Acute Exercise Improves Large-Scale Brain Network Segregation in Healthy Older Adults.

Introduction: Age-related cognitive decline and mental health problems are accompanied by changes in resting-state functional connectivity (rsFC) indices, such as reduced brain network segregation. Meanwhile, exercise can improve cognition, mood, and neural network function in older adults. Studies on effects of exercise on rsFC outcomes in older adults have chiefly focused on changes after exercise training and suggest improved network segregation through enhanced within-network connectivity. However, effects of acute exercise on rsFC measures of neural network integrity in older adults, which presumably underlie changes observed after exercise training, have received less attention. In this study, we hypothesized that acute exercise in older adults would improve functional segregation of major cognition and affect-related brain networks. Methods: To test this, we analyzed rsFC data from 37 healthy and physically active older adults after they completed 30 min of moderate-to-vigorous intensity cycling and after they completed a seated rest control condition. Conditions were performed in a counterbalanced order across separate days in a within-subject crossover design. We considered large-scale brain networks associated with cognition and affect, including the frontoparietal network (FPN), salience network (SAL), default mode network (DMN), and affect-reward network (ARN). Results: We observed that after acute exercise, there was greater segregation between SAL and DMN, as well as greater segregation between SAL and ARN. Conclusion: These findings indicate that acute exercise in active older adults alters rsFC measures in key cognition and affect-related networks in a manner that opposes age-related dedifferentiation of neural networks that may be detrimental to cognition and mental health.

An inclusive multivariate approach to neural localization of language components.

To determine how language is implemented in the brain, it is important to know which brain areas are primarily engaged in language processing and which are not. Existing protocols for localizing language are typically univariate, treating each small unit of brain volume as independent. One prominent example that focuses on the overall language network in functional magnetic resonance imaging (fMRI) uses a contrast between neural responses to sentences and sets of pseudowords (pronounceable nonwords). This contrast reliably activates peri-sylvian language areas but is less sensitive to extra-sylvian areas that are also known to support aspects of language such as word meanings (semantics). In this study, we assess areas where a multivariate, pattern-based approach shows high reproducibility across multiple measurements and participants, identifying these areas as multivariate regions of interest (mROI). We then perform a representational similarity analysis (RSA) of an fMRI dataset where participants made familiarity judgments on written words. We also compare those results to univariate regions of interest (uROI) taken from previous sentences > pseudowords contrasts. RSA with word stimuli defined in terms of their semantic distance showed greater correspondence with neural patterns in mROI than uROI. This was confirmed in two independent datasets, one involving single-word recognition, and the other focused on the meaning of noun-noun phrases by contrasting meaningful phrases > pseudowords. In all cases, areas of spatial overlap between mROI and uROI showed the greatest neural association. This suggests that ROIs defined in terms of multivariate reproducibility can help localize components of language such as semantics. The multivariate approach can also be extended to focus on other aspects of language such as phonology, and can be used along with the univariate approach for inclusively mapping language cortex.

The English Sublexical Toolkit: Methods for indexing sound-spelling consistency.

This work introduces the English Sublexical Toolkit, a suite of tools that utilizes an experience-dependent learning framework of sublexical knowledge to extract regularities from the English lexicon. The Toolkit quantifies the empirical regularity of sublexical units in both the reading and spelling directions (i.e., grapheme-to-phoneme and phoneme-to-grapheme) and at multiple grain sizes (i.e., phoneme/grapheme and onset/rime unit size). It can extract multiple experience-dependent regularity indices for words or pseudowords, including both frequency indices (e.g., grapheme frequency) and conditional probability indices (e.g., grapheme-to-phoneme probability). These tools provide (1) superior estimates of the regularities that better reflect the complexity of the sublexical system relative to previously published indices and (2) completely novel indices of sublexical units such as phonographeme frequency (i.e., combined units of individual phonemes and graphemes that are independent of processing direction). We demonstrate that measures from the toolkit explain significant amounts of variance in empirical data (naming of real words and lexical decision), and either outperform or are comparable to the best available consistency measures. The flexibility of the toolkit is further demonstrated by its ability to readily index the probability of different pseudowords pronunciations, and we report that the measures account for the majority of variance in these empirically observed probabilities. Overall, this work provides a framework and resources that can be flexibly used to identify optimal corpus-based consistency measures that help explain reading/spelling behaviors for real and pseudowords.

Corrigendum: Distinct neural substrates support phonological and orthographic working memory: implications for theories of working memory.

[This corrects the article DOI: 10.3389/fneur.2021.681141.].

