Improvement in OCD symptoms associated with serotoninergic psychedelics: a retrospective online survey.

A renewed interest in the use of psychedelics for treating obsessive compulsive disorder (OCD) has emerged in the last 20 years. But pre-clinical and clinical evidence remain scarce, and little is known about the factor determining the magnitude and persistence of the therapeutic effect. We therefore designed a retrospective online survey to explore, in the general population using psychoactive drugs, their impact on OCD symptoms. We also assessed the attitude of the participants towards the substance in term of frequency of intakes. In a sample of 174 participants, classic psychedelics were reported as the only substances effective at reducing OCD symptoms. In classic psychedelics users, symptoms reduction was associated with the intensity of acute effects, itself correlated to the dose. Reports on the persistence of the therapeutic effect varied from weeks to months, but we could not find any predicting factor. Finally, the occurrence and frequency of subsequent intakes, which seemed to be limited in our sample, were predicted by the magnitude and persistence of the therapeutic effect, respectively. Our observations support the hypothesis of classic psychedelics efficacy in reducing OCD symptoms but a careful evaluation of the persistence of this effect is still needed.

No effect of subthalamic deep brain stimulation on metacognition in Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a powerful treatment in Parkinson's disease (PD), which provides a positive effect on motor symptoms although the way it operates on high cognitive processes such as metacognition remains unclear. To address this issue, we recorded electroencephalogram (EEG) of PD patients treated with STN-DBS that performed a reversal learning (RL) paradigm endowed with metacognitive self-assessment. We considered two stimulation conditions, namely DBS-ON (stimulation on) and DBS-OFF (stimulation off), and focused our EEG-analysis on the frontal brain region due to its involvement on high cognitive processes. We found a trend towards a significant difference in RL ability between stimulation conditions. STN-DBS showed no effect on metacognition, although a significant association between accuracy and decision confidence level held for DBS OFF, but not in the case of DBS ON. In summary, our study revealed no significant effect of STN-DBS on RL or metacognition.

Face Processing in Developmental Prosopagnosia: Altered Neural Representations in the Fusiform Face Area.

Rationale: Face expertise is a pivotal social skill. Developmental prosopagnosia (DP), i.e., the inability to recognize faces without a history of brain damage, affects about 2% of the general population, and is a renowned model system of the face-processing network. Within this network, the right Fusiform Face Area (FFA), is particularly involved in face identity processing and may therefore be a key element in DP. Neural representations within the FFA have been examined with Representational Similarity Analysis (RSA), a data-analytical framework in which multi-unit measures of brain activity are assessed with correlation analysis. Objectives: Our study intended to scrutinize modifications of FFA-activation during face encoding and maintenance based on RSA. Methods: Thirteen participants with DP (23-70 years) and 12 healthy control subjects (19-62 years) participated in a functional MRI study, including morphological MRI, a functional FFA-localizer and a modified Sternberg paradigm probing face memory encoding and maintenance. Memory maintenance of one, two, or four faces represented low, medium, and high memory load. We examined conventional activation differences in response to working memory load and applied RSA to compute individual correlation-matrices on the voxel level. Group correlation-matrices were compared via Donsker's random walk analysis. Results: On the functional level, increased memory load entailed both a higher absolute FFA-activation level and a higher degree of correlation between activated voxels. Both aspects were deficient in DP. Interestingly, control participants showed a homogeneous degree of correlation for successful trials during the experiment. In DP-participants, correlation levels between FFA-voxels were significantly lower and were less sustained during the experiment. In behavioral terms, DP-participants performed poorer and had longer reaction times in relation to DP-severity. Furthermore, correlation levels were negatively correlated with reaction times for the most demanding high load condition. Conclusion: We suggest that participants with DP fail to generate robust and maintained neural representations in the FFA during face encoding and maintenance, in line with poorer task performance and prolonged reaction times. In DP, alterations of neural coding in the FFA might therefore explain curtailing in working memory and contribute to impaired long-term memory and mental imagery.

Joint contributions of metacognition and self-beliefs to uncertainty-guided checking behavior.

