Xiaoqian J. Chai

Anticorrelations in resting state networks without global signal regression

Anticorrelated relationships in spontaneous signal fluctuation have been previously observed in resting-state functional magnetic resonance imaging (fMRI). In particular, it was proposed that there exists two systems in the brain that are intrinsically organized into anticorrelated networks, the default mode network, which usually exhibits task-related deactivations, and the task-positive network, which usually exhibits task-related activations during tasks that demands external attention. However, it is currently under debate whether the anticorrelations observed in resting state fMRI were valid or were instead artificially introduced by global signal regression, a common preprocessing technique to remove physiological and other noise in resting-state fMRI signal. We examined positive and negative correlations in resting-state connectivity using two different preprocessing methods: a component base noise reduction method (CompCor, Behzadi et al., 2007), in which principal components from noise regions-of-interest were removed, and the global signal regression method. Robust anticorrelations between a default mode network seed region in the medial prefrontal cortex and regions of the task-positive network were observed under both methods. Specificity of the anticorrelations was similar between the two methods. Specificity and sensitivity for positive correlations were higher under CompCor compared to the global regression method. Our results suggest that anticorrelations observed in resting-state connectivity are not an artifact introduced by global signal regression and might have biological origins, and that the CompCor method can be used to examine valid anticorrelations during rest.

Abnormal Medial Prefrontal Cortex Resting-State Connectivity in Bipolar Disorder and Schizophrenia

Bipolar disorder and schizophrenia overlap in symptoms and may share some underlying neural substrates. The medial prefrontal cortex (MPFC) may have a crucial role in the psychophysiology of both these disorders. In this study, we examined the functional connectivity between MPFC and other brain regions in bipolar disorder and schizophrenia using resting-state functional magnetic resonance imaging (fMRI). Resting-state fMRI data were collected from 14 patients with bipolar disorder, 16 patients with schizophrenia, and 15 healthy control subjects. Functional connectivity maps from the MPFC were computed for each subject and compared across the three groups. The three groups showed distinctive patterns of functional connectivity between MPFC and anterior insula, and between MPFC and ventral lateral prefrontal cortex (VLPFC). The bipolar disorder group exhibited positive correlations between MPFC and insula, and between MPFC and VLPFC, whereas the control group exhibited anticorrelations between these regions. The schizophrenia group did not exhibit any resting-state correlation or anticorrelation between the MPFC and the VLPFC or insula. In contrast, neither patient group exhibited the significant anticorrelation between dorsal lateral prefrontal cortex (DLPFC) and MPFC that was exhibited by the control group. The decoupling of DLPFC with MPFC in bipolar disorder and schizophrenia is consistent with the impaired executive functioning seen in these disorders. Functional connectivity between MPFC and insula/VLPFC distinguished bipolar disorder from schizophrenia, and may reflect differences in the affective disturbances typical of each illness.

Selective development of anticorrelated networks in the intrinsic functional organization of the human brain

We examined the normal development of intrinsic functional connectivity of the default network (brain regions typically deactivated for attention-demanding tasks) as measured by resting-state fMRI in children, adolescents, and young adults ages 8–24 years. We investigated both positive and negative correlations and employed analysis methods that allowed for valid interpretation of negative correlations and that also minimized the influence of motion artifacts that are often confounds in developmental neuroimaging. As age increased, there were robust developmental increases in negative correlations, including those between medial pFC (MPFC) and dorsolateral pFC (DLPFC) and between lateral parietal cortices and brain regions associated with the dorsal attention network. Between multiple regions, these correlations reversed from being positive in children to negative in adults. Age-related changes in positive correlations within the default network were below statistical threshold after controlling for motion. Given evidence in adults that greater negative correlation between MPFC and DLPFC is associated with superior cognitive performance, the development of an intrinsic anticorrelation between MPFC and DLPFC may be a marker of the large growth of working memory and executive functions that occurs from childhood to young adulthood.

