Elizabeth Dvorak's research while affiliated with Georgetown University Medical Center and other places

Language function in the brain, once thought to be highly localized, is now appreciated as relying on a connected but distributed network. The semantic system is of particular interest in the language domain because of its hypothesized integration of information across multiple cortical regions. Previous work in healthy individuals has focused on group-level functional connectivity (FC) analyses of the semantic system, which may obscure interindividual differences driving variance in performance. These studies also overlook the contributions of white matter networks to semantic function. Here, we identified semantic network nodes at the individual level with a semantic decision fMRI task in 53 typically aging adults, characterized network organization using structural connectivity (SC), and quantified the segregation and integration of the network using FC. Hub regions were identified in left inferior frontal gyrus. The individualized semantic network was composed of three interacting modules: (1) default-mode module characterized by bilateral medial prefrontal and posterior cingulate regions and also including right-hemisphere homotopes of language regions; (2) left frontal module extending dorsally from inferior frontal gyrus to pre-motor area; and (3) left temporoparietal module extending from temporal pole to inferior parietal lobule. FC within Module3 and integration of the entire network related to a semantic verbal fluency task, but not a matched phonological task. These results support and extend the tri-network semantic model (Xu in Front Psychol 8: 1538 1538, 2017) and the controlled semantic cognition model (Chiou in Cortex 103: 100 116, 2018) of semantic function.

People use cognitive control across many contexts in daily life, yet it remains unclear how cognitive control is used in contexts involving language. Distinguishing language-specific cognitive control components may be critical to understanding aphasia, which can co-occur with cognitive control deficits. For example, deficits in control of semantic representations (i.e., semantic control), are thought to contribute to semantic deficits in aphasia. Conversely, little is known about control of phonological representations (i.e., phonological control) in aphasia. We developed a switching task to investigate semantic and phonological control in 32 left hemisphere stroke survivors with aphasia and 37 matched controls. We found that phonological and semantic control were related, but dissociate in the presence of switching demands. People with aphasia exhibited group-wise impairment at phonological control, although individual impairments were subtle except in one case. Several individuals with aphasia exhibited frank semantic control impairments, and these individuals had relative deficits on other semantic tasks. The present findings distinguish semantic control from phonological control, and confirm that semantic control impairments contribute to semantic deficits in aphasia.

Background and Objectives A prominent theory proposes that neuroplastic recruitment of perilesional tissue supports aphasia recovery, especially when language-capable cortex is spared by smaller lesions. This theory has rarely been tested directly, and findings have been inconclusive. Here, we test the perilesional plasticity hypothesis using two fMRI tasks in two groups of patients with prior aphasia diagnosis. Methods Two cohorts totaling 82 chronic left-hemisphere stroke patients with prior aphasia diagnosis, and 82 control participants underwent fMRI using either a naming task or a reliable semantic decision task. Individualized perilesional tissue was defined by dilating anatomical lesions, and language regions were defined using meta-analyses. Mixed modeling examined differences in activity between groups. Relationships with lesion size and aphasia severity were examined. Results Patients exhibited reduced activity in perilesional language tissue relative to controls in both tasks. Although a few cortical regions exhibited greater activity irrespective of distance from the lesion, or only when distant from the lesion, no regions exhibited increased activity only when near the lesion. Larger lesions were associated with reduced language activity irrespective of distance from the lesion. Using the reliable fMRI task, reduced language activity related to aphasia severity independent of lesion size. Discussion We find no evidence for neuroplastic recruitment of perilesional tissue in aphasia beyond its typical role in language. Rather, our findings are consistent with alternative hypotheses that changes in left-hemisphere activation during recovery relate to normalization of language network dysfunction and possibly recruitment of alternate cortical processors. These findings clarify left-hemisphere neuroplastic mechanisms supporting language recovery after stroke.

Language function in the brain, once thought to be highly localized, is now appreciated as relying on a connected but distributed network. The semantic system is of particular interest in the language domain because of its hypothesized integration of information across multiple cortical regions. Previous work in healthy individuals has focused on group-level functional connectivity (FC) analyses of the semantic system, which may obscure interindividual differences driving variance in performance. These studies also overlook the contributions of white matter networks to semantic function. Here, we identified semantic network nodes with a semantic decision fMRI task in 53 typically-aging adults, characterized network organization using structural connectivity (SC), and quantified the segregation and integration of the network using FC. Hub regions were identified in left inferior frontal gyrus. The individualized semantic network was composed of three interacting modules: 1) default-mode module characterized by bilateral medial prefrontal and posterior cingulate regions and also including right-hemisphere homotopes of language regions; 2) left frontal module extending dorsally from inferior frontal gyrus to pre-motor area; and 3) left temporoparietal module extending from temporal pole to inferior parietal lobule. FC within Module3 and integration of the entire network related to a semantic verbal fluency task, but not a matched phonological task. These results support and extend the tri-network semantic model (Xu et al., 2017) and the controlled semantic cognition model (Chiou et al., 2018) of semantic function.

People use cognitive control across many contexts in daily life, yet it remains unclear how cognitive control is used in contexts involving language. Distinguishing language-specific cognitive control components may be critical to understanding aphasia, which can co-occur with cognitive control deficits. For example, deficits in control of semantic representations (i.e., semantic control), are thought to contribute to semantic deficits in aphasia. Conversely, little is known about control of phonological representations (i.e., phonological control) in aphasia. We developed a switching task to investigate semantic and phonological control in 32 left hemisphere stroke survivors with aphasia and 37 matched controls. We found that phonological and semantic control were related, but dissociate in the presence of switching demands. People with aphasia exhibited group-wise impairment at phonological control, although individual impairments were subtle. Several individuals with aphasia exhibited frank semantic control impairments, and these individuals had relative deficits on other semantic tasks. The present findings distinguish semantic control from phonological control, and confirm that semantic control impairments contribute to semantic deficits in aphasia.