Hippocampal functional connectivity mediates the association between cardiorespiratory fitness and cognitive function in healthy young adults.

OBJECTIVE: Higher cardiorespiratory fitness (CRF) induces neuroprotective effects in the hippocampus, a key brain region for memory and learning. We investigated the association between CRF and functional connectivity (FC) of the hippocampus in healthy young adults. We also examined the association between hippocampal FC and neurocognitive function. Lastly, we tested whether hippocampal FC mediates the association between 2-Min Walk Test (2MWT) and neurocognitive function. METHODS: 913 young adults (28.7 ± 3.7 years) from the Human Connectome Project were included in the analyses. The 2MWT performance result was used as a proxy for cardiovascular endurance. Fluid and crystalized composite neurocognitive scores were used to assess cognition. Resting-state functional MRI data were processed to measure hippocampal FC. Linear regression was used to examine the association between 2MWT, hippocampal FC, and neurocognitive outcomes after controlling for age, sex, years of education, body mass index, systolic blood pressure, and gait speed. RESULTS: Better 2MWT performance was associated with greater FC between the anterior hippocampus and right posterior cingulate and left middle temporal gyrus. No associations between 2MWT and posterior hippocampal FC, whole hippocampal FC, and caudate FC (control region) were observed. Greater anterior hippocampal FC was associated with better crystalized cognition scores. Lastly, greater FC between the anterior hippocampus and right posterior cingulate mediated the association between better 2MWT scores and higher crystalized cognition scores. CONCLUSIONS: Anterior hippocampal FC may be one underlying neurophysiological mechanism that promotes the association between 2MWT performance and crystalized composite cognitive function in healthy young adults.

Increased neural differentiation after a single session of aerobic exercise in older adults.

Aging is associated with decreased cognitive function. One theory posits that this decline is in part due to multiple neural systems becoming dedifferentiated in older adults. Exercise is known to improve cognition in older adults, even after only a single session. We hypothesized that one mechanism of improvement is a redifferentiation of neural systems. We used a within-participant, cross-over design involving 2 sessions: either 30 minutes of aerobic exercise or 30 minutes of seated rest (n = 32; ages 55-81 years). Both functional Magnetic Resonance Imaging (fMRI) and Stroop performance were acquired soon after exercise and rest. We quantified neural differentiation via general heterogeneity regression. There were 3 prominent findings following the exercise. First, participants were better at reducing Stroop interference. Second, while there was greater neural differentiation within the hippocampal formation and cerebellum, there was lower neural differentiation within frontal cortices. Third, this greater neural differentiation in the cerebellum and temporal lobe was more pronounced in the older ages. These data suggest that exercise can induce greater neural differentiation in healthy aging.

Emotional processing and positive affect after acute exercise in healthy older adults.

The well-elucidated improvement of mood immediately after exercise in older adults presumably involves adaptations in emotion-processing brain networks. However, little is known about effects of acute exercise on appetitive and aversive emotion-related network recruitment in older adults. The purpose of this study was to determine the effect of acute exercise, compared to a seated rest control condition, on pleasant and unpleasant emotion-related regional activation in healthy older adults. Functional MRI data were acquired from 32 active older adults during blocked presentations of pleasant, neutral and unpleasant images from the International Affective Pictures System. fMRI data were collected after participants completed 30 min of moderate to vigorous intensity cycling or seated rest, performed in a counterbalanced order across separate days in a within-subject design. The findings suggest three ways that emotional processing in the brain may be different immediately after exercise (relative to immediately after rest): First, reduced demands on emotional regulation during pleasant emotional processing as indicated by lower precuneus activation for pleasant stimuli; second, reduced processing of negative emotional stimuli in visual association areas as indicated by lower activation for unpleasant stimuli in the bilateral fusiform and ITG; third, an increased recruitment in activation associated with regulating/inhibiting unpleasant emotional processing in the bilateral medial superior frontal gyrus (dorsomedial prefrontal cortex), angular gyri, supramarginal gyri, left cerebellar crus I/II and a portion of right dorsolateral prefrontal cortex. Overall, these findings support that acute exercise in active older adults alters activation in key emotional processing and regulating brain regions.

Basal forebrain functional connectivity as a mediator of associations between cardiorespiratory fitness and cognition in healthy older women.

