Pélagie M. Beeson

Evaluating Single-Subject Treatment Research: Lessons Learned from the Aphasia Literature

The mandate for evidence-based practice has prompted careful consideration of the weight of the scientific evidence regarding the therapeutic value of various clinical treatments. In the field of aphasia, a large number of single-subject research studies have been conducted, providing clinical outcome data that are potentially useful for clinicians and researchers; however, it has been difficult to discern the relative potency of these treatments in a standardized manner. In this paper we describe an approach to quantify treatment outcomes for single-subject research studies using effect sizes. These values provide a means to compare treatment outcomes within and between individuals, as well as to compare the relative strength of various treatments. Effect sizes also can be aggregated in order to conduct meta-analyses of specific treatment approaches. Consideration is given to optimizing research designs and providing adequate data so that the value of treatment research is maximized.

Cost function masking during normalization of brains with focal lesions: Still a necessity?

Although normalization of brain images is critical to the analysis of structural damage across individuals, loss of tissue due to focal lesions presents challenges to the available normalization algorithms. Until recently, cost function masking, as advocated by Brett and colleagues (2001), was the accepted method to overcome difficulties encountered when normalizing damaged brains; however, development of the unified segmentation approach for normalization in SPM5 (Ashburner & Friston, 2005) offered an alternative. Crinion et al. (2007) demonstrated this approach produced normalization results without cost function masking that appeared to be robust to lesion effects when tested using the same simulated lesions studied by Brett et al. (2001). The present study sought to confirm the validity of this approach in brains with focal damage due to vascular events. To do so, we examined outcomes of normalization using unified segmentation with and without cost function masking in 49 brain images with chronic stroke. Lesion masks were created using two approaches (precise and rough drawings of lesion boundaries), and normalization was implemented with both smoothed and unsmoothed versions of the masks. We found that failure to employ cost function masking produced less accurate results in real and simulated lesions, compared to masked normalization, both in terms of deformation field displacement and voxelwise intensity differences. Additionally, unmasked normalization led to significant underestimation of lesion volume relative to all four masking conditions, especially in patients with large lesions. Taken together, these findings suggest cost function masking is still necessary when normalizing brain images with chronic infarcts.

Phonological dyslexia and dysgraphia: Cognitive mechanisms and neural substrates

To examine the validity of different theoretical assumptions about the neuropsychological mechanisms and lesion correlates of phonological dyslexia and dysgraphia, we studied written and spoken language performance in a large cohort of patients with focal damage to perisylvian cortical regions implicated in phonological processing. Despite considerable variation in accuracy for both words and non-words, the majority of participants demonstrated the increased lexicality effects in reading and spelling that are considered the hallmark features of phonological dyslexia and dysgraphia. Increased lexicality effects were also documented in spoken language tasks such as oral repetition, and patients performed poorly on a battery of phonological tests that did not involve an orthographic component. Furthermore, a composite measure of general phonological ability was strongly predictive of both reading and spelling accuracy, and we obtained evidence that the continuum of severity that characterized the written language disorder of our patients was attributable to an underlying continuum of phonological impairment. Although patients demonstrated qualitatively similar deficits across measures of written and spoken language processing, there were quantitative differences in levels of performance reflecting task difficulty effects. Spelling was more severely affected than reading by the reduction in phonological capacity and this differential vulnerability accounted for occasional disparities between patterns of impairment on the two written language tasks. Our findings suggest that phonological dyslexia and dysgraphia in patients with perisylvian lesions are manifestations of a central or modality-independent phonological deficit rather than the result of damage to cognitive components dedicated to reading or spelling. Our results also provide empirical support for shared-components models of written language processing, according to which the same central cognitive systems support both reading and spelling. Lesion-deficit correlations indicated that phonological dyslexia and dysgraphia may be produced by damage to a variety of perisylvian cortical regions, consistent with distributed network models of phonological processing.

