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1.  Biomarkers in the primary progressive aphasias 
Aphasiology  2014;28(8-9):922-940.
Primary progressive aphasia (PPA) is a progressive disorder of language that is increasingly recognised as an important presentation of a specific spectrum of neurodegenerative conditions.
In an era of etiologically specific treatments for neurodegenerative conditions, it is crucial to establish the histopathologic basis for PPA. In this review, I discuss biomarkers for identifying the pathology underlying PPA.
Main Contribution
Clinical syndromes suggest a probabilistic association between a specific PPA variant and an underlying pathology, but there are also many exceptions. A considerable body of work with biomarkers is now emerging as an important addition to clinical diagnosis. I review genetic, neuroimaging and biofluid studies that can help determine the pathologic basis for PPA.
Together with careful clinical examination, there is great promise that supplemental biomarker assessments will lead to accurate diagnosis of the pathology associated with PPA during life and serve as the basis for clinical trials in this spectrum of disease.
PMCID: PMC4287262  PMID: 25580048
Frontotemporal degeneration; Primary progressive aphasia; Biomarker
2.  Use of the Progressive Aphasia Severity Scale (PASS) in monitoring speech and language status in PPA 
Aphasiology  2014;28(8-9):993-1003.
Primary progressive aphasia (PPA) is a devastating neurodegenerative syndrome involving the gradual development of aphasia, slowly impairing the patient’s ability to communicate. Pharmaceutical treatments do not currently exist and intervention often focuses on speech-language behavioral therapies, although further investigation is warranted to determine how best to harness functional benefits. Efforts to develop pharmaceutical and behavioral treatments have been hindered by a lack of standardized methods to monitor disease progression and treatment efficacy.
Here we describe our current approach to monitoring progression of PPA, including the development and applications of a novel clinical instrument for this purpose, the Progressive Aphasia Severity Scale (PASS). We also outline some of the issues related to initial evaluation and longitudinal monitoring of PPA.
Methods & Procedures
In our clinical and research practice we perform initial and follow-up assessments of PPA patients using a multi-faceted approach. In addition to standardized assessment measures, we use the PASS to rate presence and severity of symptoms across distinct domains of speech, language, and functional and pragmatic aspects of communication. Ratings are made using the clinician’s best judgment, integrating information from patient test performance in the office as well as a companion’s description of routine daily functioning.
Outcomes & Results
Monitoring symptom characteristics and severity with the PASS can assist in developing behavioral therapies, planning treatment goals, and counseling patients and families on clinical status and prognosis. The PASS also has potential to advance the implementation of PPA clinical trials.
PPA patients display heterogeneous language profiles that change over time given the progressive nature of the disease. The monitoring of symptom progression is therefore crucial to ensure that proposed treatments are appropriate at any given stage, including speech-language therapy and potentially pharmaceutical treatments once these become available. Because of the discrepancy that can exist between a patient’s daily functioning and standardized test performance, we believe a comprehensive assessment and monitoring battery must include performance-based instruments, interviews with the patient and partner, questionnaires about functioning in daily life, and measures of clinician judgment. We hope that our clinician judgment-based rating scale described here will be a valuable addition to the PPA assessment and monitoring battery.
PMCID: PMC4235969  PMID: 25419031
PPA; aphasia; monitoring
3.  Psycholinguistics of Aphasia Pharmacotherapy: Asking the Right Questions 
Aphasiology  2013;28(2):133-154.
Among the obstacles to demonstrating efficacy of pharmacological intervention for aphasia is quantifying patients’ responses to treatment in a statistically valid and reliable manner. In many of the review papers on this topic (e.g., Berthier et al., 2011; de Boissezon, Peran, de Boysson, & Démonet, 2007; Small & Llano, 2009), detailed discussions of various methodological problems are highlighted, with some suggestions on how these shortcomings should be addressed. Given this deep understanding of caveats associated with the experimental design of aphasia pharmacotherapy studies (e.g., Berthier et al., 2011), investigations continue to produce inconsistent results.
In this review paper we suggest that inclusion of theory-driven linguistic measures in aphasia pharmacotherapy studies would add an important step toward elucidating precise patterns of improvement in language performance resulting from pharmacotherapeutic intervention.
Main Contribution
We provide a brief review of the clinical approaches currently used in pharmacotherapy studies of aphasia, which often lack psycholinguistic grounding. We then present ways in which psycholinguistic models can complement this approach, offering a rationale for task selection, and as a result, lead to a better understanding of treatment effects. We then follow with an example of how such an integrative approach can be implemented in studies targeting stress reduction in people with aphasia, via beta-blocking agents, as a means to augment language performance, using the psycholinguistic framework of “linguistic anxiety” outlined in Cahana-Amitay et al, 2011 as our guideline.
We conclude that the incorporation of psycholinguistic models into aphasia pharmacotherapy studies can increase the resolution with which we can identify functional changes.
PMCID: PMC3904395  PMID: 24489425
4.  Treating apraxia of speech with an implicit protocol that activates speech motor areas via inner speech 
Aphasiology  2014;28(5):515-532.
Treatments of apraxia of speech (AOS) have traditionally relied on overt practice. One alternative to this method is implicit phoneme manipulation which was derived from early models on inner speech. Implicit phoneme manipulation requires the participant to covertly move and combine phonemes to form a new word. This process engages a system of self-monitoring which is referred to as fully conscious inner speech.
The present study aims to advance the understanding and validity of a new treatment for AOS, implicit phoneme manipulation. Tasks were designed to answer the following questions. 1. Would the practice of implicit phoneme manipulation improve the overt production of complex consonant blends in words? 2. Would this improvement generalize to untrained complex and simpler consonant blends in words? 3. Would these treatment tasks activate regions known to support motor planning and programming as verified by fMRI?
