Reward-driven modulation of spatial attention in the human frontal eye-field.

Attentional selection and the decision of where to make an eye-movement are driven by various factors such as the representation of salience, task goal, and stimulus relevance, as well as expectations or predictions based on past experience. Brain systems implicated in these processes recruit cortico-subcortical areas including the Frontal Eye-Field (FEF), parietal cortex, or superior colliculus. How these areas interact to govern attention remains elusive. Priority maps of space have been observed in several brain regions, but the neural substrates where different sources of information are combined and integrated to guide attentional selection has not been elucidated. We investigated here the neural mechanisms subserving how reward cues influence the voluntary deployment of attention, in conditions where stimulus-driven capture and task-related goals compete for attention selection. Using fMRI in a visual search task in n = 23 participants, we found a selective modulation of FEF by the reward value of distractors during attentional shifts, particularly after high-predictive cueing to invalid locations. Reward information also modulated FEF connectivity to superior colliculus, striatum, and visual cortex. We conclude that FEF may occupy a central position within brain circuits integrating different sources of top-down biases for the generation of spatial saliency maps and guidance of selective attention.

Fear in dreams and in wakefulness: Evidence for day/night affective homeostasis.

Recent neuroscientific theories have proposed that emotions experienced in dreams contribute to the resolution of emotional distress and preparation for future affective reactions. We addressed one emerging prediction, namely that experiencing fear in dreams is associated with more adapted responses to threatening signals during wakefulness. Using a stepwise approach across two studies, we identified brain regions activated when experiencing fear in dreams and showed that frightening dreams modulated the response of these same regions to threatening stimuli during wakefulness. Specifically, in Study 1, we performed serial awakenings in 18 participants recorded throughout the night with high-density electroencephalography (EEG) and asked them whether they experienced any fear in their dreams. Insula and midcingulate cortex activity increased for dreams containing fear. In Study 2, we tested 89 participants and found that those reporting higher incidence of fear in their dreams showed reduced emotional arousal and fMRI response to fear-eliciting stimuli in the insula, amygdala and midcingulate cortex, while awake. Consistent with better emotion regulation processes, the same participants displayed increased medial prefrontal cortex activity. These findings support that emotions in dreams and wakefulness engage similar neural substrates, and substantiate a link between emotional processes occurring during sleep and emotional brain functions during wakefulness.

Cortical reactivations during sleep spindles following declarative learning.

Increasing evidence suggests that sleep spindles are involved in memory consolidation, but few studies have investigated the effects of learning on brain responses associated with spindles in humans. Here we used simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) during sleep to assess haemodynamic brain responses related to spindles after learning. Twenty young healthy participants were scanned with EEG/fMRI during (i) a declarative memory face sequence learning task, (ii) subsequent sleep, and (iii) recall after sleep (learning night). As a control condition an identical EEG/fMRI scanning protocol was performed after participants over-learned the face sequence task to complete mastery (control night). Results demonstrated increased responses in the fusiform gyrus both during encoding before sleep and during successful recall after sleep, in the learning night compared to the control night. During sleep, a larger response in the fusiform gyrus was observed in the presence of fast spindles during the learning as compared to the control night. Our findings support a cortical reactivation during fast spindles of brain regions previously involved in declarative learning and subsequently activated during memory recall, thereby promoting the cortical consolidation of memory traces.

