Exploring the relationship between acute stress, resting state
functional connectivity and Mindfulness Based Interventions:
A narrative review
Literature Thesis Brain and Cognitive Sciences - Final Version By: Loulou Koppenol
Abstract
Adapting to acute stress has been related to configuration of large-scale brain networks involved in cognitive and affective processes including the salience network (SN), default mode network (DMN), and executive control network (ECN). Sustained or altered activation of large-scale brain networks during the adaptation to acute stress may play a critical role in long-term pathologies including depression, anxiety, burnout, and sleeping problems.
Mindfulness Based Interventions (MBI) may help prevent these long-term pathologies through cultivating emotional regulation and attentional control, fostering resilience against stressful situations. By understanding how brain network configurations play a role in adapting to acute stress and the effectiveness of MBIs, clinical treatment for individuals prone to stress may be improved. Recent studies have indicated that MBIs reduce stress through self-regulation of the same large-scale brain networks involved in adapting to acute stress, namely the SN, DMN and ECN. Despite its relevance, studies adopting an interdisciplinary approach that integrate findings from different areas surrounding acute stress and MBIs are currently limited. This narrative review will therefore explore current literature on resting state functional connectivity and activity, acute stress and MBIs in relation to the large-scale brain networks. In turn, these
findings are integrated to identify gaps in the literature and will propose ideas for future research.
Table of Contents
Abstract 1
1. Introduction and definition of problem 3
2. Overview and critical discussion of studied literature 6
2.1 Short explanation of resting state functional connectivity and activity 6
2.2 Acute stress and large-scale brain network configurations 9
2.2.1 Acute stress upregulates brain regions within the SN 9 2.2.2 Acute stress causes general and regional upregulation within the DMN 9 2.2.3 Acute stress does not alter resting-state connectivity within the ECN 11
2.3 Acute stress and large-scale brain networks interactions 11
2.3.1 Acute stress increases functional coupling between the SN-DMN 12 2.3.2 No evidence for resting-state alterations between SN-ECN after acute stress 12 2.3.3 No evidence for resting-state alterations between DMN-ECN after acute stress 13
2.4 Network perspective on acute stress; short summary 13
2.5 Mindfulness Based Interventions and large-scale network configurations 16
2.5.1 MBIs alter functional connectivity and activity within the SN 16 2.5.2 MBIs increase connectivity between DMN and sensory cortex 17
2.5.3 MBIs increase connectivity within the ECN 18
2.6 Network perspective on mindfulness; short summary 18
2.7. Acute stress, MBIs and between-network connectivity 20
3. Personal critical opinion 20
4. Limitations 22
5. Conclusion 23
References 24
1. Introduction and definition of problem
Stress is an adaptive response to challenges or demands in the environment of an individual that may pose as a threat. These challenges or demands in one's environment that trigger stress are referred to as stressors. Stress is thus an adaptive response to social or physical stressors and occurs at multiple different levels both mentally and physically and may include psychological, physiological, and metabolic adaptations (McEwen et al., 2015). The brain plays a central role in this response and can therefore be seen as the central organ in adapting to stress; it determines what is threatening, stores memories, and regulates the physiological and
behavioural responses to these stressors (McEwen et al., 2015). Adaptation to stress can be seen as a complicated process as different stressors may also require different physiological and behavioural responses. Furthermore, the duration of the stress response may play an important role in the long-term effects of stress on both physical and mental health. To specify, stress can present itself briefly, which is called acute stress, or chronically spanning over a longer period of time referred to as chronic stress (American Psychological Association, 2018)
During an acute stress response, the brain may alter cognitive, physiological, and
psychological functioning in response to stressors in the environment (Hermans, Henckens, Joëls & Fernández, 2014). More specifically, the brain may adjust neural functioning by strategically reallocating neural resources to functions which are essential for an appropriate response to threat (Maron-Katz, Vaisvaser, Lin, Hendler & Shamir, 2016; Soares et al., 2013). This neural resource reallocation leads to an increase in vigilance, arousal, and memory encoding of stressful experiences—adaptations which are functional when short-lived (Maron-Katz et al., 2016; Soares et al., 2013). In healthy individuals, recovery from acute stress responses therefore has a short duration as mental and physiological alterations quickly return to baseline, referred to as homeostasis (Van Oort at al., 2017). Contrarily, in some individuals this homeostasis is not quickly regained due to repeated activation of an acute stress response causing both mental and physical adaptations. This recurrent triggering of an acute stress response thus may become dysfunctional as these adaptations do not return to baseline. Over time this type of chronic stress may have harmful implications as it is damaging to the body to be in a prolonged state of stress. In addition, recurrent acute stress or chronic stress may also increase the risks for mental health problems.