The development of brain systems associated with successful memory retrieval of scenes

Neuroanatomical and psychological evidence suggests prolonged maturation of declarative memory systems in the human brain from childhood into young adulthood. Here, we examine functional brain development during successful memory retrieval of scenes in children, adolescents, and young adults ages 8–21 via functional magnetic resonance imaging. Recognition memory improved with age, specifically for accurate identification of studied scenes (hits). Successful retrieval (correct old–new decisions for studied vs unstudied scenes) was associated with activations in frontal, parietal, and medial temporal lobe (MTL) regions. Activations associated with successful retrieval increased with age in left parietal cortex (BA7), bilateral prefrontal, and bilateral caudate regions. In contrast, activations associated with successful retrieval did not change with age in the MTL. Psychophysiological interaction analysis revealed that there were, however, age-relate changes in differential connectivity for successful retrieval between MTL and prefrontal regions. These results suggest that neocortical regions related to attentional or strategic control show the greatest developmental changes for memory retrieval of scenes. Furthermore, these results suggest that functional interactions between MTL and prefrontal regions during memory retrieval also develop into young adulthood. The developmental increase of memory-related activations in frontal and parietal regions for retrieval of scenes and the absence of such an increase in MTL regions parallels what has been observed for memory encoding of scenes.

Sex Differences in Directional Cue Use in a Virtual Landscape

How males and females differ in their use of cues for spatial navigation is an important question. Although women and men appear to respond differently to close and distant objects, object features and the geometry of spaces, the common denominator of these sex-specific cue preferences is unknown. By constructing virtual landscapes from either directional (graded, gradient) or positional (pinpoint) cues, the authors tested the hypothesis that sex differences arise from preferences for cues that provide primarily direction or position, as predicted by the parallel map model of the cognitive map. Women and men learned a target location in the presence of either one or the other class of cues. Men were more accurate in estimating the target location overall, but the navigation accuracy difference between men and women was greater in the presence of directional cues. Our findings provide support for the parallel map model and suggest that the previously reported male advantage in the presence of distant objects and geometric cues derives from their function as directional cues.

Scene Complexity: Influence on Perception, Memory, and Development in the Medial Temporal Lobe

Regions in the medial temporal lobe (MTL) and prefrontal cortex (PFC) are involved in memory formation for scenes in both children and adults. The development in children and adolescents of successful memory encoding for scenes has been associated with increased activation in PFC, but not MTL, regions. However, evidence suggests that a functional subregion of the MTL that supports scene perception, located in the parahippocampal gyrus (PHG), goes through a prolonged maturation process. Here we tested the hypothesis that maturation of scene perception supports the development of memory for complex scenes. Scenes were characterized by their levels of complexity defined by the number of unique object categories depicted in the scene. Recognition memory improved with age, in participants ages 8–24, for high-, but not low-, complexity scenes. High-complexity compared to low-complexity scenes activated a network of regions including the posterior PHG. The difference in activations for high- versus low-complexity scenes increased with age in the right posterior PHG. Finally, activations in right posterior PHG were associated with age-related increases in successful memory formation for high-, but not low-, complexity scenes. These results suggest that functional maturation of the right posterior PHG plays a critical role in the development of enduring long-term recollection for high-complexity scenes.

Effects of cue types on sex differences in human spatial memory

We examined the effects of cue types on human spatial memory in 3D virtual environments adapted from classical animal and human tasks. Two classes of cues of different functions were investigated: those that provide directional information, and those that provide positional information. Adding a directional cue (geographical slant) to the spatial delayed-match-to-sample task improved performance in males but not in females. When the slant directional cue was removed in a hidden-target location task, male performance was impaired but female performance was unaffected. The removal of positional cues, on the other hand, impaired female performance but not male performance. These results are consistent with results from laboratory rodents and thus support the hypothesis that sex differences in spatial memory arise from the dissociation between a preferential reliance on directional cues in males and on positional cues in females.

