Elena Rykhlevskaia

Decoding Subject-Driven Cognitive States with Whole-Brain Connectivity Patterns

Decoding specific cognitive states from brain activity constitutes a major goal of neuroscience. Previous studies of brain-state classification have focused largely on decoding brief, discrete events and have required the timing of these events to be known. To date, methods for decoding more continuous and purely subject-driven cognitive states have not been available. Here, we demonstrate that free-streaming subject-driven cognitive states can be decoded using a novel whole-brain functional connectivity analysis. Ninety functional regions of interest (ROIs) were defined across 14 large-scale resting-state brain networks to generate a 3960 cell matrix reflecting whole-brain connectivity. We trained a classifier to identify specific patterns of whole-brain connectivity as subjects rested quietly, remembered the events of their day, subtracted numbers, or (silently) sang lyrics. In a leave-one-out cross-validation, the classifier identified these 4 cognitive states with 84% accuracy. More critically, the classifier achieved 85% accuracy when identifying these states in a second, independent cohort of subjects. Classification accuracy remained high with imaging runs as short as 30-60 s. At all temporal intervals assessed, the 90 functionally defined ROIs outperformed a set of 112 commonly used structural ROIs in classifying cognitive states. This approach should enable decoding a myriad of subject-driven cognitive states from brief imaging data samples.

Dissociable Connectivity within Human Angular Gyrus and Intraparietal Sulcus: Evidence from Functional and Structural Connectivity

The inferior parietal lobule (IPL) of the human brain is a heterogeneous region involved in visuospatial attention, memory, and mathematical cognition. Detailed description of connectivity profiles of subdivisions within the IPL is critical for accurate interpretation of functional neuroimaging studies involving this region. We separately examined functional and structural connectivity of the angular gyrus (AG) and the intraparietal sulcus (IPS) using probabilistic cytoarchitectonic maps. Regions-of-interest (ROIs) included anterior and posterior AG subregions (PGa, PGp) and 3 IPS subregions (hIP2, hIP1, and hIP3). Resting-state functional connectivity analyses showed that PGa was more strongly linked to basal ganglia, ventral premotor areas, and ventrolateral prefrontal cortex, while PGp was more strongly connected with ventromedial prefrontal cortex, posterior cingulate, and hippocampus-regions comprising the default mode network. The anterior-most IPS ROIs, hIP2 and hIP1, were linked with ventral premotor and middle frontal gyrus, while the posterior-most IPS ROI, hIP3, showed connectivity with extrastriate visual areas. In addition, hIP1 was connected with the insula. Tractography using diffusion tensor imaging revealed structural connectivity between most of these functionally connected regions. Our findings provide evidence for functional heterogeneity of cytoarchitectonically defined subdivisions within IPL and offer a novel framework for synthesis and interpretation of the task-related activations and deactivations involving the IPL during cognition.

Neuroanatomical correlates of aging, cardiopulmonary fitness level, and education.

Fitness and education may protect against cognitive impairments in aging. They may also counteract age-related structural changes within the brain. Here we analyzed volumetric differences in cerebrospinal fluid and gray and white matter, along with neuropsychological data, in adults differing in age, fitness, and education. Cognitive performance was correlated with fitness and education. Voxel-based morphometry was used for a whole-brain analysis of structural magnetic resonance images. We found age-related losses in gray and white matter in medial-temporal, parietal, and frontal areas. As in previous work, fitness within the old correlated with preserved gray matter in the same areas. In contrast, higher education predicted preserved white matter in inferior frontal areas. These data suggest that fitness and education may both be predictive of preserved cognitive function in aging through separable effects on brain structure.

