Margherita Melloni

The extended fronto-striatal model of obsessive compulsive disorder: convergence from event-related potentials, neuropsychology and neuroimaging

In this work, we explored convergent evidence supporting the fronto-striatal model of obsessive-compulsive disorder (FSMOCD) and the contribution of event-related potential (ERP) studies to this model. First, we considered minor modifications to the FSMOCD model based on neuroimaging and neuropsychological data. We noted the brain areas most affected in this disorder -anterior cingulate cortex (ACC), basal ganglia (BG), and orbito-frontal cortex (OFC) and their related cognitive functions, such as monitoring and inhibition. Then, we assessed the ERPs that are directly related to the FSMOCD, including the error-related negativity (ERN), N200, and P600. Several OCD studies present enhanced ERN and N2 responses during conflict tasks as well as an enhanced P600 during working memory (WM) tasks. Evidence from ERP studies (especially regarding ERN and N200 amplitude enhancement), neuroimaging and neuropsychological findings suggests abnormal activity in the OFC, ACC, and BG in OCD patients. Moreover, additional findings from these analyses suggest dorsolateral prefrontal and parietal cortex involvement, which might be related to executive function (EF) deficits. Thus, these convergent results suggest the existence of a self-monitoring imbalance involving inhibitory deficits and executive dysfunctions. OCD patients present an impaired ability to monitor, control, and inhibit intrusive thoughts, urges, feelings, and behaviors. In the current model, this imbalance is triggered by an excitatory role of the BG (associated with cognitive or motor actions without volitional control) and inhibitory activity of the OFC as well as excessive monitoring of the ACC to block excitatory impulses. This imbalance would interact with the reduced activation of the parietal-DLPC network, leading to executive dysfunction. ERP research may provide further insight regarding the temporal dynamics of action monitoring and executive functioning in OCD.

The Neural Basis of Decision-Making and Reward Processing in Adults with Euthymic Bipolar Disorder or Attention-Deficit/Hyperactivity Disorder (ADHD)

Background Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) share DSM-IV criteria in adults and cause problems in decision-making. Nevertheless, no previous report has assessed a decision-making task that includes the examination of the neural correlates of reward and gambling in adults with ADHD and those with BD. Methodology/Principal Findings We used the Iowa gambling task (IGT), a task of rational decision-making under risk (RDMUR) and a rapid-decision gambling task (RDGT) which elicits behavioral measures as well as event-related potentials (ERPs: fERN and P3) in connection to the motivational impact of events. We did not observe between-group differences for decision-making under risk or ambiguity (RDMUR and IGT); however, there were significant differences for the ERP-assessed RDGT. Compared to controls, the ADHD group showed a pattern of impaired learning by feedback (fERN) and insensitivity to reward magnitude (P3). This ERP pattern (fERN and P3) was associated with impulsivity, hyperactivity, executive function and working memory. Compared to controls, the BD group showed fERN- and P3-enhanced responses to reward magnitude regardless of valence. This ERP pattern (fERN and P3) was associated with mood and inhibitory control. Consistent with the ERP findings, an analysis of source location revealed reduced responses of the cingulate cortex to the valence and magnitude of rewards in patients with ADHD and BD. Conclusions/Significance Our data suggest that neurophysiological (ERPs) paradigms such as the RDGT are well suited to assess subclinical decision-making processes in patients with ADHD and BD as well as for linking the cingulate cortex with action monitoring systems.

Empathy and contextual social cognition

Empathy is a highly flexible and adaptive process that allows for the interplay of prosocial behavior in many different social contexts. Empathy appears to be a very situated cognitive process, embedded with specific contextual cues that trigger different automatic and controlled responses. In this review, we summarize relevant evidence regarding social context modulation of empathy for pain. Several contextual factors, such as stimulus reality and personal experience, affectively link with other factors, emotional cues, threat information, group membership, and attitudes toward others to influence the affective, sensorimotor, and cognitive processing of empathy. Thus, we propose that the frontoinsular-temporal network, the so-called social context network model (SCNM), is recruited during the contextual processing of empathy. This network would (1) update the contextual cues and use them to construct fast predictions (frontal regions), (2) coordinate the internal (body) and external milieus (insula), and (3) consolidate the context–target associative learning of empathic processes (temporal sites). Furthermore, we propose these context-dependent effects of empathy in the framework of the frontoinsular-temporal network and examine the behavioral and neural evidence of three neuropsychiatric conditions (Asperger syndrome, schizophrenia, and the behavioral variant of frontotemporal dementia), which simultaneously present with empathy and contextual integration impairments. We suggest potential advantages of a situated approach to empathy in the assessment of these neuropsychiatric disorders, as well as their relationship with the SCNM.

