Two Sides of the Same Coin in Female Borderline Personality Disorder: Self-Reported Guilt and Shame and Their Neurofunctional Correlates.

OBJECTIVE: Patients with borderline personality disorder (BPD) report to be especially prone to social emotions like shame and guilt. At the same time, these emotions seem to play an important role in BPD pathology. The present study aimed to deepen the knowledge about the processes behind shame and guilt in patients with BPD. METHODS: Twenty patients with BPD and twenty healthy controls (HCs) took part in an experiment that induced shame and guilt by imagining scenarios during scanning using functional brain imaging. Participants also filled out self-report questionnaires and took part in diagnostic interviews. RESULTS: BPD patients reported more proneness to guilt but not to shame than the HCs. There was no difference in the self-reported intensity rating of experimentally induced emotions between the groups. Between-group contrast of neural signals in the shame condition revealed a stronger activation of cingulate and fusiform gyrus for the BPD patients compared to the controls, and a more pronounced activation in the lingual gyrus and cuneus for the HCs. In the guilt condition, activation in the caudate nucleus, the fusiform gyrus, and the posterior cingulate cortex was stronger in BPD patients, while HC showed stronger activations in cuneus, lingual gyrus, and fronto-temporal regions. CONCLUSIONS: Differences in the neuro-functional processes between BPD patients and HC were found, even though the two groups did not differ in their self-report of subjective proneness to guilt and emotional intensity of shame and guilt during the experiment. While the HCs may be engaged more by the emotional scenarios themselves, the BPD patients may be more occupied with cognitive regulatory and self-referential processing.

Two Sides of Theory of Mind: Mental State Attribution to Moving Shapes in Paranoid Schizophrenia Is Independent of the Severity of Positive Symptoms.

BACKGROUND: Theory of Mind (ToM) impairment has repeatedly been found in paranoid schizophrenia. The current study aims at investigating whether this is related to a deficit in ToM (undermentalizing) or an increased ToM ability to hyperattribute others' mental states (overmentalizing). METHODS: Mental state attribution was examined in 24 patients diagnosed with schizophrenia (12 acute paranoid (APS) and 12 post-acute paranoid (PPS)) with regard to positive symptoms as well as matched healthy persons using a moving shapes paradigm. We used 3-T-functional magnetic resonance imaging (fMRI) to provide insights into the neural underpinnings of ToM due to attributional processes in different states of paranoid schizophrenia. RESULTS: In the condition that makes demands on theory of mind skills (ToM condition), in patients with diagnosed schizophrenia less appropriate mental state descriptions have been used, and they attributed mental states less often to the moving shapes than healthy persons. On a neural level, patients suffering from schizophrenia exhibited within the ToM network hypoactivity in the medial prefrontal cortex (MPFC) and hyperactivity in the temporo-parietal junction (TPJ) as compared to the healthy sample. CONCLUSIONS: Our results indicate both undermentalizing and hypoactivity in the MPFC and increased overattribution related to hyperactivity in the TPJ in paranoid schizophrenia, providing new implications for understanding ToM in paranoid schizophrenia.

The Interplay of Oxytocin and Attachment in Schizophrenic Patients: An fMRI Study.

BACKGROUND: Attachment theory offers an important framework for understanding interpersonal interaction experiences. In the present study, we examined the neural correlates of attachment patterns and oxytocin in schizophrenic patients (SZP) compared to healthy controls (HC) using fMRI. We assumed that male SZP shows a higher proportion of insecure attachment and an altered level of oxytocin compared to HC. On a neural level, we hypothesized that SZP shows increased neural activation in memory and self-related brain regions during the activation of the attachment system compared to HC. METHODS: We used an event-related design for the fMRI study based on stimuli that were derived from the Adult Attachment Projective Picture System to examine attachment representations and their neural and hormonal correlates in 20 male schizophrenic patients compared to 20 male healthy controls. RESULTS: A higher proportion of insecure attachment in schizophrenic patients compared to HC could be confirmed. In line with our hypothesis, Oxytocin (OXT) levels in SZP were significantly lower than in HC. We found increasing brain activations in SZP when confronted with personal relevant sentences before attachment relevant pictures in the precuneus, TPJ, insula, and frontal areas compared to HC. Moreover, we found positive correlations between OXT and bilateral dlPFC, precuneus, and left ACC in SZP only. CONCLUSION: Despite the small sample sizes, the patients' response might be considered as a mode of dysregulation when confronted with this kind of personalized attachment-related material. In the patient group, we found positive correlations between OXT and three brain areas (bilateral dlPFC, precuneus, left ACC) and may conclude that OXT might modulate within this neural network in SZP.

