Cortical Midline Research Articles

Anosognosia in Alzheimer disease: Disconnection between memory and self-related brain networks.

Impaired awareness is a common symptom in many mental disorders including Alzheimer disease (AD). This study aims at improving our understanding of the neural mechanisms underlying anosognosia of memory deficits in AD by combining measures of regional brain metabolism (resting state fluorodeoxyglucose positron emission tomography [FDG-PET]) and intrinsic connectivity (resting state functional magnetic resonance imaging [fMRI]). Twenty-three patients diagnosed with probable AD based on clinical and biomarker data and 30 matched healthy control subjects were recruited in this study. An anosognosia index (difference between subjective and objective memory scores) was obtained in each participant. Resting state FDG-PET for glucose metabolism measurement and resting state fMRI for intrinsic connectivity measurement were also performed. AD and control groups were compared on behavioral data, and voxelwise correlations between anosognosia and neuroimaging data were conducted within the AD group. AD patients underestimated their memory deficits. Anosognosia in AD patients correlated with hypometabolism in orbitofrontal (OFC) and posterior cingulate (PCC) cortices. Using OFC and PCC as seed regions, intrinsic connectivity analyses in AD revealed a significant association between anosognosia and reduced intrinsic connectivity between these regions as well as with the medial temporal lobe. Anosognosia in AD is due not only to functional changes within cortical midline structures involved in self-referential processes (OFC, PCC), but also to disconnection between these regions as well as with the medial temporal lobe. These findings suggest that the lack of awareness of memory deficits in AD results from a disruption of the communication within, but also between, the self-related and the memory-related brain networks.

Aberrant Salience Is Related to Dysfunctional Self-Referential Processing in Psychosis.

A dysfunctional differentiation between self-relevant and irrelevant information may affect the perception of environmental stimuli as abnormally salient. The aberrant salience hypothesis assumes that positive symptoms arise from an attribution of salience to irrelevant stimuli accompanied by the feeling of self-relevance. Self-referential processing relies on the activation of cortical midline structures which was demonstrated to be impaired in psychosis. We investigated the neural correlates of self-referential processing, aberrant salience attribution, and the relationship between these 2 measures across the psychosis continuum. Twenty-nine schizophrenia patients, 24 healthy individuals with subclinical delusional ideation, and 50 healthy individuals participated in this study. Aberrant salience was assessed behaviorally in terms of reaction times to task irrelevant cues. Participants performed a self-reference task during fMRI in which they had to apply neutral trait words to them or to a public figure. The correlation between self-referential processing and aberrant salience attribution was tested. Schizophrenia patients displayed increased aberrant salience attribution compared with healthy controls and individuals with subclinical delusional ideation, while the latter exhibited intermediate aberrant salience scores. In the self-reference task, schizophrenia patients showed reduced activation in the ventromedial prefrontal cortex (vmPFC), but individuals with subclinical delusional ideation did not differ from healthy controls. In schizophrenia patients, vmPFC activation correlated negatively with implicit aberrant salience attribution. Higher aberrant salience attribution in schizophrenia patients is related to reduced vmPFC activation during self-referential judgments suggesting that aberrant relevance coding is reflected in decreased neural self-referential processing as well as in aberrant salience attribution.

P84. High-frequency anterior thalamus stimulation interrupts cortical midline theta rhythm during drowsiness in an epileptic patient

