Prefrontal Regions Research Articles

Sensitivity to and Control of Distraction: Distractor-Entrained Oscillation and Frontoparietal EEG Gamma Synchronization.

While recent advancements have been made towards a better understanding of the involvement of the prefrontal cortex (PFC) in the context of cognitive control, the exact mechanism is still not fully understood. Successful behavior requires the correct detection of goal-relevant cues and resisting irrelevant distractions. Frontal parietal networks have been implicated as important for maintaining cognitive control in the face of distraction. The present study investigated the role of gamma-band power in distraction resistance and frontoparietal networks, as its increase is linked to cholinergic activity. We examined changes in gamma activity and their relationship to frontoparietal top-down modulation for distractor challenges and to bottom-up distractor processing. Healthy young adults were tested using a modified version of the distractor condition sustained attention task (dSAT) while wearing an EEG. The modified distractor was designed so that oscillatory activities could be entrained to it, and the strength of entrainment was used to assess the degree of distraction. Increased top-down control during the distractor challenge increased gamma power in the left parietal regions rather than the right prefrontal regions predicted from rodent studies. Specifically, left parietal gamma power increased in response to distraction where the amount of this increase was negatively correlated with the neural activity reflecting bottom-up distractor processing in the visual area. Variability in gamma power in right prefrontal regions was associated with increased response time variability during distraction. This may suggest that the right prefrontal region may contribute to the signaling needed for top-down control rather than its implementation.

Threat- and reward-related brain circuitry, perceived stress, and anxiety in adolescents during the COVID-19 pandemic: a longitudinal investigation.

The Coronavirus disease (COVID-19) pandemic led to heightened anxiety in adolescents. The basolateral amygdala (BLA) and the nucleus accumbens (NAcc) are implicated in response to stress and may contribute to anxiety. The role of threat- and reward-related circuitry in adolescent anxiety during the COVID-19 pandemic, however, is not clear. Ninety-nine adolescents underwent resting-state fMRI ∼1 year before the pandemic. Following shelter-in-place orders, adolescents reported their perceived stress and, 1 month later, their anxiety. Generalized multivariate analyses identified BLA and NAcc seed-based whole-brain functional connectivity maps with perceived stress. In the resulting significant clusters, we examined the association between seed-based connectivityand subsequent anxiety. Perceived stress was associated with bilateral BLA and NAcc connectivity across distributed clusters that included prefrontal, limbic, temporal, and cerebellar regions. Several NAcc connectivity clusters located in ventromedial prefrontal, parahippocampal, and temporal cortices were positively associated with anxiety; NAcc connectivity with the inferior frontal gyrus was negatively associated. BLA connectivity was not associated with anxiety. These results underscore the integrative role of the NAcc in responding to acute stressors and its relation to anxiety in adolescents. Elucidating the involvement of subcortical-cortical circuitry in adolescents' capacity to respond adaptively to environmental challenges can inform treatment for anxiety-related disorders.

Estradiol modulates changes in effective connectivity in emotion regulation networks

Hormonal changes in ovarian hormones like estradiol (E2) during the menstrual cycle affect emotional processes, including emotion recognition, memory, and regulation. So far, the neural underpinnings of the effect of E2 on emotional experience have been investigated using task-based functional magnetic resonance imaging (fMRI) and functional connectivity. In the present study, we examined whether the intrinsic network dynamics at rest (i.e., directed effective connectivity) related to emotion regulation are (1) modulated by E2 levels and (2) linked to behavioral emotion regulation ability. Hence, 29 naturally cycling women participated in two resting-state fMRI scans in their early follicular phase after being administered a placebo or an E2 valerate, respectively. Emotion regulation ability was assessed using a standard emotion regulation task in which participants were asked to down-regulate their emotions in response to negative images. The regions of two functionally predefined neural networks related to emotional down-regulation and reactivity were used to investigate effective connectivity at rest using spectral dynamic causal modelling. We found that E2, compared to placebo, resulted in changes in effective connectivity in both networks. In the regulation network, prefrontal regions showed distinct connectivity in the E2 compared to the placebo condition, while mixed results evolved in the emotional reactivity network. Stepwise regressions revealed that in the E2 condition a connection from the parietal to the prefrontal cortex predicted regulation ability. Our results demonstrate that E2 levels influence effective connectivity in networks underlying emotion regulation and emotional reactivity. Thus, E2 and its potential modification via hormonal administration may play a supporting role in the treatment of mental disorders that show a dysregulation of emotions.

