David E. Osher

Tracking the Roots of Reading Ability: White Matter Volume and Integrity Correlate with Phonological Awareness in Prereading and Early-Reading Kindergarten Children

Developmental dyslexia, an unexplained difficulty in learning to read, has been associated with alterations in white matter organization as measured by diffusion-weighted imaging. It is unknown, however, whether these differences in structural connectivity are related to the cause of dyslexia or if they are consequences of reading difficulty (e.g., less reading experience or compensatory brain organization). Here, in 40 kindergartners who had received little or no reading instruction, we examined the relation between behavioral predictors of dyslexia and white matter organization in left arcuate fasciculus, inferior longitudinal fasciculus, and the parietal portion of the superior longitudinal fasciculus using probabilistic tractography. Higher composite phonological awareness scores were significantly and positively correlated with the volume of the arcuate fasciculus, but not with other tracts. Two other behavioral predictors of dyslexia, rapid naming and letter knowledge, did not correlate with volumes or diffusion values in these tracts. The volume and fractional anisotropy of the left arcuate showed a particularly strong positive correlation with a phoneme blending test. Whole-brain regressions of behavioral scores with diffusion measures confirmed the unique relation between phonological awareness and the left arcuate. These findings indicate that the left arcuate fasciculus, which connects anterior and posterior language regions of the human brain and which has been previously associated with reading ability in older individuals, is already smaller and has less integrity in kindergartners who are at risk for dyslexia because of poor phonological awareness. These findings suggest a structural basis of behavioral risk for dyslexia that predates reading instruction.

Structural Connectivity Fingerprints Predict Cortical Selectivity for Multiple Visual Categories across Cortex

A fundamental and largely unanswered question in neuroscience is whether extrinsic connectivity and function are closely related at a fine spatial grain across the human brain. Using a novel approach, we found that the anatomical connectivity of individual gray-matter voxels (determined via diffusion-weighted imaging) alone can predict functional magnetic resonance imaging (fMRI) responses to 4 visual categories (faces, objects, scenes, and bodies) in individual subjects, thus accounting for both functional differentiation across the cortex and individual variation therein. Furthermore, this approach identified the particular anatomical links between voxels that most strongly predict, and therefore plausibly define, the neural networks underlying specific functions. These results provide the strongest evidence to date for a precise and fine-grained relationship between connectivity and function in the human brain, raise the possibility that early-developing connectivity patterns may determine later functional organization, and offer a method for predicting fine-grained functional organization in populations who cannot be functionally scanned.

Functional Evidence for a Cerebellar Node of the Dorsal Attention Network

The “dorsal attention network” or “frontoparietal network” refers to a network of cortical regions that support sustained attention and working memory. Recent work has demonstrated that cortical nodes of the dorsal attention network possess intrinsic functional connections with a region in ventral cerebellum, in the vicinity of lobules VII/VIII. Here, we performed a series of task-based and resting-state fMRI experiments to investigate cerebellar participation in the dorsal attention network in humans. We observed that visual working memory and visual attention tasks robustly recruit cerebellar lobules VIIb and VIIIa, in addition to canonical cortical dorsal attention network regions. Across the cerebellum, resting-state functional connectivity with the cortical dorsal attention network strongly predicted the level of activation produced by attention and working memory tasks. Critically, cerebellar voxels that were most strongly connected with the dorsal attention network selectively exhibited load-dependent activity, a hallmark of the neural structures that support visual working memory. Finally, we examined intrinsic functional connectivity between task-responsive portions of cerebellar lobules VIIb/VIIIa and cortex. Cerebellum-to-cortex functional connectivity strongly predicted the pattern of cortical activation during task performance. Moreover, resting-state connectivity patterns revealed that cerebellar lobules VIIb/VIIIa group with cortical nodes of the dorsal attention network. This evidence leads us to conclude that the conceptualization of the dorsal attention network should be expanded to include cerebellar lobules VIIb/VIIIa. SIGNIFICANCE STATEMENT The functional participation of cerebellar structures in nonmotor cortical networks remains poorly understood and is highly understudied, despite the fact that the cerebellum possesses many more neurons than the cerebral cortex. Although visual attention paradigms have been reported to activate cerebellum, many researchers have largely dismissed the possibility of a cerebellar contribution to attention in favor of a motor explanation, namely, eye movements. The present study demonstrates that a cerebellar subdivision (mainly lobules VIIb/VIIIa), which exhibits strong intrinsic functional connectivity with the cortical dorsal attention network, also closely mirrors a myriad of cortical dorsal attention network responses to visual attention and working memory tasks. This evidence strongly supports a reconceptualization of the dorsal attention network to include cerebellar lobules VIIb/VIIIa.

Structural and functional connectivity of visual and auditory attentional networks: insights from the Human Connectome Project

Recent work in our laboratory has suggested that human caudal lateral frontal cortex contains four interleaved regions in each hemisphere that exhibit strong sensory-specific biases in attention tasks (Michalka et al, 2014). Two visually-biased attention regions, superior and inferior pre-central sulcus (sPCS, iPCS), anatomically alternate with two auditory-biased attention regions, caudal inferior frontal sulcus (cIFS) and the transverse gyrus intersection the precentral sulcus (tgPCS). These small regions were identified in fMRI studies in a small number of individual subjects. Here, we have investigated these regions and their putative networks by mining the WashU-Minn Human Connectome Project (HCP) dataset. We used data from the 482 HCP participants with both diffusion-weighted imaging and resting-state fMRI. We defined seed regions from our individual subject data in a task that contrasted auditory and visual spatial attention. Probabilistic activation maps were constructed and thresholded to generate ROIs. These ROIs served as seed regions for resting state and tractography analyses of the HCP dataset. Stronger functional connectivity was observed for the sPCS and iPCS than for tgPCS and cIFS with superior parietal lobule visual attention regions, and conversely stronger connectivity was observed for the tgPCS and cIFS than for sPCS and iPCS with superior temporal lobe auditory attention regions. A similar pattern was observed with tractography for all ROIs, except for tgPCS. We next analyzed the whole-brain connectivity patterns of these ROIs using a multivariate approach; we found that the modality of sensory-bias can be predicted well above chance in both hemispheres at a voxelwise scale (L:71%, R:80%), using only the connectivity pattern of an individual voxel. A long-term goal of this analysis is to develop reliable methods for identifying fine-scale brain networks in large population datasets, which could have important clinical applications. Our preliminary results reveal both successes and challenges of these efforts. Meeting abstract presented at VSS 2015.

