Specificity in Generalization Effects of Transcranial Direct Current Stimulation Over the Left Inferior Frontal Gyrus in Primary Progressive Aphasia.

OBJECTIVES: Generalization (or near-transfer) effects of an intervention to tasks not explicitly trained are the most desirable intervention outcomes. However, they are rarely reported and even more rarely explained. One hypothesis for generalization effects is that the tasks improved share the same brain function/computation with the intervention task. We tested this hypothesis in this study of transcranial direct current stimulation (tDCS) over the left inferior frontal gyrus (IFG) that is claimed to be involved in selective semantic retrieval of information from the temporal lobes. MATERIALS AND METHODS: In this study, we examined whether tDCS over the left IFG in a group of patients with primary progressive aphasia (PPA), paired with a lexical/semantic retrieval intervention (oral and written naming), may specifically improve semantic fluency, a nontrained near-transfer task that relies on selective semantic retrieval, in patients with PPA. RESULTS: Semantic fluency improved significantly more in the active tDCS than in the sham tDCS condition immediately after and two weeks after treatment. This improvement was marginally significant two months after treatment. We also found that the active tDCS effect was specific to tasks that require this IFG computation (selective semantic retrieval) but not to other tasks that may require different computations of the frontal lobes. CONCLUSIONS: We provided interventional evidence that the left IFG is critical for selective semantic retrieval, and tDCS over the left IFG may have a near-transfer effect on tasks that depend on the same computation, even if they are not specifically trained. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02606422.

Sleep as a predictor of tDCS and language therapy outcomes.

STUDY OBJECTIVES: To determine whether sleep at baseline (before therapy) predicted improvements in language following either language therapy alone or coupled with transcranial direct current stimulation (tDCS) in individuals with primary progressive aphasia (PPA). METHODS: Twenty-three participants with PPA (mean age 68.13 ± 6.21) received written naming/spelling therapy coupled with either anodal tDCS over the left inferior frontal gyrus (IFG) or sham condition in a crossover, sham-controlled, double-blind design (ClinicalTrials.gov identifier: NCT02606422). The outcome measure was percent of letters spelled correctly for trained and untrained words retrieved in a naming/spelling task. Given its particular importance as a sleep parameter in older adults, we calculated sleep efficiency (total sleep time/time in bed x100) based on subjective responses on the Pittsburgh Sleep Quality Index (PSQI). We grouped individuals based on a median split: high versus low sleep efficiency. RESULTS: Participants with high sleep efficiency benefited more from written naming/spelling therapy than participants with low sleep efficiency in learning therapy materials (trained words). There was no effect of sleep efficiency in generalization of therapy materials to untrained words. Among participants with high sleep efficiency, those who received tDCS benefitted more from therapy than those who received sham condition. There was no additional benefit from tDCS in participants with low sleep efficiency. CONCLUSION: Sleep efficiency modified the effects of language therapy and tDCS on language in participants with PPA. These results suggest sleep is a determinant of neuromodulation effects.Clinical Trial: tDCS Intervention in Primary Progressive Aphasia https://clinicaltrials.gov/ct2/show/NCT02606422.

Neural Correlates of Letter and Semantic Fluency in Primary Progressive Aphasia.

Verbal fluency (VF) is an informative cognitive task. Lesion and functional imaging studies implicate distinct cerebral areas that support letter versus semantic fluency and the understanding of neural and cognitive mechanisms underlying task performance. Most lesion studies include chronic stroke patients. People with primary progressive aphasia (PPA) provide complementary evidence for lesion-deficit associations, as different brain areas are affected in stroke versus PPA. In the present study we sought to determine imaging, clinical and demographic correlates of VF in PPA. Thirty-five patients with PPA underwent an assessment with letter and category VF tasks, evaluation of clinical features and an MRI scan for volumetric analysis. We used stepwise regression models to determine which brain areas are associated with VF performance while acknowledging the independent contribution of clinical and demographic factors. Letter fluency was predominantly associated with language severity (R2 = 38%), and correlated with the volume of the left superior temporal regions (R2 = 12%) and the right dorsolateral prefrontal area (R2 = 5%). Semantic fluency was predominantly associated with dementia severity (R2 = 47%) and correlated with the volume of the left inferior temporal gyrus (R2 = 7%). No other variables were significantly associated with performance in the two VF tasks. We concluded that, independently of disease severity, letter fluency is significantly associated with the volume of frontal and temporal areas whereas semantic fluency is associated mainly with the volume of temporal areas. Furthermore, our findings indicated that clinical severity plays a critical role in explaining VF performance in PPA, compared to the other clinical and demographic factors.

