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Background: Sleep deprivation (SD) negatively affects brain function. Most brain imaging studies have investigated the effects of SD on static brain function. SD effects on functional brain dynamics and their relationship with molecular changes remain relatively unexplored., Methods: We used functional magnetic resonance imaging to examine resting-brain state dynamics after one night of SD compared with rested wakefulness (N = 41) and assessed the association of brain state dynamics with striatal brain dopamine D 2 receptor availability measured by positron emission tomography [ 11 C]raclopride using network control theory., Results: SD reduced dwell time and persistence probabilities, with the strongest effects in two brain states, one characterized by high default mode network and low dorsal attention network activity and the other by high frontoparietal network and low somatomotor network activity. Using network control theory, we showed that after SD, there was an overall increase in the control energy required for brain state transitions, with effects varying for different brain state transitions. Control energy requirement was negatively associated with transition probabilities under SD and restful wakefulness and accounted for SD-induced changes in transition probabilities. Alteration in the energy landscape was associated with SD-induced changes in striatal D 2 receptor distribution., Conclusions: These findings demonstrate altered occurrence of internally and externally oriented brain states following acute SD and suggest an association with energy requirements for brain state transitions modulated by striatal D 2 receptors., (Published by Elsevier Inc.)

Background: Daylength and the rates of changes in daylength have been associated with seasonal fluctuations in psychiatric symptoms and in cognition and mood in healthy adults. However, variations in human brain glucose metabolism in concordance with seasonal changes remain under explored., Methods: In this cross-sectional study, we examined seasonal effects on brain glucose metabolism, which we measured using 18F-fluorodeoxyglucose-PET in 97 healthy participants. To maximize the sensitivity of regional effects, we computed relative metabolic measures by normalizing the regional measures to white matter metabolism. Additionally, we explored the role of rest-activity rhythms/sleep-wake activity measured with actigraphy in the seasonal variations of regional brain metabolic activity., Results: We found that seasonal variations of cerebral glucose metabolism differed across brain regions. Glucose metabolism in prefrontal regions increased with longer daylength and with greater day-to-day increases in daylength. The cuneus and olfactory bulb had the maximum and minimum metabolic values around the summer and winter solstice respectively (positively associated with daylength), whereas the temporal lobe, brainstem, and postcentral cortex showed maximum and minimum metabolic values around the spring and autumn equinoxes, respectively (positively associated with faster daylength gain). Longer daylength was associated with greater amplitude and robustness of diurnal activity rhythms suggesting circadian involvement., Conclusions: The current findings advance our knowledge of seasonal patterns in a key indicator of brain function relevant for mood and cognition. These data could inform treatment interventions for psychiatric symptoms that peak at specific times of the year.

Substance use disorder (SUD) is a chronic relapsing disorder with long-lasting changes in brain intrinsic networks. While most research to date has focused on static functional connectivity, less is known about the effect of chronic drug use on dynamics of brain networks. Here we investigated brain state dynamics in individuals with opioid use (OUD) and alcohol use disorder (AUD) and assessed how concomitant nicotine use, which is frequent among individuals with OUD and AUD, affects brain dynamics. Resting-state functional magnetic resonance imaging data of 27 OUD, 107 AUD, and 137 healthy participants were included in the analyses. To identify recurrent brain states and their dynamics, we applied a data-driven clustering approach that determines brain states at a single time frame. We found that OUD and AUD non-smokers displayed similar changes in brain state dynamics including decreased fractional occupancy or dwell time in default mode network (DMN)-dominated brain states and increased appearance rate in visual network (VIS)-dominated brain states, which were also reflected in transition probabilities of related brain states. Interestingly, co-use of nicotine affected brain states in an opposite manner by lowering VIS-dominated and enhancing DMN-dominated brain states in both OUD and AUD participants. Our finding revealed a similar pattern of brain state dynamics in OUD and AUD participants that differed from controls, with an opposite effect for nicotine use suggesting distinct effects of various drugs on brain state dynamics. Different strategies for treating SUD may need to be implemented based on patterns of co-morbid drug use., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The relevance of interactions between autonomic and central nervous systems remains unclear for human brain function and health, particularly when both systems are challenged under sleep deprivation (SD). We measured brain activity (with fMRI), pulse and respiratory signals, and baseline brain amyloid beta burden (with PET) in healthy participants. We found that SD relative to rested wakefulness (RW) resulted in a significant increase in synchronized low frequency (LF, < 0.1 Hz) activity in an autonomically-related network (AN), including dorsal attention, visual, and sensorimotor regions, which we previously found to have consistent temporal coupling with LF pulse signal changes (regulated by sympathetic tone). SD resulted in a significant phase coherence between the LF component of the pulse signal and a medial network with peak effects in the midbrain reticular formation, and between LF component of the respiratory variations (regulated by respiratory motor output) and a cerebellar network. The LF power of AN during SD was significantly and independently correlated with pulse-medial network and respiratory-cerebellar network phase coherences (total adjusted R 2 = 0.78). Higher LF power of AN during SD (but not RW) was associated with lower amyloid beta burden (Cohen's d = 0.8). In sum, SD triggered an autonomic mode of synchronized brain activity that was associated with distinct autonomic-central interactions. Findings highlight the direct relevance of global cortical synchronization to brain clearance mechanisms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Background: Decision-making deficits in obesity and alcohol use disorder (AUD) may contribute to the choice of immediate rewards despite their long-term deleterious consequences., Methods: Gambling task functional MRI in Human connectome project (HCP) dataset was used to investigate neural activation differences associated with reward or punishment (a key component of decision-making behavior) in 418 individuals with obesity (high BMI) and without obesity (lean BMI) and either at high (HR) or low (LR) risk of AUD based on their alcohol drinking levels., Results: Interaction between BMI and alcohol drinking was seen in regions of the default mode network (DMN) and those implicated in self-related processing, memory, and salience attribution. ObesityHR relative to obesityLR also recruited DMN along with primary motor and regions implicated in inattention, negative perception, and uncertain choices, which might facilitate impulsive choices in obesityHR. Furthermore, obesityHR compared to leanHR/leanLR also demonstrated heightened activation in DMN and regions implicated in uncertain decisions., Conclusions: These results suggest that BMI is an independent variable from that of alcohol drinking levels in neural processing of gambling tasks. Moreover, leanLR relative to leanHR, showed increased activation in motor regions [precentral and superior frontal gyrus] suggestive of worse executive function from excessive alcohol use. Delayed discounting measures failed to distinguish between obesity and high alcohol drinking levels, which as for gambling task results suggests independent negative effects of obesity and chronic alcohol drinking on decision-making. These findings highlight distinct associations of obesity and high-risk alcohol drinking with two key constituents of decision-making behavior., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