Checking behavior is a natural and adaptive strategy for resolving uncertainty in everyday situations. Here, we aimed at investigating the psychological drivers of checking and its regulation by uncertainty, in non-clinical participants and controlled experimental settings. We found that the sensitivity of participants' explicit confidence judgments to actual performance (explicit metacognition) predicted the extent to which their checking strategy was regulated by uncertainty. Yet, a more implicit measure of metacognition (derived from asking participants to opt between trials) did not contribute to the regulation of checking behavior. Meanwhile, how participants scaled on questionnaires eliciting self-beliefs such as self-confidence and self-reported obsessive-compulsive symptoms also predicted participants' uncertainty-guided checking tendencies. Altogether, these findings demonstrate that checking behavior is likely the outcome of a core explicit metacognitive process operating at the scale of single decisions, while remaining influenced by general self-beliefs. Our findings are thus consistent with two mechanisms (micro vs. macro) through which this otherwise adaptive behavior could go awry in certain psychiatric disorders such as obsessive-compulsive disorder.

A cross-species assessment of behavioral flexibility in compulsive disorders.

Lack of behavioral flexibility has been proposed as one underlying cause of compulsions, defined as repetitive behaviors performed through rigid rituals. However, experimental evidence has proven inconsistent across human and animal models of compulsive-like behavior. In the present study, applying a similarly-designed reversal learning task in two different species, which share a common symptom of compulsivity (human OCD patients and Sapap3 KO mice), we found no consistent link between compulsive behaviors and lack of behavioral flexibility. However, we showed that a distinct subgroup of compulsive individuals of both species exhibit a behavioral flexibility deficit in reversal learning. This deficit was not due to perseverative, rigid behaviors as commonly hypothesized, but rather due to an increase in response lability. These cross-species results highlight the necessity to consider the heterogeneity of cognitive deficits in compulsive disorders and call for reconsidering the role of behavioral flexibility in the aetiology of compulsive behaviors.

I can't get it off my mind: Attentional bias in former and current cocaine addiction.

BACKGROUND: Cocaine addiction is a global health issue with limited therapeutic options and a high relapse rate. Attentional bias towards substance-related cues may be an important factor for relapse. However, it has never been compared in former and current cocaine-dependent patients. METHODS: Attentional bias towards cocaine-related words was assessed using an emotional Stroop task in cocaine-dependent patients (N = 40), long-term abstinent former cocaine-dependent patients (N = 24; mean abstinence: 2 years) and control subjects (N = 28). Participants had to name the colour of cocaine-related words, neutral words and colour names. We assessed response times using an automatic voice-onset detection method we developed and we measured attentional bias as the difference in response times between cocaine-related and neutral conditions. RESULTS: There was an overall group effect on attentional bias towards cocaine, but no group effect on the colour Stroop effect. Two-by-two comparison showed a difference in attentional bias between cocaine-dependent patients and controls, whereas long-term abstinent former cocaine-dependent patients were not different from either. Although cocaine-dependent patients showed a significant attentional bias, consistent with the literature, neither long-term abstinent former cocaine-dependent patients nor controls showed a significant attentional bias towards cocaine-related words. We found no link between attentional bias size and either addiction severity or craving. CONCLUSIONS: Cocaine abstinence was associated with an absence of significant attentional bias towards cocaine-related words, which may be interpreted either as an absence of attentional bias predicting success in maintaining abstinence, or as attentional bias being able to disappear with long-term cocaine abstinence. Further research is needed to distinguish the role of attentional bias in maintaining abstinence.

Motor symptom asymmetry in Parkinson's disease predicts emotional outcome following subthalamic nucleus deep brain stimulation.