Age-related cholinergic dysfunction within the basal forebrain (BF) is one of the key hallmarks for age-related cognitive decline. Given that higher cardiorespiratory fitness (CRF) induces neuroprotective effects that may differ by sex, we investigated the moderating effects of sex on the associations between CRF, BF cholinergic function, and cognitive function in older adults. 176 older adults (68.5 years) were included from the Nathan Kline Institute Rockland Sample. Functional connectivity (rsFC) of the BF subregions including the medial septal nucleus/diagonal band of Broca (MS/DB) and nucleus basalis of Meynert (NBM) were computed from resting-sate functional MRI. Modified Astrand-Ryhming submaximal cycle ergometer protocol was used to estimate CRF. Trail making task and inhibition performance during the color word interference test from the Delis-Kaplan Executive Function System and Rey Auditory Verbal Learning Test were used to examine cognitive function. Linear regression models were used to assess the associations between CRF, BF rsFC, and cognitive performance after controlling for age, sex, and years of education. Subsequently, we measured the associations between the variables in men and women separately to investigate the sex differences. There was an association between higher CRF and greater rsFC between the NBM and right middle frontal gyrus in older men and women. There were significant associations between CRF, NBM rsFC, and trail making task number-letter switching performance only in women. In women, greater NBM rsFC mediated the association between higher CRF and better trail making task number-letter switching performance. These findings provide evidence that greater NBM rsFC, particularly in older women, may be an underlying neural mechanism for the relationship between higher CRF and better executive function.

Correspondence between cognitive and neural representations for phonology, orthography, and semantics in supramarginal compared to angular gyrus.

The angular and supramarginal gyri (AG and SMG) together constitute the inferior parietal lobule (IPL) and have been associated with cognitive functions that support reading. How those functions are distributed across the AG and SMG is a matter of debate, the resolution of which is hampered by inconsistencies across stereotactic atlases provided by the major brain image analysis software packages. Schematic results from automated meta-analyses suggest primarily semantic (word meaning) processing in the left AG, with more spatial overlap among phonological (auditory word form), orthographic (visual word form), and semantic processing in the left SMG. To systematically test for correspondence between patterns of neural activation and phonological, orthographic, and semantic representations, we re-analyze a functional magnetic resonance imaging data set of participants reading aloud 465 words. Using representational similarity analysis, we test the hypothesis that within cytoarchitecture-defined subregions of the IPL, phonological representations are primarily associated with the SMG, while semantic representations are primarily associated with the AG. To the extent that orthographic representations can be de-correlated from phonological representations, they will be associated with cortex peripheral to the IPL, such as the intraparietal sulcus. Results largely confirmed these hypotheses, with some nuanced exceptions, which we discuss in terms of neurally inspired computational cognitive models of reading that learn mappings among distributed representations for orthography, phonology, and semantics. De-correlating constituent representations making up complex cognitive processes, such as reading, by careful selection of stimuli, representational formats, and analysis techniques, are promising approaches for bringing additional clarity to brain structure-function relationships.

Pseudoword spelling: insights into sublexical representations and lexical interactions.

ABSTRACTIn this work we introduce a new tool for measuring English spelling-sound consistency, the PG Toolkit, which we use to conduct detailed analyses of pseudoword spellings that provide new insights into the nature of sublexical and lexical representations. There are several key findings: first, sound-spelling consistency measured at two different "grain sizes", phonographeme and onset/rime, each explained unique variance in pseudoword spelling. Second, lexical skill was more related to pseudoword accuracy at the onset/rime level than at the phonographeme level, and individuals who chose more consistent mappings to spell pseudowords tended to have better lexical skill. Finally, no unique contribution of consistency in the reading direction ("feedback") was found after controlling for consistency in the spelling direction. Taken together, the results validate the various measures provided by the PG Toolkit and establish new evidence that supports an interpretation of sublexical processes as operations over hierarchically-structured representations.

Neurite dispersion and density mediates the relationship between cardiorespiratory fitness and cognition in healthy younger adults.

