Social Cognition and Functional Connectivity in Early and Chronic Schizophrenia.

BACKGROUND: Individuals with schizophrenia (SZ) experience impairments in social cognition that contribute to poor functional outcomes. However, mechanisms of social cognitive dysfunction in SZ remain poorly understood, which impedes the design of novel interventions to improve outcomes. This pre-registered project (https://doi.org/10.17605/OSF.IO/JH5FC) examines the representation of social cognition in the brain's functional architecture across early and chronic SZ. METHODS: The study contains two parts: a confirmatory and an exploratory portion. In the confirmatory portion, we identified resting-state connectivity disruptions evident in early and chronic SZ. We performed a connectivity analysis using regions associated with social cognitive dysfunction in early and chronic SZ to test whether aberrant connectivity observed in chronic SZ (N=47; HC=52) was also present in early SZ (N=71, HC=47). In the exploratory portion, we assessed the out-of-sample generalizability and precision of predictive models of social cognition. We used machine learning to predict social cognition and established generalizability with out-of-sample testing and confound control. RESULTS: Results reveal decreases between left inferior frontal gyrus and intraparietal sulcus in early and chronic SZ, which are significantly associated with social and general cognition and global functioning in chronic SZ and with general cognition and global functioning in early SZ. Predictive modeling reveals the importance of out-of-sample evaluation and confound control. CONCLUSION: This work provides insights into the functional architecture in early and chronic SZ and suggests that IFG-IPS connectivity could be a prognostic biomarker of social impairments and a target for future interventions (e.g. neuromodulation) focused on improved social functioning.

Transcranial photobiomodulation on the left inferior frontal gyrus enhances Mandarin Chinese L1 and L2 complex sentence processing performances.

This study investigated the causal enhancing effect of transcranial photobiomodulation (tPBM) over the left inferior frontal gyrus (LIFG) on syntactically complex Mandarin Chinese first language (L1) and second language (L2) sentence processing performances. Two (L1 and L2) groups of participants (thirty per group) were recruited to receive the double-blind, sham-controlled tPBM intervention via LIFG, followed by the sentence processing, the verbal working memory (WM), and the visual WM tasks. Results revealed a consistent pattern for both groups: (a) tPBM enhanced sentence processing performance but not verbal WM for linear processing of unstructured sequences and visual WM performances; (b) Participants with lower sentence processing performances under sham tPBM benefited more from active tPBM. Taken together, the current study substantiated that tPBM enhanced L1 and L2 sentence processing, and would serve as a promising and cost-effective noninvasive brain stimulation (NIBS) tool for future applications on upregulating the human language faculty.

Heroes and villains: opposing narrative roles engage neural synchronization in the inferior frontal gyrus.

Neuroscientific studies have highlighted the role of the default mode network (DMN) in processing narrative information. Here, we examined whether the neural synchronization of the DMN tracked the appearances of protagonists and antagonists when viewing highly engaging, socially rich audiovisual narratives. Using inter-subject correlation analysis on two independent, publicly available movie-watching fMRI datasets, we computed whole-brain neural synchronization during the appearance of the protagonists and antagonists. Results showed that the inferior frontal gyrus (IFG) had higher ISC values during the appearance of the protagonists than the antagonists. Importantly, these findings were generalized in both datasets. We discuss the results in the context of information integration and emotional empathy, which are relevant to functions of the IFG. Our study presents generalizable evidence that the IFG show distinctive synchronization patterns due to differences in narrative roles.

The impact of the left inferior frontal gyrus on fear extinction: A transcranial direct current stimulation study.

