Search

Several cortical structures are involved in theory of mind (ToM), including the dorsolateral prefrontal cortex (dlPFC), the ventromedial prefrontal cortex (vmPFC), and the right temporo- parietal junction (rTPJ). We investigated the role of these regions in mind reading with respect to the valence of mental states. Sixty-five healthy adult participants were recruited and received transcranial direct current stimulation (tDCS) (1.5 mA, 20 min) with one week interval in three separate studies. The stimulation conditions were anodal tDCS over the dlPFC coupled with cathodal tDCS over the vmPFC, reversed stimulation conditions, and sham in the first study, and anodal tDCS over the vmPFC, or dlPFC, and sham stimulation, with an extracranial return electrode in the second and third study. During stimulation, participants underwent the reading mind from eyes/voice tests (RMET or RMVT) in each stimulation condition. Anodal left dlPFC/cathodal right vmPFC stimulation increased the accuracy of negative mental state attributions, anodal rTPJ decreased the accuracy of negative and neutral mental state attributions, and decreased the reaction time of positive mental state attributions. Our results imply that the neural correlates of ToM are valence-sensitive. [ABSTRACT FROM AUTHOR]

Introduction: Emotion recognition, the ability to interpret the emotional state of individuals by looking at their facial expressions, is essential for healthy social interactions and communication. There is limited research on the effects of tDCS on emotion recognition in the literature. This study aimed to investigate the effects of anodal stimulation of the ventromedial prefrontal cortex (vmPFC), a key region for emotion recognition from facial expressions, on emotion recognition and brain oscillations. Method: A single-blind randomized-controlled study was conducted with 54 healthy participants. Before and after brain stimulation emotion recognition tasks were administered and resting-state EEG were recorded. The changes in task performances and brain oscillations were analyzed using repeated-measures two-way ANOVA analysis. Results: There was no significant difference in the emotion recognition tasks between groups in pre-post measurements. The changes in delta, theta, alpha, beta and gamma frequency bands in the frontal, temporal, and posterio-occipital regions, which were determined as regions of interest in resting state EEG data before and after tDCS, were compared between groups. The results showed that there was a significant difference between groups only in delta frequency before and after tDCS in the frontal and temporal regions. While an increase in delta activity was observed in the experimental group in the frontal and temporal regions, a decrease was observed in the control group., Conclusions: The tDCS may not have improved emotion recognition because it may not have had the desired effect on the vmPFC, which is in the lower part of the prefrontal lobe. The changes in EEG frequencies observed section tDCS may be similar to those seen in some pathological processes, which could explain the lack of improvement in emotion recognition. Future studies to be carried out for better understand this effect are important. [ABSTRACT FROM AUTHOR]

Individuals with attention deficit-hyperactivity disorder (ADHD) struggle with the interaction of attention and emotion. The ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) are assumed to be involved in this interaction. In the present study, we aimed to explore the effect of stimulation applied over the dlPFC and vmPFC on attention bias in individuals with ADHD. Twenty-three children with ADHD performed the emotional Stroop and dot probe tasks during transcranial direct current stimulation (tDCS) in 3 conditions: anodal dlPFC (F3)/cathodal vmPFC (Fp2), anodal vmPFC (Fp2)/cathodal dlPFC (F3), and sham stimulation. Findings suggest reduction of attention bias in both real conditions based on emotional Stroop task and not dot probe task. These results were independent of emotional states. The dlPFC and vmPFC are involved in attention bias in ADHD. tDCS can be used for attention bias modification in children with ADHD. [ABSTRACT FROM AUTHOR]

This editorial published in Frontiers in Behavioral Neuroscience explores the neurobiological and cognitive aspects of appetitive and aversive motivation. The authors emphasize the importance of motivation in survival and well-being, while acknowledging its potential negative effects in certain conditions. They discuss the growing body of research on the neural correlates of motivation and its impact on cognition, including attention, learning, memory, and decision-making. The article presents specific studies on the role of brain regions such as the ventromedial prefrontal cortex and the insular cortex in reward processing and cognitive control. The authors aim to advance our understanding of motivation and its influence on cognition, with the potential for targeted interventions to improve mental health and well-being. [Extracted from the article]

Background and Aims: Mind wandering refers to spontaneously occurring, often disruptive thoughts during an ongoing task or resting state. The ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) are two main cortical areas which are involved in this process. This study aimed to explore the interaction of these areas during mind wandering by enhancing specific oscillatory activity of these areas via transcranial alternating current stimulation (tACS) in the theta frequency range. Material and Methods: Eighteen healthy adults participated in a randomized, single-blinded, crossover study. tACS (1.5 mA, 6 Hz) was applied in five sessions with one week interval via (1) two channels with synchronized stimulation over the left dlPFC and right vmPFC, (2) the same electrode placement with anti-phase stimulation, (3) stimulation over the left dlPFC only, (4) stimulation over right vmPFC only, and (5) sham stimulation. The return electrodes were placed over the contralateral shoulder in all conditions. The sustained attention to response task (SART) with embedded probes about task-unrelated-thoughts and awareness of these thoughts was performed during intervention. Results: Stimulation did not alter SART performance. Right vmPFC stimulation decreased mind wandering and increased awareness of mind wandering. Left dlPFC stimulation and desynchronized stimulation over the dlPFC and vmPFC increased mind wandering compared to the sham stimulation condition. Synchronized stimulation had no effect on mind wandering, but increased awareness of mind wandering. Conclusion: The results suggest that regional entrainment of the vmPFC decreases mind wandering and increases awareness of mind wandering, whereas regional entrainment of the dlPFC increases mind wandering, but decreases awareness. Under desynchronized stimulation of both areas, the propensity of mind wandering was increased, whereas synchronized stimulation increased the awareness of mind wandering. These results suggest a role of the dlPFC in initiation of mind wandering, whereas the vmPFC downregulates mind wandering, and might exert this function by counteracting respective dlPFC effects via theta oscillations. [ABSTRACT FROM AUTHOR]

