Dorsal Anterior Insula Research Articles

Neural bases of social facilitation and inhibition: how peer presence affects elementary eye movements.

Social Facilitation/Inhibition (SFI) refers to how others' presence influences task performance positively or negatively. Our previous study revealed that peer presence modulated saccadic eye movements, a fundamental sensorimotor activity. Pro- and anti-saccades were either facilitated or inhibited depending on trial block complexity (Tricoche et al., 2020). In the present fMRI study, we adapted our paradigm to investigate the neural basis of SFI on saccades. Considering inter- and intra-individual variabilities, we evaluated the shared and distinct neural patterns between social facilitation and inhibition. We predicted an involvement of the saccade-related and attention networks, alongside the Theory-of-Mind (ToM) network, with opposite activity changes between facilitation and inhibition. Results confirmed peer presence modulation in fronto-parietal areas related to saccades and attention, in opposite directions for facilitation and inhibition. Additionally, the ventral attention network was modulated during inhibition. Default mode regions, including ToM areas, were also modulated. Finally, pupil size, often linked to arousal, increased with peers and correlated with dorsal attention regions and anterior insula activities. These results suggest that SFI engages task-specific and domain-general networks, modulated differently based on observed social effect. Attention network seemed to play a central role at both basic (linked to arousal or vigilance) and cognitive control levels.

Thalamocortical dysrhythmia and reward deficiency syndrome as uncertainty disorders

A common anatomical core has been described for psychiatric disorders, consisting of the dorsal anterior cingulate cortex (dACC) and anterior insula, processing uncertainty. A common neurophysiological core has been described for other brain related disorders, called thalamocortical dysrhythmia (TCD), consisting of persistent cross-frequency coupling between low and high frequencies. And a common genetic core has been described for yet another set of hypodopaminergic pathologies called reward deficiency syndromes (RDS). Considering that some RDS have the neurophysiological features of TCD, it can be hypothesized that TCD and RDS have a common anatomical core, yet a differentiating associated neurophysiological mechanism. The EEGs of 683 subjects are analysed in source space for both differences and conjunction between TCD and healthy controls, RDS and healthy controls, and between TCD and RDS. A balance between current densities of the pregenual anterior cingulate cortex (pgACC) extending into the ventromedial prefrontal cortex (vmPFC) and dACC is calculated as well. TCD and RDS share a common anatomical and neurophysiological core, consisting of beta activity in the dACC and theta activity in dACC extending into precuneus and dorsolateral prefrontal cortex. TCD and RDS differ in pgACC/vmPFC activity and demonstrate an opposite balance between pgACC/vmPFC and dACC. Based on the Bayesian brain model TCD and RDS can be defined as uncertainty disorders in which the pgACC/vmPFC and dACC have an opposite balance, possibly explained by an inverted-U curve profile of both pgACC/vmPFC and dACC.

A chronometric relationship between circuits underlying learning and error monitoring in the basal ganglia and salience network

Abstract Healthy individuals readily adjust their behaviour in response to errors using learning mechanisms. This raises the question of how error-related neural mechanisms underlie the learning process and its progress. In this study, 21 healthy participants performed a challenging functional magnetic resonance imaging (fMRI) task to answer this question. We assessed the evolution of error-related neural response as a function of learning progress. We tested the hypothesis that the dorsal anterior cingulate cortex (dACC) and anterior insula, key regions of the error monitoring neural circuitry, reflect both the performance of an action and its improvement. Given the nature of trial-and-error learning, we also expected an involvement of the striatum, particularly the putamen. We found that error-related neural activity (in the dACC and anterior insula) was similar following correct responses and errors in an initial learning period. However, as learning progressed, the activity continuously decreased in response to correct events and increased after errors. In opposition, during the initial learning phase, the putamen activity was modulated by errors, but, as it progressed, this region became unaffected by response outcomes. In sum, our study provides neural evidence for an interaction between the mechanisms underlying error monitoring and learning, contributing to clarifying how error-related neural responses evolve with learning.

Pathologic Substrates of Structural Brain Network Resilience and Topology in Parkinson Disease Decedents.