Deep brain stimulation (DBS) of anterior thalamic nuclei (ANT) reduces frequency and intensity of epileptic partial and secondarily-generalized seizures. However, exact mechanisms of action and the effects of ANT-DBS on cortical activity are unknown. Recently, we demonstrated in one of our patients who had non-lesional epilepsy the correlation of ANT-DBS with bilateral frontal epileptic patterns ( Bucurenciu et al., 2014 ). We report the case of a 27-years old male epileptic patient with dyscognitive focal seizures, due to a left-hemispheric inoperable lesion, interpreted as focal cortical dysplasia and polymicrogyria, comprising the upper temporal lobe, the insula and the entire parietal lobe. At the age of 25, quadripolar DBS-electrodes (Model 3389, Medtronic®, Minneapolis, MN, USA), connected to a subclavicular dual-channel programmable stimulation device (Activa PC, Medtronic®), were stereotactically implanted in both ANTs. The stimulation parameters were 5 V and 5.5 V, 180 Hz, 150 μ s pulse width, cycling mode with 1min on/3min off. Stimulation on-phases were identified based on periodical reduction of QRS-complex-amplitudes in electrocardiograms. A 20% reduction of seizure frequencies with no side effects were reported after initiation of ANT-DBS. In several long-term EEGs of the patient, prominent non-specific midline-theta frontal rhythms of uncertain significance were observed during drowsiness. During bilateral stimulation via the most upper (superior-lateral) electrode-contacts (3 and 11) a reliable interruption of midline-theta rhythm was observed in EEGs, density-spectral-arrays and power-spectra, similarly to the effect of activating the patient. When the lowest (inferio-medial) electrode contacts (0 and 8) were used for stimulation the midline-theta rhythm was less affected. Other cortical rhythms, such as occipital-alpha or sleep-spindles, were only unspecifically reduced in amplitude by stimulation of both the most upper and the lowest contact-pairs, respectively. The contact-specificity and the selective inhibition of midline-theta rhythm, associated with changes of the power-spectra shape, prove that the observed EEG-amplitude reduction during stimulation is a real desynchronization of midline-theta rhythm and not an artefact. This is the first direct proof of an acute, electrode-contact specific influence of high-frequency ANT-DBS with standard stimulation-parameters on a cortical rhythm and might be relevant for epilepsies involving frontal cortical regions.

Increase in glutamate/glutamine concentration in the medial prefrontal cortex during mental imagery: A combined functional mrs and fMRI study.

Recent functional magnetic resonance spectroscopy (fMRS) studies have shown changes in glutamate/glutamine (Glx) concentrations between resting-state and active-task conditions. However, the types of task used have been limited to sensory paradigms, and the regions from which Glx concentrations have been measured limited to sensory ones. This leaves open the question as to whether the same effect can be seen in higher-order brain regions during cognitive tasks. Cortical midline structures, especially the medial prefrontal cortex (MPFC), have been suggested to be involved in various such cognitive tasks. We, therefore set out to use fMRS to investigate the dynamics of Glx concentrations in the MPFC between resting-state and mental imagery task conditions. The auditory cortex was used as a control region. In addition, functional magnetic resonance imaging was used to explore task-related neural activity changes. The mental imagery task consisted of imagining swimming and was applied to a large sample of healthy participants (n = 46). The participants were all competitive swimmers, ensuring proficiency in mental-swimming. Glx concentrations in the MPFC increased during the imagery task, as compared to resting-state periods preceding and following the task. These increases mirror BOLD activity changes in the same region during the task. No changes in either Glx concentrations or BOLD activity were seen in the auditory cortex. These findings contribute to our understanding of the biochemical basis of generating or manipulating mental representations and the MPFC's role in this.

Neurofunctional correlates of environmental cognition: an FMRI study with images from episodic memory.

This study capitalizes on individual episodic memories to investigate the question, how dif-ferent environments affect us on a neural level. Instead of using predefined environmental stimuli, this study relied on individual representations of beauty and pleasure. Drawing upon episodic memories we conducted two experiments. Healthy subjects imagined pleasant and non-pleasant environments, as well as beautiful and non-beautiful environments while neural activity was measured by using functional Magnetic Resonance Imaging. Although subjects found the different conditions equally simple to visualize, our results revealed more distribut-ed brain activations for non-pleasant and non-beautiful environments than for pleasant and beautiful environments. The additional regions activated in non-pleasant (left lateral prefrontal cortex) and non-beautiful environments (supplementary motor area, anterior cortical midline structures) are involved in self-regulation and top-down cognitive control. Taken together, the results show that perceptual experiences and emotional evaluations of environments within a positive and a negative frame of reference are based on distinct patterns of neural activity. We interpret the data in terms of a different cognitive and processing load placed by exposure to different environments. The results hint at the efficiency of subject-generated representations as stimulus material.

Default mode network dissociation in depressive and anxiety states.

The resting state brain networks, particularly the Default Mode Network (DMN), have been found to be altered in several psychopathological conditions such as depression and anxiety. In this study we hypothesized that cortical areas of the DMN, particularly the anterior regions--medial prefrontal cortex and anterior cingulate cortex--would show an increased functional connectivity associated with both anxiety and depression. Twenty-four healthy participants were assessed using Hamilton Depression and Anxiety Rating Scales and completed a resting-state functional magnetic resonance imaging scan. Multiple regression was performed in order to identify which areas of the DMN were associated with anxiety and depression scores. We found that the functional connectivity of the anterior portions of DMN, involved in self-referential and emotional processes, was positively correlated with anxiety and depression scores, whereas posterior areas of the DMN, involved in episodic memory and perceptual processing were negatively correlated with anxiety and depression scores. The dissociation between anterior and posterior cortical midline regions, raises the possibility of a functional specialization within the DMN in terms of self-referential tasks and contributes to the understanding of the cognitive and affective alterations in depressive and anxiety states.