Method & Procedures
The participant was asked to covertly manipulate phonemes to create a new word and to associate this newly formed word to a target picture among 4 phonologically-related choices. To avoid overt practice, probes were collected only after each block of training was completed. Probe sessions assessed the effects of implicit practice on the overt production of simple and complex consonant blends in words. An imaging protocol compared semantic baseline tasks to treatment tasks to verify that implicit phoneme manipulation activated brain regions of interest.
Outcomes & Results
Behavioral: Response to implicit training of complex consonant blends resulted in improvements which were maintained 6 weeks after treatment. Further, this treatment generalized to simpler consonant blends in words. Imaging: Functional imaging during implicit phoneme manipulation showed significant activation in brain regions responsible for phonological processing when compared to the baseline semantic task.
Implicit phoneme manipulation offers an alternative to traditional methods that require overt production for treatment of AOS. Additionally, this implicit treatment method was shown to activate neural areas known to be involved in phonological processing, motor planning and programming.
PMCID: PMC4136530  PMID: 25147422
5.  Effects of Verb Bias and Syntactic Ambiguity on Reading in People with Aphasia 
Aphasiology  2013;27(10-12):1408-1425.
The Lexical Bias Hypothesis (Gahl, 2002) claims that people with aphasia have difficulty understanding sentences when the verb’s argument structure bias conflicts with the sentence structure. This hypothesis can account for comprehension deficits that affect simple sentences, but the role of verb bias has not been clearly demonstrated in temporarily ambiguous sentences.
This study examined how verb bias affects comprehension of temporarily ambiguous and unambiguous sentences using self-paced reading.
Methods & Procedures:
People with aphasia and controls read sentences that contained sentential complements (e.g., The talented photographer accepted (that) the fire could not have been prevented.). The main verb was biased to take a direct object (e.g., accepted) or a sentential complement (e.g., admitted). In addition, the sentential complement was either introduced by the complementizer that (i.e., unambiguous) or unmarked (i.e., ambiguous).
The people with aphasia’s reading times were affected more by verb bias than by the presence of the complementizer, whereas the control group’s reading times were more affected by the presence or absence of the complementizer.
The results were generally consistent with the Lexical Bias Hypothesis, and showed that a mismatch between verb bias and sentence structure affected processing of unambiguous and temporarily ambiguous sentences in people with aphasia.
PMCID: PMC3966628  PMID: 24683286
Reading comprehension; temporary syntactic ambiguity; aphasia; Lexical Bias Hypothesis
6.  Automated analysis of the Cinderella story 
Aphasiology  2010;24(6-8):856-868.
AphasiaBank is a collaborative project whose goal is to develop an archival database of the discourse of individuals with aphasia. Along with databases on first language acquisition, classroom discourse, second language acquisition, and other topics, it forms a component of the general TalkBank database. It uses tools from the wider system that are further adapted to the particular goal of studying language use in aphasia.
The goal of this paper is to illustrate how TalkBank analytic tools can be applied to AphasiaBank data.
Methods & Procedures
Both aphasic (n = 24) and non-aphasic (n = 25) participants completed a 1-hour standardised videotaped data elicitation protocol. These sessions were transcribed and tagged automatically for part of speech. One component of the larger protocol was the telling of the Cinderella story. For these narratives we compared lexical diversity across the groups and computed the top 10 nouns and verbs across both groups. We then examined the profiles for two participants in greater detail.
Using these tools we showed that, in a story-retelling task, aphasic speakers had a marked reduction in lexical diversity and a greater use of light verbs. For example, aphasic speakers often substituted “girl” for “stepsister” and “go” for “disappear”. These findings illustrate how it is possible to use TalkBank tools to analyse AphasiaBank data.
PMCID: PMC4110243  PMID: 25067870
Lexicon; Narrative; Computer analysis
7.  Neural Basis of Action Understanding: Evidence from Sign Language Aphasia 
Aphasiology  2013;27(9):1147-1158.
The neural basis of action understanding is a hotly debated issue. The mirror neuron account holds that motor simulation in fronto-parietal circuits is critical to action understanding including speech comprehension, while others emphasize the ventral stream in the temporal lobe. Evidence from speech strongly supports the ventral stream account, but on the other hand, evidence from manual gesture comprehension (e.g., in limb apraxia) has led to contradictory findings.
Here we present a lesion analysis of sign language comprehension. Sign language is an excellent model for studying mirror system function in that it bridges the gap between the visual-manual system in which mirror neurons are best characterized and language systems which have represented a theoretical target of mirror neuron research.
Methods & Procedures
Twenty-one life long deaf signers with focal cortical lesions performed two tasks: one involving the comprehension of individual signs and the other involving comprehension of signed sentences (commands). Participants' lesions, as indicated on MRI or CT scans, were mapped onto a template brain to explore the relationship between lesion location and sign comprehension measures.
Outcomes & Results
Single sign comprehension was not significantly affected by left hemisphere damage. Sentence sign comprehension impairments were associated with left temporal-parietal damage. We found that damage to mirror system related regions in the left frontal lobe were not associated with deficits on either of these comprehension tasks.
We conclude that the mirror system is not critically involved in action understanding.
PMCID: PMC3767459  PMID: 24031116
8.  Effects of Noun-Verb Conceptual/ Phonological Relatedness on Verb Production Changes in Broca’s Aphasia 
Aphasiology  2013;27(7):811-827.
