The reward system may provide an interesting intermediate phenotype for anhedonia in affective disorders. Reward anticipation is characterized by an increase in arousal, and previous studies have ...linked the anterior cingulate cortex (ACC) to arousal responses such as dilation of the pupil. Here, we examined pupil dynamics during a reward anticipation task in forty-six healthy human subjects and evaluated its neural correlates using functional magnetic resonance imaging (fMRI). Pupil size showed a strong increase during monetary reward anticipation, a moderate increase during verbal reward anticipation and a decrease during control trials. For fMRI analyses, average pupil size and pupil change were computed in 1-s time bins during the anticipation phase. Activity in the ventral striatum was inversely related to the pupil size time course, indicating an early onset of activation and a role in reward prediction processing. Pupil dilations were linked to increased activity in the salience network (dorsal ACC and bilateral insula), which likely triggers an increase in arousal to enhance task performance. Finally, increased pupil size preceding the required motor response was associated with activity in the ventral attention network. In sum, pupillometry provides an effective tool for disentangling different phases of reward anticipation, with relevance for affective symptomatology.
•Pupil dilation increases during reward anticipation.•Salience network activity correlates with pupil dilation during reward anticipation.•Ventral striatal activity temporally precedes salience network activity.•Salience network activity is followed by ventral attention network activity.•Reward anticipation-related pupil dilation bears potential for anhedonia assessment.
Fear conditioning and extinction are prevailing experimental and etiological models for normal and pathological anxiety. Pupil dilations in response to conditioned stimuli are increasingly used as a ...robust psychophysiological readout of fear learning, but their neural correlates remain unknown. We aimed at identifying the neural correlates of pupil responses to threat and safety cues during a fear learning task.
Thirty-four healthy subjects underwent a fear conditioning and extinction paradigm with simultaneous functional magnetic resonance imaging (fMRI) and pupillometry. After a stringent preprocessing and artifact rejection procedure, trial-wise pupil responses to threat and safety cues were entered as parametric modulations to the fMRI general linear models.
Trial-wise magnitude of pupil responses to both conditioned and safety stimuli correlated positively with activity in dorsal anterior cingulate cortex (dACC), thalamus, supramarginal gyrus and insula for the entire fear learning task, and with activity in the dACC during the fear conditioning phase in particular. Phasic pupil responses did not show habituation, but were negatively correlated with tonic baseline pupil diameter, which decreased during the task. Correcting phasic pupil responses for the tonic baseline pupil diameter revealed thalamic activity, which was also observed in an analysis employing a linear (declining) time modulation.
Pupil dilations during fear conditioning and extinction provide useful readouts to track fear learning on a trial-by-trial level, particularly with simultaneous fMRI. Whereas phasic pupil responses reflect activity in brain regions involved in fear learning and threat appraisal, most prominently in dACC, tonic changes in pupil diameter may reflect changes in general arousal.
•Pupil responses during fear learning are associated with dACC and thalamus activity.•Phasic pupil responses do not show substantial habituation during fear learning.•Phasic pupil responses are negatively correlated with tonic pupil size.•Pupillometry can track conditioned responses on a trial-by-trial level.
Recent climatic change is causing spring events in northern temperate regions to occur earlier in the year. As a result, migratory birds returning from tropical wintering sites may arrive too late to ...take full advantage of the food resources on their breeding grounds. Under these conditions, selection will favour earlier spring arrival that could be achieved by overwintering closer to the breeding grounds. However, it is unknown how daylength conditions at higher latitudes will affect the timing of life cycle stages. Here, we show in three species of Palaearctic-African migratory songbirds that a shortening of migration distance induces an advancement of springtime activities. Birds exposed to daylengths simulating migration to and wintering in southern Europe considerably advanced their spring migratory activity and testicular development. This response to the novel photoperiodic environment will enable birds wintering further north to advance spring arrival and to start breeding earlier. Thus, phenotypic flexibility in response to the photoperiod may reinforce selection for shorter migration distance if spring temperatures continue to rise.
We investigated human hippocampal functional connectivity in wakefulness and throughout non-rapid eye movement sleep. Young healthy subjects underwent simultaneous EEG and functional magnetic ...resonance imaging (fMRI) measurements at 1.5 T under resting conditions in the descent to deep sleep. Continuous 5 min epochs representing a unique sleep stage (i.e., wakefulness, sleep stages 1 and 2, or slow-wave sleep) were extracted. fMRI time series of subregions of the hippocampal formation (HF) (cornu ammonis, dentate gyrus, and subiculum) were extracted based on cytoarchitectonical probability maps. We observed sleep stage-dependent changes in HF functional coupling. The HF was integrated to variable strength in the default mode network (DMN) in wakefulness and light sleep stages but not in slow-wave sleep. The strongest functional connectivity between the HF and neocortex was observed in sleep stage 2 (compared with both slow-wave sleep and wakefulness). We observed a strong interaction of sleep spindle occurrence and HF functional connectivity in sleep stage 2, with increased HF/neocortical connectivity during spindles. Moreover, the cornu ammonis exhibited strongest functional connectivity with the DMN during wakefulness, while the subiculum dominated hippocampal functional connectivity to frontal brain regions during sleep stage 2. Increased connectivity between HF and neocortical regions in sleep stage 2 suggests an increased capacity for possible global information transfer, while connectivity in slow-wave sleep is reflecting a functional system optimal for segregated information reprocessing. Our data may be relevant to differentiating sleep stage-specific contributions to neural plasticity as proposed in sleep-dependent memory consolidation.
