be trained to read semantically impoverished words (e.g., functors) by pairing them with phonologically-related semantically rich words (e.g, nouns). What mechanisms underlie success in this cognitive re-training approach? Does the mechanism change if the skill is "overlearned", i.e., practiced beyond criterion? We utilized fMRI pre- and post-treatment, and after overlearning, to assess treatment-related functional reorganization in a patient with phonologic alexia, two years post left temporoparietal stroke. Pre-treatment, there were no statistically significant differences in activation profiles across the sets of words. Post-treatment, accuracy on the two trained sets improved. Compared with untrained words, reading trained words recruited larger and more significant clusters of activation in the right hemisphere, including right inferior frontal and inferior parietal cortex. Post-overlearning, with near normal performance on overlearned words, predominant activation shifted to left hemisphere regions, including perilesional activation in superior parietal lobe, when reading overlearned vs. untrained words.

People with phonologic alexia often have difficulty reading functors and verbs, in addition to pseudowords. Friedman et al. [Friedman, R. B., Sample, D. M, & Lott, S. N. (2002). The role of level of representation in the use of paired associate learning for rehabilitation of alexia. Neuropsychologia, 40, 223-234] reported a successful treatment for phonologic alexia that paired problematic functors and verbs with easily read relays that were homophonous nouns (e.g. "be" paired with "bee"). The current study evaluates the efficacy of pairing problematic grammatical words with relays that share initial phonemes, but vary in the relationship of their final phonemes. Results showed that reading of target grammatical words improved to criterion level (90% accuracy over two consecutive probes) in all experimental conditions with shared phonology, but remained far below criterion level in control conditions. There was a significant correlation between degree of phonologic relatedness and error rate. Maintenance of the treatment effect was poor as assessed by traditional measurement, however a dramatic savings during relearning was demonstrated during a subsequent treatment phase. The finding that reading can be re-organized by pairing target words not only with homophones, but with other phonologically related relays, suggests that this approach could be applied to a wide corpus of words and, therefore, potentially be of great use clinically. We suggest, within a connectionist account, that the treatment effect results from relays priming the initial phonologic units of the targets.

Patients with Alzheimer's disease (AD) and patients with semantic dementia (SD) both exhibit deficits on explicit tasks of semantic memory such as picture naming and category fluency. These deficits have been attributed to a degradation of the stored semantic network. An alternative explanation attributes the semantic deficit in AD to an impaired ability to consciously retrieve items from the semantic network. The present study used an implicit lexical-decision priming task to examine the integrity of the underlying semantic network in AD and SD patients matched for degree of impairment on explicit semantic memory tasks. The AD (n=11) and SD (n=11) patient groups were matched for age, education, level of dementia and impairment on four explicit semantic memory tasks. Healthy elderly participants (n=22) were matched for age and education. Semantic priming effects were evaluated for three types of semantic relationships (attributes, category coordinates, and category superordinates) and compared to lexical associative priming. Healthy controls showed significant priming across all conditions. In contrast, AD patients showed normal superordinate priming, and significant (although somewhat reduced) coordinate priming, but no attribute priming. SD patients showed no priming effect for any semantic relationship. All groups showed significant associative priming. The results indicate that SD patients do indeed have substantial degradation of semantic memory, while AD patients have a partially intact network, accounting for priming in superordinate and coordinate conditions. These findings suggest that AD patients' impairment on explicit semantic tasks is the product of deficient explicit retrieval in combination with a partially degraded semantic network.

A computational model of reading was developed based upon the notion that the structural relationship between orthography and phonology is of greater importance than the dimension of semantics for the reading aloud of single words. Degradation of this model successfully simulated the reading performance of two patients with atypical acquired dyslexia. The first patient CAV, studied and described in the literature by Warrington in 1981, presented with unusual concrete word dyslexia, i.e., he had a category-specific reading deficit for concrete words compared with abstract words. The second patient BG is a phonological dyslexic who, although displaying a strong concreteness effect (concrete words read better than abstract words), was able to read functors individually perfectly well, a pattern that is rarely if ever seen. The computational model was used to generate a set of words for which it was predicted that BG would show no concreteness effect. The results of BG's reading of these words were consistent with this prediction, thereby providing greater support for the validity of the model. It is concluded that a computational approach that attempts not only to reproduce the core symptoms of the major varieties of acquired dyslexia but also to simulate clinical data from specific patients has much to contribute to the understanding of cognitive deficits and to the design of effective rehabilitation strategies.