Individuals with Broca’s aphasia show better performance on nouns than on verbs, but distinction between nouns and verbs is not always clear; some verbs are conceptually and/ or phonologically related to nouns, while others are not. Inconsistent results on effects of noun-verb relatedness on verb production have been reported in the literature.
We investigated (1) whether verb instrumentality (a conceptual relationship to nouns) or homonymy (a phonological relationship to nouns) would affect verb production in individuals with Broca’s aphasia and (2) whether conceptual/ phonological noun-verb relationship would affect responsiveness to aphasia therapy that focused on verb production.
Methods & Procedures
Three English speaking individuals with Broca’s aphasia produced 96 verbs in sentences in response to picture stimuli. The target verbs included those that use an instrument and those that do not (e.g., to hammer vs. to yawn) and verbs that are phonologically identical to a related noun (e.g., to comb – a comb), morpho-phonologically-related to a noun (e.g., to grind – a grinder), and verbs for which there is no phonologically similar noun (e.g., to lean). The participants’ verb retrieval ability was assessed before and after a 4-week period of aphasia therapy.
Outcomes & Results
The participants produced more accurate instrumental than non-instrumental verbs both pre- and post-treatment. They also produced more verbs correctly that are homonyms of nouns than verbs that are phonologically related or unrelated to nouns before treatment. However, the effect of homonymy was not observed following treatment.
Individuals with Broca’s aphasia were more accurate in their production of verbs that were conceptually and phonologically related to nouns than on verb that were not. The performance on verb production improved significantly after therapy. We interpret the results to indicate that whereas prior to treatment the participants relied on phonologically related nouns to retrieve the target verbs, this reliance on knowledge of nouns decreased following therapy that was designed to improve verb production.
PMCID: PMC3727282  PMID: 23914001
Broca's aphasia; Verbs; Instrumentality; Homonymy; Therapy; Efficacy
9.  Formulaic Language in Alzheimer’s Disease 
Aphasiology  2013;27(7):10.1080/02687038.2012.757760.
Studies of productive language in Alzheimer’s disease (AD) have focused on formal testing of syntax and semantics but have directed less attention to naturalistic discourse and formulaic language. Clinical observations suggest that individuals with AD retain the ability to produce formulaic language long after other cognitive abilities have deteriorated.
This study quantifies production of formulaic expressions in the spontaneous speech of individuals with AD. Persons with early- and late-onset forms of the disease were compared.
Methods & Procedures
Conversational language samples of individuals with early- (n = 5) and late-onset (n = 6) AD and healthy controls (n = 5) were analyzed to determine whether formulaic language, as measured by the number of words in formulaic expressions, differs between groups.
Outcomes & Results
Results indicate that individuals with AD, regardless of age of onset, used significantly more formulaic expressions than healthy controls. The early- and late-onset AD groups did not differ on formulaic language measures.
These findings contribute to a dual process model of cerebral function, which proposes differing processing principles for formulaic and novel expressions. In this model, subcortical areas, which remain intact into late in the progression of Alzheimer’s disease, play an important role in the production of formulaic language. Applications to clinical practice include identifying preserved formulaic language and providing informed counseling to patient and family.
PMCID: PMC3811161  PMID: 24187417
Formulaic language; Alzheimer’s disease; Dual-process model
10.  Brain Regions Underlying Repetition and Auditory-Verbal Short-term Memory Deficits in Aphasia: Evidence from Voxel-based Lesion Symptom Mapping 
Aphasiology  2011;26(3-4):338-354.
A deficit in the ability to repeat auditory-verbal information is common among individuals with aphasia. The neural basis of this deficit has traditionally been attributed to the disconnection of left posterior and anterior language regions via damage to a white matter pathway, the arcuate fasciculus. However, a number of lesion and imaging studies have called this notion into question.
The goal of this study was to identify the neural correlates of repetition and a related process, auditory-verbal short-term memory (AVSTM). Both repetition and AVSTM involve common elements such as auditory and phonological analysis and translation to speech output processes. Based on previous studies, we predicted that both repetition and AVSTM would be most dependent on posterior language regions in left temporo-parietal cortex.
Methods & Procedures
We tested 84 individuals with left hemisphere lesions due to stroke on an experimental battery of repetition and AVSTM tasks. Participants were tested on word, pseudoword, and number-word repetition, as well as digit and word span tasks. Brain correlates of these processes were identified using a statistical, lesion analysis approach known as voxel-based lesion symptom mapping (VLSM). VLSM allows for a voxel-by-voxel analysis of brain areas most critical to performance on a given task, including both grey and white matter regions.
Outcomes & Results
The VLSM analyses showed that left posterior temporo-parietal cortex, not the arcuate fasciculus, was most critical for repetition as well as for AVSTM. The location of maximal foci, defined as the voxels with the highest t values, varied somewhat among measures: Word and pseudoword repetition had maximal foci in the left posterior superior temporal gyrus, on the border with inferior parietal cortex, while word and digit span, as well as number-word repetition, were centered on the border between the middle temporal and superior temporal gyri and the underlying white matter.
Findings from the current study show that 1) repetition is most critically mediated by cortical regions in left posterior temporo-parietal cortex; 2) repetition and AVSTM are mediated by partially overlapping networks; and 3) repetition and AVSTM deficits can be observed in different types of aphasia, depending on the site and extent of the brain injury. These data have implications for the prognosis of chronic repetition and AVSTM deficits in individuals with aphasia when lesions involve critical regions in left temporo-parietal cortex.
