Previous fMRI Research Articles

Symptomatic psychosis risk and physiological fluctuation in functional MRI data

BackgroundPhysiological brain pulsations have been shown to play a critical role in maintaining interstitial homeostasis in the glymphatic brain clearance mechanism. We investigated whether psychotic symptomatology is related to the physiological variation of the human brain using fMRI. MethodsThe participants (N = 277) were from the Northern Finland Birth Cohort 1986. Psychotic symptoms were evaluated with the Positive Symptoms Scale of the Structured Interview for Prodromal Syndromes (SIPS). We used the coefficient of variation of BOLD signal (CVBOLD) as a proxy for physiological brain pulsatility. The CVBOLD-analyses were controlled for motion, age, sex, and educational level. The results were also compared with fMRI and voxel-based morphometry (VBM) meta-analyses of schizophrenia patients (data from the Brainmap database). ResultsAt the global level, participants with psychotic-like symptoms had higher CVBOLD in cerebrospinal fluid (CSF) and white matter (WM), when compared to participants with no psychotic symptoms. Voxel-wise analyses revealed that CVBOLD was increased, especially in periventricular white matter, basal ganglia, cerebellum and parts of the cortical structures. Those brain regions, which included alterations of physiological fluctuation in symptomatic psychosis risk, overlapped <6% with the regions that were found to be affected in the meta-analyses of previous fMRI and VBM studies in schizophrenia patients. Motion did not vary as a function of SIPS. ConclusionsPsychotic-like symptoms were associated with elevated CVBOLD in a variety of brain regions. The CVBOLD findings may produce new information about cerebral physiological fluctuations that have been out of reach in previous fMRI and VBM studies.

Functional alteration of brain network in schizophrenia: An fMRI study based on mutual information

Schizophrenia is a severe psychiatric disorder with complex neural mechanisms. Previous functional magnetic resonance imaging (fMRI) studies of schizophrenia often focused on single brain regions or selected networks. In recent years, neurophysiological alterations of schizophrenia are thought to be related with connectivity between distinct brain functional regions. The present study attempted to explore the alterations of resting-state functional connectivity to understand the neural mechanisms for adults with schizophrenia comprehensively. Here we perform a whole brain data-driven functional network analysis using resting-state fMRI data of 128 schizophrenia patients and 103 matched healthy controls. A whole brain large-scale graph theory based network is constructed using the mutual information method instead of the traditional correlation method. Significant nodal differences of network measures are found at several regions including the prefrontal cortex, hippocampus, temporal gyrus between patients and controls. Furthermore, we construct a pathological subnetwork and find intra-subnetwork edge strength differences located at the bilateral orbital gyrus and right hippocampus and the connection within temporal gyrus. Motif analysis reveal the network topological reorganization in schizophrenia happens mainly at the frontal, anterior cingulate gyrus and parahippocampal gyrus. These findings may help understand the neural basis more comprehensively and serve as a potential diagnosis marker in schizophrenia clinical application.

The Impact of Spatial Normalization Strategies on the Temporal Features of the Resting-State Functional MRI: Spatial Normalization Before rs-fMRI Features Calculation May Reduce the Reliability.

Previous resting-state functional magnetic resonance imaging (rs-fMRI) studies frequently applied the spatial normalization on fMRI time series before the calculation of temporal features (here referred to as “Prenorm”). We hypothesized that calculating the rs-fMRI features, for example, functional connectivity (FC), regional homogeneity (ReHo), or amplitude of low-frequency fluctuation (ALFF) in individual space, before the spatial normalization (referred to as “Postnorm”) can be an improvement to avoid artifacts and increase the results’ reliability. We utilized two datasets: (1) simulated images where temporal signal-to-noise ratio (tSNR) is kept a constant and (2) an empirical fMRI dataset with 50 healthy young subjects. For simulated images, the tSNR is constant as generated in individual space but increased after Prenorm and intersubject variability of tSNR was induced. In contrast, tSNR was kept constant after Postnorm. Consistently, for empirical images, higher tSNR, ReHo, and FC (default mode network, seed in precuneus) and lower ALFF were found after Prenorm compared to those of Postnorm. Coefficient of variability of tSNR and ALFF was higher after Prenorm compared to those of Postnorm. Moreover, the significant correlation was found between simulated tSNR after Prenorm and empirical tSNR, ALFF, and ReHo after Prenorm, indicating algorithmic variation in empirical rs-fMRI features. Furthermore, comparing to Prenorm, ALFF and ReHo showed higher intraclass correlation coefficients between two serial scans after Postnorm. Our results indicated that Prenorm may induce algorithmic intersubject variability on tSNR and reduce its reliability, which also significantly affected ALFF and ReHo. We suggest using Postnorm instead of Prenorm for future rs-fMRI studies using ALFF/ReHo.