The objective of this study was to explore the brain modifications associated with vocal emotion (i.e., emotional prosody) processing deficits in patients with Parkinson's disease after deep brain stimulation of the subthalamic nucleus, and the impact of motor asymmetry on these deficits. We therefore conducted 18-fluorodeoxyglucose positron emission tomography scans of 29 patients with left- or right-sided motor symptoms of Parkinson's disease before and after surgery, and correlated changes in their glucose metabolism with modified performances on the recognition of emotional prosody. Results were also compared with those of a matched healthy control group. Patients with more left-sided motor symptoms exhibited a deficit in vocal emotion recognition for neutral, anger, happiness and sadness in the preoperative condition that was normalized postoperatively. Patients with more right-sided motor symptoms performed comparably to controls in the preoperative condition, but differed significantly on fear postoperatively. At the metabolic level, the improvement observed among patients with left-sided motor symptoms was correlated with metabolic modifications in a right-lateralized network known to be involved in emotional prosody, while the behavioral worsening observed among patients with right-sided motor symptoms was correlated with metabolic modifications in the left parahippocampal gyrus and right cerebellum. We suggest that surgery has a differential impact on emotional processing according to motor symptom lateralization, and interpret these results as reflecting the (de)synchronization of the limbic loop in the postoperative condition.

Assessment of Metacognition and Reversal Learning in Parkinson's Disease: Preliminary Results.

Reversal learning (RL) has been widely used for assessment of behavioral adaptation, impulsivity, obsession, and compulsion in healthy controls as well as people suffering from psychiatric and neurological disorders such as Parkinson's disease (PD). Nevertheless, studies addressing high cognitive functions such as metacognition in PD are scarce. Here, we address for the first time the effect of levodopa and PD on metacognition within the framework of a RL paradigm. In agreement with previous reports, PD patients exhibited reversal shifting impairment with respect to healthy controls (CTRL) regardless of medication condition (MED-ON and MED-OFF), which was supported by a well-known model of learning conditioning (Rescorla-Wagner). In spite that we found a significant association between accuracy and decision confidence level for MED-OFF and CTRL, analysis of metacognitive sensitivity assessed by type 2 signal detection theory (SDT) revealed only a significant underperformance for patients without medication (MED-OFF). This finding points toward a non-compromising positive effect of dopaminergic medication on metacognition for PD.

Hemispheric specialization of the basal ganglia during vocal emotion decoding: Evidence from asymmetric Parkinson's disease and 18FDG PET.

The possible hemispheric specialization of the basal ganglia during emotional prosody (i.e., vocal emotion) processing has still to be elucidated. Coupled with affective measures and neuroimaging, Parkinson's disease offers a unique opportunity to study this question, on account of its characteristically asymmetric striatal dysfunction, which translates into predominantly contralateral motor symptoms. We investigated the cerebral metabolic bases of emotional prosody recognition in patients with Parkinson's disease with left- versus right-lateralized motor symptoms, postulating that patients with greater right hemispheric brain dysfunction have a specific impairment that correlates with the metabolic modification of a brain network known to be involved in emotional prosody. A total of 38 patients performed a validated emotional prosody recognition task and underwent a resting-state F-18 fluorodeoxyglucose PET scan, as well as clinical, motor, neuropsychological, and psychiatric assessments. Patients' performances were compared with those of 45 healthy controls. As expected, vocal emotion recognition was significantly poorer among patients with left-sided motor symptoms than among both right-sided patients and controls. There was no significant difference between right-sided patients and controls. This effect was observed for both the total score and the happiness subscore. Interestingly, regressions showed that the greater the emotional misattribution, the greater the patients' age and asymmetric motor symptom severity. Finally, at the metabolic level, positive correlations were found between the happiness recognition subscore and the metabolism of the right orbitofrontal cortex in patients with left-sided motor symptoms. A right orbitofrontal-basal ganglia coupling seems to be specifically involved in the vocal emotion recognition deficit observed in Parkinson's disease. The asymmetry of motor symptoms is thus an important clinical factor, in that it may influence the presence or severity of affective disorders in Parkinson's disease.

Cognitive Dysfunction in Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is a mental disorder featuring obsessions (intrusive thoughts) and compulsions (repetitive behaviors performed in the context of rigid rituals). There is strong evidence for a neurobiological basis of this disorder, involving limbic cortical regions and related basal ganglion areas. However, more research is needed to lift the veil on the precise nature of that involvement and the way it drives the clinical expression of OCD. Altered cognitive functions may underlie the symptoms and thus draw a link between the clinical expression of the disorder and its neurobiological etiology. Our extensive review demonstrates that OCD patients do present a broad range of neuropsychological dysfunctions across all cognitive domains (memory, attention, flexibility, inhibition, verbal fluency, planning, decision-making), but some methodological issues temper this observation. Thus, future research should have a more integrative approach to cognitive functioning, gathering contributions of both experimental psychology and more fundamental neurosciences.

