Biology subjects

Turkeltaub, P. E.

Publications and source records attributed to Turkeltaub, P. E..

10 recordsLinked to original sources

bioRxiv2026

Dispelling the Plateau Assumption: Case-Based Evidence for Language Recovery in Chronic-Post Stroke Aphasia

ObjectiveRecovery from post-stroke aphasia is traditionally thought to plateau within a year after stroke. As such, no studies have characterized long-term recovery using comprehensive behavioral assessment and longitudinal functional MRI. We sought to characterize behavioral and neuroplastic changes over nearly six years in a patient with chronic post-stroke aphasia. MethodsA patient with chronic left hemisphere stroke underwent behavioral assessment and task-based fMRI at 9, 22, 33 and 71 months after stroke. Testing assessed auditory comprehension, semantic and phonological processing, naming, reading, spelling, motor speech, and executive function. Task-related activation during an adaptive semantic matching paradigm was quantified within language and semantic regions of interest. ResultsBehavior improved across multiple language domains. WAB-R Aphasia Quotient increased from 49.2 to 69.2, along with the large gains in word finding, connected speech, reading and spelling, whereas auditory comprehension remained relatively stable. fMRI demonstrated progressively increasing activation within left-hemisphere language regions, reaching normative range by the final assessment, along with increasing activation in semantic/executive regions. DiscussionRecovery of language production abilities can continue for years after stroke, supported by neuroplastic changes in the brain. Neurologists should inform stroke survivors that aphasia recovery can continue indefinitely after stroke.

neuroscience↗

bioRxiv2026

Language remains strongly left-lateralized in older adults: A cross-sectional and longitudinal study

Language is typically supported by the left hemisphere, but the prevalence and stability of language lateralization in older adults remain unclear. Although acquired language disorders disproportionately affect older adults, most studies of language lateralization have focused on younger populations. We examined language lateralization and its relationship with age in a large cohort of healthy older adults. 115 healthy adults (57 F, 58 M; mean age 59.6 years) completed functional MRI during an adaptive semantic decision task. Lateralization indices were calculated using a bootstrap-based laterality index (LI) approach for whole-hemisphere, frontal, and temporal regions. Relationships between age and lateralization were examined using Pearsons and Bayesian correlation analyses. Fifteen participants completed repeat imaging after a mean interval of 44.2 months. Language activation was strongly left-lateralized, with 96% of participants classified as left-lateralized and 3% as right-lateralized. Frontal and temporal LIs were strongly correlated. No significant relationship was observed between age and lateralization, and no significant longitudinal changes in lateralization were observed. Bayesian analyses supported absence of both age-related effects and longitudinal change in lateralization. Language lateralization remains strongly left-lateralized and unchanging in healthy aging. Findings suggest that aging should not be a factor in the incidence and severity of aphasia from lateralized pathology.

neuroscience↗

bioRxiv2026

Simulating the spectrum, not the syndrome: Large scale individualized modeling of oral reading in stroke aphasia

Computational models are a linchpin in our understanding of the neurocognitive basis of reading. These models can simulate idealized profiles of alexia syndromes, but in reality, individuals with alexia present with a wide range of mixed deficits rather than idealized syndromes. To provide a complete cognitive theory of reading, computational models must be able to account for this individual variation. However, this has never been demonstrated. We test oral reading and non-reading phonological and semantic processing in 83 left-hemisphere stroke survivors. We show that individual alexia profiles can be simulated by applying graded phonology and semantic lesions to an artificial neural network model of reading, creating "matched models" that represent individual stroke survivors. The severity of damage to the semantic and phonological layers of the matched models was highly correlated with directly-measured semantic and phonological processing deficits. However, we also identify systematic ways in which the models fail to simulate the reading performance of their matched stroke survivors. Our results support theories of alexia that rely on process-based deficits, demonstrate the feasibility of large-scale individualized modelling of alexia, and suggest ways to further improve the correspondence of models and human reading behavior.

neuroscience↗

bioRxiv2025

Identifying left and right hemispheres using functional connectivity

Many studies have analyzed what organizational features distinguish the left and right hemispheres of the human brain, with differences typically being found in language areas and in fine motor control (i.e., handedness). In this analysis, we test whether supervised learning can categorize ("fingerprint") an unseen hemisphere as right or left based on functional connectivity. Using data from the Human Connectome Project, we find success to be extremely high (accuracies > .90) in models trained on right-handed participants (Edinburgh Handedness Inventory [EHI] > 0) and in models trained on left-handed participants (EHI [≤] 0). In a second analysis, we test whether the same can be done to identify handedness alongside hemisphere left/right sidedness. While individuals hemispheres are less distinct the more left-handed they are, hemiconnectomes cannot be reliably classified as belonging to a left- or right-handed person. Our approach can inform developmental and post-injury work on hemispheric organization and reorganization.

neuroscience↗

bioRxiv2025

Dissecting the sublexical route for reading: Frontal and parietal networks support learned orthography-to-phonology mappings

Oral reading relies on lexical and sublexical processes with distinct neural mechanisms. Damage within the sublexical system causes phonological alexia, a blanket diagnosis describing acquired deficits in reading unfamiliar words. Improving the precision of alexia diagnosis requires understanding the neurocognitive basis of specific reading subprocesses. This study investigated the neural correlates of sublexical reading in 64 adults with chronic left-hemisphere stroke (LHS), focusing on lesions that impair the use of learned orthography-to-phonology (OP) mappings to read new words. Participants read aloud real words and three types of pseudowords varying in the number of plausible OP mappings at the level of the orthographic body: zero mappings (0M), one mapping (1M), and multiple mappings (MM). LHS participants exhibited phonological reading deficits with an exaggerated lexicality effect compared to 71 neurotypical controls. Across both groups, pseudowords with learned OP mappings were read more accurately than those without. Voxelwise and connectome-based lesion-symptom mapping revealed that relative lexical reading deficits were associated with lateral temporal lesions, while sublexical reading deficits were associated with lesions or disconnections of the left inferior frontal (IFG), supramarginal, and pre/postcentral gyri. Applying learned OP mappings relied on anterior IFG and frontoparietal connections, while resolving multiple plausible OP mappings relied on intraparietal connections. These results underscore the role of learned mutigraphemic OP mappings in sublexical reading, and demonstrate that disruptions of different sublexical reading subprocesses result in subtly different deficit patterns. Dissecting the neurocognitive basis of reading subprocesses may improve the precision of alexia diagnosis and point to new treatments.

