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Frank Krueger

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11 papers

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YNIMG Journal 2026 Journal Article

Compensatory and impaired trust updating in mild cognitive impairment: Evidence from computational modeling and fMRI

Yiqi Chen
Hao He
Yiyang Ding
Wuhai Tao
Qing Guan
Frank Krueger

Trust dynamics, how trust is formed, maintained, and adjusted, are essential to interpersonal functioning. Older adults with mild cognitive impairment (MCI) are known to exhibit social vulnerabilities, but the dynamic updating of trust during social interactions and its neural basis in this population remain unclear. Here, we combined computational modeling with task-based functional magnetic resonance imaging (fMRI) to investigate trust updating in 39 older adults with MCI (mean age = 67.8 years) compared to 45 normal healthy controls (NHC, mean age = 67.2 years). At the behavioral level, MCI participants showed slower trust reduction, larger prediction errors (PE), lower learning rates, and greater interference when interacting with non-cooperative partners, while responding similarly to cooperative ones compared to NHC. At the neural level, fMRI analyses revealed that, relative to the NHC group, MCI participants exhibited compensatory recruitment of central executive and default mode network regions during cooperative interactions. Conversely, during non-cooperative interactions, the MCI group showed reduced activation in social and executive cognition-related regions compared to controls. Critically, PE-modulated psychophysiological interaction analyses revealed diminished functional connectivity between the superior frontal gyrus and temporoparietal junction under non-cooperative conditions in the MCI group. Our findings suggest that while older adults with MCI can recruit compensatory neural resources during supportive interactions, they struggle to adaptively update trust when facing adverse social contexts. This impaired updating may underlie their heightened susceptibility to social exploitation and declining interpersonal functioning.

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YNIMG Journal 2026 Journal Article

Neural signatures of context-dependent trust: How strategic interaction and social value orientation shape prosocial decisions

Yan Wu
Davood Bayat
Fatemeh Zahra Shahraki Pour
Frank Krueger

Trust is a cornerstone of human cooperation, yet it unfolds differently depending on who we interact with and under what circumstances. Understanding how the brain integrates social traits and contextual demands is key to explaining why we sometimes choose to trust-and sometimes refrain. Although prior studies have identified neural regions involved in trust, it remains unclear how dispositional factors, such as Social Value Orientation (SVO), interact with the strategic context of the decision. Few experiments have jointly manipulated both partner characteristics and game structure, limiting our understanding of how context-dependent trust is represented in the brain. This study examined how partner SVO and game context jointly shape trust behavior and its neural correlates. Thirty-one adults completed a multi-game fMRI paradigm, acting as trustors in the Trust Game (TG), which involves reciprocity, and the Tripled Dictator Game (TDG), assessing altruism. Partner SVOs ranged from aggressive to altruistic. Behaviorally, participants transferred more with prosocial partners, particularly in the TG, and this tendency was strongest among individuals who were themselves more prosocial, indicating that personal dispositions amplify sensitivity to cooperative partners in strategic contexts. Neurally, activity in the precuneus/posterior cingulate cortex increased with higher amount sent during the TG, and regions involved in social cognition, such as the right angular gyrus, reflected how the brain distinguishes cooperative from selfish partners depending on whether trust requires reciprocity. In conclusion, strategic context dynamically modulates both the behavioral expression and neural representation of trust, showing how social preferences and situational demands jointly guide prosocial decision-making.

