The structural integrity of an amygdala-prefrontal pathway predicts trait anxiety
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Here, we used diffusion tensor imaging (DTI) and showed that the strength of an axonal pathway identified between the amygdala and prefrontal cortex predicted individual differences in trait anxiety. A functional magnetic resonance imaging (fMRI) functional localizer that has been shown to produce reliable amygdala activation was collected in 20 psychiatrically healthy subjects. Voxelwise regression analyses using this fMRI amygdala reactivity as a regressor were performed on fractional anisotropy images derived from DTI. This analysis identified a white matter pathway between the amygdala and ventromedial prefrontal cortex. Individual differences in the structural integrity of this putative amygdala–prefrontal pathway were inversely correlated with trait anxiety levels (i.e., higher pathway strength predicted lower anxiety). More generally, this study illustrates a strategy for combining fMRI and DTI to identify individual differences in structural pathways that predict behavioral outcomes.
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Projections to the nuclei of the amygdala reported in Ebeling and von Cramon (1992) refer to the entorhinal cortex and should not be mistaken for the amygdala proper.
“Importantly, projections to the nuclei of the amygdala reported in Ebeling and von Cramon (1992) refers to the entorhinal cortex and should not be mistaken for the amygdala proper as is often done (Schmahmann and Pandya, 2006; Kim and Whalen, 2009).”
From Cortical Terminations of the Inferior Fronto-Occipital and Uncinate Fasciculi: Anatomical Stem-Based Virtual Dissection (2016) · cites this paper as Kim and Whalen, 2009
The Discussion (page unavailable) says the uncinate fasciculus interconnects the amygdala and orbitofrontal lobe, explicitly citing Ebeling and von Cramon (1992). It does not make the claimed distinction that those projections concern the entorhinal cortex rather than the amygdala proper; its statement points the other way. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThese discrepancies may be due to the existence of adjacent tracts, such as the amygdalo-temporo or amygdala-prefrontal pathways, which may have been sometimes misattributed to the UF.
“These discrepancies may be due to the existence of adjacent tracts, such as the amygdalo-temporo or amygdala-prefrontal pathways (Klinger and Gloor, 1960; Kim and Whalen, 2009) which may have been sometimes misattributed to the UF.”
From Cortical Terminations of the Inferior Fronto-Occipital and Uncinate Fasciculi: Anatomical Stem-Based Virtual Dissection (2016) · cites this paper as Kim and Whalen, 2009
Individual differences in amygdala responsivity have been associated with integrity of white matter fibers, including the uncinate fasciculus, in healthy control subjects.
“Furthermore, individual differences in amygdala responsivity have been associated with integrity of white matter fibers, including the uncinate fasciculus in healthy control subjects (24), suggesting a relation between frontolimbic activity and structural connectivity.”
From Relation Between Structural and Functional Connectivity in Major Depressive Disorder (2013) · cites this paper as [24]
Connectivity analyses within anterior mPFC have revealed a ventrally mediated viscerolimbic affective and self-relevance network and a dorsally mediated cognitive network.
“Connectivity analyses within anterior mPFC have revealed a ventrally mediated viscerolimbic affective and self-relevance network (with connections to amygdala, insula, and nucleus accumbens) and a dorsally mediated cognitive network (with connections to dorsolateral PFC and hippocampus) (Kim & Whalen, 2009; Price, Carmichael, & Drevets, 1996; Schmitz & Johnson, 2006).”
From A Meta-analysis of Functional Neuroimaging Studies of Self- and Other Judgments Reveals a Spatial Gradient for Mentalizing in Medial Prefrontal Cortex (2012) · cites this paper as Kim & Whalen, 2009
Reduced grey matter volume in the mPFC and weaker integrity of the uncinate fasciculus have been reported in adults with anxious temperament and anxiety disorders.
“Structural abnormalities, such as reduced grey matter volume in the mPFC and weaker integrity of the uncinate fasciculus, have been reported in adults with anxious temperament and anxiety disorders24–28.”
From Multimodal evidence for delayed threat extinction learning in adolescence and young adulthood (2019) · cites this paper as [24]
Weaker structural integrity of the uncinate fasciculus has been found in populations with anxious temperament, suggesting that this tract may play a crucial role in anxiety aetiology.
“Notably, weaker structural integrity of the uncinate fasciculus has been found in populations with anxious temperament24–27,32, suggesting that this tract may play a crucial role in anxiety aetiology.”
From Multimodal evidence for delayed threat extinction learning in adolescence and young adulthood (2019) · cites this paper as [24]
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“Importantly, projections to the nuclei of the amygdala reported in Ebeling and von Cramon (1992) refers to the entorhinal cortex and should not be mistaken for the amygdala proper as is often done (Schmahmann and Pandya, 2006; Kim and Whalen, 2009).”
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“Specifically, altered frontoamygdala connectivity has been observed in anxiety (Kim and Whalen, 2009; Roy et al., 2013), depression (Tang et al., 2013) and post-traumatic stress disorder (PTSD; Edwards et al., 2013, Stevens et al., 2013, Brown et al., 2014).”
BackgroundPrefrontal cortex reactivity underlies trait vulnerability to chronic social defeat stress
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The Importance of Early Experiences for Neuro-Affective Development
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Volumetric associations between uncinate fasciculus, amygdala, and trait anxiety
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Self-regulatory depletion increases emotional reactivity in the amygdala
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Functional and structural neural indices of risk aversion in obsessive-compulsive disorder (OCD)
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- Authors
- Kim, M. J., & Whalen, P. J.
- Affiliations
- Dartmouth College (US)
- ORCID
- Kim, M. Justin
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-09-16
- Volume
- 29
- Issue
- 37
- Pages
- 11614-11618
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2791525
- OpenAlex
- W2049511110
- Cited by
- 433
- References
- 36
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 7 · 2023: 18 · 2022: 21 · 2021: 19 · 2020: 35 · 2019: 29 · 2018: 32 · 2017: 25 · 2016: 35 · 2015: 20 · 2014: 39 · 2013: 49 · 2012: 33
- FWCI
- 20.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH080716, R01MH080716, R56MH080716)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- trait anxiety, amygdala, ventromedial prefrontal cortex, white matter integrity, fractional anisotropy, individual differences, amygdala reactivity, structural connectivity, anxiety prediction
- MeSH terms
- Adolescent, Adult, Amygdala, Anxiety, Brain Mapping, Emotions, Facial Expression, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Neural Pathways, Neuropsychological Tests, Oxygen, Pattern Recognition, Visual, Photic Stimulation, Predictive Value of Tests, Regression Analysis, Prefrontal Cortex, Diffusion Magnetic Resonance Imaging, Young Adult
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