Supracricoid partial laryngectomy: swallowing, voice, and speech outcomes.

OBJECTIVES: The purpose of the study was to describe the swallowing and vocal function of patients after supracricoid partial laryngectomy (SCPL) as they changed over the first postoperative year. METHODS: Ten patients with laryngeal carcinoma underwent SCPL at Johns Hopkins Hospital between August 2003 and May 2005. Clinical and videofluoroscopic swallowing examinations and perceptual, acoustic, aerodynamic, and video-stroboscopic voice evaluations were completed before operation and at 3 weeks (swallowing only) and 2 (voice only), 6, and 12 months after operation. RESULTS: The mean time to gastrostomy tube removal was 82 days. The patients tolerated an increased variety of foods over the first postoperative year. All patients initially used therapeutic strategies to swallow safely, and some still required them at 1 postoperative year. Over the year, the perceptual ratings of voice quality improved significantly. There were no consistent changes in acoustic or aerodynamic measures. The number of patients who used multiple vibratory sources to phonate increased over the year. CONCLUSIONS: The patients tolerated regular diets, yet continued to exhibit silent aspiration and a variety of decompensations. Their voices were breathy, rough, and strained. Their voice quality ratings improved over the year. Group changes were not captured, and it appears that the changes in speech and voice 2 months after surgery were subtle.

Brain volumes as predictors of tDCS effects in primary progressive aphasia.

The current study aims to determine the brain areas critical for response to anodal transcranial direct current stimulation (tDCS) in PPA. Anodal tDCS and sham were administered over the left inferior frontal gyrus (IFG), combined with written naming/spelling therapy. Thirty people with PPA were included in this study, and assessed immediately, 2 weeks, and 2 months post-therapy. We identified anatomical areas whose volumes significantly predicted the additional tDCS effects. For trained words, the volumes of the left Angular Gyrus and left Posterior Cingulate Cortex predicted the additional tDCS gain. For untrained words, the volumes of the left Middle Frontal Gyrus, left Supramarginal Gyrus, and right Posterior Cingulate Cortex predicted the additional tDCS gain. These findings show that areas involved in language, attention and working memory contribute to the maintenance and generalization of stimulation effects. The findings highlight that tDCS possibly affects areas anatomically or functionally connected to stimulation targets.

Written Verb Naming Improves After tDCS Over the Left IFG in Primary Progressive Aphasia.

Transcranial direct current stimulation (tDCS), a non-invasive neuromodulation technique, is an effective adjunct to naming treatments in post-stroke aphasia and primary progressive aphasia (PPA). Enhanced performance in oral and written naming and spelling of nouns with tDCS has been quantified in detail, but it is not known whether it is effective for verb treatment in PPA. We addressed the question of whether performance in naming and spelling of verbs can be augmented with anodal tDCS over the left inferior frontal gyrus (IFG). We compared tDCS coupled with oral and written verb naming/spelling treatment with oral and written verb naming/spelling treatment alone. In a double-blind, sham-controlled, crossover design, 11 participants with logopenic or non-fluent variant PPA received approximately 15 consecutive sessions of anodal tDCS and sham over the left IFG coupled with oral and written verb-naming + spelling treatment. Written verb-naming performance improved significantly more for trained verbs in the tDCS than the sham condition. Importantly, tDCS effects generalized to untrained items for written verb naming and were significant even at 2 months post-treatment. We conclude that tDCS over the left IFG can improve written verb naming and spelling in PPA.