Resting state functional magnetic resonance imaging (rs-fMRI) is increasingly applied for the development of functional biomarkers in brain disorders. Recent studies have revealed spontaneous ...vigilance drifts during the resting state, involving changes in brain activity and connectivity that challenge the validity of uncontrolled rs-fMRI findings. In a combined rs-fMRI/eye tracking study, the pupil size of 32 healthy subjects after 2h of sleep restriction was recorded as an indirect index for activity of the locus coeruleus, the brainstem's noradrenergic arousal center. The spontaneous occurrence of pupil dilations, but not pupil size per se, was associated with increased activity of the salience network, thalamus and frontoparietal regions. In turn, spontaneous constrictions of the pupil were associated with increased activity in visual and sensorimotor regions. These results were largely replicated in a sample of 36 healthy subjects who did not undergo sleep restriction, although in this sample the correlation between thalamus and pupil dilation fell below whole-brain significance. Our data show that spontaneous pupil fluctuations during rest are indeed associated with brain circuitry involved in tonic alertness and vigilance. Pupillometry is an effective method to control for changes in tonic alertness during rs-fMRI.
•Pupil size is not associated with robust brain network activity.•Spontaneous pupil dilations are associated with salience network activation.•Pupil constrictions involve activation of visual and sensorimotor areas.•Pupillometry provides a marker for alertness/vigilance during resting state fMRI.
Background
Stress exposure as well as psychiatric disorders are often associated with abnormalities in brain structure or connectivity. The co‐chaperone FK506‐binding protein 51 (FKBP51) is a ...regulator of the stress system and is associated with a risk to develop stress‐related mental illnesses.
Purpose
To assess the effect of a general FKBP51 knockout on brain structure and connectivity in male mice.
Study Type
Animal study.
Animal Model
Two cohorts of FKBP51 knockout (51KO) and wildtype (WT) mice. The first cohort was comprised of n = 18 WT and n = 17 51KOs; second cohort n = 10 WT and n = 9 51KOs.
Field Strength/Sequence
9.4T/3D gradient echo (VBM), DTI‐EPI (DTI).
Assessment
Voxel‐based morphometry (VBM) and diffusion tensor imaging (DTI). For VBM, all procedures were executed in SPM12. DTI: FMRIB Software Library (FSL) Tract Based Statistics (TBSS) were integrated within DTI‐TK, allowing the creation of a mean FA skeleton. A voxelwise statistical analysis was applied between WT and 51KO mice.
Statistical Test
Volumetric differences were collected at a threshold of P < 0.005, and only clusters surviving a familywise error correction on the cluster level (pFWE, cluster <0.05) were further considered. VBM data were analyzed using a two‐sample t‐test. The Threshold Free Cluster Enhancement (TFCE) method was used to derive uncorrected‐P statistical results at a P‐level of 0.01.
Results
The structural analysis revealed two clusters of significantly larger volumes in the hypothalamus, periaqueductal gray, and dorsal raphe region of WT animals. DTI measurements, however, demonstrated statistically higher fractional anisotropy (FA) values for 51KO animals in locations including the anterior commissure, fornix, and posterior commissure/superior colliculus commissure region.
Data Conclusion
This study used in vivo structural MRI and DTI to demonstrate that a lack of FKBP51 leads to alterations in brain architecture and connectivity in male mice. These findings are of particular translational relevance for our understanding of the neuroanatomy underlying the interaction of FKBP5 genetic status, stress susceptibility, and psychiatric disorders.
Level of Evidence
1
Technical Efficacy Stage
1
To investigate the neural correlates of lucid dreaming.
Parallel EEG/fMRI recordings of night sleep.
Sleep laboratory and fMRI facilities.
Four experienced lucid dreamers.
N/A.
Out of 4 participants, ...one subject had 2 episodes of verified lucid REM sleep of sufficient length to be analyzed by fMRI. During lucid dreaming the bilateral precuneus, cuneus, parietal lobules, and prefrontal and occipito-temporal cortices activated strongly as compared with non-lucid REM sleep.
In line with recent EEG data, lucid dreaming was associated with a reactivation of areas which are normally deactivated during REM sleep. This pattern of activity can explain the recovery of reflective cognitive capabilities that are the hallmark of lucid dreaming.
Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common ...genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. These results provide a proof of concept (albeit based on a limited set of structural brain measures) and define a roadmap for future studies investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders.
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