Notably, sustained activation of large-scale brain networks during the aftermath of acute stress may play a critical role in triggering long-term pathologies including depression, anxiety, burnout, and sleeping problems (Hermans et al., 2014). The debilitating long-term impact of severe acute stress is also evident in the Diagnostic and Statistical Manual of Mental Disorders - 5 (DSM-5), where acute stress disorder is listed under the disorder class of Trauma-and
Stressor-Related Disorders (American Psychiatric Association, 2013). Acute stress disorder can be the result of exposure to a traumatic event triggering a chronic stress response leading to serious adverse symptoms including negative mood, distressing memories, dissociative
symptoms, and intense or prolonged psychological distress (American Psychiatric Association, 2013). Repeated acute stress or severe acute stress leading to chronic stress may negatively impact health of the body and may increase the risk for mental-health problems highlighting the importance of effective interventions for the management of stress. Taken together, acute stress initiates a functional response in the brain but may become dysfunctional when repeatedly
triggered. For this reason, evidence-based stress-reducing interventions may play a critical role in managing or even preventing stress-related symptomatology.
One such evidence-based stress-reducing intervention is Mindfulness Based Stress Reduction (MBSR). MBSR is a specific type of Mindfulness Based Intervention (MBI)
consisting of an eight-week evidence-based program offering intensive mindfulness training to promote stress-reduction. Mindfulness can be defined as actively paying attention to the present moment by observing internal or external sensations that arise into consciousness including body sensations, sounds, thoughts, or emotions (Kabat-Zinn, 1994). By practicing mindfulness
meditation, an individual becomes aware of their emotional, cognitive, or behavioural patterns while fostering a non-judgmental accepting stance towards these observations (Kabat-Zinn, 1994). Through extensive mindfulness meditation, MBSR thus seeks to downregulate emotional reactivity and alter cognitive appraisal towards stressful situations (Khoury, Sharma, Rush & Fournier, 2015). For this reason, MBSR was developed in 1979 by Professor Jon Kabat-Zinn to treat medical patients with maladaptive health behaviours, stress-related conditions, chronic pain and low mood (Kabat-Zinn, 1994). Nowadays, MBSR is widely used in both general and clinical populations for treatment of stress, anxiety and depression (Virgili, 2015).
Although the efficacy of MBSR in the treatment of stress-related symptomatology has been implicated in a multitude of studies (Khoury et al., 2015), its neural working mechanisms
remain to be fully elucidated (Mooneyham, Mrazek, Mrazek & Schooler, 2016). Broadening our understanding of how MBSR works in the brain may contribute to improved clinical treatment of stress and help alleviate physical and mental health conditions experienced by individuals prone to stress. As MBSR is a stress-reducing intervention (Virgili, 2015), its working mechanism may alter neural pathways that are activated when stress is induced. Therefore, by looking at how stress-induction alters neural functioning, the mechanism of action of MBSR may be better understood.
Previous research investigating acute stress responses have demonstrated alterations in large-scale distributed brain networks during adaptation to acute stress (Hermans et al., 2014). Interestingly, recent studies on the neurocognitive working mechanisms of MBIs have also indicated the involvement of large-scale brain networks (Taren et al., 2017). More specifically, according to a theoretical review on acute stress (van Oort et al., 2017) and another on MBIs (Mooneyham et al., 2016), alterations in resting-state functional connectivity of three large-scale brain networks are most consistently reported across literature and include the salience network (SN), default mode network (DMN), and executive control network (ECN). Resting-state networks provide information about the distribution and organization of major functional systems in the brain (Fox & Greicius, 2010). Specifically, van Oort et al. (2017) suggest that sustained or altered activation of these three large-scale brain networks while adapting to acute stress may play a critical role in triggering long-term pathologies such as depression, anxiety, burnout, and sleeping problems. On the other hand, MBIs may have stress-reducing implications through self-regulation of these same large-scale brain networks (Mooneyham et al., 2016).
Currently, studies utilising an interdisciplinary approach, one that integrates these neuroscientific findings on resting state functional connectivity in relation to acute stress and MBIs do not exist. This paucity of neuroscientific reviews integrating existing literature into an understandable framework is a major limitation in current literature. Therefore, the development of an interdisciplinary theoretical framework that integrates findings across different research areas may help us to better understand how brain network configurations play a role in adapting to acute stress, and also inform us on the effectiveness of MBIs (Alsubaie et al., 2017).
For this reason, this paper will integrate neuroscientific findings on resting-state
functional connectivity and activity, acute stress, and MBIs. This integration will be conducted by writing a narrative review, which is a comprehensive, critical and objective analysis of the
current knowledge on a topic that helps to establish a theoretical framework on a specific area of research. Therefore, by writing a narrative review on how the relationship between acute stress and large-scale network configuration is influenced by MBIs, this paper aims to identify current gaps in the literature. We will first introduce the three large-scale brain networks, SN, DMN, and ECN, and how they may be altered after acute stress induction according to a recent theoretical review from van Oort et al. (2017). Subsequently, evidence on the relationship between MBIs and large-scale brain network adaptations will be summarised using a recent theoretical review from Mooneyham et al. (2016). In addition, other relevant empirical studies on either acute stress or MBI and large-scale brain network configurations will also be included in this review. Finally, this narrative review will synthesise this literature on acute stress and MBIs to form an
interdisciplinary theoretical framework. With this integration, the goal is to identify gaps in current research and propose ideas for future studies.