The role of left posterior inferior temporal cortex in spelling

Objective: To determine whether damage to left posterior inferior temporal cortex (PITC) is associated with agraphia and to characterize the nature of the spelling impairment. Background: Left angular gyrus may play a critical role in spelling. However, this traditional view is challenged by reports of agraphia after left temporo-occipital lesions and by functional imaging studies demonstrating activation of left PITC during writing in normal individuals. Methods: Patients with focal damage to the left temporo-occipital cortex and normal control subjects were administered a comprehensive spelling battery that included regular words, irregular words, and nonwords as stimuli. Results: Although patients performed worse than control subjects in all experimental conditions, the spelling deficit was particularly severe for irregular words, whereas regular word and nonword spelling were less impaired. Additional analyses indicated that orthographic regularity and word frequency had a much more pronounced effect on spelling accuracy in patients compared with control subjects. Most errors on irregular words were phonologically plausible, consistent with reliance on a sublexical phonologic spelling strategy (i.e., phoneme-grapheme conversion). Overall, the spelling impairment of the patients showed the characteristic profile of lexical agraphia. Lesion analyses indicated that the damage in the majority of patients encompassed an area within the left PITC (BA 37/20) where the authors previously obtained evidence of activation in a functional imaging study of writing in normal participants. Conclusions: The behavioral and neuroanatomic observations in the patients are consistent with functional imaging studies of writing in neurologically intact individuals and provide converging evidence for the role of left PITC in spelling. Together, these findings implicate left PITC as a possible neural substrate of the putative orthographic lexicon that contains stored memory representations for the written forms of familiar words.

The neural substrates of writing: A functional magnetic resonance imaging study

Background: Hypotheses regarding the neural substrates of writing have been derived from the study of individuals with acquired agraphia. Functional neuroimaging offers another methodology to test these hypotheses in neurologically intact individuals. Aims: This study was designed to identify possible neural substrates for the linguistic and motor components of writing in normal English-speaking individuals. Methods & Procedures: Functional magnetic resonance imaging was used with 12 adults to examine activation associated with generative writing of words from semantic categories contrasted with writing letters of the alphabet and drawing circles. In addition, the generative writing condition was contrasted with a subvocal generative naming condition. Outcomes & Results: Semantically guided retrieval of orthographic word forms for the generative writing condition revealed activation in the left inferior and dorsolateral prefrontal cortex, as well as the left posterior inferior temporal lobe (BA 37). However, no activation was detected in the left angular gyrus (BA 39). The motor components of writing were associated with activation in left fronto-parietal cortex including the region of the intraparietal sulcus, superior parietal lobule, dorsolateral and medial premotor cortex, and sensorimotor areas for the hand. Conclusions: These observations suggest an important role of the left posterior inferior temporal cortex in lexical-orthographic processing and fail to support the long-held notion that the dominant angular gyrus is the storage site for orthographic representations of familiar words. Our findings also demonstrate the involvement of left superior parietal and frontal premotor regions in translating orthographic information into appropriate hand movements.

Treating acquired writing impairment: strengthening graphemic representations

A writing treatment protocol was designed for a 75 year-old man with severe Wernickes aphasia. Four treatment phases were implemented: (1) a multiple baseline design that documented improvement in single-word writing for targeted words; (2) a clinician-directed home program that increased the corpus of correctly-spelled single words; (3) another multiple baseline series that documented acquisition of additional written words, as well as pragmatic training in the use of single-word writing to support conversational communication; and (4) a self-directed home treatment to further expand written vocabulary. The patients acquisition of targeted words suggested an item-specific treatment effect that strengthened weakened graphemic representations. The patients continued acquisition of correctly spelled words during the self-directed home treatment supported the use of this approach to supplement more traditional clinician-directed treatment.

Positive Effects of Language Treatment for the Logopenic Variant of Primary Progressive Aphasia

Despite considerable recent progress in understanding the underlying neurobiology of primary progressive aphasia (PPA) syndromes, relatively little attention has been directed toward the examination of behavioral interventions that may lessen the pervasive communication problems associated with PPA. In this study, we report on an individual with a behavioral profile and cortical atrophy pattern consistent with the logopenic variant of PPA. At roughly two-and-a-half years post onset, his marked lexical retrieval impairment prompted administration of a semantically based intervention to improve word retrieval. The treatment was designed to improve self-directed efforts to engage the participant’s relatively preserved semantic system in order to facilitate word retrieval. His positive response to an intensive (2-week) dose of behavioral treatment was associated with improved lexical retrieval of items within trained categories, and generalized improvement for naming of untrained items that lasted over a 6-month follow-up interval. These findings support the potential value of intensive training to achieve self-directed strategic compensation for lexical retrieval difficulties in logopenic PPA. Additional insight was gained regarding the neural regions that supported improved performance by the administration of a functional magnetic resonance imaging protocol before and after treatment. In the context of a picture-naming task, post-treatment fMRI showed increased activation of left dorsolateral prefrontal regions that have been implicated in functional imaging studies of generative naming in healthy individuals. The increased activation in these frontal regions that were not significantly atrophic in our patient (as determined by voxel-based morphometry) is consistent with the notion that neural plasticity can support compensation for specific language loss, even in the context of progressive neuronal degeneration.