Background: Preclinical findings suggest that transcranial infrared laser stimulation (TILS) improves fear extinction learning and cognitive function by enhancing prefrontal cortex (PFC) oxygen metabolism. These findings prompted our investigation of treating pathological fear using this non-invasive stimulation approach either alone to the dorsolateral PFC (dlPFC), or to the ventromedial PFC (vmPFC) in combination with exposure therapy. Methods: Volunteers with pathological fear of either enclosed spaces, contamination, public speaking, or anxiety-related bodily sensations were recruited for this randomized, single-blind, sham-controlled trial with four arms: (a) Exposure + TILS_vmPFC (n = 29), (b) Exposure + sham TILS_vmPFC (n = 29), (c) TILS_dlPFC alone (n = 26), or (d) Sham TILS _dlPFC alone (n = 28). Post-treatment assessments occurred immediately following treatment. Follow-up assessments occurred 2 weeks after treatment. Results: A total of 112 participants were randomized [age range: 18–63 years; 96 females (85.71%)]. Significant interactions of Group × Time and Group × Context indicated differential treatment effects on retention (i.e. between time-points, averaged across contexts) and on generalization (i.e. between contexts, averaged across time-points), respectively. Among the monotherapies, TILS_dlPFC outperformed SHAM_dlPFC in the initial context, b = −13.44, 95% CI (−25.73 to −1.15), p = 0.03. Among the combined treatments, differences between EX + TILS_vmPFC and EX + SHAM_vmPFC were non-significant across all contrasts. Conclusions: TILS to the dlPFC, one of the PFC regions implicated in emotion regulation, resulted in a context-specific benefit as a monotherapy for reducing fear. Contrary to prediction, TILS to the vmPFC, a region implicated in fear extinction memory consolidation, did not enhance exposure therapy outcome. [ABSTRACT FROM AUTHOR]

Cortical-subcortical hyperconnectivity related to affective-behavioral integration and cortical network hypoconnectivity related to cognitive control have been demonstrated in obsessive-compulsive disorder (OCD); the study objective was to examine whether these connectivity patterns predict treatment response. Adolescents (ages 12–17) and adults (ages 24–45) were randomly assigned to 12 sessions of exposure and response prevention (ERP) or stress management therapy (SMT), an active control. Before treatment, resting-state connectivity of ventromedial prefrontal cortical (vmPFC), cingulo-opercular, frontoparietal, and subcortical regions was assessed with functional MRI. OCD severity was assessed with the Yale-Brown Obsessive Compulsive Scale before, during, and after treatment. Usable fMRI and longitudinal symptom data were obtained from 116 patients (68 female; 54 adolescents; 60 medicated). ERP produced greater decreases in symptom scores than SMT. ERP was selectively associated with less vmPFC-subcortical (caudate and thalamus) connectivity in both age groups and primarily in unmedicated participants. Greater symptom improvement with both ERP and SMT was associated with greater cognitive-control (cingulo-opercular and frontoparietal) and subcortical (putamen) connectivity across age groups. Developmental specificity was observed across ERP and SMT treatments, such that greater improvements with ERP than SMT were associated with greater frontoparietal-subcortical (nucleus accumbens) connectivity in adolescents but greater connectivity between frontoparietal regions in adults. Comparison of response-predictive connections revealed no significant differences compared with a matched healthy control group. The results suggest that less vmPFC-subcortical connectivity related to affect-influenced behavior may be important for ERP engagement, whereas greater cognitive-control and motor circuit connectivity may generally facilitate response to psychotherapy. Finally, neural predictors of treatment response may differ by age. [ABSTRACT FROM AUTHOR]

Due to the similarities in behavioral characteristics between romantic love and addictive disorders, the concept of being "addicted to someone" transcends mere literary metaphor, expanding perspectives on the study of romantic love and inspiring interventions for addiction. However, there has been a lack of studies systematically exploring the similarities and differences between romantic love and addiction at the neural level. In this study, we conducted an extensive literature search, incorporating 21 studies on romantic love and 28 on addictive disorders, focusing on fMRI research utilizing the cue reactivity paradigm. Using Activation Likelihood Estimation, we examined the similarities and differences in the neural mechanisms underlying love and addiction. The results showed that the anterior cingulate cortex (ACC) exhibited both shared and distinct activation clusters between romantic love and addictive disorders. Furthermore, ventromedial prefrontal cortex (VMPFC) was more frequently activated in romantic love than in addictive disorders, while greater activation within the posterior cingulate cortex (PCC) was found in addictive disorder compared with romantic love. We discussed that the activation of ACC and VMPFC may symbolize self-expansion, a process that characterizes the development of romantic love, contributing to a more enriched self. Our study suggests that while romantic love and addictive disorders share a common neural foundation, the discernible differences in their neural representations distinguish them as joyful growth versus compulsive hedonism., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Individuals with major depressive disorder (MDD) have deficits in emotion regulation, which plays a putative role in psychopathology. The ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) are assumed to be involved in respective processes. In the present study, we aimed to explore the effect of stimulation over the dlPFC and vmPFC on emotion regulation in female with MDD. Twenty women with MDD performed the Emotional Stroop, Emotional Go/No-Go, and Emotional 1-Back tasks during transcranial direct current stimulation (tDCS) in three separate sessions with the following electrode montages: anodal dlPFC (F3)/cathodal vmPFC (Fp2), anodal vmPFC (Fp2)/cathodal dlPFC (F3), and sham stimulation. Independent of the valence of the respective stimuli, accuracy and speed of interference control, accuracy of pre-potent inhibition, and accuracy, but not speed, of working memory performance improved during anodal left dlPFC/cathodal right vmPFC stimulation. Independent of stimulation conditions, interference control was reduced for sad faces, as compared to happy and neutral faces, and working memory performance was faster for happy than for neutral and sad faces. For the impact of stimulation on specific emotional qualities, anodal left dlPFC/cathodal right vmPFC, compared to sham stimulation, led to improved interference control of sad and neutral faces in the emotional Stroop task, as shown by faster reaction times. Furthermore, in that task accuracy with respect to neutral and happy face conditions was higher during both real stimulation conditions, as compared to sham stimulation. The dlPFC is involved in emotion regulation in MDD. Emotional valence is moreover relevant for the effect of stimulation over this area on interference control in MDD. [ABSTRACT FROM AUTHOR]

