[Show abstract][Hide abstract] ABSTRACT: A fundamental component of brain development is the formation of large-scale networks across the cortex. One such network, the default network, undergoes a protracted development, displaying weak connectivity in childhood that strengthens in adolescence and becomes most robust in adulthood. Little is known about the genetic contributions to default network connectivity in adulthood or during development. Alterations in connectivity between posterior and frontal portions of the default network have been associated with several psychological disorders, including anxiety, autism spectrum disorders, schizophrenia, depression, and attention-deficit/hyperactivity disorder. These disorders have also been linked to variants of the serotonin transporter linked polymorphic region (5-HTTLPR). The LA allele of 5-HTTLPR results in higher serotonin transporter expression than the S allele or the rarer LG allele. 5-HTTLPR may influence default network connectivity, as the superior medial frontal region has been shown to be sensitive to changes in serotonin. Also, serotonin as a growth factor early in development may alter large-scale networks such as the default network. The present study examined the influence of 5-HTTLPR variants on connectivity between the posterior and frontal structures and its development in a cross-sectional study of 39 healthy children and adolescents. We found that children and adolescents homozygous for the S allele (S/S, n=10) showed weaker connectivity in the superior medial frontal cortex compared to those homozygous for the LA allele (LA/LA, n=13) or heterozygotes (S/LA, S/LG, n=16). Moreover, there was an age-by-genotype interaction, such that those with LA/LA genotype had the steepest age-related increase in connectivity between the posterior hub and superior medial frontal cortex, followed by heterozygotes. In contrast, individuals with the S/S genotype had the least age-related increase in connectivity strength. This preliminary report expands our understanding of the genetic influences on the development of large-scale brain connectivity and lays down the foundation for future research and replication of the results with a larger sample.
[Show abstract][Hide abstract] ABSTRACT: Healthy individuals show robust functional connectivity during rest, which is stronger in adults than in children. Connectivity occurs between the posterior and anterior portions of the default network, a group of structures active in the absence of a task, including the posterior cingulate cortex and the superior frontal gyrus. Previous studies found weaker posterior-anterior connectivity in the default network in adults and adolescents with autism spectrum disorders (ASD). However, these studies used small a priori regions of interest ("seeds") to calculate connectivity. Since seed location for all participants was chosen based on controls' brains, these studies' analyses are more tailored to controls than individuals with ASD. An alternative is to use a data-driven approach, such as self-organizing maps (SOM), to create a reference for each participant to calculate connectivity. We used individualized resting-state clusters identified by an SOM algorithm to corroborate previous findings of weaker posterior-anterior connectivity in the ASD group and examine age-related changes in the ASD and control groups. Thirty-nine adolescents with ASD and 41 controls underwent a 10-minute, eyes-open, resting-state functional MRI scan. The SOM analysis revealed that adolescents with ASD versus controls have weaker connectivity between the posterior hub of the default network and the right superior frontal gyrus. Additionally, controls have larger increases in connectivity with age compared to the ASD group. These findings indicate that SOM is a complementary method for calculating connectivity in a clinical population. Additionally, adolescents with ASD have a different developmental trajectory of the default network compared to controls.
Brain research 10/2010; 1380:187-97. DOI:10.1016/j.brainres.2010.10.102 · 2.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autism spectrum disorders (ASD) involve a core deficit in social functioning and impairments in the ability to recognize face emotions. In an emotional faces task designed to constrain group differences in attention, the present study used functional MRI to characterize activation in the amygdala, ventral prefrontal cortex (vPFC), and striatum, three structures involved in socio-emotional processing in adolescents with ASD.
Twenty-two adolescents with ASD and 20 healthy adolescents viewed facial expressions (happy, fearful, sad and neutral) that were briefly presented (250 ms) during functional MRI acquisition. To monitor attention, subjects pressed a button to identify the gender of each face.
The ASD group showed greater activation to the faces relative to the control group in the amygdala, vPFC and striatum. Follow-up analyses indicated that the ASD relative to control group showed greater activation in the amygdala, vPFC and striatum (p < .05 small volume corrected), particularly to sad faces. Moreover, in the ASD group, there was a negative correlation between developmental variables (age and pubertal status) and mean activation from the whole bilateral amygdala; younger adolescents showed greater activation than older adolescents. There were no group differences in accuracy or reaction time in the gender identification task.
When group differences in attention to facial expressions were limited, adolescents with ASD showed greater activation in structures involved in socio-emotional processing.
Journal of Child Psychology and Psychiatry 10/2010; 52(3):296-305. DOI:10.1111/j.1469-7610.2010.02317.x · 6.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autism spectrum disorders (ASD) are associated with severe impairments in social functioning. Because faces provide nonverbal cues that support social interactions, many studies of ASD have examined neural structures that process faces, including the amygdala, ventromedial prefrontal cortex and superior and middle temporal gyri. However, increases or decreases in activation are often contingent on the cognitive task. Specifically, the cognitive domain of attention influences group differences in brain activation. We investigated brain function abnormalities in participants with ASD using a task that monitored attention bias to emotional faces.
Twenty-four participants (12 with ASD, 12 controls) completed a functional magnetic resonance imaging study while performing an attention cuing task with emotional (happy, sad, angry) and neutral faces.
In response to emotional faces, those in the ASD group showed greater right amygdala activation than those in the control group. A preliminary psychophysiological connectivity analysis showed that ASD participants had stronger positive right amygdala and ventromedial prefrontal cortex coupling and weaker positive right amygdala and temporal lobe coupling than controls. There were no group differences in the behavioural measure of attention bias to the emotional faces.
