Identification of discrete functional subregions of the human periaqueductal gray

Department of Psychology, Northeastern University, Boston, MA, 02115.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 09/2013; 110(42). DOI: 10.1073/pnas.1306095110
Source: PubMed

ABSTRACT 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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    • "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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    • "While there has been some implications of PAG involvement in respiratory control (Corfield et al., 1995; Pattinson et al., 2009a; Topolovec et al., 2004) this research has been limited by functional resolution, extensive smoothing, or registration issues that have impeded group-level analysis, making accurate localisation to the PAG or its subdivisions impossible. In addition, significant results within the PAG have been found using statistics uncorrected for multiple comparisons (Mobbs et al., 2007), and a more recent 7 tesla study used a column segmentation of the PAG that is inconsistent with animal literature, uncorrected statistics and masking of the cerebral aqueduct to dissociate activity within PAG columns (Satpute et al., 2013). Therefore, the results of this study demonstrate the potential for 7 tesla MRI to be used to investigate the roles of the subdivisions of the PAG within respiratory control using robust statistical methodology, when careful attention is paid to registration and noise correction of functional data. "
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