PMCID: PMC4070523  PMID: 24976669
repetition; short-term memory; aphasia; conduction aphasia; temporal cortex; parietal cortex
11.  Verb Transitivity Bias Affects On-line Sentence Reading in People with Aphasia 
Aphasiology  2012;27(3):326-343.
Studies of sentence comprehension in non-disordered populations have convincingly demonstrated that probabilistic cues influence on-line syntactic processing. One well-studied cue is verb argument structure bias, which refers to the probability that a verb will occur in a particular syntactic frame. According to the Lexical Bias Hypothesis, people with aphasia have difficulty understanding sentences in which the verb’s argument structure bias conflicts with the sentence structure (e.g., a transitively biased verb in an intransitive sentence). This hypothesis may provide an account of why people with aphasia have difficulty understanding both simple and complex sentences.
The purpose of this study was to test the Lexical Bias Hypothesis using an on-line measure of written sentence comprehension, self-paced reading.
Methods & Procedures
The participants were ten people with aphasia and ten non-brain-damaged controls. The stimuli were syntactically simple transitive and intransitive sentences that contained transitively- or intransitively-biased verbs. For example, the transitively-biased verb “called” appeared in sentences such as “The agent called (the writer) from overseas to make an offer.” The intransitively-biased verb “danced” appeared in sentences such as “The couple danced (the tango) every Friday night last summer.”
Outcomes & Results
Both groups’ reading times for critical segments were longer when the verb’s transitivity bias did not match the sentence structure, particularly in intransitive sentences.
The results were generally consistent with the Lexical Bias Hypothesis, and demonstrated that lexical biases affect on-line processing of syntactically simple sentences in people with aphasia and controls.
PMCID: PMC3611885  PMID: 23554543
Self-paced reading; sentence comprehension impairments; aphasia; Lexical Bias Hypothesis
12.  A tutorial on aphasia test development in any language: Key substantive and psychometric considerations 
Aphasiology  2013;27(8):891-920.
There are a limited number of aphasia language tests in the majority of the world's commonly spoken languages. Furthermore, few aphasia tests in languages other than English have been standardized and normed, and few have supportive psychometric data pertaining to reliability and validity. The lack of standardized assessment tools across many of the world's languages poses serious challenges to clinical practice and research in aphasia.
The current review addresses this lack of assessment tools by providing conceptual and statistical guidance for the development of aphasia assessment tools and establishment of their psychometric properties.
Main Contribution
A list of aphasia tests in the 20 most widely spoken languages is included. The pitfalls of translating an existing test into a new language versus creating a new test are outlined. Factors to consider in determining test content are discussed. Further, a description of test items corresponding to different language functions is provided, with special emphasis on implementing important controls in test design. Next, a broad review of principal psychometric properties relevant to aphasia tests is presented, with specific statistical guidance for establishing psychometric properties of standardized assessment tools.
This article may be used to help guide future work on developing, standardizing and validating aphasia language tests. The considerations discussed are also applicable to the development of standardized tests of other cognitive functions.
PMCID: PMC3747007  PMID: 23976813
psychometrics; test development; standardized testing; aphasia; language assessment; validity; reliability
13.  Slave systems in verbal short-term memory 
Aphasiology  2012;26(3-4):10.1080/02687038.2011.642795.
The model of performance in short-term memory (STM) tasks that has been most influential in cognitive neuropsychological work on deficits of STM is the “working memory” model mainly associated with the work of Alan Baddeley and his colleagues.
This paper reviews the model. We examine the development of this theory in studies that account for STM performances in normal (non-brain-damaged) individuals, and then review the application of this theory to neuropsychological cases and specifications, modifications, and extensions of the theory that have been suggested on the basis of these cases. Our approach is to identify the major phenomena that have been discussed and to examine selected papers dealing with those phenomena in some detail.
Main Contribution
The main contribution is a review of the WM model that includes both normative and neuropsychological data.
We conclude that the WM model has many inconsistencies and empirical inadequacies, and that cognitive neuropsychologists might benefit from considering other models when they attempt to describe and explain patients’ performances on STM tasks.
PMCID: PMC3859463  PMID: 24347786
Aphasia; Aphasiology; Neuropsychology; Psychosocial; Language; Brain
14.  Cognitive Neuropsychology Has Been, Is, And Will Be Significant To Aphasiology 
Aphasiology  2012;26(11):1362-1376.
In recent years, some critical voices have been raised in regard to the significance of cognitive neuropsychology (CNP) to the study of brain and mind. Given the central role of language disorders in CNP research, it is time to consider the relevance of this research approach in aphasiology.
We analyze the main points of criticism raised against the CNP research approach, evaluate the significance of this approach to the study of acquired language disorders, and make some suggestions concerning further development of the field.
Main Contribution
The main points of criticism against CNP (reliance on single-case studies; single-minded hunt for dissociations; emptiness of theorizing) have been important long-term concerns but do not take into account the fact that during its history of circa four decades, the CNP approach has diversified. There are thus CNP studies that rely on case series analyses, focus on error analyses rather than mere dissociations, or employ computational modeling rather than the “boxes-and-arrows” models of the mental architecture. The CNP approach to cognition and its disorders is thus applicable to different research questions and theoretical stances, providing experimental rigor to single-case patient studies. With regard to clinical applications in aphasia diagnostics and treatment, the CNP approach provides a richer view on the strengths and weaknesses of a patient’s cognitive-linguistic abilities.
We believe that CNP case studies continue to be an important source of information for generating hypotheses and providing converging evidence for research on the mind and on the brain. There is however a need for further research development especially in computational modeling of language processes, their impairments, and recovery. This research is expected to provide further benefit to clinical diagnostics and treatment of aphasia.
