Sarah Marchina

Evidence for Plasticity in White‐Matter Tracts of Patients with Chronic Broca's Aphasia Undergoing Intense Intonation‐based Speech Therapy

Recovery from aphasia can be achieved through recruitment of either perilesional brain regions in the affected hemisphere or homologous language regions in the nonlesional hemisphere. For patients with large left‐hemisphere lesions, recovery through the right hemisphere may be the only possible path. The right‐hemisphere regions most likely to play a role in this recovery process are the superior temporal lobe (important for auditory feedback control), premotor regions/posterior inferior frontal gyrus (important for planning and sequencing of motor actions and for auditory‐motor mapping), and the primary motor cortex (important for execution of vocal motor actions). These regions are connected reciprocally via a major fiber tract called the arcuate fasciculus (AF), however, this tract is not as well developed in the right hemisphere as it is in the dominant left. We tested whether an intonation‐based speech therapy (i.e., melodic intonation therapy [MIT]), which is typically administered in an intense fashion with 75–80 daily therapy sessions, would lead to changes in white‐matter tracts, particularly the AF. Using diffusion tensor imaging (DTI), we found a significant increase in the number of AF fibers and AF volume comparing post‐ with pretreatment assessments in six patients that could not be attributed to scan‐to‐scan variability. This suggests that intense, long‐term MIT leads to remodeling of the right AF and may provide an explanation for the sustained therapy effects that were seen in these six patients.

Melodic Intonation Therapy: Shared Insights on How it is Done and Why it Might Help

For more than 100 years, clinicians have noted that patients with nonfluent aphasia are capable of singing words that they cannot speak. Thus, the use of melody and rhythm has long been recommended for improving aphasic patients’ fluency, but it was not until 1973 that a music‐based treatment [Melodic Intonation Therapy (MIT)] was developed. Our ongoing investigation of MITs efficacy has provided valuable insight into this therapys effect on language recovery. Here we share those observations, our additions to the protocol that aim to enhance MITs benefit, and the rationale that supports them.

Intensive therapy induces contralateral white matter changes in chronic stroke patients with Broca's aphasia

Using a pre-post design, eleven chronic stroke patients with large left hemisphere lesions and nonfluent aphasia underwent diffusion tensor imaging and language testing before and after receiving 15 weeks of an intensive intonation-based speech therapy. This treated patient group was compared to an untreated patient group (n=9) scanned twice over a similar time period. Our results showed that the treated group, but not the untreated group, had reductions in fractional anisotropy in the white matter underlying the right inferior frontal gyrus (IFG, pars opercularis and pars triangularis), the right posterior superior temporal gyrus, and the right posterior cingulum. Furthermore, we found that greater improvements in speech production were associated with greater reductions in FA in the right IFG (pars opercularis). Thus, our findings showed that an intensive rehabilitation program for patients with nonfluent aphasia led to structural changes in the right hemisphere, which correlated with improvements in speech production.

When right is all that is left: plasticity of right-hemisphere tracts in a young aphasic patient

Using an adapted version of Melodic Intonation Therapy (MIT), we treated an adolescent girl with a very large left‐hemisphere lesion and severe nonfluent aphasia secondary to an ischemic stroke. At the time of her initial assessment 15 months after her stroke, she had reached a plateau in her recovery despite intense and long‐term traditional speech‐language therapy (approximately five times per week for more than one year). Following an intensive course of treatment with our adapted form of MIT, her performance improved on both trained and untrained phrases, as well as on speech and language tasks. These behavioral improvements were accompanied by functional MRI changes in the right frontal lobe as well as by an increased volume of white matter pathways in the right hemisphere. No increase in white matter volume was seen in her healthy twin sister, who was scanned twice over the same time period. This case study not only provides further evidence for MITs effectiveness, but also indicates that intensive treatment can induce functional and structural changes in a right‐hemisphere fronto‐temporal network.

