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. Here, we propose 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.

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.

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.

Objective Alterations in the normal developmental trajectory of amygdala resting state-functional connectivity (rs-FC) have been associated with atypical emotional processes and psychopathology. Little is known, however, regarding amygdala rs-FC at birth or its relevance to outcomes. This study examined amygdala rs-FC in healthy, full-term (FT) infants and in very preterm (VPT) infants and tested whether variability of neonatal amygdala rs-FC predicted internalizing symptoms at age 2 years. Method Resting state-fMRI data were obtained shortly after birth from 65 FT infants (gestational age [GA] ≥36 weeks) and 57 VPT infants (GA <30 weeks) at term-equivalent. Voxel-wise correlation analyses were performed using individual-specific bilateral amygdala regions of interest. Total internalizing symptoms and the behavioral inhibition, depression/withdrawal, general anxiety, and separation distress subdomains were assessed in a subset (n=44) at age 2 years using the Infant Toddler Social Emotional Assessment. Results In FT and VPT infants, the amygdala demonstrated positive correlations with subcortical and limbic structures and negative correlations with cortical regions, though magnitudes were decreased in VPT infants. Neonatal amygdala rs-FC predicted internalizing symptoms at age 2 with regional specificity consistent with known pathophysiology in older populations: connectivity with the anterior insula related to depressive symptoms, with the dorsal anterior cingulate related to generalized anxiety, and with the medial prefrontal cortex related to behavioral inhibition. Conclusion Amygdala rs-FC is well-established in neonates. Variability in regional neonatal amygdala rs-FC predicted internalizing symptoms at 2 years, suggesting that risk for internalizing symptoms may be established in neonatal amygdala functional connectivity patterns.

Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations1,2, despite evidence for concentric functional zones3 and maps of complex actions4. Here, using precision functional magnetic resonance imaging (fMRI) methods, we find that the classic homunculus is interrupted by regions with distinct connectivity, structure and function, alternating with effector-specific (foot, hand and mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, as well as to the cingulo-opercular network (CON), critical for action5 and physiological control6, arousal7, errors8 and pain9. This interdigitation of action control-linked and motor effector regions was verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant and child) precision fMRI suggested cross-species homologues and developmental precursors of the inter-effector system. A battery of motor and action fMRI tasks documented concentric effector somatotopies, separated by the CON-linked inter-effector regions. The inter-effectors lacked movement specificity and co-activated during action planning (coordination of hands and feet) and axial body movement (such as of the abdomen or eyebrows). These results, together with previous studies demonstrating stimulation-evoked complex actions4 and connectivity to internal organs10 such as the adrenal medulla, suggest that M1 is punctuated by a system for whole-body action planning, the somato-cognitive action network (SCAN). In M1, two parallel systems intertwine, forming an integrate–isolate pattern: effector-specific regions (foot, hand and mouth) for isolating fine motor control and the SCAN for integrating goals, physiology and body movement.

Objective This study tested the hypothesis that poverty experienced in early childhood, as measured by income-to-needs ratio, impacts 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 were annually assessed behaviorally for up to 12 years. Healthy preschoolers and those with a history of depression symptoms participated in neuroimaging at school age. Using fMRI, we examined whole brain resting state functional connectivity with bilateral hippocampus and amygdala. Results Lower income-to-needs in preschool was associated with reduced connectivity between hippocampus and amygdala and a number of regions at school-age, including superior frontal cortex, lingual gyrus, posterior cingulate and putamen. Lower income-to-needs predicted greater negative mood/depression severity at school age, as did connectivity between left hippocampus and right superior frontal cortex and between right amygdala and right lingual gyrus. Connectivity mediated the relationship between income-to-needs and negative mood/depression at the time of scan. Conclusions The finding that lower income-to-needs in early childhood related to connectivity of the hippocampus and the amygdala, which in turn predicted negative mood/depression at school age, further highlights a critical role for poverty in shaping brain development and elucidates a relationship to negative child outcomes.

The amygdala is central to the pathophysiology of many psychiatric illnesses. An imprecise understanding of how the amygdala fits into the larger network organization of the human brain, however, limits our ability to create models of dysfunction in individual patients to guide personalized treatment. Therefore, we investigated the position of the amygdala and its functional subdivisions within the network organization of the brain in 10 highly sampled individuals (5 h of fMRI data per person). We characterized three functional subdivisions within the amygdala of each individual. We discovered that one subdivision is preferentially correlated with the default mode network; a second is preferentially correlated with the dorsal attention and fronto-parietal networks; and third subdivision does not have any networks to which it is preferentially correlated relative to the other two subdivisions. All three subdivisions are positively correlated with ventral attention and somatomotor networks and negatively correlated with salience and cingulo-opercular networks. These observations were replicated in an independent group dataset of 120 individuals. We also found substantial across-subject variation in the distribution and magnitude of amygdala functional connectivity with the cerebral cortex that related to individual differences in the stereotactic locations both of amygdala subdivisions and of cortical functional brain networks. Finally, using lag analyses, we found consistent temporal ordering of fMRI signals in the cortex relative to amygdala subdivisions. Altogether, this work provides a detailed framework of amygdala–cortical interactions that can be used as a foundation for models relating aberrations in amygdala connectivity to psychiatric symptoms in individual patients.

Synopsis 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 physiological 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 etiology, risk treatment and protective factors for preschool-onset internalizing disorders.