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.

1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Freezing is widely used as the main outcome measure for fear in animal studies. Freezing is also getting attention more frequently in human stress research, as it is considered to play an important role in the development of psychopathology. Human models on defense behavior are largely based on animal models. Unfortunately, direct translations between animal and human studies are hampered by differences in definitions and methods. The present review therefore aims to clarify the conceptualization of freezing. Neurophysiological and neuroanatomical correlates are discussed and a translational model is proposed. We review the upcoming research on freezing in humans that aims to match animal studies by using physiological indicators of freezing (bradycardia and objective reduction in movement). Finally, we set the agenda for future research in order to optimize mutual animal-human translations and stimulate consistency and systematization in future empirical research on the freezing phenomenon.
    Neuroscience & Biobehavioral Reviews 11/2014; 47. DOI:10.1016/j.neubiorev.2014.07.021 · 10.28 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
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Current theories suggest that the brain is the sole source of mental illness. However, affective disorders, and major depressive disorder (MDD) in particular, may be better conceptualized as brain-body disorders that involve peripheral systems as well. This perspective emphasizes the embodied, multifaceted physiology of well-being, and suggests that afferent signals from the body may contribute to cognitive and emotional states. In this review, we focus on evidence from preclinical and clinical studies suggesting that afferent thermosensory signals contribute to well-being and depression. Although thermoregulatory systems have traditionally been conceptualized as serving primarily homeostatic functions, increasing evidence suggests neural pathways responsible for regulating body temperature may be linked more closely with emotional states than previously recognized, an affective warmth hypothesis. Human studies indicate that increasing physical warmth activates brain circuits associated with cognitive and affective functions, promotes interpersonal warmth and prosocial behavior, and has antidepressant effects. Consistent with these effects, preclinical studies in rodents demonstrate that physical warmth activates brain serotonergic neurons implicated in antidepressant-like effects. Together, these studies suggest that (1) thermosensory pathways interact with brain systems that control affective function, (2) these pathways are dysregulated in affective disorders, and (3) activating warm thermosensory pathways promotes a sense of well-being and has therapeutic potential in the treatment of affective disorders.
    Frontiers in Psychology 01/2014; 5:1580. DOI:10.3389/fpsyg.2014.01580 · 2.80 Impact Factor