Sensory-Tactile Functional Mapping and Use-Associated Structural Variation of the Human Female Genital Representation Field.

The precise location of the human female genital representation field in the primary somatosensory cortex (S1) is controversial and its capacity for use-associated structural variation as a function of sexual behavior remains unknown. We used a functional magnetic resonance imaging (fMRI)-compatible sensory-tactile stimulation paradigm to functionally map the location of the female genital representation field in 20 adult women. Neural response to tactile stimulation of the clitoral region (vs right hand) identified individually-diverse focal bilateral activations in dorsolateral areas of S1 (BA1-BA3) in alignment with anatomic location. We next used cortical surface analyses to assess structural thickness across the 10 individually most activated vertices per hemisphere for each woman. We show that frequency of sexual intercourse within 12 months is correlated with structural thickness of the individually-mapped left genital field. Our results provide a precise functional localization of the female genital field and provide support for use-associated structural variation of the human genital cortex.SIGNIFICANCE STATEMENT We provide a precise location of the human female genital field in the somatosensory cortex and, for the first time, provide evidence in support of structural variation of the human genital field in association with frequency of genital contact. Our study represents a significant methodological advance by individually mapping genital fields for structural analyses. On a secondary level, our results suggest that any study investigating changes in the human genital field must map the field individually to achieve sufficient precision. Our results pave the way for future research into the plasticity of the human genital cortex as a function of normal or adverse experience as well as changes in pathologic conditions, i.e., sexual dysfunction, sexual deviation, or sexual risk-taking behavior.

Interacting and dissociable effects of alexithymia and depression on empathy.

Major-depressive-disorder (MDD) and alexithymia have both been associated with empathy deficits. We examined whether depression and alexithymia show dissociable or interacting effects on cognitive and emotional trait and state empathy. Healthy controls with high and low alexithymia and MDD-patients with high and low alexithymia were assessed. We used the Interpersonal-Reactivity-Index-questionnaire (IRI) for trait cognitive and emotional empathy and the Multifaceted-Empathy-Test (MET) for state cognitive and emotional empathy. Firstly, we found a main effect of alexithymia, irrespective of depression, on trait and state cognitive empathy: High alexithymia subjects showed lower scores in perspective taking (IRI) and in the cognitive-empathy-component of the MET. Secondly, we found main effects of alexithymia and depression on trait emotional empathy (IRI-subscale personal distress). Moreover, we found a significant depression-by-alexithymia-interaction on trait emotional empathy: MDD-patients showed particularly high personal distress when affected by alexithymia (IRI). Thirdly, alexithymia and depression had no impact on state emotional empathy (MET). However, analyzing positive and negative trials separately, we found more emotional empathy in MDD-patients concerning negatively valenced stimuli. Our data suggest dissociable and interacting effects of MDD and alexithymia on empathy. Importantly, except for heightened personal distress, empathy deficits in MDD-patients were entirely due to concurrent alexithymia.

Decreased medial prefrontal cortex activation during self-referential processing in bipolar mania.

BACKGROUND: Patients with bipolar disorder in mania exhibit symptoms pointing towards altered self-referential processing, such as decreased self-focus, flight of ideas and high distractibility. In depression, the opposite pattern of symptoms has been connected to increased activation of medial prefrontal cortex (mPFC) during self-referential processing. In this study, we hypothesized that (1) patients with mania will exhibit decreased activation in the mPFC during self-referential processing and (2) will be more alexithymic and that levels of alexithymia will correlate negatively with mPFC activation. METHODS: The neural response to standardized pictures was compared in 14 patients with bipolar I disorder in mania to 14 healthy controls using blood oxygen level dependent contrast magnetic resonance imaging. Participants were asked to indicate with button press during the scanning session for each picture whether the pictures personally related to them or not. Toronto alexithymia scale (TAS) scores were recorded from all participants. RESULTS: In the group analysis, patients with mania exhibited decreased activation in a predefined region of interest in the mPFC during self-referential processing compared to healthy controls. Patients with mania showed significantly higher levels of alexithymia, attributable to difficulties in identifying and describing emotions. Activation in the mPFC correlated negatively with levels of alexithymia. LIMITATIONS: Results presented here should be replicated in a larger group, potentially including unmedicated patients. CONCLUSIONS: The finding of decreased mPFC activation during self-referential processing in mania may reflect decreased self-focus and high distractibility. Support for this view comes from the negative correlation between higher alexithymia scores and decreased mPFC activation. These findings represent an opposite clinical and neuroimaging pattern to findings in depression.