INTRODUCTION: Fear extinction is a fundamental component of exposure-based therapies for anxiety-related disorders. The renewal of fear in a different context after extinction highlights the importance of contextual factors. In this study, we aimed to investigate the causal role of the left inferior frontal gyrus (LiFG) in the context-dependency of fear extinction learning via administration of transcranial direct current stimulation (tDCS) over this area. METHODS: 180 healthy subjects were assigned to 9 groups: 3 tDCS conditions (anodal, cathodal, and sham) × 3 context combinations (AAA, ABA, and ABB). The fear conditioning/extinction task was conducted over three consecutive days: acquisition, extinction learning, and extinction recall. tDCS (2 mA, 10min) was administered during the extinction learning phase over the LiFG via a 4-electrode montage. Skin conductance response (SCR) data and self-report assessments were collected. RESULTS: During the extinction learning phase, groups with excitability-enhancing anodal tDCS showed a significantly higher fear response to the threat cues compared to cathodal and sham stimulation conditions, irrespective of contextual factors. This effect was stable until the extinction recall phase. Additionally, excitability-reducing cathodal tDCS caused a significant decrease of the response difference between the threat and safety cues during the extinction recall phase. The self-report assessments showed no significant differences between the conditions throughout the experiment. CONCLUSION: Independent of the context, excitability enhancement of the LiFG did impair fear extinction, and led to preservation of fear memory. In contrast, excitability reduction of this area enhanced fear extinction retention. These findings imply that the LiFG plays a role in the fear extinction network, which seems to be however context-independent.

The role of frontal cortex in novel-word learning and consolidation: Evidence from focal transcranial direct current stimulation.

Previous studies have demonstrated that conventional transcranial direct current stimulation (tDCS) can enhance novel-word learning. However, because of the widespread current that is induced by these setups and lack of appropriate control conditions, little is known about the underlying neural mechanisms. In the present double-blinded and sham-tDCS controlled study, we investigated for the first time if regionally precise focal tDCS targeting two key nodes of the novel-word learning network at different time points would result in regionally and temporally distinct effects. 156 participants completed a contextual novel-word-learning paradigm and learning success was probed immediately after the acquisition period and 30-min later. Participants were randomly assigned to six stimulation conditions: Active tDCS (1.5 mA) was administered to left inferior frontal (IFG) or middle temporal gyrus (MTG), either during acquisition or delayed recall. Control groups received sham-tDCS either during acquisition or delayed recall (50% IFG/MTG). Data were analyzed with a generalized linear mixed model with a binomial link function in a Bayesian framework. Our results showed that frontal tDCS selectively increased accuracy gains from immediate to delayed recall, irrespective of timing of the stimulation. There was no evidence for beneficial effects of middle temporal gyrus tDCS. Our findings confirm that IFG tDCS can enhance novel-word learning in a regionally, but not timing specific way. Tentatively, this may be explained by enhancement of semantic selection processes resulting in more effective consolidation and/or retrieval. Future studies using longer time intervals between assessments are required to clarify the potential contribution of neurophysiological after-effects of IFG tDCS administered during acquisition to enhanced consolidation.

Cortical modulations before lower limb motor blocks are associated with freezing of gait in Parkinson's disease: an EEG source localization study.

BACKGROUND: Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD) characterized by paroxysmal episodes in which patients are unable to step forward. A research priority is identifying cortical changes before freezing in PD-FOG. METHODS: We tested 19 patients with PD who had been assessed for FOG (n=14 with FOG and 5 without FOG). While seated, patients stepped bilaterally on pedals to progress forward through a virtual hallway while 64-channel EEG was recorded. We assessed cortical activities before and during lower limb motor blocks (LLMB), defined as a break in rhythmic pedaling, and stops, defined as movement cessation following an auditory stop cue. This task was selected because LLMB correlates with FOG severity in PD and allows recording of high-quality EEG. Patients were tested after overnight withdrawal from dopaminergic medications ("off" state) and in the "on" medications state. EEG source activities were evaluated using individual MRI and standardized low resolution brain electromagnetic tomography (sLORETA). Functional connectivity was evaluated by phase lag index between seeds and pre-defined cortical regions of interest. RESULTS: EEG source activities for LLMB vs. cued stops localized to right posterior parietal area (Brodmann area 39), lateral premotor area (Brodmann area 6), and inferior frontal gyrus (Brodmann area 47). In these areas, PD-FOG (n=14) increased alpha rhythms (8-12 Hz) before LLMB vs. typical stepping, whereas PD without FOG (n=5) decreased alpha power. Alpha rhythms were linearly correlated with LLMB severity, and the relationship became an inverted U-shape when assessing alpha rhythms as a function of percent time in LLMB in the "off" medication state. Right inferior frontal gyrus and supplementary motor area connectivity was observed before LLMB in the beta band (13-30 Hz). This same pattern of connectivity was seen before stops. Dopaminergic medication improved FOG and led to less alpha synchronization and increased functional connections between frontal and parietal areas. CONCLUSIONS: Right inferior parietofrontal structures are implicated in PD-FOG. The predominant changes were in the alpha rhythm, which increased before LLMB and with LLMB severity. Similar connectivity was observed for LLMB and stops between the right inferior frontal gyrus and supplementary motor area, suggesting that FOG may be a form of "unintended stopping." These findings may inform approaches to neurorehabilitation of PD-FOG.

