Core-Shell Fe3O4@C Nanoparticles as Highly Effective T2 Magnetic Resonance Imaging Contrast Agents: In Vitro and In Vivo Studies.

Magnetite nanoparticles (Fe3O4 NPs) have been intensively investigated because of their potential biomedical applications due to their high saturation magnetization. In this study, core-shell Fe3O4@C NPs (core = Fe3O4 NPs and shell = amorphous carbons, davg = 35.1 nm) were synthesized in an aqueous solution. Carbon coating terminated with hydrophilic -OH and -COOH groups imparted excellent biocompatibility and hydrophilicity to the NPs, making them suitable for biomedical applications. The Fe3O4@C NPs exhibited ideal relaxometric properties for T2 magnetic resonance imaging (MRI) contrast agents (i.e., high transverse and negligible longitudinal water proton spin relaxivities), making them exclusively induce only T2 relaxation. Their T2 MRI performance as contrast agents was confirmed in vivo by measuring T2 MR images in mice before and after intravenous injection.

Neural mechanisms of acceptance-commitment therapy for obsessive-compulsive disorder: a resting-state and task-based fMRI study.

BACKGROUND: There is growing evidence for the use of acceptance-commitment therapy (ACT) for the treatment of obsessive-compulsive disorder (OCD). However, few fully implemented ACT have been conducted on the neural mechanisms underlying its effect on OCD. Thus, this study aimed to elucidate the neural correlates of ACT in patients with OCD using task-based and resting-state functional magnetic resonance imaging (fMRI). METHODS: Patients with OCD were randomly assigned to the ACT (n = 21) or the wait-list control group (n = 21). An 8-week group-format ACT program was provided to the ACT group. All participants underwent an fMRI scan and psychological measurements before and after 8 weeks. RESULTS: Patients with OCD showed significantly increased activation in the bilateral insula and superior temporal gyri (STG), induced by the thought-action fusion task after ACT intervention. Further psycho-physiological interaction analyses with these regions as seeds revealed that the left insular-left inferior frontal gyrus (IFG) connectivity was strengthened in the ACT group after treatment. Increased resting-state functional connectivity was also found in the posterior cingulate cortex (PCC), precuneus, and lingual gyrus after ACT intervention Most of these regions showed significant correlations with ACT process measures while only the right insula was correlated with the obsessive-compulsive symptom measure. CONCLUSIONS: These findings suggest that the therapeutic effect of ACT on OCD may involve the salience and interoception processes (i.e. insula), multisensory integration (i.e. STG), language (i.e. IFG), and self-referential processes (i.e. PCC and precuneus). These areas or their interactions could be important for understanding how ACT works psychologically.

Connectome-based predictive models using resting-state fMRI for studying brain aging.

Changes in the brain with age can provide useful information regarding an individual's chronological age. studies have suggested that functional connectomes identified via resting-state functional magnetic resonance imaging (fMRI) could be a powerful feature for predicting an individual's age. We applied connectome-based predictive modeling (CPM) to investigate individual chronological age predictions via resting-state fMRI using open-source datasets. The significant feature for age prediction was confirmed in 168 subjects from the Southwest University Adult Lifespan Dataset. The higher contributing nodes for age production included a positive connection from the left inferior parietal sulcus and a negative connection from the right middle temporal sulcus. On the network scale, the subcortical-cerebellum network was the dominant network for age prediction. The generalizability of CPM, which was constructed using the identified features, was verified by applying this model to independent datasets that were randomly selected from the Autism Brain Imaging Data Exchange I and the Open Access Series of Imaging Studies 3. CPM via resting-state fMRI is a potential robust predictor for determining an individual's chronological age from changes in the brain.

Aberrant functional connectivity of neural circuits associated with thought-action fusion in patients with obsessive-compulsive disorder.

