Does inappropriate behavior hurt or stink? The interplay between neural representations of somatic experiences and moral decisions.

Embodied models suggest that moral judgments are strongly intertwined with first-hand somatic experiences, with some pointing to disgust, and others arguing for a role of pain/harm. Both disgust and pain are unpleasant, arousing experiences, with strong relevance for survival, but with distinctive sensory qualities and neural channels. Hence, it is unclear whether moral cognition interacts with sensory-specific properties of one somatic experience or with supramodal dimensions common to both. Across two experiments, participants evaluated ethical dilemmas and subsequently were exposed to disgusting (olfactory) or painful (thermal) stimulations of matched unpleasantness. We found that moral scenarios enhanced physiological and neural activity to subsequent disgust (but not pain), as further supported by an independently validated whole-brain signature of olfaction. This effect was mediated by activity in the posterior cingulate cortex triggered by dilemma judgments. Our results thus speak in favor of an association between moral cognition and sensory-specific properties of disgust.

Impaired emotional biases in visual attention after bilateral amygdala lesion.

It is debated whether the amygdala is critical for the emotional modulation of attention. While some studies show reduced attentional benefits for emotional stimuli in amygdala-damaged patients, others report preserved emotional effects. Various factors may account for these discrepant findings, including the temporal onset of the lesion, the completeness and severity of tissue damage, or the extent of neural plasticity and compensatory mechanisms, among others. Here, we investigated a rare patient with focal acute destruction of bilateral amygdala and adjacent hippocampal structures after late-onset herpetic encephalitis in adulthood. We compared her performance in two classic visual attention paradigms with that of healthy controls. First, we tested for any emotional advantage during an attentional blink task. Whereas controls showed better report of fearful and happy than neutral faces on trials with short lags between targets, the patient showed no emotional advantage, but also globally reduced report rates for all faces. Second, to ensure that memory disturbance due to hippocampal damage would not interfere with report performance, we also used a visual search task with either emotionally or visually salient face targets. Although the patient still exhibited efficient guided search for visually salient, non-emotional faces, her search slopes for emotional versus neutral faces showed no comparable benefit. In both tasks, however, changes in the patient predominated for happy more than fear stimuli, despite her normal explicit recognition of happy expressions. Our results provide new support for a causal role of the amygdala in emotional facilitation of visual attention, especially under conditions of increasing task-demands, and not limited to negative information. In addition, our data suggest that such deficits may not be amenable to plasticity and compensation, perhaps due to sudden and late-onset damage occurring in adulthood.

Emotional learning promotes perceptual predictions by remodeling stimulus representation in visual cortex.

Emotions exert powerful effects on perception and memory, notably by modulating activity in sensory cortices so as to capture attention. Here, we examine whether emotional significance acquired by a visual stimulus can also change its cortical representation by linking neuronal populations coding for different memorized versions of the same stimulus, a mechanism that would facilitate recognition across different appearances. Using fMRI, we show that after pairing a given face with threat through conditioning, viewing this face activates the representation of another viewpoint of the same person, which itself was never conditioned, leading to robust repetition-priming across viewpoints in the ventral visual stream (including medial fusiform, lateral occipital, and anterior temporal cortex). We also observed a functional-anatomical segregation for coding view-invariant and view-specific identity information. These results indicate emotional signals may induce plasticity of stimulus representations in visual cortex, serving to generate new sensory predictions about different appearances of threat-associated stimuli.

Pain management decisions in emergency hospitals are predicted by brain activity during empathy and error monitoring.

OBJECTIVE: Pain undertreatment, or oligoanalgesia, is frequent in the emergency department (ED), with major medical, ethical, and financial implications. Across different hospitals, healthcare providers have been reported to differ considerably in the ways in which they recognise and manage pain, with some prescribing analgesics far less frequently than others. However, factors that could explain this variability remain poorly understood. Here, we used neuroscience approaches for neural signal modelling to investigate whether individual decisions in the ED could be explained in terms of brain patterns related to empathy, risk-taking, and error monitoring. METHODS: For 15 months, we monitored the pain management behaviour of 70 ED nurses at triage, and subsequently invited 33 to a neuroimaging study involving three well-established tasks probing relevant cognitive and affective dimensions. Univariate and multivariate regressions were used to predict pain management decisions from neural activity during these tasks. RESULTS: We found that the brain signal recorded when empathising with others predicted the frequency with which nurses documented pain in their patients. In addition, neural activity sensitive to errors and negative outcomes predicted the frequency with which nurses denied analgesia by registering potential side-effects. CONCLUSIONS: These results highlight the multiple processes underlying pain management, and suggest that the neural representations of others' states and one's errors play a key role in individual treatment decisions. Neuroscience models of social cognition and decision-making are a powerful tool to explain clinical behaviour and might be used to guide future educational programs to improve pain management in ED.