Patients with phonological alexia (difficulty reading pseudowords) frequently have concomitant difficulty reading functor words and verbs compared with concrete nouns. The current study compares two techniques for helping two patients with phonological alexia regain the ability to read functors and verbs. One technique follows the approach of reorganization of function, while the other relies on the stimulation approach. Study 1, employing a reorganization approach, resulted in both patients increasing their reading accuracy from approximately 10 to 90% or greater. Study 2, using a stimulation approach, resulted in significant improvement, however neither patient was able to achieve accuracy greater than 59%. Study 3 reverted back to the reorganization approach using the same words from Study 2. Both patients demonstrated significant success, achieving 90% or greater accuracy. Whereas the reorganization approach meets with far greater success than the stimulation approach, both approaches can be seen as instances of paired associate learning. An explanation of the advantage of the reorganization approach is developed which focuses on the nature of the pairings in the paired associate learning paradigm: it is proposed that pairings within the same level of representation are easier to learn than pairings that cut across levels of representation.

The hypothesis that ventral/anterior left inferior frontal gyrus (LIFG) subserves semantic processing and dorsal/posterior LIFG subserves phonological processing was tested by determining the pattern of functional connectivity of these regions with regions in left occipital and temporal cortex during the processing of words and word-like stimuli. In accordance with the hypothesis, we found strong functional connectivity between activity in ventral LIFG and activity in occipital and temporal cortex only for words, and strong functional connectivity between activity in dorsal LIFG and activity in occipital and temporal cortex for words, pseudowords, and letter strings, but not for false font strings. These results demonstrate a task-dependent functional fractionation of the LIFG in terms of its functional links with posterior brain areas.

Following the notion that patients with pure alexia have access to two distinct reading strategies-letter-by-letter reading and semantic reading-a training program was devised to facilitate reading via semantics in a patient with pure alexia. Training utilized brief stimulus presentations and required category judgments rather than explicit word identification. The training was successful for trained words, but generalized poorly to untrained words. Additional studies involving oral reading of nouns and of functors also resulted in improved reading of trained words. Pseudowords could not be trained to criterion. The results suggest that improved reading can be achieved in pure alexia by pairing rapidly presented words with feedback. Focusing on semantic processing is not essential to this process. It is proposed that the training strengthens connections between the output of visual processing and preexisting orthographic representations., (Copyright 2000 Academic Press.)

Brain activation studies of orthographic stimuli typically start with the premise that different types of orthographic strings (e.g., words, pseudowords) differ from each other in discrete ways, which should be reflected in separate and distinct areas of brain activation. The present study starts from a different premise: Words, pseudowords, letterstrings, and false fonts vary systematically across a continuous dimension of familiarity to English readers. Using a one-back matching task to force encoding of the stimuli, the four types of stimuli were visually presented to healthy adult subjects while fMRI activations were obtained. Data analysis focused on parametric comparisons of fMRI activation sites. We did not find any region that was exclusively activated for real words. Rather, differences among these string types were mainly expressed as graded changes in the balance of activations among the regions. Our results suggest that there is a widespread network of brain regions that form a common network for the processing of all orthographic string types.

Patients with probable Alzheimer's disease (AD) are reported to show mild, but reliable, difficulties reading aloud and spelling to dictation exception words, which have unusual or unpredictable correspondence between their spelling and pronunciation (e.g., touch). To understand the cognitive dysfunction responsible for these impairments, 21 patients and 27 age-and education-matched controls completed specially designed tests of single-word oral reading and spelling to dictation. AD patients performed slightly below controls on all tasks and showed mildly exaggerated regularity effects (i.e., the difference in response accuracy between words with regular spellings minus exception words) in reading and spelling. Qualitative analyses, however, did not demonstrate response patterns consistent with impairment in central lexical orthographic processing. The authors conclude that the mild alexia and agraphia in AD reflect semantic deficits and nonlinguistic impairments rather than a specific disturbance in lexical orthographic processing.