Association of schizotypy with striatocortical functional connectivity and its asymmetry in healthy adults.

Altered striatocortical functional connectivity has been suggested to be a trait marker of schizophrenia spectrum disorders, including schizotypal personality. In the present study, we examined the association between schizotypal personality traits and striatocortical functional connectivity in a sample of healthy adults. The German version of the Schizotypal Personality Questionnaire was obtained from N = 111 participants recruited from the general public. Resting-state functional magnetic resonance imaging scans were acquired at 3T. Six striatal seed regions in each hemisphere were defined and striatocortical resting-state functional connectivity (rsFC) as well as its lateralization indices was calculated. Regression analysis showed that schizotypy scores, especially from the positive dimension, were positively correlated with rsFC between ventral striatum and frontal cortex and negatively associated with rsFC between dorsal striatum and posterior cingulate. No significant associations were found between negative dimension schizotypy and striatocortical rsFC. We also found positive correlations between schizotypy total scores and lateralization index of right dorsal caudate and right rostral putamen. In conclusion, the present study extends previous evidence of altered striatocortical rsFC in the schizophrenia spectrum. The observed associations resemble in part the alterations observed in psychotic patients and their relatives, providing support for dimensionality from schizotypal personality to the clinical disorder. Hum Brain Mapp 39:288-299, 2018. © 2017 Wiley Periodicals, Inc.

Prefrontal Transcranial Direct Current Stimulation for Treatment of Schizophrenia With Predominant Negative Symptoms: A Double-Blind, Sham-Controlled Proof-of-Concept Study.

Negative symptoms are highly relevant in the long-term course of schizophrenia and are an important target domain for the development of novel interventions. Recently, transcranial direct current stimulation (tDCS) of the prefrontal cortex has been investigated as a treatment option in schizophrenia. In this proof-of-concept study, 20 schizophrenia patients with predominantly negative symptoms were randomized to either 10 sessions of add-on active (2 mA, 20min) or sham tDCS (anode: left DLPFC/F3; cathode: right supraorbital/F4). Primary outcome measure was the change in the Scale for the Assessment of Negative Symptoms (SANS) sum score; secondary outcomes included reduction in Positive and Negative Syndrome Scale (PANSS) scores and improvement of depressive symptoms, cognitive processing speed, and executive functioning. Sixteen patients underwent 4 functional connectivity magnetic resonance imaging (fcMRI) scans (pre and post 1st and pre and post 10th tDCS) to investigate changes in resting state network connectivity after tDCS. Per-protocol analysis showed a significantly greater decrease in SANS score after active (-36.1%) than after sham tDCS (-0.7%). PANSS sum scores decreased significantly more with active (-23.4%) than with sham stimulation (-2.2%). Explorative analysis of fcMRI data indicated changes in subgenual cortex and dorsolateral prefrontal cortex (DLPFC) connectivity within frontal-thalamic-temporo-parietal networks. The results of this first proof-of-concept study indicate that prefrontal tDCS may be a promising intervention for treatment of schizophrenia with predominant negative symptoms. Large-scale randomized controlled studies are needed to further establish prefrontal tDCS as novel treatment for negative symptoms in schizophrenia.

Effects of rivastigmine on visual attention in subjects with amnestic mild cognitive impairment: A serial functional MRI activation pilot-study.

A pilot study to investigate the effects of rivastigmine on the brain activation pattern due to visual attention tasks in a group of amnestic Mild Cognitive Impaired patients (aMCI). The design was an initial three-month double blind period with a rivastigmine and placebo arms, followed by a nine-month open-label period. All patients underwent serial functional magnetic resonance imaging (fMRI) at baseline, and after three and six months of follow-up. Primary endpoint was the effect of rivastigmine on functional brain changes during visual attention (face and location matching) tasks. There were five in the rivastigmine arm and two in the placebo arm. The face matching task showed higher activation of visual areas after three months of treatment but no differences compared to baseline at six months. The location matching task showed a higher activation along the dorsal visual pathway at both three and six months follow ups. Treatment with rivastigmine demonstrates a significant effect on brain activation of the dorsal visual pathway during a location matching task in patients with aMCI. Our data support the potential use of task fMRI to map specific treatment effects of cholinergic drugs during prodromal stages of Alzheimer's disease (AD).

