Chad M. Sylvester

Top-Down Control of Human Visual Cortex by Frontal and Parietal Cortex in Anticipatory Visual Spatial Attention

Advance information about an impending stimulus facilitates its subsequent identification and ensuing behavioral responses. This facilitation is thought to be mediated by top-down control signals from frontal and parietal cortex that modulate sensory cortical activity. Here we show, using Granger causality measures on blood oxygen level-dependent time series, that frontal eye field (FEF) and intraparietal sulcus (IPS) activity predicts visual occipital activity before an expected visual stimulus. Top-down levels of Granger causality from FEF and IPS to visual occipital cortex were significantly greater than both bottom-up and mean cortex-wide levels in all individual subjects and the group. In the group and most individual subjects, Granger causality was significantly greater from FEF to IPS than from IPS to FEF, and significantly greater from both FEF and IPS to intermediate-tier than lower-tier ventral visual areas. Moreover, top-down Granger causality from right IPS to intermediate-tier areas was predictive of correct behavioral performance. These results suggest that FEF and IPS modulate visual occipital cortex, and FEF modulates IPS, in relation to visual attention. The current approach may prove advantageous for the investigation of interregional directed influences in other human brain functions.

Functional network dysfunction in anxiety and anxiety disorders.

A recent paradigm shift in systems neuroscience is the division of the human brain into functional networks. Functional networks are collections of brain regions with strongly correlated activity both at rest and during cognitive tasks, and each network is believed to implement a different aspect of cognition. We propose here that anxiety disorders and high trait anxiety are associated with a particular pattern of functional network dysfunction: increased functioning of the cingulo-opercular and ventral attention networks as well as decreased functioning of the fronto-parietal and default mode networks. This functional network model can be used to differentiate the pathology of anxiety disorders from other psychiatric illnesses such as major depression and provides targets for novel treatment strategies.

Asymmetry of Anticipatory Activity in Visual Cortex Predicts the Locus of Attention and Perception

Humans can use advance information to direct spatial attention before stimulus presentation and respond more accurately to stimuli at the attended location compared with unattended locations. Likewise, spatially directed attention is associated with anticipatory activity in the portion of visual cortex representing the attended location. It is unknown, however, whether and how anticipatory signals predict the locus of spatial attention and perception. Here, we show that prestimulus, preparatory activity is highly correlated across regions representing attended and unattended locations. Comparing activity representing attended versus unattended locations, rather than measuring activity for only one location, dramatically improves the accuracy with which preparatory signals predict the locus of attention, largely by removing this positive correlation common across locations. In V3A, moreover, only the difference in activity between attended and unattended locations predicts whether upcoming visual stimuli will be accurately perceived. These results suggest that the locus of attention is coded in visual cortex by an asymmetry of anticipatory activity between attended and unattended locations and that this asymmetry predicts the accuracy of perception. This coding strategy may bias activity in downstream brain regions to represent the stimulus at the attended location.

Anticipatory and Stimulus-Evoked Blood Oxygenation Level-Dependent Modulations Related to Spatial Attention Reflect a Common Additive Signal

Covert attention is associated with prestimulus blood oxygenation level-dependent (BOLD) modulations in visual cortex. In some situations, this preparatory activity can predict how well human subjects will perceive upcoming visual objects. Preparatory activity may mediate this behavioral effect by affecting the stimulus-evoked response, but the relationship between preparatory and stimulus-evoked BOLD modulations is unclear. Here, we examine this relationship by comparing the effects of spatial attention on anticipatory and stimulus-evoked signals and by measuring the trial-to-trial correlation between prestimulus and poststimulus modulations. We find that in extrastriate visual cortex (V4), modulations related to spatial attention are relatively large, extend from prestimulus through the peak of the evoked response, and are slightly larger in the evoked response compared with the prestimulus response. In striate cortex (V1), the frontal eye fields (FEF), and the intraparietal sulcus (IPS), modulations related to spatial attention are relatively small, are confined primarily to the prestimulus period, and are slightly larger in preparatory versus stimulus-evoked activity. Importantly, across visual cortex, the attentional biases (activity for attended versus unattended locations) in preparatory and evoked activity are more positively correlated, trial-by-trial, than would be expected on the basis of activity measured in subjects at rest. We argue that this pattern of results suggests that the same mechanisms underlie preparatory and stimulus-evoked BOLD modulations related to spatial attention and that incoming sensory signals add to preexistent biases in preparatory activity to generate the stimulus-evoked response.

