Short-form Philadelphia Naming Test: Rationale and Empirical Evaluation

This project translates research findings from the Philadelphia (picture) Naming Test into a clinical tool for diagnosis and measurement of change. The tool is a pair of 5-minute naming tests, each involving a different, representative set of 30 PNT targets. In an evaluation carried out with a well-distributed sample of 25 individuals with chronic aphasia, accuracy scores on the short forms, PNT30-A and –B, were highly correlated with the full PNT and with each other. By utilizing the extensive research database from the PNT, score equivalents and norms are calculated that can be applied in the clinical setting

Power in Voxel-based Lesion–Symptom Mapping

Lesion analysis in brain-injured populations complements what can be learned from functional neuroimaging. Voxelbased approaches to mapping lesion–behavior correlations in brain-injured populations are increasingly popular, and have the potential to leverage image analysis methods drawn from functional magnetic resonance imaging. However, power is a major concern for these studies, and is likely to vary regionally due to the distribution of lesion locations. Here, we outline general considerations for voxel-based methods, characterize the use of a nonparametric permutation test adapted from functional neuroimaging, and present methods for regional power analysis in lesion studies

Facilitation of Verb Retrieval Skills in Aphasia: A Comparison of Two Approaches

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The simulation of action disorganisation in complex activities of daily living

Action selection in everyday goal-directed tasks of moderate complexity is known to be subject to breakdown following extensive frontal brain injury. A model of action selection in such tasks is presented and used to explore three hypotheses concerning the origins of action disorganisation: that it is a consequence of reduced top-down excitation within a hierarchical action schema network coupled with increased bottom-up triggering of schemas from environmental sources, that it is a more general disturbance of schema activation modelled by excessive noise in the schema network, and that it results from a general disturbance of the triggering of schemas by object representations. Results suggest that the action disorganisation syndrome is best accounted for by a general disturbance to schema activation, while altering the balance between top-down and bottom-up activation provides an account of a related disorder - utilisation behaviour. It is further suggested that ideational apraxia (which may result from lesions to left temporoparietal areas and which has similar behavioural consequences to action disorganisation syndrome on tasks of moderate complexity) is a consequence of a generalised disturbance of the triggering of schemas by object representations. Several predictions regarding differences between action disorganisation syndrome and ideational apraxia that follow from this interpretation are detailed

Temporal characteristics of semantic perseverations induced by blocked-cyclic picture naming

When unimpaired participants name pictures quickly, they produce many perseverations that bear a semantic relation to the target, especially when the pictures are blocked by category. Evidence suggests that the temporal properties of these "semantic perseverations" may differ from typical lexical perseverations in aphasia. To explore this, we studied semantic perseverations generated by participants with aphasia on a naming task with semantic blocking [Schnur, T. T., Schwartz, M. F., Brecher, A., & Hodgson, C. (2006). Semantic interference during blocked-cyclic naming: Evidence from aphasia. Journal of Memory and Language, 54, 199-227]. The properties of these perseverations were investigated by analyzing how often they occurred at each lag (distance from prior occurrence) and how time (response-stimulus interval) influenced the lag function. Chance data sets were created by reshuffling stimulus-response pairs in a manner that preserved unique features of the blocking design. We found that the semantic blocking manipulation did not eliminate the expected bias for short-lag perseverations (recency bias). However, immediate (lag 1) perseverations were not invariably the most frequent, which hints at a source of inconsistency within and across studies. Importantly, there was not a reliable difference between the lag functions for perseverations generated with a 5 s, compared to 1 s, responsestimulus interval. The combination of recency bias and insensitivity to elapsed time indicates that the perseveratory impetus in a named response does not passively decay with time but rather is diminished by interference from related trials. We offer an incremental learning account of these findings

A Proof-Of-Principle Study of Epigenetic Therapy Added to Neoadjuvant Doxorubicin Cyclophosphamide for Locally Advanced Breast Cancer