BACKGROUND: Cognitive theories of obsessive-compulsive disorder (OCD) stress the importance of dysfunctional beliefs in the development and maintenance of the disorder. However, a neurobiological understanding of these cognitive models, including thought-action fusion (TAF), is surprisingly lacking. Thus, this functional magnetic resonance imaging study aimed to investigate whether altered functional connectivity (FC) is associated with the TAF paradigm in OCD patients. METHODS: Forty-one OCD patients and 47 healthy controls (HCs) participated in a functional magnetic resonance imaging study using a TAF task, in which they were asked to read the name of a close or a neutral person in association with positive and negative statements. RESULTS: The conventional TAF condition (negative statements/close person) induced significant FC between the regions of interest (ROIs) identified using multivoxel pattern analysis and the visual association areas, default mode network subregions, affective processing, and several subcortical regions in both groups. Notably, sparser FC was observed in OCD patients. Further analysis confined to the cortico-striato-thalamo-cortical (CSTC) and affective networks demonstrated that OCD patients exhibited reduced ROI FC with affective regions and greater ROI FC with CSTC components in the TAF condition compared to HCs. Within the OCD patients, middle cingulate cortex-insula FC was correlated with TAF and responsibility scores. CONCLUSIONS: Our TAF paradigm revealed altered context-dependent engagement of the CSTC and affective networks in OCD patients. These findings suggest that the neurobiology of cognitive models corresponds to current neuroanatomical models of OCD. Further, they elucidate the underlying neurobiological mechanisms of OCD at the circuit-based level.

Impact of fractional amplitude of low-frequency fluctuations in motor- and sensory-related brain networks on spinal cord injury severity.

Spinal cord injury (SCI) can cause motor, sensory, and autonomic dysfunctions and may affect the cerebral functions. However, the mechanisms of plastic changes in the brain according to SCI severity remain poorly understood. Therefore, in the current study, we compared the brain activity of the entire neural network according to severity of SCI using fractional amplitude of low-frequency fluctuations (fALFF) analysis in resting-state functional magnetic resonance imaging (rs-fMRI). A total of 59 participants were included, consisting of 19 patients with complete SCI, 20 patients with incomplete SCI, and 20 healthy individuals. Their motor and sensory functions were evaluated. The rs-fMRI data of low-frequency fluctuations were analyzed based on fALFF. Differences in fALFF values among complete-SCI patients, incomplete-SCI patients, and healthy controls were assessed using ANOVA. Then post hoc analysis and two-sample t-tests were conducted to assess the differences between the three groups. Pearson correlation analyses were used to determine correlations between clinical measures and the z-score of the fALFF in the SCI groups. Patients with SCI (complete and incomplete) showed lower fALFF values in the superior medial frontal gyrus than the healthy controls, and were associated with poor motor and sensory function (p < .05). Higher fALFF values were observed in the putamen and thalamus, and were negatively associated with motor and sensory function (p < .05). In conclusion, alterations in the neural activity of the motor- and sensory-related networks of the brain were observed in complete-SCI and incomplete-SCI patients. Moreover, plastic changes in these brain regions were associated with motor and sensory function.

The Neural Correlates of Positive Versus Negative Thought-action Fusion in Healthy Young Adults.

OBJECTIVE: Thought-action fusion (TAF), one of the most-studied dysfunctional beliefs in obsessive-compulsive disorder, represents an individual's belief that his/her thoughts directly influence events. TAF belief types are divided into personal thoughts relating to positive (positive TAF) and negative outcomes (negative TAF). However, the neural mechanisms underlying both aspects of the TAF response remain elusive. METHODS: This functional magnetic resonance imaging study aimed to investigate the neural circuits related to positive and negative TAF and their relationships with psychological measures. Thirty-one healthy male volunteers participated in a modified TAF task wherein they were asked to read the name of a close person embedded in positive statements (PS) or negative statements (NS). RESULTS: Conjunction analysis revealed activation of the fusiform and lingual gyri, midcingulate and superior medial frontal gyri, inferior orbitofrontal gyrus, and temporoparietal junction. The NS > PS comparison showed additional activation in the precuneus and medial prefrontal cortex, superior frontal gyrus, insula, globus pallidus, thalamus, and midbrain. Precuneus activity was associated with the TAF score among these areas. Moreover, activity in the inferior orbitofrontal gyrus, insula, superior, middle and medial frontal gyri, globus pallidus, inferior parietal lobule, and precuneus was associated with dimensional obsessive-compulsive scores. In contrast, the PS > NS comparison revealed no significant activation. CONCLUSION: These results suggest that negative TAF, relative to positive TAF, recruits additional regions for self-referential processing, salience, and habitual responding, which may contribute to the activation of the belief that a negative thought increases the probability of that negative outcome.

Reconciliation of Two Cognitive Models in Obsessive-Compulsive Disorder: An fMRI Study.