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YNIMG Journal 2024 Journal Article

Connectome-based prediction of decreased trust propensity in older adults with mild cognitive impairment: A resting-state functional magnetic resonance imaging study

Yiqi Chen
Hao He
Yiyang Ding
Wuhai Tao
Qing Guan
Frank Krueger

Trust propensity (TP) relies more on social than economic rationality to transform the perceived probability of betrayal into positive reciprocity expectations in older adults with normal cognition. While deficits in social rationality have been observed in older adults with mild cognitive impairment (MCI), there is limited research on TP and its associated resting-state functional connectivity (RSFC) mechanisms in this population. To measure TP and related psychological functions (affect, motivation, executive cognition, and social cognition), MCI (n = 42) and normal healthy control (NHC, n = 115) groups completed a one-shot trust game and additional assessments of related psychological functions. RSFC associated with TP was analyzed using connectome-based predictive modeling (CPM) and lesion simulations. Our behavioral results showed that the MCI group trusted less (i.e., had lower TP) than the NHC group, with lower TP associated with higher sensitivity to the probability of betrayal in the MCI group. In the MCI group, only negative CPM models (RSFC negatively correlated with TP) significantly predicted TP, with a high salience network (SN) contribution. In contrast, in the NHC group, positive CPM models (RSFC positively correlated with TP) significantly predicted TP, with a high contribution from the default mode network (DMN). In addition, the total network strength of the NHC-specific positive network was lower in the MCI group than in the NHC group. Our findings demonstrated a decrease in TP in the MCI group compared to the NHC group, which is associated with deficits in social rationality (social cognition, associated with DMN) and increased sensitivity to betrayal (affect, associated with SN) in a trust dilemma. In conclusion, our study contributes to understanding MCI-related alterations in trust and their underlying neural mechanisms.

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YNIMG Journal 2021 Journal Article

The neural signatures of social hierarchy-related learning and interaction: A coordinate- and connectivity-based meta-analysis

Siying Li
Frank Krueger
Julia A. Camilleri
Simon B. Eickhoff
Chen Qu

Numerous neuroimaging studies have investigated the neural mechanisms of two mutually independent yet closely related cognitive processes aiding humans to navigate complex societies: social hierarchy-related learning (SH-RL) and social hierarchy-related interaction (SH-RI). To integrate these heterogeneous results into a more fine-grained and reliable characterization of the neural basis of social hierarchy, we combined coordinate-based meta-analyses with connectivity and functional decoding analyses to understand the underlying neuropsychological mechanism of SH-RL and SH-RI. We identified the anterior insula and temporoparietal junction (dominance detection), medial prefrontal cortex (information updating and computation), and intraparietal sulcus region, amygdala, and hippocampus (social hierarchy representation) as consistent activated brain regions for SH-RL, but the striatum, amygdala, and hippocampus associated with reward processing for SH-RI. Our results provide an overview of the neural architecture of the neuropsychological processes underlying how we understand, and interact within, social hierarchy.

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YNICL Journal 2019 Journal Article

Brain activity mediators of PTSD symptom reduction during real-time fMRI amygdala neurofeedback emotional training

Masaya Misaki
Raquel Phillips
Vadim Zotev
Chung-Ki Wong
Brent E. Wurfel
Frank Krueger
Matthew Feldner
Jerzy Bodurka

Self-regulation of brain activation with real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) is emerging as a promising treatment for psychiatric disorders. The association between the regulation and symptom reduction, however, has not been consistent, and the mechanisms underlying the symptom reduction remain poorly understood. The present study investigated brain activity mediators of the amygdala rtfMRI-nf training effect on combat veterans' PTSD symptom reduction. The training was designed to increase a neurofeedback signal either from the left amygdala (experimental group; EG) or from a control region not implicated in emotion regulation (control group; CG) during positive autobiographical memory recall. We employed a structural equation model mapping analysis to identify brain regions that mediated the effects of the rtfMRI-nf training on PTSD symptoms. Symptom reduction was mediated by low activation in the dorsomedial prefrontal cortex (DMPFC) and the middle cingulate cortex. There was a trend toward less activation in these regions for the EG compared to the CG. Low activation in the precuneus, the right superior parietal, the right insula, and the right cerebellum also mediated symptom reduction while their effects were moderated by the neurofeedback signal; a higher signal was linked to less effect on symptom reduction. This moderation was not specific to the EG. MDD comorbidity was associated with high DMPFC activation, which resulted in less effective regulation of the feedback signal. These results indicated that symptom reduction due to the neurofeedback training was not specifically mediated by the neurofeedback target activity, but broad regions were involved in the process.