Stimuli in reality rarely co-occur with primary reward or punishment to allow direct associative learning of value. Instead, value is thought to be inferred through complex higher-order associations. Rodent research has demonstrated that the formation and maintenance of first-order and higher-order associations are supported by distinct neural substrates. In this study, we explored whether this pattern of findings held true for humans. Participants underwent first-order and subsequent higher-order conditioning using an aversive burst of white noise or neutral tone as the unconditioned stimuli. Four distinct tones, initially neutral, served as first-order and higher-order conditioned stimuli. Autonomic and neural responses were indexed by pupillometry and evoked response potentials (ERPs) respectively. Conditioned aversive values of first-order and higher-order stimuli led to increased autonomic responses, as indexed by pupil dilation. Distinct temporo-spatial auditory evoked response potentials were elicited by first-order and high-order conditioned stimuli. Conditioned first-order responses peaked around 260 ms and source estimation suggested a primary medial prefrontal and amygdala source. Conversely, conditioned higher-order responses peaked around 120 ms with an estimated source in the medial temporal lobe. Interestingly, pupillometry responses to first-order conditioned stimuli were diminished after higher order training, possibly signifying concomitant incidental extinction, while responses to higher-order stimuli remained. This suggests that once formed, higher order associations are at least partially independent of first order conditioned representations. This experiment demonstrates that first-order and higher-order conditioned associations have distinct neural signatures, and like rodents, the medial temporal lobe may be specifically involved with higher-order conditioning. [ABSTRACT FROM AUTHOR]

Stimuli in reality rarely co-occur with primary reward or punishment to allow direct associative learning of value. Instead, value is thought to be inferred through complex higher-order associations. Rodent research has demonstrated that the formation and maintenance of first-order and higher-order associations are supported by distinct neural substrates. In this study, we explored whether this pattern of findings held true for humans. Participants underwent first-order and subsequent higher-order conditioning using an aversive burst of white noise or neutral tone as the unconditioned stimuli. Four distinct tones, initially neutral, served as first-order and higher-order conditioned stimuli. Autonomic and neural responses were indexed by pupillometry and evoked response potentials (ERPs) respectively. Conditioned aversive values of first-order and higher-order stimuli led to increased autonomic responses, as indexed by pupil dilation. Distinct temporo-spatial auditory evoked response potentials were elicited by first-order and high-order conditioned stimuli. Conditioned first-order responses peaked around 260 ms and source estimation suggested a primary medial prefrontal and amygdala source. Conversely, conditioned higher-order responses peaked around 120 ms with an estimated source in the medial temporal lobe. Interestingly, pupillometry responses to first-order conditioned stimuli were diminished after higher order training, possibly signifying concomitant incidental extinction, while responses to higher-order stimuli remained. This suggests that once formed, higher order associations are at least partially independent of first order conditioned representations. This experiment demonstrates that first-order and higher-order conditioned associations have distinct neural signatures, and like rodents, the medial temporal lobe may be specifically involved with higher-order conditioning.

Traumatic stress is associated with risk of psychiatric and physical illnesses. However, the differential and separable effects of past versus recent traumas on maladaptive coping and neural responses are not known. We conducted two studies to assess separate and combined effects of cumulative recent and past trauma on health outcomes (study 1) and on neural responses to acute stress exposure in a subsample of individuals (study 2). Study 1 assessed a large cohort of 677 community adults cross-sectionally, and findings indicated that both high recent (within the last 12 months) and past trauma (prior to the last twelve months) were associated with more physical and psychological symptoms, including increased depression (all p's <.05). However, recent trauma alone was associated with higher problematic alcohol use, a greater maximum number of alcohol drinks consumed, greater emotional eating scores, higher state and trait anxiety scores, and poorer lifestyle habits (all p's <.05). Past trauma alone was associated with higher BMI, decreased social support, and a lower average cortisol relative to ACTH ratio (all p's <.02). Study 2 involving a functional brain scan on a subsample (N = 75) indicated greater recent trauma was associated with a hyperactive response in the ventromedial prefrontal cortex (VmPFC) to neutral-relaxed exposure, but blunted VmPFC response to acute stress exposure (p <.05: whole brain corrected-WBC). By contrast, high past trauma was associated with a hyper-sensitized neural response to stress in the cortico-limbic-striatal regions (p <.05, WBC) critical for reward and emotion processing. Together, these findings suggest differential neurobehavioral and health effects of cumulative past versus recent trauma exposure. [ABSTRACT FROM AUTHOR]

Background: Females are more likely to develop posttraumatic stress disorder (PTSD) than males. Impaired inhibition has been identified as a mechanism for PTSD development, but studies on potential sex differences in this neurobiological mechanism and how it relates to PTSD severity and progression are relatively rare. Here, we examined sex differences in neural activation during response inhibition and PTSD following recent trauma., Methods: Participants (n = 205, 138 female sex assigned at birth) were recruited from emergency departments within 72 hours of a traumatic event. PTSD symptoms were assessed 2 weeks and 6 months posttrauma. A Go/NoGo task was performed 2 weeks posttrauma in a 3T magnetic resonance imaging scanner to measure neural activity during response inhibition in the ventromedial prefrontal cortex, right inferior frontal gyrus, and bilateral hippocampus. General linear models were used to examine the interaction effect of sex on the relationship between our regions of interest and the whole brain, PTSD symptoms at 6 months, and symptom progression between 2 weeks and 6 months., Results: Lower response inhibition-related ventromedial prefrontal cortex activation 2 weeks posttrauma predicted more PTSD symptoms at 6 months in females but not in males, while greater response inhibition-related right inferior frontal gyrus activation predicted lower PTSD symptom progression in males but not females. Whole-brain interaction effects were observed in the medial temporal gyrus and left precentral gyrus., Conclusions: There are sex differences in the relationship between inhibition-related brain activation and PTSD symptom severity and progression. These findings suggest that sex differences should be assessed in future PTSD studies and reveal potential targets for sex-specific interventions., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

