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Compared to neurologically healthy adults, persons with aphasia (PWA) demonstrate impaired performance on working memory (WM) tasks. These deficits in WM are thought to underlie language processing problems in PWA. However, most studies use WM tasks that are verbal in nature, making it difficult to determine if these deficits are due to domain-general attentional processes related to WM or domain-specific verbal abilities. The purpose of the current study was to examine WM performance in PWA and healthy controls using verbal and spatial WM tasks. Additionally, this study investigated the relationship among WM performance and performance on short-term memory and domain-general attentional tasks. Fourteen PWA and 13 control participants completed verbal and spatial n-back tasks, the Flanker arrows task, and forward digit and spatial span tasks. The results revealed that the PWA performed worse than the control participants on the verbal tasks, but there were no group differences on the spatial tasks. Further, PWA showed significantly greater conflict and interference effects on the Flanker arrows task than control participants. These findings suggest that although WM deficits are primarily evident in the verbal domain in PWA, they are not solely the result of domain-specific verbal deficits; the ability to inhibit irrelevant information may contribute to WM deficits in PWA.

Background: Researchers have found that many individuals with aphasia (IWA) present with cognitive deficits that may impact their communication, and perhaps underlie their language-processing deficits (e.g., Erickson et al., 1996; Murray et al., 1997; Wright et al., 2003). However, many investigations of cognitive ability in aphasia have included measures that may be considered “language heavy”; they require overt lexical, semantic, and/or phonological processing to follow the task instructions and/or formulate a response. Few have considered the amount of linguistic processing required to perform the task. Subsequently, it is not clear if poorer performance by IWA on cognitive tasks compared to neurologically intact (NI) participants is due to a deficit in the respective cognitive domain or due to the inability of IWA to perform the task because of their language difficulties. Aims: The purpose of the current study was to explore the effect of varying linguistic processing demands in the context of a dyn...

Background: Individuals with aphasia (IWA) present with language impairments at the discourse level. Recently researchers have found a relationship between discourse measures in aphasia and raters' perceptions of the quality of language produced by IWA. However, the relationship between naive raters' perceptions of language quality and linguistic measures of discourse in individuals without aphasia is less clear. Due to variations in researchers' intentions, discourse tasks used, objective measures analysed, and methods used to assess language quality, a cogent understanding of what linguistic measures impact the perception of language quality is still lacking. If certain discourse measures important for differentiating the language quality of individuals with language impairments are also important to distinguishing the quality of stories produced by individuals without language impairments, those elements should have a significant impact on communicative success for IWA. Aims: The purpose of this study ...

Purpose The objective of this study was to quantify cognitive effort that individuals with aphasia and neurologically intact participants dedicate to verbal compared with spatial working memory tasks by using a physiological measure of effort: heart rate variability (HRV). Method Participants included 8 individuals with aphasia and 19 neurologically intact adults. Participants completed 3 verbal and 3 spatial working memory tasks that varied in difficulty. Performance accuracy and effort allocated to tasks was recorded. Effort was quantified as the change in the 0.07–0.14 Hz band of HRV from baseline to task conditions. Results Results indicated that individuals with aphasia and control participants allocated effort to verbal and spatial working memory tasks. Unlike the control participants, participants with aphasia did not differentially invest effort based on task difficulty. Neither group allocated effort differentially based on task type. Conclusions Results of the physiological data provide preliminary support for accounts indicating that individuals with aphasia do not properly allocate effort to cognitive–linguistic tasks. Analysis of the Group × Difficulty interaction indicated that the aphasia group did not allocate extra effort when it was required. The lack of a difference in HRV for spatial and verbal tasks suggests that this difference is not specific to verbal stimuli.