Memory Impairment and Executive Control in Individuals with Stroke-Induced Aphasia

The purpose of this study was to examine memory abilities of aphasic individuals in relation to site of neurological lesion. Fourteen individuals with stroke-induced aphasia (7 with anterior lesions; 7 with posterior lesions) and 14 demographically matched control subjects were given selected tests of short-term memory (STM) and long-term memory (LTM). Stroke patients were impaired relative to control subjects on tests of verbal memory, with greater impairment of LTM associated with anterior lesions and greater impairment of STM associated with posterior lesions. Verbal memory performance did not correlate highly with language ability, and did not appear to be simply a consequence of language impairment. Executive control deficits were postulated as explanatory of the LTM impairment associated with anterior lesions.

Lexical retrieval and semantic knowledge in patients with left inferior temporal lobe lesions.

Background: It has been proposed that anomia following left inferior temporal lobe lesions may have two different underlying mechanisms with distinct neural substrates. Specifically, naming impairment following damage to more posterior regions (BA 37) has been considered to result from a disconnection between preserved semantic knowledge and phonological word forms (pure anomia), whereas anomia following damage to anterior temporal regions (BAs 38, 20/21) has been attributed to the degradation of semantic representations (semantic anomia). However, the integrity of semantic knowledge in patients with pure anomia has not been demonstrated convincingly, nor were lesions in these cases necessarily confined to BA 37. Furthermore, evidence of semantic anomia often comes from individuals with bilateral temporal lobe damage, so it is unclear whether unilateral temporal lobe lesions are sufficient to produce significant semantic impairment. This research was supported by a Graduate Imaging Fellowship from the University of Arizona and by NIH grants RO1DC008286 and RO1DC07464. Scans were funded through Arizona Alzheimers Research Consortium, Cognition and NeuroImaging Lab, Arizona Department of Health Services HB2354. Many thanks to Jen Parrott, Kristin Boruff, and Cathy West for their time and assistance. The authors thank Mark Borgstrom, statistical consultant at the University of Arizona, for his assistance with this project. We also thank Chris Rorden for advice regarding lesion analyses. Aims: The main goals of this study were to determine whether anomia following unilateral left inferior temporal lobe damage reflected a loss of semantic knowledge or a post‐semantic deficit in lexical retrieval and to identify the neuroanatomical correlates of the naming impairment. Methods & Procedures: Eight individuals who underwent left anterior temporal lobectomy (L ATL) and eight individuals who sustained left posterior cerebral artery strokes (L PCA) completed a battery of language measures that assessed lexical retrieval and semantic processing, and 16 age‐ and education‐matched controls also completed this battery. High‐resolution structural brain scans were collected to conduct lesion analyses. Outcomes & Results: Performance of L ATL and L PCA patients was strikingly similar, with both groups demonstrating naming performance ranging from moderately impaired to unimpaired. Anomia in both groups occurred in the context of mild deficits to semantic knowledge, which manifested primarily as greater difficulty in naming living things than nonliving things and greater difficulty in processing visual/perceptual as opposed to functional/associative semantic attributes. Lesion analyses indicated that both patient groups sustained damage to anterior inferior temporal lobe regions implicated in semantic processing. Conclusions: These results contribute to a better understanding of the cognitive mechanism of naming impairment in patients with temporal lobe damage and support the notion that pure anomia and semantic anomia represent two endpoints along a continuum of semantic impairment. Unilateral left temporal lobe lesions in our patients resulted in relatively mild semantic deficits that were apparent primarily in lexical production tasks, whereas severe semantic impairment likely requires bilateral temporal lobe damage.

Do dual-route models accurately predict reading and spelling performance in individuals with acquired alexia and agraphia?

Coltheart and co-workers [Castles, A., Bates, T. C., & Coltheart, M. (2006). John Marshall and the developmental dyslexias. Aphasiology, 20, 871-892; Coltheart, M., Rastle, K., Perry, C., Langdon, R., & Ziegler, J. (2001). DRC: A dual route cascaded model of visual word recognition and reading aloud. Psychological Review, 108, 204-256] have demonstrated that an equation derived from dual-route theory accurately predicts reading performance in young normal readers and in children with reading impairment due to developmental dyslexia or stroke. In this paper, we present evidence that the dual-route equation and a related multiple regression model also accurately predict both reading and spelling performance in adult neurological patients with acquired alexia and agraphia. These findings provide empirical support for dual-route theories of written language processing.