Frontoparietal Connectivity and Hierarchical Structure of the Brain’s Functional Network during Sleep

Frontal and parietal regions are associated with some of the most complex cognitive functions, and several frontoparietal resting-state networks can be observed in wakefulness. We used functional magnetic resonance imaging data acquired in polysomnographically validated wakefulness, light sleep, and slow-wave sleep to examine the hierarchical structure of a low-frequency functional brain network, and to examine whether frontoparietal connectivity would disintegrate in sleep. Whole-brain analyses with hierarchical cluster analysis on predefined atlases were performed, as well as regression of inferior parietal lobules (IPL) seeds against all voxels in the brain, and an evaluation of the integrity of voxel time-courses in subcortical regions-of-interest. We observed that frontoparietal functional connectivity disintegrated in sleep stage 1 and was absent in deeper sleep stages. Slow-wave sleep was characterized by strong hierarchical clustering of local submodules. Frontoparietal connectivity between IPL and superior medial and right frontal gyrus was lower in sleep stages than in wakefulness. Moreover, thalamus voxels showed maintained integrity in sleep stage 1, making intrathalamic desynchronization an unlikely source of reduced thalamocortical connectivity in this sleep stage. Our data suggest a transition from a globally integrated functional brain network in wakefulness to a disintegrated network consisting of local submodules in slow-wave sleep, in which frontoparietal inter-modular nodes may play a role, possibly in combination with the thalamus

Acoustic Oddball during NREM Sleep: A Combined EEG/fMRI Study

Background: A condition vital for the consolidation and maintenance of sleep is generally reduced responsiveness to external stimuli. Despite this, the sleeper maintains a level of stimulus processing that allows to respond to potentially dangerous environmental signals. The mechanisms that subserve these contradictory functions are only incompletely understood. Methodology/Principal Findings: Using combined EEG/fMRI we investigated the neural substrate of sleep protection by applying an acoustic oddball paradigm during light NREM sleep. Further, we studied the role of evoked K-complexes (KCs), an electroencephalographic hallmark of NREM sleep with a still unknown role for sleep protection. Our main results were: (1) Other than in wakefulness, rare tones did not induce a blood oxygenation level dependent (BOLD) signal increase in the auditory pathway but a strong negative BOLD response in motor areas and the amygdala. (2) Stratification of rare tones by the presence of evoked KCs detected activation of the auditory cortex, hippocampus, superior and middle frontal gyri and posterior cingulate only for rare tones followed by a KC. (3) The typical high frontocentral EEG deflections of KCs were not paralleled by a BOLD equivalent. Conclusions/Significance: We observed that rare tones lead to transient disengagement of motor and amygdala responses during light NREM sleep. We interpret this as a sleep protective mechanism to delimit motor responses and to reduce the sensitivity of the amygdala towards further incoming stimuli. Evoked KCs are suggested to originate from a brain state wit

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Data-driven pupil response profiles as transdiagnostic readouts for the detection of neurocognitive functioning in affective and anxiety disorders.

INTRODUCTION Neurocognitive functioning is a relevant transdiagnostic dimension in psychiatry. As pupil size dynamics track cognitive load during a working memory task, we aimed to explore if this parameter allows to identify psychophysiological subtypes in healthy participants and patients with affective and anxiety symptomatology. METHODS Our sample consisted of 226 participants who completed the N-back task during simultaneous fMRI and pupillometry measurements. We used Latent Class Growth Modeling to identify clusters based on pupil size in response to cognitive load. In a second step, these clusters were compared on affective and anxiety symptom levels, performance in neurocognitive tests, and fMRI activity. RESULTS The clustering analysis resulted in two distinct pupil response profiles: one with a stepwise increasing pupil size with increasing cognitive load (reactive group), the other one with a constant pupil size across conditions (non-reactive group). A larger increase in pupil size was significantly associated with better performance in neurocognitive tests in executive functioning and sustained attention. Statistical maps of parametric modulation of pupil size during the N-back task showed the frontoparietal network in the positive and the default mode network in the negative contrast. The pupil response profile of the reactive group was associated with more thalamic activity, likely reflecting better arousal upregulation, and less deactivation of the limbic system. CONCLUSION To conclude, pupil measurements have the potential to serve as a highly sensitive psychophysiological readout for detection of neurocognitive deficits in the core domain of executive functioning adding to the development of valid transdiagnostic constructs in psychiatry