This blog post has been triggered by a recent news article that found that the default network in schizophrenics was both hyperactive and hyperconnected during rest, and it remained so as they performed demanding cognitive tasks. To quote:

The researchers were especially interested in the default system, a network of brain regions whose activity is suppressed when people perform demanding mental tasks. This network includes the medial prefrontal cortex and the posterior cingulate cortex, regions that are associated with self-reflection and autobiographical memories and which become connected into a synchronously active network when the mind is allowed to wander.

Whitfield-Gabrieli found that in the schizophrenia patients, the default system was both hyperactive and hyperconnected during rest, and it remained so as they performed the memory tasks. In other words, the patients were less able than healthy control subjects to suppress the activity of this network during the task. Interestingly, the less the suppression and the greater the connectivity, the worse they performed on the hard memory task, and the more severe their clinical symptoms.

“We think this may reflect an inability of people with schizophrenia to direct mental resources away from internal thoughts and feelings and toward the external world in order to perform difficult tasks,” Whitfield-Gabrieli explained.

The hyperactive default system could also help to explain hallucinations and paranoia by making neutral external stimuli seem inappropriately self-relevant. For instance, if brain regions whose activity normally signifies self-focus are active while listening to a voice on television, the person may perceive that the voice is speaking directly to them.

The default system is also overactive, though to a lesser extent, in first-degree relatives of schizophrenia patients who did not themselves have the disease. This suggests that overactivation of the default system may be linked to the genetic cause of the disease rather than its consequences.

The study on which this report is based , is supposedly published in advanced online PNAS edition of 19 jan, but I am unable to locate it. However, my readers know my obsession with Autism and Schizophrenia as diametrically opposed disorders theory and so I was seen reading all the other relevant studies related to default Network and especially how it may be differentially and oppositely activated in Autism and Schizophrenia.

First I would like to refer you to an extremely good overview of Default Network by Buckner, Schacter et al which is freely available. I’ll now present some quotes from the paper that are relevant to my thesis. I start with the abstract:

Thirty years of brain imaging research has converged to define the brain’s default network—a novel and only recently appreciated brain system that participates in internal modes of cognition. Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment. Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system. Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others. Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems. The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation. The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self-relevant mental simulations. These two subsystems converge on important nodes of integration including the posterior cingulate cortex. The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world. We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer’s disease.

Some snippets from the introduction:

A common observation in brain imaging research is that a specific set of brain regions—referred to as the default network—is engaged when individuals are left to think to themselves undisturbed . Probing this phenomenon further reveals that other kinds of situations, beyond freethinking, engage the default network. For example, remembering the past, envisioning future events, and considering the thoughts and perspectives of other people all activate multiple regions within the default network . These observations prompt one to ask such questions as: What do these tasks and spontaneous cognition share in common? and what is the significance of this network to adaptive function? The default network is also disrupted in autism, schizophrenia, and Alzheimer’s disease, further encouraging one to consider how the functions of the default network might be important to understanding diseases of the mind. (emphasis mine)

Then they review some history including how default brain activity was recognized when it was found that metabolic demands and blood glucose consumption of brain as a whole remained the same even when the brain was at ‘rest’ viv-a-vis involved in an active task. They also review how when baseline PET/fMRI rest activity was compared to many disparate tasks related fMRI/ PET activity , then while some task-relevant areas showed activations related to baseline, many correlated areas of brain, the default network, showed deactivation in the task-related conditions as compared to baseline. The modern interpretation is that the default network is active at rest and places metabolic demands on the brain. They then reference the seminal work of Rachile et al and how that made the default network as a study area in itself.

They further elaborate on how the default network may be identified as an interconnected and functional brain system and list various approaches like spontaneous correlations at rest, seeding from a RoI and determining the areas correlated to activity in seed region etc, to determine the components of the default network. While dMPFC and PCC are implicated in all analysis, the case for vMPFC, IPL, HF+ and LTC is also strong.

I’ll skip most of this stuff , including comparative analysis. Suffice it to note here that the default brain regions are up to 30% more metabolically demanding then the rest of the brain and are recently evolved/ selected for. this becomes significant in view of recent studies showing that schizophrenia may be a result of selection for metabolism related genes.

The interesting part begins when trying to determine the behavioral/cognitive correlates of this default brain activity. The consensus seems to be that it is used for daydreaming, reconstructing the past, simulating the future, taking other peoples perspective, self-referential processes and in general stimulus independent thought.

