Cingulate Research Articles

Post-hospitalisation COVID-19 cognitive deficits at one year are global and associated with elevated brain injury markers and grey matter volume reduction.

The spectrum, pathophysiology, and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the one-year cognitive, serum biomarker, and neuroimaging findings from a prospective, national study of cognition in 351 COVID-19 patients who had required hospitalisation, compared to 2,927 normative matched controls. Cognitive deficits were global and associated with elevated brain injury markers, and reduced anterior cingulate cortex volume one year after COVID-19. The severity of the initial infective insult, post-acute psychiatric symptoms, and a history of encephalopathy were associated with greatest deficits. There was strong concordance between subjective and objective cognitive deficits. Longitudinal follow-up in 106 patients demonstrated a trend toward recovery. Together, these findings support the hypothesis that brain injury in moderate to severe COVID-19 may be immune-mediated, and should guide the development of therapeutic strategies.

Understanding Depression in Autism: The Role of Subjective Perception and Anterior Cingulate Cortex Volume.

The prevalence of depression is elevated in individuals with autism spectrum disorder (ASD) compared to the general population, yet the reasons for this disparity remain unclear. While social deficits central to ASD may contribute to depression, it is uncertain whether social interaction behavior themselves or individuals' introspection about their social behaviors are more impactful. Although the anterior cingulate cortex (ACC) and amygdala are frequently implicated in ASD, depression, and social functioning, it is unknown if these regions explain differences between ASD adults with and without co-occurring depression. The present study contrasted observed vs. subjective perception of autism symptoms and social performances assessed with both standardized measures and a lab task, in 65 sex-balanced (52.24% male) autistic young adults. We also quantified ACC and amygdala volume with 7-Tesla structural neuroimaging to examine correlations with depression and social functioning. We found that ASD individuals with depression exhibited differences in subjective evaluations including heightened self-awareness of ASD symptoms, lower subjective satisfaction with social relations, and less perceived affiliation during the social interaction task, yet no differences in corresponding observed measures, compared to those without depression. Larger ACC volume was related to depression, greater self-awareness of ASD symptoms, and worse subjective satisfaction with social interactions. In contrast, amygdala volume, despite its association with clinician-rated ASD symptoms, was not related to depression. Due to the cross-sectional nature of our study, we cannot determine the directionality of the observed relationships. Additionally, we included only individuals with an IQ over 60 to ensure participants could complete the social task, which excluded many on the autism spectrum. We also utilized self-reported depression indices instead of clinically diagnosed depression, which may limit the comprehensiveness of the findings. Our approach highlights the unique role of subjective perception of autism symptoms and social interactions, beyond the observable manifestation of social interaction in ASD, in contributing to depression, with the ACC playing a crucial role. These findings imply possible heterogeneity of ASD concerning co-occurring depression. Using neuroimaging, we were able to demarcate depressive phenotypes co-occurring alongside autistic phenotypes.

Neuroplasticity of the white matter tracts underlying recovery of diarrhea-predominant irritable bowel syndrome following acupuncture treatment.

Irritable bowel syndrome (IBS) is a functional bowel disorder frequently associated with other pain syndromes and psychiatric conditions, including depression and anxiety. These abnormalities coincide with alterations in the brain's structure, particularly in the thalamus and cingulate system. Acupuncture has been demonstrated to be highly effective in treating IBS. However, it remains unclear how white matter (WM) tracts change after acupuncture treatment, and whether the neuroplasticity of these tracts can serve as a neural marker to assist in the development of novel treatments. In this study, we aim to answer these questions by investigating longitudinal changes in the WM of the thalamus and cingulate system in a group of diarrhea-predominant irritable bowel syndrome (IBS-D) patients before and after acupuncture treatment. We found that after acupuncture treatment, as IBS symptoms improved, there were significant changes in the microstructure of the right thalamus radiation (TR) (p < 0.05) and the right cingulum hippocampus (CH) (p < 0.05). At the same time, patients with reduced IBS symptom severity scores (SSSs) were associated with the change of the right CH (p = 0.015, r = -0.491), while reduced depressive conditions correlated with the change of the left TR (p = 0.019, r = 0.418). In addition, the consequences for the quality of life (QOL) showed a correlation with the right cingulum [cingulate cortex (CC)] (p = 0.012, r = 0.504) and left TR (p = 0.027, r = -0.397). Our study highlighted the potential implications of neuroplasticity in WM tracts for IBS. Furthermore, these findings suggested that the right CH, TR, and right CC can serve as potential "biomarkers" of IBS-D recovery under acupuncture treatments.