Guilt-specific processing in the prefrontal cortex.

Guilt is a central moral emotion due to its inherent link to norm violations, thereby affecting both individuals and society. Furthermore, the nature and specificity of guilt is still debated in psychology and philosophy, particularly with regard to the differential involvement of self-referential representations in guilt relative to shame. Here, using functional magnetic resonance imaging (fMRI) in healthy volunteers, we identified specific brain regions associated with guilt by comparison with the 2 most closely related emotions, shame and sadness. To induce high emotional intensity, we used an autobiographical memory paradigm where participants relived during fMRI scanning situations from their own past that were associated with strong feelings of guilt, shame, or sadness. Compared with the control emotions, guilt episodes specifically recruited a region of right orbitofrontal cortex, which was also highly correlated with individual propensity to experience guilt (Trait Guilt). Guilt-specific activity was also observed in the paracingulate dorsomedial prefrontal cortex, a critical "Theory of Mind" region, which overlapped with brain areas of self-referential processing identified in an independent task. These results provide new insights on the unique nature of guilt as a "self-conscious" moral emotion and the neural bases of antisocial disorders characterized by impaired guilt processing.

Decrease of prefrontal metabolism after subthalamic stimulation in obsessive-compulsive disorder: a positron emission tomography study.

BACKGROUND: High-frequency bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) is a promising treatment in refractory obsessive-compulsive disorder (OCD). METHOD: Using the crossover, randomized, and double-blind procedure adopted by the STOC study, 10 patients treated with high-frequency bilateral STN DBS underwent am 18-fluorodeoxyglucose positron emission tomography (PET) investigation to highlight the neural substratum of this therapeutic approach. RESULTS: The median Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores for all 10 patients were 31 (minimum = 18, maximum = 36) with "Off-Stimulation" status and 19 (minimum = 0, maximum = 30) with "On-Stimulation" status (p = .05). The OCD patients in Off-Stimulation status showed a hypermetabolism in the right frontal middle and superior gyri, right parietal lobe, postcentral gyrus, and bilateral putamen compared with healthy control subjects. A significant decrease in cerebral metabolism was observed in the left cingulate gyrus and the left frontal medial gyrus in On-Stimulation conditions compared with Off-Stimulation conditions. In addition, the improvement assessed by Y-BOCS scores during the On-Stimulation conditions was positively correlated with PET signal changes at the boundary of the orbitofrontal cortex and the medial prefrontal cortex, between PET signal changes and the Y-BOCS scores modifications in On-Stimulation status. CONCLUSION: This study suggests that the therapeutic effect of STN DBS is related to a decrease in prefrontal cortex metabolism.

Integration of gaze direction and facial expression in patients with unilateral amygdala damage.

Affective and social processes play a major role in everyday life, but appropriate methods to assess disturbances in these processes after brain lesions are still lacking. Past studies have shown that amygdala damage can impair recognition of facial expressions, particularly fear, as well as processing of gaze direction; but the mechanisms responsible for these deficits remain debated. Recent accounts of human amygdala function suggest that it is a critical structure involved in self-relevance appraisal. According to such accounts, responses to a given facial expression may vary depending on concomitant gaze direction and perceived social meaning. Here we investigated facial emotion recognition and its interaction with gaze in patients with unilateral amygdala damage (n = 19), compared to healthy controls (n = 10), using computer-generated dynamic face stimuli expressing variable intensities of fear, anger or joy, with different gaze directions (direct versus averted). If emotion perception is influenced by the self-relevance of expression based on gaze direction, a fearful face with averted gaze should be more relevant than the same expression with direct gaze because it signals danger near the observer; whereas anger with direct gaze should be more relevant than with averted gaze because it directly threatens the observer. Our results confirm a critical role for the amygdala in self-relevance appraisal, showing an interaction between gaze and emotion in healthy controls, a trend for such interaction in left-damaged patients but not in right-damaged patients. Impaired expression recognition was generally more severe for fear, but with a greater deficit for right versus left damage. These findings do not only provide new insights on human amygdala function, but may also help design novel neuropsychological tests sensitive to amygdala dysfunction in various patient populations.