Social cognition in aggressive offenders: Impaired empathy, but intact theory of mind.

Aggressive, violent behaviour is a major burden and challenge for society. It has been linked to deficits in social understanding, but the evidence is inconsistent and the specifics of such deficits are unclear. Here, we investigated affective (empathy) and cognitive (Theory of Mind) routes to understanding other people in aggressive individuals. Twenty-nine men with a history of legally relevant aggressive behaviour (i.e. serious assault) and 32 control participants were tested using a social video task (EmpaToM) that differentiates empathy and Theory of Mind and completed questionnaires on aggression and alexithymia. Aggressive participants showed reduced empathic responses to emotional videos of others' suffering, which correlated with aggression severity. Theory of Mind performance, in contrast, was intact. A mediation analysis revealed that reduced empathy in aggressive men was mediated by alexithymia. These findings stress the importance of distinguishing between socio-affective and socio-cognitive deficits for understanding aggressive behaviour and thereby contribute to the development of more efficient treatments.

Behavioral impulsivity mediates the relationship between decreased frontal gray matter volume and harmful alcohol drinking: A voxel-based morphometry study.

Alcohol use disorder (AUD) with harmful drinking patterns is on the one hand characterized by impulsive behavior and is on the other hand known to involve structural brain alterations with lower gray matter volume (GMV), especially in the prefrontal cortex (PFC). So far it is unclear whether frontal brain volumes are associated to harmful alcohol drinking and impulsivity, while controlling simultaneously for a wide array of important confounding factors, which are related to alcohol consumption. We used voxel-based morphometry in 99 adults ranging within a continuum of normal to harmful drinking behavior and alcohol dependence, measured by the 'Alcohol Use Disorders Identification Test', to examine whether the severity of harmful drinking is correlated with structural markers, in particular in the PFC and whether such markers are linked to self-reported impulsivity. We included alcohol and nicotine lifetime exposure, age, education, and BMI as covariates to control that GMV decreases were not related to those factors. Harmful drinking was associated with lower GMV in the right frontal pole, left inferior frontal gyrus, and bilateral inferior parietal lobe. GMV loss in the PFC regions was correlated with increased impulsivity. Follow-up mediation analyses showed that the relationship between GMV in the frontal pole and harmful drinking was mediated by impulsivity. Our findings show that PFC reductions are associated with harmful drinking and impulsivity. Our data suggest that reduced frontal pole GM, independent of a number of alcohol drinking associated covariates, e.g. lifetime alcohol consumption, is related to impaired top-down control of alcohol drinking behavior.

To drink or not to drink: Harmful drinking is associated with hyperactivation of reward areas rather than hypoactivation of control areas in men.

BACKGROUND: The maintenance of harmful alcohol use can be considered a reiterated decision in favour of alcohol in concrete drinking occasions. These decisions are often made despite an intention to quit or reduce alcohol consumption. We tested if a hyperactive reward system and/or an impaired cognitive control system contribute to such unfavourable decision-making. METHODS: In this fMRI study, men with modest to harmful drinking behaviour, which was measured using the Alcohol Use Disorders Identification Test (AUDIT), repeatedly made decisions between alcoholic and nonalcoholic drinks. Based on prior individual ratings, decision pairs were created with an alcoholic decision option considered more desirable but less beneficial by the participant. By correlating AUDIT scores with brain activation during decision-making, we determined areas explicitly related to pro-alcohol decisions in men with greater drinking severity. RESULTS: Thirty-eight men participated in our study. Behaviourally, we found a positive correlation between AUDIT scores and the number of decisions for desired alcoholic drinks compared with beneficial nonalcoholic drinks. The fMRI results show that AUDIT scores were positively associated with activation in areas associated with reward and motivation processing (i.e., ventral striatum, amygdala, medial prefrontal cortex) during decisions favouring a desired, nonbeneficial alcoholic drink. Conversely, we did not find hypoactivation in areas associated with self-control (dorsolateral prefrontal cortex). These effects were not present when participants chose a desired, nonbenefical, nonalcoholic drink. LIMITATIONS: The men participating in our study had to be abstinent and would potentially consume an alcoholic drink at the end of the experiment. Hence, we did not define manifest alcohol dependence as an inclusion criterion and instead focused on less severely affected individuals. CONCLUSION: Our results indicate that with growing drinking severity, decisions for alcoholic drinks are associated with increasing activity in reward-associated neural systems, rather than decreasing activity in self-control-associated systems.

