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Default Mode Network (DMN) is a series of co-activated sub-systems that remains active when an individual is in a state of wakeful rest. While there are no definitive functions of DMN as of yet, many potential functions has been proposed and correlated ranging from internal processes such as self-reflection to diffused passive attention[1] . DMN is generally inhibited by most cognitive tasks, however, tasks involving episodic memory does not deactivates DMN, suggesting a link[2] . Additionally, the regions containing beta-amyloid plaques found in Alzheimer's Disease overlaps with the regions of DMN, further consolidate the link and is of importance clinically[3] . Age differences in the ability to deactivate DMN has also been found between older and younger adults, which may reflect the cognitive change experienced in normal aging[4] .

1.Anatomy of the DMN

Multiple imaging approaches has indicated posterior cingulate cortex (PCC), dorso- and ventromedial prefrontal cortex (dMPFC, vMPFC), inferior parietal lobe (IPL), and medial temporal lobe (MTL) as parts of DMN in human. The functional anatomy was originally identified by using a task-induced deactivation paradigm with Positron Emission Tomography (PET)[5] [6] . The paradigm involved using active tasks such as finger movement and vocalization[7] to deactivate DMN, the regions with decreased cerebral blood flow due to the shift from a rest state to active state were taken as regions of the DMN.

A separate method uses functional connectivity Magnetic Resonance Imaging (fcMRI), which correlates brain regions that share spontaneous fluctuation of activities temporally[8] . The areas found with fcMRI were similar to those found with task-induced deactivation[9] . The regions of DMN are thus found to be functionally connected which was thought to reflect some underlying anatomical connections. Recent study used both Diffuse Tensor Imaging (DTI) to track white matter tracts and fcMRI to track functional connection, has shown that many regions of DMN are structurally connected, although a direct anatomical connection between MPFC and MTL, as well as between angular gyri and other regions were not observed[10] .

PCC, IPL, and vMPFC are major nodes that all other regions of DMN are functionally connected to[11] . DMN also contain subsystems, one example is that the dMPFC and hippocampal formation are both functionally connected to all the major nodes previously mentioned, but are not functionally and structurally connected[12] to each other . The separate subsystems may also interact with brain regions outside of DMN as explained in the section on the function of DMN.

2. Functions of DMN

Based on the functional anatomy of DMN, 2 majors hypothesis has been proposed to address its cognitive functions. There are evidence that supports and refutes both hypothesis and a consensus has yet to be reached.

2.1 Internal Mentation Hypothesis

The internal mentation hypothesis holds that DMN is important in introspection and internal attention. Internal tasks that activate the DMN can be roughly divided into three categories:
FIgure 1. Overlapping activation of DMN nodes in internal mentation tasks. Click figure for more info on d) from neurobiology of morality wikipage. Taken from Reference 1.

2.1.1 Mental time travel for past memories or imagining a future scene

When participants were asked to retrieve an autobiographical memory, fMRI showed activation of regions within DMN[13] . In addition, when asked to retrieve previously learnt episodic memories, DMN activity was greater for successfully retrieved memories than those that were forgotten[14] . Similar areas were also activated when participants were asked to imagine a personal scene in the future[15] . However, when participants were given an internal-encoded vs an external-encoded event (Ex. Internal asked a participant to imagine a duck quack and pair with a target while external played the audio of a duck with a target), greater DMN activation did not predict whether an episodic memory (tested with a source memory task) was successfully encoded[16] . This is significant since internal mentation hypothesis would predict internal-encoded memories to benefit from DMN activation, which was not found.

2.1.2 Mind wandering

Mind wandering as measured by sustained attention to response (SART) task activates PCC, MPFC, and posterior temporoparietal cortex, sharing some of the nodes to the DMN[17] . This effect was lessened if the participant self-reported that no mind wandering has occurred or if an error is made during a trial, which is consistent with the finding that greater DMN activation predicts errors in the modified flanker task[18] . However, mind wandering also recruits parts of the executive network, most notably anterior cingulate cortex (ACC) and dorsollateral pre-frontal cortex (DLPFC), and the recruitment of executive network is more pronounced during trials where participants reports no meta-awareness of their mind wandering[19] . The recruitment of both networks which are usually mutually inhibitory is also seen during tasks involving creative thinking.

