Identification of discrete functional subregions of the human periaqueductal gray

Harvard University, Cambridge, Massachusetts, United States
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 09/2013; 110(42). DOI: 10.1073/pnas.1306095110
Source: PubMed


The midbrain periaqueductal gray (PAG) region is organized into distinct subregions that coordinate survival-related responses during threat and stress [Bandler R, Keay KA, Floyd N, Price J (2000) Brain Res 53 (1):95-104]. To examine PAG function in humans, researchers have relied primarily on functional MRI (fMRI), but technological and methodological limitations have prevented researchers from localizing responses to different PAG subregions. We used high-field strength (7-T) fMRI techniques to image the PAG at high resolution (0.75 mm isotropic), which was critical for dissociating the PAG from the greater signal variability in the aqueduct. Activation while participants were exposed to emotionally aversive images segregated into subregions of the PAG along both dorsal/ventral and rostral/caudal axes. In the rostral PAG, activity was localized to lateral and dorsomedial subregions. In caudal PAG, activity was localized to the ventrolateral region. This shifting pattern of activity from dorsal to ventral PAG along the rostrocaudal axis mirrors structural and functional neurobiological observations in nonhuman animals. Activity in lateral and ventrolateral subregions also grouped with distinct emotional experiences (e.g., anger and sadness) in a factor analysis, suggesting that each subregion participates in distinct functional circuitry. This study establishes the use of high-field strength fMRI as a promising technique for revealing the functional architecture of the PAG. The techniques developed here also may be extended to investigate the functional roles of other brainstem nuclei.

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Available from: Lisa Feldman Barrett, Apr 13, 2015
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    • "al gray ( PAG ) is also a cytoarchitecturally and neurochemically highly complex intergrative area , both in human and rodent brain ( Behbehani , 1995 ; Fu et al . , 2010 ) . It is involved in the emotional regulation ( e . g . , in circuitries underlying fear , depression and anxiety ) , but also in autonomic control and pain ( Behbehani , 1995 ; Satpute et al . , 2013 ) . Its ventrolateral subdivision ( VLPAG ) , where the NPSR1 mRNA - expressing neurons are especially abundant , is critical for the expression of passive coping responses to non - immediate " distal " danger ( Johnson et al . , 2004 ) , but neurons in the vlPAG contribute to the regulation of REM sleep as well ( Luppi et al . , 2012 )"
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    • "Despite centrality of the PAG in non-human affective research (Panksepp, 1998, 2005), less is known about its role in human emotions and defensive behaviours (Buhle et al., 2013; Satpute et al., 2013). A recent study using high resolution fMRI indicated a rostrocaudal functional subdivision of the PAG with respect to emotional processing of aversive images, mirroring neurobiological observations in non-human animals (Satpute et al., 2013). Interestingly, activity in dorsal PAG was also demonstrated using fMRI when the perceived threat proximity of a virtual predator became closer (Mobbs et al., 2007, 2009), and when threatening facial expressions (e.g., anger) evoked covert defensive behaviour with concomitant activation of premotor cortices (Pichon et al., 2012). "
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    • "Clusters are corrected at P < 0.00001, k 5 10. Coordinates are in MNI space. in vivo human UHF work has shown that the PAG does not operate as a unitary functional node [De Oca et al., 1998; Satpute et al., 2013]. In rodents, for example, the ventral PAG is thought to be involved in freezing responses, while the dorsal PAG is preferentially involved in paininduced increases in vocalization [McLemore et al., 1999]. "
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