Common and distinct networks for self-referential and social stimulus processing in the human brain.

Self-referential processing is a complex cognitive function, involving a set of implicit and explicit processes, complicating investigation of its distinct neural signature. The present study explores the functional overlap and dissociability of self-referential and social stimulus processing. We combined an established paradigm for explicit self-referential processing with an implicit social stimulus processing paradigm in one fMRI experiment to determine the neural effects of self-relatedness and social processing within one study. Overlapping activations were found in the orbitofrontal cortex and in the intermediate part of the precuneus. Stimuli judged as self-referential specifically activated the posterior cingulate cortex, the ventral medial prefrontal cortex, extending into anterior cingulate cortex and orbitofrontal cortex, the dorsal medial prefrontal cortex, the ventral and dorsal lateral prefrontal cortex, the left inferior temporal gyrus, and occipital cortex. Social processing specifically involved the posterior precuneus and bilateral temporo-parietal junction. Taken together, our data show, not only, first, common networks for both processes in the medial prefrontal and the medial parietal cortex, but also, second, functional differentiations for self-referential processing versus social processing: an anterior-posterior gradient for social processing and self-referential processing within the medial parietal cortex and specific activations for self-referential processing in the medial and lateral prefrontal cortex and for social processing in the temporo-parietal junction.

Alterations in neural Theory of Mind processing in euthymic patients with bipolar disorder and unaffected relatives.

OBJECTIVES: Behavioral deficits in the Theory of Mind (ToM) have been robustly demonstrated in bipolar disorder. These deficits may represent an intermediate phenotype of the disease. The aim of this study was: (i) to investigate alterations in neural ToM processing in euthymic patients with bipolar disorder, and (ii) to examine whether similar effects are present in unaffected relatives of patients with bipolar disorder suggesting that ToM functional activation may be, in part, due to genetic risk for the disease. METHODS: A total of 24 euthymic patients with bipolar disorder, 21 unaffected first-degree relatives, and 81 healthy controls completed a ToM task while undergoing functional magnetic resonance imaging. RESULTS: We observed reduced bilateral activation of the temporoparietal junction (TPJ) and diminished functional fronto-temporoparietal connectivity in patients compared to controls. Relatives tended towards intermediate temporoparietal activity and functional coupling with medial prefrontal areas. There was also evidence for a potentially compensatory enhanced recruitment of the right middle temporal gyrus and stronger connectivity between this region and the medial prefrontal cortex in relatives. CONCLUSIONS: These findings provide further evidence of altered neural ToM processing in euthymic patients with bipolar disorder. Further, our findings in relatives lend support to the idea that altered ToM processing may act as an intermediate phenotype of the disorder.

Decreased gray matter volume in inferior frontal gyrus is related to stop-signal task performance in alcohol-dependent patients.

Impairment in inhibitory control has been proposed to contribute to habitual alcohol use, abuse and eventually dependence. Moreover, alcohol-dependent (AD) patients have shown a loss of gray matter volume (GMV) in the brain, specifically in prefrontal regions associated with executive functions, including response inhibition. To date, no study has evaluated whether this prefrontal GMV reduction is related to response inhibition in alcohol dependence. To address this issue, we acquired high-resolution T1-weighted magnetic resonance mages from recently detoxified AD patients (n = 22) and healthy controls (HC; n = 21). Differences in local GMV between groups were assessed by means of voxel-based morphometry (VBM). Moreover, within the AD group, mean local GMV reductions were extracted and correlated with behavioral performance on the stop-signal task. We found a significantly decrease in GMV in the left inferior frontal gyrus (IFG) in AD patients compared with HC subjects. Further, mean local GMV in this area correlated positively with reaction times on go trials during the stop-signal task in AD patients. Our findings suggest that GMV losses in the IFG in AD patients are related to faster go responses on the stop-signal task.