The Corpus Callosum in Schizoaffective Disorder: A Shape Analysis Study

Objective: The corpus callosum is the largest white matter structure in the human brain that connects the cortical regions of both hemispheres. Diseases could lead to degenerative alterations in brain structures such as the corpus callosum (CC). Studies have associated CC abnormalities with Schizoaffective Disorder (SAD) symptoms. We predicted that there may be differences in the CC, an important structure connecting the two halves of the brain, in patients with SAD. The present study aims to analyze the CC of patients with statistical shape analysis (SSA) and compare the findings with healthy controls. Methods: Thirty-nine SAD patients and 39 healthy individuals (11 females and 28 males) of similar age that included subjects participated in the study. CC landmarks were marked on the mid-sagittal images of each participant. The mean ‘Procrustes’ point was determined, and shape deformations were analyzed with thin plate spline analysis. Results: Significant differences were observed between the shapes of CC in the two groups, and maximum CC deformation was observed in the posterior regions of SAD patients. There was no significant difference between the CC area of the SAD patients and the controls. Conclusion: In the present study, the maximum deformation was observed in the posterior region (isthmus and splenium) and the rostrum of the CC. The first CC region, the rostrum (+genu), connects prefrontal and premotor regions, which are associated with cognitive information (landmarks = 1, 7, 8, 9, 13, 15, and 12). The second area, the splenium, connects temporal and occipital cortical areas. These predominantly have auditory, peripheral, and central visual stimulation functions (landmarks = 5, 3, and 4). The current study could assist future studies on the etiology, diagnosis, and treatment of SAD.

Impacts of early deprivation on behavioral and neural measures of executive function in early adolescence

Children reared in institutional settings experience early deprivation that has lasting implications for multiple aspects of neurocognitive functioning, including executive function (EF). Changes in brain development are thought to contribute to these persistent EF challenges, but little research has used fMRI to investigate EF-related brain activity in children with a history of early deprivation. This study examined behavioral and neural data from a response conflict task in 12–14-year-olds who spent varying lengths of time in institutional care prior to adoption (N = 84; age at adoption – mean: 15.85 months, median: 12 months, range: 4–60 months). In initial analyses, earlier- and later-adopted (EA, LA) youth were compared to a group of children raised in their biological families (non-adopted, NA). NA youth performed significantly more accurately than LA youth, with EA youth falling in between. Imaging data suggested that previously institutionalized (PI) youth activated additional frontoparietal regions, including dorsolateral prefrontal cortex, as compared to NA youth. In addition, EA youth uniquely activated medial prefrontal regions, and LA uniquely activated parietal regions during this task. A separate analysis in a larger group of PI youth examined whether behavioral or brain measures of EF varied with the duration of deprivation experienced. Duration of deprivation was negatively associated with activation of default mode network (DMN) regions. Overall, results suggest that there are lasting effects of deprivation on EF, but that those who are removed from institutional care earlier may be able to recruit additional neural resources as a compensatory mechanism.

Family and parenting factors are associated with emotion regulation neural function in early adolescent girls with elevated internalizing symptoms.

A prominent tripartite model proposes that parent role modeling of emotion regulation, emotion socialization behaviors, and the emotional climate of the family are important for young people's emotional development. However, limited research has examined the neural mechanisms at play. Here, we examined the associations between family and parenting factors, the neural correlates of emotional reactivity and regulation, and internalizing symptoms in early adolescent girls. Sixty-four female adolescents aged 10-12 years with elevated internalizing symptoms completed emotional reactivity, implicit (affect labeling) and explicit (cognitive reappraisal) emotion regulation tasks during functional magnetic resonance imaging. Positive family emotional climate was associated with greater activation in the anterior cingulate and middle temporal cortices during emotional reactivity. Maternal emotion regulation difficulties were associated with increased frontal pole and supramarginal gyrus activation during affect labeling, whereas supportive maternal emotion socialization and positive family emotional climate were associated with activation in prefrontal regions, including inferior frontal and superior frontal gyri, respectively, during cognitive reappraisal. No mediating effects of brain function were observed in the associations between family/parenting factors and adolescent symptoms. These findings highlight the role of family and parenting behaviors in adolescent emotion regulation neurobiology, and contribute to prominent models of adolescent emotional development.