How do you feel when you can't feel your body? Interoception, functional connectivity and emotional processing in depersonalization-derealization disorder.

Depersonalization-Derealization Disorder (DD) typically manifests as a disruption of body self-awareness. Interoception −defined as the cognitive processing of body signals− has been extensively considered as a key processing for body self-awareness. In consequence, the purpose of this study was to investigate whether there are systematic differences in interoception between a patient with DD and controls that might explain the disembodiment symptoms suffered in this disease. To assess interoception, we utilized a heartbeat detection task and measures of functional connectivity derived from fMRI networks in interoceptive/exteroceptivo/mind-wandering states. Additionally, we evaluated empathic abilities to test the association between interoception and emotional experience. The results showed patients impaired performance in the heartbeat detection task when compared to controls. Furthermore, regarding functional connectivity, we found a lower global brain connectivity of the patient relative to controls only in the interoceptive state. He also presented a particular pattern of impairments in affective empathy. To our knowledge, this is the first experimental research that assesses the relationship between interoception and DD combining behavioral and neurobiological measures. Our results suggest that altered neural mechanisms and cognitive processes regarding body signaling might be engaged in DD phenomenology. Moreover, our study contributes experimental data to the comprehension of brain-body interactions and the emergence of self-awareness and emotional feelings.

Feeling, learning from and being aware of inner states: interoceptive dimensions in neurodegeneration and stroke

Interoception is a complex process encompassing multiple dimensions, such as accuracy, learning and awareness. Here, we examined whether each of those dimensions relies on specialized neural regions distributed throughout the vast interoceptive network. To this end, we obtained relevant measures of cardiac interoception in healthy subjects and patients offering contrastive lesion models of neurodegeneration and focal brain damage: behavioural variant fronto-temporal dementia (bvFTD), Alzheimers disease (AD) and fronto-insular stroke. Neural correlates of the three dimensions were examined through structural and functional resting-state imaging, and online measurements of the heart-evoked potential (HEP). The three patient groups presented deficits in interoceptive accuracy, associated with insular damage, connectivity alterations and abnormal HEP modulations. Interoceptive learning was differentially impaired in AD patients, evidencing a key role of memory networks in this skill. Interoceptive awareness results showed that bvFTD and AD patients overestimated their performance; this pattern was related to abnormalities in anterior regions and associated networks sub-serving metacognitive processes, and probably linked to well-established insight deficits in dementia. Our findings indicate how damage to specific hubs in a broad fronto-temporo-insular network differentially compromises interoceptive dimensions, and how such disturbances affect widespread connections beyond those critical hubs. This is the first study in which a multiple lesion model reveals fine-grained alterations of body sensing, offering new theoretical insights into neuroanatomical foundations of interoceptive dimensions. This article is part of the themed issue ‘Interoception beyond homeostasis: affect, cognition and mental health’.

Cortical dynamics and subcortical signatures of motor-language coupling in Parkinson’s disease

Impairments of action language have been documented in early stage Parkinson’s disease (EPD). The action-sentence compatibility effect (ACE) paradigm has revealed that EPD involves deficits to integrate action-verb processing and ongoing motor actions. Recent studies suggest that an abolished ACE in EPD reflects a cortico-subcortical disruption, and recent neurocognitive models highlight the role of the basal ganglia (BG) in motor-language coupling. Building on such breakthroughs, we report the first exploration of convergent cortical and subcortical signatures of ACE in EPD patients and matched controls. Specifically, we combined cortical recordings of the motor potential, functional connectivity measures, and structural analysis of the BG through voxel-based morphometry. Relative to controls, EPD patients exhibited an impaired ACE, a reduced motor potential, and aberrant frontotemporal connectivity. Furthermore, motor potential abnormalities during the ACE task were predicted by overall BG volume and atrophy. These results corroborate that motor-language coupling is mainly subserved by a cortico-subcortical network including the BG as a key hub. They also evince that action-verb processing may constitute a neurocognitive marker of EPD. Our findings suggest that research on the relationship between language and motor domains is crucial to develop models of motor cognition as well as diagnostic and intervention strategies.