Different kinds of real words and pronounceable pseudowords (PWs) were presented for writing to dictation to patients with the diagnosis of probable Alzheimer's disease (AD) and to age- and education-matched healthy controls. Though spelling less accurately on all tasks, AD patients responded in a manner generally qualitatively similar to controls. Except for a slightly enhanced effect of spelling regularity in real word writing accuracy, AD patients showed the same sensitivity to various lexical, orthographic and phonological variables as controls. Both groups showed no difference in spelling accuracy for words and PWs with regular vs ambiguous spelling patterns, and groups also showed similar orthographic preferences when spelling PWs having several different acceptable pronunciations. Finally, AD patients and controls produced similar types of errors when spelling real words. Dementia severity was related to the overall accuracy, but not to the pattern, of spelling responses. It is suggested that the decline in response accuracy in cognitively demanding writing tasks in patients with more advanced dementia is most likely due to semantic impairment and impairments of nonlinguistic functions of attention, executive control and praxis, rather than to a disturbance within language specific processes.

An experimental treatment study designed to improve both the accuracy and the speed of reading was administered to a patient with pure alexia and impaired letter naming. The study focused on the use of letter-by-letter reading. A two-stage approach was employed. The first stage implemented a tactile-kinesthetic strategy to improve accuracy. The second stage concentrated on speed. At the end of the treatment, patient DL was reading both trained and untrained words more accurately and with considerably greater speed than prior to treatment. Accuracy and speed of reading at the sentence level improved as well., (Copyright 1999 Academic Press.)

Purpose: Chemotherapy and accelerated superfractionated radiotherapy were prospectively applied for inflammatory breast carcinoma with the intent of breast conservation. The efficacy, failure patterns, and patient tolerance utilizing this approach were analyzed., Methods and Materials: Between 1983 and 1996, 52 patients with inflammatory breast carcinoma presented to the Medical College of Virginia Hospitals of VCU and the New England Medical Center. Thirty-eight of these patients were jointly evaluated in multidisciplinary breast clinics and managed according to a defined prospectively applied treatment policy. Patients received induction chemotherapy, accelerated superfractionated radiotherapy, selected use of mastectomy, and concluded with additional chemotherapy. The majority were treated with 1.5 Gy twice daily to field arrangements covering the entire breast and regional lymphatics. An additional 18-21 Gy was then delivered to the breast and clinically involved nodal regions. Total dose to clinically involved areas was 63-66 Gy. Following chemoradiotherapy, patients were evaluated with physical examination, mammogram, and fine needle aspiration x 3. Mastectomy was reserved for those patients with evidence of persistent or progressive disease in the involved breast. All patients received additional chemotherapy., Results: Median age was 51 years. Median follow-up was 23.9 months (6-86) months. The breast preservation rate at the time of last follow-up was 74%. The treated breast or chest wall as the first site of failure occurred in only 13%, and the ultimate local control rate with the selected use of mastectomy was 74%. Ten patients underwent mastectomy, 2 of which had pathologically negative specimens despite a clinically palpable residual mass. Response to chemotherapy was predictive of treatment outcome. Of the 15 patients achieving a complete response, 87% remain locoregionally controlled without the use of mastectomy. Five-year overall survival for complete responders was 68%. This is in contrast to the 14% 5-year overall survival observed with incomplete responders. The 5-year actuarial disease-free survival and overall survival for the entire patient cohort was 11% and 33%, respectively. All patients tolerated irradiation with limited acute effects, of which all were managed conservatively., Conclusion: Our experience demonstrates that induction chemotherapy, accelerated superfractionated radiotherapy, and the selected use of mastectomy results in excellent locoregional control rates, is well tolerated, and optimizes breast preservation. Based on our present results, we recommend that a patient's response to induction chemotherapy guide the treatment approach used for locoregional disease, such that mastectomy be reserved for incomplete responders and avoided in those achieving a complete response.