PMCID: PMC3532518  PMID: 23280004
cognitive neuropsychology; single-case study; aphasiology
15.  Finding the Right Words: Transcranial Magnetic Stimulation Improves Discourse Productivity in Non-fluent Aphasia After Stroke 
Aphasiology  2012;26(9):1153-1168.
Loss of fluency is a significant source of functional impairment in many individuals with aphasia. Repetitive transcranial magnetic stimulation (rTMS) administered to the right inferior frontal gyrus (IFG) has been shown to facilitate naming in persons with chronic left hemisphere stroke and non-fluent aphasia. However, changes in fluency in aphasic subjects receiving rTMS have not been adequately explored.
To determine whether rTMS improves fluency in individuals with chronic nonfluent aphasia, and to identify aspects of fluency that are modulated in persons who respond to rTMS.
Methods & Procedures
Ten individuals with left hemisphere MCA strokes and mild to moderate non-fluent aphasia participated in the study. Before treatment, subjects were asked to describe the Cookie Theft picture in three separate sessions. During treatment, all subjects received 1200 pulses of 1 Hz rTMS daily in 10 sessions over two weeks at a site that had previously been shown to improve naming. Subjects repeated the Cookie Theft description two months after treatment. Five subjects initially received sham stimulation instead of real TMS. Two months after sham treatment, these individuals received real rTMS. Performance both at baseline and after stimulation was coded using Quantitative Production Analysis (Saffran, Berndt & Schwartz, 1989) and Correct Information Unit (Nicholas & Brookshire, 1993) analysis.
Outcomes & Results
Across all subjects (n=10), real rTMS treatment resulted in a significant increase in multiple measures of discourse productivity compared to baseline performance. There was no significant increase in measures of sentence productivity or grammatical accuracy. There was no significant increase from baseline in the sham condition (n=5) on any study measures.
Stimulation of the right IFG in patients with chronic non-fluent aphasia facilitates discourse production. We posit that this effect may be attributable to improved lexical-semantic access.
PMCID: PMC3532848  PMID: 23280015
Language; aphasia; TMS; pars triangularis; fluency; neurorehabilitation
16.  Epidural cortical stimulation and aphasia therapy 
Aphasiology  2011;26(9):1192-1217.
There are several methods of delivering cortical brain stimulation to modulate cortical excitability and interest in their application as an adjuvant strategy in aphasia rehabilitation after stroke is growing. Epidural cortical stimulation, although more invasive than other methods, permits high frequency stimulation of high spatial specificity to targeted neuronal populations.
First, we review evidence supporting the use of epidural cortical stimulation for upper limb recovery after focal cortical injury in both animal models and human stroke survivors. These data provide the empirical and theoretical platform underlying the use of epidural cortical stimulation in aphasia. Second, we summarize evidence for the application of epidural cortical stimulation in aphasia. We describe the procedures and primary outcomes of a safety and feasibility study (Cherney, Erickson & Small, 2010), and provide previously unpublished data regarding secondary behavioral outcomes from that study.
Main Contribution
In a controlled study comparing epidural cortical stimulation plus language treatment (CS/LT) to language treatment alone (LT), eight stroke survivors with nonfluent aphasia received intensive language therapy for 6 weeks. Four of these participants also underwent surgical implantation of an epidural stimulation device which was activated only during therapy sessions. Behavioral data were collected before treatment, immediately after treatment, and at 6 and 12 weeks following the end of treatment. The effect size for the primary outcome measure, the Western Aphasia Battery Aphasia Quotient, was benchmarked as moderate from baseline to immediately post-treatment, and large from baseline to the 12-week follow-up. Similarly, effect sizes obtained at the 12-week follow-up for the Boston Naming Test, the Communicative Effectiveness Index, and for correct information units on a picture description task were greater than those obtained immediately post treatment. When effect sizes were compared for individual subject pairs on discourse measures of content and rate, effects were typically larger for the investigational subjects receiving CS/LT than for the control subjects receiving LT alone. These analyses support previous findings regarding therapeutic efficacy of CS/LT compared to LT i.e. epidural stimulation of ipsilesional premotor cortex may augment behavioral speech-language therapy, with the largest effects after completion of therapy.
Continued investigation of epidural cortical stimulation in combination with language training in post-stroke aphasia should proceed cautiously. Carefully planned studies that customize procedures to individual profiles are warranted. Information from research on non-invasive methods of CS/LT may also inform future studies of epidural cortical stimulation.
PMCID: PMC3647471  PMID: 23667287
17.  Generalization of a Novel, Implicit Treatment for Coarse Coding Deficit in Right Hemisphere Brain Damage: A Single Subject Experiment 
Aphasiology  2012;26(5):689-708.
This manuscript reports generalization effects of Contextual Constraint Treatment for an adult with right hemisphere brain damage (RHD). Contextual Constraint Treatment is designed to stimulate inefficient language comprehension processes implicitly, by providing linguistic context to prime, or constrain, the intended interpretations of treatment stimuli. The study participant had a coarse coding deficit, defined as delayed mental activation of particularly distant semantic features of words (e.g., rotten as a feature of “apple”). Treatment effects were expected to generalize to auditory comprehension of narrative discourse, and perhaps to figurative language interpretation, because coarse coding has been hypothesized and/or demonstrated to support these abilities.
This treatment study aimed to induce generalization of Contextual Constraint Treatment in an adult with RHD with inefficient coarse coding.
