Evaluating circumlocution in naming as a predictor of communicative informativeness and efficiency in discourse.

Background: Discourse analyses yield quantitative measures of functional communication in aphasia. However, they are historically underutilized in clinical settings. Confrontation naming assessments are used widely clinically and have been used to estimate discourse-level production. Such work shows that naming accuracy explains moderately high proportions of variance in measures of discourse, but proportions of variance remain unexplained. We propose that the inclusion of circumlocution productions into predictive models will account for a significant amount more of the variance. Circumlocution productions at the naming-level, while they may not contain the target word, are similar to the content that contributes to discourse informativeness and efficiency. Thus, additionally measuring circumlocution may improve our ability to estimate discourse performance and functional communication. Aim: This study aimed to test whether, after controlling for naming accuracy, the addition of a measure of circumlocution into predictive models of discourse-level informativeness and efficiency would account for a significant amount more of the variance in these discourse-level outcomes. Methods & Procedures: Naming and discourse data from 43 people with poststroke aphasia were analyzed. Naming data were collected using 120 pictured items and discourse data were collected using two picture description prompts. Data scoring and coding yielded measures of naming accuracy, incorrect response type, communicative informativeness, and efficiency. We used robust hierarchical regression to evaluate study predictions. Outcomes & Results: After controlling for naming accuracy, the inclusion of circumlocution into predictive models accounted for a significant amount more of the variance in both informativeness and efficiency. The subsequent inclusion of other response types, such as real word and nonword errors, did not account for a significant amount more of the variance in either outcome. Conclusions: In addition to naming accuracy, the production of circumlocution during naming assessments may correspond with measures of informativeness and efficiency at the discourse-level. Reducing the burden of estimating patients' functional communication will increase our ability to estimate functional communication using tools that are easy to administer and interpret.

Rapid auditory and phonemic processing relies on the left planum temporale.

After initial bilateral acoustic processing of the speech signal, much of the subsequent language processing is left-lateralized. The reason for this lateralization remains an open question. Prevailing hypotheses describe a left hemisphere (LH) advantage for rapidly unfolding information-such as the segmental (e.g., phonetic and phonemic) components of speech. Here we investigated whether and where damage to the LH predicted impaired performance on judging the directionality of frequency modulated (FM) sweep stimuli that changed within short (25ms) or longer (250ms) temporal windows. Performance was significantly lower for stroke survivors (n = 50; 18 female) than controls (n = 61; 34 female) on FM Sweeps judgments, particularly on the short sweeps. Support vector regression lesion-symptom mapping (SVR-LSM) revealed that part of the left planum temporale (PT) was related to worse performance on judging the short FM sweeps, controlling for performance on the long sweeps. We then investigated whether damage to this particular area related to diminished performance on two levels of linguistic processing that theoretically depend on rapid auditory processing: stop consonant identification and pseudoword repetition. We separated stroke participants into subgroups based on whether their LH lesion included the part of the left PT that related to diminished short sweeps judgments. Participants with PT lesions (PT lesion+, n = 24) performed significantly worse than those without (PT lesion-, n = 26) on stop consonant identification and pseudoword repetition, controlling for lesion size and hearing ability. Interestingly, PT lesions impacted pseudoword repetition more than real word repetition (PT lesion-by-repetition trial type interaction), which is of interest because pseudowords rely solely on sound perception and sequencing, whereas words can also rely on lexical-semantic knowledge. We conclude that the left PT is a critical region for processing auditory information in short temporal windows, and it may also be an essential transfer point in auditory-to-linguistic processing.

The neuroanatomy of developmental language disorder: a systematic review and meta-analysis.

Developmental language disorder (DLD) is a common neurodevelopmental disorder with adverse impacts that continue into adulthood. However, its neural bases remain unclear. Here we address this gap by systematically identifying and quantitatively synthesizing neuroanatomical studies of DLD using co-localization likelihood estimation, a recently developed neuroanatomical meta-analytic technique. Analyses of structural brain data (22 peer-reviewed papers, 577 participants) revealed highly consistent anomalies only in the basal ganglia (100% of participant groups in which this structure was examined, weighted by group sample sizes; 99.8% permutation-based likelihood the anomaly clustering was not due to chance). These anomalies were localized specifically to the anterior neostriatum (again 100% weighted proportion and 99.8% likelihood). As expected given the task dependence of activation, functional neuroimaging data (11 peer-reviewed papers, 414 participants) yielded less consistency, though anomalies again occurred primarily in the basal ganglia (79.0% and 95.1%). Multiple sensitivity analyses indicated that the patterns were robust. The meta-analyses elucidate the neuroanatomical signature of DLD, and implicate the basal ganglia in particular. The findings support the procedural circuit deficit hypothesis of DLD, have basic research and translational implications for the disorder, and advance our understanding of the neuroanatomy of language.