Growing evidence suggests physical activity and cardiorespiratory fitness are associated with better cognition across the lifespan. However, the neurobiological underpinnings relating fitness and cognition remain unclear, particularly in healthy younger adults. Using a well-established and popular multi-compartment diffusion modeling approach, called Neurite Orientation and Dispersion and Density Imaging (NODDI), we investigated the relationship between physical fitness (measured via a 2-min walk test), cognition (fluid and crystallized), and gray and white matter microstructure, in a large sample (n = 816) of healthy younger adults (ages 22-35 years) from the human connectome project (HCP). Concurrent with previous literature, we found that fitness was positively associated with both fluid and crystallized cognition. Furthermore, we found that physical fitness was negatively associated with white matter orientation dispersion index (ODIWM) around the cerebellar peduncle and was negatively associated with widespread cortical and subcortical gray matter neurite density index (NDIGM). Lower ODIWM of the cerebral peduncle was associated with better fluid cognitive performance, while lower NDIGM was associated with better crystallized cognition. Finally, we found that while ODIWM partially mediated the relationship between fitness and fluid cognition, NDIGM partially mediated the relationship between fitness and crystallized cognition. This study is the first to explore the relationship between physical fitness and white and gray matter microstructure measures using NODDI. Our findings suggest that in addition to improved cognitive performance, higher physical fitness may be associated with lower white matter tract dispersion and lower neurite density in the cortical and subcortical gray matter of healthy younger adults.

Differential associations of regional cerebellar volume with gait speed and working memory.

The relationship between gait speed and working memory is well-understood in older adults. However, it remains to be determined whether this relationship also exists in younger adults; and there is little known regarding the possible neural mechanism underlying the association between gait speed and working memory. The aims of this study are to determine if there is: (1) an association between gait speed and working memory performance; and (2) a mediating role of cerebellar subregion volume in the correlation between gait speed and working memory in healthy younger adults. 1054 younger adults (28.7 ± 3.6 years) from the Human Connectome Project were included in the analyses. A four-meter gait test was used to assess gait speed. The 2-back task was used to measure working memory performance [accuracy and response time (RT)]. T1-weighted structural MRI data (obtained using Siemens 3 T MRI scanner) was used to assess cerebellar subregion volumes. Linear regression and mediation analysis were used to examine the relationships between the variables after controlling for age, sex, and education. There was no association between gait speed and 2-back working memory performance in younger adults. Greater Crus I and whole cerebellar volumes were associated with better 2-back working memory accuracy. Greater VIIIa volume was associated with faster gait speed. Greater Crus 1 and VIIIa volumes were also associated with higher fluid cognition. The present study suggests that specific subregions of the cerebellar volumes are distinctively associated with gait speed and working memory performance in healthy younger adults.

Distinct Neural Substrates Support Phonological and Orthographic Working Memory: Implications for Theories of Working Memory.

Prior behavioral and neuroimaging evidence supports a separation between working memory capacities in the phonological and orthographic domains. Although these data indicate distinct buffers for orthographic and phonological information, prior neural evidence does indicate that nearby left inferior parietal regions support both of these working memory capacities. Given that no study has directly compared their neural substrates based on data from the same individuals, it is possible that there is a common left inferior parietal region shared by both working memory capacities. In fact, those endorsing an embedded processes account of working memory might suggest that parietal involvement reflects a domain-general attentional system that directs attention to long-term memory representations in the two domains, implying that the same neural region supports the two capacities. Thus, in this work, a multivariate lesion-symptom mapping approach was used to assess the neural basis of phonological and orthographic working memory using behavioral and lesion data from the same set of 37 individuals. The results showed a separation of the neural substrates, with regions in the angular gyrus supporting orthographic working memory and with regions primarily in the supramarginal gyrus supporting phonological working memory. The results thus argue against the parietal involvement as supporting a domain-general attentional mechanism and support a domain-specific buffer account of working memory.

Microstructural Plasticity in the Hippocampus of Healthy Older Adults after Acute Exercise.

INTRODUCTION: The hippocampus experiences structural and functional decline with age and is a critical region for memory and many cognitive processes. Exercise is beneficial for the aging brain and shows preferential benefits for hippocampal volume, activation, and memory-related cognitive processes. However, research thus far has primarily focused on the effects of exercise on long-term volumetric changes in the hippocampus using structural magnetic resonance imaging. Critically, microstructural alterations within the hippocampus over short time intervals are associated with neuroplasticity and cognitive changes that do not alter its volume but are still functionally relevant. However, it is not yet known if microstructural neuroplasticity occurs in the hippocampus in response to a single session of exercise. METHODS: We used a within-subject design to determine if a 30-min bout of moderate-intensity aerobic exercise altered bilateral hippocampal diffusion tensor imaging measures in healthy older adults (n = 30) compared with a seated rest control condition. RESULTS: Significantly lower fractional anisotropy and higher mean diffusivity were found after exercise relative to seated rest within the bilateral hippocampus, and this effect was driven by higher radial diffusivity. No significant differences in axial diffusivity were observed. CONCLUSIONS: These findings suggest that a single exercise session can lead to microstructural alterations in the hippocampus of healthy older adults. These differences may be associated with changes in the extracellular space and glial, synaptic, and dendritic processes within the hippocampus. Repeated microstructural alterations resulting from acute bouts of exercise may accumulate and precede larger volumetric and functional improvements in the hippocampus.