Functional connectivity increase in the default-mode network of patients with Alzheimer's disease after long-term treatment with Galantamine.

Acetylcholinesterase inhibitors (AChEIs) are efficacious for the treatment of mild to moderate forms of Alzheimer's dementia (AD). Default-mode network (DMN) connectivity is considered to be early impaired in AD. Long-term effects of AChEIs on the DMN in AD have not yet been investigated. Twenty-eight AD patients and 11 age-matched healthy volunteers (HC) participated in the prospective study. AD patients were randomly assigned to either a pharmacotherapy arm (Galantamine, AD G) or to a placebo arm (AD P+G) for the period of 6 months followed by open-label Galantamine therapy from month 7-12. All subjects underwent neuropsychological testing, resting-state functional and structural MRI at baseline and after 12 months, AD patients additionally in between after 6 months. Thirteen AD patients completed the treatment trial and underwent all functional MRI follow-up sequences of good quality. Functional connectivity significantly increased within the AD G group in the posterior cingulate cortex and in the Precuneus between baseline and 12 months follow-up (pcorr<0.05). Between-group analyses demonstrated that functional connectivity in the AD G group significantly increased in the posterior cingulate cortex as well as in the Precuneus compared to the HC group and in the anteromedial aspect of the temporal lobes compared to the AD P+G group, respectively, at 12 months follow-up (pcorr<0.05). Cognitive performance remained stable within groups over time indicating that resting-state fMRI may be sensitive for the detection of pharmacologically induced effects on brain function of AD patients.

Association of COMT and SLC6A3 polymorphisms with impulsivity, response inhibition and brain function.

Evidence of the genetic correlates of inhibitory control is scant. Two previously studied dopamine-related polymorphisms, COMT rs4680 and the SLC6A3 3' UTR 40-base-pair VNTR (rs28363170), have been associated with response inhibition, however with inconsistent findings. Here, we investigated the influence of these two polymorphisms in a large healthy adult sample (N = 515) on a response inhibition battery including the antisaccade, stop-signal, go/no-go and Stroop tasks as well as a psychometric measure of impulsivity (Barratt Impulsiveness Scale) (Experiment 1). Additionally, a subsample (N = 144) was studied while performing the go/no-go, stop-signal and antisaccade tasks in 3T fMRI (Experiment 2). In Experiment 1, we did not find any significant associations of COMT or SLC6A3 with inhibitory performance or impulsivity. In Experiment 2, no association of COMT with BOLD was found. However, there were consistent main effects of SLC6A3 genotype in all inhibitory contrasts: Homozygosity of the 10R allele was associated with greater fronto-striatal BOLD response than genotypes with at least one 9R allele. These findings are consistent with meta-analyses showing that the 10R allele is associated with reduced striatal dopamine transporter expression, which in animal studies has been found to lead to increased extracellular dopamine levels. Our study thus supports the involvement of striatal dopamine in the neural mechanisms of cognitive control, in particular response inhibition.

Obsessive-compulsive disorder--A question of conscience? An fMRI study of behavioural and neurofunctional correlates of shame and guilt.

Shame and guilt can be described as 'self-conscious emotions' and are an essential part of the psychopathology in obsessive-compulsive disorder (OCD). Our primary aim was to explore whether individuals with OCD are processing shame and guilt differently from healthy individuals (N = 20 in both groups; 50% female; age: 20-40 years) on the behavioural and neurobiological level. For the experimental task, participants were scanned with functional magnetic resonance tomography (functional magnetic resonance imaging, 3 T) while imagining neutral, shame inducing and guilt inducing scenarios. In addition to clinical questionnaires, participants were asked to complete questionnaires measuring shame and guilt. The functional data indicate an increased activity in OCD patients in the shame condition in the limbic, temporal and sub-lobar (hypothalamus) areas, in the guilt condition inter alia in frontal, limbic and temporal areas. In summary we found activity in OCD patients in neural networks which are responsible for stimulus filtering, emotion regulation, impulse control and memory. The results from our study may contribute to a better understanding of the origins and maintenance of OCD in association with the pathological processing of shame and guilt on different functional levels.

