Elucidating the underlying components of metacognitive systematic bias in the human dorsolateral prefrontal cortex and inferior parietal cortex.

Metacognitive systematic bias impairs human learning efficiency, which is characterized by the inconsistency between predicted and actual memory performance. However, the underlying mechanism of metacognitive systematic bias remains unclear in existing studies. In this study, we utilized judgments of learning task in human participants to compare the neural mechanism difference in metacognitive systematic bias. Participants encoded words in fMRI sessions that would be tested later. Immediately after encoding each item, participants predicted how likely they would remember it. Multivariate analyses on fMRI data demonstrated that working memory and uncertainty decisions are represented in patterns of neural activity in metacognitive systematic bias. The available information participants used led to overestimated bias and underestimated bias. Effective connectivity analyses further indicate that information about the metacognitive systematic bias is represented in the dorsolateral prefrontal cortex and inferior parietal cortex. Different neural patterns were found underlying overestimated bias and underestimated bias. Specifically, connectivity regions with the dorsolateral prefrontal cortex, anterior cingulate cortex, and supramarginal gyrus form overestimated bias, while less regional connectivity forms underestimated bias. These findings provide a mechanistic account for the construction of metacognitive systematic bias.

Cortico-limbic interactions and carotid atherosclerotic burden during chronic stress exposure.

BACKGROUND AND AIMS: Chronic stress associates with cardiovascular disease, but mechanisms remain incompletely defined. Advanced imaging was used to identify stress-related neural imaging phenotypes associated with atherosclerosis. METHODS: Twenty-seven individuals with post-traumatic stress disorder (PTSD), 45 trauma-exposed controls without PTSD, and 22 healthy controls underwent 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). Atherosclerotic inflammation and burden were assessed using 18F-FDG PET (as maximal target-to-background ratio, TBR max) and MRI, respectively. Inflammation was assessed using high-sensitivity C-reactive protein (hsCRP) and leucopoietic imaging (18F-FDG PET uptake in spleen and bone marrow). Stress-associated neural network activity (SNA) was assessed on 18F-FDG PET as amygdala relative to ventromedial prefrontal cortex (vmPFC) activity. MRI diffusion tensor imaging assessed the axonal integrity (AI) of the uncinate fasciculus (major white matter tract connecting vmPFC and amygdala). RESULTS: Median age was 37 years old and 54% of participants were female. There were no significant differences in atherosclerotic inflammation between participants with PTSD and controls; adjusted mean difference in TBR max (95% confidence interval) of the aorta 0.020 (-0.098, 0.138), and of the carotids 0.014 (-0.091, 0.119). Participants with PTSD had higher hsCRP, spleen activity, and aorta atherosclerotic burden (normalized wall index). Participants with PTSD also had higher SNA and lower AI. Across the cohort, carotid atherosclerotic burden (standard deviation of wall thickness) associated positively with SNA and negatively with AI independent of Framingham risk score. CONCLUSIONS: In this study of limited size, participants with PTSD did not have higher atherosclerotic inflammation than controls. Notably, impaired cortico-limbic interactions (higher amygdala relative to vmPFC activity or disruption of their intercommunication) associated with carotid atherosclerotic burden. Larger studies are needed to refine these findings.

Information-based TMS to mid-lateral prefrontal cortex disrupts action goals during emotional processing.

The ability to respond to emotional events in a context-sensitive and goal-oriented manner is essential for adaptive functioning. In models of behavioral and emotion regulation, the lateral prefrontal cortex (LPFC) is postulated to maintain goal-relevant representations that promote cognitive control, an idea rarely tested with causal inference. Here, we altered mid-LPFC function in healthy individuals using a putatively inhibitory brain stimulation protocol (continuous theta burst; cTBS), followed by fMRI scanning. Participants performed the Affective Go/No-Go task, which requires goal-oriented action during affective processing. We targeted mid-LPFC (vs. a Control site) based on the individualized location of action-goal representations observed during the task. cTBS to mid-LPFC reduced action-goal representations in mid-LPFC and impaired goal-oriented action, particularly during processing of negative emotional cues. During negative-cue processing, cTBS to mid-LPFC reduced functional coupling between mid-LPFC and nodes of the default mode network, including frontopolar cortex-a region thought to modulate LPFC control signals according to internal states. Collectively, these results indicate that mid-LPFC goal-relevant representations play a causal role in governing context-sensitive cognitive control during emotional processing.