Altered static brain activity and functional connectivity after heat stroke.

This study aimed to investigate the alteration of brain function based on resting-state functional MRI in patients after heat stroke. This study included 10 cases of patients after heat stroke and 10 cases of healthy controls. Abnormal brain function was calculated using amplitude of low-frequency fluctuations (ALFF) and degree centrality analysis, as well as functional connectivity analysis based on regions of interest (ROI). Correlation analyses were performed to evaluate the association between brain function changes and clinical scales. Combining ALFF and degree centrality results, the decreased brain regions included the left cuneus and the right angular gyrus, while the increased brain regions included the right cerebellar_Crus1. Using the left cuneus with significant differences in ALFF and degree centrality as ROI, the functional connectivity results revealed decreased brain regions including bilateral lingual gyrus, bilateral postcentral cingulate gyrus, and left precentral gyrus. The degree centrality value of the right cerebellar_Crus1 was positively correlated with glasgow coma scale (GCS) scores ( r = 0.726, P = 0.027), and the functional connectivity value of the right posterior cingulate gyrus was positively correlated with GCS scores ( r = 0.717, P = 0.030). Heat stroke patients exhibit abnormal activity in multiple brain regions, which has important clinical significance for evaluating the severity of the disease.

Ventrolateral prefrontal cortex in macaques guides decisions in different learning contexts.

Flexibly adjusting our behavioral strategies based on the environmental context is critical to maximize rewards. Ventrolateral prefrontal cortex (vlPFC) has been implicated in both learning and decision-making for probabilistic rewards, although how context influences these processes remains unclear. We collected functional neuroimaging data while rhesus macaques performed a probabilistic learning task in two contexts: one with novel and another with familiar visual stimuli. We found that activity in vlPFC encoded rewards irrespective of the context but encoded behavioral strategies that depend on reward outcome (win-stay/lose-shift) preferentially in novel contexts. Functional connectivity between vlPFC and anterior cingulate cortex varied with behavioral strategy in novel learning blocks. By contrast, connectivity between vlPFC and mediodorsal thalamus was highest when subjects repeated a prior choice. Furthermore, pharmacological D2-receptor blockade altered behavioral strategies during learning and resting-state vlPFC activity. Taken together, our results suggest that multiple vlPFC-linked circuits contribute to adaptive decision-making in different contexts.

Disrupted functional connectivity of bilateral nucleus accumbens in major depressive disorder with and without melancholic features.

Our study aims to explore the differences in functional connectivity in the nucleus accumbens (NAc) between patients with melancholic depression and non-melancholic depression (NMD) and their relation to melancholic depression's pathogenesis. We recruited 60 melancholic depression, 58 NMD, and 80 healthy controls, all matched for gender, age, and education. Functional connectivity analysis focused on bilateral NAc as the region of interest, comparing it with the whole brain and correlating significant differences with clinical scores. Melancholic depression patients showed reduced functional connectivity between the left NAc and anterior brain regions, and between the right NAc and temporal and frontal areas, compared to healthy controls. In contrast, NMD patients displayed reduced functional connectivity only between the left NAc and the posterior cingulate cortex. Melancholic depression patients also exhibited increased functional connectivity between the right NAc and the middle frontal gyrus, unlike NMD patients. The findings suggest that melancholic depression patients exhibit unique NAc functional connectivity patterns, particularly with the default mode network and prefrontal areas, suggesting atypical reward-circuitry interactions. The right NAc's connection to the prefrontal gyrus may distinguish melancholic depression from NMD.