A shared human experience is our active internal mental life. Left without an immediate task that demands full attention, our minds wander jumping from one passing thought to next—what William James (1890) called the “stream of consciousness.” We muse about past happenings, envision possible future events, and lapse into ideations about worlds that are far from our immediate surroundings. In lay terms, these are the mental processes that make up fantasy, imagination, daydreams, and thought. A central issue for our present purposes is to understand to what degree, if any, the default network mediates these forms of spontaneous cognition. The observation that the default network is most active during passive cognitive states, when thought is directed toward internal channels, encourages serious consideration of the possibility that the default network is the core brain system associated with spontaneous cognition, and further that people have a strong tendency to engage the default network during moments when they are not otherwise occupied by external tasks.

Support for the same is then provided. The next task the authors undertake is that of determining the function, usefulness and evolutionary rationale for this default brain activity. Two ,in my opinion not mutually exclusive, theories are offered. One is simulation of something that is not tied to current reality (whether it be past memories, future expectations and scenarios or other peoples intentions, beliefs, perspectives). The other theory is that the default mode is a diffused attentional/ exploration state and is suppressed by foveal attention/task focus. The over activity of default network in Schizophrenia can be related to both theories equally well.

In this section, we explore two possible functions of the network, while recognizing that it is too soon to rule out various alternatives. One possibility is that the default network directly supports internal mentation that is largely detached from the external world. Within this possibility, the default network plays a role in constructing dynamic mental simulations based on personal past experiences such as used during remembering, thinking about the future, and generally when imagining alternative perspectives and scenarios to the present. This possibility is consistent with a growing number of studies that activate components of the default network during diverse forms of self-relevant mentalizing as well as with the anatomic observation that the default network is coupled to memory systems and not sensory systems. Another possibility is that the default network functions to support exploratory monitoring of the external environment when focused attention is relaxed. This alternative possibility is consistent with more traditional ideas of posterior parietal function but does not explain other aspects of the data such as the default network’s association with memory structures. It is important to recognize that the correlational nature of available data makes it difficult to differentiate between possibilities, especially because focus on internal channels of thought is almost always correlated with a change in external attention . We also explore in this section an intriguing functional property of the default network: the default network operates in opposition to other brain systems that are used for focused external attention and sensory processing. When the default network is most active, the external attention system is attenuated and vice versa.

To me both the Sentinel and the Internal Mentation hypothesis appear to be somewhat valid and relevant to Schizophrenia. One can attribute Psychosis to both increased ‘watchfulness’ and and increased internal mentation or mentalizing and I have written about the second hypothesis in detail previously.

The most relevant part of the paper is their discussion of Autism, Schizophrenia and Alzheimer’s. I reproduce the entire autism and Schizophrenia section , highlighting a few points:

Autism Spectrum Disorders

The autism spectrum disorders (ASD) are developmental disorders characterized by impaired social interactions and communication. Symptoms emerge by early childhood and include stereotyped (repetitive) behaviors. Baron-Cohen and colleagues (1985) proposed that a core deficit in many children with ASD is the failure to represent the mental states of others, as needed to solve theory-of-mind tasks. Based on an extensive review of the functional anatomy that supports theory-of-mind and social interaction skills, Mundy (2003) proposed that the MPFC may be central for understanding the disturbances in ASD. Given the convergent evidence presented here that suggests the default network contributes to such functions, it is natural to explore whether the default network is disrupted in ASD.

Developmental disruption of the default network, in particular disruption linked to the MPFC, might result in a mind that is environmentally focused and absent a conception of other people’s thoughts. The inability to interact with others in social contexts would be an expected behavioral consequence. It is important to also note that such disruptions, if identified, may not be linked to the originating developmental events that cause ASD but rather reflect a developmental endpoint. That is, dysfunction of the default network and associated symptoms may emerge as an indirect consequence of early developmental events that begin outside the network.

Many studies have explored whether ASD is associated with morphological differences in brain structure. The general conclusion from this literature is that the brain changes are complex, reflecting differences in growth rates and attenuation of growth (see Brambilla et al. 2003 for review). At certain developmental stages these differences are manifest as overgrowth and at later stages as undergrowth. Early observations have implicated the cerebellum. A further consistent observation has been that the amygdala is increased in volume in children with ASD (e.g., Abell et al. 1999, Schumann et al. 2004), perhaps as a reflection of abnormal regulation of brain growth (Courchesne et al. 2001). While not discussed earlier because of our focus on cortical regions, the amygdala is known to contribute to social cognition (Brothers 1990, Adolphs 2001, Phelps 2006) and interacts with regions within the default network. The amygdala has extensive projections to orbital frontal cortex (OFC) and vMPFC (Carmichael & Price 1995).