Increased Reactivity of the Mesolimbic Reward System after Ketamine Injection in Patients with Treatment-resistant Major Depressive Disorder.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: The antidepressant effect of ketamine is associated with increased activity in the reward circuitry of the brain and a suppression of circuitry that mediates perceptual processing of negative emotions. The duration of ketamine effect on these brain structures remains to be defined. WHAT THIS ARTICLE TELLS US THAT IS NEW: As expected, ketamine administration led to an improvement in mood and global vigilance. The improvement in mood was accompanied by an increased recruitment of the orbitofrontal cortex, ventral striatum, medial substantial nigra and ventral tegmental area, structures that are part of the reward circuitry.Responses in the mesolimbic structures (amygdala, medial substantial nigra and ventral tegmental area, orbitofrontal cortex) to negative stimuli were decreased after ketamine administration.The data are consistent with the premise that ketamine induces sustained changes in the mesolimbic neural circuits to reset pathological reward and emotional processing. BACKGROUND: Ketamine rapidly improves maladaptive mood states in major depressive disorder, and some of the neural substrates underlying this therapeutic effect have been identified. This study aimed to identify functional changes within neural networks that may underlie the impact of ketamine on both reward and emotional processing in patients with treatment-resistant major depression. METHODS: Ten adult patients with a Montgomery-Åsberg Depression Rating Scale score above 25 were enrolled to receive a single intravenous administration of ketamine (0.5 mg/kg). Patients' performance along with related neural network activations were analyzed in a game-like reward task and in an emotional judgment task using functional magnetic resonance imaging 1 day before and 1 and 7 days after ketamine administration. RESULTS: A significant correlation (R = 0.46, P = 0.03) between the improvement of depression scores and the enhanced reaction time for positive items was found in the game-like reward task 1 day after ketamine administration. This enhanced sensitivity for rewarded items was accompanied by increased activity of reward-related brain regions, including the orbitofrontal cortex, ventral striatum, and the ventral tegmental area, an effect that persisted up to 1 week after ketamine injection. In the emotional judgment task, it was found that ketamine rapidly modified local brain activities in response to emotionally negative, positive, or neutral stimuli in the amygdala, insula, anterior cingulate cortex, and in the ventral tegmental area. CONCLUSIONS: Single bolus ketamine administration rapidly triggers lasting changes in mesolimbic neural networks to improve pathologic reward and emotional processing in patients with major depressive disorder.

Goal-relevant situations facilitate memory of neutral faces.

Emotional situations are typically better remembered than neutral situations, but the psychological conditions and brain mechanisms underlying this effect remain debated. Stimulus valence and affective arousal have been suggested to explain the major role of emotional stimuli in memory facilitation. However, neither valence nor arousal are sufficient affective dimensions to explain the effect of memory facilitation. Several studies showed that negative and positive details are better remembered than neutral details. However, other studies showed that neutral information encoded and coupled with arousal did not result in a memory advantage compared with neutral information not coupled with arousal. Therefore, we suggest that the fundamental affective dimension responsible for memory facilitation is goal relevance. To test this hypothesis at behavioral and neural levels, we conducted a functional magnetic resonance imaging study and used neutral faces embedded in goal-relevant or goal-irrelevant daily life situations. At the behavioral level, we found that neutral faces encountered in goal-relevant situations were better remembered than those encountered in goal-irrelevant situations. To explain this effect, we studied neural activations involved in goal-relevant processing at encoding and in subsequent neutral face recognition. At encoding, activation of emotional brain regions (anterior cingulate, ventral striatum, ventral tegmental area, and substantia nigra) was greater for processing of goal-relevant situations than for processing of goal-irrelevant situations. At the recognition phase, despite the presentation of neutral faces, brain activation involved in social processing (superior temporal sulcus) to successfully remember identities was greater for previously encountered faces in goal-relevant than in goal-irrelevant situations.

Efficacy and Safety of a Rapid Intravenous Injection of Ketamine 0.5 mg/kg in Treatment-Resistant Major Depression: An Open 4-Week Longitudinal Study.

BACKGROUND: Ketamine has been documented for its rapid antidepressant effects. However, optimal dose and delivery route have not yet been thoroughly investigated. The objectives of this study were to document the safety and test the antidepressant and antisuicidal effects of a single rapid 1-minute injection of ketamine 0.5 mg/kg in treatment-resistant depression (TRD). METHODS: Ten patients with TRD were included in an open, noncontrolled 4-week study and received a rapid intravenous dose of ketamine 0.5 mg/kg. Main outcome measure was the Montgomery-Åsberg Depression Rating Scale and suicidality was assessed using the Scale for Suicide Ideation. RESULTS: Rapid injection of ketamine elicited transient increase of blood pressure and altered states of consciousness in all patients and mild psychotomimetic effects in 4 patients, which all resolved without any intervention. Decrease of depression severity was observed from 40-minute postinjection until day 15. Eight patients became responders within 1 day and all were nonresponders after 4 weeks. The decrease of suicidal ideation was significant until day 7. Analysis indicated that higher severity of depression and anxiety at baseline predicted a larger Montgomery-Åsberg Depression Rating Scale decrease after 4 weeks. CONCLUSIONS: This study suggests that in well-controlled medical settings with adequate monitoring, a single rapid 1-minute injection of ketamine 0.5 mg/kg can be well tolerated and is efficacious in rapidly reducing depression symptoms and suicidal thoughts in outpatients with TRD. These findings are relevant to the practice of general clinical psychiatry and emergency departments were ketamine can have a place in acute management of TRD. Larger studies are necessary to confirm these results.