In Parkinson disease (PD), α-synuclein spreading through connected brain regions leads to neuronal loss and brain network disruptions. With diffusion-weighted imaging (DWI), it is possible to capture conventional measures of brain network organization and more advanced measures of brain network resilience. We aimed to investigate which neuropathologic processes contribute to regional network topologic changes and brain network resilience in PD. Using a combined postmortem MRI and histopathology approach, PD and control brain donors with available postmortem in situ 3D T1-weighted MRI, DWI, and brain tissue were selected from the Netherlands Brain Bank and Normal Aging Brain Collection Amsterdam. Probabilistic tractography was performed, and conventional network topologic measures of regional eigenvector centrality and clustering coefficient, and brain network resilience (change in global efficiency upon regional node failure) were calculated. PSer129 α-synuclein, phosphorylated-tau, β-amyloid, neurofilament light-chain immunoreactivity, and synaptophysin density were quantified in 8 cortical regions. Group differences and correlations were assessed with rank-based nonparametric tests, with age, sex, and postmortem delay as covariates. Nineteen clinically defined and pathology-confirmed PD (7 F/12 M, 81 ± 7 years) and 15 control (8 F/7 M, 73 ± 9 years) donors were included. With regional conventional measures, we found lower eigenvector centrality only in the parahippocampal gyrus in PD (d = -1.08, 95% CI 0.003-0.010, p = 0.021), which did not associate with underlying pathology. No differences were found in regional clustering coefficient. With the more advanced measure of brain network resilience, we found that the PD brain network was less resilient to node failure of the dorsal anterior insula compared with the control brain network (d = -1.00, 95% CI 0.0012-0.0015, p = 0.018). This change was not directly driven by neuropathologic processes within the dorsal anterior insula or in connected regions but was associated with higher Braak α-synuclein staging (rs = -0.40, p = 0.036). Although our cohort might suffer from selection bias, our results highlight that regional network disturbances are more complex to interpret than previously believed. Regional neuropathologic processes did not drive regional topologic changes, but a global increase in α-synuclein pathology had a widespread effect on brain network reorganization in PD.

Meta-Analysis Reveals That Explore-Exploit Decisions are Dissociable by Activation in the Dorsal Lateral Prefrontal Cortex, Anterior Insula, and the Anterior Cingulate Cortex.

Explore-exploit research faces challenges in generalizability due to a limited theoretical basis for exploration and exploitation. Neuroimaging can help identify whether explore-exploit decisions involve an opponent processing system to address this issue. Thus, we conducted a coordinate-based meta-analysis (N=23 studies) finding activation in the dorsal lateral prefrontal cortex, anterior insula, and anterior cingulate cortex during exploration versus exploitation, which provides some evidence for opponent processing. However, the conjunction of explore-exploit decisions was associated with activation in the dorsal anterior cingulate cortex and dorsal medial prefrontal cortex, suggesting that these brain regions do not engage in opponent processing. Furthermore, exploratory analyses revealed heterogeneity in brain responses between task types during exploration and exploitation respectively. Coupled with results suggesting that activation during exploration and exploitation decisions is generally more similar than it is different suggests, there remain significant challenges in characterizing explore-exploit decision making. Nonetheless, dlPFC, AI, and ACC activation differentiate explore and exploit decisions and identifying these responses can aid in targeted interventions aimed at manipulating these decisions.

Bulimia nervosa selectively reshapes the structure and intrinsic function of anterior insula subregions associated with cognition-emotion integration

BackgroundExisting evidence suggests that anterior insula plays a crucial role in cognitive control and emotional regulation and is implicated in the onset and maintenance of bulimia nervosa (BN). However, it remains unclear how structural and functional abnormalities in specific subregions of anterior insula contribute to BN. MethodsIn this study, we analyzed structural MRI and resting-state functional MRI data from 54 BN patients and 56 healthy controls (HCs). We conducted voxel-based morphometry, amplitude of low frequency fluctuation (conventional band: 0.01–0.08 Hz, slow-5: 0.01–0.027 Hz) and seed-based whole-brain functional connectivity (FC) analysis of the anterior insula subregions for both groups. Additionally, we investigated the correlation between neuroimaging findings and clinical characteristics in the BN group. ResultsOur findings revealed that BN patients exhibited reduced gray matter volume in the right dorsal anterior insula (dAI) and bilateral ventral anterior insula (vAI) and demonstrated decreased ALFF in slow-5 band of bilateral dAI. The BN group also showed increased FC between bilateral dAI and precuneus or right superior frontal gyri which significantly correlated with the severity of BN or its key symptom. In addition, the decreased FC between bilateral vAI and anterior cingulate and paracingulate gyri and/or median cingulate and paracingulate gyri were both significantly correlated with the severity and its restrained eating behavior. ConclusionsOur findings further indicate that the functional separation of anterior insula subregions may underlie the pathophysiology of BN. Notably, the vAI associated with emotional processing may serve as a promising neuroimaging biomarker which could inform therapeutic strategy.