The vmPFC-IPL functional connectivity as the neural basis of future self-continuity impacted procrastination: the mediating role of anticipated positive outcomes.

Procrastination is universally acknowledged as a problematic behavior with wide-ranging consequences impacting various facets of individuals' lives, including academic achievement, social accomplishments, and mental health. Although previous research has indicated that future self-continuity is robustly negatively correlated with procrastination, it remains unknown about the neural mechanisms underlying the impact of future self-continuity on procrastination. To address this issue, we employed a free construction approach to collect individuals' episodic future thinking (EFT) thoughts regarding specific procrastination tasks. Next, we conducted voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) analysis to explore the neural substrates underlying future self-continuity. Behavior results revealed that future self-continuity was significantly negatively correlated with procrastination, and positively correlated with anticipated positive outcome. The VBM analysis showed a positive association between future self-continuity and gray matter volumes in the right ventromedial prefrontal cortex (vmPFC). Furthermore, the RSFC results indicated that the functional connectivity between the right vmPFC and the left inferior parietal lobule (IPL) was positively correlated with future self-continuity. More importantly, the mediation analysis demonstrated that anticipated positive outcome can completely mediate the relationship between the vmPFC-IPL functional connectivity and procrastination. These findings suggested that vmPFC-IPL functional connectivity might prompt anticipated positive outcome about the task and thereby reduce procrastination, which provides a new perspective to understand the relationship between future self-continuity and procrastination.

Brain activity during Stroop task performance at age 74 after exposure to the Dutch famine during early gestation.

OBJECTIVE: Poorer performance on the Stroop task has been reported after prenatal famine exposure at age 58, potentially indicating cognitive decline. We investigated whether brain activation during Stroop task performance at age 74 differed between individuals exposed to famine prenatally, individuals born before and individuals conceived after the famine. METHOD: In the Dutch famine birth cohort, we performed a Stroop task fMRI study of individuals exposed (n = 22) or unexposed (born before (n = 18) or conceived after (n = 25)) to famine in early gestation. We studied group differences in task-related mean activation of the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC) and posterior parietal cortex (PPC). Additionally, we explored potential disconnectivity of the DLPFC using psychophysiological interaction analysis. RESULTS: We observed similar activation patterns in the DLPFC, ACC and PPC in individuals born before and individuals exposed to famine, while individuals conceived after famine had generally higher activation patterns. However, activation patterns were not significantly different between groups. Task-related decreases in connectivity were observed between left DLPFC-left PPC and right DLPFC-right PPC, but were not significantly different between groups. CONCLUSIONS: Although not statistically significant, the observed patterns of activation may reflect a combined effect of general brain aging and prenatal famine exposure.

Prefrontal tDCS modulates risk-taking in male violent offenders.

Detrimental decision-making is a major problem among violent offenders. Non-invasive brain stimulation offers a promising method to directly influence decision-making and has already been shown to modulate risk-taking in non-violent controls. We hypothesize that anodal transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex beneficially modulates the neural and behavioral correlates of risk-taking in a sample of violent offenders. We expect offenders to show more risky decision-making than non-violent controls and that prefrontal tDCS will induce stronger changes in the offender group. In the current study, 22 male violent offenders and 24 male non-violent controls took part in a randomized double-blind sham-controlled cross-over study applying tDCS over the right dorsolateral prefrontal cortex. Subsequently, participants performed the Balloon Analogue Risk Task (BART) during functional magnetic resonance imaging (fMRI). Violent offenders showed significantly less optimal decision-making compared to non-violent controls. Active tDCS increased prefrontal activity and improved decision-making only in violent offenders but not in the control group. Also, in offenders only, prefrontal tDCS influenced functional connectivity between the stimulated area and other brain regions such as the thalamus. These results suggest baseline dependent effects of tDCS and pave the way for treatment options of disadvantageous decision-making behavior in this population.