"The effect of tDCS on functional connectivity in primary progressive aphasia" NeuroImage: Clinical, volume 19 (2018), pages 703-715.

Transcranial direct current stimulation (tDCS) is an innovative technique recently shown to improve language outcomes even in neurodegenerative conditions such as primary progressive aphasia (PPA), but the underlying brain mechanisms are not known. The present study tested whether the additional language gains with repetitive tDCS (over sham) in PPA are caused by changes in functional connectivity between the stimulated area (the left inferior frontal gyrus (IFG)) and the rest of the language network. We scanned 24 PPA participants (11 female) before and after language intervention (written naming/spelling) with a resting-state fMRI sequence and compared changes before and after three weeks of tDCS or sham coupled with language therapy. We correlated changes in the language network as well as in the default mode network (DMN) with language therapy outcome measures (letter accuracy in written naming). Significant tDCS effects in functional connectivity were observed between the stimulated area and other language network areas and between the language network and the DMN. TDCS over the left IFG lowered the connectivity between the above pairs. Changes in functional connectivity correlated with improvement in language scores (letter accuracy as a proxy for written naming) evaluated before and after therapy. These results suggest that one mechanism for anodal tDCS over the left IFG in PPA is a decrease in functional connectivity (compared to sham) between the stimulated site and other posterior areas of the language network. These results are in line with similar decreases in connectivity observed after tDCS over the left IFG in aging and other neurodegenerative conditions.

Effects of laryngeal cancer on voice and swallowing.

Specific deficits that may be encountered as well as interventional strategies and evidence-based practice are discussed. When discussing the voice, it is important to consider that for many people the voice is not just a tool for communication, but also an identifying feature that allows expression of personality. Eating and swallowing are vital to life sustenance and also allow for a myriad of social interactions. Laryngeal cancer can have a dramatic impact on this delicately balanced system leading to disturbances of voice and swallowing.

The effect of tDCS on functional connectivity in primary progressive aphasia.

Transcranial direct current stimulation (tDCS) is an innovative technique recently shown to improve language outcomes even in neurodegenerative conditions such as primary progressive aphasia (PPA), but the underlying brain mechanisms are not known. The present study tested whether the additional language gains with repetitive tDCS (over sham) in PPA are caused by changes in functional connectivity between the stimulated area (the left inferior frontal gyrus (IFG)) and the rest of the language network. We scanned 24 PPA participants (11 female) before and after language intervention (written naming/spelling) with a resting-state fMRI sequence and compared changes before and after three weeks of tDCS or sham coupled with language therapy. We correlated changes in the language network as well as in the default mode network (DMN) with language therapy outcome measures (letter accuracy in written naming). Significant tDCS effects in functional connectivity were observed between the stimulated area and other language network areas and between the language network and the DMN. TDCS over the left IFG lowered the connectivity between the above pairs. Changes in functional connectivity correlated with improvement in language scores (letter accuracy as a proxy for written naming) evaluated before and after therapy. These results suggest that one mechanism for anodal tDCS over the left IFG in PPA is a decrease in functional connectivity (compared to sham) between the stimulated site and other posterior areas of the language network. These results are in line with similar decreases in connectivity observed after tDCS over the left IFG in aging and other neurodegenerative conditions.

Electrical brain stimulation in different variants of primary progressive aphasia: A randomized clinical trial.

INTRODUCTION: Transcranial direct current stimulation (tDCS) has been recently shown to improve language outcomes in primary progressive aphasia (PPA) but most studies are small and the influence of PPA variant is unknown. METHODS: Thirty-six patients with PPA participated in a randomized, sham-controlled, double-blind, within-subject crossover design for 15 daily sessions of stimulation coupled with written naming/spelling therapy. Outcome measures were letter accuracy of treated and untreated words immediately after and at 2 weeks and 2 months posttreatment. RESULTS: tDCS treatment was more effective than sham: gains for treated words were maintained 2 months posttreatment; gains from tDCS also generalized to untreated words and were sustained 2 months posttreatment. Different effects were obtained for each PPA variant, with no tDCS advantage for semantic variant PPA. DISCUSSION: The study supports using tDCS as an adjunct to written language interventions in individuals with logopenic or nonfluent/agrammatic PPA seeking compensatory treatments in clinical settings.