Atypical hemispheric asymmetry in the arcuate fasciculus of completely nonverbal children with autism

Despite the fact that as many as 25% of the children diagnosed with autism spectrum disorders are nonverbal, surprisingly little research has been conducted on this population. In particular, the mechanisms that underlie their absence of speech remain unknown. Using diffusion tensor imaging, we compared the structure of a language‐related white matter tract (the arcuate fasciculus, AF) in five completely nonverbal children with autism to that of typically developing children. We found that, as a group, the nonverbal children did not show the expected left–right AF asymmetry—rather, four of the five nonverbal children actually showed the reversed pattern. It is possible that this unusual pattern of asymmetry may underlie some of the severe language deficits commonly found in autism, particularly in children whose speech fails to develop. Furthermore, novel interventions (such as auditory‐motor mapping training) designed to engage brain regions that are connected via the AF may have important clinical potential for facilitating expressive language in nonverbal children with autism.

Predicting speech fluency and naming abilities in aphasic patients

There is a need to identify biomarkers that predict degree of chronic speech fluency/language impairment and potential for improvement after stroke. We previously showed that the Arcuate Fasciculus lesion load (AF-LL), a combined variable of lesion site and size, predicted speech fluency in patients with chronic aphasia. In the current study, we compared lesion loads of such a structural map (i.e., AF-LL) with those of a functional map [i.e., the functional gray matter lesion load (fGM-LL)] in their ability to predict speech fluency and naming performance in a large group of patients. The fGM map was constructed from functional brain images acquired during an overt speaking task in a group of healthy elderly controls. The AF map was reconstructed from high-resolution diffusion tensor images also from a group of healthy elderly controls. In addition to these two canonical maps, a combined AF-fGM map was derived from summing fGM and AF maps. Each canonical map was overlaid with individual lesion masks of 50 chronic aphasic patients with varying degrees of impairment in speech production and fluency to calculate a functional and structural lesion load value for each patient, and to regress these values with measures of speech fluency and naming. We found that both AF-LL and fGM-LL independently predicted speech fluency and naming ability; however, AF lesion load explained most of the variance for both measures. The combined AF-fGM lesion load did not have a higher predictability than either AF-LL or fGM-LL alone. Clustering and classification methods confirmed that AF lesion load was best at stratifying patients into severe and non-severe outcome groups with 96% accuracy for speech fluency and 90% accuracy for naming. An AF-LL of greater than 4 cc was the critical threshold that determined poor fluency and naming outcomes, and constitutes the severe outcome group. Thus, surrogate markers of impairments have the potential to predict outcomes and can be used as a stratifier in experimental studies.

Acid‐suppressive medication use in acute stroke and hospital‐acquired pneumonia

Pneumonia is a morbid complication of stroke, but evidence‐based strategies for its prevention are lacking. Acid‐suppressive medications have been associated with increased risk for nosocomial pneumonia in hospitalized patients. It is unclear whether these results can be extrapolated to stroke patients, where other factors strongly modulate pneumonia risk. We investigated the association between acid‐suppressive medication and hospital‐acquired pneumonia in patients with acute stroke.

Risk of Stroke-Associated Pneumonia and Oral Hygiene

Background: Pneumonia is a major complication of stroke, but effective prevention strategies are lacking. Since aspiration of oropharyngeal secretions is the primary mechanism for development of stroke-associated pneumonia, strategies that decrease oral colonization with pathogenic bacteria may help curtail pneumonia risk. We therefore hypothesized that systematic oral care protocols can help decrease pneumonia risk in hospitalized stroke patients. In this study, we investigated the impact of a systematic oral hygiene care (OHC) program in reducing hospital-acquired pneumonia in patients with acute-subacute stroke. Methods: This study compared the proportion of pneumonia cases in hospitalized stroke patients before and after implementation of a systematic OHC intervention. All patients hospitalized with acute ischemic stroke or intracerebral hemorrhage admitted to a large, urban academic medical center in Boston, Mass., USA from May 31, 2008, to June 1, 2010 (epoch prior to implementation of OHC), and from January 1, 2012, to December 31, 2013 (epoch after full implementation of OHC), who were 18 years of age and hospitalized for ≥2 days were eligible for inclusion. The cohort in the first epoch constituted the control group whereas the cohort in the second epoch formed the intervention group. Multivariate logistic regression was used to control for confounders. The main outcome measure was hospital-acquired pneumonia, defined via International Classification of Diseases, Ninth Revision, Clinical Modification codes. Results: The cohort comprised 1,656 admissions (707 formed historical controls; 949 were in the intervention group). The unadjusted incidence of hospital-acquired pneumonia was lower in the group assigned to OHC compared to controls (14 vs. 10.33%; p = 0.022) with an unadjusted OR of 0.68 (95% CI 0.48-0.95; p = 0.022). After adjustment for influential confounders, the OR of hospital-acquired pneumonia in the intervention group remained significantly lower at 0.71 (95% CI 0.51-0.98; p = 0.041). Conclusion: In this large hospital-based cohort of patients admitted with acute stroke, systematic OHC use was associated with decreased odds of hospital-acquired pneumonia.