Errors recruit both cognitive and emotional monitoring systems: simultaneous intracranial recordings in the dorsal anterior cingulate gyrus and amygdala combined with fMRI.

We studied error monitoring in a human patient with unique implantation of depth electrodes in both the left dorsal cingulate gyrus and medial temporal lobe prior to surgery. The patient performed a speeded go/nogo task and made a substantial number of commission errors (false alarms). As predicted, intracranial Local Field Potentials (iLFPs) in dorsal anterior cingulate indexed the detection of errors, showing an early differential activity around motor execution for false alarms, relative to correct responses (either hits or correct inhibitions). More surprisingly, we found that the left amygdala also participated to error monitoring (although no emotional stimuli were used), but with a very different neurophysiological profile as compared with the dorsal cingulate cortex. Amygdala iLFPs showed a precise and reproducible temporal unfolding, characterized by an early monophasic response for correct hits around motor execution, which was delayed by approximately 300ms for errors (even though actual RTs were almost identical in these two conditions). Moreover, time-frequency analyses demonstrated a reliable and transient coupling in the theta band around motor execution between these two distant regions. Additional fMRI investigation in the same patient confirmed a differential involvement of the dorsal cingulate cortex vs. amygdala in error monitoring during this go/nogo task. Finally, these intracranial results for the left amygdala were replicated in a second patient with intracranial electrodes in the right amygdala. Altogether, these results suggest that the amygdala may register the motivational significance of motor actions on a trial-by-trial basis, while the dorsal anterior cingulate cortex may provide signals concerning failures of cognitive control and behavioral adjustment. More generally, these data shed new light on neural mechanisms underlying self-monitoring by showing that even "simple" motor actions recruit not only executive cognitive processes (in dorsal cingulate) but also affective processes (in amygdala).

Self-relevance processing in the human amygdala: gaze direction, facial expression, and emotion intensity.

How the processing of emotional expression is influenced by perceived gaze remains a debated issue. Discrepancies between previous results may stem from differences in the nature of stimuli and task characteristics. Here we used a highly controlled set of computer-generated animated faces combining dynamic emotional expressions with varying intensity, and gaze shifts either directed at or averted from the observer. We predicted that perceived self-relevance of fearful faces would be higher with averted gaze-signaling a nearby danger; whereas conversely, direct gaze would be more relevant for angry faces-signaling aggressiveness. This interaction pattern was observed behaviorally for emotion intensity ratings, and neurally for functional magnetic resonance imaging activation in amygdala, as well as fusiform and medial prefrontal cortices, but only for mild- and not high-intensity expressions. These results support an involvement of human amygdala in the appraisal of self-relevance and reveal a crucial role of expression intensity in emotion and gaze interactions.

Spatial frequencies or emotional effects? A systematic measure of spatial frequencies for IAPS pictures by a discrete wavelet analysis.

The influence of the emotional attributes of a visual scene on early perception processes remains a key question in contemporary affective neurosciences. The International Affective Picture System (IAPS; Lang et al., 2005) was developed to provide a set of standardized stimuli for experimental investigations of emotional processes. These stimuli have been widely used in brain activity investigations to study the influence of valence and/or arousal on visual processing. However, visual perception is strongly influenced by the physical properties of the images shown, especially their spatial frequency content, an aspect that has been unexpectedly neglected at large. In this study, we examine the complete set of IAPS with a discrete wavelet transform to highlight relations between the energy in different spatial frequencies and the emotional features of the pictures. Our results showed that these associations are weak when the complete dataset is considered, but for selected subsets of pictures, clear differences are present in both affective and spatial frequency content. The IAPS remains a powerful tool to explore emotional processing, but we strongly suggest that researchers use subsets of images that are controlled for the energy of their spatial frequencies when investigating emotional influence on visual processing.

When eye creates the contact! ERP evidence for early dissociation between direct and averted gaze motion processing.