Real-Time fMRI Neurofeedback Training of Selective Attention in Older Adults.

Selective attention declines with age, due to age-related functional changes in dorsal anterior cingulate cortex (dACC). Real-time functional magnetic resonance imaging (rtfMRI) neurofeedback has been used in young adults to train volitional control of brain activity, including in dACC. For the first time, this study used rtfMRI neurofeedback to train 19 young and 27 older adults in volitional up- or down-regulation of bilateral dACC during a selective attention task. Older participants in the up-regulation condition (experimental group) showed greater reward points and dACC BOLD signal across training sessions, reflective of neurofeedback training success; and faster reaction time and better response accuracy, suggesting behavioral benefits on selective attention. These effects were not observed for older participants in the down-regulation condition (inverse condition control group), supporting specificity of volitional dACC up-regulation training in older adults. These effects were, unexpectedly, also not observed for young participants in the up-regulation condition (age control group), perhaps due to a lack of motivation to continue the training. These findings provide promising first evidence of functional plasticity in dACC in late life via rtfMRI neurofeedback up-regulation training, enhancing selective attention, and demonstrate proof of concept of rtfMRI neurofeedback training in cognitive aging.

Generalized Encoding of the Relative Subjective Value of Cognitive Effort in the Dorsal ACC.

Making choices about whether and when to engage cognitive effort are a common feature of everyday experience, with important consequences for academic, career, and health outcomes. Yet, despite their hypothesized importance, very little is understood about the underlying mechanisms that support this form of human cost-benefit decision-making. To investigate these mechanisms, we used the Cognitive Effort Discounting Paradigm (Cog-ED) during fMRI scanning to precisely quantify the neural encoding of varying cognitive effort demands relative to reward outcomes, within two distinct cognitive domains (working memory, speech comprehension). The findings provide strong evidence that the dorsal anterior cingulate cortex (dACC) plays a central and selective role in this decision-making process. Trial-by-trial modulations in dACC activation tracked the relative subjective value of the low-effort, low-reward option, with the strongest activity occurring when this was of greater value than the high-effort, high-reward option. In contrast, dACC activity was not modulated by decision difficulty, though such effects were found in other frontoparietal regions. Critically, dACC activity was also strongly correlated across the two decision-making task domains and further predicted subsequent choice behavior in both. Together, the results suggest that dACC activity modulation reflects a domain-general valuation comparison mechanism, which acts to bias participants away from decisions to engage in cognitive effort, when the perceived subjective costs of such engagement outweigh the reward-related benefits. These findings complement work in other cost domains and species by pointing to a clear role of the dACC in representing subjective value differences between choice options during cost-benefit decision-making.

Using deep learning and pretreatment EEG to predict response to sertraline, bupropion, and placebo

ObjectivePredicting an individual’s response to antidepressant medication remains one of the most challenging tasks in the treatment of major depressive disorder (MDD). Our objective was to use the large EMBARC study database to develop an electroencephalography (EEG)-based method to predict response to antidepressant treatment. MethodsPre-treatment EEG data were collected from study participants treated with either sertraline (N = 105), placebo (N = 119), or bupropion (N = 35). After preprocessing, the robust exact low-resolution electromagnetic tomography (ReLORETA) brain source localization method was used to reconstruct the source signals in 54 brain regions. Connectivity between regions was determined using symbolic transfer entropy (STE). A convolutional neural network (CNN) classified participants as responders or non-responders to each treatment. ResultsClassification accuracy was 91.0%, 95.4%, and 86.8% for sertraline, placebo, and bupropion, respectively. The most highly predictive features were connectivity between i) the anterior cingulate cortex and superior parietal lobule (alpha frequency), ii) the anterior cingulate cortex and orbitofrontal area (beta frequency), and iii) the orbitofrontal area and anterior cingulate cortex (gamma frequency). ConclusionCNN analysis of EEG connectivity may accurately predict response to sertraline, bupropion, and placebo. SignificanceThe suggested method may offer clinicians an accessible and cost-effective tool for speedy treatment and helps pharmaceutical firms to test new antidepressants efficiently.