Doing good or bad: How interactions between action and emotion expectations shape the sense of agency.

The emotional consequences of our own and others' actions can influence our agentive self-awareness in social contexts. Positive outcomes are usually linked to the self and used for self-enhancement, whereas negative outcomes are more often attributed to others. In most situations, these causal attribution tendencies seem to be immediately present instead of involving reflective interpretations of the action experience. To address the question at which level of the cognitive hierarchy emotions and action perception interact, we adopted a social reward anticipation paradigm. Here, participants or their interaction partner received positive or negative action outcomes and performed speeded attribution choices regarding causation of the action outcome. Event-Related Potential (ERP) results showed that the emotional value of an outcome already influenced the classical N1 self-attenuation effect, with reduced embodied agentive self-awareness for negative outcomes at initial sensorimotor stages. At the level of the N300, the degree of updating and affective evaluation associated with the respective attributive decision was reflected and particularly associated to attribution tendencies for positive events. Our results show an early interaction between emotion and agency processes, and suggest that self-serving cognition can be grounded in embodied knowledge from low-level sensorimotor mechanisms.

Perception of social stimuli in mania: an fMRI study.

Patients with mania show alterations of social behaviour. Neuropsychological studies in euthymic bipolar disorder (BD) have revealed deficits in cognitive, but not emotional aspects of social cognition (SC). Here, we studied the neural signature of social stimulus processing in mania. We expected alterations in regions associated with cognitive SC (dorsal-medial prefrontal cortex, dMPFC). Participants comprised 14 manic patients and 14 matched healthy controls who viewed standardized pictures with social and non-social content during functional magnetic resonance imaging (fMRI). Region-of-interest-analyses focused on areas related to SC (dorsal/ventral medial prefrontal cortex; temporo-parietal junction), determined by a quantitative meta-analysis. Between-group comparisons ('social>non-social') revealed reduced BOLD responses in the right dMPFC in manic patients, but no significant group difference in the ventral MPFC. In addition, manic patients showed elevated BOLD activation in the right temporo-parietal junction during perception of social stimuli, which was correlated with increased delusional ideation. Patients with mania show diminished BOLD responses to social stimuli in the right dMPFC, associated with cognitive SC and this may be related to reported deficits in understanding others' mental states. At the same time, manic patients show hyperactivation of the right temporo-parietal junction, likely related to exaggerated attribution of meaning to social stimuli.

Imagining triadic interactions simultaneously activates mirror and mentalizing systems.

Coordinated triadic interactions, involving oneself, another person, and an external object, are considered a uniquely human skill. However, the exact mechanisms underlying the ability to engage in such social interactions remain hitherto unknown. We used functional neuroimaging to investigate the neural signature of triadic interactions. For this purpose, participants viewed pictures of objects in a 3T functional magnetic resonance imaging scanner and were asked whether they could imagine this object in a social interaction with another person. We also aimed to dissociate this process from, as well as to find commonalities with, purely self-referential or other-referential processing. In all trial-types, we found activations in core mentalizing brain areas (medial prefrontal cortex, posterior cingulate cortex, precuneus and temporoparietal junction). Furthermore, triadic engagements, but not self-referential or other-referential processing, were associated with activations in classical mirror neuron areas (inferior frontal gyrus and inferior parietal lobe). Finally, mentalizing networks showed a strong functional connectivity with mirror neuron areas exclusively during triadic engagements. These results suggest that the imagined interaction of two agents is processed in a more complex neural social cognitive network than purely self- or other-referential considerations.

Hyperimitation of actions is related to reduced understanding of others' minds in autism spectrum conditions.