2. Overview and critical discussion of studied literature
2.1 Short explanation of resting state functional connectivity and activity
Resting-state functional connectivity measures temporal correlation of spontaneous Blood Oxygen Level Dependent (BOLD) signals among spatially distributed brain regions using functional Magnetic Resonance Imaging (fMRI) (Woodward & Cascio, 2015). The analysis of task-free functional connectivity using temporal correlations has identified resting-state networks across different brain regions (Menon & Krishnamurthy, 2019). These resting state networks may provide information about the distribution and organization of major functional systems in the brain supporting core perceptual and cognitive processes (Fox & Greicius, 2010). Moreover, a distinction can be made between resting-state functional connectivity and resting-state
functional activity. Namely, alterations in functional connectivity refer to changes in connectivity between spatially distributed brain regions, alterations in functional activity on the other hand, refer to changes in activity within a single brain network.
Here we define resting-state scans as scans in which the subject did not perform a task. This method can be implemented in acute stress research by measuring the period directly after stress induction (Maron-Katz et al., 2016; van Marle, Hermans, Qin & Fernández, 2010;
Quaedflieg et al., 2015). Resting-state scans of three coherent large-scale brain networks will be 6
reviewed: the salience network, the default mode network and the executive control network. Even though each network consists of mainly different groups of brain regions, there are inconsistencies in current literature with respect to which brain regions are involved in each network (van Oort et al., 2017). However, some brain regions are more consistently reported as part of a specific network than other networks (van Oort et al., 2017). For clarity reasons, here we adhere to the structural organization of brain regions within each network as listed in Table 1.
Table 1
An overview of anatomical brain regions involved in the salience network, the default mode network, and the executive control network (Hermans et al., 2014; van Oort et al., 2017)
Note. Structural brain images in the third column are templates from the Functional Imaging in Neuropsychiatric Disorders Laboratory, taken from Young et al. (2017)
8
Brain networks Regions Visualization
Salience Network
● Amygdala
● Dorsal anterior cingulate cortex ● Hypothalamus ● Anterior insula ● Thalamus ● Temporoparietal junction ● Midbrain ● Brainstem
Default Mode Network
● Medial prefrontal cortex (anterior part) ● Posterior cingulate cortex + precuneus
(posterior part)
● Inferior parietal lobule
○ Supramarginal gyrus ○ Angular gyrus ● Hippocampus
● Superior prefrontal cortices ● Temporoparietal regions
Executive Control Network
● Dorsolateral PFC
● Precentral/superior frontal sulci ● Frontal eye fields
● Dorsomedial PFC
● Dorsal posterior parietal cortex ● Supplementary motor cortex
2.2 Acute stress and large-scale brain network configurations
2.2.1 Acute stress upregulates brain regions within the SN
The human nervous system is subject to a constant stream of sensory inputs (Menon, 2015). In dangerous situations, the ability to detect salient threat-laden information from this stream of input, reorient attention and take rapid action, is crucial for survival (Hermans et al., 2014). The SN has been related to the detection of salient stimuli and is involved in orienting attention towards these stimuli, especially in situations that involve acute stressors (van Oort et al., 2017; van Marle et al., 2010). Indeed, brain regions within the SN (Table 1) serve essential functions including processing of fear, visceral perception, and attention that might underlie this highly adaptive acute stress response (Hermans et al., 2014).
An acute stress response appears to cause a stress-induced network shift towards the SN, upregulating the brain regions within the SN (Hermans et al., 2011, 2014). This is confirmed by a study demonstrating increased resting-state functional coupling of the amygdala, dorsal
anterior cingulate cortex, anterior insula and other regions within the SN (van Marle et al., 2010). Moreover, this study shows that adaptation to acute stress is qualified by prolonged activation within this amygdala connectivity network of the SN (van Marle et al., 2010). Thus, adapting to acute stress appears to be characterised by increased functional connectivity within the SN together with prolonged activation of brain regions within the SN. This increased functional connectivity and prolonged activation within the SN leads to an extended state of hypervigilance and sustained salience, functions which are thought to be important for the rapid
stimulus-response behaviours triggered by an acute stress response (van Marle et al., 2010; Hermans et al.,2014).
2.2.2 Acute stress causes general and regional upregulation within the DMN
Whereas the SN is important for orienting attention to external or internal stimuli, the DMN plays an important role in spontaneous and self-generated thought processes (van Oort et al., 2017). Moreover, there is evidence for functional regional specializations within the DMN (Pruessner et al., 2008; Soares et al., 2013). Specifically, the anterior part of the DMN (Table 1) has been related to self-referential processing and emotional regulation, whilst the posterior part has been related to consciousness and memory processing (Andrews-Hanna, Reidler, Sepulcre,
Poulin & Buckner, 2010; van Oort et al., 2017). These regional specialisations within the DMN may be indicative of subsystems executing different functions that can be activated or
deactivated in line with varying external demands (van Oort et al., 2017). One such external demand may be threat detection leading to an acute stress response. Indeed, this acute stress response appears to trigger widespread activation within the DMN with possible dissociation between the anterior and posterior part of the DMN (van Oort et al., 2017).