Re-learning to be different: Increased neural differentiation supports post-stroke language recovery.

Identifying the neural changes that support recovery of cognitive functions after a brain lesion is important to advance our understanding of human neuroplasticity, which, in turn, forms the basis for the development of effective treatments. To date, the preponderance of neuroimaging studies has focused on localizing changes in average brain activity associated with functional recovery. Here, we took a novel approach by evaluating whether cognitive recovery in chronic stroke is related to increases in the differentiation of local neural response patterns. This approach is supported by research indicating that, in the intact brain, local neural representations become more differentiated (dissimilar) with learning (Glezer et al., 2015). We acquired fMRI data before and after 21 individuals received approximately 12 weeks of behavioral treatment for written language impairment due to a left-hemisphere stroke. We used Local-Heterogeneity Regression Analysis (Purcell and Rapp, 2018) to measure local neural response differentiation associated with written language processing, assuming that greater heterogeneity in the pattern of activity across adjacent neural areas indicates more well-differentiated neural representations. First, we observed pre to post-treatment increases in local neural differentiation (Local-Hreg) in the ventral occipital-temporal cortex of the left hemisphere. Second, we found that, in this region, higher local neural response differentiation prior to treatment was associated with less severe written language impairment, and that it also predicted greater future responsiveness to treatment. Third, we observed that changes in neural differentiation were systematically related to performance changes for trained and untrained items. Fourth, we did not observe these brain-behavior relationships for mean BOLD responses, only for Local-Hreg. Thus, this is the first investigation to quantify changes in local neural differentiation in the recovery of a cognitive function and the first to demonstrate the clear behavioral relevance of these changes. We conclude that the findings provide strong support for the novel hypothesis that the local re-differentiation of neural representations can play a significant role in functional recovery after brain lesion.

High-level Integrative Networks: A Resting-state fMRI Investigation of Reading and Spelling.

Orthographic processing skills (reading and spelling) are evolutionarily recent and mastered late in development, providing an opportunity to investigate how the properties of the neural networks supporting skills of this type compare to those supporting evolutionarily older, well-established "reference" networks. Although there has been extensive research using task-based fMRI to study the neural substrates of reading, there has been very little using resting-state fMRI to examine the properties of orthographic networks. In this investigation using resting-state fMRI, we compare the within-network and across-network coherence properties of reading and spelling networks directly to these properties of reference networks, and we also compare the network properties of the key node of the orthographic networks-the visual word form area-to those of the other nodes of the orthographic and reference networks. Consistent with previous results, we find that orthographic processing networks do not exhibit certain basic network coherence properties displayed by other networks. However, we identify novel distinctive properties of the orthographic processing networks and establish that the visual word form area has unusually high levels of connectivity with a broad range of brain areas. These characteristics form the basis of our proposal that orthographic networks represent a class of "high-level integrative networks" with distinctive properties that allow them to recruit and integrate multiple, lower level processes.

Local response heterogeneity indexes experience-based neural differentiation in reading.

The ability to read requires learning letter-string representations whose neural codes would be expected to vary depending on the amount of experience that an individual has with reading them. Motivated by sparse coding theories (e.g., Rolls and Tovee, 1995; Olshausen and Field, 1996), recent work has demonstrated that better-learned relative to less well-learned neural representations are associated with more strongly differentiated, locally heterogeneous blood oxygenation level dependent (BOLD) responses (e.g., Jiang et al., 2013). Here we report a novel analysis method we call local heterogeneity regression (Local-Hreg) that quantifies the cross-voxel heterogeneity of BOLD responses, thereby providing a sensitive and methodologically flexible method for quantifying the local neural differentiation of neural representations. In a study of literate adults, we applied Local-Hreg to fMRI data obtained when participants read letter strings that varied in their frequency of occurrence in the written language. Consistent with previous research identifying the left ventral occipitotemporal cortex (vOTC) as a key site for orthographic representation in reading and spelling, we found that the cross-voxel heterogeneity of neural responses in this region varies according to the frequency with which the written letter strings have been experienced. This work provides a novel approach for examining the local differentiation of neural representations, and demonstrates that well-learned words have greater representational differentiation than less well-learned or unfamiliar words.

Recovery of orthographic processing after stroke: A longitudinal fMRI study.