Functional partitioning of sentence processing and emotional prosody in the right perisylvian cortex after perinatal stroke.

In healthy adults different language abilities-sentence processing versus emotional prosody-are supported by the left (LH) versus the right hemisphere (RH), respectively. However, after LH stroke in infancy, RH regions support both abilities with normal outcomes. We investigated how these abilities co-exist in RH regions after LH perinatal stroke by evaluating the overlap in the activation between two fMRI tasks that probed auditory sentence processing and emotional prosody processing. We compared the overlap for these two functions in the RH of individuals with perinatal stroke with the symmetry of these functions in the LH and RH of their healthy siblings. We found less activation overlap in the RH of individuals with LH perinatal stroke than would be expected if both functions retained their typical spatial layout, suggesting that their spatial segregation may be an important feature of a functioning language system.

Baseline Conceptual-Semantic Impairment Predicts Longitudinal Treatment Effects for Anomia in Primary Progressive Aphasia and Alzheimer's Disease.

Background: An individual's diagnostic subtype may fail to predict the efficacy of a given type of treatment for anomia. Classification by conceptual-semantic impairment may be more informative. Aims: This study examined the effects of conceptual-semantic impairment and diagnostic subtype on anomia treatment effects in primary progressive aphasia (PPA) and Alzheimer's disease (AD). Methods & Procedures: At baseline, the picture and word versions of the Pyramids and Palm Trees and Kissing and Dancing tests were used to measure conceptual-semantic processing. Based on norming that was conducted with unimpaired older adults, participants were classified as being impaired on both the picture and word versions (i.e., modality-general conceptual-semantic impairment), the picture version (Objects or Actions) only (i.e., visual-conceptual impairment), the word version (Nouns or Verbs) only (i.e., lexical-semantic impairment), or neither the picture nor the word version (i.e., no impairment). Following baseline testing, a lexical treatment and a semantic treatment were administered to all participants. The treatment stimuli consisted of nouns and verbs that were consistently named correctly at baseline (Prophylaxis items) and/or nouns and verbs that were consistently named incorrectly at baseline (Remediation items). Naming accuracy was measured at baseline, and it was measured at three, seven, eleven, fourteen, eighteen, and twenty-one months. Outcomes & Results: Compared to baseline naming performance, lexical and semantic treatments both improved naming accuracy for treated Remediation nouns and verbs. For Prophylaxis items, lexical treatment was effective for both nouns and verbs, and semantic treatment was effective for verbs, but the pattern of results was different for nouns -- the effect of semantic treatment was initially nonsignificant or marginally significant, but it was significant beginning at 11 Months, suggesting that the effects of prophylactic semantic treatment may become more apparent as the disorder progresses. Furthermore, the interaction between baseline Conceptual-Semantic Impairment and the Treatment Condition (Lexical vs. Semantic) was significant for verb Prophylaxis items at 3 and 18 Months, and it was significant for noun Prophylaxis items at 14 and 18 Months. Conclusions: The pattern of results suggested that individuals who have modality-general conceptual-semantic impairment at baseline are more likely to benefit from lexical treatment, while individuals who have unimpaired conceptual-semantic processing at baseline are more likely to benefit from semantic treatment as the disorder progresses. In contrast to conceptual-semantic impairment, diagnostic subtype did not typically predict the treatment effects.

Rethinking Remapping: Circuit Mechanisms of Recovery after Stroke.