An acute stress response appears to cause a stress-induced network shift towards the DMN by altering connectivity and activity of brain regions within the DMN (Soares et al., 2013). More specifically, according to studies performing resting-state scans after stress-induction the PCC, a key node in the DMN, shows increased functional coupling to other nodes in the DMN (Vaisvaser et al., 2013; Veer et al., 2011). This increased functional coupling may be indicative of an enhancement of self-referential mental processes and immediate reflection of the stressful experience (Vaisvaser et al., 2013). Furthermore, another study has shown increased functional connectivity between the mPFC and pCC of the DMN in a cohort of participants exposed to prolonged stress, which is indicative for an upregulation of brain regions within the DMN after repeated acute stress (Soares et al., 2013).
In addition to unsystematic upregulation of brain areas within the DMN, there is also evidence for specific regional upregulation within the DMN following an acute stress response (Pruessner et al., 2008; Soares et al., 2013). Indeed, one study has demonstrated that increased activation of the anterior part of the DMN in participants exposed to prolonged stress leads to increased self-reflective thoughts and increased dynamic interaction between emotional
processing and cognitive functions (Soares et al., 2013). On the other hand, increased activation in the posterior regions of the DMN of the same participants was also associated with prolonged processing of emotionally salient stimuli and episodic memory retrieval (Soares et al., 2013).
Taken together, an acute stress response causes a stress-induced network shift towards the DMN as well as the SN. In addition, there is evidence to suggest both unsystematic
upregulation and specific regional upregulation within brain areas of the DMN after acute stress where parts of the DMN may be activated or deactivated in accordance with the type of external demands triggered by the acute stressor.
2.2.3 Acute stress does not alter resting-state connectivity within the ECN
While the DMN can be seen as the neurological basis for self-referential processing, the ECN has mainly been associated with voluntary direction of attention, executive functioning and higher-order cognition (van Oort et al., 2017). The ECN consists of a fronto-parietal network of brain regions (Table 1) with the dorsolateral PFC as a key hub implicated in behavioural control, regulation of attention, decision making, working memory and cognitive control (Menon & Uddin, 2010). Whereas these functions underlie executive functioning and goal-directed behaviour, they may be less functional for the rapid action required by an acute stressor (van Oort et al., 2017). Indeed, a thorough theoretical review shows that according to resting-state studies, stress paradigms do not induce changes in the ECN, however task-related studies indicate that the ECN may be involved with higher-order cognitive tasks under stress (van Oort et al., 2017). Results regarding the involvement of the ECN in an acute stress response thus appear to be inconsistent (van Oort et al., 2017).
Specifically, studies conducted on resting-state connectivity and acute stress do not report on any changes in the ECN after stress induction (Maron-Katz et al., 2016; van Marle et al., 2010; Quaedflieg et al., 2015; Vaisvaser et al., 2013). Task-related studies, on the other hand, demonstrate increased ECN activation during an acute stressor with higher-order cognitive elements (Porcelli et al., 2008; Weerda, Muehlhan, Wolf & Thiel, 2010). It could be argued that this discrepancy indicates involvement of the ECN solely in acute stressors with higher-order cognitive elements. Although, due to the limited number of studies confirming this, this proposal is only hypothetical. Hence, more research on this network is needed to make more robust conclusions about resting-state connectivity within the ECN during adaptation to acute stress. 2.3 Acute stress and large-scale brain networks interactions
From the above, it appears that acute stress alters functional connectivity and activity within several large-scale brain networks. As these networks dynamically interact with one another, it is also valuable to explore how an acute stress response may trigger between-network connectivity changes of the SN, DMN and ECN.
2.3.1 Acute stress increases functional coupling between the SN-DMN
Firstly, according to the theoretical review of van Oort et al. (2017), between network connectivity of the SN and DMN may be an important factor for memory consolidation after a stressful event. This hypothesis is supported by studies demonstrating increased coupling of the amygdala (a key node of the SN) to the hippocampus and parahippocampal gyrus (nodes of the DMN) after stress-induction (Quaedflieg et al., 2015; Vaisvaser et al., 2013). Moreover, this enhanced functional coupling between the SN and DMN was shown to last for up to two hours after stress induction and was positively correlated with reported subjective stress levels (Vaisvaser et al., 2013). Although memory of the stressful event was not investigated in the aforementioned studies, the hippocampus and parahippocampal gyrus are known to play an important role in memory encoding and retrieval (Quaedflieg et al., 2015; Vaisvaser et al., 2013). Therefore, these findings may indicate that increased functional coupling of the SN and DMN alters memory consolidation after an acute stressor. The exact mechanism of how memory consolidation may be altered by increased functional coupling of the SN and DMN remains unknown however, and hence, more studies are needed to clarify this relationship. Given the above, evidence suggests increased functional coupling of the DMN and SN during adaptation to acute stress.