The functional connectivity between right insula and anterior cingulate cortex underlying the association between future self-continuity and delay discounting.

Delay discounting refers to the tendency of individuals to devalue future rewards as the delay in their receipt increases over time. Previous studies have indicated that future self-continuity correlates with delay discounting rates. However, the neural basis underlying the relationship between future self-continuity and delay discounting is not clear. To address this question, we used voxel-based morphometry and resting-state functional connectivity analyses to investigate the neural basis underlying the association between future self-continuity and delay discounting. Behavioral result showed that future self-continuity was positively associated with delay discounting. Voxel-based morphometry analysis result indicated that gray matter volume in the right dorsal anterior insula was positively correlated with future self-continuity. Resting-state functional connectivity analysis found that functional connectivity between the right dorsal anterior insula and anterior cingulate cortex was positively associated with future self-continuity. Mediation analysis showed that the right dorsal anterior insula-right anterior cingulate cortex functional connectivity partially mediated the relationship between future self-continuity and delay discounting. These results suggested that right dorsal anterior insula-right anterior cingulate cortex functional connectivity could be the neural basis underlying the association between future self-continuity and delay discounting. In summary, the study provided novel insights into how future self-continuity affected delay discounting and offers new explanations from a neural perspective.

359 Low-Intensity Focused Ultrasound to Human Dorsal Anterior Cingulate Cortex and Insula Attenuates Measures of Central Sensitization

INTRODUCTION: Central sensitization is the abnormal amplified response to pain and is associated with chronic pain. Increased insula and dorsal anterior cingulate cortex (dACC) activity is associated with central sensitization. Low-intensity focused ultrasound (LIFU) is a novel form of non-invasive neuromodulation that can precisely target the anterior insula (AI), posterior insula (PI) and dACC. METHODS: N = 18 healthy participants underwent conditioned pain modulation (CPM) and temporal summation of pain (TSP) tasks before and after 10 minutes of LIFU or sham stimulations. For CPM, the conditioning stimulus (CS) was a cold pressor test to the left hand and the test stimulus (TS) was a brief transient heat stimulus to the dorsum of the right hand. For TSP, 10 transient heat stimuli (>0.33 Hz) were administered to the dorsum of the right hand. The primary outcome measure for both tasks was perceived pain ratings (0-9). Electrodermal response and electrocardiogram was collected to evaluate the effect of LIFU on autonomic reactivity. RESULTS: LIFU to PI increased CPM 0.5 ± 0.181 compared to sham (p = 0.024). LIFU to PI also significantly reduced perceived pain during the TSP task compared to sham (p < 0.001). We also found a significant difference between dACC and sham conditions during TSP by -0.55 ± 0.05 (p < 0.001). LIFU to the AI increases frequency domain measures of heart-rate variability. CONCLUSIONS: LIFU to the insula and dACC affects pain processing in measures of central sensitization. This demonstrates the neuromodulation abilities of LIFU and is a promising tool to develop noninvasive clinical therapies for chronic pain conditions.

Effector-independent Representations Guide Sequential Target Selection Biases in Action.

Previous work shows that automatic attention biases toward recently selected target features transfer across action and perception and even across different effectors such as the eyes and hands on a trial-by-trial basis. Although these findings suggest a common neural representation of selection history across effectors, the extent to which information about recently selected target features is encoded in overlapping versus distinct brain regions is unknown. Using fMRI and a priming of pop-out task where participants selected unpredictable, uniquely colored targets among homogeneous distractors via reach or saccade, we show that color priming is driven by shared, effector-independent underlying representations of recent selection history. Consistent with previous work, we found that the intraparietal sulcus (IPS) was commonly activated on trials where target colors were switched relative to those where the colors were repeated; however, the dorsal anterior insula exhibited effector-specific activation related to color priming. Via multivoxel cross-classification analyses, we further demonstrate that fine-grained patterns of activity in both IPS and the medial temporal lobe encode information about selection history in an effector-independent manner, such that ROI-specific models trained on activity patterns during reach selection could predict whether a color was repeated or switched on the current trial during saccade selection and vice versa. Remarkably, model generalization performance in IPS and medial temporal lobe also tracked individual differences in behavioral priming sensitivity across both types of action. These results represent a first step to clarify the neural substrates of experience-driven selection biases in contexts that require the coordination of multiple actions.

