Search

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.

Introduction: 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.Methods: 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 N-back task was conducted to measure working memory performance [accuracy and response time(RT)]. T1-weighted structural MRI data (obtained using Siemens 3T 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. Results: Faster gait speed was associated with faster working memory RT in younger adults. Greater cerebellar subregion volumes were associated with faster gait speed and better working memory performance. Faster gait speed was correlated with faster working memory RT through greater volume of cerebellar region VIIIa. Conclusions: The present study suggests faster gait speed is associated with faster RT during working memory tasks in younger individuals. The specific subregion of the cerebellum (VIIIa) may serve as an important neural basis linking 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.

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.

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.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.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.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.

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-minute 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 (ODI(WM)) around the cerebellar peduncle and was negatively associated with widespread cortical and subcortical gray matter neurite density index (NDI(GM)). Lower ODI(WM) of the cerebral peduncle was associated with better fluid cognitive performance, while lower NDI(GM) was associated with better crystallized cognition. Finally, we found that while ODI(WM) partially mediated the relationship between fitness and fluid cognition, NDI(GM) 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.

The domain-specific approach to working memory assumes specialized working memory systems dedicated to maintaining different types of information (e.g. orthographic, phonological, semantic, visuospatial) which serve to support processing in that domain. These storage systems are assumed to be separate from long-term memory representations in each domain and also from attentional and cognitive control processes. This chapter provides an overview of support for this approach drawn mainly from neuropsychological case study and case series approaches, though it also integrates findings from behavioural and imaging studies of healthy individuals that were motivated by the neuropsychological findings or provide confirmation of those findings. The neuropsychological findings not only demonstrate dissociations between working memory in different domains but also provide a rich source of evidence to address the nature of forgetting in working memory, the interactions between working memory and long-term memory, and the role of aspects of working memory in language comprehension and production.

Development of an inclusive scientific community necessitates doing more than simply bringing science to diverse groups of people. Ideally, the sciences evolve through incorporation of diverse backgrounds, experiences, and worldviews. Efforts to promote inclusion of historically underrepresented racial, ethnic, cultural, religious, gender, and socioeconomic groups among science scholars are currently underway. Examination of these efforts yields valuable lessons to inform next steps in engaging diverse audiences with science. The Emory-Tibet Science Initiative may serve as one example of such efforts. The Dalai Lama invited Emory University to develop and teach a curriculum in Western science to Tibetan Buddhist monks and nuns. As the science curriculum has been taught and refined over the past decade, monastic scholars increasingly have taken ownership of the material. As Western scientific ideas and practices take hold in this setting, the experiences of monks and nuns offer unique insights into the process of translation, modes of communication, and long-term impacts of integrating diverse systems of knowledge. Given that the dominant language of science is English, Tibetan interpreters have been essential throughout the implementation of this project. Through the process of translating scientific terms we have considered differences in how words categorize, and therefore how we conceptualize, the world. We have moved toward comprehensive, culturally-responsive communication where scientific language is used as a tool to build and strengthen connections between monastics and their local and global communities. The intertwining of these complementary systems of knowledge iteratively informs translation, modes of communication, and broader impacts in the community.

Most of the current understanding of how we produce written language comes from psycholinguistic and cognitive neuropsychological investigations. More recently, both neuroimaging and lesion-based investigations have provided valuable information not only regarding the neural bases of the cognitive processes of written language production, but also regarding key cognitive processes and representations. This chapter focuses on contributions to current understanding of written word production that come from the study of the brain. Four fundamental issues of cognitive representation and processing in spelling are reviewed: the distinction between orthographic long-term and working-memory; the distinction between lexical and sublexical spelling processes; the relationship between reading and spelling; and the role of abstract letter representations in spelling. It specifically highlights the neural findings that have contributed significantly to current understanding of these issues. In some cases, the neural data provide convergence with behavioral findings; in others, they constitute unique contributions. The work reviewed here exemplifies the role of neurolinguistics evidence in furthering understanding of language processing and representation.

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.

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.

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.

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.

Spelling a word involves the retrieval of information about the word's letters and their order from long-term memory as well as the maintenance and processing of this information by working memory in preparation for serial production by the motor system. While it is known that brain lesions may selectively affect orthographic long-term memory and working memory processes, relatively little is known about the neurotopographic distribution of the substrates that support these cognitive processes, or the lesions that give rise to the distinct forms of dysgraphia that affect these cognitive processes. To examine these issues, this study uses a voxel-based mapping approach to analyse the lesion distribution of 27 individuals with dysgraphia subsequent to stroke, who were identified on the basis of their behavioural profiles alone, as suffering from deficits only affecting either orthographic long-term or working memory, as well as six other individuals with deficits affecting both sets of processes. The findings provide, for the first time, clear evidence of substrates that selectively support orthographic long-term and working memory processes, with orthographic long-term memory deficits centred in either the left posterior inferior frontal region or left ventral temporal cortex, and orthographic working memory deficits primarily arising from lesions of the left parietal cortex centred on the intraparietal sulcus. These findings also contribute to our understanding of the relationship between the neural instantiation of written language processes and spoken language, working memory and other cognitive skills.

