Response to Comment on “Homeostatic Sleep Pressure and Responses to Sustained Attention in the Suprachiasmatic Area”

Abstract

Astafiev et al. question whether the blood oxygen level-dependent (BOLD) response that we reported in the brainstem was located in the locus coeruleus (LC). Using high-resolution T1-turbo spin echo images (T1-TSE) acquired in an independent group of subjects, we show that the reported task-related BOLD response in the brainstem is actually compatible with the anatomical location of the LC. (1) illustrates the fast pace at which neuroimaging techniques are currently progressing. Long-term studies requiring the recruitment of highly selective populations and complex, timeconsuming designs constrained by the physiology of sleep/wake regulation are bound to be outdated by some of their technical aspects when they come to be published. However, this does not necessarily entail that their findings are invalidated.We used functional magnetic resonance imaging to study the effects of sleep-wake regulation on the cerebral mechanisms supporting cognition (2). We originally identified the localization of the blood oxygen level-dependent (BOLD) response using human brainstem atlases (3, 4). Statistical inferences were based on a priori coordinates from previous independent publications reporting responses in the LC [see methods described in the Supporting Online Material for (2)]. The potential anatomical inaccuracy of these approaches led us to cautiously label the reported activation as LCcompatible, a localization disputed by Astafiev et al.Here, we confirm the localization of the reported activation in the LC in a follow-up investigation with an independent group of 20 healthy young subjects (mean age, 23.6 T 2.35), using a magnetic resonance (MR) sequence sensitive to neuromelanin-related contrast. Three data sets were consecutively acquired using a 3 Tesla Allegra MR scanner (Siemens, Erlangen, Germany): (i) an echo planar imaging (EPI) temporal series [voxel size, 3.4 ; matrix size, 400 × 512 × 10 voxels; TR, 600 ms; TE, 14 ms; FA, 90°) (Fig. 1A). The LC was manually outlined on the T1-TSE image for each subject (masked-LC image, mLC).Each individual data set was processed using the same procedure as in (2), allowing reliable comparisons with our published data set. The warped T1 and mLC images averaged across subjects reflected group-wise variability in overall brain, brainstem, and LC anatomy, as observed in (2). Figure 1B (left panel) shows the location of the peak activation reported as "LC compatible" in Schmidt et al.(1) on the mean T1 image, overlaid with the mean mLC image. The activation peak was located in the ventral and rostral part of the independently and anatomically identified LC, confirming our original claim that this activation was localized in an area compatible with this nuclear structure.To make sure that this result was not induced by an inadequate warping of the brainstem, we further applied an optimized brainstem normalization procedure to the data (5). Warped T1 images were submitted to a second brainstemspecific normalization step (affine transform, brainstem-masked T1 template), and T1, ...

Neuroimaging, cognition, light and circadian rhythms

“…Taken together these data and those of Schmidt et al (2009, 2010) confirm that the daily temporal organization of executive brain activity depends on the endogenous mechanisms regulating sleep and wakefulness, i.e., the interplay between sleep homeostasis and the circadian clock. A question, then asked by Vandewalle et al (2011a) was how this daily temporal organization was affected in the presence of an exogenous factor impinging on sleep and wakefulness: light exposure.…”

“…The result of Schmidt et al (2009) suggests therefore that, with higher homeostatic sleep pressure and compared to evening types, morning types are under more demanding condition and recruit relatively more the pulvinar for maintaining a normal global alertness level. In addition, maintaining optimal alertness in the subjective evening was associated with larger responses, in evening compared to morning chronotypes, in a brainstem region compatible with the locus coeruleus (LC; Schmidt et al, 2010), and the suprachiasmatic area (SCA), i.e., an anterior hypothalamus region that encompassed the SCN (Figure 1B). The LC is the major source of norepinephrine and has widespread thalamic and cortical connections, so that it can potentially modulate higher-order cognitive functions (Aston-Jones, 2005).…”

Neural indicators of interpersonal anger as cause and consequence of combat training stress symptoms

“…This BS cluster overlaps with the anatomical location of the LC (Keren et al 2009). Localizing the LC from blood oxygen level-dependent brain activity measured with fMRI has been debated (Astafiev et al 2010; Minzenberg et al 2010; Schmidt et al 2010), yet the specific location of this cluster, and that activation before combat training correlated with skin-conductance sympathetic arousal and with aggressive behavior, together support that the cluster indeed corresponds to the LC.…”

Neural substrates underlying the tendency to accept anger-infused ultimatum offers during dynamic social interactions

“…This cluster seems to correspond to the anatomical location of the Locus Coeruleus (LC; Keren et al, 2009), a subcortical nucleus located in the dorsorostral Pons and the major source for Noradrenalin in the brain, thus critically involved in arousal and stress response (Samuels and Szabadi, 2008a,b). Localizing the LC from BOLD fMRI has been debated (Astafiev et al, 2010;Minzenberg et al, 2010;Schmidt et al, 2010), yet the specific location of the BS activation cluster, the relation found between its' activity and sympathetic arousal as measured by SCRlatency, and the fact that the LC has been consistently and reliably involved in human aggression (Haden and Scarpa, 2007), together supports that the BS activity indeed corresponds to the LC region. Interestingly, the inverse relationship found between vmPFC and BS/ LC suggests that the vmPFC might have had a role in attenuating arousal-related brain activity.…”