• Self-referential processing (SRP) is an underlying cognitive mechanism of self-esteem. • High self-esteem is associated with biased attention to self-facial pictures and self-related words. • 2 mA anodal & cathodal tDCS over vmPFC promoted self-esteem rating. • Enhanced SRP and cognitive/emotional control over self-related information may explain vmPFC contribution to self-esteem. • 2 mA cathodal tDCS showed similar anodal excitatory-enhancing effects on self-esteem. Despite growing interest in underlying cognitive mechanisms of self-esteem, its neurocognitive correlates are not fully-understood. Attention bias to self-related stimuli is an example of self-referential processing (SRP) and its association with self-esteem is not well-studied. Moreover, previous studies showed that the medial prefrontal regions are involved in SRP which might suggest its involvement in self-esteem too. We investigated attentional bias to self-related stimuli and its association with the level of self-esteem in the first study (N = 30). In the second study (N = 15), we modulated activity of the ventromedial prefrontal cortex (VMPFC), as one of the medial prefrontal regions, using transcranial direct current stimulation (tDCS) to see how it affects different domains of self-esteem. Results showed that individuals with a higher level of self-esteem have more attentional bias to their own facial pictures (compared to other-facial pictures) and self-related words (compared to self-unrelated words) suggesting an impact of self-esteem on attentional and perceptual processes. Additionally, modulating activity of the VMPFC with 2 mA anodal and cathodal tDCS was associated with significantly higher ratings of global and total self-esteem but not other self-esteem domains. Our findings provide supporting evidence of neurocognitive correlates of self-esteem indicating a biasing influence of self-esteem on attention toward "self" and suggesting self-esteem as a function of SRP at behavioural and neural levels. [ABSTRACT FROM AUTHOR]

Cognitive behavioral therapy (CBT) including exposure and response prevention is a well-established treatment for obsessive–compulsive disorder (OCD) and is based on the principles of fear extinction. Fear extinction is linked to structural and functional variability in the ventromedial prefrontal cortex (vmPFC) and has been consistently associated with glutamate neurotransmission. The relationship between vmPFC glutamate and fear extinction and its effects on CBT outcome have not yet been explored in adults with OCD. We assessed glutamate levels in the vmPFC using 3T magnetic resonance spectroscopy, and fear extinction (learning and recall) using skin conductance responses during a 2-day experimental paradigm in OCD patients (n = 17) and in healthy controls (HC; n = 13). Obsessive–compulsive patients (n = 12) then received manualized CBT. Glutamate in the vmPFC was negatively associated with fear extinction recall and positively associated with CBT outcome (with higher glutamate levels predicting a better outcome) in OCD patients. Glutamate levels in the vmPFC in OCD patients were not significantly different from those in HC, and were not associated with OCD severity. Our results suggest that glutamate in the vmPFC is associated with fear extinction recall and CBT outcome in adult OCD patients. [ABSTRACT FROM AUTHOR]

To decide whether or not to participate in an upcoming activity, people can use their memories of intrinsically-motivating or non-intrinsically-motivating experiences during previous participations. To understand the underlying neural mechanism of intrinsic motivation memories, we used a block-design functional magnetic resonance imaging (fMRI) experiment to compare the neural activations during intrinsically-motivating memories versus during non-intrinsically-motivating memories. Results showed that both the ventromedial prefrontal cortex (VMPFC) and anterior cingulate cortex (ACC) were more activated during the recall of intrinsically-motivating memories rather than during the recall of non-intrinsically-motivating memories. Greater negative functional interactions between the VMPFC and ACC were also observed in the intrinsically-motivating situations. These findings suggest that the two complementary neural processes are employed to reconstruct intrinsically-motivating experiences: pleasure (reward related to VMPFC activity) and personal meaning (self-endorsement related to ACC activity). [ABSTRACT FROM AUTHOR]

Background: Psychological stress can influence the severity of multiple sclerosis (MS), but little is known about neurobiological factors potentially counteracting these effects.Objective: To identify gray matter (GM) brain regions related to relaxation after stress exposure in persons with MS (PwMS).Methods: 36 PwMS and 21 healthy controls (HCs) reported their feeling of relaxation during a mild stress task. These markers were related to regional GM volumes, heart rate, and depressive symptoms.Results: Relaxation was differentially linked to heart rate in both groups (t = 2.20, p = 0.017), i.e., both markers were only related in HCs. Relaxation was positively linked to depressive symptoms across all participants (t = 1.99, p = 0.045) although this link differed weakly between groups (t = 1.62, p = 0.108). Primarily, the volume in medial temporal gyrus was negatively linked to relaxation in PwMS (t = −5.55, pfamily−wise−error(FWE)corrected = 0.018). A group-specific coupling of relaxation and GM volume was found in ventromedial prefrontal cortex (VMPFC) (t = −4.89, pFWE = 0.039).Conclusion: PwMS appear unable to integrate peripheral stress signals into their perception of relaxation. Together with the group-specific coupling of relaxation and VMPFC volume, a key area of the brain reward system for valuation of affectively relevant stimuli, this finding suggests a clinically relevant misinterpretation of stress-related affective stimuli in MS.

Using contextual information to predict aversive events is a critical ability that protects from generalizing fear responses to safe contexts. Animal models have demonstrated the importance of spatial context representations within the hippocampal formation in contextualization of fear learning. The ventromedial prefrontal cortex (vmPFC) is known to play an important role in safety learning, possibly also through the incorporation of context information. However, if contextual representations are related to context-dependent expression of fear memory in humans remains unclear. Twenty-one healthy participants underwent functional MRI combined with a cue-context conditioning paradigm within a self-navigated virtual reality environment. The environment included two buildings (Threat and Safe context), which had distinct features outside but were identical inside. Within each context, participants saw two cues (CS+, CS-). The CS+ was consistently (100% reinforcement rate) paired with an electric shock in the Threat context, but never in the Safe context. The CS- was never paired with a shock. We found robust differential skin conductance responses (SCRs; CS+ ​> ​CS-) in the Threat context, but also within the Safe context, indicating fear generalization. Within the Safe context, vmPFC responses to the CS+ were larger than those in the Threat context. We furthermore found environment-specific representations for the two contexts in the training paradigm (i.e., before conditioning took place) in the hippocampus to be related to fear expression and generalization. Namely, participants with a weak context representation (z-score 1.65). Thus, a weak neural representation strength of spatial context may explain overgeneralization of memory to safe contexts. In addition, our findings demonstrate that context-dependent regulation of fear expression engages ventromedial prefrontal pathways suggesting this involves a similar mechanism that is known to be involved in retrieval of extinction memory.