An intact orthographic processing system is critical for normal reading and spelling. Here we investigate the neural changes associated with impairment and subsequent recovery of the orthographic lexical processing system in an individual with an ischemic left posterior cerebral artery (PCA) stroke. This work describes a longitudinal case study of a patient, whose initials are MMY, with impairments in orthographic lexical processing for reading and spelling at stroke onset, and who recovered these skills within 1 year post stroke. We tested the hypothesis that this acute impairment to reading and spelling would be associated with a selective loss of neural activation in the left fusiform gyrus (FG), and that subsequent recovery would be associated with a gain of neural activation in this region. MMY's case provided a unique opportunity to assess the selectivity of neural changes because she demonstrated a behavioral recovery of naming as well; i.e., if there is neural recovery for reading and spelling, but not naming, then these neural changes are selective to the recovery of orthographic processing. To test our hypothesis, we examined longitudinal behavioral and functional magnetic resonance imaging (fMRI) data of reading, spelling, and visual object naming acquired acutely, 3 weeks, 5 months, and one year post stroke. In confirmation of our hypothesis, the loss and subsequent gain of orthographic lexical processing was associated with up-regulation of neural activation in areas previously associated with orthographic lexical processing: i.e., the left mid-FG and inferior frontal junction (IFJ). Furthermore, these neural changes were found to be selective to orthographic processing, as they were observed for reading and spelling, but not for visual object naming within the left mid-FG. This work shows that left PCA stroke can temporarily and selectively disrupt the orthographic lexical processing system, not only in the posterior region adjacent to the stroke, but also in relatively distant frontal orthographic processing regions.

Shared orthographic neuronal representations for spelling and reading.

A central question in the study of the neural basis of written language is whether reading and spelling utilize shared orthographic representations. While recent studies employing fMRI to test this question report that the left inferior frontal gyrus (IFG) and ventral occipitotemporal cortex (vOTC) are active during both spelling and reading in the same subjects (Purcell et al., 2011a; Rapp and Lipka, 2011), the spatial resolution of fMRI limits the interpretation of these findings. Specifically, it is unknown if the neurons which encode orthography for reading are also involved in spelling of the same words. Here we address this question by employing an event-related functional magnetic resonance imaging-adaptation (fMRI-A) paradigm designed to examine shared orthographic representations across spelling and reading. First, we identified areas that independently showed adaptation to reading, and adaptation to spelling. Then we identified spatial convergence for these two separate maps via a conjunction analysis. Consistent with previous studies (Purcell et al., 2011a; Rapp and Lipka, 2011), this analysis revealed the left dorsal IFG, vOTC and supplementary motor area. To further validate these observations, we then interrogated these regions using an across-task adaptation technique, and found adaptation across reading and spelling in the left dorsal IFG (BA 44/9). Our final analysis focused specifically on the Visual Word Form Area (VWFA) in the vOTC, whose variability in location among subjects requires the use of subject-specific identification mechanisms (Glezer and Riesenhuber, 2013). Using a functional localizer for reading, we defined the VWFA in each subject, and found adaptation effects for both within the spelling and reading conditions, respectively, as well as across spelling and reading. Because none of these effects were observed during a phonological/semantic control condition, we conclude that the left dorsal IFG and VWFA are involved in accessing the same orthography-specific representations for spelling and reading.

Imaging network level language recovery after left PCA stroke.

PURPOSE: The neural mechanisms that support aphasia recovery are not yet fully understood. Our goal was to evaluate longitudinal changes in naming recovery in participants with posterior cerebral artery (PCA) stroke using a case-by-case analysis. METHODS: Using task based and resting state functional magnetic resonance imaging (fMRI) and detailed language testing, we longitudinally studied the recovery of the naming network in four participants with PCA stroke with naming deficits at the acute (0 week), sub acute (3-5 weeks), and chronic time point (5-7 months) post stroke. Behavioral and imaging analyses (task related and resting state functional connectivity) were carried out to elucidate longitudinal changes in naming recovery. RESULTS: Behavioral and imaging analysis revealed that an improvement in naming accuracy from the acute to the chronic stage was reflected by increased connectivity within and between left and right hemisphere "language" regions. One participant who had persistent moderate naming deficit showed weak and decreasing connectivity longitudinally within and between left and right hemisphere language regions. CONCLUSIONS: These findings emphasize a network view of aphasia recovery, and show that the degree of inter- and intra- hemispheric balance between the language-specific regions is necessary for optimal recovery of naming, at least in participants with PCA stroke.