No time for drifting: Comparing performance and applicability of signal detrending algorithms for real-time fMRI.

As a consequence of recent technological advances in the field of functional magnetic resonance imaging (fMRI), results can now be made available in real-time. This allows for novel applications such as online quality assurance of the acquisition, intra-operative fMRI, brain-computer-interfaces, and neurofeedback. To that aim, signal processing algorithms for real-time fMRI must reliably correct signal contaminations due to physiological noise, head motion, and scanner drift. The aim of this study was to compare performance of the commonly used online detrending algorithms exponential moving average (EMA), incremental general linear model (iGLM) and sliding window iGLM (iGLMwindow). For comparison, we also included offline detrending algorithms (i.e., MATLAB's and SPM8's native detrending functions). Additionally, we optimized the EMA control parameter, by assessing the algorithm's performance on a simulated data set with an exhaustive set of realistic experimental design parameters. First, we optimized the free parameters of the online and offline detrending algorithms. Next, using simulated data, we systematically compared the performance of the algorithms with respect to varying levels of Gaussian and colored noise, linear and non-linear drifts, spikes, and step function artifacts. Additionally, using in vivo data from an actual rt-fMRI experiment, we validated our results in a post hoc offline comparison of the different detrending algorithms. Quantitative measures show that all algorithms perform well, even though they are differently affected by the different artifact types. The iGLM approach outperforms the other online algorithms and achieves online detrending performance that is as good as that of offline procedures. These results may guide developers and users of real-time fMRI analyses tools to best account for the problem of signal drifts in real-time fMRI.

Predicting drug efficacy in chronic low back pain by quantitative sensory tests.

BACKGROUND: Drugs are prescribed for chronic low back pain without knowing in advance whether a patient will respond to them or not. Quantitative sensory tests (QST) can discriminate patients according to sensory phenotype, possibly reflecting underlying mechanisms of pain processing. QST may therefore be a screening tool to identify potential responders to a certain drug. The aim of this study was to investigate whether QST can predict analgesic effects of oxycodone, imipramine and clobazam in chronic low back pain. METHODS: Oxycodone 15 mg (n = 50), imipramine 75 mg (n = 50) and clobazam 20 mg (n = 49) were compared to active placebo tolterodine 1 mg in a randomized, double-blinded, crossover fashion. Electrical, pressure and thermal QST were performed at baseline and after 1 and 2 h. Pain intensity was assessed on a 0-10 numeric rating scale every 30 min for up to 2 h. The ability of baseline QST to predict pain reduction after 2 h was analysed using linear mixed models. Genetic variants of drug-metabolizing enzymes and genes affecting pain sensitivity were examined as covariables. RESULTS: No predictor of analgesic effect was found for oxycodone and clobazam. Thermal QST was associated with analgesic effect of imipramine: patients more sensitive to heat or cold were more likely to experience an effect of imipramine. Pharmacogenetic variants and pain-related candidate genes were not associated with drug efficacy. CONCLUSIONS: Thermal QST have the potential to predict imipramine effect in chronic low back pain. Oxycodone and clobazam effects could not be predicted by any of the selected QST or genetic variants. SIGNIFICANCE: Predicting drug efficacy in chronic low back pain remains difficult. There is some evidence that patients more sensitive to heat and cold pain respond better to imipramine.

Neural correlates of working memory in children and adolescents with agenesis of the corpus callosum: An fMRI study.