neuroscience↗

bioRxiv2025

Meaning for reading: The neurocognitive basis of semantic reading impairment after stroke

Diagnosis of alexia has historically focused on syndromes, such as surface alexia, which capture discrete patterns of reading deficits observed in some patients, but do not describe the breadth of reading deficits observed in practice. Aphasia research has recently shifted focus to language process impairments rather than syndromic classifications. A similar shift in focus to reading process impairments may improve our diagnostic approach to alexia. Behavioural evidence suggests that semantic processing influences reading aloud, and that semantic deficits in the context of semantic dementia underlie surface alexia. Because stroke rarely causes loss of semantic knowledge and surface alexia as a syndromic diagnosis is unusual after stroke, semantic reading deficits in stroke alexia have not previously been examined systematically. Semantic reading deficits in stroke may not relate to semantic deficits per se, but rather an inability to use semantics to support reading. Imageability, the degree to which a word brings to mind an image, is one index of semantic influences on reading. High imageability words are read more quickly by healthy persons and more accurately following brain damage. Here, we test if deficits of semantic reading after stroke, as indexed by reduced imageability effects, result from semantic or post-semantic processes. Examining nonverbal semantic processing, semantics-phonology mapping, and semantic control in a sample of 56 left-hemisphere stroke survivors, only semantics-phonology mappings predicted the reading advantage for high imageability words over low imageability words. Support vector regression voxel-based lesion symptom mapping revealed that damage along the superior temporal sulcus and underlying white matter, extending into both the middle and superior temporal gyri, reduced the advantage of high imageability over low imageability words during reading, reflecting an inability to use semantics to support reading. A similar cluster related to impairments in semantics-phonology mapping. The imageability and semantics-phonology mapping results overlapped in the left posterior superior temporal sulcus. Support vector regression connectome lesion symptom mapping revealed white matter disconnections within a broad temporoparietal network important for both phonological and semantic processing were associated with a reduction of the imageability advantage during reading. These results demonstrate that, irrespective of syndromic classification, semantic reading deficits occur in left-hemisphere stroke survivors as a result of impaired integration of semantic and phonological representations, and that the left posterior superior temporal sulcus underlies this process. Our results clarify the neurobiology of reading aloud, and support the existence of a post-semantic impairment of semantic reading in left-hemisphere stroke survivors.

neuroscience↗

bioRxiv2021

Simulated attack reveals how lesions affect network properties in post-stroke aphasia

Aphasia is one of the most prevalent cognitive syndromes caused by stroke. The rarity of premorbid imaging and heterogeneity of lesion size and extent obfuscates the links between the local effects of the lesion, global anatomical network organization, and aphasia symptoms. We applied a simulated attack approach to examine the effects of 39 stroke lesions on network topology by simulating their effects in a control sample of 36 healthy 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 post-stroke connectomes to that observed in the randomly permuted data. Overall, global measures of 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 can provide modest statistical value 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.

neuroscience↗

bioRxiv2021

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 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.

neuroscience↗

bioRxiv2021

Testing the perilesional neuroplastic recruitment hypothesis in aphasia

ObjectiveA 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. MethodsTwo 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. ResultsStroke 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. InterpretationWe 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 AcceptedO_ST_ABSTwitter handleC_ST_ABS@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.

neuroscience↗

bioRxiv2018

Precision inhibitory stimulation of individual-specific cortical hubs slows information processing in humans

Non-invasive brain stimulation (NIBS) is a promising treatment for psychiatric and neurologic conditions, but outcomes are variable across treated individuals. This variability may be due in part to uncertainty in the selection of the stimulation site - a challenge complicated further by the variable organization of individual human brains. In principle, precise targeting of individual-specific brain areas serving outsized roles in cognition could improve the efficacy of NIBS. Network theory predicts that the importance of a node in network can be inferred from its connections; as such, we hypothesized that targeting individual-specific \"hub\" brain areas with NIBS would impact cognition more than non-hub brain areas. We first demonstrate that the spatial positioning of hubs is variable across individuals, but highly-reproducible when mapped with sufficient per-individual rsfMRI data. We then tested our hypothesis in healthy individuals using a prospective, within-subject, double-blind design. We found that inhibiting a hub with NIBS disrupted information processing during working-memory to a greater extent than inhibiting a non-hub area of the same gyrus. Furthermore, inhibition of hubs linking specific control networks and sensorimotor systems was retrospectively found to be most impactful. Based on these findings, we propose that precise mapping of individual-specific brain network features could inform future interventions in patients.\n\nSIGNIFICANCE STATEMENTThe network organization of every persons brain is different, but non-invasive brain stimulation (NIBS) interventions do not take this variation into account. Here we demonstrate that the spatial positions of brain areas theoretically serving important roles in cognition, called hubs, differs across individual humans, but are stable within an individual upon repeated neuroimaging. We found that administering NIBS to these individual-specific hub brain areas impacted cognition more than stimulation of non-hub areas. This finding indicates that future NIBS interventions can target individual-specific, but cognitively-relevant features of human brains.

neuroscience↗