Altered neural anticipation of reward and loss but not receipt in adolescents with obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is characterized by persistent, unwanted thoughts and repetitive actions. Such repetitive thoughts and/or behaviors may be reinforced either by reducing anxiety or by avoiding a potential threat or harm, and thus may be rewarding to the individual. The possible involvement of the reward system in the symptomatology of OCD is supported by studies showing altered reward processing in reward-related regions, such as the ventral striatum (VS) and the orbitofrontal cortex (OFC), in adults with OCD. However, it is not clear whether this also applies to adolescents with OCD. METHODS: Using functional magnetic resonance imaging, two sessions were conducted focusing on the anticipation and receipt of monetary reward (1) or loss (2), each contrasted to a verbal (control) condition. In each session, adolescents with OCD (n1=31/n2=26) were compared with typically developing (TD) controls (n1=33/ n2=31), all aged 10-19 years, during the anticipation and feedback phase of an adapted Monetary Incentive Delay task. RESULTS: Data revealed a hyperactivation of the VS, but not the OFC, when anticipating both monetary reward and loss in the OCD compared to the TD group. CONCLUSIONS: These findings suggest that aberrant neural reward and loss processing in OCD is associated with greater motivation to gain or maintain a reward but not with the actual receipt. The greater degree of reward 'wanting' may contribute to adolescents with OCD repeating certain actions more and more frequently, which then become habits (i.e., OCD symptomatology).

Charitable crowdfunding donation-intention estimation depending on emotional project images using fNIRS-based functional connectivity.

Charitable fundraising increasingly relies on online crowdfunding platforms. Project images of charitable crowdfunding use emotional appeals to promote helping behavior. Negative emotions are commonly used to motivate helping behavior because the image of a happy child may not motivate donors to donate as willingly. However, some research has found that happy images can be more beneficial. These contradictory results suggest that the emotional valence of project imagery and how fundraisers frame project images effectively remain debatable. Thus, we compared and analyzed brain activation differences in the prefrontal cortex governing human emotions depending on donation decisions using functional near-infrared spectroscopy, a neuroimaging device. We advance existing theory on charitable behavior by demonstrating that little correlation exists in donation intentions and brain activity between negative and positive project images, which is consistent with survey results on donation intentions by victim image. We also discovered quantitative brain hemodynamic signal variations between donors and nondonors, which can predict and detect donor mental brain functioning using functional connectivity, that is, the statistical dependence between the time series of electrophysiological activity and oxygenated hemodynamic levels in the prefrontal cortex. These findings are critical in developing future marketing strategies for online charitable crowdfunding platforms, especially project images.

Forming cognitive maps for abstract spaces: the roles of the human hippocampus and orbitofrontal cortex.

How does the human brain construct cognitive maps for decision-making and inference? Here, we conduct an fMRI study on a navigation task in multidimensional abstract spaces. Using a deep neural network model, we assess learning levels and categorized paths into exploration and exploitation stages. Univariate analyses show higher activation in the bilateral hippocampus and lateral prefrontal cortex during exploration, positively associated with learning level and response accuracy. Conversely, the bilateral orbitofrontal cortex (OFC) and retrosplenial cortex show higher activation during exploitation, negatively associated with learning level and response accuracy. Representational similarity analysis show that the hippocampus, entorhinal cortex, and OFC more accurately represent destinations in exploitation than exploration stages. These findings highlight the collaboration between the medial temporal lobe and prefrontal cortex in learning abstract space structures. The hippocampus may be involved in spatial memory formation and representation, while the OFC integrates sensory information for decision-making in multidimensional abstract spaces.