Objective A prominent theory proposes that neuroplastic recruitment of perilesional tissue supports aphasia recovery, especially when language-capable cortex is spared by smaller lesions. This theory has rarely been tested directly, and findings have been inconclusive. Here, we test the perilesional plasticity hypothesis using two fMRI tasks in two groups of stroke survivors. Methods Two cohorts totaling 84 chronic left-hemisphere stroke survivors with prior aphasia diagnosis, and 80 control participants underwent fMRI using either a naming task or a reliable semantic decision task. Individualized perilesional tissue was defined by dilating anatomical lesions, and language regions were defined using meta-analyses. Mixed modeling examined differences in activity between groups. Relationships with lesion size and aphasia severity were examined. Results Stroke survivors exhibited reduced activity in perilesional language tissue relative to controls in both tasks. Although a few cortical regions exhibited greater activity irrespective of distance from the lesion, or only when distant from the lesion, no regions exhibited increased activity only when near the lesion. Larger lesions were associated with reduced language activity irrespective of distance from the lesion. Using the reliable fMRI task, reduced language activity related to aphasia severity independent of lesion size. Interpretation We find no evidence for neuroplastic recruitment of perilesional tissue in aphasia beyond its typical role in language. Rather, our findings are consistent with alternative hypotheses that left-hemisphere activation changes during recovery relate to normalization of language network dysfunction and possibly recruitment of alternate cortical processors. These findings clarify left-hemisphere neuroplastic mechanisms supporting language recovery after stroke. Summary for Social Media If Accepted Twitter handle @crlgeorgetown What is the current knowledge on the topic? After left-hemisphere stroke, many individuals experience long-term language impairment (aphasia) while others recover their communication abilities. Although there are several hypotheses concerning the kind of brain neuroplasticity that allows some individuals to recover, these mechanisms are not understood in aphasia. What question did this study address? This study tested the perilesional plasticity hypothesis as it relates to aphasia recovery. This predominant theory posits that tissue around the stroke lesion boundary becomes recruited to support recovered language function in post-stroke aphasia. What does this study add to our knowledge? This study clarifies the mechanisms of neuroplasticity in stroke aphasia recovery. The results are not consistent with the conventional perilesional plasticity hypothesis, but rather favor an interpretation that recovery is supported by normalization of language network dysfunction and possibly recruitment of alternate brain regions How might this potentially impact on the practice of neurology? These conclusions will give practicing neurologists a better understanding of how the brain recovers from aphasia after stroke.

Background: Aphasia is a common, debilitating consequence of stroke, and speech therapy is often inadequate to achieve a satisfactory outcome. Neuromodulation techniques have emerged as a potential augmentative treatment for improving aphasia outcomes. Most studies have targeted the cerebrum, but there are theoretical and practical reasons that stimulation over the cerebral hemispheres might not be ideal. On the other hand, the right cerebellum is functionally and anatomically linked to major language areas in the left hemisphere, making it a promising alternative target site for stimulation. Objective: To provide preliminary effect sizes for the ability of a short course of anodal transcranial direct current stimulation (tDCS) targeted over the right cerebellum to enhance language processing in individuals with chronic poststroke aphasia. Method: Ten individuals received five sessions of open-label anodal tDCS targeting the right cerebellum. The effects of the tDCS were compared with the effects of sham tDCS on 14 controls from a previous clinical trial. In total, 24 individuals with chronic poststroke aphasia participated in the study. Behavioral testing was conducted before treatment, immediately following treatment, and at the 3-month follow-up. Results: Cerebellar tDCS did not significantly enhance language processing measured either immediately following treatment or at the 3-month follow-up. The effect sizes of tDCS over sham treatment were generally nil or small, except for the mean length of utterance on the picture description task, for which medium to large effects were observed. Conclusion: These results may provide guidance for investigators who are planning larger trials of tDCS for individuals with chronic poststroke aphasia.

Background: Health-related quality of life (HRQL) in stroke survivors is related to numerous factors, but more research is needed to delineate factors related to HRQL in people with aphasia. Objective: To examine the relationship between HRQL and demographic factors, impairment-based measures, and lesion characteristics in chronic aphasia. Methods: A total of 41 left-hemisphere stroke survivors with aphasia underwent cognitive testing and magnetic resonance imaging. To address relationships with demographic and impairment-based measures, test scores were entered into a principal component analysis (PCA) and multiple linear regression was performed for overall and domain (physical, communication, psychosocial) scores of the Stroke and Aphasia Quality of Life Scale (SAQOL-39g). Independent variables included factor scores from the PCA, motricity, lesion volume, depressed mood, and demographic variables. To address relationships with lesion location, multivariate support vector regression lesion-symptom mapping (SVR-LSM) was used to localize lesions associated with SAQOL-39g scores. Results: The PCA yielded 3 factors, which were labeled Language Production, Nonlinguistic Cognition, and Language Comprehension. Multiple linear regression revealed that depression symptoms predicted lower SAQOL-39g average and domain scores. Lower motricity scores predicted lower SAQOL-39g average and physical scores, and lower Language Production factor scores predicted lower communication scores. SVR-LSM demonstrated that basal ganglia lesions were associated with lower physical scores, and inferior frontal lesions were associated with lower psychosocial scores. Conclusions: HRQL in chronic left-hemisphere stroke survivors with aphasia relates to lesion location, depression symptoms, and impairment-based measures. This information may help identify individuals at risk for specific aspects of low HRQL and facilitate targeted interventions to improve well-being.