Transcutaneous auricular vagus nerve stimulation improves anxiety symptoms and cortical activity during verbal fluency task in Parkinson's disease with anxiety.

OBJECTIVE: To investigate the effect of 20/4Hz transcutaneous auricular vagus nerve stimulation (taVNS) on anxiety symptoms in Parkinson's disease (PD) and the potential neural mechanism. METHODS: In the current randomized, double-blind, sham-controlled trial, 30 PD patients with anxiety (PD-A), 30 PD patients without anxiety (PD-nA), and 30 healthy controls (HCs) were enrolled. PD-A patients were randomly (1:1) allotted to real taVNS stimulation group (RS) or sham stimulation group (SS) to explore the efficacy of a two-week treatment of taVNS to promote anxiety recovery. Simultaneously, all participants were measured activation in the bilateral prefrontal cortex during verbal fluency task (VFT) using functional near-infrared spectroscopy. RESULTS: PD-A patients showed significantly decreased oxyhemoglobin in the left triangle part of the inferior frontal gyrus (IFG) during VFT, which was negatively related to the severity of anxiety symptoms. After two-week treatment of taVNS, the interaction of group and time had significant effect on HAMA scores (F = 18.476, p < 0.001, η2 = 0.398). In RS group, compared with baseline, HAMA scores decreased significantly in the post-treatment and follow-up condition (both p < 0.001). Meanwhile, in RS group, HAMA scores were lower than those in SS group in the post-treatment and follow-up condition (p = 0.006, <0.001, respectively). Furthermore, the 20/4Hz taVNS remarkably ameliorated anxiety symptoms in PD patients, directly correlated with the increased activation of the left triangle part of the IFG during VFT in RS group. CONCLUSION: Our results depicted that taVNS could ameliorate the anxiety symptoms of PD-A patients and regulated the function of the left triangle part of the IFG.

Continuous Theta-Burst Stimulation on the Left Posterior Inferior Frontal Gyrus Perturbs Complex Syntactic Processing Stability in Mandarin Chinese.

The structure of human language is inherently hierarchical. The left posterior inferior frontal gyrus (LpIFG) is proposed to be a core region for constructing syntactic hierarchies. However, it remains unclear whether LpIFG plays a causal role in syntactic processing in Mandarin Chinese and whether its contribution depends on syntactic complexity, working memory, or both. We addressed these questions by applying inhibitory continuous theta-burst stimulation (cTBS) over LpIFG. Thirty-two participants processed sentences containing embedded relative clauses (i.e., complex syntactic processing), syntactically simpler coordinated sentences (i.e., simple syntactic processing), and non-hierarchical word lists (i.e., word list processing) after receiving real or sham cTBS. We found that cTBS significantly increased the coefficient of variation, a representative index of processing stability, in complex syntactic processing (esp., when subject relative clause was embedded) but not in the other two conditions. No significant changes in d' and reaction time were detected in these conditions. The findings suggest that (a) inhibitory effect of cTBS on the LpIFG might be prominent in perturbing the complex syntactic processing stability but subtle in altering the processing quality; and (b) the causal role of the LpIFG seems to be specific for syntactic processing rather than working memory capacity, further evidencing their separability in LpIFG. Collectively, these results support the notion of the LpIFG as a core region for complex syntactic processing across languages.

Neurobiological Effects of Transcranial Direct Current Stimulation over the Inferior Frontal Gyrus: A Systematic Review on Cognitive Enhancement in Healthy and Neurological Adults.