Of perhaps more direct relevance to the default network, dMPFC has shown volume reduction in several studies of ASD that used survey methods to explore regional differences in brain volume (Abell et al. 1999, McAlonan et al. 2005). The effects are subtle and will require further exploration, but it is noteworthy that, of those studies that have looked, several have noted dMPFC volume reductions in ASD. Of interest, a study using voxel-based morphometry to investigate grey matter differences in male adolescents with ASD noted that several regions within the default network exhibited a relative increase in grey matter volume compared to the control population (Waiter et al. 2004). Because this observation has generally not been replicated in adult ASD groups, future studies should investigate whether complex patterns of overgrowth and undergrowth of the regions within the default network exist in ASD and, if so, whether they track behavioral improvement on tests of social function (see also Carper & Courchesne 2005).

Kennedy and colleagues (2006) recently used fMRI to directly explore the functional integrity of the default network in ASD. In their study, young adults with ASD and age-matched individuals without ASD were imaged during passive tasks and demanding active tasks that elicit strong activity differences in the default network. While the control participants showed the typical pattern of activity in the default network during the passive tasks, such activity was absent in the individuals with ASD. Direct comparison between the groups revealed differences in vMPFC and PCC. Moreover, in an exploratory analysis of individual differences within the ASD group, those individuals with the greatest social impairment (measured using a standardized diagnostic inventory) were those with the most atypical vMPFC activity levels (Fig. 16). An intriguing possibility suggested by the authors of the study and extended by Iacoboni (2006) is that the failure to modulate the default network in ASD is driven by differential cognitive mentation during rest, specifically a lack of self-referential processing.

Another recent study using analysis of intrinsic functional correlations showed that the default network correlations were weaker in ASD (Cherkassky et al. 2006).Of note, the individuals with ASD showed differences in a fronto-parietal network that has been recently hypothesized to control interactions between the default network and brain systems linked to external attention (Vincent et al. 2007b). These data in ASD suggest an interesting possibility: the default network may be largely intact in ASD but under utilized perhaps because of a dysfunction in control systems that regulate its use.

Schizophrenia

Schizophrenia is a mental illness characterized by altered perceptions of reality. Auditory hallucinations, paranoid and bizarre delusions, and disorganized speech are common positive clinical symptoms (Liddle 1987). Cognitive tests also reveal negative symptoms, including impaired memory and attention (Kuperberg & Heckers 2000). These symptoms lead to questions about their relationship to the default network for a few reasons. The first reason surrounds the association of the default network with internal mentation. Many symptoms of schizophrenia stem from misattributions of thought and therefore raise the question of an association with the default network because of its functional connection with mental simulation. A second related reason has to do with the broader context of control of the default network. While still poorly understood, there appears to be dynamic competition between the default network and brain systems supporting focused external attention (Fransson 2005, Fox et al. 2005, Golland et al. 2007, Tian et al. 2007, see also Williamson 2007). Frontal-parietal systems are candidates for controlling these interactions (Vincent et al. 2007b). The complex symptoms of schizophrenia could arise from a disruption in this control system resulting in an overactive (or inappropriately active) default network. The normally strongly defined boundary between perceptions arising from imagined scenarios and those from the external world might become blurry, including the boundary between self and other (similar to that proposed by Frith 1996).

Three studies have provided preliminary data supporting the possibility that the default network is functionally overactive. Garrity and colleagues (2007) recently reported an analysis of correlations among default network regions in patients with schizophrenia. Studying a sizable data sample (21 patients and 22 controls), they explored task-associated activity modulations within the default network and identified largely similar correlations among default network regions in patients and controls. Differences were noted in specific subregions, as were differences in the dynamics of activity as measured from the timecourses of the fMRI signal. Of particular interest, they noted that within the patient group, the positive symptoms of the disease (e.g., hallucinations, delusions, and thought confusions) were correlated with increased default network activity during the passive epochs, including MPFC and PCC/Rsp. In a related analysis, Harrison et al. (2007) noted accentuated default network activity during passive task epochs in patients with schizophrenia as contrasted to controls, again suggesting an overactive default network. Moreover, within the patient group, poor performance was again correlated with MPFC activation during the passive as compared to the active tasks. Finally, Zhou and colleagues (2007) found that regions constituting the default network were functionally correlated with each other to a significantly higher degree in patients than in control participants. Thus, while the data are limited, these studies converge to suggest that patients with schizophrenia have an overactive default network, as would be expected if the boundary between imagination and reality were disrupted. Overactivity within the network correlates with task performance (Harrison et al. 2007) and clinical symptoms (Garrity et al. 2007).

I now link to two abstracts form Autism and default network research by Kennedy et al:

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 rest-associated 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.

In their discussion they make explicit the fact that in Autism, the default Netwrok may be under active.