Speech-language pathology care and short- and long-term outcomes of oropharyngeal cancer treatment in the elderly.

OBJECTIVE: To examine associations between speech-language pathology (SLP) care and pretreatment variables, short-term and long-term swallowing and airway impairment, and survival in elderly patients treated for oropharyngeal squamous cell cancer (SCCA). STUDY DESIGN: Retrospective analysis of Surveillance, Epidemiology, and End Results-Medicare data. METHODS: We evaluated longitudinal data from 666 patients diagnosed with oropharyngeal SCCA from 2004 to 2007 using cross-tabulations, multivariate logistic regression, and survival analysis. RESULTS: SLP care was documented in 25% of patients. High-volume hospital care (odds ratio (OR) = 3.2 [1.0-10.0]) and dysphagia during treatment (OR = 13.0 [3.6-47.1]) were the only significant predictors of SLP care during the initial treatment period. SLP care was significantly more likely during the first year (OR = 5.3 [3.1-9.1]) and second year (OR = 4.5 [2.4-8.2]) following initial treatment. Subsequent dysphagia (OR = 32.5 [16.9-62.4]), stricture (OR = 2.2 [1.2-4.0]), gastrostomy (OR = 1.7 [1.1-2.7]), and tracheostomy tube use (OR = 2.4 [1.2-4.8]) were significantly associated with long-term SLP care. After controlling for patient, tumor, and treatment-related variables, SLP care was associated with significant relative attenuation of the OR for dysphagia (93%), stricture (35%), weight loss (8%), and airway obstruction (34%). Survival analysis, controlling for all other variables, demonstrated improved survival for patients under SLP care (hazard ratio = 0.73 [0.57-0.95]). CONCLUSION: SLP care is underutilized in elderly oropharyngeal SCCA patients and largely utilized after the onset of impaired airway and swallowing function, but is associated with improved outcomes. These data suggest a need for treatment guidelines that incorporate the routine use of SLP care in this population during the initial treatment period and beyond. LEVEL OF EVIDENCE: 2c. Laryngoscope, 128:1403-1411, 2018.

Swallowing and speech therapy after definitive treatment for laryngeal cancer.

As the trend in laryngeal cancer treatment shifts towards organ-conservation surgeries and organ-preservation protocols, patients will more often retain anatomy vital to communication and swallowing. Despite a conservative approach, results of treatment may have debilitating effects. Rehabilitation efforts are directed towards a return to functional, if not normal, status. Although there are predictable trends in voice and swallowing disorders of patients with laryngeal cancer, posttreatment dysphonia and dysphagia are diverse in presentation. Considering the significant diversity of this population, speech pathologists should work closely with otolaryngologists to determine the most appropriate treatment for each patient. As this article demonstrates, voice and swallowing therapy are necessary components of the rehabilitation process following treatment for head and neck cancers. As always, treatment is tailored to the specific individual and based on information obtained during a thorough evaluation by a speech pathologist. Fortunately, with the help of voice and swallowing therapy, many patients return to functional communication and oral feeding.

Rehabilitation needs of patients with oropharyngeal cancer.

Swallowing and swallowing-related impairments present important posttreatment challenges in individuals undergoing organ preservation therapy for head and neck cancer. Literature pertinent to this topic is reviewed. A protocol for treatment of speech and swallowing deficits related to oropharyngeal cancer and treatment performed at Johns Hopkins Hospital is described. Data collected from a sample of oropharyngeal patients with cancer, with and without human papillomavirus-related disease, are summarized. Future directions for further study of this population are discussed.