Assessing social anhedonia in a transdiagnostic sample: Insights from a computational psychiatry lens.

Anhedonia, a reduced ability to experience positive affect and seek rewards, is present across many psychiatric disorders, notably among individuals who experienced trauma. Within the social domain, anhedonia manifests as an altered sense of belonging and social isolation and is associated with poorer clinical outcomes. Yet, mechanistic operationalizations of social anhedonia are lacking, limiting our understanding of the relationship between these mechanisms and affective symptoms. To address these questions, we developed a social reward exploration task which was administered to a transdiagnostic sample of trauma-exposed Veterans (N = 33) while they underwent functional magnetic resonance imaging. The goal was to maximize compliments from two unknown partners, as participants were told these partners selected compliments based on seeing their picture. A Bayesian reinforcement learning modeling approach was used to extract cognitive and neural markers of compliment (reward) exploration. To address these questions, we developed a social reward exploration task which was administered to a transdiagnostic sample of trauma-exposed Veterans (N = 33) while they underwent functional magnetic resonance imaging. The goal was to maximize compliments from two unknown partners, as participants were told these partners selected compliments based on seeing their picture. A Bayesian reinforcement learning modeling approach was used to extract cognitive and neural markers of compliment (reward) exploration. Higher social connectedness (β = 0.51; 95 % CI=[0.11,0.94]) and anxiety (β = 0.57; 95 % CI=[0.13,1.00]) were independently associated with more model-based choices of the partner they anticipated to be most complimenting. In the dorsal anterior cingulate cortex (ACC; z = 3.89, p .001) and left inferior parietal lobule (z = 3.96, p .001), neural responses to reward prediction errors (RPE) were more positive in response to compliment relative to non-compliment outcomes. Greater positive RPE ACC activation was associated with lower anxiety (β = −0.51; 95 % CI=[−0.99,−0.10]. Computational approaches to social reinforcement learning can help identify important neurocognitive differences in social reward sensitivity among individuals with complex affective profiles, such as trauma-exposed individuals. Understanding these differences may help develop new prediction and treatment tools for social anhedonia.

Here Comes Revenge: Peer Victimization Relates to Neural and Behavioral Responses to Social Exclusion.

The aim of this study was to examine whether repeated victimization relates to differential processing of social exclusion experiences. It was hypothesized that experiences of repeated victimization would modulate neural processing of social exclusion in the insula, anterior cingulate cortex, and lateral prefrontal cortex. Furthermore, we hypothesized that repeated victimization relates positively to intentions to punish excluders. Exploratively, associations between neural processing and intentions to punish others were examined. The sample consisted of children with known victimization in the past two years (n = 82 (behavioral) / n = 73 (fMRI), 49.4% girls, Mage = 10.6). The participants played Cyberball, an online ball-tossing game, which was manipulated so that in the first block participants were equally included and in the second block they were excluded from play. Victimization was not related to neural activation during social exclusion, although there were indications that victimization may be related to increased insula activation during explicit exclusion. Behaviorally, repeated victimization was related to more intention to punish excluders. Neural activation during social exclusion did not predict intentions to punish excluders, but results tentatively suggested that increased insula activation during social exclusion may be related to increased intentions to punish. Together, these results provide a replication of earlier Cyberball studies and point toward differential processing of social exclusion by children who are victimized.

Neural processing of audiovisual and painful analogue trauma and its relationship with subsequent audiovisual and pain intrusions