Pharyngeal Swallowing Mechanics Secondary to Hemispheric Stroke

BACKGROUND Computational analysis of swallowing mechanics (CASM) is a method that utilizes multivariate shape change analysis to uncover covariant elements of pharyngeal swallowing mechanics associated with impairment using videofluoroscopic swallowing studies. The goals of this preliminary study were to (1) characterize swallowing mechanics underlying stroke-related dysphagia, (2) decipher the impact of left and right hemispheric strokes on pharyngeal swallowing mechanics, and (3) determine pharyngeal swallowing mechanics associated with penetration-aspiration status. METHODS Videofluoroscopic swallowing studies of 18 dysphagic patients with hemispheric infarcts and age- and gender-matched controls were selected from well-controlled data sets. Patient data including laterality and penetration-aspiration status were collected. Coordinates mapping muscle group action during swallowing were collected from videos. Multivariate morphometric analyses of coordinates associated with stroke, affected hemisphere, and penetration-aspiration status were performed. RESULTS Pharyngeal swallowing mechanics differed significantly in the following comparisons: stroke versus controls (D = 2.19, P < .0001), right hemispheric stroke versus controls (D = 3.64, P < .0001), left hemispheric stroke versus controls (D = 2.06, P < .0001), right hemispheric stroke versus left hemispheric stroke (D = 2.89, P < .0001), and penetration-aspiration versus within normal limits (D = 2.25, P < .0001). Differences in pharyngeal swallowing mechanics associated with each comparison were visualized using eigenvectors. CONCLUSIONS Whereas current literature focuses on timing changes in stroke-related dysphagia, these data suggest that mechanical changes are also functionally important. Pharyngeal swallowing mechanics differed by the affected hemisphere and the penetration-aspiration status. CASM can be used to identify patient-specific swallowing impairment associated with stroke injury that could help guide rehabilitation strategies to improve swallowing outcomes.

Study Design for the Fostering Eating after Stroke with Transcranial Direct Current Stimulation Trial: A Randomized Controlled Intervention for Improving Dysphagia after Acute Ischemic Stroke

GOAL Dysphagia is a major stroke complication but lacks effective therapy that can promote recovery. Noninvasive brain stimulation with and without peripheral sensorimotor activities may be an attractive treatment option for swallowing recovery but has not been systematically investigated in the stroke population. This article describes the study design of the first prospective, single-center, double-blinded trial of anodal versus sham transcranial direct current stimulation (tDCS) used in combination with swallowing exercises in patients with dysphagia from an acute ischemic stroke. The aim of this study is to gather safety data on cumulative sessions of tDCS in acute-subacute phases of stroke, obtain information about effects of this intervention on important physiologic and clinically relevant swallowing parameters, and examine possible dose effects. METHODS Ninety-nine consecutive patients with dysphagia from an acute unilateral hemispheric infarction with a Penetration and Aspiration Scale (PAS) score of 4 or more and without other confounding reasons for dysphagia will be enrolled at a single tertiary care center. Subjects will be randomized to either a high or low dose tDCS or a sham group and will undergo 10 sessions over 5 consecutive days concomitantly with effortful swallowing maneuvers. The main efficacy measures are a change in the PAS score before and after treatment; the main safety measures are mortality, seizures, neurologic, motor, and swallowing deterioration. CONCLUSIONS The knowledge gained from this study will help plan a larger confirmatory trial for treating stroke-related dysphagia and advance our understanding of important covariates influencing swallowing recovery and response to the proposed intervention.