The ability to temporarily maintain relevant information in mind in the presence of interference or distracting information, also called working memory (WM), is critical for higher cognitive functions and cognitive development. In typically developing (TD) children, WM is underpinned by a fronto-parietal network of interacting left and right brain regions. Developmental absence (agenesis) of the corpus callosum (AgCC) is a congenital brain malformation resulting from disruption of corpus callosum formation. This study aims to investigate functional organisation of WM in children and adolescents with AgCC using functional magnetic resonance imaging (fMRI). Nine children with AgCC and a comparison group of sixteen TD children aged 8-17 years completed an fMRI WM paradigm designed to enable investigation of different WM processes, i.e., encoding, maintenance and retrieval. We found that AgCC children recruited globally similar brain regions as the TD comparison group during the WM task, despite significant disparity in brain development, i.e., bilateral occipito-frontal activations during verbal encoding, and bilateral fronto-parietal executive control network during retrieval. However, compared to their TD peers, children with AgCC seemed less able to engage lateralised brain systems specialised for particular memory material (i.e. less supramarginal activations for verbal material and less fusiform activations for face processing) and particular memory process (i.e. absence of right-predominant activations during retrieval). Group differences in the pattern of activation might also reflect different cognitive strategies to cope with competition in processing resources with different susceptibility to concurrent tasks (verbal vs visual), such as differential recruitment of associative visual areas and executive prefrontal regions in the AgCC compared with the TD group depending on the concurrent task completed during maintenance. This study provides a first step towards a better understanding of functional brain networks underlying higher cognitive functions in children with AgCC.

Analgesic effect of clobazam in chronic low-back pain but not in experimentally induced pain.

BACKGROUND: Chronic pain is frequently associated with hypersensitivity of the nervous system, and drugs that increase central inhibition are therefore a potentially effective treatment. Benzodiazepines are potent modulators of GABAergic neurotransmission and are known to exert antihyperalgesic effects in rodents, but translation into patients are lacking. This study investigates the effect of the benzodiazepine clobazam in chronic low-back pain in humans. The aim of this study is to explore the effect of GABA modulation on chronic low-back pain and on quantitative sensory tests. METHODS: In this double-blind cross-over study, 49 patients with chronic low-back pain received a single oral dose of clobazam 20 mg or active placebo tolterodine 1 mg. Pain intensity on the 0-10 numeric rating scale and quantitative sensory tests were assessed during 2 h after drug intake. RESULTS: Pain intensity in the supine position was significantly reduced by clobazam compared to active placebo (60 min: 2.9 vs. 3.5, p = 0.008; 90 min: 2.7 vs. 3.3, p = 0.024; 120 min: 2.4 vs. 3.1, p = 0.005). Pain intensity in the sitting position was not significantly different between groups. No effects on quantitative sensory tests were observed. CONCLUSIONS: This study suggests that clobazam has an analgesic effect in patients with chronic low-back pain. Muscle relaxation or sedation may have contributed to the effect. Development of substances devoid of these side effects would offer the potential to further investigate the antihyperalgesic action of GABAergic compounds. SIGNIFICANCE: Modulation of GABAergic pain-inhibitory pathways may be a potential future therapeutic target.

Neurofeedback Tunes Scale-Free Dynamics in Spontaneous Brain Activity.

Brain oscillations exhibit long-range temporal correlations (LRTCs), which reflect the regularity of their fluctuations: low values representing more random (decorrelated) while high values more persistent (correlated) dynamics. LRTCs constitute supporting evidence that the brain operates near criticality, a state where neuronal activities are balanced between order and randomness. Here, healthy adults used closed-loop brain training (neurofeedback, NFB) to reduce the amplitude of alpha oscillations, producing a significant increase in spontaneous LRTCs post-training. This effect was reproduced in patients with post-traumatic stress disorder, where abnormally random dynamics were reversed by NFB, correlating with significant improvements in hyperarousal. Notably, regions manifesting abnormally low LRTCs (i.e., excessive randomness) normalized toward healthy population levels, consistent with theoretical predictions about self-organized criticality. Hence, when exposed to appropriate training, spontaneous cortical activity reveals a residual capacity for "self-tuning" its own temporal complexity, despite manifesting the abnormal dynamics seen in individuals with psychiatric disorder. Lastly, we observed an inverse-U relationship between strength of LRTC and oscillation amplitude, suggesting a breakdown of long-range dependence at high/low synchronization extremes, in line with recent computational models. Together, our findings offer a broader mechanistic framework for motivating research and clinical applications of NFB, encompassing disorders with perturbed LRTCs.