ABSTRACT Background: Posttraumatic stress disorder and medically unexplained pain frequently co-occur. While pain is common during traumatic events, the processing of pain during trauma and its relation to audiovisual and pain intrusions is poorly understood. Objective: Here we investigate neural activations during painful analogue trauma, focusing on areas that have been related to threat and pain processing, and how they predict intrusion formation. We also examine the moderating role of cumulative lifetime adversity. Methods: Sixty-five healthy women were assessed using functional magnetic resonance imaging. An analogue trauma was induced by an adaptation of the trauma-film paradigm extended by painful electrical stimulation in a 2 (film: aversive, neutral) x 2 (pain: pain, no-pain) design, followed by 7-day audiovisual and pain intrusion assessment using event-based ecological momentary assessment. Intrusions were fitted with Bayesian multilevel regression and a hurdle lognormal distribution. Results: Conjunction analysis confirmed a wide network including anterior insula (AI) and dorsal anterior cingulate cortex (dACC) being active both, during aversive films and pain. Pain resulted in activation in areas amongst posterior insula and deactivation in a network around ventromedial prefrontal cortex (VMPFC). Higher AI and dACC activity during aversive>neutral film predicted greater audiovisual intrusion probability over time and predicted greater audiovisual intrusion frequency particularly for participants with high lifetime adversity. Lower AI, dACC, hippocampus, and VMPFC activity during pain>no-pain predicted greater pain intrusion probability particularly for participants with high lifetime adversity. Weak regulatory VMPFC activation was associated with both increased audiovisual and pain intrusion frequency. Conclusions: Enhanced AI and dACC processing during aversive films, poor pain vs. no-pain discrimination in AI and dACC, as well as weak regulatory VMPFC processing may be driving factors for intrusion formation, particularly in combination with high lifetime adversity. Results shed light on a potential path for the etiology of PTSD and medically unexplained pain.

Immunomodulatory treatment may change functional and structural brain imaging in severe mental disorders

Neuroinflammation has been implicated in the pathophysiology of schizophrenia and obsessive-compulsive disorder (OCD) and deviations in brain structure and connectivity are seen in these disorders. Here, we explore the effects of a potent immunomodulatory treatment on neuroimaging. In a pilot study of rituximab treatment in schizophrenia and OCD, a subgroup (n = 13) underwent structural and functional magnetic resonance imaging before and 5 months after treatment, to study longitudinal changes in resting-state functional connectivity (rsFC) and voxel-based morphometry (VBM).A hypothesis-free exploratory whole-brain analysis was performed twice to assess changes in rsFC, using anterior cingulate cortex, anterior insula, posterior insula and nucleus accumbens as seed regions. There were significant interactions (diagnosis x time) in connectivity between right posterior insula and two clusters encompassing basal ganglia and anterior frontal pole, and between left anterior insula and a cluster in basal ganglia, where connectivity decreased in OCD and increased in schizophrenia. The increase of connectivity after rituximab, between left anterior insula and parts of cerebellum and lingual gyrus and between left posterior insula and parts of cerebellum, correlated with improved global psychosocial functioning according to the Personal and Social Performance Scale, especially in schizophrenia. VBM analysis identified two clusters with increased grey matter volumes (GMV) after rituximab, one in right insula overlapping one of the seed regions with significant rsFC changes. This pilot study implies that rituximab may influence both brain structure and connectivity and that GMV changes and rsFC changes are regionally associated.

Functional architecture of visual responses in dorsal and ventral banks of anterior cingulate cortex

Functional architecture of visual responses in dorsal and ventral banks of anterior cingulate cortex

Neuroanatomical and functional correlates in tic disorders and Tourette's syndrome: A narrative review

AbstractTic disorders represent a developmental neuropsychiatric condition whose causes can be attributed to a variety of environmental, neurobiological, and genetic factors. From a neurophysiological perspective, the disorder has classically been associated with neurochemical imbalances (particularly dopamine and serotonin) and structural and functional alterations affecting, in particular, brain areas and circuits involved in the processing and coordination of movements: the basal ganglia, thalamus, motor cortical area, and cingulate cortex; however, more recent research is demonstrating the involvement of many more brain regions and neurotransmission systems than previously observed, such as the prefrontal cortex and cerebellum. In this paper, therefore, we summarize the evidence to date on these abnormalities with the intent to illustrate and clarify the main neuroanatomical differences between patients with tic disorders and healthy individuals.