BACKGROUNDCertain components of rest-activity rhythms such as greater eveningness (delayed phase), physical inactivity (blunted amplitude), and shift work (irregularity) are associated with increased risk for drug use. Dopaminergic (DA) signaling has been hypothesized to mediate the associations, though clinical evidence is lacking.METHODSWe examined associations between rhythm components and striatal D1 (D1R) and D2/3 receptor (D2/3R) availability in 32 healthy adults (12 female, 20 male; age 42.40 ± 12.22 years) and its relationship to drug reward. Rest-activity rhythms were assessed by 1-week actigraphy combined with self-reports. [11C]NNC112 and [11C]raclopride positron emission tomography (PET) scans were conducted to measure D1R and D2/3R availability, respectively. Additionally, self-reported drug-rewarding effects of 60 mg oral methylphenidate were assessed.RESULTSWe found that delayed rhythm was associated with higher D1R availability in caudate, which was not attributable to sleep loss or so-called social jet lag, whereas physical inactivity was associated with higher D2/3R availability in nucleus accumbens (NAc). Delayed rest-activity rhythm, higher caudate D1R, and NAc D2/3R availability were associated with greater sensitivity to the rewarding effects of methylphenidate.CONCLUSIONThese findings reveal specific components of rest-activity rhythms associated with striatal D1R, D2/3R availability, and drug-rewarding effects. Personalized interventions that target rest-activity rhythms may help prevent and treat substance use disorders.TRIAL REGISTRATIONClinicalTrials.gov: NCT03190954.FUNDINGNational Institute on Alcohol Abuse and Alcoholism (ZIAAA000550).

Sleep disturbances are prominent in patients with alcohol use disorder (AUD) and predict relapse. So far, the mechanisms underlying sleep disruptions in AUD are poorly understood. Because sleep-related regions vastly overlap with regions, where patients with AUD showed pronounced grey matter (GM) reduction; we hypothesized that GM structure could contribute to sleep disturbances associated with chronic alcohol use. We combined sleep EEG recording and high-resolution structural brain imaging to examine the GM-sleep associations in 36 AUD vs. 26 healthy controls (HC). The patterns of GM-sleep associations differed for N3 vs. REM sleep and for AUD vs. HC. For cortical thickness (CT), CT-sleep associations were significant in AUD but not in HC and were lateralized such that lower CT in right hemisphere was associated with shorter N3, whereas in left hemisphere was associated with shorter REM sleep. For the GM density (GMD), we observed a more extensive positive GMD-N3 association in AUD (right orbitofrontal cortex, cerebellum, dorsal cingulate and occipital cortex) than in HC (right orbitofrontal cortex), and the GMD-REM association was positive in AUD (midline, motor and paralimbic regions) whereas negative in HC (the left supramarginal gyrus). GM structure mediated the effect of chronic alcohol use on the duration of N3 and the age by alcohol effect on REM sleep. Our findings provide evidence that sleep disturbances in AUD were associated with GM reductions. Targeting sleep-related regions might improve sleep in AUD and enhance sleep-induced benefits in cognition and emotional regulation for recovery., (© 2021. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Visual presentation of appetitive and negative cues triggers fast responses in the human brain. Here we assessed functional MRI (fMRI) responses to food, cocaine, and neutral cues presented at a subliminal ("unconscious", 33 ms) and supraliminal ("conscious", 750 and 3000 ms) level in healthy, cocaine naïve volunteers. Because there is evidence of circadian variability in reward sensitivity, our second aim was to assess diurnal variability in the brain's reactivity to cues. Sixteen participants completed two randomly ordered fMRI sessions (once 9-11 AM and another 5-7 PM). in which food, cocaine, and neutral cues were presented for 33, 750 and 3000 ms. Participants rated food cues as positive and "wanted" (more so in evenings than mornings), and cocaine cues as negative (no diurnal differences). fMRI showed occipital cortex activation for food>neutral, cocaine>neutral and cocaine>food; dorsolateral prefrontal cortex for cocaine>neutral and cocaine>food, and midbrain for cocaine>food (all p FWE  < 0.05). When comparing unconscious (33 ms) > conscious (750 and 3000 ms) presentations, we observed significant differences for cocaine>neutral and cocaine>food in occipital cortex, for cocaine>neutral in the insula/temporal lobe, and for food>neutral in the middle temporal gyrus (p FWE  < 0.05). No diurnal differences for brain activations were observed. We interpret these findings to suggest that negative items (e.g., cocaine) might be perceived at a faster speed than positive ones (e.g., food), although we cannot rule out that the higher saliency of cocaine cues, which would be novel to non-drug using individuals, contributed to the faster speed of detection.