Preliminary evidence about the effects of meditation on interoceptive sensitivity and social cognition

BackgroundInteroception refers to the conscious perception of body signals. Mindfulness is a meditation practice that encourages individuals to focus on their internal experiences such as bodily sensations, thoughts, and emotions. In this study, we selected a behavioral measure of interoceptive sensitivity (heartbeat detection task, HBD) to compare the effect of meditation practice on interoceptive sensitivity among long term practitioners (LTP), short term meditators (STM, subjects that completed a Mindfulness-Based Stress Reduction (MBSR) program) and controls (non-meditators). All participants were examined with a battery of different tasks including mood state, executive function and social cognition tests (emotion recognition, empathy and theory of mind).FindingsCompared to controls, both meditators’ groups showed lower levels of anxiety and depression, but no improvement in executive function or social cognition performance was observed (except for lower scores compared to controls only in the personal distress dimension of empathy). More importantly, meditators’ performance did not differ from that of nonmeditators regarding cardiac interoceptive sensitivity.ConclusionResults suggest no influence of meditation practice in cardiac interoception and in most related social cognition measures. These negative results could be partially due to the fact that awareness of heartbeat sensations is not emphasized during mindfulness/vipassana meditation and may not be the best index of the awareness supported by the practice of meditation.

Brain network organization and social executive performance in frontotemporal dementia

OBJECTIVES Behavioral variant frontotemporal dementia (bvFTD) is characterized by early atrophy in the frontotemporoinsular regions. These regions overlap with networks that are engaged in social cognition-executive functions, two hallmarks deficits of bvFTD. We examine (i) whether Network Centrality (a graph theory metric that measures how important a node is in a brain network) in the frontotemporoinsular network is disrupted in bvFTD, and (ii) the level of involvement of this network in social-executive performance. METHODS Patients with probable bvFTD, healthy controls, and frontoinsular stroke patients underwent functional MRI resting-state recordings and completed social-executive behavioral measures. RESULTS Relative to the controls and the stroke group, the bvFTD patients presented decreased Network Centrality. In addition, this measure was associated with social cognition and executive functions. To test the specificity of these results for the Network Centrality of the frontotemporoinsular network, we assessed the main areas from six resting-state networks. No group differences or behavioral associations were found in these networks. Finally, Network Centrality and behavior distinguished bvFTD patients from the other groups with a high classification rate. CONCLUSIONS bvFTD selectively affects Network Centrality in the frontotemporoinsular network, which is associated with high-level social and executive profile.

The roles of interoceptive sensitivity and metacognitive interoception in panic

BackgroundInteroception refers to the ability to sense body signals. Two interoceptive dimensions have been recently proposed: (a) interoceptive sensitivity (IS) –objective accuracy in detecting internal bodily sensations (e.g., heartbeat, breathing)–; and (b) metacognitive interoception (MI) –explicit beliefs and worries about one’s own interoceptive sensitivity and internal sensations. Current models of panic assume a possible influence of interoception on the development of panic attacks. Hypervigilance to body symptoms is one of the most characteristic manifestations of panic disorders. Some explanations propose that patients have abnormal IS, whereas other accounts suggest that misinterpretations or catastrophic beliefs play a pivotal role in the development of their psychopathology. Our goal was to evaluate these theoretical proposals by examining whether patients differed from controls in IS, MI, or both. Twenty-one anxiety disorders patients with panic attacks and 13 healthy controls completed a behavioral measure of IS motor heartbeat detection (HBD) and two questionnaires measuring MI.FindingsPatients did not differ from controls in IS. However, significant differences were found in MI measures. Patients presented increased worries in their beliefs about somatic sensations compared to controls. These results reflect a discrepancy between direct body sensing (IS) and reflexive thoughts about body states (MI).ConclusionOur findings support the idea that hypervigilance to body symptoms is not necessarily a bottom-up dispositional tendency (where patients are hypersensitive about bodily signals), but rather a metacognitive process related to threatening beliefs about body/somatic sensations.