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YNICL Journal 2018 Journal Article

Connectome-wide investigation of altered resting-state functional connectivity in war veterans with and without posttraumatic stress disorder

Masaya Misaki
Raquel Phillips
Vadim Zotev
Chung-Ki Wong
Brent E. Wurfel
Frank Krueger
Matthew Feldner
Jerzy Bodurka

Altered resting-state functional connectivity in posttraumatic stress disorder (PTSD) suggests neuropathology of the disorder. While seed-based fMRI connectivity analysis is often used for the studies, such analysis requires defining a seed location a priori, which restricts search scope and could bias findings toward presupposed areas. Recently, a comprehensive exploratory voxel-wise connectivity analysis, the connectome-wide association approach, has been introduced using multivariate distance matrix regression (MDMR) for resting-state functional connectivity analysis. The current study performed a connectome-wide investigation of resting-state functional connectivity for war veterans with and without PTSD compared to non-trauma-exposed healthy controls using MDMR. Thirty-five male combat veterans with PTSD (unmedicated), 18 male combat veterans without PTSD (veterans control, VC), and 28 age-matched non-trauma-exposed healthy males (NC) participated in a resting-state fMRI scan. MDMR analysis was used to identify between-groups differences in regions with altered connectivity. The identified regions were used as a seed for post-hoc functional connectivity analysis. The analysis revealed that PTSD patients had hypoconnectivity between the left lateral prefrontal regions and the salience network regions as well as hypoconnectivity between the parahippocampal gyrus and the visual cortex areas. Connectivity between the ventromedial prefrontal cortex and the middle frontal gyrus and between the parahippocampal gyrus and the anterior insula were negatively correlated with PTSD symptom severity. VC subjects also had altered functional connectivity compared to NC, including increased connectivity between the posterior insula and several brain regions and decreased connectivity between the precuneus region and several other brain areas. The decreased connectivity between the lateral prefrontal regions and the salience network regions in PTSD was consistent with previous reports that indicated lowered emotion-regulation function in these regions. The decreased connectivity between the parahippocampal gyrus and visual cortex supported the dual representation theory of PTSD, which suggests dissociation between sensory and contextual memory representations in PTSD. The theory also supposes that the precuneus is a region that triggers retrieval of sensory memory of traumatic events. The decreased connectivity at the precuneus for VC might be associated with suppressing such a process.

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YNICL Journal 2018 Journal Article

Real-time fMRI amygdala neurofeedback positive emotional training normalized resting-state functional connectivity in combat veterans with and without PTSD: a connectome-wide investigation

Masaya Misaki
Raquel Phillips
Vadim Zotev
Chung-Ki Wong
Brent E. Wurfel
Frank Krueger
Matthew Feldner
Jerzy Bodurka

Self-regulation of brain activation using real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) is an emerging approach for treating mood and anxiety disorders. The effect of neurofeedback training on resting-state functional connectivity warrants investigation as changes in spontaneous brain activation could reflect the association between sustained symptom relief and brain alteration. We investigated the effect of amygdala-focused rtfMRI-nf training on resting-state functional connectivity in combat veterans with and without posttraumatic stress disorder (PTSD) who were trained to increase a feedback signal reflecting left amygdala activity while recalling positive autobiographical memories (Zotev et al., 2018). The analysis was performed in three stages: i) first, we investigated the connectivity in the left amygdala region; ii) next, we focused on the abnormal resting-state functional connectivity identified in our previous analysis of this data (Misaki et al., 2018); and iii) finally, we performed a novel data-driven longitudinal connectome-wide analysis. We introduced a longitudinal multivariate distance matrix regression (MDMR) analysis to comprehensively examine neurofeedback training effects beyond those associated with abnormal baseline connectivity. These comprehensive exploratory analyses suggested that abnormal resting-state connectivity for combat veterans with PTSD was partly normalized after the training. This included hypoconnectivities between the left amygdala and the left ventrolateral prefrontal cortex (vlPFC) and between the supplementary motor area (SMA) and the dorsal anterior cingulate cortex (dACC). The increase of SMA-dACC connectivity was associated with PTSD symptom reduction. Longitudinal MDMR analysis found a connectivity change between the precuneus and the left superior frontal cortex. The connectivity increase was associated with a decrease in hyperarousal symptoms. The abnormal connectivity for combat veterans without PTSD - such as hypoconnectivity in the precuneus with a superior frontal region and hyperconnectivity in the posterior insula with several regions - could also be normalized after the training. These results suggested that the rtfMRI-nf training effect was not limited to a feedback target region and symptom relief could be mediated by brain modulation in several regions other than in a feedback target area. While further confirmatory research is needed, the results may provide valuable insight into treatment effects on the whole brain resting-state connectivity.