Uncovering Hemispheric Asymmetry and Directed Oscillatory Brain-Heart Interplay in Anxiety Processing: An fMRI Study.

Brain-heart interactions (BHI) are critical for generating and processing emotions, including anxiety. Understanding specific neural correlates would be instrumental for greater comprehension and potential therapeutic interventions of anxiety disorders. While prior work has implicated the pontine structure as a central processor in cardiac regulation in anxiety, the distributed nature of anxiety processing across the cortex remains elusive. To address this, we performed a whole-brain-heart analysis using the full frequency directed transfer function to study resting-state spectral differences in BHI between high and low anxiety groups undergoing fMRI scans. Our findings revealed a hemispheric asymmetry in low-frequency interplay (0.05 Hz - 0.15 Hz) characterized by ascending BHI to the left insula and descending BHI from the right insula. Furthermore, we provide evidence supporting the "pacemaker hypothesis", highlighting the pons' function in regulating cardiac activity. Higher frequency interplay (0.2 Hz - 0.4Hz) demonstrate a preference for ascending interactions, particularly towards ventral prefrontal cortical activity in high anxiety groups, suggesting the heart's role in triggering a cognitive response to regulate anxiety. These findings highlight the impact of anxiety on BHI, contributing to a better understanding of its effect on the resting-state fMRI signal, with further implications for potential therapeutic interventions in treating anxiety disorders.

The neural mechanism of communication between graduate students and advisers in different adviser-advisee relationships.

Communication is crucial in constructing the relationship between students and advisers, ultimately bridging interpersonal interactions. Only a few studies however explore the communication between postgraduate students and advisers. To fill the gaps in the empirical researches, this study uses functional near-infrared spectroscopy (FNIRS) techniques to explore the neurophysiology differences in brain activation of postgraduates with different adviser-advise relationships during simulated communication with their advisers. Results showed significant differences in the activation of the prefrontal cortex between high-quality and the low-quality students during simulating and when communicating with advisers, specifically in the Broca's areas, the frontal pole, and the orbitofrontal and dorsolateral prefrontal cortices. This further elucidated the complex cognitive process of communication between graduate students and advisers.

Cerebral cortex activation and functional connectivity during low-load resistance training with blood flow restriction: An fNIRS study.

Despite accumulating evidence that blood flow restriction (BFR) training promotes muscle hypertrophy and strength gain, the underlying neurophysiological mechanisms have rarely been explored. The primary goal of this study is to investigate characteristics of cerebral cortex activity during BFR training under different pressure intensities. 24 males participated in 30% 1RM squat exercise, changes in oxygenated hemoglobin concentration (HbO) in the primary motor cortex (M1), pre-motor cortex (PMC), supplementary motor area (SMA), and dorsolateral prefrontal cortex (DLPFC), were measured by fNIRS. The results showed that HbO increased from 0 mmHg (non-BFR) to 250 mmHg but dropped sharply under 350 mmHg pressure intensity. In addition, HbO and functional connectivity were higher in M1 and PMC-SMA than in DLPFC. Moreover, the significant interaction effect between pressure intensity and ROI for HbO revealed that the regulation of cerebral cortex during BFR training was more pronounced in M1 and PMC-SMA than in DLPFC. In conclusion, low-load resistance training with BFR triggers acute responses in the cerebral cortex, and moderate pressure intensity achieves optimal neural benefits in enhancing cortical activation. M1 and PMC-SMA play crucial roles during BFR training through activation and functional connectivity regulation.

Belief inference for hierarchical hidden states in spatial navigation.