The neurobiological effects of transcranial direct current stimulation (tDCS) have still not been unequivocally clarified. Some studies have suggested that the application of tDCS over the inferior frontal gyrus (IFG) enhances different aspects of cognition in healthy and neurological individuals, exerting neural changes over the target area and its neural surroundings. In this systematic review, randomized sham-controlled trials in healthy and neurological adults were selected through a database search to explore whether tDCS over the IFG combined with cognitive training modulates functional connectivity or neural changes. Twenty studies were finally included, among which twelve measured tDCS effects through functional magnetic resonance (fMRI), two through functional near-infrared spectroscopy (fNIRS), and six through electroencephalography (EEG). Due to the high heterogeneity observed across studies, data were qualitatively described and compared to assess reliability. Overall, studies that combined fMRI and tDCS showed widespread changes in functional connectivity at both local and distant brain regions. The findings also suggested that tDCS may also modulate electrophysiological changes underlying the targeted area. However, these outcomes were not always accompanied by corresponding significant behavioral results. This work raises the question concerning the general efficacy of tDCS, the implications of which extend to the steadily increasing tDCS literature.

Brain alterations in individuals with exercise dependence: A multimodal neuroimaging investigation.

Background: Exercise dependence (ED) is characterised by behavioural and psychological symptoms that resemble those of substance use disorders. However, it remains inconclusive whether ED is accompanied by similar brain alterations as seen in substance use disorders. Therefore, we investigated brain alterations in individuals with ED and inactive control participants. Methods: In this cross-sectional neuroimaging investigation, 29 individuals with ED as assessed with the Exercise Dependence Scale (EDS) and 28 inactive control participants (max one hour exercising per week) underwent structural and functional resting-state magnetic resonance imaging (MRI). Group differences were explored using voxel-based morphometry and functional connectivity analyses. Analyses were restricted to the striatum, amygdala, and inferior frontal gyrus (IFG). Exploratory analyses tested whether relationships between brain structure and function were differently related to EDS subscales among groups. Results: No structural differences were found between the two groups. However, right IFG and bilateral putamen volumes were differently related to the EDS subscales "time" and "tolerance", respectively, between the two groups. Resting-state functional connectivity was increased from right IFG to right superior parietal lobule in individuals with ED compared to inactive control participants. Furthermore, functional connectivity of the angular gyrus to the left IFG and bilateral caudate showed divergent relationships to the EDS subscale "tolerance" among groups. Discussion: The findings suggest that ED may be accompanied by alterations in cognition-related brain structures, but also functional changes that may drive compulsive habitual behaviour. Further prospective studies are needed to disentangle beneficial and detrimental brain effects of ED.

The role of pre-supplementary motor cortex in action control with emotional stimuli: A repetitive transcranial magnetic stimulation study.

Swiftly halting ongoing motor actions is essential to react to unforeseen and potentially perilous circumstances. However, the neural bases subtending the complex interplay between emotions and motor control have been scarcely investigated. Here, we used an emotional stop signal task (SST) to investigate whether specific neural circuits engaged by action suppression are differently modulated by emotional signals with respect to neutral ones. Participants performed an SST before and after the administration of one session of repetitive transcranial magnetic stimulation (rTMS) over the pre-supplementary motor cortex (pre-SMA), the right inferior frontal gyrus (rIFG), and the left primary motor cortex (lM1). Results show that rTMS over the pre-SMA improved the ability to inhibit prepotent action (i.e., better action control) when emotional stimuli were presented. In contrast, action control in a neutral context was fostered by rTMS over the rIFG. No changes were observed after lM1 stimulation. Intriguingly, individuals with higher impulsivity traits exhibited enhanced motor control when facing neutral stimuli following rIFG stimulation. These results further our understanding of the interplay between emotions and motor functions, shedding light on the selective modulation of neural pathways underpinning these processes.

Negation and social avoidance in language recruits the right inferior frontal gyrus: a tDCS study.