The relationship between changes in functional networks and cognitive changes and PTSD symptoms in maltreated children before and after TF-CBT

Several studies have found that maltreated children show neuropsychological deficits in various cognitive domains such as memory and attention, language, visuospatial skills, emotional regulation, social cognition, and executive functioning. In terms of functional connectivity, abused children show an increased connectivity in the salience network (SN) as opposed to a decreased connectivity within the default (DMN) and executive networks (CEN). Children who suffer maltreatment may develop post-traumatic stress disorder (PTSD), which in turn, can increase psychological and cognitive sequelae. The present study examined the relation between resting state functional connectivity (RSFC), PTSD symptoms and neuropsychological profiles in abused children before and after following a psychological therapy named Trauma Focused Cognitive Behavioral therapy (TF-CBT). Resting state functional magnetic resonance imaging, neuropsychological (attention, memory and executive functions) and clinical evaluations were performed in 13 abused children with PTSD (mean age=8.77 years old, S.D.=1.83) recruited from a non-governmental shelter in Mexico and in a control group of 10 children from the general population (mean age = 9.57 years old, S.D. = 1.91). Both groups were matched according to age and gender. Changes in PTSD symptoms correlated with changes in the left insula node. Additionally, significant correlations were identified between changes in the average connectivity of the DMN, intra-nodal connectivity of lateral parietal and medial prefrontal regions, and performance in attention and memory tasks.

Neural activity and connectivity are related to food preference changes induced by food go/no-go training

Simply withholding a response while viewing an appetizing food, over the course of many presentations (i.e., during food go/no-go training) can modify individuals' food preferences—which could, in turn, promote healthier eating behaviors. However, the neural mechanisms underlying this food go/no-go training-induced change in food preferences are still relatively unclear. We addressed this issue in the present functional magnetic resonance imaging (fMRI) study. To this end, we administered a novel passive viewing task before and after food go/no-go training to 91 participants in the scanner. Participants’ food preferences were measured with a binary food choice task. At the behavioral level, we found the expected training effect on food preferences: Participants preferred go over no-go foods following training. At the neural level, we found that changes in food preferences were associated with training-related go vs. no-go differences in activity and functional connectivity, such as less activity in the anterior cingulate cortex and superior frontal gyrus but greater functional connectivity between the superior frontal gyrus and middle occipital gyrus. Critically, Dynamic causal modeling showed that this preference change effect was largely driven by top-down influence from the superior frontal gyrus to the middle occipital gyrus. Together, these findings suggest a neural mechanism of the food go/no-go training effect—namely, that the food-viewing-related interplay between prefrontal regions and visual regions might be related to the food preference change following food go/no-go training.

Boosting Prefrontal Brain Responsiveness by Interoceptive Attentiveness during Synchronized Breathing, Motor, and Cognitive Task

Background: this study explored the prefrontal cortex (PFC) hemodynamic variations produced by the association of an Interoceptive Attentiveness (IA) condition with a simple breath, motor, and cognitive synchronization task. Methods: 18 healthy individuals performed different synchronization activities (breath, motor, and cognitive) under both IA and control conditions, while levels of oxygenated (O2Hb) and deoxygenated hemoglobin were measured using functional Near-Infrared Spectroscopy (fNIRS). Results: findings revealed higher O2Hb levels in the prefrontal brain region during the experimental condition (IA) in contrast to the control condition. Notably, this difference was particularly evident during the cognitive task as opposed to the other tasks (breath and motor). In contrast, no significant differences were found for the PFC lateralization effect. Conclusions: This evidence holds potential for rehabilitation professionals suggesting that the combination of deliberate attention to the breath and a cognitive synchronization task (such as a vocal exercise executed simultaneously) could boost PFC responsiveness.

Common Relationship Between Causality Orientation and the Prefrontal Region in Psychiatric Disorders as Revealed by Diffusional Kurtosis Imaging.