Uncertainty abounds in the real world, and in environments with multiple layers of unobservable hidden states, decision-making requires resolving uncertainties based on mutual inference. Focusing on a spatial navigation problem, we develop a Tiger maze task that involved simultaneously inferring the local hidden state and the global hidden state from probabilistically uncertain observation. We adopt a Bayesian computational approach by proposing a hierarchical inference model. Applying this to human task behaviour, alongside functional magnetic resonance brain imaging, allows us to separate the neural correlates associated with reinforcement and reassessment of belief in hidden states. The imaging results also suggest that different layers of uncertainty differentially involve the basal ganglia and dorsomedial prefrontal cortex, and that the regions responsible are organised along the rostral axis of these areas according to the type of inference and the level of abstraction of the hidden state, i.e. higher-order state inference involves more anterior parts.

Mapping the differential impact of spontaneous and conversational laughter on brain and mind: an fMRI study in autism.

Spontaneous and conversational laughter are important socio-emotional communicative signals. Neuroimaging findings suggest that non-autistic people engage in mentalizing to understand the meaning behind conversational laughter. Autistic people may thus face specific challenges in processing conversational laughter, due to their mentalizing difficulties. Using fMRI, we explored neural differences during implicit processing of these two types of laughter. Autistic and non-autistic adults passively listened to funny words, followed by spontaneous laughter, conversational laughter, or noise-vocoded vocalizations. Behaviourally, words plus spontaneous laughter were rated as funnier than words plus conversational laughter, and the groups did not differ. However, neuroimaging results showed that non-autistic adults exhibited greater medial prefrontal cortex activation while listening to words plus conversational laughter, than words plus genuine laughter, while autistic adults showed no difference in medial prefrontal cortex activity between these two laughter types. Our findings suggest a crucial role for the medial prefrontal cortex in understanding socio-emotionally ambiguous laughter via mentalizing. Our study also highlights the possibility that autistic people may face challenges in understanding the essence of the laughter we frequently encounter in everyday life, especially in processing conversational laughter that carries complex meaning and social ambiguity, potentially leading to social vulnerability. Therefore, we advocate for clearer communication with autistic people.

The neural basis of resting-state fMRI functional connectivity in fronto-limbic circuits revealed by chemogenetic manipulation.

Measures of fMRI resting-state functional connectivity (rs-FC) are an essential tool for basic and clinical investigations of fronto-limbic circuits. Understanding the relationship between rs-FC and the underlying patterns of neural activity in these circuits is therefore vital. Here we introduced inhibitory designer receptors exclusively activated by designer drugs (DREADDs) into the amygdala of two male macaques. We evaluated the causal effect of activating the DREADD receptors on rs-FC and neural activity within circuits connecting amygdala and frontal cortex. Activating the inhibitory DREADD increased rs-FC between amygdala and ventrolateral prefrontal cortex. Neurophysiological recordings revealed that the DREADD-induced increase in fMRI rs-FC was associated with increased local field potential coherency in the alpha band (6.5-14.5 Hz) between amygdala and ventrolateral prefrontal cortex. Thus, our multi-modal approach reveals the specific signature of neuronal activity that underlies rs-FC in fronto-limbic circuits.

Bilateral Prefrontal Cortex Blood Flow Dynamics during Silent and Oral Reading Using Near-Infrared Spectroscopy.

This study aimed to investigate blood flow dynamics in the bilateral prefrontal cortex during silent and oral reading using near-infrared spectroscopy (NIRS). The subjects were 40 right-handed university students (20.5±1.8 years old, 20 men and 20 women). After completing the NIRS measurements, the subjects were asked to rate their level of proficiency in silent and oral reading, using a 5-point Likert scale. During oral reading, the left lateral prefrontal cortex (Broca's area) was significantly more active than the right side. During silent reading, prefrontal cortex activity was lower than that during oral reading, and there was no significant difference between both sides of the brain. A significant negative correlation was found between the change in oxy-hemoglobin (oxy-Hb) concentration in the left and right lateral prefrontal cortex during silent reading and silent reading speed. In addition, students with lower self-reported reading proficiency had significantly greater changes in oxy-Hb concentrations in the left and right lateral prefrontal cortex during silent/oral reading than did students with higher self-reported reading proficiency. Reading task assessment using NIRS may be useful for identifying language lateralization and Broca's area. The results demonstrate that NIRS is useful for assessing effortful reading and may be used to diagnose developmental dyslexia in children. J. Med. Invest. 71 : 92-101, February, 2024.