Differentiating self-projection from simulation during mentalizing: evidence from fMRI.

We asked participants to predict which of two colors a similar other (student) and a dissimilar other (retiree) likes better. We manipulated if color-pairs were two hues from the same color-category (e.g. green) or two conceptually different colors (e.g. green versus blue). In the former case, the mental state that has to be represented (i.e., the percept of two different hues of green) is predominantly non-conceptual or phenomenal in nature, which should promote mental simulation as a strategy for mentalizing. In the latter case, the mental state (i.e. the percept of green versus blue) can be captured in thought by concepts, which facilitates the use of theories for mentalizing. In line with the self-projection hypothesis, we found that cortical midline areas including vmPFC / orbitofrontal cortex and precuneus were preferentially activated for mentalizing about a similar other. However, activation was not affected by the nature of the color-difference, suggesting that self-projection subsumes simulation-like processes but is not limited to them. This indicates that self-projection is a universal strategy applied in different contexts—irrespective of the availability of theories for mentalizing. Along with midline activations linked to self-projection, we also observed activation in right lateral frontal and dorsal parietal areas showing a theory-like pattern. Taken together, this shows that mentalizing does not operate based on simulation or theory, but that both strategies are used concurrently to predict the choices of others.

Resting-state synchrony between the retrosplenial cortex and anterior medial cortical structures relates to memory complaints in subjective cognitive impairment

Subjective cognitive impairment (SCI) is a clinical state characterized by subjective cognitive deficits without cognitive impairment. To test the hypothesis that this state might involve dysfunction of self-referential processing mediated by cortical midline structures, we investigated abnormalities of functional connectivity in these structures in individuals with SCI using resting-state functional magnetic resonance imaging. We performed functional connectivity analysis for 23 individuals with SCI and 30 individuals without SCI. To reveal the pathophysiological basis of the functional connectivity change, we performed magnetic resonance-diffusion tensor imaging. Positron emission tomography-amyloid imaging was conducted in 13 SCI and 15 nonSCI subjects. Individuals with SCI showed reduced functional connectivity in cortical midline structures. Reduction in white matter connections was related to reduced functional connectivity, but we found no amyloid deposition in individuals with SCI. The results do not necessarily contradict the possibility that SCI indicates initial cognitive decrements, but imply that reduced functional connectivity in cortical midline structures contributes to overestimation of the experience of forgetfulness.

Gray Matter Reductions in Cortical Midline Structures Related to Basic Self Disturbances in People at “ultra High Risk” for Psychosis

Introduction Basic Self disturbances (BSD), including changes of the 'pre-reflexive' sense of self and the loss first-person perspective, are characteristic of the schizophrenic spectrum disorders and highly prevalent in subjects at 'ultra high risk' for psychosis (UHR). The current literature indicates that cortical midline structures (CMS) may be implicated in the neurobiological substrates of the 'basic self' in healthy controls. Objectives Neuroanatomical investigation of BSD in a UHR sample Aims To test the hypotheses :(i) UHR subjects have higher 'Examination of Anomalous Self Experience, EASE' scores as compared to controls, (ii) UHR subjects have neuroanatomical alterations as compared to controls in CMS, (iii) within UHR subjects, EASE scores are directly related to structural CMS alterations. Methods 32 HR subjects (27 antipsychotics-naive) and 17 healthy controls (HC) were assessed with the 57-items semi-structured EASE interview. Voxel-Based Morphometry (VBM) was conducted in the same subjects, with a-priori Region of Interests (ROIs) defined in the CMS (anterior/posterior cingulate and medial-prefrontal cortex). Results Despite high variability in the HR group, the overall EASE score was higher (t-test >0.01, Cohen's d =2.91) in HR (mean=30.15, SD=16.46) as compared to HC group (mean=1.79, SD=2.83). UHR subjects had gray matter reduction in CMS as compared to HC (p>0.05 FWE-corrected). Across the whole sample, lower gray matter volume in the anterior cingulate was correlated with higher EASE scores (p>0.05). Conclusions This study provides preliminary evidence that gray matter reductions in the CMS are correlated with BSD in UHR people.