Alterations in neural systems mediating cognitive flexibility and inhibition in mood disorders.

Impairment in mental flexibility may be a key component contributing to cardinal cognitive symptoms among mood disorders patients, particularly thought control disorders. Impaired ability to switch from one thought to another might reflect difficulties in either generating new mental states, inhibiting previous states, or both. However, the neural underpinnings of impaired cognitive flexibility in mood disorders remain largely unresolved. We compared a group of mood disorders patients (n = 29) and a group of matched healthy subjects (n = 32) on a novel task-switching paradigm involving happy and sad faces, that allowed us to separate generation of a new mental set (Switch Cost) and inhibition of the previous set during switching (Inhibition Cost), using fMRI. Behavioral data showed a larger Switch Cost in patients relative to controls, but the average Inhibition Cost did not differ between groups. At the neural level, a main effect of group was found with stronger activation of the subgenual cingulate cortex in patients. The larger Switch Cost in patients was reflected by a stronger recruitment of brain regions involved in attention and executive control, including the left intraparietal sulcus, precuneus, left inferior fontal gyrus, and right anterior cingulate. Critically, activity in the subgenual cingulate cortex was not downregulated by inhibition in patients relative to controls. In conclusion, mood disorder patients have exaggerated Switch Cost relative to controls, and this deficit in cognitive flexibility is associated with increased activation of the fronto-parietal attention networks, combined with impaired modulation of the subgenual cingulate cortex when inhibition of previous mental states is needed.

The impact of visual perceptual learning on sleep and local slow-wave initiation.

During non-rapid eye movement (NREM) sleep, a global decrease in synaptic strength associated with slow waves (SWs) would enhance signal-to-noise ratio of neural responses during subsequent wakefulness. To test this prediction, 32 human volunteers were trained to a coarse orientation discrimination task, in either the morning or evening. They were retested after 8 h of wakefulness or sleep, respectively. Performance was enhanced only after a night of sleep, in the absence of any change in the abundance of NREM SWs but in proportion to the number of SWs "initiated" in lateral occipital areas during posttraining NREM sleep. The sources of these waves overlapped with the lateral occipital complex, in which responses to the learned stimulus, as assessed by fMRI, were selectively increased the next morning. This response enhancement was proportional to rapid eye movement (REM) sleep duration. These results provide an example of local sleep in which local initiation of SWs during NREM sleep predicts later skill improvement and foreshadows locally enhanced neural signals the next day. In addition, REM sleep also promotes local learning-dependent activity, possibly by promoting synaptic plasticity.

Sleep sharpens sensory stimulus coding in human visual cortex after fear conditioning.

Efficient perceptual identification of emotionally-relevant stimuli requires optimized neural coding. Because sleep contributes to neural plasticity mechanisms, we asked whether the perceptual representation of emotionally-relevant stimuli within sensory cortices is modified after a period of sleep. We show combined effects of sleep and aversive conditioning on subsequent discrimination of face identity information, with parallel plasticity in the amygdala and visual cortex. After one night of sleep (but neither immediately nor after an equal waking interval), a fear-conditioned face was better detected when morphed with another identity. This behavioral change was accompanied by increased selectivity of the amygdala and face-responsive fusiform regions. Overnight neural changes can thus sharpen the representation of threat-related stimuli in cortical sensory areas, in order to improve detection in impoverished or ambiguous situations. These findings reveal an important role of sleep in shaping cortical selectivity to emotionally-relevant cues and thus promoting adaptive responses to new dangers.