Methylphenidate effects on brain activity as a function of SLC6A3 genotype and striatal dopamine transporter availability.

We pharmacologically challenged catecholamine reuptake, using methylphenidate, to investigate its effects on brain activity during a motor response inhibition task as a function of the 3'-UTR variable number of tandem repeats (VNTR) polymorphism of the dopamine transporter (DAT) gene (SLC6A3) and the availability of DATs in the striatum. We measured the cerebral hemodynamic response of 50 healthy males during a Go/No-Go task, a measure of cognitive control, under the influence of 40 mg methylphenidate and placebo using 3T functional magnetic resonance imaging. Subjects were grouped into 9-repeat (9R) carriers and 10/10 homozygotes on the basis of the SLC6A3 VNTR. During successful no-go trials compared with oddball trials, methylphenidate induced an increase of blood oxygen level-dependent (BOLD) signal for carriers of the SLC6A3 9R allele but a decrease in 10/10 homozygotes in a thalamocortical network. The same pattern was observed in caudate and inferior frontal gyrus when successful no-go trials were compared with successful go trials. We additionally investigated in a subset of 35 participants whether baseline striatal DAT availability, ascertained with (123)I-FP-CIT single photon emission computed tomography, predicted the amount of methylphenidate-induced change in hemodynamic response or behavior. Striatal DAT availability was nominally greater in 9R carriers compared with 10/10 homozygotes (d=0.40), in line with meta-analyses, but did not predict BOLD or behavioral changes following MPH administration. We conclude that the effects of acute MPH administration on brain activation are dependent on DAT genotype, with 9R carriers showing enhanced BOLD following administration of a prodopaminergic compound.

Preliminary findings on the heritability of the neural correlates of response inhibition.

Imaging genetics examines genetic influences on brain structure and function. This preliminary study tested a fundamental assumption of that approach by estimating the heritability of the blood oxygen level dependent (BOLD) signal during antisaccades, a measure of response inhibition impaired in different psychiatric conditions. One hundred thirty-two healthy same-sex reared-together twins (90 monozygotic (MZ; 32 male) and 42 dizygotic (DZ; 24 male)) performed antisaccades in the laboratory. Of these, 96 twins (60 MZ, 28 male; 36 DZ, 22 male) subsequently underwent functional magnetic resonance imaging (fMRI) during antisaccades. Variation in antisaccade direction errors in the laboratory showed significant heritability (47%; 95% confidence interval (CI) 22-65). In fMRI, the contrast of antisaccades with prosaccades yielded BOLD signal in fronto-parietal-subcortical networks. Twin modelling provided tentative evidence of significant heritability (50%, 95% CI: 18-72) of BOLD in the left thalamus only. However, due to the limited power to detect heritability in this study, replications in larger samples are needed.

Dysregulated daily rhythmicity of neuronal resting-state networks in MCI patients.

In young healthy participants, the degree of daily rhythmicity largely varies across different neuronal resting-state networks (RSNs), while it is to date unknown whether this temporal pattern of activity is conserved in healthy and pathological aging. Twelve healthy elderly (mean age=65.1±5.7 years) and 12 patients with amnestic mild cognitive impairment (aMCI; mean age=69.6±6.2 years) underwent four resting-state functional magnetic resonance imaging scans at fixed 2.5 h intervals throughout a day. Time courses of a RSN were extracted by a connectivity strength and a spatial extent approach performed individually for each participant. Highly rhythmic RSNs included a sensorimotor, a cerebellar and a visual network in healthy elderly; the least rhythmic RSNs in this group included a network associated with executive control and an orbitofrontal network. The degree of daily rhythmicity in aMCI patients was reduced and dysregulated. For healthy elderly, the findings are in accordance with results reported for young healthy participants suggesting a comparable distribution of daily rhythmicity across RSNs during healthy aging. In contrast, the reduction and dysregulation of daily rhythmicity observed in aMCI patients is presumably indicative of underlying neurodegenerative processes in this group.

The effects of methylphenidate on whole brain intrinsic functional connectivity.