Attentional control influence habituation through modulation of connectivity patterns within the prefrontal cortex: Insights from stereo-EEG.

Attentional control, guided by top-down processes, enables selective focus on pertinent information, while habituation, influenced by bottom-up factors and prior experiences, shapes cognitive responses by emphasizing stimulus relevance. These two fundamental processes collaborate to regulate cognitive behavior, with the prefrontal cortex and its subregions playing a pivotal role. Nevertheless, the intricate neural mechanisms underlying the interaction between attentional control and habituation are still a subject of ongoing exploration. To our knowledge, there is a dearth of comprehensive studies on the functional connectivity between subsystems within the prefrontal cortex during attentional control processes in both primates and humans. Utilizing stereo-electroencephalogram (SEEG) recordings during the Stroop task, we observed top-down dominance effects and corresponding connectivity patterns among the orbitofrontal cortex (OFC), the middle frontal gyrus (MFG), and the inferior frontal gyrus (IFG) during heightened attentional control. These findings highlighting the involvement of OFC in habituation through top-down attention. Our study unveils unique connectivity profiles, shedding light on the neural interplay between top-down and bottom-up attentional control processes, shaping goal-directed attention.

Exaggerated sensitivity to threat and reduced medial prefrontal engagement during threat generalization in reactive aggressive adolescents.

Aggressive adolescents tend to exhibit abnormal fear acquisition and extinction, and reactive aggressive adolescents are often more anxious. However, the relationship between fear generalization and reactive aggression (RA) remains unknown. According to Reactive-Proactive Aggression Questionnaire (RPQ) scores, 61 adolescents were divided into two groups, namely, a high RA group (N = 30) and a low aggression (LA) group (N = 31). All participants underwent three consecutive phases of the Pavlovian conditioning paradigm (i.e., habituation, acquisition, and generalization), and neural activation of the medial prefrontal cortex (mPFC) was assessed by functional near-infrared spectroscopy (fNIRS). The stimuli were ten circles with varying sizes, including two conditioned stimuli (CSs) and eight generalization stimuli (GSs). A scream at 85 dB served as the auditory unconditioned stimulus (US). The US expectancy ratings of both CSs and GSs were higher in the RA group than in the LA group. The fNIRS results showed that CSs and GSs evoked lower mPFC activation in the RA group compared to the LA group during fear generalization. These findings suggest that abnormalities in fear acquisition and generalization are prototypical dysregulations in adolescents with RA. They provide neurocognitive evidence for dysregulated fear learning in the mechanisms underlying adolescents with RA, highlighting the need to develop emotional regulation interventions for these individuals.

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.

Dynamical and individualised approach of transcranial ultrasound neuromodulation effects in non-human primates.

Low-frequency transcranial ultrasound stimulation (TUS) allows to alter brain functioning with a high spatial resolution and to reach deep targets. However, the time-course of TUS effects remains largely unknown. We applied TUS on three brain targets for three different monkeys: the anterior medial prefrontal cortex, the supplementary motor area and the perigenual anterior cingulate cortex. For each, one resting-state fMRI was acquired between 30 and 150 min after TUS as well as one without stimulation (control). We captured seed-based brain connectivity changes dynamically and on an individual basis. We also assessed between individuals and between targets homogeneity and brain features that predicted TUS changes. We found that TUS prompts heterogenous functional connectivity alterations yet retain certain consistent changes; we identified 6 time-courses of changes including transient and long duration alterations; with a notable degree of accuracy we found that brain alterations could partially be predicted. Altogether, our results highlight that TUS induces heterogeneous functional connectivity alterations. On a more technical point, we also emphasize the need to consider brain changes over-time rather than just observed during a snapshot; to consider inter-individual variability since changes could be highly different from one individual to another.