Failing to deactivate: Resting functional abnormalities in autism

Abstract

Several regions of the brain (including medial prefrontal cortex, rostral anterior cingulate, posterior cingulate, and precuneus) are known to have high metabolic activity during rest, which is suppressed during cognitively demanding tasks. With functional magnetic resonance imaging (fMRI), this suppression of activity is observed as ''deactivations,'' which are thought to be indicative of an interruption of the mental activity that persists during rest. Thus, measuring deactivation provides a means by which restassociated functional activity can be quantitatively examined. Applying this approach to autism, we found that the autism group failed to demonstrate this deactivation effect. Furthermore, there was a strong correlation between a clinical measure of social impairment and functional activity within the ventral medial prefrontal cortex. We speculate that the lack of deactivation in the autism group is indicative of abnormal internally directed processes at rest, which may be an important contribution to the social and emotional deficits of autism.default mode ͉ functional MRI ͉ introspection ͉ medial prefrontal cortex ͉ precuneus I nternally directed processes, such as self-reflective thought and most higher-order social and emotional processes, consistently activate a medial cortical network involving several brain regions, namely, the medial prefrontal cortex (MPFC) and adjacent rostral anterior cingulate cortex (rACC), posterior cingulate cortex (PCC), and precuneus (PrC) (1-4). Interestingly, this network is active when normal subjects are passively resting (5), leading many to speculate that these internally directed thoughts dominate the resting state (6-9). Self-reports from subjects while at rest further support this interpretation, wherein they typically describe ''autobiographical reminiscences, either recent or ancient, consisting of familiar faces, scenes, dialogues, stories, and melodies'' (8). Conversely, activity in this midline ''resting network'' is reduced when subjects perform externally directed, attention-demanding, goal-oriented tasks (such as the Stroop task or math calculations), and the resulting ''deactivation'' of this network is thought to be an indicator of an interruption of ongoing internally directed thought processes (5, 6, 9-11). In this context, the term deactivation simply refers to activity that is greater during rest than during task performance (i.e., the opposite of the more typically reported activations). Thus, an objective method for testing the functioning of this midline resting network is to measure whether there is deactivation in these regions during externally directed tasks as compared with passive rest. Similar approaches of examining this ''deactivation effect'' have been used in studies of patients with fragile X (12), a developmental disorder with some characteristics that overlap with autism, and in patients with dementia of the Alzheimer type (13) and Alzheimer's disease (14).There are several lines of evidence that suggest that this resting network m...

Levels of emotional awareness and autism: An fMRI study

“…It is consistent with the recently observed abnormal lack of activation in these regions during rest, and interpreted as an abnormal lack of introspection during rest conditions (Kennedy et al, 2006). Since the same brain regions are activated during mentalizing (Frith & Frith, 2006), it appears that the same network is active when monitoring the mental states of others as when monitoring one's own mental states.…”

“…This level involves an awareness of a self who has emotions and can monitor them and is different from a second-order bodily awareness of emotions. If impaired introspection or self-reflection characterizes autism (Kennedy, Redcay, & Courchesne, 2006), then we would expect the self-reflective system to be less active. In individuals with autism who also have a high degree of alexithymia this activity might be reduced still further when they are required to introspect on their emotions.…”

Resting-State Functional Connectivity in Major Depression: Abnormally Increased Contributions from Subgenual Cingulate Cortex and Thalamus

“…The relatively large effect size (Cohen's d = 1.01) of this subgenual finding lends a quantitative measure to the qualitative impression left by Figure 2 in which this appears to be a binary finding-the subgenual cingulate is a prominent node in the depressed group network and absent in the control group network. To our knowledge, none of the prior studies describing the defaultmode network in healthy controls (Fox et al 2005;Fransson 2005;Greicius et al 2003;Raichle et al 2001), dementia patients Lustig et al 2003;Rombouts et al 2005), or, most recently, autistic patients (Kennedy et al 2006) have reported this region and as such the presence of the subgenual cingulate in the default-mode network is, for now, a finding unique to depression.…”

Cortical Folding Abnormalities in Autism Revealed by Surface-Based Morphometry

“…Recent functional neuroimaging studies have identified abnormalities in broad networks of regions that are "active" during rest (Kennedy et al, 2006) as well as abnormalities in specific brain regions associated with particular deficits in autism, such as the amygdala and fusiform gyrus in eye-gaze and face/emotion processing (Dalton et al, 2005). Although the location of the cortical shape abnormalities identified in this study appear to be spatially distinct from these areas, future studies using integration of functional and diffusion tensor imaging with surfacebased morphometry will be useful in discerning the precise abnormalities in the patterns of connectivity and functional consequences in autism.…”