Methylphenidate (MPH) is an indirect dopaminergic and noradrenergic agonist that is used to treat attention deficit hyperactivity disorder and that has shown therapeutic potential in neuropsychiatric diseases such as depression, dementia, and Parkinson's disease. While effects of MPH on task-induced brain activation have been investigated, little is known about how MPH influences the resting brain. To investigate the effects of 40 mg of oral MPH on intrinsic functional connectivity, we used resting state fMRI in 54 healthy male subjects in a double-blind, randomized, placebo-controlled study. Functional connectivity analysis employing ICA revealed seven resting state networks (RSN) of interest. Connectivity strength between the dorsal attention network and the thalamus was increased after MPH intake. Other RSN located in association cortex areas, such as the left and right frontoparietal networks and the executive control network, showed MPH-induced connectivity increase to sensory-motor and visual cortex regions and connectivity decrease to cortical and subcortical components of cortico-striato-thalamo-cortical circuits (CST). RSN located in sensory-motor cortex areas showed the opposite pattern with MPH-induced connectivity increase to CST components and connectivity decrease to sensory-motor and visual cortex regions. Our results provide evidence that MPH does not only alter intrinsic connectivity between brain areas involved in sustained attention, but that it also induces significant changes in the cortico-cortical and cortico-subcortical connectivity of many other cognitive and sensory-motor RSN.

Self processing in the brain: a paradigmatic fMRI case study with a professional singer.

Understanding the mechanisms involved in perception and conception of oneself is a fundamental psychological topic with high relevance for psychiatric and neurological issues, and it is one of the great challenges in neuroscientific research. The paradigmatic single-case study presented here aimed to investigate different components of self- and other-processes and to elucidate corresponding neurobiological underpinnings. An eminent professional opera singer with profound performance experience has undergone functional magnetic resonance imaging and was exposed to excerpts of Mozart arias, sung by herself or another singer. The results indicate a distinction between self- and other conditions in cortical midline structures, differentially involved in self-related and self-referential processing. This lends further support to the assumption of cortical midline structures being involved in the neural processing of self-specific stimuli and also confirms the power of single case studies as a research tool.

Task preparation and neural activation in stimulus-specific brain regions: an fMRI study with the cued task-switching paradigm.

To investigate the role of posterior brain regions related to task-relevant stimulus processing in task preparation, we used a cued task-switching paradigm in which a pre-cue informed participants about the upcoming task on a trial: face discrimination or number comparison. Employing an event-related fMRI design, we examined for changes of activity in face- and number-related posterior brain regions (right fusiform face area (FFA) and right intraparietal sulcus (IPSnum), respectively), and explored the functional connectivity of these areas with other brain regions, during the (preparation) interval between cue onset and onset of the (to-be-responded) target stimulus. The results revealed task-relevant posterior brain regions to be modulated during this period: activation in task-relevant stimulus-specific regions was selectively enhanced and their functional connectivity to task-relevant anterior brain regions strengthened (right FFA - face task, right IPSnum - number task) while participants prepared for the cued task. Additionally, activity in task-relevant posterior brain regions was influenced by residual activation from the preceding trial in the right FFA and the right IPSnum, respectively. These findings indicate that, during task preparation, the activation pattern in currently task-relevant posterior brain regions is shaped by residual activation as well as preparatory modulation prior to the onset of the critical stimulus, even without participants being instructed to imagine the stimulus.

Fractional anisotropy changes in Alzheimer's disease depend on the underlying fiber tract architecture: a multiparametric DTI study using joint independent component analysis.

Diffusion tensor imaging (DTI) allows the simultaneous measurement of several diffusion indices that provide complementary information on the substrate of white matter alterations in neurodegenerative diseases. These indices include fractional anisotropy (FA) as measure of fiber tract integrity, and the mode of anisotropy (Mode) reflecting differences in the shape of the diffusion tensor. We used a multivariate approach based on joint independent component analysis of FA and Mode in a large sample of 138 subjects with Alzheimer's disease (AD) dementia, 37 subjects with cerebrospinal fluid biomarker positive mild cognitive impairment (MCI-AD), and 153 healthy elderly controls from the European DTI Study on Dementia to comprehensively study alterations of microstructural white matter integrity in AD dementia and predementia AD. We found a parallel decrease of FA and Mode in intracortically projecting fiber tracts, and a parallel increase of FA and Mode in the corticospinal tract in AD patients compared to controls. Subjects with MCI-AD showed a similar, but spatially more restricted pattern of diffusion changes. Our findings suggest an early axonal degeneration in intracortical projecting fiber tracts in dementia and predementia stages of AD. An increase of Mode, parallel to an increase of FA, in the corticospinal tract suggests a more linear shape of diffusion due to loss of crossing fibers along relatively preserved cortico-petal and cortico-fugal fiber tracts in AD. Supporting this interpretation, we found three populations of fiber tracts, namely cortico-petal and cortico-fugal, commissural, and intrahemispherically projecting fiber tracts, in the peak area of parallel FA and Mode increase.