Background Motivation dysregulation is common in several psychiatric disorders. However, little is known about the relationships between motivation and the regional brain areas involved. We evaluated the relationships between brain microstructural features and causality orientation in patients with schizophrenia, major depressive disorder (MDD), and bipolar disorder (BD) using diffusional kurtosis imaging (DKI) techniques. Methods Forty patients with MDD, 36 with BD, and 30 with schizophrenia underwent DKI and assessment using the General Causality Orientation Scale (GCOS). We analyzed the DKI index and the GCOS subscales. Results The psychiatric patients showed significant positive correlations between the GCOS-autonomy orientation score and the mean kurtosis (MK) values in the prefrontal regions, orbitofrontal regions, and posterior cingulate cortex. When the analyses were performed separately by disease and gender, a positive correlation was found between the GCOS-autonomy orientation score and the MK values in the left prefrontal regions transdiagnostically, especially among female patients with MDD, BD, and schizophrenia. Conclusions A similar association between intrinsic motivation and MK value in the left prefrontal cortex was suggested in patients with schizophrenia, MDD, and BD. The commonality of this association among these disorders might lead to the discovery of a new biomarker for psychiatric clinical research.

Association between intra-individual variability and prefrontal cortex activity measured by functional Near Infrared Spectroscopy (fNIRS) in children with ADHD

ABSTRACT This study uses fNIRS to determine whether there is a difference in the relationship between intra-individual variability and frontal lobe activity between ADHD patients and typically developing children. A total of 28 subjects (14 in ADHD patient group and 14 in control group) participated in this study. The subjects were tested for K-SADS and intelligence, and then the frontal lobe activity of the subjects was measured by continuous performance test, using functional near-infrared spectroscopy (NIRSIT). Processing speed index was significantly lower in the ADHD patient group than in the control group (p = .04). The CPT test results showed a positive correlation in the activity of the right dorsolateral prefrontal region in the patient group, but not at a statistically significant level. In the control group, activity showed a significant level of negative correlation with commission and hit reaction time standard deviation (p = .023; p = .063 respectively). In contrary to ADHD patient group, activation of the right dorsolateral prefrontal area was significantly correlated with reduction of intra-individual variability. This result showing that the relationship between activation of the right dorsolateral prefrontal area of the ADHD patient group and intra-individual variability shows a different pattern from typically developing children.

Non-invasive electrical brain stimulation modulates human conscious perception of mental representation

Mental representation is a key concept in cognitive science; nevertheless, its neural foundations remain elusive. We employed non-invasive electrical brain stimulation and functional magnetic resonance imaging to address this. During this process, participants perceived flickering red and green visual stimuli, discerning them either as distinct, non-fused colours or as a mentally generated, fused colour (orange). The application of transcranial alternating current stimulation to the medial prefrontal region (a key node of the default-mode network) suppressed haemodynamic activation in higher-order subthalamic and central executive networks associated with the perception of fused colours. This implies that higher-order thalamocortical and default-mode networks are crucial in humans’ conscious perception of mental representation.

Possible Prophylactic Effects of Sulforaphane on LPS-Induced Recognition Memory Impairment Mediated by Regulating Oxidative Stress and Neuroinflammatory Proteins in the Prefrontal Cortex Region of the Brain.