Background: Psychological stress can influence the severity of multiple sclerosis (MS), but little is known about neurobiological factors potentially counteracting these effects. Objective: To identify gray matter (GM) brain regions related to relaxation after stress exposure in persons with MS (PwMS). Methods: 36 PwMS and 21 healthy controls (HCs) reported their feeling of relaxation during a mild stress task. These markers were related to regional GM volumes, heart rate, and depressive symptoms. Results: Relaxation was differentially linked to heart rate in both groups (t = 2.20, p = 0.017), i.e., both markers were only related in HCs. Relaxation was positively linked to depressive symptoms across all participants (t = 1.99, p = 0.045) although this link differed weakly between groups (t = 1.62, p = 0.108). Primarily, the volume in medial temporal gyrus was negatively linked to relaxation in PwMS (t = −5.55, pfamily−wise−error(FWE)corrected = 0.018). A group-specific coupling of relaxation and GM volume was found in ventromedial prefrontal cortex (VMPFC) (t = −4.89, pFWE = 0.039). Conclusion: PwMS appear unable to integrate peripheral stress signals into their perception of relaxation. Together with the group-specific coupling of relaxation and VMPFC volume, a key area of the brain reward system for valuation of affectively relevant stimuli, this finding suggests a clinically relevant misinterpretation of stress-related affective stimuli in MS. [ABSTRACT FROM AUTHOR]

Background: Recent studies show that changes in one of the brain areas related to empathic abilities (i.e. the ventromedial prefrontal cortex (vmPFC)) plays an important role in violent behavior in abusers of alcohol and cocaine. According to the models of James Blair, empathy is a potential inhibitor of violent behavior. Individuals with less empathic abilities may be less susceptible and motivated to inhibit violent behavior, which causes a higher risk of violence. Recent neuroscientific research shows that modulating (stimulation or inhibition) certain brain areas could be a promising new intervention for substance abuse and to reduce violent behavior, such as the neurostimulation technique transcranial direct current stimulation (tDCS). This study aims to investigate tDCS as an intervention to increase empathic abilities and reduce violent behavior in forensic substance use offenders.Methods/design: A total sample of 50 male forensic substance abuse patients (25 active and 25 sham stimulation) will be tested in a double-blind placebo-controlled study, from which half of the patients will receive an active stimulation plus treatment as usual (TAU) and the other half will receive sham stimulation (placebo) plus TAU. The patients in the active condition will receive multichannel tDCS targeting the bilateral vmPFC two times a day for 20 min for five consecutive days. Before and after the stimulation period, the patients will complete self-report measurements, perform the Point Subtraction Aggression Paradigm (PSAP) and a passive viewing empathy task. Resting state electroencephalography (rsEEG) will be performed before and after the treatment period. A follow up will be conducted after 6 months. The primary outcome is to investigate multichannel tDCS as a new intervention to increase empathic abilities and reduce violent behavior in offenders with substance abuse problems. In addition, we will determine whether electrophysiological responses in the brain are affected by the tDCS intervention. Finally, the effects of tDCS on reducing craving will be investigated.Discussion: This study is one of the first studies using multichannel tDCS targeting the vmPFC in a forensic sample. This study will explore the opportunities to introduce a new intervention to improve empathic abilities and reduce violence in forensic substance use offenders. Specifically, this study may give insight into how to implement the tDCS intervention in the setting of daily clinical practice in this complex, multiple-problem target group and with that contribute to reduction of recidivism.Trial Registration: Dutch Trial Register, NTR7701. Registered on 12 January 2019. Prospectively registered before the recruitment phase. https://www.trialregister.nl/trial/7459. Recruitment started on the 1st of February 2019 and will be finished approximately in the winter of 2019. Protocol version 1. 22 May 2019. [ABSTRACT FROM AUTHOR]

Previous studies demonstrate that drug addiction can share the neural circuits in the brain with normal learning and memory. Re-exposure to drug-associated contexts, one way to retrieve the drug-associated memory, can trigger strong psychic craving and even relapse in addicts after prolonged abstinence. The ventromedial prefrontal cortex (vmPFC) has been shown to be involved in time-dependent reinstatement of drug self-administration. This work is designed to investigate the role of AMPA receptor (AMPAR) in the vmPFC in the recent and remote retrieval of morphine-associated memory. Rats were re-exposed to the morphine-paired context 1 day (recent) and 3 weeks (remote) after morphine conditioned place preference (CPP) training. Results showed that membrane expression of GluA1 and GluA2 in the vmPFC was decreased following the recent retrieval, while the membrane expression of GluA1 and GluA2 in the vmPFC was increased following the remote retrieval of morphine-associated memory. Furthermore, the microinfusion of Tat-GluA2-3Y, a GluA2 endocytosis inhibitor, into the vmPFC impaired the recent retrieval of morphine-associated memory. The microinfusion of AMPAR antagonist NBQX into the vmPFC prevented the remote retrieval of morphine-associated memory. Taking together, the present study proved that AMPAR in the vmPFC played different roles in the recent and remote retrieval of morphine-associated memory. [ABSTRACT FROM AUTHOR]

Abstract Deep brain stimulation (DBS) has shown to have antidepressant effects in both human trials and animal studies. However, the optimal target and the underlying therapeutic mechanisms remain to be determined. In this study, we investigated if high frequency (HF) DBS in the dorsal peduncular cortex (DPC) alleviates depressive-like behavior in an experimental model of depression. Surprisingly, HF DBS in the DPC caused acute induction of seizures in ~ 40% of animals stimulated with clinically relevant stimulation parameters. Reducing the stimulation's amplitude by 50% did not alter seizure occurrence. Electroencephalographic (EEG) recordings showed seizures up to Racine stage IV lasting up to 4 min after cessation of stimulation. We conclude that HF DBS in the DPC is not suitable for mood-related experiments in rats but could be a potential model for seizure induction. Highlights • DBS in the DPC in rats has a high incidence of inducing seizures up to Racine stage IV-V. • The clinically relevant parameters used do not seem to induce seizure in other brain structures. • The DPC shows connections to the limbic system, which makes current spread during stimulation into this system plausible. [ABSTRACT FROM AUTHOR]

The ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) are key brain regions involved in risky decision making, affected in individuals with attention deficit hyperactivity disorder (ADHD). This study aims to examine how entrainment of these areas impacts the process and outcome of risky decision making in children with ADHD. Eighteen children with ADHD performed the balloon analogue risk-taking task (BART) during five different sessions of tACS (1.5 mA, 6 Hz), separated by one-week intervals, via (1) two channels with synchronized stimulation over the left dlPFC and right vmPFC, (2) the same electrode placement with anti-phase stimulation, (3) stimulation over the left dlPFC only, (4) stimulation over right vmPFC only, and (5) sham stimulation. Four-parameter and constant-sensitivity models were used to model the data. The study showed that synchronized stimulation was associated with a reduction in positive prior belief, risk propensity, and deterministic selection. Desynchronized stimulation was associated with accelerated learning from initial selections. Isolated stimulation of the dlPFC leads to riskier decision enhanced learning updates and risk propensity, whereas isolated stimulation of the vmPFC facilitated faster learning and increased probabilistic selection. The results highlight the important roles of the dlPFC and vmPFC and their communication in decision making, showcasing their impact on various aspects of the decision-making process. The findings provide valuable insights into the complex interplay between cognitive and emotional factors in shaping our choices. [ABSTRACT FROM AUTHOR]

Objective: Emotion recognition, which is defined as the process of interpreting the emotional state of individuals by looking at their facial expressions, is important in the healthy conduct of social relations and communication. When the literature is examined, it has been observed that studies on the effect of Transcranial Direct Current Stimulation (tDCS), one of the brain stimulation methods, on emotion recognition are limited. In this study, it was aimed to examine the effect of anodal stimulation of the ventromedial prefrontal cortex (vmPFC), which is one of the important regions in emotion recognition from facial expressions, on emotion recognition and EEG oscillations. Methods: The study is a single-blind randomized-control group study conducted with 54 healthy participants aged 18-40 years. Before and after brain stimulation, "ADFES-BIV emotion recognition task" and "Mind Reading from the Eyes Test" were applied and resting state EEG recordings were taken. The change in task performances and brain oscillations was analyzed by Repeated Measurement Two-Way ANOVA. Results: While there was no significant difference in emotion recognition tasks between groups in the pre-post measurements (p>0.05); significant difference were observed in some channels EEG frequency bands (p<0.05). Conclusion: The lack of positive effect of tDCS on emotion recognition may be due to the fact that the tDCS may not have created the desired effect in the targeted region because of the vmPFC region is located in the lower part of the prefrontal lobe, and also the changes that EEG frequencies which are modulated similarly to some pathological processes. In addition, it is thought that this finding supports the idea that brain oscillations can be affected by stimulation, leading to deterioration in cognitive functions. Future studies to be carried out for better understand this effect are important. [ABSTRACT FROM AUTHOR]

We aimed to differentiate the neural responses to cooperative and competitive contexts, which are the two of the most important social contexts in human society. Healthy male college students were asked to complete a Tetris-like task requiring mental rotation skills under individual, cooperative, and competitive contexts in an fMRI scanner. While the participants completed the task, pictures of others experiencing pain evoking emotional empathy randomly appeared to capture contextual effects on empathic neural responses. Behavioral results indicated that, in the presence of cooperation, participants solved the tasks more accurately and quickly than what they did when in the presence of competition. The fMRI results revealed activations in the dorsolateral prefrontal cortex (dlPFC) and dorsomedial prefrontal cortex (dmPFC) related to executive functions and theory of mind when participants performed the task under both cooperative and competitive contexts, whereas no activation of such areas was observed in the individual context. Cooperation condition exhibited stronger neural responses in the ventromedial prefrontal cortex (vmPFC) and dmPFC than competition condition. Competition condition, however, showed marginal neural responses in the cerebellum and anterior insular cortex (AIC). The two social contexts involved stronger empathic neural responses to other’s pain than the individual context, but no substantial differences between cooperation and competition were present. Regions of interest analyses revealed that individual’s trait empathy modulated the neural activity in the state empathy network, the AIC, and the dorsal anterior cingulate cortex (dACC) depending on the social context. These results suggest that cooperation improves task performance and activates neural responses associated with reward and mentalizing. Furthermore, the interaction between trait- and state-empathy was explored by correlation analyses between individual’s trait empathy score and changing empathic brain activations along with the exposure to the cooperative and competitive social contexts.

People tend to pay the generosity they receive from a person forward to someone else even if they have no chance to reciprocate directly. This phenomenon, known as paying-it-forward (PIF) reciprocity, crucially contributes to the maintenance of a cooperative human society by passing kindness among strangers and has been widely studied in evolutionary biology. To further examine its neural implementation and underlying computations, we used functional magnetic resonance imaging together with computational modeling. In a modified PIF paradigm, participants first received a monetary split (i.e. greedy, equal or generous) from either a human partner or a computer. They then chose between two options involving additional amounts of money to be allocated between themselves and an uninvolved person. Behaviorally, people forward the previously received greed/generosity towards a third person. The social impact of previous treatments is integrated into computational signals in the ventromedial prefrontal cortex and the right temporoparietal junction during subsequent decision making. Our findings provide insights to understand the proximal origin of PIF reciprocity. [ABSTRACT FROM AUTHOR]

In order to improve our understanding of how pictorial health warning labels (HWLs) influence smoking behavior, we examined whether brain activity helps to explain smoking behavior above and beyond self-reported effectiveness of HWLs. We measured the neural response in the ventromedial prefrontal cortex (vmPFC) and the amygdala while adult smokers viewed HWLs. Two weeks later, participants’ self-reported smoking behavior and biomarkers of smoking behavior were reassessed. We compared multiple models predicting change in self-reported smoking behavior (cigarettes per day [CPD]) and change in a biomarkers of smoke exposure (expired carbon monoxide [CO]). Brain activity in the vmPFC and amygdala not only predicted changes in CO, but also accounted for outcome variance above and beyond self-report data. Neural data were most useful in predicting behavioral change as quantified by the objective biomarker (CO). This pattern of activity was significantly modulated by individuals’ intention to quit. The finding that both cognitive (vmPFC) and affective (amygdala) brain areas contributed to these models supports the idea that smokers respond to HWLs in a cognitive-affective manner. Based on our findings, researchers may wish to consider using neural data from both cognitive and affective networks when attempting to predict behavioral change in certain populations (e.g. cigarette smokers). [ABSTRACT FROM AUTHOR]