Abnormal resting-state functional connectivity of the right anterior cingulate cortex in chronic ketamine users and its correlation with cognitive impairments

BackgroundChronic ketamine use leads to cognitive impairments, however, the neural mechanisms underpinning these impairments are still unclear. AimsMany studies showed Anterior cingulate cortex (ACC)is strongly involved in cognition and drug addiction, as supported by our previous studies. The objective of this study was to assess the variations in resting-state functional connectivity (FC) changes in the right anterior cingulate cortex (ACC) of chronic ketamine users (CKUs) and their relationship with cognitive performance. MethodsThe study enrolled 28 chronic ketamine users (CKUs) and 30 healthy controls (HCs). Resting-state functional magnetic resonance imaging (fMRI) data were gathered from both groups. Cognitive functions were evaluated using the MATRICS Consensus Cognitive Battery (MCCB). ResultsCKUs demonstrated significantly poorer cognitive performance than HCs in various cognitive domains, including Visual Learning, Speed of Processing, Working Memory, and the composite score of MCCB. Group-level comparisons revealed that CKUs exhibited enhanced functional connectivity between the right ACC and the right postcentral gyrus (PCG) compared to HCs. There was a positive relationship between the connectivity of right ACC-PCG and reasoning and problem-solving score, but there was no significant association with the characteristics of ketamine use. ConclusionCKUs showed enhanced connectivity between the right ACC and the right PCG. This enhanced functional connectivity may indicate functional compensation for cognitive deficits in CKUs, especially for reasoning and problem-solving impairments in CKUs.

Melatonin Induces Analgesic Effects through MT2 Receptor-Mediated Neuroimmune Modulation in the Mice Anterior Cingulate Cortex.

Neuropathic pain (NP) represents a considerable clinical challenge, profoundly impacting patients' quality of life. Presently, pharmacotherapy serves as a primary approach for NP alleviation, yet its efficacy often remains suboptimal. Melatonin (MLT), a biologically active compound secreted by the pineal gland, has long been associated with promoting and maintaining sleep. Although recent studies suggest analgesic effects of MLT, the underlying mechanism remains largely unknown, particularly its impact on the cortex. In this study, we induced an NP model in mice through spared nerve injury (SNI) and observed a considerable, dose-dependent alleviation in NP symptoms following intraperitoneal or anterior cingulate cortex (ACC) administration of MLT. Our findings further indicated that the NP management of MLT is selectively mediated by MLT-related receptor 2 (MT2R), rather than MT1R, on neurons and microglia within the ACC. Transcriptome sequencing, complemented by bioinformatics analysis, implicated MLT in the modulation of Gα(i) and immune-inflammatory signals. Specifically, MLT inhibited the excitability level of pyramidal cells in the ACC by activating the Gα(i) signaling pathway. Simultaneously, MLT attenuated M1 polarization and promoted M2 polarization of microglia, thereby mitigating the inflammatory response and type II interferon response within the ACC. These findings unveil a hitherto unrecognized molecular mechanism: an MLT-mediated neuroimmune modulation pathway in the ACC mediated by MT2R. This elucidation sheds light on the regulatory character of MLT in chronic nociceptive pain conditions, offering a prospective therapeutic strategy for NP management.

A - 19 Exploring White Matter Correlates of Fluid Cognitive Functioning in those 85+

Abstract Objective In individuals aged 85+, maintenance of white matter integrity (WMI) is crucial for maintaining communication between brain regions. White matter hyperintensities (WMH), common in aging, are linked with reduced cognitive function. While fluid cognitive functions typically decline with aging, some oldest older adults maintain performance akin to much younger individuals. Methods We examined the relationship between WMI, WMH, and fluid cognitive functioning in individuals aged 85+. WMI and WMH were assessed using two types of MRI imaging and fluid and crystallized cognitive performance were measured using the NIH Toolbox. Cognitive metrics were compared to WMI and WMH. Results Age significantly predicted fluid cognition (β = 0.49, p &amp;lt; 0.05, R^2 = 0.25, p &amp;lt; 0.01). Incorporating white matter measures improved prediction. Notably, cingulate gyrus FA and uncinate fasciculus FA significantly contributed to explained variance (ΔR^2 = 0.12, p &amp;lt; 0.01; ΔR^2 = 0.17, p &amp;lt; 0.01). Splenium corpus callosum MD and fornix column body ad were also significant predictors (ΔR^2 = 0.23, p &amp;lt; 0.01; ΔR^2 = 0.18, p &amp;lt; 0.01).n. Conclusion This study shows the significant impact of age and regional WMI on fluid cognitive function. Age did predict fluid cognition, and consideration of the white matter integrity of the cingulate gyrus and uncinate fasciculus integrity enhanced this association. Further, the integrity of the splenium of the corpus callosum and fornix also played crucial roles. These findings highlight the importance of preservation of white matter health for cognitive well-being in older adults 85 + .