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YNICL Journal 2018 Journal Article

Real-time fMRI neurofeedback training of the amygdala activity with simultaneous EEG in veterans with combat-related PTSD

Vadim Zotev
Raquel Phillips
Masaya Misaki
Chung Ki Wong
Brent E. Wurfel
Frank Krueger
Matthew Feldner
Jerzy Bodurka

Posttraumatic stress disorder (PTSD) is a chronic and disabling neuropsychiatric disorder characterized by insufficient top-down modulation of the amygdala activity by the prefrontal cortex. Real-time fMRI neurofeedback (rtfMRI-nf) is an emerging method with potential for modifying the amygdala-prefrontal interactions. We report the first controlled emotion self-regulation study in veterans with combat-related PTSD utilizing rtfMRI-nf of the amygdala activity. PTSD patients in the experimental group (EG, n = 20) learned to upregulate blood‑oxygenation-level-dependent (BOLD) activity of the left amygdala (LA) using the rtfMRI-nf during a happy emotion induction task. PTSD patients in the control group (CG, n = 11) were provided with a sham rtfMRI-nf. The study included three rtfMRI-nf training sessions, and EEG recordings were performed simultaneously with fMRI. PTSD severity was assessed before and after the training using the Clinician-Administered PTSD Scale (CAPS). The EG participants who completed the study showed a significant reduction in total CAPS ratings, including significant reductions in avoidance and hyperarousal symptoms. They also exhibited a significant reduction in comorbid depression severity. Overall, 80% of the EG participants demonstrated clinically meaningful reductions in CAPS ratings, compared to 38% in the CG. No significant difference in the CAPS rating changes was observed between the groups. During the first rtfMRI-nf session, functional connectivity of the LA with the orbitofrontal cortex (OFC) and the dorsolateral prefrontal cortex (DLPFC) was progressively enhanced, and this enhancement significantly and positively correlated with the initial CAPS ratings. Left-lateralized enhancement in upper alpha EEG coherence also exhibited a significant positive correlation with the initial CAPS. Reduction in PTSD severity between the first and last rtfMRI-nf sessions significantly correlated with enhancement in functional connectivity between the LA and the left DLPFC. Our results demonstrate that the rtfMRI-nf of the amygdala activity has the potential to correct the amygdala-prefrontal functional connectivity deficiencies specific to PTSD.

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YNICL Journal 2018 Journal Article

Tracking resting state connectivity dynamics in veterans with PTSD

Han Yuan
Raquel Phillips
Chung Ki Wong
Vadim Zotev
Masaya Misaki
Brent Wurfel
Frank Krueger
Matthew Feldner