Stroke is one of the most common causes of disability, and there are few treatments that can improve recovery after stroke. Therapeutic development has been hindered because of a lack of understanding of precisely how neural circuits are affected by stroke, and how these circuits change to mediate recovery. Indeed, some of the hypotheses for how the CNS changes to mediate recovery, including remapping, redundancy, and diaschisis, date to more than a century ago. Recent technological advances have enabled the interrogation of neural circuits with ever greater temporal and spatial resolution. These techniques are increasingly being applied across animal models of stroke and to human stroke survivors, and are shedding light on the molecular, structural, and functional changes that neural circuits undergo after stroke. Here we review these studies and highlight important mechanisms that underlie impairment and recovery after stroke. We begin by summarizing knowledge about changes in neural activity that occur in the peri-infarct cortex, specifically considering evidence for the functional remapping hypothesis of recovery. Next, we describe the importance of neural population dynamics, disruptions in these dynamics after stroke, and how allocation of neurons into spared circuits can restore functionality. On a more global scale, we then discuss how effects on long-range pathways, including interhemispheric interactions and corticospinal tract transmission, contribute to post-stroke impairments. Finally, we look forward and consider how a deeper understanding of neural circuit mechanisms of recovery may lead to novel treatments to reduce disability and improve recovery after stroke.

One right can make a left: sentence processing in the right hemisphere after perinatal stroke.

When brain regions that are critical for a cognitive function in adulthood are irreversibly damaged at birth, what patterns of plasticity support the successful development of that function in an alternative location? Here we investigate the consistency of language organization in the right hemisphere (RH) after a left hemisphere (LH) perinatal stroke. We analyzed fMRI data collected during an auditory sentence comprehension task on 14 people with large cortical LH perinatal arterial ischemic strokes (left hemisphere perinatal stroke (LHPS) participants) and 11 healthy sibling controls using a "top voxel" approach that allowed us to compare the same number of active voxels across each participant and in each hemisphere for controls. We found (1) LHPS participants consistently recruited the same RH areas that were a mirror-image of typical LH areas, and (2) the RH areas recruited in LHPS participants aligned better with the strongly activated LH areas of the typically developed brains of control participants (when flipped images were compared) than the weakly activated RH areas. Our findings suggest that the successful development of language processing in the RH after a LH perinatal stroke may in part depend on recruiting an arrangement of frontotemporal areas reflective of the typical dominant LH.

Listening to Yourself and Watching Your Tongue: Distinct Abilities and Brain Regions for Monitoring Semantic and Phonological Speech Errors.

Despite the many mistakes we make while speaking, people can effectively communicate because we monitor our speech errors. However, the cognitive abilities and brain structures that support speech error monitoring are unclear. There may be different abilities and brain regions that support monitoring phonological speech errors versus monitoring semantic speech errors. We investigated speech, language, and cognitive control abilities that relate to detecting phonological and semantic speech errors in 41 individuals with aphasia who underwent detailed cognitive testing. Then, we used support vector regression lesion symptom mapping to identify brain regions supporting detection of phonological versus semantic errors in a group of 76 individuals with aphasia. The results revealed that motor speech deficits as well as lesions to the ventral motor cortex were related to reduced detection of phonological errors relative to semantic errors. Detection of semantic errors selectively related to auditory word comprehension deficits. Across all error types, poor cognitive control related to reduced detection. We conclude that monitoring of phonological and semantic errors relies on distinct cognitive abilities and brain regions. Furthermore, we identified cognitive control as a shared cognitive basis for monitoring all types of speech errors. These findings refine and expand our understanding of the neurocognitive basis of speech error monitoring.

Functional anomaly mapping lateralizes temporal lobe epilepsy with high accuracy in individual patients.

Mesial temporal lobe epilepsy (mTLE) is associated with variable dysfunction beyond the temporal lobe. We used functional anomaly mapping (FAM), a multivariate machine learning approach to resting state fMRI analysis to measure subcortical and cortical functional aberrations in patients with mTLE. We also examined the value of individual FAM in lateralizing the hemisphere of seizure onset in mTLE patients. Methods: Patients and controls were selected from an existing imaging and clinical database. After standard preprocessing of resting state fMRI, time-series were extracted from 400 cortical and 32 subcortical regions of interest (ROIs) defined by atlases derived from functional brain organization. Group-level aberrations were measured by contrasting right (RTLE) and left (LTLE) patient groups to controls in a support vector regression models, and tested for statistical reliability using permutation analysis. Individualized functional anomaly maps (FAMs) were generated by contrasting individual patients to the control group. Half of patients were used for training a classification model, and the other half for estimating the accuracy to lateralize mTLE based on individual FAMs. Results: Thirty-two right and 14 left mTLE patients (33 with evidence of hippocampal sclerosis on MRI) and 94 controls were included. At group levels, cortical regions affiliated with limbic and somatomotor networks were prominent in distinguishing RTLE and LTLE from controls. At individual levels, most TLE patients had high anomaly in bilateral mesial temporal and medial parietooccipital default mode regions. A linear support vector machine trained on 50% of patients could accurately lateralize mTLE in remaining patients (median AUC =1.0 [range 0.97-1.0], median accuracy = 96.87% [85.71-100Significance: Functional anomaly mapping confirms widespread aberrations in function, and accurately lateralizes mTLE from resting state fMRI. Future studies will evaluate FAM as a non-invasive localization method in larger datasets, and explore possible correlations with clinical characteristics and disease course.