Methods & Procedures
The participant in this study was a 75 year old man with RHD and a coarse coding deficit. A single subject experimental design across behaviors (stimulus lists) was used to document performance in baseline, treatment, and follow-up phases. Treatment consisted of providing brief, spoken context sentences to prestimulate, or constrain, intended interpretations of stimulus items. The participant made no explicit associations or metalinguistic judgments about the constraint sentences or stimulus words; rather, these contexts served only as implicit primes. Probe tasks were adapted from prior work on coarse coding in RHD. The dependent measure was the percentage of responses that met predetermined response time criteria. There were two levels of contextual constraint, Strong and Moderate. Treatment for each item began with the provision of the Strong constraint context, to minimize the production or reinforcement of erroneous or exceedingly slow responses. Generalization was assessed to a well-standardized measure of narrative discourse comprehension and to several metalinguistic tasks of figurative language interpretation.
Outcomes & Results
Treatment-contingent gains, associated with respectable effect sizes, were evident after a brief period of treatment on one stimulus list. Generalization occurred to untrained items, suggesting that the treatment was facilitating the underlying coarse coding process. Most importantly, generalization was evident to narrative comprehension performance, for both overall accuracy and accuracy answering questions about implied information, and all of these gains maintained through three follow-up sessions.
Though the results are still preliminary, this single-subject experimental design documents the potential for meaningful gains from a novel treatment that implicitly targets an underlying language comprehension process in an adult with RHD.
PMCID: PMC3402378  PMID: 22837589
language comprehension; language comprehension treatment; language therapy; right hemisphere; brain damage; coarse coding
18.  Verb and noun deficits in stroke-induced and primary progressive aphasia: The Northwestern Naming Battery1 
Aphasiology  2012;26(5):632-655.
Word class naming deficits are commonly seen in aphasia resulting from stroke (StrAph) and primary progressive aphasia (PPA), with differential production of nouns (objects) and verbs (actions) found based on StrAph type or PPA variant for some individuals. Studies to date, however, have not compared word class naming (or comprehension) ability in the two aphasic disorders. In addition, there are no available measures for testing word class deficits, which control for important psycholinguistic variables across language domains. This study examined noun and verb production and comprehension in individuals with StrAph and PPA using a new test, the Northwestern Naming Battery (NNB; Thompson & Weintraub, experimental version), developed explicitly for this purpose. In addition, we tested verb type effects, based on verb argument structure characteristics, which also is addressed by the NNB.
Fifty-two participants with StrAph (33 agrammatic, Broca’s (StrAg); 19 anomic (StrAn)) and 28 PPA (10 agrammatic (PPA-G); 14 logopenic (PPA-L); 4 semantic (PPA-S)) were included in the study. Nouns and verbs were tested in the Confrontation Naming and Auditory Comprehension subtests of the NNB, with scores used to compute noun to verb ratios as well as performance by verb type. Performance patterns within and across StrAph and PPA groups were then examined. The external validity of the NNB also was tested by comparing (a) NNB Noun Naming scores to the Boston Naming Test (BNT; Kaplan, Goodglass, & Weintraub, 1983) and Western Aphasia Battery (WAB-R, Kertesz, 2007) Noun Naming subtest scores, (b) NNB Verb Naming scores to the Boston Diagnostic Aphasia Examination (BDAE; Goodglass, Kaplan & Barresi, 2001) Action Naming score (for StrAph participants only), and (c) NNB Comprehension subtest scores to WAB-R Auditory Comprehension subtest scores.
Outcomes and Results
Both agrammatic (StrAg and PPA-G) groups showed significantly greater difficulty producing verbs compared to nouns, but no comprehension impairment for either word class. Whereas, three of the four PPA-S participants showed poorer noun compared to verb production, as well as comprehension. However, neither the StrAn or PPA-L participants showed significant differences between the two word classes in production or comprehension. In addition, similar to the agrammatic participants, the StrAn participants showed a significant transitivity effect, producing intransitive (one-argument) verbs with greater accuracy than transitive (two- and three-argument) verbs. However, no transitivity effects were found for the PPA-L or PPA-S participants. There were significant correlations between NNB scores and all external validation measures.
These data indicate that the NNB is sensitive to word class deficits in stroke and neurodegenerative aphasia. This is important both clinically for treatment planning and theoretically to inform both psycholinguistic and neural models of language processing.
PMCID: PMC3505449  PMID: 23188949
primary progressive aphasia (PPA); word class deficits; naming deficit patterns; verb argument structure production
19.  Lexicality Effects in Word and Nonword Recall of Semantic Dementia and Progressive Nonfluent Aphasia 
Aphasiology  2011;26(3-4):404-427.
Verbal working memory is an essential component of many language functions, including sentence comprehension and word learning. As such, working memory has emerged as a domain of intense research interest both in aphasiology and in the broader field of cognitive neuroscience. The integrity of verbal working memory encoding relies on a fluid interaction between semantic and phonological processes. That is, we encode verbal detail using many cues related to both the sound and meaning of words. Lesion models can provide an effective means of parsing the contributions of phonological or semantic impairment to recall performance.
Methods and Procedures
We employed the lesion model approach here by contrasting the nature of lexicality errors incurred during recall of word and nonword sequences by 3individuals with progressive nonfluent aphasia (a phonological dominant impairment) compared to that of 2 individuals with semantic dementia (a semantic dominant impairment). We focused on psycholinguistic attributes of correctly recalled stimuli relative to those that elicited a lexicality error (i.e., nonword → word OR word → nonword).
Outcomes and results
Patients with semantic dementia showed greater sensitivity to phonological attributes (e.g., phoneme length, wordlikeness) of the target items relative to semantic attributes (e.g., familiarity). Patients with PNFA showed the opposite pattern, marked by sensitivity to word frequency, age of acquisition, familiarity, and imageability.