Atypical Amygdala-Neocortex Interaction During Dynamic Facial Expression Processing in Autism Spectrum Disorder.

Atypical reciprocal social interactions involving emotional facial expressions are a core clinical feature of autism spectrum disorder (ASD). Previous functional magnetic resonance imaging (fMRI) studies have demonstrated that some social brain regions, including subcortical (e.g., amygdala) and neocortical regions (e.g., fusiform gyrus, FG) are less activated during the processing of facial expression stimuli in individuals with ASD. However, the functional networking patterns between the subcortical and cortical regions in processing emotional facial expressions remain unclear. We investigated this issue in ASD (n = 31) and typically developing (TD; n = 31) individuals using fMRI. Participants viewed dynamic facial expressions of anger and happiness and their corresponding mosaic images. Regional brain activity analysis revealed reduced activation of several social brain regions, including the amygdala, in the ASD group compared with the TD group in response to dynamic facial expressions vs. dynamic mosaics (p < 0.05, = 0.19). Dynamic causal modeling (DCM) analyses were then used to compare models with forward, backward, and bi-directional effective connectivity between the amygdala and neocortical networks. The results revealed that: (1) the model with effective connectivity from the amygdala to the neocortex best fit the data of both groups; and (2) the same model best accounted for group differences. Coupling parameter (i.e., effective connectivity) analyses showed that the modulatory effects of dynamic facial processing were substantially weaker in the ASD group than in the TD group. These findings suggest that atypical modulation from the amygdala to the neocortex underlies impairment in social interaction involving dynamic facial expressions in individuals with ASD.

Individuation of parts of a single object and multiple distinct objects relies on a common neural mechanism in inferior intraparietal sulcus

Object identification and enumeration rely on the ability to distinguish, or individuate, objects from the background. Does multiple object individuation operate only over bounded, separable objects or does it operate equally over connected features within a single object? While previous fMRI experiments suggest that connectedness affects the processing and enumeration of objects, recent behavioral and EEG studies demonstrated that parallel individuation occurs over both object parts and distinct objects. However, it is unclear whether individuation of object parts and distinct objects relies on a common or independent neural mechanisms. Using fMRI-based multivariate pattern analyses, we here demonstrate that activity patterns in inferior and superior intraparietal sulci (IPS) encode numerosity independently of whether the individuated items are connected parts of a single object or distinct objects. Lateral occipital cortex is more sensitive to perceptual aspects of the two stimulus types and the targets of the stimuli, suggesting a dissociation between ventral and dorsal areas in representing perceptual object properties and more general information about numerosity, respectively. Our results suggest that objecthood is not a necessary prerequisite for parallel individuation in IPS. Rather, our results point toward a common individuation mechanism that selects targets over a flexible object hierarchy, independently of whether the targets are distinct separable objects or parts of a single object.