Impaired value-based decision-making in Parkinson's disease apathy.

Apathy is a common and disabling complication of Parkinson's disease characterized by reduced goal-directed behaviour. Several studies have reported dysfunction within prefrontal cortical regions and projections from brainstem nuclei whose neuromodulators include dopamine, serotonin and noradrenaline. Work in animal and human neuroscience have confirmed contributions of these neuromodulators on aspects of motivated decision-making. Specifically, these neuromodulators have overlapping contributions to encoding the value of decisions, and influence whether to explore alternative courses of action or persist in an existing strategy to achieve a rewarding goal. Building upon this work, we hypothesized that apathy in Parkinson's disease should be associated with an impairment in value-based learning. Using a four-armed restless bandit reinforcement learning task, we studied decision-making in 75 volunteers; 53 patients with Parkinson's disease, with and without clinical apathy, and 22 age-matched healthy control subjects. Patients with apathy exhibited impaired ability to choose the highest value bandit. Task performance predicted an individual patient's apathy severity measured using the Lille Apathy Rating Scale (R = -0.46, P < 0.001). Computational modelling of the patient's choices confirmed the apathy group made decisions that were indifferent to the learnt value of the options, consistent with previous reports of reward insensitivity. Further analysis demonstrated a shift away from exploiting the highest value option and a reduction in perseveration, which also correlated with apathy scores (R = -0.5, P < 0.001). We went on to acquire functional MRI in 59 volunteers; a group of 19 patients with and 20 without apathy and 20 age-matched controls performing the Restless Bandit Task. Analysis of the functional MRI signal at the point of reward feedback confirmed diminished signal within ventromedial prefrontal cortex in Parkinson's disease, which was more marked in apathy, but not predictive of their individual apathy severity. Using a model-based categorization of choice type, decisions to explore lower value bandits in the apathy group activated prefrontal cortex to a similar degree to the age-matched controls. In contrast, Parkinson's patients without apathy demonstrated significantly increased activation across a distributed thalamo-cortical network. Enhanced activity in the thalamus predicted individual apathy severity across both patient groups and exhibited functional connectivity with dorsal anterior cingulate cortex and anterior insula. Given that task performance in patients without apathy was no different to the age-matched control subjects, we interpret the recruitment of this network as a possible compensatory mechanism, which compensates against symptomatic manifestation of apathy in Parkinson's disease.

Acute stress reduces effortful prosocial behaviour.

Acute stress can change our cognition and emotions, but what specific consequences this has for human prosocial behaviour is unclear. Previous studies have mainly investigated prosociality with financial transfers in economic games and produced conflicting results. Yet a core feature of many types of prosocial behaviour is that they are effortful. We therefore examined how acute stress changes our willingness to exert effort that benefits others. Healthy male participants - half of whom were put under acute stress - made decisions whether to exert physical effort to gain money for themselves or another person. With this design, we could independently assess the effects of acute stress on prosocial, compared to self-benefitting, effortful behaviour. Compared to controls (n = 45), participants in the stress group (n = 46) chose to exert effort more often for self- than for other-benefitting rewards at a low level of effort. Additionally, the adverse effects of stress on prosocial effort were particularly pronounced in more selfish participants. Neuroimaging combined with computational modelling revealed a putative neural mechanism underlying these effects: more stressed participants showed increased activation to subjective value in the dorsal anterior cingulate cortex and anterior insula when they themselves could benefit from their exerted effort relative to when someone else could. By using an effort-based task that better approximates real-life prosocial behaviour and incorporating trait differences in prosocial tendencies, our study provides important insights into how acute stress affects prosociality and its associated neural mechanisms.