Contextual Impairments in Schizophrenia and the FN400

Our brains are good at extracting and processing social contextual cues. Ongoing information is rapidly linked to memory traces of previous experiences, allowing us to generate predictions which help us interpret daily situations. These predictions are a core aspect of human cognition as long as they make social behaviors more efficient. Current evidence, however, suggests that schizophrenia patients are less able to benefit from context and, consequently, social impairments are commonly observed in this complex disorder. Over the last decades, event-related potentials (ERPs) have been used to investigate the electrophysiological correlates of several memory processes. In classical explicit memory experiments, familiarity (the subjective experience of knowing an item – e.g., a face-without being able to retrieve any further episodic information) has been associated with a mid-frontal old/new difference occurring in the 300–500 ms window, often called “FN400” (Rugg and Curran, 2007). For example, the comparison of ERPs on hits and correct rejections (old/new effects) during face recognition, lead to higher FN400 amplitudes for correctly rejected new items than for correctly recognized old ones. Importantly, this difference is observed despite recognition is followed by the recollection of specific details associated to the item (e.g., occupations associated with the faces, Curran and Hancock, 2007). This lack of ability in retrieving episodic details is attributed to the fact that it is perceived out of the context in which is commonly embedded. Recently, Guillaume et al. (2012) have investigated FN400 old/new effects in schizophrenia during face recognition. The aim of their study was to evaluate if familiarity was affected by contextual information mismatching in schizophrenia patients versus controls by manipulating the background in which faces appeared. This resulted in three conditions: old (faces that were presented on the study phase with the same background), different (faces that were presented on the study phase with a different background), and new condition (faces that were not presented on the study phase). They found that, across conditions, schizophrenia patients showed greater FN400 amplitude compared to controls. Moreover, in the patients, the FN400 amplitude was the same in the different and new conditions suggesting that familiarity was severely disrupted when the context in which faces appeared was changed. Although correlates of familiarity have been classically linked to the FN400 (Rugg and Curran, 2007), recent work (Voss et al., 2012) has called into question this traditionally accepted linkage, suggesting that modulations in this component could be actually indexing implicit conceptual memory processing instead of familiarity per se. It is important to note that the “F” in FN400 indicates a more frontal topographical distribution compared to the similar N400 component found for words semantically anomalous to the preceding context. While this difference in the scalp activity is consistent with the existence of distinct roles for each negativity (FN400 in familiarity versus N400 in language), it has been suggested (Kutas and Federmeier, 2011) that the classical N400 and the FN400 could be indexing an analog process. In our view, both proposals are justified and can explain, in a more parsimonious fashion, current FN400-related data. However, based on the possible functional analogy between the FN400 and the N400 and also on current neuroanatomical evidence suggesting frontal and temporal sources (Halgren et al., 2002; Voss et al., 2008; Ibanez et al., 2012), we propose that this component might be reflecting a more general process regarding implicit contextual facilitation. We have recently proposed that the N400 reflects the activation of a contextual frontotemporal network responsible for the instantiation of meaning construction under the crucial role of context-based information (Amoruso et al., 2011; Ibanez and Manes, 2012). In our model, similar to the one proposed by Bar (2004) for object recognition, frontal regions would play a key role in updating ongoing contextual information in working memory and integrating it with semantic knowledge about target-context associations and their learning value stored in temporal regions. Taken together, information about current and previous experiences is used by the brain in order to make focused predictions to facilitate the interpretation of the ongoing situation. Furthermore, our model is supported by current experimental evidence from electrocorticography (ECoG) direct recordings (Ibanez et al., 2012) and source estimation (Halgren et al., 2002) which suggests that the scalp-recorded N400 reflects the coordinated activity of multiple brain areas, including temporal and frontal regions. Importantly, these two regions, also thought to be involved in the FN400 generation (Voss et al., 2012), are the most affected in schizophrenia, at structural, and functional level (Wong and Van Tol, 2003). Contextual deficits seem to be the core of N400 abnormal modulations found in schizophrenia (Kumar and Debruille, 2004; Ibanez et al., 2011). Moreover, contextual impairments seem to be present in this condition, from the basic perceptual level (Chambon et al., 2008) to the higher aspects of social cognition (Chung et al., 2011). FN400 abnormal modulations in schizophrenia patients found by Guillaume et al. (2012) can be explained as a disruption in the integration of contextual cues in the frontotemporal network. More specifically, the greater FN400 amplitude showed by these patients compared to controls suggests that they are not able to benefit from context, maybe due to a reduction in functional connections between frontal and temporal lobes. This aforementioned disruption can be more specifically understood in terms of an inability to maintain a representation of context in working memory (Cohen and Servan-Schreiber, 1999). In this view, the FN400 component would indexes a more general and constructive process regarding implicit context-based facilitation in the brain, a process that is severely disrupted in schizophrenia. By this means, our approach would be able to explain not only normal old-new FN400 effects and N400 classic modulations, but also schizophrenia abnormal ones, providing a broader and unified framework to interpret the N400 findings and the contextual impairments observed in this complex disorder.