Cingulo-hippocampal effective connectivity positively correlates with drug-cue attentional bias in opioid use disorder

Individuals with opioid use disorder (OUD) often relapse when exposed to opioid-related cues. Previous functional magnetic resonance imaging (fMRI) studies have identified neuronal corticolimbic changes related to drug cue reactivity in OUD. However, the corresponding manner in which brain regions interact is still unclear. Effective (directional) connectivity was analyzed using dynamic causal modeling of fMRI data acquired from 27 OUD participants (13 with OUD and 14 with OUD and cocaine use disorder [OUD+CUD]), while performing an opioid-word Stroop task. Participants were shown opioid and neutral words presented in different colors and were instructed to indicate word color but ignore word meaning. The effects of opioid words relative to neutral words on effective connectivity and on behavioral reaction time were defined as modulatory change and attentional bias, respectively. For all the 27 participants, left anterior cingulate cortex (ACC) to right hippocampus effective connectivity exhibited the largest modulatory change, which was positively correlated with attentional bias. The findings for the ACC to hippocampus EC were consistent across OUD and CUD found in a previous study.

Long-Term Potentiation of Prelimbic Cortex Ascribed to Heat-Sensitization Responses of Moxibustion.

Heat-sensitization responses occurred in certain patients while exposed to suspended moxibustion. The response often indicated that the efficacy of moxibustion to those with it tended to triumph over those without. However, its mechanism remains to be explained. Our previous fMRI and EEG studies confirmed the changes of activities in cerebral certain regions accompanied with heat-sensitization responses, especially in prefrontal cortex. Therefore, we hypothesize that neurological system is involved in moxibustion-induced heat-sensitization responses. In the present study, phosphorylation of Cofilin representing long-term potentiation in synapse of prelimbic cortex of medial prefrontal cortex in stroke rats over suspended moxibustion was assessed, and the size of phosphorylated Cofilin positive spine in synapse was also measured. The result showed that heat-sensitization responses were observed to augment cerebral ischemic stroke-induced phosphorylation of Cofilin in prelimbic cortex of rats and increase the numbers of large synapses. This indicated that long-term potentiation of prelimbic cortex was attributed to heat-sensitization responses that were certain neurological responses of medial prefrontal cortex to suspended moxibustion.

Prior Emotional Context Modulates Early Event-Related Potentials to Neutral Retrieval Cues.

Memory retrieval is thought to involve the reactivation of encoding processes. Previous fMRI work has indicated that reactivation processes are modulated by the residual effects of the prior emotional encoding context; different spatial patterns emerge during retrieval of memories previously associated with negative compared with positive or neutral context. Other research suggests that event-related potential (ERP) indicators of memory retrieval processes, like the left parietal old/new effect, can also be modulated by emotional context, but the spatial distribution and temporal dynamics of these effects are unclear. In the current study, we examined "when" emotion affects recognition memory and whether that timing reflects processes that come before and may guide successful retrieval or postrecollection recovery of emotional episodic detail. While recording EEG, participants (n = 25) viewed neutral words paired with negative, positive, or neutral pictures during encoding, followed by a recognition test for the words. Analyses focused on ERPs during the recognition test. In line with prior ERP studies, we found an early positive-going parietally distributed effect starting around 200 msec after retrieval-cue onset. This effect emerged for words that had been encoded in an emotional compared with neutral context (no valence differences), before the general old/new effect. This emotion-dependent effect occurred in an early time window, suggesting that emotion-related reactivation is a precursor to successful recognition.

Default mode and visual network activity in an attention task: Direct measurement with intracranial EEG

Dynamic attention states are necessary to navigate the ever changing task demands of daily life. Previous investigations commonly utilize a block paradigm to study sustained and transient changes in attention networks. fMRI investigations have shown that sustained attention in visual block design attention tasks corresponds to decreased signal in the default mode and visual processing networks. While task negative networks are anticipated to decrease during active task engagement, it is unexpected that visual networks would also be suppressed during a visual task where event-related fMRI studies have found transient increases to visual stimuli. To resolve these competing results, the current investigations utilized intracranial EEG to directly interrogate visual and default mode network dynamics during a visual continuous performance task. We used the electrophysiological data to model expected fMRI signals and to maximize interpretation of current results with previous investigations. Results show broadband gamma power decreases in the default mode network, corresponding to previous EEG and fMRI findings. Meanwhile, visual processing regions including the primary visual cortex and fusiform gyrus demonstrate both sustained decreases during task engagement and stimuli-driven transient increases in gamma power. Modeled fMRI based on gamma power reproduces signal decreases reported in the fMRI literature, and emphasizes the insensitivity of fMRI to transient, regularly spaced signal changes embedded within sustained network dynamics. The signal processing functions of the dynamic visual and default mode network changes explored in this study are unknown but may be elucidated through further investigation.