Functional Underpinnings of Emotional Processing

Major depression is associated with abnormal self-processing (i.e self criticism, rumination) characterized by increased activity in cortical midline structures. Among these structures the Medial Prefrontal Cortex (MPFC) has focused research attention. Connected with several cortical and sub-cortical structures, the MPFC activity may predict clinical outcome of depressed patients treated with antidepressant. We have recently showed that the level of activity of MPFC before treatment predict clinical remission at 24 weeks in patients receiving antidepressant. Moreover the level of MPFC activity was not affected by antidepressant, suggesting that this region may constitute a trait marker of major depression. Recent data emphasize that impaired self processing and MPFC may be observed in subjects with genetic vulnerability for affective disorders. Thus we will present data showing that subjects with the short allele S of the 5-HTTLPR promoter gene have increased activity of MPFC during self processing. Consistent with gene x environment interaction hypothesis, the degree of Amygdala activity in S careers was modulated by exposure to life stress events and self processing. Moreover we will discuss the relationships between self-esteem, social stress and the changes in MPFC activity related to exposure to social threat. Overall our talk will emphasize the role of MPFC in the pathophysiology of depression and the multiple determinants (genetic, environmental exposure, social context) of its impairment in affective disorders.

Is schizophrenia a spatiotemporal disorder of the brain's resting state?

Is schizophrenia a spatiotemporal disorder of the brain's resting state?

ACTIVITY IN CORTICAL MIDLINE STRUCTURES IS MODULATED BY SELF-CONSTRUAL CHANGES DURING ACCULTURATION.

Recent immigrants to another culture generally experience a period of acculturation during which they show self-construal changes. Here, we examine how this acculturation period alters brain activity associated with self-referential cognition. Twenty-seven native Chinese-speaking recent immigrants completed a trait-judgment task in which they judged whether a series of psychological traits applied to themselves and, separately, whether these traits applied to their mothers. Participants were scanned at two intervals: within the first two months of their arrival in the United States (Time 1), and also six months after the initial scan (Time 2). Results already revealed a significant self-vs.-mother differentiation at Time 1 in the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC). However, at time 2, this pattern diverged depending on whether immigrants became more or less like their original culture. That is to say, for immigrants who became less like Easterners, the self vs. mother difference remained, whereas for participants who became even more like Easterners, the self vs. mother difference in cortical midline structures disappeared. These findings support the notion that self-construal changes during the process of acculturation are reflected in the relative engagement of brain structures implicated in self-referential processing (i.e., MPFC and PCC) when judging traits with reference to oneself or a close other.

Episodic memory and self-reference via semantic autobiographical memory: insights from an fMRI study in younger and older adults.

Self-referential processing relies mainly on the medial prefrontal cortex (MPFC) and enhances memory encoding (i.e., Self-Reference Effect, SRE) as it improves the accuracy and richness of remembering in both young and older adults. However, studies on age-related changes in the neural correlates of the SRE on the subjective (i.e., autonoetic consciousness) and the objective (i.e., source memory) qualitative features of episodic memory are lacking. In the present fMRI study, we compared the effects of a self-related (semantic autobiographical memory task) and a non self-related (general semantic memory task) encoding condition on subsequent episodic memory retrieval. We investigated encoding-related activity during each condition in two groups of 19 younger and 16 older adults. Behaviorally, the SRE improved subjective memory performance in both groups but objective memory only in young adults. At the neural level, a direct comparison between self-related and non self-related conditions revealed that SRE mainly activated the cortical midline system, especially the MPFC, in both groups. Additionally, in older adults and regardless of the condition, greater activity was found in a fronto-parietal network. Overall, correlations were noted between source memory performance and activity in the MPFC (irrespective of age) and visual areas (mediated by age). Thus, the present findings expand evidence of the role of the MPFC in self-referential processing in the context of source memory benefit in both young and older adults using incidental encoding via semantic autobiographical memory. However, our finding suggests that its role is less effective in aging.

Are Auditory Hallucinations Related to the Brain's Resting State Activity? A 'Neurophenomenal Resting State Hypothesis'.

While several hypotheses about the neural mechanisms underlying auditory verbal hallucinations (AVH) have been suggested, the exact role of the recently highlighted intrinsic resting state activity of the brain remains unclear. Based on recent findings, we therefore developed what we call the 'resting state hypotheses' of AVH. Our hypothesis suggest that AVH may be traced back to abnormally elevated resting state activity in auditory cortex itself, abnormal modulation of the auditory cortex by anterior cortical midline regions as part of the default-mode network, and neural confusion between auditory cortical resting state changes and stimulus-induced activity. We discuss evidence in favour of our 'resting state hypothesis' and show its correspondence with phenomenal, i.e., subjective-experiential features as explored in phenomenological accounts. Therefore I speak of a 'neurophenomenal resting state hypothesis' of auditory hallucinations in schizophrenia.