Neural substrates of cognitive switching and inhibition in a face processing task.

We frequently need to change our current occupation, an operation requiring additional effortful cognitive demands. Switching from one task to another may involve two distinct processes: inhibition of the previously relevant task-set, and initiation of a new one. Here we tested whether these two processes are underpinned by separate neural substrates, and whether they differ depending on the nature of the task and the emotional content of stimuli. We used functional magnetic resonance imaging in healthy human volunteers who categorize emotional faces according to three different judgment rules (color, gender, or emotional expression). Our paradigm allowed us to separate neural activity associated with inhibition and switching based on the sequence of the tasks required on successive trials. We found that the bilateral medial superior parietal lobule and left intraparietal sulcus showed consistent activation during switching regardless of the task. On the other hand, no common region was activated (or suppressed) as a consequence of inhibition across all tasks. Rather, task-specific effects were observed in brain regions that were more activated when switching to a particular task but less activated after inhibition of the same task. In addition, compared to other conditions, the emotional task elicited a similar switching cost but lower inhibition cost, accompanied by selective decrease in the anterior cingulate cortex when returning to this task shortly after inhibiting it. These results demonstrate that switching relies on domain-general processes mediated by postero-medial parietal areas, engaged across all tasks, but also provide novel evidence that task inhibition produces domain-specific decreases as a function of particular task demands, with only the latter inhibition component being modulated by emotional information.

Sleep stabilizes visuomotor adaptation memory: a functional magnetic resonance imaging study.

The beneficial effect of sleep on motor memory consolidation is well known for motor sequence memory, but remains unsettled for visuomotor adaptation in humans. The aim of this study was to characterize more clearly the influence of sleep on consolidation of visuomotor adaptation using a between-subjects functional magnetic resonance imaging (fMRI) design contrasting sleep to total sleep deprivation. Our behavioural results, based on seven different parameters, show that sleep stabilizes performance whereas sleep deprivation deteriorates it. During training, while a set of cerebellar, striatal and cortical areas is activated in proportion to performance improvement, the recruitment of the hippocampus and frontal cortex protects motor memory against the detrimental effects of sleep deprivation. During retest after sleep loss a cerebello-cortical network, usually involved in the earliest stage of learning, was recruited to perform the task. In contrast, no changes in cerebral activity were observed after sleep, suggesting that it may only support the stabilization of the visuomotor adaptation memory trace.

Evidence for an emotional adaptive function of dreams: a cross-cultural study.

The function of dreams is a longstanding scientific research question. Simulation theories of dream function, which are based on the premise that dreams represent evolutionary past selective pressures and fitness improvement through modified states of consciousness, have yet to be tested in cross-cultural populations that include small-scale forager societies. Here, we analyze dream content with cross-cultural comparisons between the BaYaka (Rep. of Congo) and Hadza (Tanzania) foraging groups and Global North populations, to test the hypothesis that dreams in forager groups serve a more effective emotion regulation function due to their strong social norms and high interpersonal support. Using a linear mixed effects model we analyzed 896 dreams from 234 individuals across these populations, recorded using dream diaries. Dream texts were processed into four psychosocial constructs using the Linguistic Inquiry and Word Count (LIWC-22) dictionary. The BaYaka displayed greater community-oriented dream content. Both the BaYaka and Hadza exhibited heightened threat dream content, while, at the same time, the Hadza demonstrated low negative emotions in their dreams. The Global North Nightmare Disorder group had increased negative emotion content, and the Canadian student sample during the COVID-19 pandemic displayed the highest anxiety dream content. In conclusion, this study supports the notion that dreams in non-clinical populations can effectively regulate emotions by linking potential threats with non-fearful contexts, reducing anxiety and negative emotions through emotional release or catharsis. Overall, this work contributes to our understanding of the evolutionary significance of this altered state of consciousness.

Neural correlates of performance variability during motor sequence acquisition.