Baseline Functional Connectivity Features of Neural Network Nodes Can Predict Improvement After Sound Therapy Through Adjusted Narrow Band Noise in Tinnitus Patients.

Previous resting-state functional magnetic resonance imaging (fMRI) studies have shown neural connectivity alterations after the treatment of tinnitus. We aim to study the value of the baseline functional connectivity features of neural network nodes to predict outcomes of sound therapy through adjusted narrow band noise. The fMRI data of 27 untreated tinnitus patients and 27 matched healthy controls were analyzed. We calculated the graph-theoretical metric degree centrality (DC) to characterize the functional connectivity of the neural network nodes. Therapeutic outcomes are determined by the changes in the Tinnitus Handicap Inventory (THI) score after a 12-week intervention. The connectivity of 10 brain nodes in tinnitus patients was significantly increased at baseline. The functional connectivity of right insula, inferior parietal lobule (IPL), bilateral thalami, and left middle temporal gyrus was significantly modified with the sound therapy, and such changes correlated with THI changes in tinnitus patients. Receiver operating characteristic curve analyses revealed that the measurements from the five brain regions were effective at classifying improvement after therapy. After age, gender, and education correction, the adjusted area under the curve (AUC) values for the bilateral thalami were the highest (left, 0.745; right, 0.708). Our study further supported the involvement of the fronto-parietal-cingulate network in tinnitus and found that the connectivity of the thalamus at baseline is an object neuroimaging-based indicator to predict clinical outcome of sound therapy through adjusted narrow band noise.

Comparing the Design Neurocognition of Mechanical Engineers and Architects: A Study of the Effect of Designer’s Domain

AbstractNew tools from neuroscience allow design researchers to explore design neurocognition. By taking the advantage of EEG's temporal resolution we give up spatial resolution to focus on the performance of time-related design tasks. This paper presents results from an experiment using EEG to measure brain activation to study mechanical engineers and architects to compare their design neurocognition. In this study, we adopted and extended the tasks described in a previous fMRI study of design neurocognition reported in the literature. The block experiment consists of a sequence of 3 tasks: problem solving, basic design and open design using a physical interface. The block is preceded by a familiarizing pre-task using the physical interface and then extended to a fourth task using free-hand sketching. Brainwaves were collected from both mechanical engineers and architects. Results comparing 36 mechanical engineers and architects while designing were produced. These results indicate design cognition differences between the two domains in task-related power between the problem-solving task and the design tasks, in temporal resolution and transformed power.

Changing the Real Viewing Distance Reveals the Temporal Evolution of Size Constancy in Visual Cortex

Our visual system provides a distance-invariant percept of object size by integrating retinal image size with viewing distance (size constancy). Single-unit studies with animals have shown that some distance cues, especially oculomotor cues such as vergence and accommodation, can modulate the signals in the thalamus or V1 at the initial processing stage [1-7]. Accordingly, one might predict that size constancy emerges much earlier in time [8-10], even as visual signals are being processed in the thalamus. So far, the studies that have looked directly at size coding have either used fMRI (poor temporal resolution [11-13]) or relied on inadequate stimuli (pictorial illusions presented on a monitor at a fixed distance [11, 12, 14, 15]). Here, we physically moved the monitor to different distances, a more ecologically valid paradigm that emulates what happens in everyday life and is an example of the increasing trend of "bringing the real world into the lab." Using this paradigm in combination with electroencephalography (EEG), we examined the computation of size constancy in real time with real-world viewing conditions. Our study provides strong evidence that, even though oculomotor distance cues have been shown to modulate the spiking rate of neurons in the thalamus and in V1, the integration of viewing distance cues and retinal image size takes at least 150ms to unfold, which suggests that the size-constancy-related activation patterns in V1 reported in previous fMRI studies (e.g., [12, 13]) reflect the later processing within V1 and/or top-down input from other high-level visual areas.