In this study we employed a novel technique to examine the neural basis of written spelling by having subjects touch-type single words on an fMRI compatible QWERTY keyboard. Additionally, in the same group of participants we determined if task-related signal changes associated with typed spelling were also co-localized with or separate from those for reading. Of particular interest were the left inferior frontal gyrus, left inferior parietal lobe as well as an area in the left occipitotemporal cortex termed the Visual Word Form Area (VWFA), each of which have been associated with both spelling and reading. Our results revealed that typed spelling was associated with a left hemisphere network of regions which included the inferior frontal gyrus, intraparietal sulcus, inferior temporal/fusiform gyrus, as well as a region in the superior/middle frontal gyrus, near Exner's area. A conjunction analysis of activation associated with spelling and reading revealed a significant overlap in the left inferior frontal gyrus and occipitotemporal cortex. Interestingly, within the occipitotemporal cortex just lateral and superior to the VWFA we identified an area that was selectively associated with spelling, as revealed by a direct comparison of the two tasks. These results demonstrate that typed spelling activates a predominantly left hemisphere network, a subset of which is functionally relevant to both spelling and reading. Further analysis revealed that the left occipitotemporal cortex contains regions with both conjoint and dissociable patterns of activation for spelling and reading.

Previous research has shown that damage to the neural substrates of orthographic processing can lead to functional reorganization during reading (Tsapkini et al., 2011); in this research we ask if the same is true for spelling. To examine the functional reorganization of spelling networks we present a novel three-stage Individual Peak Probability Comparison (IPPC) analysis approach for comparing the activation patterns obtained during fMRI of spelling in a single brain-damaged individual with dysgraphia to those obtained in a set of non-impaired control participants. The first analysis stage characterizes the convergence in activations across non-impaired control participants by applying a technique typically used for characterizing activations across studies: Activation Likelihood Estimate (ALE) (Turkeltaub et al., 2002). This method was used to identify locations that have a high likelihood of yielding activation peaks in the non-impaired participants. The second stage provides a characterization of the degree to which the brain-damaged individual’s activations correspond to the group pattern identified in Stage 1. This involves performing a Mahalanobis distance statistics analysis (Tsapkini et al., 2011) that compares each of a control group’s peak activation locations to the nearest peak generated by the brain-damaged individual. The third stage evaluates the extent to which the brain-damaged individual’s peaks are atypical relative to the range of individual variation among the control participants. This IPPC analysis allows for a quantifiable, statistically sound method for comparing an individual’s activation pattern to the patterns observed in a control group and, thus, provides a valuable tool for identifying functional reorganization in a brain-damaged individual with impaired spelling. Furthermore, this approach can be applied more generally to compare any individual’s activation pattern with that of a set of other individuals.

Producing written words requires “central” cognitive processes (such as orthographic long-term and working memory) as well as more peripheral processes responsible for generating the motor actions needed for producing written words in a variety of formats (handwriting, typing, etc.). In recent years, various functional neuroimaging studies have examined the neural substrates underlying the central and peripheral processes of written word production. This study provides the first quantitative meta-analysis of these studies by applying Activation Likelihood Estimation methods (Turkeltaub et al., 2002). For alphabet languages, we identified 11 studies (with a total of 17 experimental contrasts) that had been designed to isolate central and/or peripheral processes of word spelling (total number of participants = 146). Three ALE meta-analyses were carried out. One involved the complete set of 17 contrasts; two others were applied to subsets of contrasts to distinguish the neural substrates of central from peripheral processes. These analyses identified a network of brain regions reliably associated with the central and peripheral processes of word spelling. Among the many significant results, is the finding that the regions with the greatest correspondence across studies were in the left inferior temporal/fusiform gyri and left inferior frontal gyrus. Furthermore, although the angular gyrus has traditionally been identified as a key site within the written word production network, none of the meta-analyses found it to be a consistent site of activation, identifying instead a region just superior/medial to the left angular gyrus in the left posterior intraparietal sulcus. In general these meta-analyses and the discussion of results provide a valuable foundation upon which future studies that examine the neural basis of written word production can build.

[This corrects the article DOI: 10.3389/fneur.2021.681141.]., (Copyright © 2024 Purcell, Rapp and Martin.)