Transcranial Alternating Current Stimulation (tACS) as a Treatment for Insomnia.

We investigated the effects of transcranial alternating stimulation (tACS) in patients with insomnia. Nine patients with chronic insomnia underwent two in-laboratory polysomnography, 2 weeks apart, and were randomized to receive tACS either during the first or second study. The stimulation was applied simultaneously and bilaterally at F3/M1 and F4/M2 electrodes (0.75 mA, 0.75 Hz, 5-minute). Sleep onset latency and wake after sleep onset dropped on the stimulation night but they did not reach statistical significance; however, there were significant improvements in spontaneous and total arousals, sleep quality, quality of life, recall memory, sleep duration, sleep efficiency, and daytime sleepiness.

Effects of healthy aging and left hemisphere stroke on statistical language learning.

Spoken sentences are continuous streams of sound, without reliable acoustic cues to word boundaries. We have previously proposed that language learners identify words via an implicit statistical learning mechanism that computes transitional probabilities between syllables. Neuroimaging studies in healthy young adults associate this learning with left inferior frontal gyrus, left arcuate fasciculus, and bilateral striatum. Here, we test the effects of healthy aging and left hemisphere (LH) injury on statistical learning. Following 10-minute exposure to an artificial language, participants rated familiarity of Words, Part-words (sequences spanning word boundaries), and Non-words (unfamiliar sequences). Young controls (N=14) showed robust learning, rating Words>Part-words>Non-words. Older controls (N=28) showed this pattern to a weaker degree. Stroke survivors (N=24) as a group showed no learning. A lesion comparison examining individual differences revealed that "non-learners" are more likely to have anterior lesions. Together, these findings demonstrate that word segmentation is sensitive to healthy aging and LH injury.

Language and developmental plasticity after perinatal stroke.

The mature human brain is lateralized for language, with the left hemisphere (LH) primarily responsible for sentence processing and the right hemisphere (RH) primarily responsible for processing suprasegmental aspects of language such as vocal emotion. However, it has long been hypothesized that in early life there is plasticity for language, allowing young children to acquire language in other cortical regions when LH areas are damaged. If true, what are the constraints on functional reorganization? Which areas of the brain can acquire language, and what happens to the functions these regions ordinarily perform? We address these questions by examining long-term outcomes in adolescents and young adults who, as infants, had a perinatal arterial ischemic stroke to the LH areas ordinarily subserving sentence processing. We compared them with their healthy age-matched siblings. All participants were tested on a battery of behavioral and functional imaging tasks. While stroke participants were impaired in some nonlinguistic cognitive abilities, their processing of sentences and of vocal emotion was normal and equal to that of their healthy siblings. In almost all, these abilities have both developed in the healthy RH. Our results provide insights into the remarkable ability of the young brain to reorganize language. Reorganization is highly constrained, with sentence processing almost always in the RH frontotemporal regions homotopic to their location in the healthy brain. This activation is somewhat segregated from RH emotion processing, suggesting that the two functions perform best when each has its own neural territory.

Aphasia severity is modulated by race and lesion size in chronic survivors: A retrospective study.