A - 1 Informant Report of Practical Judgment Is Associated with Mild Cognitive Impairment and Measures of Brain Structure in a Nondemented Sample of Older Adults

Abstract Objective Given the potential risks associated with compromised judgment in older adulthood, we examined whether informant-reported practical judgment abilities were associated with cognitive impairment and measures of brain structure. Method 97 community-dwelling older adults with informants (Mage = 74.64 ± 7.42, Medu = 15.76 ± 2.42, 74%female, 92%white) underwent neuropsychological evaluation, including the Test of Practical Judgment-Informant (TOP-J-INF), a 15-item informant-reported scale of judgment ability. Participants were diagnosed with mild cognitive impairment (MCI; n = 33) or as neuropsychologically unimpaired (n = 64). Participants completed an MRI study including T1-weighted image processed with FreeSurfer software (v 6.0.0) to obtain estimates of gray matter volume and cortical thickness (parcellated with the Desikan-Killiany atlas). Logistic and linear models analyzed the association of TOP-J-INF with MCI diagnosis and brain volume/thickness (in separate models). To better support the exploratory nature of this analysis of associations with structural brain variables, we did not apply correction for multiple comparisons. Results Each additional point on the TOP-J-INF increased the odds of MCI diagnosis by 16.8% (OR = 1.168, p = 0.004). Worse judgment was associated with reduced brain volume in the right parahippocampal gyrus (β = −11.688, p = 0.032), superior temporal gyrus (β = −51.330, p = 0.040), rostral anterior cingulate cortex (β = −25.704, p = 0.004); and reduced thickness of the left transverse temporal gyrus (β = −0.010, p = 0.041). Conclusions To our knowledge, this is the first study to investigate the relationship between informant report of judgment and measures of brain structure, providing support that informant concerns about a loved one’s compromised judgment is associated with volume/thickness reduction in key brain regions. Assessing practical judgment abilities via informants could provide critical clinical information when working with vulnerable older individuals.

Decision-Making with Predictions of Others' Likely and Unlikely Choices in the Human Brain.

For better decisions in social interactions, humans often must understand the thinking of others and predict their actions. Since such predictions are uncertain, multiple predictions may be necessary for better decision-making. However, the neural processes and computations underlying such social decision-making remain unclear. We investigated this issue by developing a behavioral paradigm and performing functional magnetic resonance imaging and computational modeling. In our task, female and male participants were required to predict others' choices in order to make their own value-based decisions, as the outcome depended on others' choices. Results showed, to make choices, the participants mostly relied on a value difference (primary) generated from the case where others would make a likely choice, but sometimes they additionally used another value difference (secondary) from the opposite case where others make an unlikely choice. We found that the activations in the posterior cingulate cortex (PCC) correlated with the primary difference while the activations in the right dorsolateral prefrontal cortex (rdlPFC) correlated with the secondary difference. Analysis of neural coupling and temporal dynamics suggested a three-step processing network, beginning with the left amygdala signals for predictions of others' choices. Modulated by these signals, the PCC and rdlPFC reflect the respective value differences for self-decisions. Finally, the medial prefrontal cortex integrated these decision signals for a final decision. Our findings elucidate the neural process of constructing value-based decisions by predicting others and illuminate their key variables with social modulations, providing insight into the differential functional roles of these brain regions in this process.