Immune escape from graft-versus-tumor (GVT) contributes to relapse after allogeneic stem cell transplantation (SCT). High-dose radiation (XRT) mobilizes a tumor-specific immune response following direct damage to the tumor and microenvironment. Radiation's abscopal effect is also immune mediated. We hypothesized that local radiation of relapsed tumor would rekindle a GVT effect and yield abscopal tumor responses. We tested the safety and systemic effects of single-fraction XRT followed by donor lymphocyte infusion (DLI) in patients with lymphoid malignancy and refractory relapse after SCT. Eligible subjects (Table) had tumor progression following donor engraftment, withdrawal of immune suppression and/or DLI, and XRT-amenable tumor. Subjects received 8 Gy XRT to 1 or more tumors; all but 1 (with chronic GVHD) received DLI 24 hours later. Clinical monitoring included marrow function, GVHD, XRT toxicity and tumor response. Correlative monitoring for systemic immunologic and GVT effects included FDG-PET imaging, serial peripheral blood sampling, and biopsy of radiated and nonirradiated tumor. Immune effects were characterized by flow cytometry and gene expression analysis. Local XRT toxicity of Grade 3 or less presented as expected in all subjects. Grade 4 neutropenia (2) was transient and GCSF-responsive; GVHD flare was not observed. Unexpected toxicity was observed in 1 subject who developed Grade 4 diffuse alveolar hemorrhage and Grade 3 cardiomyopathy that responded to therapy. Sustained response in radiated sites was observed in 6 of 8 evaluable subjects (nonevaluable: 1 MM bony lesion; 1 subject received further Rx). RECIST responses outside the radiation field included 2 PR and 5 SD. 2 subjects with SD had regression after initial tumor flare. 3 of 4 regressions were transient, with progression by 6 months; 3 subjects demonstrated progression. A single subject who received radiation alone demonstrated systemic tumor response as well as improvement in chronic GVHD (sclerotic skin). By FDG-PET, all subjects' radiated tumors showed substantially decreased uptake at D28; SUV changes were variable at D7. Changes in non-XRT tumors demonstrated far greater variability, even within single subjects. Consistent with systemic immune activation resulting from radiation-DLI therapy, within 1 week, peripheral blood T cell proliferation (%Ki-67+) increased significantly in CD4 and CD8 T cells, as well as FoxP3+ Tregs (Wilcoxon paired nonparametric analyses; p =.004, .004 and .01, respectively). A trend (p=.078) toward increased frequency of Th1 effector CD4 cells (T-bet+CD28-) was also observed. Comparison of gene expression in nonirradiated (abscopal) tumor in 4 patients collected pre and 1 month post XRT was consistent with an IFN-mediated response to cell damage. Genes were upregulated for receptors for nuclear materials released by damaged cells (TLR2, TLR4, CLEC4E), high- and low- affinity FcgR (FCGR1A and FCGR2A) used for phagocytosis, and an annexin receptor for phagocytic cells (FPR2). The inflammasome component genes NLRP3 and CASP1 were upregulated, as was IFIT1, a Type 1 IFN inducible gene. After SCT, XRT results in local tumor regression; abscopal responses were also observed, with systemic immune responses suggested by T cell proliferation in the peripheral blood and upregulation of tissue damage receptors and IFN-inducible genes in nonirradiated tumor. Systemic tumor responses were delayed, with peak regression occurring 3-4 months after XRT, consistent with an immune-mediated effect. GVHD was not observed; significant, reversible pulmonary and marrow toxicities were infrequent. Transient abscopal responses in these DLI-refractory patients suggest plausible synergy between radiation and allogeneic GVT effects. Further investigation into posttransplant immunomodulatory radiation is warranted. Funding: Intramural NCI/CCR and NCI Contract No. HHSN261200800001E Table 1. DX Age/Sex Years Post-Allo XRT Site Donor / DLI CD3 Dose (10e6) XRT Response NonXRT Response NonXRT Response Duration CLL 65/M 2.3 B Neck, L Groin URD/1 -90% -69% 2M HL 36/M 2.8 B Axillae MRD/10 -6% +51% CLL 64/M 1.4 R Axilla URD/1 -82% -19% 3M HL 37/M 7.0 R Axilla MRD/10 -69% +2% 4M MM 60/F 6.9 R Ileum MRD/10 NE PD - HL 25/F 1.2 Lumbar 3-5 URD/1 7% -69% 3M HL 37/F 5.8 R Neck MRD/10 -100% -30% 3M HL 27/M 2.7 L Pelvis MRD/10 NE NE - MCL 57/M 3.1 L Groin URD/1 -100% +28% HL 28/M 1.8 L Neck MRD/None -73% -9% 3M Disclosures No relevant conflicts of interest to declare.

Summary Purpose The Voice Handicap Index (VHI) is widely used and accepted into adult clinical practice. The present study was initiated to adapt the VHI to the pediatric population and to validate it in the form of a parental proxy. Methods The initial modification of the adult VHI involved changing the language of the statements to reflect a parent's responses about their child and eliminating questions that would not relate to children. It was administered in conjunction with 10 open-ended questions regarding the impact of the child's voice quality on overall communication, development, education, social and family life. The pVHI was then modified in content and language, and the final 23-item parental proxy product was used for the validation process. The modified pVHI was administered to two groups of patients following IRB approval from Cincinnati Children's Hospital Medical Center. Results Normative data was obtained from 45 parents of healthy children. The group consisted of 21 males, age ranges 3–12 years old. The mean scores of the total pVHI and its subscales are: functional (F) 1.47, physical (P) 0.20, emotional (E) 0.18 and total (T) 1.84. The test group consisted of 33 guardians of children presenting for a voice evaluation pre- or post-laryngotracheal reconstruction. This group differed greatly from the control group on each subscale and total score. The mean scores of the airway group were as follows: F 13.94, P 15.48, E 12.15 and T 41.58. Test–retest reliability of the total pVHI score was measured using Pearson's correlation coefficient. The scores were 0.95, 0.77, 0.79 and 0.82, respectively. A correlation matrix for pVHI subscore and total score showed significance, with results similar to those reported for the original adult VHI. Conclusions The aim of the present study was to modify the VHI to serve a similar role in the evaluation of the effects of dysphonia on the pediatric population. The statistical results reveal a high correlation between the VHI and the pVHI. The pVHI provides a high internal consistency and test–retest reliability. This tool will be utilized to follow a child's development following surgical, medical and behavioral interventions.