During the initial training of a motor sequence, performance becomes progressively faster but also increasingly reproducible and consistent. However, performance temporarily becomes more variable at mid-training, reflecting a change in the motor representation and the eventual selection of the optimal performance mode (Adi-Japha et al., 2008). At the cerebral level, whereas performance speed is known to be related to the activity in cerebello-cortical and striato-cortical networks, the neural correlates of performance variability remain unknown. We characterized the latter using functional magnetic resonance imaging (fMRI) during the initial training to the Finger Tapping Task (FTT), during which participants produced a 5-element finger sequence on a keyboard with their left non-dominant hand. Our results show that responses in the precuneus decrease whereas responses in the caudate nucleus increase as performance becomes more consistent. In addition, a variable performance is associated with enhanced interaction between the hippocampus and fronto-parietal areas and between the striatum and frontal areas. Our results suggest that these dynamic large-scale interactions represent a cornerstone in the implementation of consistent motor behavior in humans.

Quarreling After a Sleepless Night: Preliminary Evidence of the Impact of Sleep Deprivation on Interpersonal Conflict.

Although poor sleep has been found to correlate with deteriorations in romantic relationships, its causal impact on interpersonal conflict has not previously been studied. Therefore, 30 couples were randomly assigned to either a single night of total sleep deprivation or a night of normal sleep to test the effects of sleep deprivation on couples' conflict. After the experimental night, all participants discussed a topic of recurrent conflict for 15 min. We collected pre- and post-conflict measures of cortisol, self-reports of feelings, and satisfaction with the conflictual discussion. Multilevel analyses revealed higher cortisol levels during conflict and less positive affect prior to and after the conflict for sleep-deprived couples compared to couples in the control condition. These findings provide initial evidence for a causal negative impact of sleep deprivation on couples' conflicts. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-021-00076-4.

Brain reactivity to emotion persists in NREM sleep and is associated with individual dream recall.

The waking brain efficiently detects emotional signals to promote survival. However, emotion detection during sleep is poorly understood and may be influenced by individual sleep characteristics or neural reactivity. Notably, dream recall frequency has been associated with stimulus reactivity during sleep, with enhanced stimulus-driven responses in high vs. low recallers. Using electroencephalography (EEG), we characterized the neural responses of healthy individuals to emotional, neutral voices, and control stimuli, both during wakefulness and NREM sleep. Then, we tested how these responses varied with individual dream recall frequency. Event-related potentials (ERPs) differed for emotional vs. neutral voices, both in wakefulness and NREM. Likewise, EEG arousals (sleep perturbations) increased selectively after the emotional voices, indicating emotion reactivity. Interestingly, sleep ERP amplitude and arousals after emotional voices increased linearly with participants' dream recall frequency. Similar correlations with dream recall were observed for beta and sigma responses, but not for theta. In contrast, dream recall correlations were absent for neutral or control stimuli. Our results reveal that brain reactivity to affective salience is preserved during NREM and is selectively associated to individual memory for dreams. Our findings also suggest that emotion-specific reactivity during sleep, and not generalized alertness, may contribute to the encoding/retrieval of dreams.

Does sleep promote false memories?

Memory is constructive in nature so that it may sometimes lead to the retrieval of distorted or illusory information. Sleep facilitates accurate declarative memory consolidation but might also promote such memory distortions. We examined the influence of sleep and lack of sleep on the cerebral correlates of accurate and false recollections using fMRI. After encoding lists of semantically related word associates, half of the participants were allowed to sleep, whereas the others were totally sleep deprived on the first postencoding night. During a subsequent retest fMRI session taking place 3 days later, participants made recognition memory judgments about the previously studied associates, critical theme words (which had not been previously presented during encoding), and new words unrelated to the studied items. Sleep, relative to sleep deprivation, enhanced accurate and false recollections. No significant difference was observed in brain responses to false or illusory recollection between sleep and sleep deprivation conditions. However, after sleep but not after sleep deprivation (exclusive masking), accurate and illusory recollections were both associated with responses in the hippocampus and retrosplenial cortex. The data suggest that sleep does not selectively enhance illusory memories but rather tends to promote systems-level consolidation in hippocampo-neocortical circuits of memories subsequently associated with both accurate and illusory recollections. We further observed that during encoding, hippocampal responses were selectively larger for items subsequently accurately retrieved than for material leading to illusory memories. The data indicate that the early organization of memory during encoding is a major factor influencing subsequent production of accurate or false memories.

