Amygdala Reactivity in Healthy Adults Is Correlated with Prefrontal Cortical Thickness

Laboratory of Neuro Imaging, Department of Neurology, Department of Psychiatry and Biobehavioral Sciences, and Department of Psychology, University of California, Los Angeles, California 90095, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 12/2010; 30(49):16673-8. DOI: 10.1523/JNEUROSCI.4578-09.2010
Source: PubMed


Recent evidence suggests that putting feelings into words activates the prefrontal cortex (PFC) and suppresses the response of the amygdala, potentially helping to alleviate emotional distress. To further elucidate the relationship between brain structure and function in these regions, structural and functional magnetic resonance imaging (MRI) data were collected from a sample of 20 healthy human subjects. Structural MRI data were processed using cortical pattern-matching algorithms to produce spatially normalized maps of cortical thickness. During functional scanning, subjects cognitively assessed an emotional target face by choosing one of two linguistic labels (label emotion condition) or matched geometric forms (control condition). Manually prescribed regions of interest for the left amygdala were used to extract percentage signal change in this region occurring during the contrast of label emotion versus match forms. A correlation analysis between left amygdala activation and cortical thickness was then performed along each point of the cortical surface, resulting in a color-coded r value at each cortical point. Correlation analyses revealed that gray matter thickness in left ventromedial PFC was inversely correlated with task-related activation in the amygdala. These data add support to a general role of the ventromedial PFC in regulating activity of the amygdala.