Anatomical properties of the arcuate fasciculus predict phonological and reading skills in children

For more than a century, neurologists have hypothesized that the arcuate fasciculus carries signals that are essential for language function; however, the relevance of the pathway for particular behaviors is highly controversial. The primary objective of this study was to use diffusion tensor imaging to examine the relationship between individual variation in the microstructural properties of arcuate fibers and behavioral measures of language and reading skills. A second objective was to use novel fiber-tracking methods to reassess estimates of arcuate lateralization. In a sample of 55 children, we found that measurements of diffusivity in the left arcuate correlate with phonological awareness skills and arcuate volume lateralization correlates with phonological memory and reading skills. Contrary to previous investigations that report the absence of the right arcuate in some subjects, we demonstrate that new techniques can identify the pathway in every individual. Our results provide empirical support for the role of the arcuate fasciculus in the development of reading skills.

Neuroanatomical Correlates of Developmental Dyscalculia: Combined Evidence from Morphometry and Tractography

Poor mathematical abilities adversely affect academic and career opportunities. The neuroanatomical basis of developmental dyscalculia (DD), a specific learning deficit with prevalence rates exceeding 5%, is poorly understood. We used structural MRI and diffusion tensor imaging (DTI) to examine macro- and micro-structural impairments in 7- to 9-year-old children with DD, compared to a group of typically developing (TD) children matched on age, gender, intelligence, reading abilities and working memory capacity. Voxel-based morphometry (VBM) revealed reduced grey matter (GM) bilaterally in superior parietal lobule, intra-parietal sulcus, fusiform gyrus, parahippocampal gyrus and right anterior temporal cortex in children with DD. VBM analysis also showed reduced white matter (WM) volume in right temporal-parietal cortex. DTI revealed reduced fractional anisotropy (FA) in this WM region, pointing to significant right hemisphere micro-structural impairments. Furthermore, FA in this region was correlated with numerical operations but not verbal mathematical reasoning or word reading. Atlas-based tract mapping identified the inferior longitudinal fasciculus, inferior fronto-occipital fasciculus and caudal forceps major as key pathways impaired in DD. DTI tractography suggests that long-range WM projection fibers linking the right fusiform gyrus with temporal-parietal WM are a specific source of vulnerability in DD. Network and classification analysis suggest that DD in children may be characterized by multiple dysfunctional circuits arising from a core WM deficit. Our findings link GM and WM abnormalities in children with DD and they point to macro- and micro-structural abnormalities in right hemisphere temporal-parietal WM, and pathways associated with it, as key neuroanatomical correlates of DD.

Bound pool fractions complement diffusion measures to describe white matter micro and macrostructure

Diffusion imaging and bound pool fraction (BPF) mapping are two quantitative magnetic resonance imaging techniques that measure microstructural features of the white matter of the brain. Diffusion imaging provides a quantitative measure of the diffusivity of water in tissue. BPF mapping is a quantitative magnetization transfer (qMT) technique that estimates the proportion of exchanging protons bound to macromolecules, such as those found in myelin, and is thus a more direct measure of myelin content than diffusion. In this work, we combined BPF estimates of macromolecular content with measurements of diffusivity within human white matter tracts. Within the white matter, the correlation between BPFs and diffusivity measures such as fractional anisotropy and radial diffusivity was modest, suggesting that diffusion tensor imaging and bound pool fractions are complementary techniques. We found that several major tracts have high BPF, suggesting a higher density of myelin in these tracts. We interpret these results in the context of a quantitative tissue model.

COMT genotype affects prefrontal white matter pathways in children and adolescents

Diffusion tensor imaging is widely used to evaluate the development of white matter. Information about how alterations in major neurotransmitter systems, such as the dopamine (DA) system, influence this development in healthy children, however, is lacking. Catechol-O-metyltransferase (COMT) is the major enzyme responsible for DA degradation in prefrontal brain structures, for which there is a corresponding genetic polymorphism (val158met) that confers either a more or less efficient version of this enzyme. The result of this common genetic variation is that children may have more or less available synaptic DA in prefrontal brain regions. In the present study we examined the relation between diffusion properties of frontal white matter structures and the COMT val158met polymorphism in 40 children ages 9-15. We found that the val allele was associated with significantly elevated fractional anisotropy values and reduced axial and radial diffusivities. These results indicate that the development of white matter in healthy children is related to COMT genotype and that alterations in white matter may be related to the differential availability of prefrontal DA. This investigation paves the way for further studies of how common functional variants in the genome might influence the development of brain white matter.