Acute stress reduces effortful prosocial behaviour

Acute stress can change our cognition and emotions, but what specific consequences this has for human prosocial behaviour is unclear. Previous studies have mainly investigated prosociality with financial transfers in economic games and produced conflicting results. Yet a core feature of many types of prosocial behaviour is that they are effortful. We therefore examined how acute stress changes our willingness to exert effort that benefits others. Healthy male participants – half of whom were put under acute stress – made decisions whether to exert physical effort to gain money for themselves or another person. With this design, we could independently assess the effects of acute stress on prosocial, compared to self-benefitting, effortful behaviour. Compared to controls (n = 45), participants in the stress group (n = 46) chose to exert effort more often for self- than for other-benefitting rewards at a low level of effort. Additionally, the adverse effects of stress on prosocial effort were particularly pronounced in more selfish participants. Neuroimaging combined with computational modelling revealed a putative neural mechanism underlying these effects: more stressed participants showed increased activation to subjective value in the dorsal anterior cingulate cortex and anterior insula when they themselves could benefit from their exerted effort relative to when someone else could. By using an effort-based task that better approximates real-life prosocial behaviour and incorporating trait differences in prosocial tendencies, our study provides important insights into how acute stress affects prosociality and its associated neural mechanisms.

Association of executive function with suicidality based on resting-state functional connectivity in young adults with subthreshold depression

Subthreshold depression (StD) is associated an increased risk of developing major depressive disorder (MDD) and suicidality. Suicidality could be linked to distress intolerance and use of context-dependent strategies. We identified neural correlates of executive functioning among the hubs in the resting-state functional connectome (rs-FCN) and examined associations with recent suicidality in StD and MDD. In total, 79 young adults [27 StD, 30 MDD, and 23 healthy controls (HC)] were scanned using magnetic resonance imaging. Neurocognitive measures of the mean latency to correct five moves in the One Touch Stockings of Cambridge (OTSMLC5), spatial working memory between errors (SWMBE), rapid visual information processing A′ (RVPA′), and the stop signal reaction time in the stop signal test (SSTSSRT) were obtained. Global graph metrics were calculated to measure the network integration, segregation, and their balance in the rs-FCN. Regional graph metrics reflecting the number of neighbors (degree centrality; DC), participation in the shortcuts (betweenness centrality; BC), and accessibility to intersections (eigenvector centrality; EC) in the rs-FCN defined group-level hubs for StD, HC, and MDD, separately. Global network metrics were comparable among the groups (all P > 0.05). Among the group-level hubs, regional graph metrics of left dorsal anterior insula (dAI), right dorsomedial prefrontal cortex (dmPFC), right rostral temporal thalamus, right precuneus, and left postcentral/middle temporal/anterior subgenual cingulate cortices were different among the groups. Further, significant associations with neurocognitive measures were found in the right dmPFC with SWMBE, and left dAI with SSTSSRT and RVPA′. Shorter OTSMLC5 was related to the lower centralities of right thalamus and suffer of recent 1-year suicidal ideation (all Ps < 0.05 in ≥ 2 centralities out of DC, BC, and EC). Collectively, salience and thalamic networks underlie spatial strategy and planning, response inhibition, and suicidality in StD and MDD. Anti-suicidal therapies targeting executive function and modulation of salience-thalamic network in StD and MDD are required.

Fractionation of neural reward processing into independent components by novel decoding principle

How to retrieve latent neurobehavioural processes from complex neurobiological signals is an important yet unresolved challenge. Here, we develop a novel approach, orthogonal-Decoding multi-Cognitive Processes (DeCoP), to reveal underlying latent neurobehavioural processing and show that its performance is superior to traditional non-orthogonal decoding in terms of both false inference and robustness. Processing value and salience information are two fundamental but mutually confounded pathways of reward reinforcement essential for decision making. During reward/punishment anticipation, we applied DeCoP to decode brain-wide responses into spatially overlapping, yet functionally independent, evaluation and readiness processes, which are modulated differentially by meso‑limbic vs nigro-striatal dopamine systems. Using DeCoP, we further demonstrated that most brain regions only encoded abstract information but not the exact input, except for dorsal anterior cingulate cortex and insula. Furthermore, we anticipate our novel analytical principle to be applied generally in decoding multiple latent neurobehavioral processes and thus advance both the design and hypothesis testing for cognitive tasks.