The role of ventromedial prefrontal cortex and temporo-parietal junction in third-party punishment behavior

Third parties punish, sacrificing personal interests, offenders who violate either fairness or cooperation norms. This behavior is defined altruistic punishment and the degree of punishment typically increases with the severity of the norm violation. An opposite and apparently paradoxical behavior, namely anti-social punishment, is the tendency to spend own money to punish cooperative or fair behaviors. Previous fMRI studies correlated punishment behavior with increased activation of brain areas belonging to the reward system (e.g. the ventromedial prefrontal cortex, VMPFC), the mentalizing (e.g. the temporoparietal junction, TPJ) and central-executive networks. In the present study, we aimed at investigating the causal role of VMPFC and TPJ in punishment behaviors through the application of anodal transcranial direct current stimulation (tDCS).Sixty healthy participants were randomly assigned to three tDCS conditions: (1) anodal tDCS over VMPFC, (2) anodal tDCS over right TPJ (rTPJ), (3) sham stimulation. At the end of the stimulation, participants played a third-party punishment game, consisting in viewing a series of fair or unfair monetary allocations between unknown proposers and recipients. Participants were asked whether and how much they would punish the proposers using their own monetary endowment. To test membership effects, proposers and recipients could be either Italian or Chinese.Anodal tDCS over VMPFC increased altruistic punishment behavior whereas anodal tDCS over rTPJ increased anti-social punishment choices compared with sham condition, while membership did not influence participant's choices. Our results support the idea that the two types of punishment behaviors rely upon different brain regions, suggesting that reward and mentalizing systems underlie, respectively, altruistic and anti-social punishment behaviors.

Martial Arts "Kendo" and the Motivation Network During Attention Processing: An fMRI Study.

Japanese martial arts, Budo, have been reported to improve cognitive function, especially attention. However, the underlying neural mechanisms of the effect of Budo on attention processing has not yet been investigated. Kendo, a type of fencing using bamboo swords, is one of the most popular forms of Budo worldwide. We investigated the difference in functional connectivity (FC) between Kendo players (KPs) and non-KPs (NKPs) during an attention-related auditory oddball paradigm and during rest. The analyses focused on the brain network related to “motivation.” Resting-state functional magnetic resonance imaging (rs-fMRI) and task-based fMRI using the oddball paradigm were performed in healthy male volunteers (14 KPs and 11 NKPs). Group differences in FC were tested using CONN-software within the motivation network, which consisted of 22 brain regions defined by a previous response-conflict task-based fMRI study with a reward cue. Daily general physical activities were assessed using the International Physical Activity Questionnaire (IPAQ). We also investigated the impact of major confounders, namely, smoking habits, alcohol consumption, IPAQ score, body mass index (BMI), and reaction time (RT) in the oddball paradigm. Resting-state fMRI revealed that KPs had a significantly lower FC than NKPs between the right nucleus accumbens and right frontal eye field (FEF) within the motivation network. Conversely, KPs exhibited a significantly higher FC than NKPs between the left intraparietal sulcus (IPS) and the left precentral gyrus (PCG) within the network during the auditory oddball paradigm [statistical thresholds, False Discovery Rate (FDR) < 0.05]. These results remained significant after controlling for major covariates. Our results suggest that attenuated motivation network integrity at rest together with enhanced motivation network integrity during attentional demands might underlie the instantaneous concentration abilities of KPs.

Functional Brain Networks Underlying Evidence Integration and Delusions in Schizophrenia.

