Amygdala and Ventromedial Prefrontal Cortex Are Inversely Coupled During Regulation of Negative Affect and Predict the Diurnal Pattern of Cortisol Secretion Among Older Adults

Department of Psychiatry, University of Wisconsin–Madison, Madison, Wisconsin, United States
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 05/2006; 26(16):4415-25. DOI: 10.1523/JNEUROSCI.3215-05.2006
Source: PubMed


Among younger adults, the ability to willfully regulate negative affect, enabling effective responses to stressful experiences, engages regions of prefrontal cortex (PFC) and the amygdala. Because regions of PFC and the amygdala are known to influence the hypothalamic-pituitary-adrenal axis, here we test whether PFC and amygdala responses during emotion regulation predict the diurnal pattern of salivary cortisol secretion. We also test whether PFC and amygdala regions are engaged during emotion regulation in older (62- to 64-year-old) rather than younger individuals. We measured brain activity using functional magnetic resonance imaging as participants regulated (increased or decreased) their affective responses or attended to negative picture stimuli. We also collected saliva samples for 1 week at home for cortisol assay. Consistent with previous work in younger samples, increasing negative affect resulted in ventral lateral, dorsolateral, and dorsomedial regions of PFC and amygdala activation. In contrast to previous work, decreasing negative affect did not produce the predicted robust pattern of higher PFC and lower amygdala activation. Individuals demonstrating the predicted effect (decrease < attend in the amygdala), however, exhibited higher signal in ventromedial prefrontal cortex (VMPFC) for the same contrast. Furthermore, participants displaying higher VMPFC and lower amygdala signal when decreasing compared with the attention control condition evidenced steeper, more normative declines in cortisol over the course of the day. Individual differences yielded the predicted link between brain function while reducing negative affect in the laboratory and diurnal regulation of endocrine activity in the home environment.

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    • "subjects showed hypoactivity in the dlPFC and lOFC ( Carlsson et al . , 2004 ) as well as mPFC ( Hermann et al . , 2007 , 2009 ) . However , in addition to activation of the vlPFC and down - regulation of the amygdala during some effortful regulation tasks with negative emotional stimuli , some studies have found possible mediation via the vmPFC ( Urry et al . , 2006 ; Johnstone et al . , 2007 ) . While this may be similar to pathway p4 , it does not explain lOFC activity in some studies ( Phillips et al . , 2003 ; Carlsson et al . , 2004 ; Wager et al . , 2008 ; Golkar et al . , 2012 ) ."
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    ABSTRACT: A hypothesis is proposed for five visual fear signaling pathways in humans, based on an analysis of anatomical connectivity from primate studies and human functional connectvity and tractography from brain imaging studies. Earlier work has identified possible subcortical and cortical fear pathways known as the “low road” and “high road,” which arrive at the amygdala independently. In addition to a subcortical pathway, we propose four cortical signaling pathways in humans along the visual ventral stream. All four of these traverse through the LGN to the visual cortex (VC) and branching off at the inferior temporal area, with one projection directly to the amygdala; another traversing the orbitofrontal cortex; and two others passing through the parietal and then prefrontal cortex, one excitatory pathway via the ventral-medial area and one regulatory pathway via the ventral-lateral area. These pathways have progressively longer propagation latencies and may have progressively evolved with brain development to take advantage of higher-level processing. Using the anatomical path lengths and latency estimates for each of these five pathways, predictions are made for the relative processing times at selective ROIs and arrival at the amygdala, based on the presentation of a fear-relevant visual stimulus. Partial verification of the temporal dynamics of this hypothesis might be accomplished using experimental MEG analysis. Possible experimental protocols are suggested.
    Frontiers in Systems Neuroscience 08/2015; 9(101). DOI:10.3389/fnsys.2015.00101
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    • "Similarly, in humans, recall of extinguished fear memories increases vmPFC reactivity in response to the CS+ (Milad et al., 2007; Phelps et al., 2004), and is positively associated with vmPFC thickness (Milad et al., 2005). Also, on a different emotion regulation task involving cognitive reappraisal of a negative event, the amygdala showed stronger coupling with the dlPFC, OFC, Subgenual ACC, and dmPFC, with the extent of such coupling being positively associated with post-reappraisal attenuation of negative affect (Banks et al., 2007; Ochsner et al., 2002; Urry et al., 2006). Indeed, weak amygdala-mPFC connections result in pathological emotional over-arousal (Milad et al., 2008; Milad et al., 2009; Motzkin et al., 2015). "
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    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 07/2015; DOI:10.1038/npp.2015.204 · 7.05 Impact Factor
    • "Thus, the amygdalo-hippocampal complex, orbitofrontal cortex , anterior cingulum and insula have been shown to be activated by both mental and physical tests, which are useful to evoke an autonomic stress response (Critchley et al., 2003; Williamson et al., 1997; Soufer et al., 1998; Harper et al., 1998). Stressors which require the completion of demanding and uncontrollable cognitive challenges in a context of negative social evaluation, such as the Trier Social Stress Test (TSST) induce increased activity of the medial prefrontal cortex (Kern et al., 2008; Urry et al., 2006), anterior cingulum (which may be of particular importance for generating autonomic cardiovascular responses; Critchley et al., 2000a,b, 2005; Critchley, 2005), insula (which probably works together with anterior cingulum, as both are components of a system underlying self awareness; Medford and Critchley, 2010), and deactivation of the hippocampalamygdala complex (Kern et al., 2008), probably to disinhibit the hypothalamus which commands the HPA and ANS (McEwen and Gianaros, 2010) responses. Dedovic et al. (2005) have used a variety of tests to induce stress by generating a social evaluative threat combining an arithmetic task and a social evaluative component, such as the Montreal Imaging Stress Task (MIST). "
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    ABSTRACT: Environmental influences are critical for the expression of genes putatively related to the behavioral and cognitive phenotypes of schizophrenia. Among such factors, psychosocial stress has been proposed to play a major role in the expression of symptoms. However, it is unsettled how stress interacts with pathophysiological pathways to produce the disease. We studied 21 patients with schizophrenia and 21 healthy controls aged 18 to 50years with 3T-fMRI, in which a period of 6min of resting state acquisition was followed by a block design, with three blocks of 1-min control-task, 1-min stress-task and 1-min rest after-task. Self-report of stress and PANSS were measured. Limbic structures were activated in schizophrenia patients by simple tasks and remained active during, and shortly after stress. In controls, stress-related brain activation was more time-focused, and restricted to the stressful task itself. Negative symptom severity was inversely related to activation of anterior cingulum and orbitofrontal cortex. Results might represent the neurobiological aspect of hyper-reactivity to normal stressful situations previously described in schizophrenia, thus providing evidence on the involvement of limbic areas in the response to stress in schizophrenia. Patients present a pattern of persistent limbic activation probably contributing to hypervigilance and subsequent psychotic thought distortions. Copyright © 2015 Elsevier B.V. All rights reserved.
    Schizophrenia Research 07/2015; DOI:10.1016/j.schres.2015.07.008 · 3.92 Impact Factor
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