How motivation and reward learning modulate selective attention.

Motivational stimuli such as rewards elicit adaptive responses and influence various cognitive functions. Notably, increasing evidence suggests that stimuli with particular motivational values can strongly shape perception and attention. These effects resemble both selective top-down and stimulus-driven attentional orienting, as they depend on internal states but arise without conscious will, yet they seem to reflect attentional systems that are functionally and anatomically distinct from those classically associated with frontoparietal cortical networks in the brain. Recent research in human and nonhuman primates has begun to reveal how reward can bias attentional selection, and where within the cognitive system the signals providing attentional priority are generated. This review aims at describing the different mechanisms sustaining motivational attention, their impact on different behavioral tasks, and current knowledge concerning the neural networks governing the integration of motivational influences on attentional behavior.

Imaging studies of functional neurologic disorders.

Brain imaging techniques provide unprecedented opportunities to study the neural mechanisms underlying functional neurologic disorder (FND, or conversion disorder), which have long remained a mystery and clinical challenge for physicians, as they arise with no apparent underlying organic disease. One of the first questions addressed by imaging studies concerned whether motor conversion deficits (e.g., hysteric paralysis) represent a form of (perhaps unconscious) simulation, a mere absence of voluntary movement, or more specific disturbances in motor control (such as abnormal inhibition). Converging evidence from several studies using different techniques and paradigms has now demonstrated distinctive brain activation patterns associated with functional deficits, unlike those seen in actors simulating similar deficits. Thus, patients with motor FND show consistent hypoactivation of both cortical and subcortical motor pathways, with frequent increases in other brain areas within the limbic system, but no recruitment of prefrontal regions usually associated with voluntary motor inhibition. Other studies point to a dysfunction in sensorimotor integration and agency - related to parietal dysfunction - and abnormal motor planning related to supplementary motor area and prefrontal areas. These findings not only suggest that functional symptoms reflect a genuine brain dysfunction, but also give new insights into how they are produced. However, fewer studies attempted to understand why these symptoms are produced and linked to potential psychologic or emotional risk/triggering factors. Results from such studies point towards abnormal limbic regulation with heightened emotional arousal and amygdalar activity, potentially related to engagement of defense systems and stereotyped motor behaviors, mediated by medial prefrontal cortex and subcortical structures, including the periaqueductal gray area and basal ganglia. In addition, across different symptom domains, several studies reported abnormal recruitment of ventromedial prefrontal cortex (vmPFC), a region known to regulate emotion appraisal, memory retrieval, and self-reflective representations. The vmPFC might provide important modulatory signals to both cortical and subcortical sensorimotor, visual, and even memory circuits, promoting maladaptive self-protective behaviors based on personal affective appraisals of particular events. A better understanding of such a role of vmPFC in FND may help link how and why these symptoms are produced. Further research is also needed to determine brain activation patterns associated with FND across different types of deficits and different evolution stages (e.g., acute vs. chronic vs. recovered).

Resting-state functional connectivity of emotion regulation networks in euthymic and non-euthymic bipolar disorder patients.

BACKGROUND: Previous functional magnetic resonance imaging studies in bipolar disorder (BD) have evidenced changes in functional connectivity (FC) in brain areas associated with emotion processing, but how these changes vary with mood state and specific clinical symptoms is not fully understood. METHODS: We investigated resting-state FC between a priori regions of interest (ROIs) from the default-mode network and key structures for emotion processing and regulation in 27 BD patients and 27 matched healthy controls. We further compared connectivity patterns in subgroups of 15 euthymic and 12 non-euthymic patients and tested for correlations of the connectivity strength with measures of mood, anxiety, and rumination tendency. No correction for multiple comparisons was applied given the small population sample and pre-defined target ROIs. RESULTS: Overall, regardless of mood state, BD patients exhibited increased FC of the left amygdala with left sgACC and PCC, relative to controls. In addition, non-euthymic BD patients showed distinctive decrease in FC between right amygdala and sgACC, whereas euthymic patients showed lower FC between PCC and sgACC. Euthymic patients also displayed increased FC between sgACC and right VLPFC. The sgACC-PCC and sgACC-left amygdala connections were modulated by rumination tendency in non-euthymic patients, whereas the sgACC-VLPFC connection was modulated by both the current mood and tendency to ruminate. CONCLUSION: Our results suggest that sgACC-amygdala coupling is critically affected during mood episodes, and that FC of sgACC play a pivotal role in mood normalization through its interactions with the VLPFC and PCC. However, these preliminary findings require replication with larger samples of patients.