Integrating evidence that contradicts a belief is a fundamental aspect of belief revision and is closely linked to delusions in schizophrenia. In a previous functional magnetic resonance imaging (fMRI) study on healthy individuals, we identified functional brain networks underlying evidence integration as visual attention network (VsAN; dorsal anterior cingulate cortex, insula, occipital regions), default-mode network (DMN), and cognitive evaluation network (CEN; orbitofrontal cortex, inferior frontal gyrus, parietal cortex). In the current clinical fMRI study, we compared network-based activity during evidence integration between healthy controls (n = 41), nondelusional (n = 37), and delusional (n = 33) patients with schizophrenia, and related this activity to cognitive processing involved in evidence integration measured outside the scanner. Task-induced coordinated activation was measured using group-constrained principal component analysis for fMRI. Increased VsAN activation, reduced DMN deactivation, and reduced CEN activation were observed for schizophrenia, with this pattern being most pronounced for the delusional group. Importantly, poor evidence integration comprehensively measured outside the scanner was significantly associated with increased VsAN activation and reduced DMN deactivation when processing confirmatory evidence, and with reduced CEN activation when processing disconfirmatory evidence. This is the first comprehensive study of the functional brain networks associated with evidence integration in schizophrenia and highlights how an imbalance of functional brain networks responding to confirmatory and disconfirmatory evidence may underlie delusions in schizophrenia.

Brain responses to virtual reality visual motion stimulation are affected by neurotic personality traits in patients with persistent postural-perceptual dizziness.

Persistent postural perceptual dizziness (PPPD) is a common vestibular disorder of persistent dizziness and unsteadiness, exacerbated by upright posture, self-motion, and exposure to complex or moving visual stimuli. Previous functional magnetic resonance imaging (fMRI) studies found dysfunctional activity in the visual-vestibular cortices in patients with PPPD. Clinical studies showed that the anxiety-related personality traits of neuroticism and introversion may predispose individuals to PPPD. However, the effects of these traits on brain function in patients with PPPD versus healthy controls (HCs) have not been studied. To investigate potential differential effects of neuroticism and introversion on functioning of their visuo-vestibular networks, 15 patients with PPPD and 15 HCs matched for demographics and motion sickness susceptibility underwent fMRI during virtual reality simulation of a rollercoaster ride in vertical and horizontal directions. Neuroticism positively correlated with activity in the inferior frontal gyrus (IFg), and enhanced connectivity between the IFg and occipital regions in patients with PPPD relative to HCs during vertical versus horizontal motion comparison. In patients with PPPD, neuroticism increased the activity and connectivity of neural networks that mediate attention to visual motion cues during vertical motion. This mechanism may mediate visual control of balance in neurotic patients with PPPD.

Neural responses for evaluating self and mother traits in adolescence depend on mother-adolescent relationships.

An important task in adolescence is to achieve autonomy while preserving a positive relationship with parents. Previous fMRI studies showed largely overlapping activation in medial prefrontal cortex (mPFC) for evaluating self and close-other traits but separable activation for self and non-close other. Possibly, more similar mPFC activation reflects closeness or warmth in relationships. We investigated neural indicators of the mother–adolescent relationship in adolescents between 11 and 21 years (N = 143). Mother–adolescent relationship was measured using (i) mothers’ and adolescents’ trait evaluations about each other, (ii) observations of warmth, negativity and emotional support in mother–adolescent conversation and (iii) similarity in adolescents’ neural activation for evaluating self vs mother traits. Results showed relatively more similar mPFC activation in adolescents who evaluated their mothers’ traits more positively, suggesting that this is possibly a neural indicator of mother–adolescent relationship quality. Furthermore, mid-adolescence was characterized by more negative mother–adolescent interaction compared to early and late adolescence. This effect co-occurred with mid-adolescent peaks in dorsal striatum, dorsal anterior cingulate cortex and superior temporal sulcus activation in evaluating traits of self vs mother. These results suggest more negative relationships and stronger self-focus in mid-adolescence.