Neural circuit selective for fast but not slow dopamine increases in drug reward

The faster a drug enters the brain, the greater its addictive potential, yet the brain circuits underlying the rate dependency to drug reward remain unresolved. With simultaneous PET-fMRI we linked dynamics of dopamine signaling, brain activity/connectivity, and self-reported ‘high’ in 20 adults receiving methylphenidate orally (results in slow delivery) and intravenously (results in fast delivery) (trial NCT03326245). We estimated speed of striatal dopamine increases to oral and IV methylphenidate and then tested where brain activity was associated with slow and fast dopamine dynamics (primary endpoint). We then tested whether these brain circuits were temporally associated with individual ‘high’ ratings to methylphenidate (secondary endpoint). A corticostriatal circuit comprising the dorsal anterior cingulate cortex and insula and their connections with dorsal caudate was activated by fast (but not slow) dopamine increases and paralleled ‘high’ ratings. These data provide evidence in humans for a link between dACC/insula activation and fast but not slow dopamine increases and document a critical role of the salience network in drug reward.

Subjective states induced by intracranial electrical stimulation matches the cytoarchitectonic organization of the human insula

Functions of the human insula have been explored extensively with neuroimaging methods and intracranial electrical stimulation studies that have highlighted a functional segregation across its subregions. A recently developed cytoarchitectonic map of the human insula has also segregated this brain region into various areas. Our knowledge of the functional organization of this brain region at the level of these fine-parceled microstructural areas remains only partially understood. We address this gap of knowledge by applying a multimodal approach linking direct electrical stimulation and task-evoked intracranial EEG recordings with microstructural subdivisions of the human insular cortex. In 17 neurosurgical patients with 142 implanted electrodes, stimulation of 40 % of the sites induced a reportable change in the conscious experience of the subjects in visceral/autonomic, anxiety, taste/olfactory, pain/temperature as well as somatosensory domains. These subjective responses showed a topographical allocation to microstructural areas defined by probabilistic cytoarchitectonic parcellation maps of the human insula. We found the pain and thermal responses to be located in areas lg2/ld2, while non-painful/non-thermal somatosensory responses corresponded to area ld3 and visceroceptive responses to area Id6. Lastly, the stimulation of area Id7 in the dorsal anterior insula, failed to induce reportable changes to subjective experience even though intracranial EEG recordings from this region captured significant time-locked high-frequency activity (HFA). Our results provide a multimodal map of functional subdivisions within the human insular cortex at the individual brain basis and characterize their anatomical association with fine-grained cytoarchitectonic parcellations of this brain structure.

Lesion network mapping of eye-opening apraxia.

Apraxia of eyelid opening (or eye-opening apraxia) is characterized by the inability to voluntarily open the eyes because of impaired supranuclear control. Here, we examined the neural substrates implicated in eye-opening apraxia through lesion network mapping. We analysed brain lesions from 27 eye-opening apraxia stroke patients and compared them with lesions from 20 aphasia and 45 hemiballismus patients serving as controls. Lesions were mapped onto a standard brain atlas using resting-state functional MRI data derived from 966 healthy adults in the Harvard Dataverse. Our analyses revealed that most eye-opening apraxia-associated lesions occurred in the right hemisphere, with subcortical or mixed cortical/subcortical involvement. Despite their anatomical heterogeneity, these lesions functionally converged on the bilateral dorsal anterior and posterior insula. The functional connectivity map for eye-opening apraxia was distinct from those for aphasia and hemiballismus. Hemiballismus lesions predominantly mapped onto the putamen, particularly the posterolateral region, while aphasia lesions were localized to language-processing regions, primarily within the frontal operculum. In summary, in patients with eye-opening apraxia, disruptions in the dorsal anterior and posterior insula may compromise their capacity to initiate the appropriate eyelid-opening response to relevant interoceptive and exteroceptive stimuli, implicating a complex interplay between salience detection and motor execution.

Pain-preferential thalamocortical neural dynamics across species.

