Friday, July 05, 2013

Degree of Early Life Stress Predicts Decreased Medial Prefrontal Cortex Activity and Shift from Internal to External Decision-Making

Another piece of research in the continuing saga of the prefrontal cortex - this time a look at how early life stress (ELS) predicts decreased prefrontal medial cortex activity, as well as a shift from internally-focused decision-making to externally-focused decision making.
This study is expected to be of great interest in the field of ELS itself in that it provides evidence about the relations among ELS, resting-state brain activity, task induced brain activity, and behavioral tendencies. Beyond elucidating the phenomena associated with ELS, this line of investigation is expected to contribute to improvement of our understanding of resting-state brain activity and self-oriented processes.
Interesting stuff - this is another piece of support for the developmental trauma diagnosis that should have been in the DSM-5.

The degree of early life stress predicts decreased medial prefrontal activations and the shift from internally to externally guided decision making: an exploratory NIRS study during resting state and self-oriented task

Takashi Nakao 1, Tomoya Matsumoto 2, Machiko Morita 3, Daisuke Shimizu 3, Shinpei Yoshimura 4, Georg Northoff 5, Shigeru Morinobu 2, Yasumasa Okamoto 2 and Shigeto Yamawaki 2
1. Department of Psychology, Graduate School of Education, Hiroshima University, Hiroshima, Japan2. Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan3. Faculty of Medicine, Hiroshima University, Hiroshima, Japan4. Faculty of Psychology, Otemon Gakuin University, Osaka, Japan5. Institute of Mental Health Research, University of Ottawa, Ottawa, ON, Canada
Early life stress (ELS), an important risk factor for psychopathology in mental disorders, is associated neuronally with decreased functional connectivity within the default mode network (DMN) in the resting state. Moreover, it is linked with greater deactivation in DMN during a working memory task. Although DMN shows large amplitudes of very low-frequency oscillations (VLFO) and strong involvement during self-oriented tasks, these features’ relation to ELS remains unclear. Therefore, our preliminary study investigated the relationship between ELS and the degree of frontal activations during a resting state and self-oriented task using near-infrared spectroscopy (NIRS). From 22 healthy participants, regional hemodynamic changes in 43 front-temporal channels were recorded during 5 min resting states, and execution of a self-oriented task (color-preference judgment) and a control task (color-similarity judgment). Using a child abuse and trauma scale, ELS was quantified. We observed that ELS showed a negative correlation with medial prefrontal cortex (MPFC) activation during both resting state and color-preference judgment. In contrast, no significant correlation was found between ELS and MPFC activation during color-similarity judgment. Additionally, we observed that ELS and the MPFC activation during color-preference judgment were associated behaviorally with the rate of similar color choice in preference judgment, which suggests that, for participants with higher ELS, decisions in the color-preference judgment were based on an external criterion (color similarity) rather than an internal criterion (subjective preference). Taken together, our neuronal and behavioral findings show that high ELS is related to lower MPFC activation during both rest and self-oriented tasks. This is behaviorally manifest in an abnormal shift from internally to externally guided decision making, even under circumstances where internal guidance is required.
Full Citation: 
Nakao T, Matsumoto T, Morita M, Shimizu D, Yoshimura S, Northoff G, Morinobu S, Okamoto Y, and Yamawaki S. (2013, Jul 3). The degree of early life stress predicts decreased medial prefrontal activations and the shift from internally to externally guided decision making: an exploratory NIRS study during resting state and self-oriented task. Frontiers in Human Neuroscience; 7:339. doi: 10.3389/fnhum.2013.00339


By definition, early life stress (ELS) derives from adverse experiences during childhood and adolescence including physical, sexual, and maltreatment abuse (Brown et al., 2009). Demonstrably, ELS is associated with deficits in cognitive and affective function (Pechtel and Pizzagalli, 2011) and is a significant risk factor for mood and anxiety disorders later in life (Heim and Nemeroff, 2001; Heim et al., 2010; Schmidt et al., 2011). Several lines of evidence have indicated that ELS elicits structural changes in the brain. For example, reports of some animal studies have described that ELS results in abnormally increased synaptic density in the infralimbic cortex (Ovtscharoff and Braun, 2001), and decreased dendritic spine density in the prefrontal cortex (PFC) (Murmu et al., 2006). Reports of human neuroimaging studies have described that ELS is associated with reduced gray matter volume including that of the PFC (De Bellis et al., 2002; Andersen et al., 2008; Paus et al., 2008; Hanson et al., 2010).

Although few functional neuroimaging studies have addressed the influence of ELS, activations within the default mode network (DMN) are known to be associated with ELS (Burghy et al., 2012; Philip et al., 2013a,b; van der Werff et al., in press; Cisler et al., 2013; Wang et al., in press). The DMN consists mainly of cortical midline structures (Northoff and Bermpohl, 2004; Raichle and Gusnard, 2005) and comprises the medial prefrontal cortex (MPFC), posterior cingulate cortex, and superior temporal/inferior parietal cortex (Fox et al., 2005; Kim et al., 2010; Qin and Northoff, 2011). The DMN is more active at rest than during goal-directed/externally guided cognitive tasks (Raichle et al., 2001; Buckner et al., 2008). Regions within the DMN show a high degree of functional connectivity during rest (Raichle et al., 2001; Beckmann et al., 2005; Raichle and Snyder, 2007;Buckner et al., 2008). Regarding these features of the DMN, ELS is known to be associated with greater deactivation of DMN during a working memory task (Philip et al., 2013b), and shows decreased functional connectivity within the DMN during a resting state (Burghy et al., 2012;van der Werff et al., in press; Cisler et al., 2013; Wang et al., in press; Philip et al., 2013a).