Introduction: In the process of comprehension, linguistic negation induces inhibition of negated scenarios. Numerous studies have highlighted the role of the right Inferior Frontal Gyrus (rIFG) - a key component of the inhibitory network - in negation processing. Social avoidance can be linguistically portrayed using attitudinal verbs such as "exclude" vs. "include", which inherently carry negative connotations. Consequently, we hypothesize that the interplay between explicit negation and the implicit negativity of avoidance verbs can be modulated via transcranial direct current stimulation (tDCS) targeting the rIFG. Methods: In our study, sixty-four participants read approach/avoidance sentences, which were either affirmative or negative, such as "Anne included (did not include) meat in her diet" vs. "Anne excluded (did not exclude) meat in her diet". This reading task followed a 20-minute tDCS session. The sentences were sequentially displayed, and at 1500 ms post-sentence, a verb was shown - either the one previously mentioned or its semantic alternative counterpart (e.g., included vs. excluded). Results: Findings revealed that anodal stimulation intensifies the inhibitory impact of negation during sentence comprehension. Under anodal conditions, negative sentences led to extended reading times for the mentioned verbs compared to their affirmative counterparts, suggesting an increased inhibitory effect on the verb. Furthermore, in avoidance sentences, anodal stimulation resulted in reduced reading times for alternative verbs (e.g. "included") in negative sentences compared to alternative verbs (e.g. "excluded") in negated approach sentences. Discussion: As "avoidance" is semantically equivalent to "non-approach", the inhibitory effect of negation is primarily applied to the implicit negation: NOT EXCLUDED = NOT→NOT (INCLUDED), which consequently activates the representation of the alternative verb making it more available. We further discuss these findings in light of the rIFG's pivotal role in processing attitudinal verbs and linguistic negation. This discussion is framed within the overarching context of the two-step model of negation processing, highlighting its significance in the realm of social communication.

Neural mechanisms underlying improved new-word learning with high-density transcranial direct current stimulation.

Neurobehavioral studies have provided evidence for the effectiveness of anodal tDCS on language production, by stimulation of the left Inferior Frontal Gyrus (IFG) or of left Temporo-Parietal Junction (TPJ). However, tDCS is currently not used in clinical practice outside of trials, because behavioral effects have been inconsistent and underlying neural effects unclear. Here, we propose to elucidate the neural correlates of verb and noun learning and to determine if they can be modulated with anodal high-definition (HD) tDCS stimulation. Thirty-six neurotypical participants were randomly allocated to anodal HD-tDCS over either the left IFG, the left TPJ, or sham stimulation. On day one, participants performed a naming task (pre-test). On day two, participants underwent a new-word learning task with rare nouns and verbs concurrently to HD-tDCS for 20 min. The third day consisted of a post-test of naming performance. EEG was recorded at rest and during naming on each day. Verb learning was significantly facilitated by left IFG stimulation. HD-tDCS over the left IFG enhanced functional connectivity between the left IFG and TPJ and this correlated with improved learning. HD-tDCS over the left TPJ enabled stronger local activation of the stimulated area (as indexed by greater alpha and beta-band power decrease) during naming, but this did not translate into better learning. Thus, tDCS can induce local activation or modulation of network interactions. Only the enhancement of network interactions, but not the increase in local activation, leads to robust improvement of word learning. This emphasizes the need to develop new neuromodulation methods influencing network interactions. Our study suggests that this may be achieved through behavioral activation of one area and concomitant activation of another area with HD-tDCS.

Baseline functional connectivity predicts who will benefit from neuromodulation: evidence from primary progressive aphasia.

Background: Identifying the characteristics of individuals who demonstrate response to an intervention allows us to predict who is most likely to benefit from certain interventions. Prediction is challenging in rare and heterogeneous diseases, such as primary progressive aphasia (PPA), that have varying clinical manifestations. We aimed to determine the characteristics of those who will benefit most from transcranial direct current stimulation (tDCS) of the left inferior frontal gyrus (IFG) using a novel heterogeneity and group identification analysis. Methods: We compared the predictive ability of demographic and clinical patient characteristics (e.g., PPA variant and disease progression, baseline language performance) vs. functional connectivity alone (from resting-state fMRI) in the same cohort. Results: Functional connectivity alone had the highest predictive value for outcomes, explaining 62% and 75% of tDCS effect of variance in generalization (semantic fluency) and in the trained outcome of the clinical trial (written naming), contrasted with <15% predicted by clinical characteristics, including baseline language performance. Patients with higher baseline functional connectivity between the left IFG (opercularis and triangularis), and between the middle temporal pole and posterior superior temporal gyrus, were most likely to benefit from tDCS. Conclusions: We show the importance of a baseline 7-minute functional connectivity scan in predicting tDCS outcomes, and point towards a precision medicine approach in neuromodulation studies. The study has important implications for clinical trials and practice, providing a statistical method that addresses heterogeneity in patient populations and allowing accurate prediction and enrollment of those who will most likely benefit from specific interventions.