The effects of acute sleep deprivation on β-amyloid (Aβ) clearance in the human brain have not been documented. Here we used PET and 18 F-florbetaben to measure brain Aβ burden (ABB) in 20 healthy controls tested after a night of rested sleep (baseline) and after a night of sleep deprivation. We show that one night of sleep deprivation, relative to baseline, resulted in a significant increase in Aβ burden in the right hippocampus and thalamus. These increases were associated with mood worsening following sleep deprivation, but were not related to the genetic risk (APOE genotype) for Alzheimer's disease. Additionally, baseline ABB in a range of subcortical regions and the precuneus was inversely associated with reported night sleep hours. APOE genotyping was also linked to subcortical ABB, suggesting that different Alzheimer's disease risk factors might independently affect ABB in nearby brain regions. In summary, our findings show adverse effects of one-night sleep deprivation on brain ABB and expand on prior findings of higher Aβ accumulation with chronic less sleep., Competing Interests: Conflict of interest statement: S.D.S. was an employee of Piramal Pharma Inc., which partly supported the radiotracer for this study., (Copyright © 2018 the Author(s). Published by PNAS.)

Object processing is affected by the gist of the scene within which it is embedded. Previous ERP research has suggested that manipulating the semantic congruency between an object and the surrounding scene affects the high level (semantic) representation of that object emerging after the presentation of the scene (Ganis & Kutas, 2003). In two ERP experiments, we investigated whether there would be a similar electrophysiological response when spatial congruency of an object in a scene was manipulated while the semantic congruency remained the same. Apart from the location of the object, all other object features were congruent with the scene (e.g., in a bedroom scene, either a painting or a cat appeared on the wall). In the first experiment, participants were shown a location cue and then a scene image for 300 ms, after which an object image appeared on the cued location for 300 ms. Spatially incongruent objects elicited a stronger centro-frontal N300-N400 effect in the 275-500 ms window relative to the spatially congruent objects. We also found early ERP effects, dominant on the left hemisphere electrodes. Strikingly, LORETA analysis revealed that these activations were mainly located in the superior and middle temporal gyrus of the right hemisphere. In the second experiment, we used a paradigm similar to Mudrik, Lamy, and Deouell (2010). The scene and the object were presented together for 300 ms after the location cue. This time, we did not observe either an early or the pronounced N300-N400 effect. In contrast to Experiment 1, LORETA analysis on the N400 time-window revealed that the generators of these weak ERP effects were mainly located in the temporal lobe of the left hemisphere. Our results suggest that, when the scene is presented before the object, top-down spatial encoding processes are initiated and the right superior temporal gyrus is activated, as previously suggested (Ellison, Schindler, Pattison, & Milner, 2004). Mismatch between the actual object features and the spatially driven top-down structural and functional features could lead to the early effect, and then to the N300-N400 effect. In contrast, when the scene is not presented before the object, the spatial encoding could not happen early and strong enough to initiate spatial object-integration effects. Our results indicate that spatial information is an early and essential part in scene-object integration, and it primes structural as well as semantic features of an object., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A fundamental question in psycholinguistic research concerns the universality of comprehension strategies. We investigated this issue by examining the so-called "subject preference" in Turkish, a language which allows for a natural (unmarked) object reading of an initial ambiguous argument. Using event-related brain potentials (ERPs), we observed increased processing difficulty in the form of a broadly distributed positivity when an initial ambiguous argument was disambiguated towards an object reading. This effect was independent of the animacy (i.e. semantic subject prototypicality) of the ambiguous argument. Our results therefore speak in favour of a universal tendency to interpret the first argument encountered as the "subject" of the clause, even in languages providing no obvious structural motivation for such a strategy. However, we argue that the underlying explanation for this preference must be modified in accordance with cross-linguistic considerations.