There are two possible reasons why the ASD group failed to show the typical deactivation effect. One possibility is that midline resting network activity during both rest and task performance is high, and, thus, a subtraction between these conditions would reveal no difference in activity levels. We believe, however, that it is unlikely that high midline network activity was maintained during the cognitively demanding number task in autism for several reasons. First, as mentioned previously, behavioral performance was similar between control and ASD groups. This result, however, would be unexpected if the ASD group were carrying out additional mental processing that control subjects inhibit during cognitively demanding conditions. Second, positron-emission tomography studies of autism, which provide an absolute measure of brain metabolism, have found reduced, as opposed to increased, glucose metabolism in rACC and PCC (36) during task performance, as compared with controls. Furthermore, one positron-emission tomography study found that lower blood flow in MPFC and rACC at rest was correlated with more severe social and communicative impairments in subjects with autism (37), a finding similar to our correlational results. Third, reduced anatomical volumes and neurochemical deficiencies have consistently been observed in MPFC?rACC in adults with autism (reviewed in ref. 26), likely indicative of a reduced functioning of these regions. Therefore, an alternative explanation, the one to which we attribute the lack of deactivation, is that midline activity is low during rest. We suggest, then, that the absence of deactivation in this network indicates that the mental processes that normally occur at rest are absent or abnormal in autism.

What are these mental processes that dominate during rest? Evidence in the literature to date seems to suggest that tasks that induce certain types of internal processing activate this resting network. Examples of such tasks are self- and other-person judgments (4, 6, 7, 19–22, 38–45), person familiarity judgments (24, 25), emotion processing (15–17, 46), perspective-taking (22, 47), passive observation of social interactions vs. nonsocial interactions (18), relaxation based on interoceptive biofeedback (48, 49), conceptual judgments (based on internal knowledge stores) vs. perceptual judgments (50), and episodic memory tasks (51), among others [moral decision making (52), joint attention experience (23), and pleasantness judgments (53)]. Therefore, the activity in these regions at rest might simply reflect the extent to which these types of internally directed thoughts are engaged at rest. In fact, a particularly intriguing behavioral study found that individuals with ASD report very different internal thoughts than control subjects (54, 55), lending support to our interpretation that an absence of this resting activity in autism may be directly related to abnormal internal thought. Admittedly, this is a speculative hypothesis but one that can be explicitly tested.

Another of their recent papers comes to the same conclusion.

Recent studies of autism have identified functional abnormalities of the default network during a passive resting state. Since the default network is also typically engaged during social, emotional and introspective processing, dysfunction of this network may underlie some of the difficulties individuals with autism exhibit in these broad domains. In the present experiment, we attempted to further delineate the nature of default network abnormality in autism using experimentally constrained social and introspective tasks. Thirteen autism and 12 control participants were scanned while making true/false judgments for various statements about themselves (SELF condition) or a close other person (OTHER), and pertaining to either psychological personality traits (INTERNAL) or observable characteristics and behaviors (EXTERNAL). In the ventral medial prefrontal cortex/ventral anterior cingulate cortex, activity was reduced in the autism group across all judgment conditions and also during a resting condition, suggestive of task-independent dysfunction of this region. In other default network regions, overall levels of activity were not different between groups. Furthermore, in several of these regions, we found group by condition interactions only for INTERNAL/EXTERNAL judgments, and not SELF/OTHER judgments, suggestive of task-specific dysfunction. Overall, these results provide a more detailed view of default network functionality and abnormality in autism.

If you want to read more about Schizophrenia – default network linkage , read here. If you want to read about Default Network in general , read here ( a very good blog I have recently discovered).

I think the case is settled that at least in the case of Default Network activations, Schizophrenia and Autism are on opposite poles. One has too much default brain activity, the other too little. Also, the function of default network suggests that it is primarily the focus on self and the ability to imagine that is disrupted in autism and heightend to dramatic effects in Schizophrenics.
ResearchBlogging.org

R. L. BUCKNER, J. R. ANDREWS-HANNA, D. L. SCHACTER (2008). The Brain’s Default Network: Anatomy, Function, and Relevance to Disease Annals of the New York Academy of Sciences, 1124 (1), 1-38 DOI: 10.1196/annals.1440.011
D. P. Kennedy, E. Courchesne (2008). Functional abnormalities of the default network during self- and other-reflection in autism Social Cognitive and Affective Neuroscience, 3 (2), 177-190 DOI: 10.1093/scan/nsn011
D. P. Kennedy (2006). Failing to deactivate: Resting functional abnormalities in autism Proceedings of the National Academy of Sciences, 103 (21), 8275-8280 DOI: 10.1073/pnas.0600674103

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