Right prefrontal activation associated with deviations from expected lipstick texture assessed with functional near-infrared spectroscopy.

Introduction: There is a continuous consumer demand for ever superior cosmetic products. In marketing, various forms of sensory evaluation are used to measure the consumer experience and provide data with which to improve cosmetics. Nonetheless, potential downsides of existing approaches have led to the exploration of the use of neuroimaging methods, such as functional near-infrared spectroscopy (fNIRS), to provide addition information about consumers' experiences with cosmetics. The aim of the present study was to investigate the feasibility of a real-time brain-based product evaluation method which detects the incongruency between a product, in this case lipstick, and a consumer's expectations. Method: Thirty healthy, female, habitual lipstick users were asked to apply six different lipsticks varying in softness and to rate the softness of and their willingness to pay (WTP) for each lipstick. Cerebral hemodynamic responses in frontal areas were measured with fNIRS during lipstick application and analyzed using the general linear model (GLM). Incongruency scores between softness and expectation were calculated in order to understand how far removed each lipstick was from a participant's optimal softness preference. The correlation between brain activation (beta scores) during the application of each lipstick and the respective incongruency scores from each participant were acquired using semi-partial correlation analysis, controlling for the effects of WTP. Results: We revealed a significant intra-subject correlation between incongruency scores and activation in the right inferior frontal gyrus (IFG). This confirms that as the texture incongruency scores increased for the lipstick samples, activation in each individual's right IFG also increased. Conclusion: The correlation observed between incongruency perceived by participants and activation of the right IFG not only suggests that the right IFG may play an important role in detecting incongruity when there is a discrepancy between the perceived texture and the consumer's expectations but also that measuring activity in the IFG may provide a new objective measurement of the consumer experience, thus contributing to the development of superior cosmetics.

Changes in Resting-State Brain Activity After Cognitive Behavioral Therapy for Chronic Pain: A Magnetoencephalography Study.

Cognitive behavioral therapy (CBT) is believed to be an effective treatment for chronic pain due to its association with cognitive and emotional factors. Nevertheless, there is a paucity of magnetoencephalography (MEG) investigations elucidating its underlying mechanisms. This study investigated the neurophysiological effects of CBT employing MEG and analytical techniques. We administered resting-state MEG scans to 30 patients with chronic pain and 31 age-matched healthy controls. Patients engaged in a 12-session group CBT program. We conducted pretreatment (T1) and post-treatment (T2) MEG and clinical assessments. MEG data were examined within predefined regions of interest, guided by the authors' and others' prior magnetic resonance imaging studies. Initially, we selected regions displaying significant changes in power spectral density and multiscale entropy between patients at T1 and healthy controls. Then, we examined the changes within these regions after conducting CBT. Furthermore, we applied support vector machine analysis to MEG data to assess the potential for classifying treatment effects. We observed normalization of power in the gamma2 band (61-90 Hz) within the right inferior frontal gyrus (IFG) and multiscale entropy within the right dorsolateral prefrontal cortex (DLPFC) of patients with chronic pain after CBT. Notably, changes in pain intensity before and after CBT positively correlated with the alterations of multiscale entropy. Importantly, responders predicted by the support vector machine classifier had significantly higher treatment improvement rates than nonresponders. These findings underscore the pivotal role of the right IFG and DLPFC in ameliorating pain intensity through CBT. Further accumulation of evidence is essential for future applications. PERSPECTIVE: We conducted MEG scans on 30 patients with chronic pain before and after a CBT program, comparing results with 31 healthy individuals. There were CBT-related changes in the right IFG and DLPFC. These results highlight the importance of specific brain regions in pain reduction through CBT.

A modified neural circuit framework for semantic memory retrieval with implications for circuit modulation to treat verbal retrieval deficits.