Memory formation for newly acquired associations typically depends on hippocampal–neocortical interactions. Through the process of system-consolidation, the mnemonic binding role of the hippocampus is subsequently replaced by cortical hubs, such as the ventromedial prefrontal cortex (vmPFC) or the anterior temporal lobe (ATL). Here, using BOLD-fMRI, we compared retrieval of semantic associations acquired through Fast Mapping (FM), an incidental, exclusion-based learning procedure, to retrieval of similar associations that were intentionally acquired through Explicit Encoding (EE). Despite an identical retrieval task, the encoding histories of the retrieved semantic associations (FM vs. EE) induced distinct neural substrates and disparate related neural dynamics in time. Retrieval of associations acquired through EE engaged the expected hippocampal and vmPFC related networks. Furthermore, retrieval intentionally encoded associations gave rise to a typical overnight increase in engagement of the vmPFC and increased vmPFC–hippocampal–neocortical functional connectivity. On the other hand, retrieval of associations acquired through FM immediately engaged an ATL related network that typically supports well-established semantic knowledge, a network that did not engage the hippocampus and the vmPFC. Moreover, FM learning was associated with minimal overnight changes in the BOLD responses and in the functional connectivity. Our findings indicate that FM may induce a direct, ATL-mediated acquisition and retention of novel arbitrary associations, bypassing the initial hippocampal–cortical representation phase. A direct, ATL-mediated vocabulary acquisition through FM could support the learning and retention of new associations in young children with presumably an immature hippocampal system, and possibly even in amnesic adults with hippocampal lesions. [ABSTRACT FROM AUTHOR]

Well-being and subjective experience of a coherent world depend on our sense of 'self' and relations between the self and the environment (e.g. people, objects and ideas). The ventromedial prefrontal cortex (vMPFC) is involved in self-related processing, and disrupted vMPFC activity is associated with disruptions of emotional/social functioning (e.g. depression and autism). Clarifying precise function(s) of vMPFC in self-related processing is an area of active investigation. In this study, we sought to more specifically characterize the function of vMPFC in self-related processing, focusing on two alternative accounts: (i) assignment of positive subjective value to self-related information and (ii) assignment of personal significance to self-related information. During functional magnetic resonance imaging (fMRI), participants imagined owning objects associated with either their perceived ingroup or outgroup. We found that for ingroup-associated objects, vMPFC showed greater activity for objects with increased than decreased post-ownership preference. In contrast, for outgroup-associated objects, vMPFC showed greater activity for objects with decreased than increased post-ownership preference. Our findings support the idea that the function of vMPFC in self-related processing may not be to represent/evaluate the 'positivity' or absolute preference of self-related information but to assign personal significance to it based on its meaning/function for the self. [ABSTRACT FROM AUTHOR]

The nucleus accumbens (NAc), ventromedial prefrontal cortex (vmPFC), and cingulate gyrus (Cg) are key regions in the control of mood-related behaviors. Electrical stimulation of these areas induces antidepressant-like effects in both patients and animal models. Another structure whose limbic connections are receiving more interest in the context of mood-related behaviors is the medial part of the subthalamic nucleus (STN). Here, we tested the hypothesis that the mood-related effects of NAc, vmPFC, and Cg are accompanied by changes in the neural activity of the STN. We performed high-frequency stimulation (HFS) of the NAc, vmPFC, and Cg. Animals were behaviorally tested for hedonia and forced swim immobility; and the cellular activities in the different parts of the STN were assessed by means of c-Fos immunoreactivity (c-Fos-ir). Our results showed that HFS of the NAc and vmPFC, but not Cg reduced anhedonic-like and forced swim immobility behaviors. Interestingly, there was a significant increase of c-Fos-ir in the medial STN with HFS of the vmPFC, but not the NAc and Cg as compared to the sham. Correlation analysis showed that the medial STN is associated with the antidepressant-like behaviors in vmPFC HFS animals. No behavioral correlation was found with respect to behavioral outcome and activity in the lateral STN. In conclusion, HFS of the vmPFC induced profound antidepressant-like effects with enhanced neural activity in the medial part of the STN. [ABSTRACT FROM AUTHOR]

The human orbitofrontal cortex, ventromedial prefrontal cortex (vmPFC), and anterior cingulate cortex are involved in reward processing and thereby in emotion but are also implicated in episodic memory. To understand these regions better, the effective connectivity between 360 cortical regions and 24 subcortical regions was measured in 172 humans from the Human Connectome Project and complemented with functional connectivity and diffusion tractography. The orbitofrontal cortex has effective connectivity from gustatory, olfactory, and temporal visual, auditory, and pole cortical areas. The orbitofrontal cortex has connectivity to the pregenual anterior and posterior cingulate cortex and hippocampal system and provides for rewards to be used in memory and navigation to goals. The orbitofrontal and pregenual anterior cortex have connectivity to the supracallosal anterior cingulate cortex, which projects to midcingulate and other premotor cortical areas and provides for action-outcome learning including limb withdrawal or flight or fight to aversive and nonreward stimuli. The lateral orbitofrontal cortex has outputs to language systems in the inferior frontal gyrus. The medial orbitofrontal cortex connects to the nucleus basalis of Meynert and the pregenual cingulate to the septum, and damage to these cortical regions may contribute to memory impairments by disrupting cholinergic influences on the neocortex and hippocampus., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Highlights: [•] Pavlovian fear conditioning and extinction relate to PTSD and other anxiety disorders. [•] Such studies in rodents inform human psychophysiological and neuroimaging studies. [•] Gene and twin studies have revealed vulnerabilities to PTSD and anxiety disorders. [•] Treatment of PTSD and anxiety disorders use Pavlovian fear extinction as a template. [Copyright &y& Elsevier]