Alzheimer's disease (AD) presents a significant global health concern, characterized by neurodegeneration and cognitive decline. Neuroinflammation is a crucial factor in AD development and progression, yet effective pharmacotherapy remains elusive. Sulforaphane (SFN), derived from cruciferous vegetables and mainly from broccoli, has shown a promising effect via in vitro and in vivo studies as a potential treatment for AD. This study aims to investigate the possible prophylactic mechanisms of SFN against prefrontal cortex (PFC)-related recognition memory impairment induced by lipopolysaccharide (LPS) administration. Thirty-six Swiss (SWR/J) mice weighing 18-25 g were divided into three groups (n = 12 per group): a control group (vehicle), an LPS group (0.75 mg/kg of LPS), and an LPS + SFN group (25 mg/kg of SFN). The total duration of the study was 3 weeks, during which mice underwent treatments for the initial 2 weeks, with daily monitoring of body weight and temperature. Behavioral assessments via novel object recognition (NOR) and temporal order recognition (TOR) tasks were conducted in the final week of the study. Inflammatory markers (IL-6 and TNF), antioxidant enzymes (SOD, GSH, and CAT), and pro-oxidant (MDA) level, in addition to acetylcholine esterase (AChE) activity and active (caspase-3) and phosphorylated (AMPK) levels, were evaluated. Further, PFC neuronal degeneration, Aβ content, and microglial activation were also examined using H&E, Congo red staining, and Iba1 immunohistochemistry, respectively. SFN pretreatment significantly improved recognition memory performance during the NOR and TOR tests. Moreover, SFN was protected from neuroinflammation and oxidative stress as well as neurodegeneration, Aβ accumulation, and microglial hyperactivity. The obtained results suggested that SFN has a potential protective property to mitigate the behavioral and biochemical impairments induced by chronic LPS administration and suggested to be via an AMPK/caspase-3-dependent manner.

Neuroanatomical substrates of depression in dementia with Lewy bodies and Alzheimer's disease.

Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are often associated with depressive symptoms from the prodromal stage. The aim of the present study was to investigate the neuroanatomical correlates of depression in prodromal to mild DLB patients compared with AD patients. Eighty-three DLB patients, 37 AD patients, and 18 healthy volunteers were enrolled in this study. Depression was evaluated with the Mini International Neuropsychiatric Interview (MINI), French version 5.0.0. T1-weighted three-dimensional anatomical images were acquired for all participants. Regression and comparison analyses were conducted using a whole-brain voxel-based morphometry (VBM) approach on the grey matter volume (GMV). DLB patients presented a significantly higher mean MINI score than AD patients (p = 0.004), 30.1% of DLB patients had clinical depression, and 56.6% had a history of depression, while 0% of AD patients had clinical depression and 29.7% had a history of depression. VBM regression analyses revealed negative correlations between the MINI score and the GMV of right prefrontal regions in DLB patients (p < 0.001, uncorrected). Comparison analyses between DLB patients taking and those not taking an antidepressant mainly highlighted a decreased GMV in the bilateral middle/inferior temporal gyrus (p < 0.001, uncorrected) in treated DLB patients. In line with the literature, our behavioral analyses revealed higher depression scores in DLB patients than in AD patients. We also showed that depressive symptoms in DLB are associated with decreased GMV in right prefrontal regions. Treated DLB patients with long-standing depression would be more likely to experience GMV loss in the bilateral middle/inferior temporal cortex. These findings should be taken into account when managing DLB patients.

Spatio-temporal electroencephalographic power distribution in experimental pigs receiving propofol.

When assessing the spatio-temporal distribution of electroencephalographic (EEG) activity, characteristic patterns have been identified for several anesthetic drugs in humans. A shift in EEG power from the occipital to the prefrontal regions has been widely observed during anesthesia induction. This has been called "anteriorization" and has been correlated with loss of consciousness in humans. The spatio-temporal distribution of EEG spectral power in pigs and its modulation by anesthetics have not been described previously. The aim of the present study was to analyze EEG power across an anterior-posterior axis in pigs receiving increasing doses of propofol to 1) characterize the region of highest EEG power during wakefulness, 2) depict its spatio-temporal modification during propofol infusion, and 3) determine the region demonstrating the most significant modulations across different doses administered. Six pigs with a body weight of 33.3 ± 3.6 kg and aged 11.3 ± 0.5 weeks were included in a prospective experimental study. Electroencephalographic activity was collected at the occipital, parietal and prefrontal regions at increasing doses of propofol (starting at 10 mg kg-1 h-1 and increasing it by 10 mg kg-1 h-1 every 15 minutes). The EEG power was assessed using a generalized linear mixed model in which propofol doses and regions were treated as fixed effects, whereas pig was used as a random effect. Pairwise comparisons of marginal linear predictions were used to assess the change in power when the specific propofol dose (or region) was considered. During both wakefulness and propofol infusion, the highest EEG power was located in the prefrontal region (p<0.001). The EEG power, both total and for each frequency band, mostly followed the same pattern, increasing from awake until propofol 20 mg kg-1 h-1 and then decreasing at propofol 30 mg kg-1 h-1. The region showing the strongest differences in EEG power across propofol doses was the prefrontal. In juvenile pigs receiving increasing doses of propofol, the prefrontal region showed the highest EEG power both during wakefulness and propofol administration and was the area in which the largest frequency-band specific variations were observed across different anesthetic doses. The assessment of the spectral EEG activity at this region could be favorable to distinguish DoA levels in pigs.