Repetition and reading of various types of pronounceable nonwords (pseudowords) was examined in patients with probable Alzheimer's disease (AD) and healthy elderly controls. Overall accuracy of performance was lower in AD patients compared to controls, but the two groups showed qualitatively similar response patterns when reading different kinds of pseudowords aloud and when repeating pseudowords composed of familiar phonological forms, analogous to those in real English words. AD patients diverged in performance from controls, however, when repeating pseudowords composed of phonologically unusual forms. These results support two conclusions: (1) Aspects of phonological processing may become disrupted in AD patients in association with increasing dementia severity, while orthographic processing remains comparatively less impaired. (2) The results are consistent with the view that the processing of pseudowords is achieved through the same system as real words, and further show that the influence of prior language experience on the processing of novel linguistic forms occurs primarily at the level of phonological, rather than orthographic processing., (Copyright 1998 Academic Press.)

Semantic memory impairment was investigated in patients with probable Alzheimer's disease (AD) using a threshold oral word reading task to assess priming of different lexical relationships. Healthy elderly controls showed significant priming for associatively related nouns (tempest-teapot) and also for nouns semantically related either because both designate basic-level exemplars of a common superordinate category (cousin-nephew) or because the target names the superordinate category of the prime (daughter-relative). AD patients, in contrast, showed preserved priming of lexical associates but impaired priming of certain semantic relationships. They showed no priming between words designating coordinate exemplars within a category, despite preserved priming of the superordinate category label. Findings are consistent with the view that at least part of the semantic deficit in AD is due to disruption of semantic knowledge that affects relationships among basic-level concepts, more than the relationships between these concepts and their corresponding superordinate category of membership.

Repetition of single words and pronounceable nonwords (pseudowords) was assessed in Alzheimer's Disease (AD) patients to evaluate how lexical phonological processing might be accomplished when semantic and conceptual knowledge is impaired. AD patients performed significantly worse than healthy elderly controls on all repetition tasks. However, repetition abilities and dementia severity were not correlated, and AD patients produced the same distribution of error types as controls. Furthermore, despite their semantic problems, AD patients, like controls, showed a significant advantage for repeating real words compared to pseudowords, even when repeating low frequency phonologically complex words whose meaning is not likely to have been retained. The results support the postulated existence of a lexical phonological system that is used to repeat both known and novel words and that processes linguistic information independent of its meaning.

Recent evidence from patients with progressive language disorders and dementia has been used to suggest that phonological and orthographic processing depend on intact semantic memory. These claims challenge the traditional view that there are functionally separate modules in the language system. The effect of a severe, but nonprogressive, semantic impairment on phonological and orthographic processing was evaluated in LA, a mentally retarded child with hyperlexia. Knowledge of a word's meaning did not affect LA's word repetition, a measure of phonological processing, or his acquisition and retention of orthographic patterns for writing to dictation low-frequency words with exceptional spellings. These findings support the assertion that both orthographic and phonological whole-word representations can be acquired, stored, and retrieved in the absence of a functional link to semantic memory.

The Internet's World Wide Web (WWW) offers educators a unique opportunity to introduce computer-assisted instructional (CAI) programs into the medical school curriculum. With the WWW, CAI programs developed at one medical school could be successfully used at other institutions without concern about hardware or software compatibility; further, programs could be maintained and regularly updated at a single central location, could be distributed rapidly, would be technology-independent, and would be presented in the same format on all computers. However, while the WWW holds promise for CAI, the author discusses ten reasons that educators' efforts to fulfill the Web's promise may fail, including the following: CAI is generally not fully integrated into the medical school curriculum; students are not tested on material taught using CAI; and CAI programs tend to be poorly designed. The author argues that medical educators must overcome these obstacles if they are to make truly effective use of the WWW in the classroom.

Reports of five patients whose deep alexic reading all evolved into phonological alexia in a similar fashion point to the hypothesis that deep alexia and phonological alexia represent different points on the same continuum. This hypothesis is explored further through an examination of previously published case reports of eleven patients with phonological alexia. Data from these patients suggest that there is a predictable succession of symptoms which form a continuum of severity of phonological alexia, with deep alexia as its endpoint. An account of the recovery from deep to phonological alexia, based upon a lexical (no-rules) model of reading, is provided (Glosser & Friedman, 1990), and the implications for therapy are considered. The significance of the notion of a continuum of phonological/deep alexia is discussed.