Highlights: [•] Gray matter volume of the subgenual anterior cingulate cortex positively associated with pattern A behavior scores. [•] TABP was positively correlated with increased resting-state functional connectivity between the left caudate and ventromedial prefrontal cortex. [•] TABP was also positively correlated with also increased functional connectivity between the left caudate and rostral anterior cingulate cortex. [ABSTRACT FROM AUTHOR]

Highlights: [•] VMPFC might be involved in the asset preference. [•] IPL was associated with the score of future time perspective. [•] Uncertain and unstable market conditions may trigger a changed brain mode in traders. [•] DLPFC and IPL might form a network predominant during the bubble. [•] Premotor area was associated with a trade strategy in the stable market state. [Copyright &y& Elsevier]

Abstract: It is widely accepted that brain maturation from adolescence to adulthood contributes to substantial behavioural changes. Despite this, however, knowledge of the precise mechanisms is still sparse. We used fMRI to investigate developmental differences between healthy adolescents (age range 14–15) and adults (age range 20–39) in feedback-related decision making using a probabilistic reversal learning task. Conventionally groups are compared based on continuous values of blood oxygen level dependent (BOLD) percentage signal change. In contrast, we transformed these values into discrete states and used the pattern of these states to compare groups. We focused our analysis on anterior cingulate cortex (ACC), ventral striatum (VS) and ventromedial prefrontal cortex (vmPFC) as their functions have been shown to be critical in feedback related decision making. Discretisation of continuous BOLD values revealed differential patterns of activity as compared to conventional statistical methods. Results showed differential representation of feedback and decision in ACC and vmPFC between adolescents and adults but no difference in VS. We argue that the pattern of activity of ACC, vmPFC and VS in adolescents resulted in several drawbacks in decision making such as redundant and imprecise representation of decision and subsequently poorer performance in terms of the number of system changes (change of contingencies). This method can be effectively used to infer group differences from within-group analysis rather than studying the differences by direct between-group comparisons. [Copyright &y& Elsevier]

Highlights: [•] Neural reactivity to cocaine, alcohol and tobacco cues is modulated by:. [•] Treatment status, length and intensity of use, addiction severity, abstinence. [•] Stress, drug availability, sensory modality and length of presentation of cues. [•] Explicit and implicit cognitive regulation. [•] These factors have both main and interactive effects. [ABSTRACT FROM AUTHOR]

Highlights: [•] We measured brain activity during self and other referential tasks. [•] We used two types of trait words defined by reaction time for each participant. [•] Activation differed across self and other only in the slow word condition. [•] The self-slow condition showed greater activation in the ventromedial PFC. [•] The other-slow condition showed greater activation in the middle temporal gyrus. [ABSTRACT FROM AUTHOR]

Abstract: Serotonin is critical for shaping the development of neural circuits regulating emotion. Pet-1 (FEV-1) is an ETS-domain transcription factor essential for differentiation and forebrain targeting of serotonin neurons. Constitutive Pet-1 knockout (KO) causes major loss of serotonin neurons and forebrain serotonin availability, and behavioral abnormalities. We phenotyped Pet-1 KO mice for fear conditioning and extinction, and on a battery of assays for anxiety- and depression-related behaviors. Morphology of Golgi-stained neurons in basolateral amygdala (BLA) and prelimbic cortex was examined. Using human imaging genetics, a common variant (rs860573) in the PET-1 (FEV) gene was tested for effects on threat-related amygdala reactivity and psychopathology in 88 Asian-ancestry subjects. Pet-1 KO mice exhibited increased acquisition and expression of fear, and elevated fear recovery following extinction, relative to wild-type (WT). BLA dendrites of Pet-1 KO mice were significantly longer than in WT. Human PET-1 variation associated with differences in amygdala threat processing and psychopathology. This novel evidence for the role of Pet-1 in fear processing and dendritic organization of amygdala neurons and in human amygdala threat processing extends a growing literature demonstrating the influence of genetic variation in the serotonin system on emotional regulation via effects on structure and function of underlying corticolimbic circuitry. [Copyright &y& Elsevier]

Abstract: Frontal lobe dysfunction is known to be associated with impairment in social behavior. We investigated the link between severe pharmacoresistant frontal lobe epilepsy and antisocial trait. We studied four patients with pharmacoresistant epilepsy involving the prefrontal cortex, presenting abnormal interictal social behavior. Noninvasive investigations (video-EEG, PET, MRI) and intracerebral recording (stereoelectroencephalography (SEEG)) were performed as part of a presurgical assessment. Comprehensive psychiatric and cognitive evaluation was performed pre- and postoperatively for frontal lobe epilepsy, with at least 7years of follow-up. All patients shared a characteristic epilepsy pattern: (1) chronic severe prefrontal epilepsy with daily seizures and (2) an epileptogenic zone as defined by intracerebral recording involving the anterior cingulate cortex, ventromedial PFC, and the posterior part of the orbitofrontal cortex, with early propagation to contralateral prefrontal and ipsilateral medial temporal structures. All patients fulfilled the diagnostic criteria (DSM-IV) of antisocial personality disorder, which proved to be reversible following seizure control. Pharmacoresistant epilepsy involving a prefrontal network is associated with antisocial personality. We hypothesize that the occurrence of frequent seizures in this region over a prolonged period produces functional damage leading to impaired prefrontal control of social behavior. This functional damage is reversible since successful epilepsy surgery markedly improved antisocial behavior in these patients. The results are in line with previous reports of impairment of social and moral behavior following ventromedial frontal lobe injury. [Copyright &y& Elsevier]

Abstract: Adolescence is the transition from childhood to adulthood, with onset marked by puberty and the offset by relative independence from parents. Across species, it is a time of incredible change that carries increased risks and rewards. The ability of the individual to respond adequately to the mental, physical and emotional stresses of life during this time is a function of both their early environment and their present state. In this article, we focus on the effects that acute threat and chronic stress have on the brain and behavior in humans and rodents. First, we highlight developmental changes in frontolimbic function as healthy individuals transition into and out of adolescence. Second, we examine genetic factors that may enhance susceptibility to stress in one individual over another using translation from genetic mouse models to human neuroimaging. Third, we examine how the timing and nature of stress varies in its impact on brain and behavior. These findings are discussed in the context of implications for adolescent mental health and illness. [Copyright &y& Elsevier]