Brain circuits implicated in psychogenic paralysis in conversion disorders and hypnosis.

Conversion disorders are defined as neurological symptoms arising without organic damage to the nervous system, presumably in relation to various emotional stress factors, but the exact neural substrates of these symptoms and the mechanisms responsible for their production remain poorly understood. In the past 15 years, novel insights have been gained with the advent of functional neuroimaging studies in patients suffering from conversion disorders in both motor and non-motor (e.g. somatosensory, visual) domains. Several studies have also compared brain activation patterns in conversion to those observed during hypnosis, where similar functional losses can be evoked by suggestion. The current review summarizes these recent results and the main neurobiological hypotheses proposed to account for conversion symptoms, in particular motor deficits. An emerging model points to an important role of ventromedial prefrontal cortex (VMPFC), precuneus, and perhaps other limbic structures (including amygdala), all frequently found to be hyperactivated in conversion disorders in parallel to impaired recruitment of primary motor and/or sensory pathways at the cortical or subcortical (basal ganglia) level. These findings are only partly shared with hypnosis, where increases in precuneus predominate, together with activation of attentional control systems, but without any activation of VMPFC. Both VMPFC and precuneus are key regions for access to internal representations about the self, integrating information from memory and imagery with affective relevance (in VMPFC) and sensory or agency representations (in precuneus). It is therefore postulated that conversion deficits might result from an alteration of conscious sensorimotor functions and self-awareness under the influence of affective and sensory representations generated in these regions, which might promote certain patterns of behaviors in response to self-relevant emotional states.

Self-regulation of inter-hemispheric visual cortex balance through real-time fMRI neurofeedback training.

Recent advances in neurofeedback based on real-time functional magnetic resonance imaging (fMRI) allow for learning to control spatially localized brain activity in the range of millimeters across the entire brain. Real-time fMRI neurofeedback studies have demonstrated the feasibility of self-regulating activation in specific areas that are involved in a variety of functions, such as perception, motor control, language, and emotional processing. In most of these previous studies, participants trained to control activity within one region of interest (ROI). In the present study, we extended the neurofeedback approach by now training healthy participants to control the interhemispheric balance between their left and right visual cortices. This was accomplished by providing feedback based on the difference in activity between a target visual ROI and the corresponding homologue region in the opposite hemisphere. Eight out of 14 participants learned to control the differential feedback signal over the course of 3 neurofeedback training sessions spread over 3 days, i.e., they produced consistent increases in the visual target ROI relative to the opposite visual cortex. Those who learned to control the differential feedback signal were subsequently also able to exert that control in the absence of neurofeedback. Such learning to voluntarily control the balance between cortical areas of the two hemispheres might offer promising rehabilitation approaches for neurological or psychiatric conditions associated with pathological asymmetries in brain activity patterns, such as hemispatial neglect, dyslexia, or mood disorders.

Functional neuro-anatomy of egocentric versus allocentric space representation.

INTRODUCTION: The functional neuroanatomy of the egocentric and allocentric representations of space remains poorly studied with neuroimaging. Here we aim to determine brain structures subserving two different kinds of spatial representations centred on the main axis of either the body or the external scene. METHOD: Sixteen healthy participants evaluated the alignment of a bar relative to the middle of their body (Ego) or relative to another stimulus (Allo) during functional MRI. In a control task (Ctrl), they had to judge the colour of the bar. RESULTS: Correct response rates and response times were similar in the three tasks. fMRI data revealed a predominant role of the right hemisphere in the egocentric task (Ego vs. Allo): selective activity was found in the occipital, superior parietal, and inferior frontal cortices, as well as in the precuneus and supplementary motor area. On the left side, the insula, thalamus, and cerebellum were also activated. Conversely, the allocentric task (Allo vs. Ctrl) showed selective activity centred on the left temporal gyrus. DISCUSSION: This study demonstrates a right hemisphere dominance for representations centred on the longitudinal body axis, but more left-sided activity for scene/object-centred representations of space. These new data shed light on the unique role of several regions involved in spatial perception and help better understand spatial deficits in patients with right hemispheric lesions.