2.3.2 No evidence for resting-state alterations between SN-ECN after acute stress
No studies reporting on alterations in resting-state connectivity between the SN and ECN during adaptation to acute stress were found in the literature. However, a particular task-related empirical study reporting on increased activity of both the ECN and SN during a higher-order cognitive task with stress-inducing negative feedback could be identified (Lederbogen et al., 2011). As previously mentioned, the ECN may be involved with higher-order cognitive tasks under stress. Therefore, it is important to note that this finding of increased activation of the ECN may have been due to a higher cognitive load in the stressful condition. Furthermore, this study does not report on alterations in functional coupling between the ECN and SN but solely reports dual activation of both the ECN and SN. In sum, due to the limited amount of evidence on resting-state connectivity robust conclusions regarding the existence of interactions between the SN and ECN after stress-induction cannot be made.
2.3.3 No evidence for resting-state alterations between DMN-ECN after acute stress
Similar to research on the interconnectivity between the SN-ECN, evidence for alterations in DMN-ECN resting-state connectivity is also non-existing in current literature. Nonetheless, task-related studies have reported on functional coupling of the DMN and ECN after stress-induction and could give an indication of the interaction between the DMN and ECN. Specifically, two studies have reported that working-memory related activation of the ECN under stress is accompanied by a failure to suppress activity in DMN regions (Qin et al., 2009; Cousijn, Rijpkema, Qin, van Wingen & Fernández, 2012). According to a theoretical review, this finding indicates that acute stress may limit allocation of processing resources to the ECN, as neural resources need to also be allocated to the DMN (Hermans et al., 2014). This functional coupling between the ECN and DMN after working-memory related stress-induction may be relevant to promote higher-order cognition (related to ECN) together with memory processing (related to DMN) of the stressful event (Hermans et al., 2014). Hence, according to task-related studies, there appears to be some evidence for an interaction between the DMN and ECN after acute stress-induction. However, in order to make conclusions about resting-state connectivity alterations after acute-stress, new studies are needed to confirm these findings in resting-state paradigms.
2.4 Network perspective on acute stress; short summary
It appears that evidence for functional correlates of different large-scale brain networks after acute stress-induction is accumulating. Overall, current findings appear to support the hypothesis that the SN is upregulated after stress induction with brain regions within the SN showing increased connectivity including the amygdala, dorsal anterior cingulate cortex and anterior insula. Moreover, evidence suggests that the DMN is also upregulated following an acute stress response with increased connectivity within the PCC and mPFC. In addition, research also suggests a dissociation between anterior and posterior regions of the DMN in response to the type of response required by acute stressors. Lastly, studies reporting on the involvement of the ECN after stress-induction show mixed results with some results indicating no changes in connectivity and other results showing upregulation of the ECN for stressors with higher-order cognitive elements.
With regards to interactions, studies have also reported on between-network connectivity changes of the SN, DMN and ECN after stress-induction. However, in this field of research, theoretical assumptions appear to by far outweigh empirical findings. Therefore, only very preliminary conclusions can be formulated about alterations in between-network connectivity after an acute stressor. These preliminary conclusions indicate that acute stress may trigger increased functional coupling of the SN with the DMN. Evidence does not support increased functional coupling of the SN and ECN nor between the ECN and DMN. That being said, dual activation of the ECN with both the SN and DMN has been demonstrated in acute stress research. A summary of the above can be found in Table 2.
Table 2.
This table summarises findings on resting-state functional connectivity alterations in the SN, DMN, and ECN after stress-induction.
Note. ↑ = increased connectivity; ↓ = decreased connectivity;
1(Maron-Katz et al., 2016; van Marle et al., 2010; Quaedflieg et al., 2015; Vaisvaser et al., 2013) 2(van Oort et al., 2017; Vaisvaser et al., 2013)
3(Andrews-Hanna, Reidler, Sepulcre, Poulin & Buckner, 2010; van Oort et al., 2017; Pruessner et al., 2008; Soares
et al., 2013)
4(Hermans et al., 2014) 5(van Oort et al., 2017) 6(Lederbogen et al., 2011)
15
Network Alterations after acute stress Interactions
Salience Network
● ↑ amygdala & hippocampus + hippocampal gyrus ● ↑ amygdala + ACC + insula ● Prolonged activation ● Upregulation 1 ● Functional coupling SN with DMN ● Dual activation SN with ECN 2
Default Mode Network
● Widespread activation ● ↑ PCC + mPFC ● Dissociation between
anterior and posterior regions ● Upregulation 3 ● Functional coupling DMN with SN ● Dual activation DMN with ECN 4
Executive Control Network
● Mixed results ● ↓ ECN
● ↑ ECN for stressor with higher cognitive elements ● Downregulation
5
● Dual activation ECN with SN
● Dual activation ECN with DMN
2.5 Mindfulness Based Interventions and large-scale network configurations Resting-state studies on Mindfulness Based Interventions (MBI) tend to be carried out after mindfulness training. As such, a theoretical review by Mooneyham et al. (2016) has explored how MBIs may alter functional connectivity of large-scale brain networks. In addition to discussing parts of Mooneyham and colleagues’ (2016) theoretical review, empirical evidence will also be reviewed to explore how MBIs may alter functional connectivity within and between the SN, ECN, and DMN in response to stress.