Anticipatory Suppression of Nonattended Locations in Visual Cortex Marks Target Location and Predicts Perception

Spatial attention is associated with modulations in prestimulus, anticipatory blood oxygen level-dependent (BOLD) activity across the brain. It is unclear, however, if these anticipatory modulations depend on the computational demands of the upcoming task. Here, we show that anticipation of low-contrast stimuli, relative to high-contrast stimuli, is associated with increased prestimulus BOLD activity in the frontal eye field (FEF) and the posterior inferior frontal sulcus (IFS) but not in the intraparietal sulcus (IPS). In visual cortex, anticipation of low-contrast stimuli is associated with increased suppression of activity corresponding to unattended (but not attended) locations, and this suppression predicts whether subjects will accurately perceive low-contrast stimuli. These results suggest that when a stimulus will be difficult to distinguish from the background, top-down signals from FEF and IFS can facilitate perception by marking its location through the suppression of unattended locations in visual cortex.

Measuring Granger Causality between Cortical Regions from Voxelwise fMRI BOLD Signals with LASSO

Functional brain network studies using the Blood Oxygen-Level Dependent (BOLD) signal from functional Magnetic Resonance Imaging (fMRI) are becoming increasingly prevalent in research on the neural basis of human cognition. An important problem in functional brain network analysis is to understand directed functional interactions between brain regions during cognitive performance. This problem has important implications for understanding top-down influences from frontal and parietal control regions to visual occipital cortex in visuospatial attention, the goal motivating the present study. A common approach to measuring directed functional interactions between two brain regions is to first create nodal signals by averaging the BOLD signals of all the voxels in each region, and to then measure directed functional interactions between the nodal signals. Another approach, that avoids averaging, is to measure directed functional interactions between all pairwise combinations of voxels in the two regions. Here we employ an alternative approach that avoids the drawbacks of both averaging and pairwise voxel measures. In this approach, we first use the Least Absolute Shrinkage Selection Operator (LASSO) to pre-select voxels for analysis, then compute a Multivariate Vector AutoRegressive (MVAR) model from the time series of the selected voxels, and finally compute summary Granger Causality (GC) statistics from the model to represent directed interregional interactions. We demonstrate the effectiveness of this approach on both simulated and empirical fMRI data. We also show that averaging regional BOLD activity to create a nodal signal may lead to biased GC estimation of directed interregional interactions. The approach presented here makes it feasible to compute GC between brain regions without the need for averaging. Our results suggest that in the analysis of functional brain networks, careful consideration must be given to the way that network nodes and edges are defined because those definitions may have important implications for the validity of the analysis.

Resting state functional connectivity of the ventral attention network in children with a history of depression or anxiety.

OBJECTIVE We examined whether depression and anxiety disorders in early childhood were associated with changes in resting state functional connectivity (RSFC) of the ventral attention network (VAN), and whether RSFC in the VAN was associated with alterations in attention specific to these disorders. Important clinical features of these illnesses, including changes in attention toward novel stimuli and changes in attention to stimuli of negative valence (threat/sad bias), indirectly implicate the VAN. METHOD We collected resting state functional magnetic resonance imaging data in children aged 8 to 12 years. Data were volume censored to reduce artifact from submillimeter movement, resulting in analyzable data from 30 children with a history of depression and/or anxiety and 42 children with no psychiatric history. We compared pairwise RSFC among the following VAN regions: right ventro-lateral prefrontal cortex (VLPFC), right posterior superior temporal gyrus (pSTG), and right ventral supramarginal gyrus (vSMG). We also collected measures of threat bias and current clinical symptoms. RESULTS Children with a history of depression and/or anxiety had reduced RSFC among the regions of the VAN compared to children with no psychiatric history. The magnitude of VAN RSFC was correlated with measures of attention bias toward threat but not with current depressive, internalizing, or externalizing symptoms. No RSFC changes were detected between groups among homotopic left hemisphere regions. CONCLUSIONS Disruption in the VAN may be an early feature of depression and anxiety disorders. VAN changes were associated with attention bias and clinical history but not with current symptoms of depression and anxiety.