Neuroimaging and epigenetic analysis reveal novel epigenetic loci in major depressive disorder.

Epigenetic modifications, such as DNA methylation, contribute to the pathophysiology of major depressive disorder (MDD). This study aimed to identify novel MDD-associated epigenetic loci using DNA methylation profiles and explore the correlations between epigenetic loci and cortical thickness changes in patients with MDD. A total of 350 patients with MDD and 161 healthy controls (HCs) were included in the epigenome-wide association studies (EWAS). We analyzed methylation, copy number alteration (CNA), and gene network profiles in the MDD group. A total of 234 patients with MDD and 135 HCs were included in neuroimaging methylation analysis. Pearson's partial correlation analysis was used to estimate the correlation between cortical thickness of brain regions and DNA methylation levels of the loci. In total, 2018 differentially methylated probes (DMPs) and 351 differentially methylated regions (DMRs) were identified. DMP-related genes were enriched in two networks involved in the central nervous system. In neuroimaging analysis, patients with MDD showed cortical thinning in the prefrontal regions and cortical thickening in several occipital regions. Cortical thickness of the left ventrolateral prefrontal cortex (VLPFC, i.e. pars triangularis) was negatively correlated with eight DMPs associated with six genes (EML6, ZFP64, CLSTN3, KCNMA1, TAOK2, and NT5E). Through combining DNA methylation and neuroimaging analyses, negative correlations were identified between the cortical thickness of the left VLPFC and DNA methylation levels of eight DMPs. Our findings could improve our understanding of the pathophysiology of MDD.

Targeting the left DLPFC and right VLPFC in unmarried romantic relationship breakup (love trauma syndrome) with intensified electrical stimulation: A randomized, single-blind, parallel-group, sham-controlled study

BackgroundEnding a romantic relationship is one of the most painful losses an adult experience. Neuroimaging studies suggest that there is a neuropsychological link between breakup experiences and bereaved individuals, and that specific prefrontal regions are involved. The aim of this study was to determine whether enhancement of left DLPFC and right VLPFC activity with a novel intensified anodal transcranial direct current stimulation protocol reduces core symptoms of love trauma syndrome (LTS) and improves treatment-related variables. MethodsIn this randomized, sham-controlled, single-blind parallel trial, we assessed the efficacy of an intensified anodal stimulation protocol (20 min, twice-daily sessions with 20 min intervals, 5 consecutive days) with two montages (left DLPFC vs right VLPFC) to reduce love trauma symptoms. 36 participants with love trauma syndrome were randomized in three tDCS condition (left DLPFC, right VLPFC, sham stimulation). LTS symptoms, treatment-related outcome variables (depressive state, anxiety, emotion regulation, positive and negative affect), and cognitive functions were assessed before, right after, and one month after intervention. ResultsBoth DLPFC and VLPFC protocols significantly reduced LTS symptoms, and improved depressive state and anxiety after the intervention, as compared to the sham group. The improving effect of the DLPFC protocol on love trauma syndrome was significantly larger than that of the VLPFC protocol. For emotion regulation and positive and negative affect, improved regulation of emotions and positive affect and reduced negative affect were revealed after intervention in the two real stimulation conditions compared to the sham. For cognitive functions, no significant difference was observed between the groups, but again a positive effect of intervention within groups in the real stimulation conditions (DLPFC and VLPFC) was found for most components of the cognitive tasks. ConclusionsEnhancement of left DLPFC and right VLPFC activity with intensified stimulation improves LTS symptoms and treatment-related variables. For LTS symptoms, DLPFC stimulation was more efficient than VLPFC stimulation., For the other variables, no significant difference was observed between these two stimulation groups. These promising results require replication in larger trials.