Bilateral brain regions associated with naming in older adults

To determine structural brain correlates of naming abilities in older adults, we tested 24 individuals aged 56-79 on two confrontation-naming tests (the Boston Naming Test (BNT) and the Action Naming Test (ANT)), then collected from these individuals structural Magnetic-Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) data. Overall, several regions showed that greater gray and white matter volume/integrity measures were associated with better task performance. Left peri-Sylvian language regions and their right-hemisphere counterparts, plus left mid-frontal gyrus correlated with accuracy and/or negatively with response time (RT) on the naming tests. Fractional anisotropy maps derived from DTI showed robust positive correlations with ANT accuracy bilaterally in the temporal lobe and in right middle frontal lobe, as well as negative correlations with BNT RT, bilaterally, in the white matter within middle and inferior temporal lobes. We conclude that those older adults with relatively better naming skills can rely on right-hemisphere peri-Sylvian and mid-frontal regions and pathways, in conjunction with left-hemisphere peri-Sylvian and mid-frontal regions, to achieve their success.

Lagged covariance structure models for studying functional connectivity in the brain

Most cognitive processes are supported by large networks of brain regions. To describe the operation of these networks, it is critical to understand how individual areas are functionally connected. Here, we establish a statistical framework for studying effective and functional brain connectivity, using data obtained with a relatively new neuroimaging method, the event-related optical signal (EROS). The novelty of our approach is the use of timing information (in the form of lagged cross-correlations) in interpreting the connections between areas. Interpretation of lagged cross-correlations exploits the combination of spatial and temporal resolution provided by EROS. In this paper, we apply dynamic factor analysis as a method for testing various structural models on the lagged covariance matrices derived from the EROS data. We first illustrate the approach by testing a simple path model of neural activity propagation from area V1 to V3 in a visual stimulation task. We then build more complex structural equation models with latent variables, describing both within-hemisphere integrity, and interactions between the two hemispheres, to interpret data from a second task involving inter-hemispheric competition. The results demonstrate how the integrity of anatomical connections between the two hemispheres explains different patterns of cross-hemispheric interactions. This approach allows for fitting brain imaging data to complex models that capture dynamic cognitive processes as they rapidly evolve over time.

Does white matter matter? spatio-temporal dynamics of task switching in aging

Older adults often encounter difficulties in switching between tasks, perhaps because of age-related decreases in executive function. Executive function may largely depend on connections between brain areas—connections that may become structurally and functionally weaker in aging. Here we investigated functional and structural age-related changes in switching between a spatial and a verbal task. These tasks were chosen because they are expected to differentially use the two hemispheres. Brain measures included anatomical information about anterior corpus callosum size (CC; the major commissure linking the left and right hemisphere), and the event-related optical signal (EROS). Behavioral results indicated that older adults had greater task-switching difficulties, which, however, were largely restricted to switching to the spatial task and to individuals with smaller anterior CCs. The EROS data showed both general switching-related activity in the left middle frontal gyrus (with approximately 300-msec latency) and task-specific activity in the inferior frontal gyrus, lateralized to the left for the switch-to-verbal condition and to the right for the switch-to-spatial condition. This lateralization was most evident in younger adults. In older adults, activity in the switch-to-spatial condition was lateralized to the right hemisphere in individuals with large CC, and to the left in individuals with small CC. These data suggest that (a) task switching may involve both task-general and task-specific processes; and (b) white matter changes may underlie some of the age-related problems in switching. These effects are discussed in terms of the hypothesis that aging involves some degree of cortical disconnection, both functional and anatomical.