BACKGROUND: Anecdotal evidence has noted that individuals with autism spectrum conditions (ASC) frequently exhibit heightened spontaneous imitative behavior, with symptoms of echolalia and echopraxia. This is contrasted by empiric reports that ASC results in decreased imitation and an underlying deficit in the mirror system, leading to impaired social understanding. Thus, it remains unclear whether automatic imitation is enhanced in ASC and how this is related to poorer social abilities. METHODS: This study investigated spontaneous imitation in 18 high-functioning adults with ASC and 18 age- and IQ-matched control participants during a simple imitation inhibition task. Mentalizing was experimentally assessed in the same participants using both behavioral and functional magnetic resonance imaging measures, as was social interaction using an observational measure. RESULTS: Individuals with ASC showed increased imitation of hand actions compared with control participants and this was associated with reduced mentalizing and poorer reciprocal social interaction abilities. In the functional magnetic resonance imaging mentalizing paradigm, ASC participants with increased imitation scores showed less brain activation in areas often found to be active in mental state attribution, namely the medial prefrontal cortex and temporoparietal junction. CONCLUSIONS: The results confirm the presence of hyperimitation in ASC, which is accompanied by reduced social cognition, suggesting that a general imitation impairment and a global mirror system deficit are absent. These findings offer an explanation for echopractic features based on theories of atypical functioning of top-down modulation processes in autism.

Resisting motor mimicry: control of imitation involves processes central to social cognition in patients with frontal and temporo-parietal lesions.

Perception and execution of actions share a common representational and neural substrate and thereby facilitate unintentional motor mimicry. Controlling automatic imitation is therefore a crucial requirement of such a "shared representational" system. Based on previous findings from neuroimaging, we suggest that resisting motor mimicry recruits the same underlying computational mechanisms also involved in higher-level social cognitive processing, such as self - other differentiation and the representation of mental states. The aim of the present study was to investigate on a behavioral level whether there is a functional association between the inhibition of imitation and tasks, assessing the understanding of mental states and of different perspectives of self and other. In a sample of neuropsychological patients with frontal lesions, a correlation between the ability for mental state attribution and the control of imitation was found, with a similar effect in the control group. Temporo-parietal lesioned patients showed a highly significant correlation between imitative control and visual and cognitive perspective-taking. Even after controlling for executive functions, the results remained significant, indicating the functional specificity of this relationship. These findings provide new insight into the functional processes underlying the control of shared representations and suggest a novel link between embodied and higher-level social cognition.

Minimizing motor mimicry by myself: self-focus enhances online action-control mechanisms during motor contagion.

Ideomotor theory of human action control proposes that activation of a motor representation can occur either through internally-intended or externally-perceived actions. Critically, sometimes these alternatives of eliciting a motor response may be conflicting, for example, when intending one action and perceiving another, necessitating the recruitment of enhanced action-control to avoid motor mimicry. Based on previous neuroimaging evidence, suggesting that reduced mimicry is associated with self-related processing, we aimed to experimentally enhance these action-control mechanisms during motor contagion by inducing self-focus. In two within-subjects experiments, participants had to enforce their action intention against an external motor contagion tendency under heightened and normal self-focus. During high self-focus participants showed reduced motor mimicry, induced either by mirror self-observation or self-referential judgments. This indicates that a self-focus provoking situation can enhance online action-control mechanisms, needed to resist unintentional motor contagion tendencies and thereby enables a modulation of automatic mirroring responses.

Inhibition of imitative behaviour and social cognition.

There is converging evidence that the observation of an action activates a corresponding motor representation in the observer through a 'mirror-matching' mechanism. However, research on such 'shared representations' of perception and action has widely neglected the question of how we can distinguish our own motor intentions from externally triggered motor representations. By investigating the inhibition of imitative response tendencies, as an index for the control of shared representations, we can show that self-other distinction plays a fundamental role in the control of shared representations. Furthermore, we demonstrate that overlapping brain activations can be found in the anterior fronto-median cortex (aFMC) and the temporo-parietal junction (TPJ) area for the control of shared representations and complex social-cognitive tasks, such as mental state attribution. In a functional magnetic resonance imaging experiment, we functionally dissociate the roles of TPJ and aFMC during the control of shared representations. Finally, we propose a hypothesis stating that the control of shared representations might be the missing link between functions of the mirror system and mental state attribution.

Control of shared representations relies on key processes involved in mental state attribution.