Word finding difficulty is a frequent complaint in older age and disease states, but treatment options are lacking for such verbal retrieval deficits. Better understanding of the neurophysiological and neuroanatomical basis of verbal retrieval function may inform effective interventions. In this article, we review the current evidence of a neural retrieval circuit central to verbal production, including words and semantic memory, that involves the pre-supplementary motor area (pre-SMA), striatum (particularly caudate nucleus), and thalamus. We aim to offer a modified neural circuit framework expanded upon a memory retrieval model proposed in 2013 by Hart et al., as evidence from electrophysiological, functional brain imaging, and noninvasive electrical brain stimulation studies have provided additional pieces of information that converge on a shared neural circuit for retrieval of memory and words. We propose that both the left inferior frontal gyrus and fronto-polar regions should be included in the expanded circuit. All these regions have their respective functional roles during verbal retrieval, such as selection and inhibition during search, initiation and termination of search, maintenance of co-activation across cortical regions, as well as final activation of the retrieved information. We will also highlight the structural connectivity from and to the pre-SMA (e.g., frontal aslant tract and fronto-striatal tract) that facilitates communication between the regions within this circuit. Finally, we will discuss how this circuit and its correlated activity may be affected by disease states and how this circuit may serve as a novel target engagement for neuromodulatory treatment of verbal retrieval deficits.

Neural Correlates of Trait Impulsivity among Adult Healthy Individuals.

Objective: : Impulsivity can be observed in individuals with or without mental illness. The discovery of neural correlates responsible for trait impulsivity can therefore help to understand the severity of psychiatric symptoms, personality characteristics and social adjustment. In this study, we aimed to identify the gray matter substrates of trait impulsivity in healthy individuals. Methods: : Seventy-five healthy individuals were enrolled. At baseline, trait impulsivity was assessed using the Barratt Impulsiveness Scale (BIS) and all participants underwent T1-weighted magnetic resonance imaging scan. Beck Anxiety Inventory (BAI), World Health Organization Quality of Life (WHOQOL-BREF) and Connor-Davidson Resilience Scale (CD-RISC) were also assessed. Mean cortical thickness (CT) and the local gyrification index (LGI) were calculated to perform whole-brain vertex-wise correlation analysis, which were performed to investigate the relationship between BIS scores and CT or LGI in each brain region. We also revealed the relationship between brain regions and psychological measurements. Results: : Total BIS scores were significantly and negatively correlated with mean CT values in the left lateral occipital cortex (OC) and LGIs in the inferior frontal gyrus (IFG). Correlation analyses revealed that the lateral OC's mean CT values were negatively correlated with BAI scores and positively correlated with WHOQOL-BREF scores, while LGI in the IFG was positively correlated with CD-RISC scores. Conclusion: : Our study showed that trait impulsivity might be associated with the lateral OC and IFG in healthy individuals. Understanding the neural correlates of trait impulsivity could provide ways to expect high impulsivity, anxiety, and poor resilience in healthy adults.

Computational Synaptic Modeling of Pitch and Duration Mismatch Negativity in First-Episode Psychosis Reveals Selective Dysfunction of the N-Methyl-D-Aspartate Receptor.

Mismatch negativity (MMN) to pitch (pMMN) and to duration (dMMN) deviant stimuli is significantly more attenuated in long-term psychotic illness compared to first-episode psychosis (FEP). It was recently shown that source-modeling of magnetically recorded MMN increases the detection of left auditory cortex MMN deficits in FEP, and that computational circuit modeling of electrically recorded MMN also reveals left-hemisphere auditory cortex abnormalities. Computational modeling using dynamic causal modeling (DCM) can also be used to infer synaptic activity from EEG-based scalp recordings. We measured pMMN and dMMN with EEG from 26 FEP and 26 matched healthy controls (HCs) and used a DCM conductance-based neural mass model including α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, N-methyl-D-Aspartate (NMDA), and Gamma-aminobutyric acid receptors to identify any changes in effective connectivity and receptor rate constants in FEP. We modeled MMN sources in bilateral A1, superior temporal gyrus, and inferior frontal gyrus (IFG). No model parameters distinguished groups for pMMN. For dMMN, reduced NMDA receptor activity in right IFG in FEP was detected. This finding is in line with literature of prefrontal NMDA receptor hypofunction in chronic schizophrenia and suggests impaired NMDA-induced synaptic plasticity may be present at psychosis onset where scalp dMMN is only moderately reduced. To the best of our knowledge, this is the first report of impaired NMDA receptor activity in FEP found through computational modeling of dMMN and shows the potential of DCM to non-invasively reveal synaptic-level abnormalities that underly subtle functional auditory processing deficits in early psychosis.

Sex Differences in Response Inhibition-Related Neural Predictors of Posttraumatic Stress Disorder in Civilians With Recent Trauma.

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.