INTRODUCTION: In stroke survivors with aphasia (SWA), differences in behavioral language performance have been observed between Black and White Americans. These racial differences in aphasia outcomes may reflect biological stroke severity, disparities in access to care, potential assessment bias, or interactions between these factors and race. Understanding the origin of disparities in aphasia outcomes is critical to any efforts to promote health equity among SWA. In this study, we explore aphasia outcomes by examining the relationship between race, socioeconomic status, and neurological factors in SWA. METHOD: Eighty-five chronic left-hemisphere SWA (31 Black, 54 White) participated in the study. The primary aphasia outcome measure was the Western Aphasia Battery-Revised (WAB-R). Lesion size was measured based on manual lesion segmentations. FLAIR and T2 images were scored for severity of white matter disease. Independent sample t-tests were used to determine differences by race in education, age, income, aphasia severity, white matter disease, and lesion size. A linear regression model was used to explore factors that predicted aphasia severity on the WAB-R. RESULT: Level of education and estimated income differed by race in our sample. For predictors of aphasia severity, the regression model revealed a significant effect of lesion size on WAB Aphasia Quotient and an interaction of race x lesion size, such that Black and White participants with small lesions had similar WAB scores, but in individuals with larger lesions, Black participants had lower WAB scores than White participants. CONCLUSION: We suggest two explanations for the difference between Black and White SWA in the relationship between lesion size and aphasia severity. First, the impact of disparities in access to rehabilitation after stroke may be more evident when a stroke is larger and causes significant aphasia. Additionally, an assessment bias in aphasia outcome measures may be more evident with increasing severity of aphasia. Future studies should further discern the drivers of observed disparities in aphasia outcomes in order to identify opportunities to improve equity in aphasia care.

The organization of individually mapped structural and functional semantic networks in aging adults.

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.

Cingulate transcranial direct current stimulation in adults with HIV.

BACKGROUND: Neuronal dysfunction plays an important role in the high prevalence of HIV-associated neurocognitive disorders (HAND) in people with HIV (PWH). Transcranial direct current stimulation (tDCS)-with its capability to improve neuronal function-may have the potential to serve as an alternative therapeutic approach for HAND. Brain imaging and neurobehavioral studies provide converging evidence that injury to the anterior cingulate cortex (ACC) is highly prevalent and contributes to HAND in PWH, suggesting that ACC may serve as a potential neuromodulation target for HAND. Here we conducted a randomized, double-blind, placebo-controlled, partial crossover pilot study to test the safety, tolerability, and potential efficacy of anodal tDCS over cingulate cortex in adults with HIV, with a focus on the dorsal ACC (dACC). METHODS: Eleven PWH (47-69 years old, 2 females, 100% African Americans, disease duration 16-36 years) participated in the study, which had two phases, Phase 1 and Phase 2. During Phase 1, participants were randomized to receive ten sessions of sham (n = 4) or cingulate tDCS (n = 7) over the course of 2-3 weeks. Treatment assignments were unknown to the participants and the technicians. Neuropsychology and MRI data were collected from four additional study visits to assess treatment effects, including one baseline visit (BL, prior to treatment) and three follow-up visits (FU1, FU2, and FU3, approximately 1 week, 3 weeks, and 3 months after treatment, respectively). Treatment assignment was unblinded after FU3. Participants in the sham group repeated the study with open-label cingulate tDCS during Phase 2. Statistical analysis was limited to data from Phase 1. RESULTS: Compared to sham tDCS, cingulate tDCS led to a decrease in Perseverative Errors in Wisconsin Card Sorting Test (WCST), but not Non-Perseverative Errors, as well as a decrease in the ratio score of Trail Making Test-Part B (TMT-B) to TMT-Part A (TMT-A). Seed-to-voxel analysis with resting state functional MRI data revealed an increase in functional connectivity between the bilateral dACC and a cluster in the right dorsal striatum after cingulate tDCS. There were no differences in self-reported discomfort ratings between sham and cingulate tDCS. CONCLUSIONS: Cingulate tDCS is safe and well-tolerated in PWH, and may have the potential to improve cognitive performance and brain function. A future study with a larger sample is warranted.

A Weak Shadow of Early Life Language Processing Persists in the Right Hemisphere of the Mature Brain.