Neural precursors of delayed insight.

The solution of a problem left unresolved in the evening can sometimes pop into mind as a sudden insight after a night of sleep in the following morning. Although favorable effects of sleep on insightful behavior have been experimentally confirmed, the neural mechanisms determining this delayed insight remain unknown. Here, using fMRI, we characterize the neural precursors of delayed insight in the number reduction task (NRT), in which a hidden task structure can be learned implicitly, but can also be recognized explicitly in an insightful process, allowing immediate qualitative improvement in task performance. Normal volunteers practiced the NRT during two fMRI sessions (training and retest), taking place 12 hours apart after a night of sleep. After this delay, half of the subjects gained insight into the hidden task structure ("solvers," S), whereas the other half did not ("nonsolvers," NS). Already at training, solvers and nonsolvers differed in their cerebral responses associated with implicit learning. In future solvers, responses were observed in the superior frontal sulcus, posterior parietal cortex, and the insula, three areas mediating controlled processes and supporting early learning and novice performance. In contrast, implicit learning was related to significant responses in the hippocampus in nonsolvers. Moreover, the hippocampus was functionally coupled with the basal ganglia in nonsolvers and with the superior frontal sulcus in solvers, thus potentially biasing participants' strategy towards implicit or controlled processes of memory encoding, respectively. Furthermore, in solvers but not in nonsolvers, response patterns were further transformed overnight, with enhanced responses in ventral medial prefrontal cortex, an area previously implicated in the consolidation of declarative memory. During retest in solvers, before they gain insight into the hidden rule, significant responses were observed in the same medial prefrontal area. After insight, a distributed set of parietal and frontal areas is recruited among which information concerning the hidden rule can be shared in a so-called global workspace.

Depression alters "top-down" visual attention: a dynamic causal modeling comparison between depressed and healthy subjects.

Using functional magnetic resonance imaging (fMRI), we recently demonstrated that nonmedicated patients with a first episode of unipolar major depression (MDD) compared to matched controls exhibited an abnormal neural filtering of irrelevant visual information (Desseilles et al., 2009). During scanning, subjects performed a visual attention task imposing two different levels of attentional load at fixation (low or high), while task-irrelevant colored stimuli were presented in the periphery. In the present study, we focused on the visuo-attentional system and used "Dynamic Causal Modeling" (DCM) on the same dataset to assess how attention influences a network of three dynamically-interconnected brain regions (visual areas V1 and V4, and intraparietal sulcus (P), differentially in MDD patients and healthy controls. Bayesian model selection (BMS) and model space partitioning (MSP) were used to determine the best model in each population. The best model for the controls revealed that the increase of parietal activity by high attention load was selectively associated with a negative modulation of P on V4, consistent with high attention reducing the processing of irrelevant colored peripheral stimuli. The best model accounting for the data from the MDD patients showed that both low and high attention levels exerted modulatory effects on P. The present results document abnormal effective connectivity across visuo-attentional networks in MDD, which likely contributes to deficient attentional filtering of information.

Cognitive and emotional processes during dreaming: a neuroimaging view.

Dream is a state of consciousness characterized by internally-generated sensory, cognitive and emotional experiences occurring during sleep. Dream reports tend to be particularly abundant, with complex, emotional, and perceptually vivid experiences after awakenings from rapid eye movement (REM) sleep. This is why our current knowledge of the cerebral correlates of dreaming, mainly derives from studies of REM sleep. Neuroimaging results show that REM sleep is characterized by a specific pattern of regional brain activity. We demonstrate that this heterogeneous distribution of brain activity during sleep explains many typical features in dreams. Reciprocally, specific dream characteristics suggest the activation of selective brain regions during sleep. Such an integration of neuroimaging data of human sleep, mental imagery, and the content of dreams is critical for current models of dreaming; it also provides neurobiological support for an implication of sleep and dreaming in some important functions such as emotional regulation.