OBJECTIVE: Although cognitive models of obsessive-compulsive disorder (OCD) fall into two categories: cognitive deficit models and dysfunctional belief models, these approaches have their own ways and have hardly been reconciled. Therefore, this study aimed to investigate the potential relationships between cognitive deficit (using the Wisconsin Card Sorting Task, WCST) and dysfunctional belief (measured by scales of dysfunctional beliefs) mediated by neural activity in OCD patients. METHODS: Thirty OCD patients and 30 healthy participants performed the WCST condition and a baseline MATCH condition during the 3T-functional magnetic resonance imaging (fMRI) acquisition. RESULTS: Engagement of additional frontoparietal networks with poorer performance of WCST was found during the fMRI scan in OCD patients. Selected regions of interest from activated regions have positive relationships with dysfunctional beliefs and with the unacceptable thoughts symptom dimension in the OCD group. CONCLUSION: Findings suggest that alteration in frontoparietal networks related to cognitive deficits can be associated with dysfunctional beliefs while performing conventional neurocognitive tasks and this association with dysfunctional beliefs may be pronounced in the unacceptable thoughts domain-dominant OCD patients.

Improved white matter integrity after contralateral seventh cervical nerve transfer measured by tractographic representation.

Contralateral C7 (CC7) nerve transfer surgery was shown to significantly improve the spasticity condition and the motor function of paralyzed arms. However, the involvement of the white matter tract in the recovery process is not well established. We here investigated the possible biologic explanation for this phenomenon. A 62-year-old female patient, who suffered from spastic hemiparesis due to intracranial hemorrhage, underwent CC7 transfer surgery 13 years after the initial stroke event. Six months after the surgery, the patient's Modified Ashworth Scale and Fugl-Myere score improved, even though no specific rehabilitation programs were applied. Diffusion tensor imaging (DTI) was performed before and 6 months after the surgery. The pre-surgery DTI showed both ipsilesional and contralesional CST from the cerebral peduncles to the cortices. After surgery, however, only the contralesional CST was observed. In conclusion, functional alterations of the brain white matter tract after CC7 nerve transfer surgery possibly provided a neurophysiological substrate for ameliorating the spasticity and improving the motor function in a spastic hemiplegia patient.

Synthesis, Characterizations, and 9.4 Tesla T2 MR Images of Polyacrylic Acid-Coated Terbium(III) and Holmium(III) Oxide Nanoparticles.

Polyacrylic acid (PAA)-coated lanthanide oxide (Ln2O3) nanoparticles (NPs) (Ln = Tb and Ho) with high colloidal stability and good biocompatibility were synthesized, characterized, and investigated as a new class of negative (T2) magnetic resonance imaging (MRI) contrast agents at high MR fields. Their r2 values were appreciable at a 3.0 T MR field and higher at a 9.4 T MR field, whereas their r1 values were negligible at all MR fields, indicating their exclusive induction of T2 relaxations with negligible induction of T1 relaxations. Their effectiveness as T2 MRI contrast agents at high MR fields was confirmed from strong negative contrast enhancements in in vivo T2 MR images at a 9.4 T MR field after intravenous administration into mice tails.

Chitosan Oligosaccharide Lactate-Coated Ultrasmall Gadolinium Oxide Nanoparticles: Synthesis, In Vitro Cytotoxicity, and Relaxometric Properties.

In this study, hydrophilic and biocompatible chitosan oligosaccharide lactate (COL)-coated ultra-small gadolinium oxide nanoparticles (NPs) were synthesized through a one-pot polyol method and characterized by various experimental techniques. The In Vitro cellular cytotoxicity assay indicated that the COL-coated gadolinium oxide NPs were non-toxic up to 500 µM Gd. In addition, their water proton spin relaxivities (i.e., r1 and r2) were estimated to be 13.0 and 27.0 s-1mM-1, respectively, which are higher than those of commercial magnetic resonance imaging (MRI) contrast agents. The application potential of the solution sample as a T1 MRI contrast agent was demonstrated In Vitro by measuring map images in which dose-dependent contrast enhancements were observed.

Believing is seeing: an fMRI study of thought-action fusion in healthy male adults.