We interpret these results in favor of a processing strategy such that in the context of a focal phonological impairment patients revert to an over-reliance on preserved semantic processing abilities. In contrast, a focal semantic impairment forces both reliance upon and hypersensitivity to phonological attributes of target words. We relate this interpretation to previous hypotheses about the nature of verbal short-term memory in progressive aphasia.
PMCID: PMC3593303  PMID: 23486736
Working Memory; Recall; Semantic Dementia; Aphasia; Progressive Nonfluent Aphasia
20.  Effects of working memory load on processing of sounds and meanings of words in aphasia 
Aphasiology  2012;26(3-4):462-493.
Language performance in aphasia can vary depending on several variables such as stimulus characteristics and task demands. This study focuses on the degree of verbal working memory (WM) load inherent in the language task and how this variable affects language performance by individuals with aphasia.
The first aim was to identify the effects of increased verbal WM load on the performance of judgments of semantic similarity (synonymy) and phonological similarity (rhyming). The second aim was to determine if any of the following abilities could modulate the verbal WM load effect: semantic or phonological access, semantic or phonological short-term memory (STM) and any of the following executive processing abilities: inhibition, verbal WM updating, and set shifting.
Method and Procedures
Thirty-one individuals with aphasia and 11 controls participated in this study. They were administered a synonymy judgment task and a rhyming judgment task under high and low verbal WM load conditions that were compared to each other. In a second set of analyses, multiple regression was used to identify which factors (as noted above) modulated the verbal WM load effect.
Outcome and Results
For participants with aphasia, increased verbal WM load significantly reduced accuracy of performance on synonymy and rhyming judgments. Better performance in the low verbal WM load conditions was evident even after correcting for chance. The synonymy task included concrete and abstract word triplets. When these were examined separately, the verbal WM load effect was significant for the abstract words, but not the concrete words. The same pattern was observed in the performance of the control participants. Additionally, the second set of analyses revealed that semantic STM and one executive function, inhibition ability, emerged as the strongest predictors of the verbal WM load effect in these judgment tasks for individuals with aphasia.
The results of this study have important implications for diagnosis and treatment of aphasia. As the roles of verbal STM capacity, executive functions and verbal WM load in language processing are better understood, measurements of these variables can be incorporated into our diagnostic protocols. Moreover, if cognitive abilities such as STM and executive functions support language processing and their impairment adversely affects language function, treating them directly in the context of language tasks should translate into improved language function.
PMCID: PMC3335394  PMID: 22544993
21.  Relations between Short-term Memory Deficits, Semantic Processing, and Executive Function 
Aphasiology  2012;26(3-4):428-461.
Previous research has suggested separable short-term memory (STM) buffers for the maintenance of phonological and lexical-semantic information, as some patients with aphasia show better ability to retain semantic than phonological information and others show the reverse. Recently, researchers have proposed that deficits to the maintenance of semantic information in STM are related to executive control abilities.
The present study investigated the relationship of executive function abilities with semantic and phonological short-term memory (STM) and semantic processing in such patients, as some previous research has suggested that semantic STM deficits and semantic processing abilities are critically related to specific or general executive function deficits.
Method and Procedures
20 patients with aphasia and STM deficits were tested on measures of short-term retention, semantic processing, and both complex and simple executive function tasks.
Outcome and Results
In correlational analyses, we found no relation between semantic STM and performance on simple or complex executive function tasks. In contrast, phonological STM was related to executive function performance in tasks that had a verbal component, suggesting that performance in some executive function tasks depends on maintaining or rehearsing phonological codes. Although semantic STM was not related to executive function ability, performance on semantic processing tasks was related to executive function, perhaps due to similar executive task requirements in both semantic processing and executive function tasks.
Implications for treatment and interpretations of executive deficits are discussed.
PMCID: PMC3377482  PMID: 22736889
22.  Conceptualizing and Measuring Working Memory and its Relationship to Aphasia 
Aphasiology  2012;26(3-4):258-278.
General agreement exists in the literature that individuals with aphasia can exhibit a working memory deficit that contributes to their language processing impairments. Though conceptualized within different working memory frameworks, researchers have suggested that individuals with aphasia have limited working memory capacity, impaired attention-control processes as well as impaired inhibitory mechanisms. However, across studies investigating working memory ability in individuals with aphasia, different measures have been used to quantify their working memory ability and identify the relationship between working memory and language performance.
The primary objectives of this article are to (1) review current working memory theoretical frameworks, (2) review tasks used to measure working memory, and (3) discuss findings from studies that have investigated working memory as they relate to language processing in aphasia.
Main Contribution
Though findings have been consistent across studies investigating working memory ability in individuals with aphasia, discussion of how working memory is conceptualized and defined is often missing, as is discussion of results within a theoretical framework. This is critical, as working memory is conceptualized differently across the different theoretical frameworks. They differ in explaining what limits capacity and the source of individual differences as well as how information is encoded, maintained, and retrieved. When test methods are considered within a theoretical framework, specific hypotheses can be tested and stronger conclusions that are less susceptible to different interpretations can be made.
Working memory ability has been investigated in numerous studies with individuals with aphasia. To better understand the underlying cognitive constructs that contribute to the language deficits exhibited by individuals with aphasia, future investigations should operationally define the cognitive constructs of interest and discuss findings within theoretical frameworks.
PMCID: PMC3358773  PMID: 22639480
23.  Testing the limits of language production in long-term survivors of major stroke: A psycholinguistic and anatomic study 
Aphasiology  2010;24(11):1455-1485.
There is still a dearth of information about grammatical aspects of language production in aphasia.