The small sample size may have affected our ability to detect additional group differences.
When attention bias to emotional faces was equivalent between ASD and control groups, ASD was associated with greater amygdala activation. Preliminary analyses showed that ASD participants had stronger connectivity between the amygdala ventromedial prefrontal cortex (a network implicated in emotional modulation) and weaker connectivity between the amygdala and temporal lobe (a pathway involved in the identification of facial expressions, although areas of group differences were generally in a more anterior region of the temporal lobe than what is typically reported for emotional face processing). These alterations in connectivity are consistent with emotion and face processing disturbances in ASD.
[Show abstract][Hide abstract] ABSTRACT: Autism spectrum disorders (ASD) are associated with disturbances of neural connectivity. Functional connectivity between neural structures is typically examined within the context of a cognitive task, but also exists in the absence of a task (i.e., "rest"). Connectivity during rest is particularly active in a set of structures called the default network, which includes the posterior cingulate cortex (PCC), retrosplenial cortex, lateral parietal cortex/angular gyrus, medial prefrontal cortex, superior frontal gyrus, temporal lobe, and parahippocampal gyrus. We previously reported that adults with ASD relative to controls show areas of stronger and weaker connectivity within the default network. The objective of the present study was to examine the default network in adolescents with ASD. Sixteen adolescents with ASD and 15 controls participated in a functional MRI study. Functional connectivity was examined between a PCC seed and other areas of the default network. Both groups showed connectivity in the default network. Relative to controls, adolescents with ASD showed widespread weaker connectivity in nine of the eleven areas of the default network. Moreover, an analysis of symptom severity indicated that poorer social skills and increases in restricted and repetitive behaviors and interests correlated with weaker connectivity, whereas poorer verbal and non-verbal communication correlated with stronger connectivity in multiple areas of the default network. These findings indicate that adolescents with ASD show weaker connectivity in the default network than previously reported in adults with ASD. The findings also show that weaker connectivity within the default network is associated with specific impairments in ASD.
Brain research 12/2009; 1313(May):202-14. DOI:10.1016/j.brainres.2009.11.057 · 2.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autism spectrum disorders (ASD) impact social functioning and communication, and individuals with these disorders often have restrictive and repetitive behaviors. Accumulating data indicate that ASD is associated with alterations of neural circuitry. Functional MRI (FMRI) studies have focused on connectivity in the context of psychological tasks. However, even in the absence of a task, the brain exhibits a high degree of functional connectivity, known as intrinsic or resting connectivity. Notably, the default network, which includes the posterior cingulate cortex, retro-splenial, lateral parietal cortex/angular gyrus, medial prefrontal cortex, superior frontal gyrus, temporal lobe, and parahippocampal gyrus, is strongly active when there is no task. Altered intrinsic connectivity within the default network may underlie offline processing that may actuate ASD impairments. Using FMRI, we sought to evaluate intrinsic connectivity within the default network in ASD. Relative to controls, the ASD group showed weaker connectivity between the posterior cingulate cortex and superior frontal gyrus and stronger connectivity between the posterior cingulate cortex and both the right temporal lobe and right parahippocampal gyrus. Moreover, poorer social functioning in the ASD group was correlated with weaker connectivity between the posterior cingulate cortex and the superior frontal gyrus. In addition, more severe restricted and repetitive behaviors in ASD were correlated with stronger connectivity between the posterior cingulate cortex and right parahippocampal gyrus. These findings indicate that ASD subjects show altered intrinsic connectivity within the default network, and connectivity between these structures is associated with specific ASD symptoms.
[Show abstract][Hide abstract] ABSTRACT: The present set of studies sought to examine functional connectivity in adolescents with autism spectrum disorders (ASD) using functional magnetic resonance imaging (fMRI). In Chapter II, functional connectivity was examined in the context of a social task with emotional faces. The task was designed to control for attention differences between groups as well as to elicit robust amygdala activation in both groups. Using a psychophysiological interaction (PPI) analytic technique, we examined relationships between the amygdala and various cortical structures involved in face processing. The results showed that although behavioral performance did not differ between groups, adolescents with ASD relative to controls, showed weaker positive amygdala-cortical connectivity within the temporal and frontal regions when viewing emotional faces relative to baseline. In addition, weaker positive connectivity was associated with the degree of social impairment in the ASD group. The findings suggest that adolescents with ASD show a disruption in functional connectivity in the neural networks involved in face processing and that these disruptions relate to social impairment, and are not driven by behavioral differences in emotion recognition. In Chapter III, functional connectivity within the default network was examined using a seed in the posterior cingulate cortex (PCC) in the absence of a cognitive task (subjects lay in the MRI and viewed a cross on a screen). The default network is of interest as others have identified it as the brain’s intrinsic activation, important in maintaining the equilibrium between excitatory and inhibitory neuronal inputs and low-level monitoring of the external surroundings. The results of the resting connectivity study revealed that relative to controls, adolescents with ASD showed weaker connectivity between the PCC and a majority of areas within the default network, with the exception of tighter connectivity between the PCC and the right superior temporal gyrus. Moreover, poorer adaptive behavior was related to weaker connectivity between the PCC and left angular gyrus in adolescents with ASD. To summarize, the present set of studies show evidence for widespread reduced connectivity and isolated areas of increased connectivity in adolescents with ASD relative to controls. Ph.D. Psychology University of Michigan, Horace H. Rackham School of Graduate Studies http://deepblue.lib.umich.edu/bitstream/2027.42/62259/1/sweng_1.pdf