Thought-action fusion (TAF) is a tendency of individuals to establish causal relations between their own thoughts and external reality. TAF can lead to maladaptive behaviors typically observed in obsessional thoughts. However, neural mechanisms underlying TAF are still unknown. In this study, 38 healthy men were informed that MR signals were able to detect thoughts of the word 'apple' and that this recognition could result in the administration of electrical shocks to a person outside the scanner. During MR acquisition, they were asked to suppress or not suppress the thought of 'apple' while sham electrical shocks were or were not administered to the other person. The main effect of the sham administration of electrical shock to another person was shown in the bilateral lingual gyri, fusiform gyri, and middle occipital cortices (FDR corrected p < 0.05). Also, fusiform gyrus, lingual gyrus, and middle occipital cortex activity correlated with scores of guilty feeling only when participants consciously tried to think of apple as less as possible. Our study demonstrates that visual association areas may play primary roles in TAF. The simple belief and visual imagery that one's thought may lead to someone's injury activated visual areas of the brain where, in turn, brain activity is associated with feelings of guilt.

Effects of emotional maltreatment on semantic network activity during cognitive reappraisal.

Maltreatment experiences alter brain development associated with emotion processing, and dysregulation of emotion may trigger mental health problems in maltreated people. However, studies revealing alterations in brain networks during cognitive reappraisal in victims of maltreatment are strikingly insufficient. In this study, 27 healthy subjects were recruited. The maltreatment experiences and positive reappraisal abilities were measured using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) and Cognitive Emotion Regulation Questionnaire (CERQ), respectively. A cognitive reappraisal task using the International Affective Picture System (IAPS) was designed for functional magnetic resonance imaging (fMRI) experiments. Cognitive reappraisal induced more activities in the bilateral inferior parietal lobes and bilateral middle temporal gyri compared to the condition of "look" (false discovery rate (FDR) corrected p < 0.05). Furthermore, the left inferior parietal lobe and right middle temporal gyrus functionally interacted with components of the default mode network, including the precuneus and the posterior cingulate cortex. In residual analyses after controlling for age and depressive symptoms, the bilateral inferior parietal and middle temporal activities exhibited positive correlations with cognitive reappraisal abilities (all ps < 0.05), and emotional maltreatment experiences were negatively correlated with the left inferior parietal cortex, bilateral middle temporal cortex activities, and left inferior parietal lobe-posterior cingulate cortex connectivity (all ps < 0.05). We found that semantic networks were significant to cognitive reappraisal, especially reinterpretation, and negative effects of emotional maltreatment experiences on semantic network activities.

Hydrophilic Biocompatible Poly(Acrylic Acid-co-Maleic Acid) Polymer as a Surface-Coating Ligand of Ultrasmall Gd2O3 Nanoparticles to Obtain a High r1 Value and T1 MR Images.

The water proton spin relaxivity, colloidal stability, and biocompatibility of nanoparticle-based magnetic resonance imaging (MRI) contrast agents depend on the surface-coating ligands. Here, poly(acrylic acid-co-maleic acid) (PAAMA) (Mw = ~3000 amu) is explored as a surface-coating ligand of ultrasmall gadolinium oxide (Gd2O3) nanoparticles. Owing to the numerous carboxylic groups in PAAMA, which allow its strong conjugation with the nanoparticle surfaces and the attraction of abundant water molecules to the nanoparticles, the synthesized PAAMA-coated ultrasmall Gd2O3 nanoparticles (davg = 1.8 nm and aavg = 9.0 nm) exhibit excellent colloidal stability, extremely low cellular toxicity, and a high longitudinal water proton spin relaxivity (r1) of 40.6 s-1mM-1 (r2/r1 = 1.56, where r2 = transverse water proton spin relaxivity), which is approximately 10 times higher than those of commercial molecular contrast agents. The effectiveness of PAAMA-coated ultrasmall Gd2O3 nanoparticles as a T1 MRI contrast agent is confirmed by the high positive contrast enhancements of the in vivo T1 MR images at the 3.0 T MR field.

Effects of Cognitive Training in Mild Cognitive Impairmentmeasured by Resting State Functional Imaging.

Mild cognitive impairment (MCI) is defined as an intermediate state of cognitive alteration between normal aging and dementia. In this study, we performed a functional network connectivity analysis using resting-state functional magnetic resonance imaging to investigate the association between changes in functional connectivity in the brain and the improvement in cognitive abilities after cognitive training. A computerized cognitive training program was used to improve the abilities of fifteen participants with MCI. The cognitive training program (Comcog), which consists of three weekly sessions totaling 90 min, was conducted with all participants over six weeks. The cognitive abilities before (pre-Comcog) and after (post-Comcog) the cognitive training process were measured using a neurocognitive function test. After the Comcog, the participants enhanced their visual and verbal memories, attention, and visuo-motor coordination. The functional connectivity between cingulo-opercular (CON) and default mode (DMN) showed significant improvements after Comcog training. Therefore, our study suggests that cognitive training may improve the cognitive abilities of participants. This improvement was associated with an increase in the functional connectivity between DMN and CON. The increase in functional connectivity after cognitive training was specifically associated with overall cognitive functions, including executive, memory, decision-making, and motivational functions.