2.5.1 MBIs alter functional connectivity and activity within the SN
According to an empirical study (Kilpatrick et al., 2011), MBSR trained subjects show increased functional connectivity within sensory networks and between regions associated with attentional processes. Specifically, participants in this study show increased functional
connectivity between the salience network, including the posterior insula, and the parietal operculum, areas dealing with taste, somatosensory and motor function (Kilpatrick et al., 2011). Additionally, MBSR trained subjects exhibit greater differentiation between regions within the SN, which may be an indication of better attentional resource allocation and more consistency in attentional focus (Kilpatrick et al., 2011). Another empirical study (Taren et al., 2015)
demonstrated decreased amygdala-subgenual anterior cingulate cortex (sgACC) functional coupling in subjects who received a mindfulness meditation training. According to the results of this study, stress may increase amygdala-sgACC resting state functional connectivity which can be reversed by an MBI. These findings provide an initial indication that MBIs may alter
connectivity within the SN, suggesting an amygdala-sgACC pathway for stress reduction effects (Taren et al., 2015).
In addition to altering resting state functional connectivity within the SN, MBIs may also alter the level of activity in brain regions within the SN. Indeed, according to a systematic review, the most consistent finding across literature is increased insula reactivity after
completion of MBSR (Young et al., 2018). This region of the frontal lobe is part of the SN and associated with self-awareness and interoception, two primary mechanisms for present-moment awareness which is trained in MBSR (Young et al., 2018). Moreover, Menon & Uddin (2010) suggest that the anterior insula may also be involved in the initiation of dynamic switching between the ECN and the DMN (Menon & Uddin, 2010). Thus, as opposed to large-scale
upregulation within the SN as demonstrated in acute stress research (Hermans et al., 2011, 2014), mindfulness appears to upregulate a singular region, the insula, which may play a role in network regulation.
According to these studies, MBIs thus may increase functional connectivity within sensory networks and between regions associated with attentional processes whilst decreasing functional coupling of the amygdala-sgACC, a potential pathway for stress (Kilpatrick et al., 2011; Taren et al., 2015). Furthermore, MBIs may increase functional activity of the insula, a key node in the SN (Young et al., 2018). It could be proposed that by altering connectivity and activity within these specific regions of the SN, MBIs initiate less automatic, mindless
processing of stimuli, more top-down control, interoception, and network regulation (Kilpatrick et al., 2011; Mooneyham et al., 2016).
2.5.2 MBIs increase connectivity between DMN and sensory cortex
As mindfulness training focuses on observing and evaluating the content of thoughts, meditation practice may alter functioning of the DMN (Mooneyham et al., 2016). Indeed, one study has reported altered connectivity between anterior DMN regions involved in
self-referential processing and the sensory cortex in MBSR trained subjects (Kilpatrick et al., 2011). More specifically, the authors find increased connectivity between the mPFC (anterior key node of DMN) and primary interoceptive awareness regions, including the posterior insula (Kilpatrick et al., 2011). This finding may indicate greater reflective awareness of sensory experiences after completion of a MBSR training, which could implicate more focus towards the present moment after mindfulness training (Kilpatrick et al., 2011).
Due to a lack in the literature, further empirical evidence for alterations in resting-state functional connectivity or activity within the DMN following MBI cannot be mentioned.
Nevertheless, studies comparing experienced meditators versus meditation-naive controls are an alternative avenue worth consideration, as they report interesting findings on altered connectivity within the DMN (Brewer et al., 2011). Note however that we cannot draw conclusions about causal relationships with regard to mindfulness from these studies since they are not intervention studies. More studies are therefore needed to draw more robust conclusions on how MBIs may alter connectivity within the DMN.
2.5.3 MBIs increase connectivity within the ECN
The ECN is broadly implicated in higher-order cognition with its functions ranging from inhibition and control of attentional focus to overall cognitive control (Mooneyham et al., 2016). With regards to mindfulness research, it may be argued that these cognitive operations serve an important function to skills that are trained in MBIs, namely cognitive and attentional control. Indeed, results from a study into brief mindfulness training has shown increased functional connectivity between the dlPFC, a hub in the ECN, and dorsal and ventral corticolimbic circuits involved in cognitive control (Taren et al., 2017). In fact, this study also demonstrates enhanced resting-state functional connectivity within the dlPFC in a group of highly stressed participants after receiving an MBSR intervention (Taren et al., 2017). This is an interesting finding as it demonstrates alterations within the ECN after a stress-reducing intervention. However, it is important to note here that, as opposed to using the eight-week evidence-based training
intervention, this study used a shortened three-day training of MBSR, which may have limited the capacity of the results in this study.