Effect of Hippocampal and Amygdala Connectivity on the Relationship Between Preschool Poverty and School-Age Depression

OBJECTIVE In this study, the authors tested the hypothesis that poverty experienced in early childhood, as measured by income-to-needs ratio, has an impact on functional brain connectivity at school age, which in turn mediates influences on child negative mood/depression. METHOD Participants were from a prospective longitudinal study of emotion development. Preschoolers 3-5 years of age were originally ascertained from primary care and day care sites in the St. Louis area and then underwent annual behavioral assessments for up to 12 years. Healthy preschoolers and those with a history of depression symptoms underwent neuroimaging at school age. Using functional MRI, the authors examined whole brain resting-state functional connectivity with the left and right hippocampus and amygdala. RESULTS Lower income-to-needs ratio at preschool age was associated with reduced connectivity between hippocampus and amygdala and a number of regions at school age, including the superior frontal cortex, lingual gyrus, posterior cingulate, and putamen. Lower income-to-needs ratio predicted greater negative mood/depression severity at school age, as did connectivity between the left hippocampus and the right superior frontal cortex and between the right amygdala and the right lingual gyrus. Connectivity mediated the relationship between income-to-needs ratio and negative mood/depression at the time of scanning. CONCLUSIONS These findings suggest that poverty in early childhood, as assessed by at least one measure, may influence the development of hippocampal and amygdala connectivity in a manner leading to negative mood symptoms during later childhood.

Altered Gray Matter Volume and School Age Anxiety in Children Born Late Preterm

OBJECTIVES To determine if late preterm (LP) children differ from full term (FT) children in volumes of the cortex, hippocampus, corpus callosum, or amygdala and whether these differences are associated with anxiety symptoms at school-age. STUDY DESIGN LP children born between 34 and 36 weeks gestation and FT children born between 39 and 41 weeks gestation from a larger longitudinal cohort had magnetic resonance imaging scans at school-age. Brain volumes, cortical surface area, and thickness measures were obtained. Anxiety symptoms were assessed using a structured diagnostic interview annually beginning at preschool-age and following the magnetic resonance imaging. RESULTS LP children (n = 21) had a smaller percentage of total, right parietal, and right temporal lobe gray matter volume than FT children (n = 87). There were no differences in hippocampal, callosal, or amygdala volumes or cortical thickness. LP children also had a relative decrease in right parietal lobe cortical surface area. LP children had greater anxiety symptoms over all assessments. The relationship between late prematurity and school-age anxiety symptoms was mediated by the relative decrease in right temporal lobe volume. CONCLUSIONS LP children, comprising 70% of preterm children, are also at increased risk for altered brain development particularly in the right temporal and parietal cortices. Alterations in the right temporal lobe cortical volume may underlie the increased rate of anxiety symptoms among these LP children. These findings suggest that LP delivery may disrupt temporal and parietal cortical development that persists until school-age with the right temporal lobe conferring risk for elevated anxiety symptoms.

Depression and Anxiety in Preschoolers: A Review of the Past 7 Years

This article reviews recent empirical literature on the prevalence, correlates, assessment, and treatment of preschool-onset internalizing disorders. Major advances in the acceptance and recognition of both preschool-onset depression and anxiety have occurred over the past decade. This work has been greatly enhanced by the discovery of genetic, neural, and physiologic indicators, which further validate these constellations of symptoms in young children. Despite this growth in research, much work still needs to be done to further elucidate the cause, risk, treatment, and protective factors for preschool-onset internalizing disorders.