2.1.3 Theory of Mind

Theory of mind (ToM) is a form of perspective taking that becomes impaired in some disorders such as autism (see DMN in mental disorders for more info). When asked to take the perspective of another person vs an inanimate object within a scenario, DMN nodes including PCC, dMPFC, temporoparietal junction were active in healthy participants[20] . In addition some regions of DMN such as PCC was only active during tasks requiring late-developed system of ToM such as understanding another persons thought.

2.2 Sentinel Hypothesis

According to the sentinel hypothesis, DMN supports a low level “exploratory” attention that surveys for unexpected stimuli. Studies on neural substrate of diffuse attention supports this hypothesis. Tasks that involves presenting stimuli to fovea will deactivate DMN more than those that are shown to non-foveal regions[21] . Additionally, participants with greater activation in DMN nodes such as PCC and angular gyrus detects uncued peripheral stimuli faster, but performance for cued central stimuli does not depend on DMN activation[22] . Lastly, Balint's Syndrome involves bilateral leison to precuneus[23] .

2.3 DMN and Episodic Memory

The link between DMN and episodic memory is well established. This relationship was particularly problematic in studies of episodic memory since early imaging study asked participants to rest as a baseline, which made differential activation of the MTL difficult to measure[24] . It is now known that retrieval of episodic memories, whether internally or externally cued, relies on DMN[25] . Furthermore, dysfunction of both grey matter of DMN nodes as well as white matter connections are implicated in Alzheimer's disease (AD), a disease with prominent effects on episodic memory.

Figure 2.Tulving on the distinction between semantic and episodic memories.
Figure 2.Tulving on the distinction between semantic and episodic memories.

3. DMN in Healthy and Pathological Aging

Figure 3. Overlap between DMN and amyloid deposit, Atrophy and metabolic disruption overlaps with the posterior regions of DMN and amyloid deposit. Taken from reference 26.

3.1 Alzheimer's Disease and DMN

An important finding that suggested a relationship between AD and DMN was the observation that the distribution of Amyloid ß protein found in AD patients overlapped with DMN distribution in young adults[26] . This led to the formation of the metabolism hypothesis which proposes that vulnerability to AD changes metabolism-cascade in regions of the DMN, creating regional conditions which promotes Amyloid ß formation. Recent study in DMN activity in APOE-//ε//4 carriers gives support to this hypothesis. It was found that healthy APOE-ε4 carriers show greater activity in PCC, MTL, MPFC than non-carriers in young adults[27] . APOE-ε4 also correlates with disturbance in white matter tract such as the cingulum, which is consistent with the finding that APOE-ε4 carriers show less activity in ACC and PCC compared to non-carriers in older adults[28] .

Dysfunction to the DMN nodes has been found in patients with mild cognitive impairment (MCI) and probable AD as well. The cingulum was again found to be affected, having functional disconnection in both patients with MCI and AD[29] . However, PCC grey matter atrophy was more wide spread in patients with AD relative to those affected by MCI, raising the possibility that PCC atrophy follows cingulum disconnection, causing the the progression from MCI to AD[30] . Another DMN node connected by the cingulum bundle, the hippocampus is also affected. There are more asynchrony within the hippocampus neurons in patient with MCI than in healthy controls, patients with probable AD has the highest amount of asynchrony as measured by fMRI[31] . In addition, the asynchrony found in hippocampus and PCC seems to spread to other regions of DMN following the progression from MCI to AD[32] .Asynchrony is an extreme form of DMN dysfunction that can also be found in normal aging.

3.2 DMN in Healthy Older Adults

The DMN organization in healthy older adults is also less efficient relative to younger adults, leading to a difficulty to deactivate DMN when needed to switch to a task-oriented network[33] . This difficulty to switch becomes more pronounced with increase in the task difficulty, and consequently older adults who are worse at deactivating DMN tend to have higher reaction time in both verbal and non-verbal tasks requiring the task-oriented network.

Figure 4. An overview of APOE's effect on neurons in Alzheimer's Disease.
Figure 4. An overview of APOE's effect on neurons in Alzheimer's Disease.

Back to 'Default Mode Network
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