Capturing spontaneous activity in the medial prefrontal cortex using near-infrared spectroscopy and its application to schizophrenia

Near-infrared spectroscopy (NIRS) is an optimal imaging modality used to examine spontaneous brain activity because it can quietly measure blood flow changes with less physical restriction during the resting state. Here, NIRS was used at rest to measure spontaneous activity in the medial prefrontal cortex (mPFC), a main locus of default mode network. Consistent with previous fMRI studies, magnitude of the spontaneous activity in this region declined with increasing age in healthy subjects. The magnitude reduced in the mPFC of patients with schizophrenia. Additionally, in the mPFC of patients with schizophrenia, the spontaneous activity did not show any age-related decline; the activity was already low in younger patients. Further analysis using fractional amplitude of low-frequency fluctuations confirmed the reduction of spontaneous activity in the mPFC of patients with schizophrenia, consistent with the findings of fMRI studies. Our findings demonstrate the ability of NIRS to evaluate the spontaneous activity in the mPFC of patients with schizophrenia, particularly younger patients. Considering the safety and ease of the NIRS measurements, the current NIRS study of the resting-state activity indicates its utility for clinical applications to schizophrenia, which may facilitate chronological assessment of larger cohorts of patients with schizophrenia in further studies.

Altered ability to access a clinically relevant control network in patients remitted from major depressive disorder.

Neurobiological models to explain vulnerability of major depressive disorder (MDD) are scarce and previous functional magnetic resonance imaging studies mostly examined “static” functional connectivity (FC). Knowing that FC constantly evolves over time, it becomes important to assess how FC dynamically differs in remitted‐MDD patients vulnerable for new depressive episodes. Using a recently developed method to examine dynamic FC, we characterized re‐emerging FC states during rest in 51 antidepressant‐free MDD patients at high risk of recurrence (≥2 previous episodes), and 35 healthy controls. We examined differences in occurrence, duration, and switching profiles of FC states after neutral and sad mood induction. Remitted MDD patients showed a decreased probability of an FC state (p < 0.005) consisting of an extensive network connecting frontal areas—important for cognitive control—with default mode network, striatum, and salience areas, involved in emotional and self‐referential processing. Even when this FC state was observed in patients, it lasted shorter (p < 0.005) and was less likely to switch to a smaller prefrontal–striatum network (p < 0.005). Differences between patients and controls decreased after sad mood induction. Further, the duration of this FC state increased in remitted patients after sad mood induction but not in controls (p < 0.05). Our findings suggest reduced ability of remitted‐MDD patients, in neutral mood, to access a clinically relevant control network involved in the interplay between externally and internally oriented attention. When recovering from sad mood, remitted recurrent MDD appears to employ a compensatory mechanism to access this FC state. This study provides a novel neurobiological profile of MDD vulnerability.

TouchScreen-based phenotyping: altered stimulus/reward association and lower perseveration to gain a reward in mu opioid receptor knockout mice

While the contribution of Mu Opioid Receptors (MORs) to hedonic aspects of reward processing is well-established, the notion that these receptors may also regulate motivation to gain a reward, and possibly other related cognitive dimensions, has been less investigated. The prefrontal cortex (PFC) is a critical site for these processes. Our previous functional magnetic resonance imaging study found alterations of functional connectivity (FC) in reward/aversion networks in MOR knockout mice. Here we pursued voxelwise seed-based FC analyses using the same dataset with a focus on the PFC. We observed significant reduction of PFC FC in mutant mice, predominantly with the nucleus accumbens, supporting the notion of altered reward-driven top-down controls. We tested motivation for palatable food in a classical operant self-administration paradigm, and found delayed performance for mutant mice. We then evaluated motivational and cognitive abilities of MOR knockout mice in TouchScreen-based behavioral tests. Learning was delayed and stimulus/reward association was impaired, suggesting lower hedonic reward value and reduced motivation. Perseverative responses were decreased, while discriminatory behavior and attention were unchanged, indicative of increased inhibitory controls with otherwise intact cognitive performance. Together, our data suggest that MORs contribute to enhance reward-seeking and facilitate perseverative behaviors. The possibility that MOR blockade could reduce maladaptive compulsivity deserves further investigation in addiction and self-control disorder research.