Differences between musicians and non-musicians in neuro-affective processing of sadness and fear expressed in music.

Music is known to convey and evoke emotional states. Musical training has been argued to lead to changes in neural architecture and enhanced processing of emotions. It is not clear, however, whether musical training is also associated with changes in behavioral and neural responses to musically conveyed discrete emotions. Using functional magnetic resonance imaging, we investigated the responses to three musically conveyed emotions (happiness, sadness, fear) in a group of musicians and a group of non-musicians. We find that musicians rate sadness and fear as significantly more arousing than non-musicians, and that musical training is associated with specific neural activations: In response to sadness expressed in music, musicians show activation increases in the right prefrontal cortex, specifically in the superior and middle frontal gyri. In response to fear, musicians show activation increases in the right parietal cortex, specifically in the supramarginal and inferior parietal gyri. No specific activations were observed in response to happiness. Our results highlight the strong association between musical training and altered processing of "negative" emotions on both the behavioral and on the neural level.

Sadness is unique: neural processing of emotions in speech prosody in musicians and non-musicians.

Musical training has been shown to have positive effects on several aspects of speech processing, however, the effects of musical training on the neural processing of speech prosody conveying distinct emotions are yet to be better understood. We used functional magnetic resonance imaging (fMRI) to investigate whether the neural responses to speech prosody conveying happiness, sadness, and fear differ between musicians and non-musicians. Differences in processing of emotional speech prosody between the two groups were only observed when sadness was expressed. Musicians showed increased activation in the middle frontal gyrus, the anterior medial prefrontal cortex, the posterior cingulate cortex and the retrosplenial cortex. Our results suggest an increased sensitivity of emotional processing in musicians with respect to sadness expressed in speech, possibly reflecting empathic processes.

The ε4 genotype of apolipoprotein E and white matter integrity in Alzheimer's disease.

BACKGROUND: In this multicenter study, we investigated a possible association between the APOE ε4 allele and white matter (WM) integrity in Alzheimer's disease (AD) using diffusion tensor imaging (DTI). METHODS: We analyzed fractional anisotropy (FA) and mean diffusivity (MD) as indices of WM integrity in 70 AD patients (35 APOE ε4 carriers, 35 noncarriers) and 56 healthy control (HC) subjects (28 APOE ε4 carriers, 28 noncarriers). APOE ε4 carriers and noncarriers were matched for age and gender within each diagnostic group. RESULTS: We found significant effects of diagnosis (Pcorrected < .05 [FWE]; i.e., smaller FA values and larger MD values in AD patients compared with HCs) and significant effects (P < .001) of APOE ε4 carrier status on MD in HCs but not in AD subjects. CONCLUSIONS: The results indicate that APOE ε4 has a moderate effect on WM integrity in HCs, but no effect on WM integrity in manifest AD.

Neurobiological underpinnings of shame and guilt: a pilot fMRI study.

In this study, a functional magnetic resonance imaging paradigm originally employed by Takahashi et al. was adapted to look for emotion-specific differences in functional brain activity within a healthy German sample (N = 14), using shame- and guilt-related stimuli and neutral stimuli. Activations were found for both of these emotions in the temporal lobe (shame condition: anterior cingulate cortex, parahippocampal gyrus; guilt condition: fusiform gyrus, middle temporal gyrus). Specific activations were found for shame in the frontal lobe (medial and inferior frontal gyrus), and for guilt in the amygdala and insula. This is consistent with Takahashi et al.'s results obtained for a Japanese sample (using Japanese stimuli), which showed activations in the fusiform gyrus, hippocampus, middle occipital gyrus and parahippocampal gyrus. During the imagination of shame, frontal and temporal areas (e.g. middle frontal gyrus and parahippocampal gyrus) were responsive regardless of gender. In the guilt condition, women only activate temporal regions, whereas men showed additional frontal and occipital activation as well as a responsive amygdala. The results suggest that shame and guilt share some neural networks, as well as having individual areas of activation. It can be concluded that frontal, temporal and limbic areas play a prominent role in the generation of moral feelings.