Sensory-biased attention networks in human lateral frontal cortex revealed by intrinsic functional connectivity

&NA; Human frontal cortex is commonly described as being insensitive to sensory modality, however several recent studies cast doubt on this view. Our laboratory previously reported two visual‐biased attention regions interleaved with two auditory‐biased attention regions, bilaterally, within lateral frontal cortex. These regions selectively formed functional networks with posterior visual‐biased and auditory‐biased attention regions. Here, we conducted a series of functional connectivity analyses to validate and expand this analysis to 469 subjects from the Human Connectome Project (HCP). Functional connectivity analyses replicated the original findings and revealed a novel hemispheric connectivity bias. We also subdivided lateral frontal cortex into 21 thin‐slice ROIs and observed bilateral patterns of spatially alternating visual‐biased and auditory‐biased attention network connectivity. Finally, we performed a correlation difference analysis that revealed five additional bilateral lateral frontal regions differentially connected to either the visual‐biased or auditory‐biased attention networks. These findings leverage the HCP dataset to demonstrate that sensory‐biased attention networks may have widespread influence in lateral frontal cortical organization. Graphical abstract Figure. No caption available. HighlightsSensory‐biased attention networks extend into human lateral frontal cortex (LFC).Small N dataset used to mine Human Connectome Project dataset (N = 469).RS‐functional connectivity confirms 4 sensory‐biased LFC regions bilaterally.5 new putative sensory‐biased attention regions observed bilaterally in LFC.

Cerebellar Contributions to Visual Attention and Visual Working Memory Revealed by Functional MRI and Intrinsic Functional Connectivity.

The study of cerebellum function has been traditionally limited to the motor domain. Recent research, however, has begun to characterize the cerebellums role in cognition (see Schmahmann, 2010) and has demonstrated intrinsic functional connectivity between cerebral cortical networks and distinct cerebellar regions (Buckner et al., 2011). Here, in two separate fMRI experiments, we investigated whether cerebro-cerebellar connectivity of dorsal attention network (DAN) predicts cerebellar activation during visual attention and visual working memory (VWM) task performance. In experiment 1 (N=8), subjects performed a multiple-object tracking task. In experiment 2 (N=9), subjects performed a VWM change detection task using oriented bars. Memory load was varied across blocks (set size: SS0, SS1, or SS4). Both experiments employed resting-state functional connectivity analysis using cortical network seeds (Yeo et al., 2011) to parcellate cerebro-cerebellar networks in individual subjects. In experiment 1, a region-of-interest analysis revealed a robust attentional effect within cerebellar regions functionally connected to the cortical DAN (p< .01). Conversely, cerebellar regions functionally connected to the cortical default mode network (DMN) showed reliable deactivation (p< .001). In experiment 2, contrasting SS4 with SS0 and SS1 resulted in a similar pattern of competitive interaction between cerebellar nodes of the DAN and DMN. Load-dependent activation spatially corresponded with cerebellar DAN nodes (SS4-SS0: p< .005; SS4-SS1: p< .0001) and load-dependent deactivation was observed within cerebellar DMN nodes (SS4-SS0: p< .005; SS4-SS1: p< .0005). Across both experiments the strength of intrinsic functional connectivity, with either the cortical DAN or the cortical DMN, significantly predicted the response of individual cerebellar voxels (Experiment 1: rDAN =.67, rDMN =-.71; Experiment 2: rDAN =.60, rDMN =-.56). Our results indicate that cerebellar nodes of the DAN contribute to network function across a diverse range of attentive and working memory conditions. Meeting abstract presented at VSS 2015.

Topographic Cortico-cerebellar Networks Revealed by Visual Attention and Working Memory

Substantial portions of the cerebellum appear to support non-motor functions; however, previous investigations of cerebellar involvement in cognition have revealed only a coarse degree of specificity. Although somatotopic maps have been observed within cerebellum, similar precision within cortico-cerebellar networks supporting non-motor functions has not previously been reported. Here, we find that human cerebellar lobule VIIb/VIIIa differentially codes key aspects of visuospatial cognition. Ipsilateral visuospatial representations were observed during both a visual working memory and an attentionally demanding visual receptive field-mapping fMRI task paradigm. Moreover, within lobule VIIb/VIIIa, we observed a functional dissociation between spatial coding and visual working memory processing. Visuospatial representations were found in the dorsomedial portion of lobule VIIb/VIIIa, and load-dependent visual working memory processing was shifted ventrolaterally. A similar functional gradient for spatial versus load processing was found in posterior parietal cortex. This cerebral cortical organization was well predicted by functional connectivity with spatial and load regions of cerebellar lobule VIIb/VIIIa. Collectively, our findings indicate that recruitment by visuospatial attentional functions within cerebellar lobule VIIb/VIIIa is highly specific. Furthermore, the topographic arrangement of these functions is mirrored in frontal and parietal cortex. These findings motivate a closer examination of cortico-cerebellar functional specialization across a broad range of cognitive domains.