Escitalopram and Language Intervention for Subacute Aphasia (ELISA)

项目摘要（项目二）

Project Summary (Project 2) Aphasia, or language impairment, is among the most devastating problems after left hemisphere stroke, because it can interfere with an individual’s social interactions, ability to return to work, and even simple daily activities, such as returning email or answering the phone. Speech and language treatment (SLT) can be helpful in restoring language function, but recovery is often incomplete. Recent studies indicate that motor and cognitive recovery after stroke can be augmented with selective serotonin reuptake inhibitors (SSRIs). With this proposal, we aim to evaluate the effect of an SSRI, escitalopram, given daily for 3 months after stroke, on augmenting language recovery. We will compare the effects of escitalopram plus SLT to placebo plus SLT in a double blind, randomized controlled trial (RCT). SLT will consist of “standard” language therapy for two months, followed by a daily, computer-delivered naming therapy (CoDeNT) over 15 sessions beginning at two months. We selected this SLT to enable us to compare the effects of escitalopram to the effect of transcranial direct current stimulation (tDCS) versus sham with the same SLT, in our ongoing study of tDCS plus aphasia treatment in subacute stroke. We will evaluate the effect of escitalopram on naming untrained objects (one of the most common deficits in aphasia), and secondarily, its effects on morphosyntactic production, content and efficiency of narrative speech, quality of life, and disability. We will evaluate the influence of treatment and demographic variables, lesion volume, white matter disease, aphasia and stroke severity, and education on outcome. Based on recent studies from the Center for the Study of Aphasia Recovery and from the literature, we will also identify neural mechanisms that may mediate the effects of language recovery with treatment, including the influence of abnormal polymorphisms in the brain derived neurotrophic factor (BDNF) gene. We will also evaluate the effects of escitalopram on “functional connectivity” at rest (or correlations in activation between regions of “the language network” in the brain versus other networks in the brain, such as the motor network), comparing resting state functional connectivity MRI before any intervention and after escitalopram or placebo with SLT. This aim may shed light on the mechanisms of how escitalopram affects language, and/or how language recovers with or without medication, independently on the effects of escitalopram on depression. We will test our hypotheses in a RCT, Escitalopram for Language Improvement in Subacute Aphasia (ELISA). Neither the participant with aphasia nor the investigator will be unmasked until the end of the study. The long- term aim of this study is to provide the basis for a Phase III randomized controlled trial of either escitalopram, anodal-tDCS, or both with concurrent SLT for treatment of subacute aphasia. This study will help us determine which intervention(s) is likely to augment SLT and allow us to select the best candidates for treatment in the larger study.