New Class of Efficient T2 Magnetic Resonance Imaging Contrast Agent: Carbon-Coated Paramagnetic Dysprosium Oxide Nanoparticles.

Nanoparticles are considered potential candidates for a new class of magnetic resonance imaging (MRI) contrast agents. Negative MRI contrast agents require high magnetic moments. However, if nanoparticles can exclusively induce transverse water proton spin relaxation with negligible induction of longitudinal water proton spin relaxation, they may provide negative contrast MR images despite having low magnetic moments, thus acting as an efficient T2 MRI contrast agent. In this study, carbon-coated paramagnetic dysprosium oxide (DYO@C) nanoparticles (core = DYO = DyxOy; shell = carbon) were synthesized to explore their potential as an efficient T2 MRI contrast agent at 3.0 T MR field. Since the core DYO nanoparticles have an appreciable (but not high) magnetic moment that arises from fast 4f-electrons of Dy(III) (6H15/2), the DYO@C nanoparticles exhibited an appreciable transverse water proton spin relaxivity (r2) with a negligible longitudinal water proton spin relaxivity (r1). Consequently, they acted as a very efficient T2 MRI contrast agent, as proven from negative contrast enhancements seen in the in vivo T2 MR images.

Alterations in power spectral density in motor- and pain-related networks on neuropathic pain after spinal cord injury.

BACKGROUND: The mechanisms by which mobility function and neuropathic pain are mutually influenced by supraspinal plasticity in motor- and pain-related brain networks following spinal cord injury (SCI) remains poorly understood. OBJECTIVE: To determine cortical and subcortical resting-state network alterations using power spectral density (PSD) analysis and investigate the relationships between these intrinsic alterations and mobility function and neuropathic pain following SCI. METHODS: A total of 41 patients with incomplete SCI and 33 healthy controls were included. The degree of mobility and balance function and severity of neuropathic pain and depressive mood were evaluated. The resting-state functional magnetic resonance imaging data of low-frequency fluctuations were analyzed based on PSD. Differences in PSD values between patients with SCI and controls were assessed using the two-sample t-test (false discovery rate-corrected P < 0.05). The relationship between PSD values and mobility function and pain intensity was assessed using Pearson's correlation coefficient adjusted for the severity of depressive mood. RESULTS: Compared with healthy controls, lower PSD values in supplementary motor and medial prefrontal areas (the anterior cingulate cortex, ventral medial prefrontal cortex, and superior orbito-prefrontal cortex) were associated with greater pain severity and poorer postural balance and mobility (P < 0.05) in patients with SCI, whereas higher PSD values in the primary motor cortex, premotor cortex, thalamus, and periaqueductal gray were associated with greater pain severity and poorer postural balance and mobility (P < 0.05). CONCLUSIONS: Cortical and subcortical plastic alterations in intrinsic motor- and pain-related networks were observed in patients with SCI and were simultaneously associated with neuropathic pain intensity and degree of mobility function.

Interhemispheric Functional Connectivity in the Primary Motor Cortex Assessed by Resting-State Functional Magnetic Resonance Imaging Aids Long-Term Recovery Prediction among Subacute Stroke Patients with Severe Hand Weakness.

This study aimed to evaluate the usefulness of interhemispheric functional connectivity (FC) as a predictor of motor recovery in severe hand impairment and to determine the cutoff FC level as a clinically useful parameter. Patients with stroke (n = 22; age, 59.9 ± 13.7 years) who presented with unilateral severe upper-limb paresis and were confirmed to elicit no motor-evoked potential responses were selected. FC was measured using resting-state functional magnetic resonance imaging (rsfMRI) scans at 1 month from stroke onset. The good recovery group showed a higher FC value than the poor recovery group (p = 0.034). In contrast, there was no statistical difference in FC value between the good recovery and healthy control groups (p = 0.182). Additionally, the healthy control group showed a higher FC value than that shown by the poor recovery group (p = 0.0002). Good and poor recovery were determined based on Brunnstrom stage of upper-limb function at 6 months as the standard, and receiver operating characteristic curve indicated that a cutoff score of 0.013 had the greatest prognostic ability. In conclusion, interhemispheric FC measurement using rsfMRI scans may provide useful clinical information for predicting hand motor recovery during stroke rehabilitation.