Posttraumatic stress disorder (PTSD) is a trauma- and stressor-related disorder that may emerge following a traumatic event. Neuroimaging studies have shown evidence of functional abnormality in many brain regions and systems affected by PTSD. Exaggerated threat detection associated with abnormalities in the salience network, as well as abnormalities in executive functions involved in emotions regulations, self-referencing and context evaluation processing are broadly reported in PTSD. Here we aimed to investigate the behavior and dynamic properties of fMRI resting state networks in combat-related PTSD, using a novel, multimodal imaging approach. Simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) was employed to measure neurobiological brain activity among 36 veterans with combat-related PTSD and 20 combat-exposed veterans without PTSD. Based on the recently established method of measuring temporal-independent EEG microstates, we developed a novel strategy to integrate EEG and fMRI by quantifying the fast temporal dynamics associated with the resting state networks. We found distinctive occurrence rates of microstates associated with the dorsal default mode network and salience networks in the PTSD group as compared with control. Furthermore, the occurrence rate of the microstate for the dorsal default mode network was positively correlated with PTSD severity, whereas the occurrence rate of the microstate for the anterior salience network was negatively correlated with hedonic tone reported by participants with PTSD. Our findings reveal a novel aspect of abnormal network dynamics in combat-related PTSD and contribute to a better understanding of the pathophysiology of the disorder. Simultaneous EEG and fMRI will be a valuable tool in continuing to study the neurobiology underlying PTSD.

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YNIMG Journal 2012 Journal Article

Normative database of judgment of complexity task with functional near infrared spectroscopy—Application for TBI

Franck Amyot
Trelawny Zimmermann
Jason Riley
Jana M. Kainerstorfer
Victor Chernomordik
Eric Mooshagian
Laleh Najafizadeh
Frank Krueger

The ability to assess frontal lobe function in a rapid, objective, and standardized way, without the need for expertise in cognitive test administration might be particularly helpful in mild traumatic brain injury (TBI), where objective measures are needed. Functional near infrared spectroscopy (fNIRS) is a reliable technique to noninvasively measure local hemodynamic changes in brain areas near the head surface. In this paper, we are combining fNIRS and frameless stereotaxy which allowed us to co-register the functional images with previously acquired anatomical MRI volumes. In our experiment, the subjects were asked to perform a task, evaluating the complexity of daily life activities, previously shown with fMRI to activate areas of the anterior frontal cortex. We reconstructed averaged oxyhemoglobin and deoxyhemoglobin data from 20 healthy subjects in a spherical coordinate. The spherical coordinate is a natural representation of surface brain activation projection. Our results show surface activation projected from the medial frontopolar cortex which is consistent with previous fMRI results. With this original technique, we will construct a normative database for a simple cognitive test which can be useful in evaluating cognitive disability such as mild traumatic brain injury.

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YNIMG Journal 2011 Journal Article

Impairment of prosocial sentiments is associated with frontopolar and septal damage in frontotemporal dementia

Jorge Moll
Roland Zahn
Ricardo de Oliveira-Souza
Ivanei E. Bramati
Frank Krueger
Bernardo Tura
Alyson L. Cavanagh
Jordan Grafman

Poets and philosophers have long acknowledged moral sentiments as key motivators of human social behavior. Prosocial sentiments, which include guilt, pity and embarrassment, enable us to care about others and to be concerned about our mistakes. Functional imaging studies have implicated frontopolar, ventromedial frontal and basal forebrain regions in the experience of prosocial sentiments. Patients with lesions of the frontopolar and ventromedial frontal areas were observed to behave inappropriately and less prosocially, which could be attributed to a generalized emotional blunting. Direct experimental evidence for brain regions distinctively associated with moral sentiment impairments is lacking, however. We investigated this issue in patients with the behavioral variant of frontotemporal dementia, a disorder in which early and selective impairments of social conduct are consistently observed. Using a novel moral sentiment task, we show that the degree of impairment of prosocial sentiments is associated with the degree of damage to frontopolar cortex and septal area, as assessed with 18-Fluoro-Deoxy-Glucose-Positron Emission Tomography, an established measure of neurodegenerative damage. This effect was dissociable from impairment of other-critical feelings (anger and disgust), which was in turn associated with dorsomedial prefrontal and amygdala dysfunction. Our findings suggest a critical role of the frontopolar cortex and septal region in enabling prosocial sentiments, a fundamental component of moral conscience.

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