[Analgesic placebo effect: contribution of the neurosciences]. / Effet placebo analgésique: apport des neurosciences.

Over the past twenty years, neuroscience has changed our understanding of placebo analgesia. Often perceived by researchers as a response bias adding noise to the assessment of efficacy, in the patients' view, it is associated with charlatanism. The origin of the word, qualifying a patient's response to "please" the doctor, did not help its rightful appreciation. However, today the placebo analgesia is considered as a psychobiological phenomenon. Thanks to pharmacological manipulations and the development of functional brain imaging, the neural circuitry involved in this effect as well as the role of endorphins and dopamine have been identified. This article describes our current knowledge about this fascinating phenomenon: a psychological modulation can lead to a biological effect.

[Neurobehavioral changes occurring during multiple sclerosis]. / Modifications neurocomportementales secondaires à la sclérose en plaques.

Behavioral changes occurring in patients affected by multiple sclerosis (MSI are often neglected by physicians but are actually part of the clinical spectrum of the disease. In addition, they are known to be responsible for a decline in the quality of life of MS patients. Recently, there has been a growing interest to investigate changes in the emotional experience of MS patients and their decision making, showing that the ability to take advantageous decisions was altered in MS. This paper reviews existing data on this topic.

[Hysteria: an historical entity, a psychiatric condition or a neurological disease?]. / L'hystérie: une entité historique, un trouble psychiatrique ou une maladie neurologique?

It has been suggested that hysteria had waned and was an old-fashioned, stigmatizing and false concept, reflecting the incapacity of the medical community to establish a diagnosis in certain situations. Nowadays, however, those disturbances, now referred to as conversion or dissociative disorders, still remain a frequent and incapacitating condition that every clinician faces. These past decades, several studies have tried to better describe their clinical presentation and their neurobiological mechanisms, with the help of the development of new neuroimaging techniques. If the neurobiological correlates are now better understood, efficient treatments are still lacking and only a multidisciplinary (general practitioners, neurologists and psychiatrists) and individually-tailored therapy might be beneficial to the patients.

Looking at human eyes affects contralesional stimulus processing after right hemispheric stroke.

Human eyes are a powerful social cue that may automatically attract the attention of an observer. Here we tested whether looking toward open human eyes, as often arises in standard clinical "confrontation" tests, may affect contralesional errors in a group of right brain-damaged patients showing visual extinction. Patients were requested to discriminate peripheral shape-targets presented on the left, right, or bilaterally. On each trial they also saw a central task-irrelevant stimulus, comprising an image of the eye sector of a human face, with those seen eyes open or closed. The conditions with central eye stimuli open (vs closed) induced more errors for contralesional peripheral targets, particularly for bilateral trials. These results suggest that seeing open eyes in central vision may attract attentional resources there, reducing attention to the periphery, particularly for the affected contralesional side. The seen gaze of the examiner may thus need to be considered during confrontation testing and may contribute to the effectiveness of that clinical procedure.

Functional neuroimaging findings on the human perception of illusory contours.

Illusory contours (IC) have attracted a considerable interest in recent years to derive models of how sensory information is processed and integrated within the visual system. In addition to various findings from neuropsychology, neurophysiology, and psychophysics, several recent studies have used functional neuroimaging to identify the cerebral substrates underlying human perception of IC (in particular Kanizsa figures). In this paper, we review the results from more than 20 neuroimaging studies on IC perception and highlight the great diversity of findings across these studies. We then provide a detailed discussion about the localization ('where' debate) and the timing ('when' debate) of IC processing as suggested by functional neuroimaging. Cortical responses involving visual areas as early as V1/V2 and latencies as rapid as 100 ms have been reported in several studies. Particular issues concerning the role of the right hemisphere and the retinotopic encoding of IC are also discussed. These different findings are tentatively brought together to propose different hypothetical cortical mechanisms that might be responsible for the visual formation of IC. Several remaining questions on IC processing that could potentially be explored with functional neuroimaging techniques are finally emphasized.