Despite the limitations pertinent to the design of this study, these results remain relevant to mention. Currently, no other studies exist to complement these findings on the involvement of the resting-state functional connectivity alterations in the ECN after an MBI. However, these results from Taren et al. (2017) do indicate some involvement of the ECN. For this reason, future research should further explore this finding in subjects undergoing the full MBSR intervention.
2.6 Network perspective on mindfulness; short summary
A summary of current findings on mindfulness and alterations in each large-scale brain network are listed next. First, studies into network alterations after a mindfulness intervention appear to be extremely limited, with no studies investigating between-network connectivity. The evidence that is available suggests increased connectivity within the sensory networks of the SN, presumably leading to more top-down control and present-moment awareness. Moreover,
empirical evidence demonstrates decreased functional coupling of the amygdala-sgACC, a potential pathway for stress, following an MBI. In addition, increased reactivity of the insula has been demonstrated in MBSR-trained subjects, which might speak for the adaptive nature of the SN following an MBI. Moreover, studies investigating the DMN suggest greater connectivity of the mPFC to primary interoceptive awareness regions (the posterior insula), which is
hypothesized to initiate more focus towards the present moment following an MBI. Furthermore, only one study has reported on alterations in the ECN after mindfulness training. This study demonstrates increased connectivity between the dlPFC and corticolimbic circuits in highly stressed participants after an MBI. A summary of these findings is depicted in Table 3
Table 3.
This table summarises findings on resting-state functional connectivity alterations in the SN, DMN, and ECN after a Mindfulness Based Intervention (MBI).
Note. ↑ = increased connectivity; ↓ = decreased connectivity
7(Young et al., 2018; Kilpatrick et al., 2011) 8(Mooneyham et al., 2016; Kilpatrick et al., 2011) 9(Taren et al., 2017)
19
Network Alterations after MBI
Salience Network
● ↓ amygdala-sgACC functional coupling ● Increased insula reactivity
● ↑ within sensory networks ● More top-down control ● Network regulation
7
Default Mode Network
● ↑ mPFC and primary interoceptive awareness regions (posterior insula)
● More present-centered default mode
8
Executive Control Network
● ↑ dlPFC and corticolimbic circuits in highly stressed participants
2.7. Acute stress, MBIs and between-network connectivity
Whereas evidence for alterations in large-scale brain networks in acute stress research is accumulating, studies into network alterations after a mindfulness intervention appear to be extremely limited. For example, our literature search did not show studies reporting on alterations in connectivity between different large-scale brain networks after an MBI. Due to this lack of evidence, this narrative review cannot compare findings of alterations in
between-network functional connectivity after stress-induction to alterations after MBIs. What this narrative review can address, however, are gaps in current literature on MBIs and large-scale brain network connectivity changes for the networks discussed in this paper.
3. Personal critical opinion
By reviewing current research into acute stress, large-scale brain networks, and MBIs, the aim of this narrative review was to identify gaps in the literature and propose ideas for future studies. Moreover, we aimed to write this review to investigate how the relationship between acute stress and large-scale network configuration is influenced by MBIs. Firstly, the results of this narrative review demonstrate a major separation between studies looking into acute stress and stress-reducing interventions, such as MBSR. While current research does not seem to adopt an interdisciplinary approach, we can see from the above sections that relevant connections can be made between large-scale brain network alterations, acute stress and stress-reducing
interventions such as MBIs. Nonetheless, not a single empirical study investigating acute stress, MBIs and resting state functional connectivity of large-scale brain networks all together in one paper could be identified. Adopting such an interdisciplinary approach however, by combining these two fields of study would provide a more comprehensive understanding of the working mechanisms of acute stress and MBIs. Specifically, by integrating neurocognitive and clinical research on acute stress and MBIs such as that mentioned in earlier sections, the neural correlates of both stress and stress resilience may be uncovered. This notion is best explained by proposing an example of a potential study, one that integrates acute stress and MBI whilst also measuring neurocognitive and clinical data.
Such a study could consist of a Randomized Controlled Trial (RCT) measuring clinical and neurocognitive data in a control group and an experimental group. The experimental group
will undergo an eight-week MBSR intervention whereas the control group will not undergo any intervention. At the start of this study, resting-state functional connectivity of the SN, DMN and ECN will be measured while participants adapt to acute stress at baseline; this would be
accompanied with clinical assessments measuring stress resilience. After implementing the eight-week MBSR intervention in the experimental group, these baseline neurocognitive and clinical measurements could be repeated in both the control and experimental group, allowing the researchers to compare the changes in resting-state connectivity pre- and post-MBSR. Moreover, the researchers can compare the results from the experimental group with the results of the control group to see what happens with resting-state connectivity when implementing an MBI. In addition, data on stress resilience can be compared to resting-state connectivity data pre-and post-MBI providing relevant information of potential neural pathways of stress
resilience. This type of integrative study could contribute to our knowledge of the neurocognitive underpinnings of acute stress as well as stress resilience. In turn, this knowledge could contribute to the development of improved clinical treatment of stress which will help alleviate physical and mental health conditions experienced by individuals prone to stress.