Searching for pain-preferential neural activity is essential for understanding and managing pain. Here, we investigated the preferential role of thalamocortical neural dynamics in encoding pain using human neuroimaging and rat electrophysiology across three studies. In study 1, we found that painful stimuli preferentially activated the medial-dorsal (MD) thalamic nucleus and its functional connectivity with the dorsal anterior cingulate cortex (dACC) and insula in two human functional magnetic resonance imaging (fMRI) datasets (n = 399 and n = 25). In study 2, human fMRI and electroencephalography fusion analyses (n = 220) revealed that pain-preferential MD responses were identified 89-295 ms after painful stimuli. In study 3, rat electrophysiology further showed that painful stimuli preferentially activated MD neurons and MD-ACC connectivity. These converging cross-species findings provided evidence for pain-preferential thalamocortical neural dynamics, which could guide future pain evaluation and management strategies.

Neurocomputational Substrates Underlying the Effect of Identifiability on Third-Party Punishment.

The identifiable target effect refers to the preference for helping identified victims and punishing identifiable perpetrators compared with equivalent but unidentifiable counterparts. The identifiable target effect is often attributed to the heightened moral emotions evoked by identified targets. However, the specific neurocognitive processes that mediate and/or modulate this effect remain largely unknown. Here, we combined a third-party punishment game with brain imaging and computational modeling to unravel the neurocomputational underpinnings of the identifiable transgressor effect. Human participants (males and females) acted as bystanders and punished identified or anonymous wrongdoers. Participants were more punitive toward identified wrongdoers than anonymous wrongdoers because they took a vicarious perspective of victims and adopted lower reference points of inequity (i.e., more stringent norms) in the identified context than in the unidentified context. Accordingly, there were larger activity of the ventral anterior insula, more distinct multivariate neural patterns in the dorsal anterior insula and dorsal anterior cingulate cortex, and lower strength between ventral anterior insula and dorsolateral PFC and between dorsal anterior insula and ventral striatum connectivity in response to identified transgressors than anonymous transgressors. These findings implicate the interplay of expectancy violations, emotions, and self-interest in the identifiability effect. Last, individual differences in the identifiability effect were associated with empathic concern/social dominance orientation, activity in the precuneus/cuneus and temporo-parietal junction, and intrinsic functional connectivity of the dorsolateral PFC. Together, our work is the first to uncover the neurocomputational processes mediating identifiable transgressor effect and to characterize psychophysiological profiles modulating the effect.SIGNIFICANCE STATEMENT The identifiable target effect, more help to identified victims or stronger punishment to identifiable perpetrators, is common in daily life. We examined the neurocomputational mechanisms mediating/modulating the identifiability effect on third-party punishment by bridging literature from economics and cognitive neuroscience. Our findings reveal that identifiable transgressor effect is mediated by lower reference points of inequity (i.e., more stringent norms), which might be associated with a stronger involvement of the emotion processes and a weaker engagement of the analytic/deliberate processes. Furthermore, personality traits, altered brain activity, and intrinsic functional connectivity contribute to the individual variance in the identifiability effect. Overall, our study advances the understanding of the identifiability effect by shedding light on its component processes and modulating factors.

Stress and streets: How the network structure of streets is associated with stress-related brain activation

Previous research has examined the relation between urban design factors and mental health, but the impact of street networks is underrepresented. This exploratory, cross-sectional study examines the association between street network variables based on the Space Syntax theory and whole-brain activation during a social stress paradigm. Forty-two individuals who lived in Berlin participated in an fMRI study during which acute social stress was induced. Saliva cortisol concentrations, subjective stress ratings, and mean heart rate were assessed as proxies for a successful stress induction. Space Syntax was used as a tool to objectively measure street network characteristics including global integration (‘proximity’ of a street to all the other streets in a network), local integration (‘proximity’ of a street to a certain number of streets within a walkable area), connectivity (‘direct street connections’ a street has), and normalized angular choice (NACH) (‘straightest and shortest’ route for a street in a street network). They were analyzed within a 1500 m radius of participants' address (i.e., neighborhood) as well as for the street closest to their address (i.e., point address). Higher mean neighborhood global and local integration, which equate to better integrated streets in the network, were associated with less activation during stress provocation in several brain regions, including dorsal anterior cingulate cortex, insula, and thalamus, which play a role in the detection of salient stimuli and threats. No association was found between brain activity and global and local integration for the point address. There was also no association between brain activity and connectivity or NACH for any conditions. The study indicates that Space Syntax is a useful tool for measuring macro-scale urban space (e.g., street networks) in neuro-urbanistic studies. The results underline the need to explore the potential of optimizing street networks to better understand pathways to urban mental health.