Development of deactivation of the default-mode network during episodic memory formation

Task-induced deactivation of the default-mode network (DMN) has been associated in adults with successful episodic memory formation, possibly as a mechanism to focus allocation of mental resources for successful encoding of external stimuli. We investigated developmental changes of deactivation of the DMN (posterior cingulate, medial prefrontal, and bilateral lateral parietal cortices) during episodic memory formation in children, adolescents, and young adults (ages 8-24), who studied scenes during functional magnetic resonance imaging (fMRI). Recognition memory improved with age. We defined DMN regions of interest from a different sample of participants with the same age range, using resting-state fMRI. In adults, there was greater deactivation of the DMN for scenes that were later remembered than scenes that were later forgotten. In children, deactivation of the default-network did not differ reliably between scenes that were later remembered or forgotten. Adolescents exhibited a pattern of activation intermediate to that of children and adults. The hippocampal region, often considered part of the DMN, showed a functional dissociation with the rest of the DMN by exhibiting increased activation for later remembered than later forgotten scene that was similar across age groups. These findings suggest that development of memory ability from childhood through adulthood may involve increased deactivation of the neocortical DMN during learning.

Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression

BACKGROUND Neuroimaging studies of patients with major depression have revealed abnormal intrinsic functional connectivity measured during the resting state in multiple distributed networks. However, it is unclear whether these findings reflect the state of major depression or reflect trait neurobiological underpinnings of risk for major depression. METHODS We compared resting-state functional connectivity, measured with functional magnetic resonance imaging, between unaffected children of parents who had documented histories of major depression (at-risk, n = 27; 8-14 years of age) and age-matched children of parents with no lifetime history of depression (control subjects, n = 16). RESULTS At-risk children exhibited hyperconnectivity between the default mode network and subgenual anterior cingulate cortex/orbital frontal cortex, and the magnitude of connectivity positively correlated with individual symptom scores. At-risk children also exhibited 1) hypoconnectivity within the cognitive control network, which also lacked the typical anticorrelation with the default mode network; 2) hypoconnectivity between left dorsolateral prefrontal cortex and subgenual anterior cingulate cortex; and 3) hyperconnectivity between the right amygdala and right inferior frontal gyrus, a key region for top-down modulation of emotion. Classification between at-risk children and control subjects based on resting-state connectivity yielded high accuracy with high sensitivity and specificity that was superior to clinical rating scales. CONCLUSIONS Children at familial risk for depression exhibited atypical functional connectivity in the default mode, cognitive control, and affective networks. Such task-independent functional brain measures of risk for depression in children could be used to promote early intervention to reduce the likelihood of developing depression.

Lower gray matter density and functional connectivity in the anterior insula in smokers compared with never smokers

Although nicotine addiction is characterized by both structural and functional abnormalities in brain networks involved in salience and cognitive control, few studies have integrated these data to understand how these abnormalities may support addiction. This study aimed to (1) evaluate gray matter density and functional connectivity of the anterior insula in cigarette smokers and never smokers and (2) characterize how differences in these measures were related to smoking behavior. We compared structural magnetic resonance imaging (MRI) (gray matter density via voxel‐based morphometry) and seed‐based functional connectivity MRI data in 16 minimally deprived smokers and 16 matched never smokers. Compared with controls, smokers had lower gray matter density in left anterior insula extending into inferior frontal and temporal cortex. Gray matter density in this region was inversely correlated with cigarettes smoked per day. Smokers exhibited negative functional connectivity (anti‐correlation) between the anterior insula and regions involved in cognitive control (left lPFC) and semantic processing/emotion regulation (lateral temporal cortex), whereas controls exhibited positive connectivity between these regions. There were differences in the anterior insula, a central region in the brains salience network, when comparing both volumetric and functional connectivity data between cigarette smokers and never smokers. Volumetric data, but not the functional connectivity data, were also associated with an aspect of smoking behavior (daily cigarettes smoked).