Moreover, future studies could also investigate resting-state functional connectivity of experienced meditators while adapting to acute stress and compare this to controls or novice meditators. Despite the fact that no causal conclusions can be made from this type of
non-interventional study design, it could provide relevant information about resting-state functional connectivity of long-term and frequent meditators. Thus, despite the relevance of combining these two fields, it appears that current research fails to come to real integration of acute stress, MBIs and resting-state functional connectivity of large-scale brain networks. Nonetheless, the above section outlines the merits of using an interdisciplinary approach, it can help find answers to very important yet lacking questions in regard to how MBIs influence the relationship between acute stress and resting-state functional connectivity.
In addition to a lack of interdisciplinarity across literature on acute stress and MBIs, this paper also sheds light on another important problem in these fields of study. Namely, it appears that theoretical assumptions outweigh empirical findings. Our literature search shows that there is an abundance of theoretical accounts such as meta-analyses and review papers explicating the neural mechanisms of both acute stress and MBIs. However, empirical research confirming these theoretical assumptions is limited, especially with regard to research on MBIs. Thus, more
empirical research is needed to make significant progressions in this field of research. Therefore, we propose that future studies focus on exploring the working-mechanisms of both acute stress and MBIs from a network-perspective. As the involvement of the SN, DMN, and ECN in studies on both acute stress and MBIs appears to be consistently reported across literature, empirical research adopting a network-perspective may help unravel the neurocognitive underpinnings of acute stress and stress reduction in MBSR further.
Taken together, by conducting a narrative literature review this paper has identified two pertinent gaps in current literature on acute stress and MBIs. First, an interdisciplinary approach towards research on acute stress and MBIs would be beneficial. Precisely by integrating
neurocognitive and clinical research on these topics, both scientific and clinical insights into the working-mechanisms of stress and stress-reduction could be elucidated. Moreover, in addition to a lack of integration, a dearth of empirical evidence within these fields also appears to be an important gap in current literature, especially in regard to MBIs. Hence, this narrative review cannot draw robust conclusions about the exact mechanisms of the moderating effects of MBIs on acute stress and large-scale network configurations. What this narrative review can do, however, is propose future research study designs that could improve our understanding of acute stress and MBIs, which have been outlined above.
4. Limitations
There are multiple limitations inherent to the nature of this paper that make it difficult to make assertive conclusions, and hence, warrant further consideration. Firstly, it is important to point out that the present report was not conducted in a strictly systematic manner. For example, in a systematic review, the goal is to provide a complete, and exhaustive summary of extant evidence in relation to the research question. However, such an approach could not be taken with a narrative review, due to its nature of output. Precisely, by taking an interdisciplinary approach, instead of being able to exhaustively review all of the research on this topic in one discipline, in the current narrative review, we were faced with looking at multiple disciplines, such as clinical psychology and neuroscience. Moreover, studies looking at acute stress often use different paradigms of inducing stress, and studies investigating MBIs often use an inconsistent set-up of the type of MBI used. Hence, we were faced with a two-fold issue. Firstly, it is difficult to exhaustively review this research topic across multiple disciplines. Secondly, the research is
operationalised and investigated differently; when looking at studies across disciplines, concepts are not defined or operationalised in the same manner. This becomes especially evident when comparing brain regions in large-scale networks, as there is currently no consensus on which brain regions belong to which networks. While a systematic review is a thorough examination of one particular topic, utilising similar methods, hence different in nature to an interdisciplinary narrative review, a narrative review bears the benefit of room for integration and
interdisciplinarity, at a much lower cost. Therefore, unlike traditional, discipline specific approaches, an interdisciplinary approach has allowed me to come to more well-rounded and integrative conclusions.
5. Conclusion
With this narrative review we aimed to investigate how the relationship between acute stress and large-scale network configuration is influenced by MBIs. According to the reviewed literature, acute stress may alter cognitive functioning by upregulating the SN and the DMN whilst downregulating the ECN. Moreover, MBIs may alter neural functioning in these networks by inducing network regulation and more top-down control within the SN; increased activity within the DMN triggering more focus toward the present moment; and comments with regards to the ECN cannot be made. Moreover, there is insufficient empirical evidence to make robust conclusions on how MBIs and acute stress may alter resting-state connectivity of large-scale brain networks. That being said, an interdisciplinary approach, integrating these findings on acute stress and MBIs across neuroscientific and clinical disciplines shows a promising avenue. Therefore, this narrative review proposes a novel study-design that can be tested by future research. This study design combines clinical and neurocognitive research into an intervention study measuring an acute stress response pre- and post-MBSR. Together with promoting increased interdisciplinarity and a more empirical approach, we hope to have demonstrated the power of adopting such an approach, an approach that can provoke more scientific discoveries in regard to acute stress and stress-inducing interventions such as MBSR.
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