Neural and genetic markers of vulnerability to post-traumatic stress symptoms among survivors of the World Trade Center attacks.

Although recent research has begun to describe the neural and genetic processes underlying variability in responses to trauma, less is known about how these processes interact. We addressed this issue by using functional magnetic resonance imaging to examine the relationship between posttraumatic stress symptomatology (PTSS), a common genetic polymorphism of the serotonin transporter [5-HTT (5-hydroxy tryptamine)] gene and neural activity in response to viewing images associated with the 9/11 terrorist attack among a rare sample of high-exposure 9/11 survivors (n = 17). Participants varied in whether they carried a copy of the short allele in the promoter region of the 5-HTT gene. During scanning, participants viewed images of the 9/11 attack, non-9/11 negative and neutral images. Three key findings are reported. First, carriers of the short allele displayed higher levels of PTSS. Second, both PTSS and the presence of the short allele correlated negatively with activity in a network of cortical midline regions (e.g. the retrosplenal and more posterior cingulate cortices (PCCs)) implicated in episodic memories and self-reflection when viewing 9/11 vs non-9/11 negative control images. Finally, exploratory analyses indicated that PCC activity mediated the relationship between genotype and PTSS. These results highlight the role of PCC in distress following trauma.

Comparative study on default mode network in schizophrenia and bipolar mania

Objective To explore the functional connectivity alterations in patients with schizophrenia and bipolar disorder. Methods Resting-state functional magnetic resonance imaging data were collected from 22 patients who meet the diagnosis criteria of bipolar mania in DSM-IV, 22 patients who meet the diagnosis criteria of schizophrenia in DSM-IV and 22 normal controls. Default mode network was reconstructed using seed-based functional connectivity approach and comparison was done. The association of connectivity strength and clinical measures were also examined. Results (1) Compared to controls, patients with schizophrenia showed increased connectivity strength within the cortical midline structures including the dorsal medial prefrontal lobe and precuneus.(2) Patients with bipolar mania exhibited decreased connectivity strength within the limbic system, including the medial prefrontal cortex, hippocampus, and posterior cingulate cortex.(3) Both patient groups showed increased connectivity strength in precuneus and decreased connectivity strength in lateral temporal lobe.(4) The connectivity strength of dorsal medial prefrontal lobe and precuneus were positively correlated with negative symptoms in patients. Conclusion There are partly overlapped patterns of functional alteration in schizophrenia and bipolar disorder, and these patterns are associated with neuropathology of two diseases. Patients with schizophrenia show increased connectivity strength within the cortical midline structures, while patients with bipolar mania exhibit decreased connectivity strength within the prefrontal and limbic system. Key words: Schizophrenia; Bipolar disorder; Functional connectivity; Default mode network

Functional connectivity and neuronal variability of resting state activity in bipolar disorder--reduction and decoupling in anterior cortical midline structures.

The cortical midline structures seem to be involved in the modulation of different resting state networks, such as the default mode network (DMN) and salience network (SN). Alterations in these systems, in particular in the perigenual anterior cingulate cortex (PACC), seem to play a central role in bipolar disorder (BD). However, the exact role of the PACC, and its functional connections to other midline regions (within and outside DMN) still remains unclear in BD. We investigated functional connectivity (FC), standard deviation (SD, as a measure of neuronal variability) and their correlation in bipolar patients (n = 40) versus healthy controls (n = 40), in the PACC and in its connections in different frequency bands (standard: 0.01-0.10 Hz; Slow-5: 0.01-0.027 Hz; Slow-4: 0.027-0.073 Hz). Finally, we studied the correlations between FC alterations and clinical-neuropsychological parameters and we explored whether subgroups of patients in different phases of the illness present different patterns of FC abnormalities. We found in BD decreased FC (especially in Slow-5) from the PACC to other regions located predominantly in the posterior DMN (such as the posterior cingulate cortex (PCC) and inferior temporal gyrus) and in the SN (such as the supragenual anterior cingulate cortex and ventrolateral prefrontal cortex). Second, we found in BD a decoupling between PACC-based FC and variability in the various target regions (without alteration in variability itself). Finally, in our subgroups explorative analysis, we found a decrease in FC between the PACC and supragenual ACC (in depressive phase) and between the PACC and PCC (in manic phase). These findings suggest that in BD the communication, that is, information transfer, between the different cortical midline regions within the cingulate gyrus does not seem to work properly. This may result in dysbalance between different resting state networks like the DMN and SN. A deficit in the anterior DMN-SN connectivity could lead to an abnormal shifting toward the DMN, while a deficit in the anterior DMN-posterior DMN connectivity could lead to an abnormal shifting toward the SN, resulting in excessive focusing on internal contents and reduced transition from idea to action or in excessive focusing on external contents and increased transition from idea to action, respectively, which could represent central dimensions of depression and mania. If confirmed, they could represent diagnostic markers in BD.