Making novel use of methods of elicited production aimed at testing the limits of competence, we studied three cases of chronic aphasia, stemming from major stroke. We asked: (1) Whether the elicited production method reveals sparing of language abilities not readily evidenced in spontaneous utterances or on conventional aphasia tests. (2) Which language production abilities survive damage to both Broca’s region and Wernicke’s region?
Materials & Procedures
Targeted words, morphological and syntactic structures were elicited by sentence completion with supporting linguistic and visual context. Targets were never modelled during the procedure. For verbs, visual and auditory contexts emphasise completed actions, targeting past tense forms. Lesion description was based on structural MRI scans.
Outcomes & Results
The three participants showed partially spared ability to produce nouns, adjectives, and verb stems in context. The elicitation method proved more productive in some cases than picture prompts or sentence prompts. Past tense inflections were usually omitted. Hence stems and inflections were dissociable. Two participants showed partial success with the passive, and no participant produced a full relative clause, including the relative pronoun, but two produced reduced forms of subject relatives. Partial sparing of production capability in these cases points to the likely importance of portions of the left hemisphere remote from Broca and Wernicke regions.
This application of elicited production methodology demonstrates possibilities of lexical, morphological, and syntactic production not evident in spontaneous utterances or by conventional aphasia tests. Some lexical and grammatical capabilities survived massive damage to both anterior and posterior portions of the left hemisphere.
PMCID: PMC3538820  PMID: 23318252
Aphasia; Grammatical production; Recovery of production
24.  Dissociations Between Fluency And Agrammatism In Primary Progressive Aphasia 
Aphasiology  2012;26(1):20-43.
Classical aphasiology, based on the study of stroke sequelae, fuses speech fluency and grammatical ability. Nonfluent (Broca's) aphasia often is accompanied by agrammatism; whereas in the fluent aphasias grammatical deficits are not typical. The assumption that a similar relationship exists in primary progressive aphasia (PPA) has led to the dichotomization of this syndrome into fluent and nonfluent subtypes.
This study compared elements of fluency and grammatical production in the narrative speech of individuals with PPA to determine if they can be dissociated from one another.
Speech samples from 37 individuals with PPA, clinically assigned to agrammatic (N=11), logopenic (N=20) and semantic (N=6) subtypes, and 13 cognitively healthy control participants telling the “Cinderella Story” were analyzed for fluency (i.e., words per minute (WPM) and mean length of utterance in words (MLU-W)) and grammaticality (i.e., the proportion of grammatically correct sentences, open-to-closed-class word ratio, noun-to-verb ratio, and correct production of verb inflection, noun morphology, and verb argument structure.) Between group differences were analyzed for each variable. Correlational analyses examined the relation between WPM and each grammatical variable, and an off-line measure of sentence production.
Outcomes And Results
Agrammatic and logopenic groups both had lower scores on the fluency measures and produced significantly fewer grammatical sentences than did semantic and control groups. However, only the agrammatic group evinced significantly impaired production of verb inflection and verb argument structure. In addition, some semantic participants showed abnormal open-to-closed and noun-to-verb ratios in narrative speech. When the sample was divided on the basis of fluency, all the agrammatic participants fell in the nonfluent category. The logopenic participants varied in fluency but those with low fluency showed variable performance on measures of grammaticality. Correlational analyses and scatter plots comparing fluency and each grammatical variable revealed dissociations within PPA participants, with some nonfluent participants showing normal grammatical skill.
Grammatical production is a complex construct comprised of correct usage of several language components, each of which can be selectively affected by disease. This study demonstrates that individuals with PPA show dissociations between fluency and grammatical production in narrative speech. Grammatical ability, and its relationship to fluency, varies from individual to individual, and from one variant of PPA to another, and can even be found in individuals with semantic PPA in whom a fluent aphasia is usually thought to accompany preserved ability to produce grammatical utterances.
PMCID: PMC3244141  PMID: 22199417
25.  Thinking About Better Speech: Mental Practice for Stroke-Induced Motor Speech Impairments 
Aphasiology  2012;26(2):127-142.
Mental practice (MP) is a mind-body technique in which physical movements are cognitively rehearsed. It has shown efficacy in reducing the severity of a number of neurological impairments.
In the present review, we highlight recent developments in MP research, and the basis for MP use after stroke-induced motor speech disorders.
Main Contribution
In this review, we: (a) propose a novel conceptual model regarding the development of learned nonuse in people with motor speech impairments; (b) review the rationale and efficacy of MP for reducing the severity of stroke-induced impairments; (c) review evidence demonstrating muscular and neural activations during and following MP use; (d) review evidence showing that MP increases skill acquisition, use, and function in stroke; (e) review literature regarding neuroplasticity after stroke, including MP-induced neuroplasticity and the neural substrates underlying motor and language reacquisition; and (f) based on the above, review the rationale and clinical application of MP for stroke-induced motor speech impairments.
Support for MP use includes decades of MP neurobiological and behavioral efficacy data in a number of populations. Most recently, these data have expanded to the application of MP in neurological populations. Given increasingly demanding managed care environments, efficacious strategies that can be easily administered are needed. We also encounter clinicians who aspire to use MP, but their protocols do not contain several of the elements shown to be fundamental to effective MP implementation. Given shortfalls of some conventional aphasia and motor speech rehabilitative techniques, and uncertainty regarding optimal MP implementation, this paper introduces the neurophysiologic bases for MP, the evidence for MP use in stroke rehabilitation, and discusses its applications and considerations in patients with stroke-induced motor speech impairments.
PMCID: PMC3269777  PMID: 22308050

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