Intoxication due to Δ9-tetrahydrocannabinol is characterized by disrupted prefrontal cortex activity

Neural states of impairment from intoxicating substances, including cannabis, are poorly understood. Cannabinoid 1 receptors, the main target of Δ9-tetrahydrocannabinol (THC), the primary intoxicating cannabinoid in cannabis, are densely localized within prefrontal cortex; therefore, prefrontal brain regions are key locations to examine brain changes that characterize acute intoxication. We conducted a double-blind, randomized, cross-over study in adults, aged 18–55 years, who use cannabis regularly, to determine the effects of acute intoxication on prefrontal cortex resting-state measures, assessed with portable functional near-infrared spectroscopy. Participants received oral THC (10–80 mg, individually dosed to overcome tolerance and achieve acute intoxication) and identical placebo, randomized for order; 185 adults were randomized and 128 completed both study days and had usable data. THC was associated with expected increases in subjective intoxication ratings (ES = 35.30, p < 0.001) and heart rate (ES = 11.15, p = 0.001). THC was associated with decreased correlations and anticorrelations in static resting-state functional connectivity within the prefrontal cortex relative to placebo, with weakest correlations and anticorrelations among those who reported greater severity of intoxication (RSFC between medial PFC-ventromedial PFC and DEQ scores, r = 0.32, p < 0.001; RSFC between bilateral mPFC and DEQ scores, r = –0.28, p = 0.001). Relative to placebo, THC was associated with increased variability (or reduced stability) in dynamic resting-state functional connectivity of the prefrontal cortex at p = 0.001, consistent across a range of window sizes. Finally, using frequency power spectrum analyses, we observed that relative to placebo, THC was associated with widespread reduced spectral power within the prefrontal cortex across the 0.073–0.1 Hz frequency range at p < 0.039. These neural features suggest a disruptive influence of THC on the neural dynamics of the prefrontal cortex and may underlie cognitive impairing effects of THC that are detectable with portable imaging. This study is registered in Clinicaltrials.gov (NCT03655717).

Recognizing ideas generated in a creative task: the roles of the hippocampus and medial prefrontal cortex in facilitating self-generated learning.

Creative idea generation plays an important role in promoting successful memory formation. Yet, its underlying neural correlates remain unclear. We investigated the self-generated learning of creative ideas motivated by the schema-linked interactions between medial prefrontal and medial temporal regions framework. This was achieved by having participants generate ideas in the alternative uses task, self-evaluating their ideas based on novelty and source (i.e. new or old), and then later being tested on the recognition performance of the generated ideas. At the behavioral level, our results indicated superior performances in discriminating novel ideas, highlighting the novelty effect on memory. At the neural level, the regions-of-interest analyses revealed that successful recognition of novel ideas was associated with greater activations in the hippocampus (HPC) and medial prefrontal cortex (mPFC) during ideation. However, only activation in the right HPC was positively related to the successful recognition of novel ideas. Importantly, the weaker the connection between the right HPC and left mPFC, the higher the recognition accuracy of novel ideas. Moreover, activations in the right HPC and left mPFC were both effective predictors of successful recognition of novel ideas. These findings uniquely highlight the role of novelty in promoting self-generated learning of creative ideas.

Effective modulation from the ventral medial to the dorsal medial portion of the prefrontal cortex in memory confidence-based behavioral control

Metacognition includes the ability to refer to one’s own cognitive states, such as confidence, and adaptively control behavior based on this information. This ability is thought to allow us to predictably control our behavior without external feedback, for example, even before we take action. Many studies have suggested that metacognition requires a brain-wide network of multiple brain regions. However, the modulation of effective connectivity within this network during metacognitive tasks remains unclear. This study focused on medial prefrontal regions, which have recently been suggested to be particularly involved in metacognition. We examined whether modulation of effective connectivity specific to metacognitive behavioral control is observed using model-based network analysis and dynamic causal modeling (DCM). The results showed that negative modulation from the ventral medial prefrontal cortex to the dorsal medial prefrontal cortex was observed in situations that required metacognitive behavioral control but not in situations that did not require such metacognitive control. Furthermore, this modulation was particularly pronounced in the group of participants who could better use metacognition for behavioral control. These results imply hierarchical properties of metacognition-related brain networks.