In Vivo Positive Magnetic Resonance Imaging Applications of Poly(methyl vinyl ether-alt-maleic acid)-coated Ultra-small Paramagnetic Gadolinium Oxide Nanoparticles.

The study of ultra-small paramagnetic gadolinium oxide (Gd2O3) nanoparticles (NPs) as in vivo positive (T1) magnetic resonance imaging (MRI) contrast agents is one of the most attractive fields in nanomedicine. The performance of the Gd2O3 NP imaging agents depends on the surface-coating materials. In this study, poly(methyl vinyl ether-alt-maleic acid) (PMVEMA) was used as a surface-coating polymer. The PMVEMA-coated paramagnetic ultra-small Gd2O3 NPs with an average particle diameter of 1.9 nm were synthesized using the one-pot polyol method. They exhibited excellent colloidal stability in water and good biocompatibility. They also showed a very high longitudinal water proton spin relaxivity (r1) value of 36.2 s-1mM-1 (r2/r1 = 2.0; r2 = transverse water proton spin relaxivity) under a 3.0 tesla MR field which is approximately 10 times higher than the r1 values of commercial molecular contrast agents. High positive contrast enhancements were observed in in vivo T1 MR images after intravenous administration of the NP solution sample, demonstrating its potential as a T1 MRI contrast agent.

Effects of a Mixed Reality-based Cognitive Training System Compared to a Conventional Computer-assisted Cognitive Training System on Mild Cognitive Impairment: A Pilot Study.

BACKGROUND: Mixed reality (MR) technology, which combines the best features of augmented reality and virtual reality, has recently emerged as a promising tool in cognitive rehabilitation therapy. OBJECTIVE: To investigate the effectiveness of an MR-based cognitive training system for individuals with mild cognitive impairment (MCI). METHODS: Twenty-one individuals aged 65 years and older who had been diagnosed with MCI were recruited for this study and were divided into two groups. Participants in the MR group (n=10, aged 70.5±4.2 years) received 30 minutes of training 3 times a week for 6 weeks using a newly developed MR-based cognitive training system. Participants in the control group (n=11, aged 72.6±5.3 years) received the same amount of training using a conventional computer-assisted cognitive training system. Both groups took the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K) both before and after intervention. To determine the effect of the intervention on cognitive function, we compared the difference in each group's CERAD-K scores. RESULTS: There was a statistically significant interaction between intervention (MR group vs control group) and time (before vs after intervention) as assessed by the Constructional Recall Test. The individuals with MCI who participated in the MR training showed significantly improved performance in visuospatial working memory compared with the individuals with MCI who participated in the conventional training. CONCLUSION: An MR-based cognitive training system can be used as a cognitive training tool to improve visuospatial working memory in individuals with MCI.

The neural correlates of thought-action fusion in healthy adults: A functional magnetic resonance imaging study.

BACKGROUND: Thought-action fusion (TAF) represents an individual's belief that a thought is like action. Inflated TAF has been considered a central mechanism for developing obsessive thoughts. However, the neural mechanisms underlying TAF are yet unknown. METHODS: We recruited 32 healthy men to participate in a functional magnetic resonance imaging (fMRI) study. Whereas inside the 3T MRI scanner, participants were asked to read negative statements describing the expectation of bad events associated with close persons (CPs condition) or neutral persons (NPs condition). They also completed the assessment of TAF and obsessive-compulsive (OC) symptoms. RESULTS: Both CP and NP conditions commonly activated the lingual gyrus, caudate nucleus, precuneus, and several areas of the frontal cortex. Importantly, many of these regions were positively correlated with measures of OC symptoms, especially for the CP condition. The CP condition showed higher activation in the insula and temporal gyrus than the NP condition. In contrast, the NP condition evoked higher activation in regions associated with mentalizing, such as the medial prefrontal cortex and dorsal anterior cingulate cortex than the CP condition. CONCLUSIONS: We introduced and validated a TAF-induction paradigm suitable for fMRI studies and characterized the neural circuits engaged during this paradigm. Further studies using this task may help us to better understand how dysfunctions in TAF neural processing may contribute to psychiatric conditions such as obsessive-compulsive disorder.