Direct gaze or eye contact is a strong social signal, which triggers distinct processes as compared to other gaze directions. Thus, direct gaze could be early dissociated from averted gaze during the processing of gaze direction. In order to examine the processing of gaze contact relative to averted gaze, we studied evoked potentials in human adults in response to the apparent motion of gaze. Deviated and frontal faces were presented with a fixed gaze direction, followed by an apparent movement of the eyes either toward the subject or away from him/her. The results showed that the perception of direct relative to averted gaze evoked a greater, later and longer lasting N170, suggesting that gaze contact recruited more resources than averted gaze in the early stage of gaze direction processing. Furthermore, direct and averted motion of gaze elicited distinct ERP components between 160 and 210 ms, initiated over centro-parietal electrodes. Source reconstruction revealed the involvement of the Theory-of-Mind network, including the regions of the superior temporal sulcus, the medial prefrontal and the orbitofrontal cortices, in this early dissociation. In addition, the perception of gaze contact relative to averted gaze yielded increased fronto-central P3a and parieto-occipital P3b. All the results were significant whatever the head orientation. Our findings show that gaze contact, as compared to other gaze directions, is an essential social cue which recruits early specific processes. The dissociation between direct and averted gaze processing occurs as soon as 160 ms, involving the social brain network.

Stimulation of subterritories of the subthalamic nucleus reveals its role in the integration of the emotional and motor aspects of behavior.

Two parkinsonian patients who experienced transient hypomanic states when the subthalamic nucleus (STN) was stimulated during postoperative adjustment of the electrical parameters for antiparkinsonian therapy agreed to have the mood disorder reproduced, in conjunction with motor, cognitive, and behavioral evaluations and concomitant functional neuroimaging. During the experiment, STN stimulation again induced a hypomanic state concomitant with activation of cortical and thalamic regions known to process limbic and associative information. This observation suggests that the STN plays a role in the control of a complex behavior that includes emotional as well as cognitive and motor components. The localization of the four contacts of the quadripolar electrode was determined precisely with an interactive brain atlas. The results showed that (i) the hypomanic state was caused only by stimulation through one contact localized in the anteromedial STN; (ii) both this contact and the contact immediately dorsal to it improved the parkinsonian motor state; (iii) the most dorsal and ventral contacts, located at the boundaries of the STN, neither induced the behavioral disorder nor improved motor performance. Detailed analysis of these data led us to consider a model in which the three functional modalities, emotional, cognitive, and motor, are not processed in a segregated manner but can be subtly combined in the small volume of the STN. This nucleus would thus serve as a nexus that integrates the motor, cognitive, and emotional components of behavior and might consequently be an effective target for the treatment of behavioral disorders that combine emotional, cognitive, and motor impairment.

Coherent neural representation of hand speed in humans revealed by MEG imaging.

The spiking activity of single neurons in the primate motor cortex is correlated with various limb movement parameters, including velocity. Recent findings obtained using local field potentials suggest that hand speed may also be encoded in the summed activity of neuronal populations. At this macroscopic level, the motor cortex has also been shown to display synchronized rhythmic activity modulated by motor behavior. Yet whether and how neural oscillations might be related to limb speed control is still poorly understood. Here, we applied magnetoencephalography (MEG) source imaging to the ongoing brain activity in subjects performing a continuous visuomotor (VM) task. We used coherence and phase synchronization to investigate the coupling between the estimated activity throughout the brain and the simultaneously recorded instantaneous hand speed. We found significant phase locking between slow (2- to 5-Hz) oscillatory activity in the contralateral primary motor cortex and time-varying hand speed. In addition, we report long-range task-related coupling between primary motor cortex and multiple brain regions in the same frequency band. The detected large-scale VM network spans several cortical and subcortical areas, including structures of the frontoparietal circuit and the cerebello-thalamo-cortical pathway. These findings suggest a role for slow coherent oscillations in mediating neural representations of hand kinematics in humans and provide further support for the putative role of long-range neural synchronization in large-scale VM integration. Our findings are discussed in the context of corticomotor communication, distributed motor encoding, and possible implications for brain-machine interfaces.