Studies of language organization show a striking change in cerebral dominance for language over development: We begin life with a left hemisphere (LH) bias for language processing, which is weaker than that in adults and which can be overcome if there is a LH injury. Over development this LH bias becomes stronger and can no longer be reversed. Prior work has shown that this change results from a significant reduction in the magnitude of language activation in right hemisphere (RH) regions in adults compared to children. Here we investigate whether the spatial distribution of language activation, albeit weaker in magnitude, still persists in homotopic RH regions of the mature brain. Children aged 4-13 (n = 39) and young adults (n = 14) completed an auditory sentence comprehension fMRI (functional magnetic resonance imaging) task. To equate neural activity across the hemispheres, we applied fixed cutoffs for the number of active voxels that would be included in each hemisphere for each participant. To evaluate homotopicity, we generated left-right flipped versions of each activation map, calculated spatial overlap between the LH and RH activity in frontal and temporal regions, and tested for mean differences in the spatial overlap values between the age groups. We found that, in children as well as in adults, there was indeed a spatially intact shadow of language activity in the right frontal and temporal regions homotopic to the LH language regions. After a LH stroke in adulthood, recovering early-life activation in these regions might assist in enhancing recovery of language abilities.

Absence of Perilesional Neuroplastic Recruitment in Chronic Poststroke 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. We tested the perilesional plasticity hypothesis using 2 fMRI tasks in 2 groups of patients with previous aphasia diagnosis. METHODS: Two cohorts totaling 82 patients with chronic left-hemisphere stroke with previous 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 was related to aphasia severity independent of lesion size. DISCUSSION: We found 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.

Simulated Attack Reveals How Lesions Affect Network Properties in Poststroke Aphasia.

Aphasia is a prevalent cognitive syndrome caused by stroke. The rarity of premorbid imaging and heterogeneity of lesion obscures the links between the local effects of the lesion, global anatomic network organization, and aphasia symptoms. We applied a simulated attack approach in humans to examine the effects of 39 stroke lesions (16 females) on anatomic network topology by simulating their effects in a control sample of 36 healthy (15 females) brain networks. We focused on measures of global network organization thought to support overall brain function and resilience in the whole brain and within the left hemisphere. After removing lesion volume from the network topology measures and behavioral scores [the Western Aphasia Battery Aphasia Quotient (WAB-AQ), four behavioral factor scores obtained from a neuropsychological battery, and a factor sum], we compared the behavioral variance accounted for by simulated poststroke connectomes to that observed in the randomly permuted data. Global measures of anatomic network topology in the whole brain and left hemisphere accounted for 10% variance or more of the WAB-AQ and the lexical factor score beyond lesion volume and null permutations. Streamline networks provided more reliable point estimates than FA networks. Edge weights and network efficiency were weighted most highly in predicting the WAB-AQ for FA networks. Overall, our results suggest that global network measures provide modest statistical value beyond lesion volume when predicting overall aphasia severity, but less value in predicting specific behaviors. Variability in estimates could be induced by premorbid ability, deafferentation and diaschisis, and neuroplasticity following stroke.SIGNIFICANCE STATEMENT Poststroke, the remaining neuroanatomy maintains cognition and supports recovery. However, studies often use small, cross-sectional samples that cannot fully model the interactions between lesions and other variables that affect networks in stroke. Alternate methods are required to account for these effects. "Simulated attack" models are computational approaches that apply virtual damage to the brain and measure their putative consequences. Using a simulated attack model, we estimated how simulated damage to anatomic networks could account for language performance. Overall, our results reveal that global network measures can provide modest statistical value predicting overall aphasia severity, but less value in predicting specific behaviors. These findings suggest that more theoretically precise network models could be necessary to robustly predict individual outcomes in aphasia.

Plasticity of the language system in children and adults.

The language system is perhaps the most unique feature of the human brain's cognitive architecture. It has long been a quest of cognitive neuroscience to understand the neural components that contribute to the hierarchical pattern processing and advanced rule learning required for language. The most important goal of this research is to understand how language becomes impaired when these neural components malfunction or are lost to stroke, and ultimately how we might recover language abilities under these circumstances. Additionally, understanding how the language system develops and how it can reorganize in the face of brain injury or dysfunction could help us to understand brain plasticity in cognitive networks more broadly. In this chapter we will discuss the earliest features of language organization in infants, and how deviations in typical development can-but in some cases, do not-lead to disordered language. We will then survey findings from adult stroke and aphasia research on the potential for recovering language processing in both the remaining left hemisphere tissue and in the non-dominant right hemisphere. Altogether, we hope to present a clear picture of what is known about the capacity for plastic change in the neurobiology of the human language system.