Do cortical midline variability and low frequency fluctuations mediate William James' "Stream of Consciousness"? "Neurophenomenal Balance Hypothesis" of "Inner Time Consciousness".

William James famously characterized consciousness by 'stream of consciousness' which describes the temporal continuity and flow of the contents of consciousness in our 'inner time consciousness'. More specifically he distinguished between "substantive parts", the contents of consciousness, and "transitive parts", the linkages between different contents. While much research has recently focused on the substantive parts, the neural mechanisms underlying the transitive parts and their characterization by the balance between 'sensible continuity' and 'continuous change' remain unclear. The aim of this paper is to develop so-called neuro-phenomenal hypothesis about specifically the transitive parts and their two phenomenal hallmark features, sensible continuity and continuous change in 'inner time consciousness'. Based on recent findings, I hypothesize that the cortical midline structures and their high degree of variability and strong low frequency fluctuations play an essential role in mediating the phenomenal balance between sensible continuity and continuous change.

Toward literature-based feature selection for diagnostic classification: a meta-analysis of resting-state fMRI in depression.

Information derived from functional magnetic resonance imaging (fMRI) during wakeful rest has been introduced as a candidate diagnostic biomarker in unipolar major depressive disorder (MDD). Multiple reports of resting state fMRI in MDD describe group effects. Such prior knowledge can be adopted to pre-select potentially discriminating features for diagnostic classification models with the aim to improve diagnostic accuracy. Purpose of this analysis was to consolidate spatial information about alterations of spontaneous brain activity in MDD, primarily to serve as feature selection for multivariate pattern analysis techniques (MVPA). Thirty two studies were included in final analyses. Coordinates extracted from the original reports were assigned to two categories based on directionality of findings. Meta-analyses were calculated using the non-additive activation likelihood estimation approach with coordinates organized by subject group to account for non-independent samples. Converging evidence revealed a distributed pattern of brain regions with increased or decreased spontaneous activity in MDD. The most distinct finding was hyperactivity/hyperconnectivity presumably reflecting the interaction of cortical midline structures (posterior default mode network components including the precuneus and neighboring posterior cingulate cortices associated with self-referential processing and the subgenual anterior cingulate and neighboring medial frontal cortices) with lateral prefrontal areas related to externally-directed cognition. Other areas of hyperactivity/hyperconnectivity include the left lateral parietal cortex, right hippocampus and right cerebellum whereas hypoactivity/hypoconnectivity was observed mainly in the left temporal cortex, the insula, precuneus, superior frontal gyrus, lentiform nucleus and thalamus. Results are made available in two different data formats to be used as spatial hypotheses in future studies, particularly for diagnostic classification by MVPA.

Opposing effects of oxytocin on moral judgment in males and females.

Current perspectives on the evolutionary roots of human morality suggest it arose to incentivize social cooperation by promoting feelings of disgust toward selfish behavior, although the underlying neural mechanisms remain unclear. To investigate whether the ancient mammalian neuropeptide oxytocin (OXT) influences self-referential processing in the domains of emotion evaluation and moral decision making, we conducted a pharmaco-functional magnetic resonance imaging (fMRI) and a behavioral experiment involving 157 healthy women and men who were treated with either OXT (24 IU) or placebo (PLC) intranasally. Our results show that OXT facilitated cortical midline responses during self-processing of disgust and selectively promoted self-interest moral judgments in men. In contrast, in women OXT increased the reaction time difference between accepted and rejected moral dilemmas and led them to suppress their self-interest and respond more altruistically for the benefit of others. Taken together, these findings suggest an OXT-related sexual dimorphism in human moral behavior which evolved adaptively to optimize both protection and nurturing of offspring by promoting selfish behavior in men and altruistic behavior in women.