Neurobehavioral response to increased treatment dosage in chronic, severe aphasia

• ¹ University of Connecticut, Speech, Language and Hearing Sciences, United States
• ² Brown University, United States

Introduction Intensive aphasia treatment has been employed with equivocal results likely due in part to variability in the severity of participants as well as in the parameters that comprise intensity (e.g., session duration). Intensive Language Action Therapy (ILAT; Difrancesco, Pulvermüller, & Mohr, 2012) is an intensive aphasia therapy that has been replicated successfully and also tends to use similar dosage parameters across replication studies (Barthel, Meinzer, Djundja, & Rockstroh, 2008; Kurland, Pulvermüller, Silva, Burke, & Andrianopoulos, 2012; Maher, 2006; Meinzer et al., 2004). Those with more severe aphasia are thought to have the most to gain from ILAT since they could potentially benefit more from the “forced use” aspect than those who have more residual language (Meinzer et al., 2008). Since Pulvermüller and colleagues’ (2001) initial study, several successful replication studies have shown increases on standardized tests, discourse measures or functional communication outcomes. The dosage for these tends to be approximately thirty hours over two weeks or less. If the dosage of ILAT contributes to gains as suggested by evidence from work in our lab (Mozeiko, Myers, & Coelho, 2011), then it is possible that increasing the dosage to sixty hours over four weeks might produce even greater outcomes. The present study employed a modified multiple probe technique (McReynolds & Kearns, 1983) in which ILAT was delivered at a dosage of three hours per day for twenty days. Discourse productivity and naming accuracy were probed daily. In addition, fMRI scanning was performed at four time points throughout the treatment process in order to compare potential language changes to changes in neural activation patterns with each participant acting as his or her own control. These results are expected to contribute to the limited fMRI results from investigations of neural recovery throughout an extended aphasia treatment period. Methods Participants Two participants were recruited from a university-based aphasia group. They were both right handed, one male (S1) and one female (S2), 51 and 31 months post left CVA. Both participants were classified as having moderate-severe aphasia with scores on the Western Aphasia Battery Aphasia Quotient (WAB AQ; Kertesz, 1982) of 38.5 for S1 and 51.7 for S2. Lesion volumes were 99,671 mm3 and 67,250 mm3 for S1 and S2 respectively. Neither fit neatly into an aphasia classification but S1 would be considered nonfluent and S2 was considered to have a more fluent aphasia type. While taking part in the study, individuals did not participate in any other form of language rehabilitation. Intervention ILAT was administered according to the protocol described by Maher and colleagues (2006) with target responses increasing in difficulty over time. Three-hour sessions were conducted five days a week, for four weeks for a total of 60 hours of treatment. The few studies that report follow-up data after ILAT, tend to report additional increases in language production four weeks post the “standard” two week treatment dosage (e.g.,Maher et al., 2006; Mozeiko et al., 2011; Szaflarski et al., 2008). In order to a) capitalize on the probable continued neural change occurring post treatment and b) provide a time-off from a very rigorous treatment schedule, a five week break was incorporated after the first 30 hours of treatment. Participants were required to produce and respond to verbal communication with the verbal modality only. Participants were instructed on linguistic targets prior to each session and the clinician provided cueing as necessary. Assessments Standardized tests, treatment and generalization probes and fMRI scans were administered at four time points: pre-treatment, mid-treatment, post-treatment and at an eight week follow-up. Standardized assessments included the WAB AQ, the Boston Naming Test (BNT; Kaplan et al., 1983) and the Computerized Revised Token Test (CRTT; McNeil et al., 2008). Probes of treatment and generalization were administered daily. These assessed performance on the trained materials, equivalent untrained materials and maintenance of mastered levels. To assess generalization of treatment to connected speech, picture descriptions were elicited. Discourse probes were administered after every six hours of treatment and analyzed for Correct Information Units (CIUs, Nicholas & Brookshire, 1993) and then the proportion of CIUs to total words and CIUs/minute were calculated to measure efficiency of verbal production. FMRI scans were conducted in order to compare corresponding language changes over time. Temporal sparse sampling was used to allow monitoring of overt responses in the scanner. Responses consisted of the naming of previously established “hard” and “easy” trained and untrained stimuli. Analyses of activation and lateralization within three bilateral regions of interest (ROIs), including the inferior frontal gyrus, were performed for each participant. Results Standardized test measures S1 and S2 increased WAB AQ scores by 14 and 12.3 points respectively and each increased by 200% on the BNT by the end of Treatment Period I (see Table 1). No further increase was observed on the WAB AQ following Treatment Period II but there were continued gains on the BNT with an additional 250% and 100% gain for S1 and S2 respectively. No change was seen on the CRTT. Probes of Treatment and Generalization Both participants improved but did not achieve criteria of 80% accuracy on Level 1 (high frequency words). After week 1, Level 2 (low frequency words) was initiated in accordance with the protocol established. See Figures 1 and 2. S1 demonstrated negligible-small effect (2.6; Beeson & Robey, 2006) following Treatment Period I but a moderate effect (7.8) following Treatment Period II. S2 demonstrated moderate effect size (6.4) in response to treatment following Treatment Period I which increased to 8.2 (approaching large effect) following Treatment Period II. Small-moderate effect sizes were also observed for untrained items for both participants following Treatment Period II only. Note that the above refers only to Level 1 items as there was negligible-small effect with Level 2 items (range of 0.8 - 3.8) Probe data of generalization to discourse demonstrated moderate increases in slope for productivity for both participants. Effect sizes following Treatment Period I were 11.9 (large) and 6.6 (moderate) and following Treatment Period II were 6.3 (moderate) and 13.7 (large) for S1 and S2 respectively. (see Figures 3 and 4). Neuroimaging In order to qualitatively compare activation across scans for each participant, an anatomical ROI was used. There was greater activation change in the right hemisphere inferior frontal gyrus than in the left for both participants (see Figures 5 and 6). Maximum activation for S1 was observed after Treatment Period I. For S2, it was observed after Treatment Period II. Discussion Behavioral results • Larger effects of treatment following Treatment Period II suggest that a second dose of intensive treatment is beneficial to those with moderate-severe chronic aphasia. • Benefits from a second dose included increases on untrained materials suggesting that more treatment may be necessary in order for generalization to untreated materials to occur. • Consistent gains on discourse probes were observed in the second treatment session during which more complex stimuli were trained. • Results from the WAB AQ showed increases well over the five point gain considered clinically significant following Treatment Period I but additional increases were not observed following Treatment Period II. This highlights the importance of non-standardized measures to document treatment responsiveness Neuroimaging results • Increased activation in S2’s bilateral inferior frontal gyrus following the second treatment session indicates that a second Treatment Period can influence continued neuroplastic change in severe, chronic aphasia. • S1 appears to show the most activation following Treatment Period I. It is possible that his greater lesion volume or site did not allow for benefit from a second dose to the same degree as S2. • Activation changes (or lack thereof) in both cases corresponded with performance on the naming task in the scanner, reflecting the effect of treatment. • For S2, neuroimaging supported the behavioral results which favor a second dose of ILAT. For S1, behavioral results, particularly in his consistent increases on the BNT, are not supported by either the behavioral results in the scanner or the BOLD response.