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Available from: Paul Thompson, Oct 01, 2015
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    • "Theoretical accounts suggest that interactions between the insula, ACC, and vmPFC underlie affective processes at multiple stages of the addiction cycle, particularly during drug withdrawal (Naqvi and Bechara 2010). Neuroimaging evidence indicates that the insula is involved in monitoring homeostatically relevant bodily sensations (Craig 2009; Critchley et al. 2004) and that the vmPFC is involved in the processing and regulation of emotion (Foland-Ross et al. 2010; Kim et al. 2011). While the insula, ACC, and vmPFC appear to constitute critical nodes in the neurocircuitry underlying alexithymia and drug addiction, little is known about the circuit–level interactions of these brain regions as a function of trait alexithymia or state tobacco craving. "
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    ABSTRACT: RATIONALE: Alexithymia is a personality trait characterized by difficulty indentifying and describing subjective emotional experiences. Decreased aptitude in the perception, evaluation, and communication of affectively laden mental states has been associated with reduced emotion regulation, more severe drug craving in addicts, and structural/functional alterations in insula and anterior cingulate cortex (ACC). The insula and ACC represent sites of convergence between the putative neural substrates of alexithymia and those perpetuating cigarette smoking. OBJECTIVES: We examined the interrelations between alexithymia, tobacco craving, and insula/ACC neurocircuitry using resting-state functional connectivity (rsFC). METHODS: Overnight-deprived smokers (n = 24) and nonsmokers (n = 20) completed six neuroimaging assessments on different days both in the absence of, and following, varenicline and/or nicotine administration. In this secondary analysis of data from a larger study, we assessed trait alexithymia and state tobacco craving using self-reports and examined the rsFC of bilateral insular subregions (anterior, middle, posterior) and dorsal ACC. RESULTS: Higher alexithymia in smokers predicted reduced rsFC strength between the right anterior insula (aI) and ventromedial prefrontal cortex (vmPFC). Higher alexithymia also predicted more severe tobacco craving during nicotine withdrawal. Critically, the identified aI-vmPFC circuit fully mediated this alexithymia-craving relation. That is, elevated alexithymia predicted decreased aI-vmPFC rsFC and, in turn, decreased aI-vmPFC rsFC predicted increased craving during withdrawal. A moderated mediation analysis indicated that this aI-vmPFC mediational effect was not observed following drug administration. CONCLUSIONS: These results suggest that a weakened right aI-vmPFC functional circuit confers increased liability for tobacco craving during smoking abstinence. Individual differences in alexithymia and/or aI-vmPFC functional coupling may be relevant factors for smoking cessation success.
    Psychopharmacology 02/2013; 228(1). DOI:10.1007/s00213-013-3018-8 · 3.88 Impact Factor
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    • "Several hypotheses could potentially explain this maturation pattern. Cortical thickness of the vmPFC has been found in adults to be inversely correlated with ipsilateral amygdala activation during an emotional processing task (Foland-Ross et al. 2010). Thus, there is some evidence that thickness in this portion of the cerebral cortex is related to hemodynamic activity within limbic structures. "
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    ABSTRACT: The relationship between anxious/depressed traits and neuromaturation remains largely unstudied. Characterizing this relationship during healthy neurodevelopment is critical to understanding processes associated with the emergence of child/adolescent onset mood/anxiety disorders. In this study, mixed-effects models were used to determine longitudinal cortical thickness correlates of Child Behavior Checklist (CBCL) and Young Adult Self Report Anxious/Depressed scores in healthy children. Analyses included 341 subjects from 4.9 to 22.3 year-old with repeated MRI at up to 3 time points, at 2-year intervals (586 MRI scans). There was a significant "CBCL Anxious/Depressed by Age" interaction on cortical thickness in the right ventromedial prefrontal cortex (vmPFC), including the medial orbito-frontal, gyrus rectus, and subgenual anterior cingulate areas. Anxious/Depressed scores were negatively associated with thickness at younger ages (<9 years), but positively associated with thickness at older ages (15-22 years), with the shift in polarity occurring around age 12. This was secondary to a slower rate of vmPFC cortical thinning in subjects with higher scores. In young adults (18-22 years), Anxious/Depressed scores were also positively associated with precuneus/posterior cingulate cortical thickness. Potential neurobiological mechanisms underlying this maturation pattern are proposed. These results demonstrate the dynamic impact of age on relations between vmPFC and negative affect in the developing brain.
    Cerebral Cortex 01/2013; DOI:10.1093/cercor/bht151 · 8.67 Impact Factor
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    • "Addiction-related alterations between amygdala and medial PFC are particularly intriguing when considered in light of a larger corpus of research relating such circuit-level interactions to emotional regulation , subjective anxiety, and other neuropsychiatric disorders (Foland- Ross et al., 2010; Hahn et al., 2011; Hariri et al., 2003; Kim et al., 2011a, 2011b; Motzkin et al., 2011; Pezawas et al., 2005). The vmPFC has been posited to actively suppress amygdala functioning (Foland-Ross et al., 2010; Hariri et al., 2003; Kim et al., 2011b), which in turn, is thought to alleviate emotional distress (Berkman and Leiberman, 2009; Ochsner et al., 2004). Such a regulation-circuit perspective is bolstered by rsFC studies demonstrating that amygdala-vmPFC rsFC strength is inversely related to self-reported anxiety levels in non-clinical samples, where increased anxiety is associated with reduced connectivity (Kim et al., 2011a; Pezawas et al., 2005). "
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    ABSTRACT: Despite intensive scientific investigation and public health imperatives, drug addiction treatment outcomes have not significantly improved in more than 50 years. Non-invasive brain imaging has, over the past several decades, contributed important new insights into the neuroplastic adaptations that result from chronic drug intake, but additional experimental approaches and neurobiological hypotheses are needed to better capture the totality of the motivational, affective, cognitive, genetic and pharmacological complexities of the disease. Recent advances in assessing network dynamics through resting-state functional connectivity (rsFC) may allow for such systems-level assessments. In this review, we first summarize the nascent addiction-related rsFC literature and suggest that in using this tool, circuit connectivity may inform specific neurobiological substrates underlying psychological dysfunctions associated with reward, affective and cognitive processing often observed in drug addicts. Using nicotine addiction as an exemplar, we subsequently provide a heuristic framework to guide future research by linking recent findings from intrinsic network connectivity studies with those interrogating nicotine's neuropharmacological actions. Emerging evidence supports a critical role for the insula in nicotine addiction. Likewise, the anterior insula, potentially together with the anterior cingulate cortex, appears to pivotally influence the dynamics between large-scale brain networks subserving internal (default-mode network) and external (executive control network) information processing. We suggest that a better understanding of how the insula modulates the interaction between these networks is critical for elucidating both the cognitive impairments often associated with withdrawal and the performance-enhancing effects of nicotine administration. Such an understanding may be usefully applied in the design and development of novel smoking cessation treatments.
    NeuroImage 02/2012; 62(4):2281-95. DOI:10.1016/j.neuroimage.2012.01.117 · 6.36 Impact Factor
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