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; 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.


Available from: Lisa Feldman Barrett, Apr 13, 2015
1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The periaqueductal gray (PAG) is a nucleus within the midbrain, and evidence from animal models has identified its role in many homeostatic systems including respiration. Animal models have also demonstrated a columnar structure that subdivides the PAG into four columns on each side, and these subdivisions have different functions with regard to respiration. In this study we used ultra-high field functional MRI (7 tesla) to image the brainstem and superior cortical areas at high resolution (1mm(3)voxels), aiming to identify activation within the columns of the PAG associated with respiratory control. Our results showed a deactivation in the lateral and dorsomedial columns of the PAG corresponding with short (~10sec) breath holds, along with cortical activations consistent with previous respiratory imaging studies. These results demonstrate the involvement of the lateral and dorsomedial PAG in the network of conscious respiratory control for the first time in humans. This study also reveals the opportunities of 7 tesla functional MRI for non-invasively investigating human brainstem nuclei at high-resolutions. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    NeuroImage 02/2015; 25. DOI:10.1016/j.neuroimage.2015.02.026 · 6.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pain is a primary driver of learning and motivated action. It is also a target of learning, as nociceptive brain responses are shaped by learning processes. We combined an instrumental pain avoidance task with an axiomatic approach to assessing fMRI signals related to prediction errors (PEs), which drive reinforcement-based learning. We found that pain PEs were encoded in the periaqueductal gray (PAG), a structure important for pain control and learning in animal models. Axiomatic tests combined with dynamic causal modeling suggested that ventromedial prefrontal cortex, supported by putamen, provides an expected value-related input to the PAG, which then conveys PE signals to prefrontal regions important for behavioral regulation, including orbitofrontal, anterior mid-cingulate and dorsomedial prefrontal cortices. Thus, pain-related learning involves distinct neural circuitry, with implications for behavior and pain dynamics.
    Nature Neuroscience 10/2014; 17(11). DOI:10.1038/nn.3832 · 14.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The increased availability of ultra-high-field (UHF) MRI has led to its application in a wide range of neuroimaging studies, which are showing promise in transforming fundamental approaches to human neuroscience. This review presents recent work on structural and functional brain imaging, at 7 T and higher field strengths. After a short outline of the effects of high field strength on MR images, the rapidly expanding literature on UHF applications of blood-oxygenation-level-dependent-based functional MRI is reviewed. Structural imaging is then discussed, divided into sections on imaging weighted by relaxation time, including quantitative relaxation time mapping, phase imaging and quantitative susceptibility mapping, angiography, diffusion-weighted imaging, and finally magnetization-transfer imaging. The final section discusses studies using the high spatial resolution available at UHF to identify explicit links between structure and function. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    NMR in Biomedicine 03/2015; DOI:10.1002/nbm.3275 · 3.56 Impact Factor