Neuronally, the DMN can be characterized by large amplitudes of spontaneous slow oscillations during a resting state (Raichle et al., 2001;Fransson, 2005; Zou et al., 2008). Slow oscillations have been observed using measurements of different types, functional magnetic resonance imaging (fMRI; Biswal et al., 1995; Fransson, 2006; Chepenik et al., 2010), electroencephalography (EEG; Horovitz et al., 2008; Helps et al., 2010;Broyd et al., 2011), and near-infrared spectroscopy (NIRS; Obrig et al., 2000; Näsi et al., 2011; Pierro et al., 2012). Slow oscillations from 0.04 to 0.15 Hz are called low-frequency oscillations (LFOs). Even lower frequency oscillations (<0.04 Hz) are designated as very low-frequency oscillations (VLFOs) (Obrig et al., 2000; Näsi et al., 2011). Although the mechanisms underlying the slow oscillations remain unclear, several reports of the literature have described these as neuronal characteristics of psychological personality traits (Kunisato et al., 2011) and psychiatric disorders such as anxiety (Hou et al., 2012) and mood disorders (Chepenik et al., 2010; Wang et al., 2012). Psychiatric disorders have shown high degrees of ELS (Heim and Nemeroff, 2001; Heim et al., 2010; Schmidt et al., 2011). Therefore, one would suspect high ELS to be related to changes in slow oscillations during the resting state. This point, however, remains to be investigated.

In addition to LFOs during the resting state, the DMN shows activation in fMRI during various tasks such as self-reference (Kelley et al., 2002;Northoff et al., 2006), episodic memory retrieval (Buckner et al., 2008), envisioning the future (Szpunar et al., 2007), mentalizing (Gusnard et al., 2001; Amodio and Frith, 2006), and internally guided decision making (Nakao et al., 2012). The DMN is often explained integratively as associated with self-oriented/internally guided psychological processes (Qin and Northoff, 2011; Whitfield-Gabrieli and Ford, 2012). Again, however, no report in the relevant literature has described the association between ELS and DMN activity during self-oriented tasks.

This preliminary study was undertaken to investigate the relations between ELS and the degree of MPFC activations during a resting state and self-oriented task using NIRS. This non-invasive technique uses near-infrared light to evaluate spatiotemporal characteristics of brain function near the brain surface. The use of NIRS enables the detection of spontaneous slow oscillations in oxygenated hemoglobin (oxy-Hb: Obrig et al., 2000). The LFOs and VLFO measured by NIRS are known to be differentiated from other oscillatory phenomena such as heart beat and respiratory cycles (Obrig et al., 2000). The activation of surface regions of MPFC during self-oriented tasks has also been measured using NIRS (Di Domenico et al., 2012).

For the experiment described hereinafter, a child abuse and trauma scale (CATS) (Sanders and Becker-Lausen, 1995) was used to assess ELS. To control the effect of the recent stress level, we used the life event stress scale (LES) (Sarason et al., 1978). Stressful life events are known to affect brain function adversely through elevated cortisol level in the blood which is acutely or chronically caused by the hormonal stress response system: the hypothalamic–pituitary–adrenal (HPA) axis (Numakawa et al., 2013). Therefore, we also measured the blood levels of cortisol to assess whether early and/or recent life stress might elevate cortisol concentrations in the blood, resulting in alteration of PFC activation. We recorded eyes-closed (EC) and eyes-open (EO) resting-state NIRS before conducting cognitive tasks. In self-oriented cognitive and control tasks, color stimulus was used (see Figure 1A for example). The same color stimulus and color stimulus pairs were used in both tasks. As a self-oriented task, color-preference judgment (Johnson et al., 2005; Nakao et al., 2013) was used while the color-similarity judgment served as control (Johnson et al., 2005; Nakao et al., 2013) (see Figure 1A). We used these tasks for the following three reasons. First, using these tasks, we can differentiate between goal-directed/externally guided and self-oriented/internally guided psychological processes (Johnson et al., 2005; Nakao et al., 2013). Although color-similarity judgment requires participants to make a decision based on the external criterion (i.e., color-similarity), color-preference judgments require participants to make a decision based on their own internal criteria. Second, the same color-set is used in both tasks: the effects of stimuli can be well controlled. Third, Johnson et al. (2005) reported that the color-preference judgment activate the DMN including the MPFC [Brodmann area (BA) 9, 10] compared to the color-similarity judgment. The MPFC is the region of interest (ROI) in this study.

Figure 1. (A) Design of cognitive tasks. (B)Schematic figure showing how to make color combinations in the color-similarity judgment and color-preference judgment tasks. The left color wheel portrays examples of the color combinations of the similarity-easy set. The right color wheel displays examples of color combinations of the similarity-difficult set. The degrees from target color to choice color signify the color similarity. (C)Approximate location of the NIRS channel positions in MNI space. (D) NIRS probe position.

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