Action observation leads to the automatic activation of the corresponding motor representation in the observer through "mirror-matching." This constitutes a "shared representational system," which is thought to subserve social understanding by motor simulation. However, it is unclear how these shared representations can be controlled and distinguished. Brain imaging suggests that controlling shared representations, indexed by the ability to control automatic imitative responses, activates anterior fronto-median cortex (aFMC), and temporo-parietal junction (TPJ). Crucially, these regions are also consistently implicated in mental state attribution and have provided an alternative account for higher-level social cognition. Here, we directly tested whether social-cognitive processes involve similar key computational mechanisms as the control of shared representations by using functional brain imaging to reveal overlapping brain circuits. We show in a within-subject design that commonly activated regions occurred selectively in aFMC and TPJ. Mentalizing and self-referential thoughts recruited a region in aFMC, which was also activated when controlling imitation. In the TPJ, an area overlapped between mentalizing, agency processing, and imitative control. Behavioral and neural correlates of mentalizing were further related to the individual ability for controlling imitation. Our findings support the assumption of shared key processes and suggest a novel link between embodied and social cognition.

Was it me or was it you? How the sense of agency originates from ideomotor learning revealed by fMRI.

One fundamental property of voluntary action is the feeling of control and causation, also referred to as self agency. Recent research suggests that the sense of agency is based on low-level, sensory-motor control processes, which compare predicted and actual action-effects. Brain imaging research revealed that the temporo-parietal junction (TPJ) plays a crucial role for signalling whether a sensory action-consequence matches the prediction or not. However, while it was assumed that sensory outcome predictions are based on ideomotor (action-effect) learning, it has rarely been investigated whether such learning can lead to a sense of agency. In this functional MRI experiment we tested whether a sense of agency develops from learning action-effect associations. In the first part of the experiment, participants learned new action-effect associations. During the following scanning session participants were exposed to matching and non-matching action-effects. In accordance with previous behavioural research, participants reported a decreased sense of agency for non-matching events. As predicted, activity in the TPJ increased with greater incongruence between predicted and actual sensory effects. Furthermore, attributing the causation of sensory events to another person was correlated with activity in fronto-median cortex, a region involved in the representation of intentional agents. This relationship was modulated by the external attribution disposition of the participants. Complementing our view on agentive processes, our findings indicate that ideomotor learning provides an essential basis for the distinction of agents' behaviour and also point to a possible high-level contribution of prefrontal cortex and personality traits to the sense of agency.

Neural correlates of overcoming interference from instructed and implemented stimulus-response associations.

One of the major evolutionary advances of human primates in the motor domain is their ability to use verbal instructions to guide their behavior. Despite this fundamental role of verbal information for our behavioral regulation, the functional and neural mechanisms underlying the transformation of verbal instructions into efficient behavior are still poorly understood. To gain deeper insights into the motor representation of verbal instructions, we investigated the neural circuits involved in overcoming interference from stimulus- response (S-R) mappings that are merely instructed and S-R mappings that are implemented. Implemented and instructed S-R mappings revealed a partly overlapping pattern of fronto-parietal brain activity when compared with a neutral condition. However, the direct contrast revealed a clear difference with stronger activation for the implemented condition in the ACC, bilateral inferior parietal cortex, the cerebellum and the precentral sulcus. This indicates that instructed S-R mappings share some properties with implemented S-R mappings but that they are lacking the motor-related properties of implemented mappings.

Contextual movement constraints of others modulate motor preparation in the observer.

Previous research demonstrated that observing an action seems to automatically activate a corresponding motor representation in the observer. It has been argued that this direct matching of observed on executed actions is modulated by contextual factors. An open question is whether observing another person being physically restrained has an influence on action execution in the observer. Using performance measures we found a slowing of response times when perceiving others' hands being physically restrained (Experiment 1). We did not find a slowing effect when participants responded with their feet ruling out a general perceptual interpretation of the present findings (Experiment 2). To further test our hypothesis, we measured event-related brain potentials (ERPs). The ERP results demonstrate that the observed slowing effect is reflected in a decrease of motor-related ERP components (Experiment 3). Perceiving others' hands physically restrained impairs motor preparation in the observer. Our findings suggest that observed environmental constraints are automatically mapped onto the observer's motor system. Such a mapping of motor restraints might facilitate action understanding.