BACKGROUND: Aberrant DNA methylation and histone deacetylation participate in cancer development and progression; hence, their reversal by inhibitors of DNA methylation and histone deacetylases (HDACs) is at present undergoing clinical testing in cancer therapy. As epigenetic alterations are common to breast cancer, in this proof-of-concept study demethylating hydralazine, plus the HDAC inhibitor magnesium valproate, were added to neoadjuvant doxorubicin and cyclophosphamide in locally advanced breast cancer to assess their safety and biological efficacy. METHODOLOGY: This was a single-arm interventional trial on breast cancer patients (ClinicalTrials.gov Identifier: NCT00395655). After signing informed consent, patients were typed for acetylator phenotype and then treated with hydralazine at 182 mg for rapid-, or 83 mg for slow-acetylators, and magnesium valproate at 30 mg/kg, starting from day –7 until chemotherapy ended, the latter consisting of four cycles of doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) every 21 days. Core-needle biopsies were taken from primary breast tumors at diagnosis and at day 8 of treatment with hydralazine and valproate. MAIN FINDINGS: 16 patients were included and received treatment as planned. All were evaluated for clinical response and toxicity and 15 for pathological response. Treatment was well-tolerated. The most common toxicity was drowsiness grades 1–2. Five (31%) patients had clinical CR and eight (50%) PR for an ORR of 81%. No patient progressed. One of 15 operated patients (6.6%) had pathological CR and 70% had residual disease <3 cm. There was a statistically significant decrease in global 5(m)C content and HDAC activity. Hydralazine and magnesium valproate up- and down-regulated at least 3-fold, 1,091 and 89 genes, respectively. CONCLUSIONS: Hydralazine and magnesium valproate produce DNA demethylation, HDAC inhibition, and gene reactivation in primary tumors. Doxorubicin and cyclophosphamide treatment is safe, well-tolerated, and appears to increase the efficacy of chemotherapy. A randomized phase III study is ongoing to support the efficacy of so-called epigenetic or transcriptional cancer therapy

Syllabic complexity effects in phonological speech errors: The role of articulatory-phonetic impairment

Research with native Italian people with aphasia (PWA) argues that syllabic complexity effects in phonological speech errors are based in articulatory encoding impairments [1, 2]. This important claim has yet to be substantiated for English. Indeed, one influential study reported no effects of syllabic complexity (a.k.a, “markedness”) on phonological error production [3]. We present evidence from an ongoing study that corroborates and extends the main claims of the Italian studies. In [1], markedness effects were contrasted in PWA with high vs. low proportions of phonetic-articulatory errors in single word repetition. We measured this “phonetic error proportion” (PEP) in 121 diverse, English-speaking PWA and found a graded distribution ranging from .00 to .55 with Mn = .10 and SD = .12. PEP scores correlated positively with apraxia of speech (AOS), WAB AQ, and lesion size (all r > .35; p < .001). From the sample of 121, we identified those who made > 20% phonological errors on the Philadelphia Naming Test. This identified 22 PWA, with a suitable range in PEP (.03-.55), AQ (25-84), and lesion volume (8-376 cc) and ample phonological naming errors to analyze (Mn. 47; range18-94). Half had AOS (measured as in [4]). For each individual, we calculated several structure-change proportions: we counted how many of their phonological errors instantiated a particular syllable-structure change and divided the number by the opportunities for that change present in the PNT targets. We report on two changes affecting the pre-vocalic (onset) position of a syllable: • fills an empty onset (onset creation) (e.g., VC→CVC) – decreases complexity • deletes a filled onset (e.g., CVC→_VC) – increases complexity and two changes affecting consonant clusters: • deletes a consonant cluster (e.g., CVCC→CVC_) – decreases complexity • creates a consonant cluster (e.g., CV→CCV) – increases complexity Fig. 1 shows the median change proportions, broken down by locus of change (1st, 2nd, or 3rd syllable). Predictably, there were far fewer opportunities for changes that decrease syllable complexity (see insert), yet the corresponding change proportions (onset creation; cluster deletion) were found to be high relative to those that increase complexity. Moreover, onset creation and cluster deletion proportions correlated strongly (r=.66), suggesting a common underlying mechanism. To investigate this mechanism, we computed an overall effect size for complexity reduction, reflecting the difference between structure decreasing and structure increasing changes: (onset creation + cluster deletion) – (onset deletion + cluster creation) We then used simultaneous multiple regression to predict this effect size from PEP, WAB AQ and lesion volume. Adjusted R2 for the model was .50 (F = 7.8; p = .001), and the strongest predictor was PEP (beta = .73; t = 4.43; p < .001). WAB was marginally significant (p=.05). In conclusion, our study corroborates the influence of syllabic complexity on phonological errors in naming and shows that the tendency for errors to transform marked structures to unmarked ones correlates with the severity of the phonetic-articulatory involvement, after controlling for aphasia severity and lesion size. This has implications for the theoretical treatment of phonological error production and its relation to AOS. Figure legend Fig. 1. Median proportion of phonological naming errors that create or delete an onset or a cluster, relative to the opportunities (shown in insert) afforded by the naming targets