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Aim: A new closed-loop functional magnetic resonance imaging method called multivoxel neuroreinforcement has the potential to alleviate the subjective aversiveness of exposure-based interventions by directly inducing phobic representations in the brain, outside of conscious awareness. The current study seeks to test this method as an intervention for specific phobia., Methods: In a randomized, double-blind, controlled single-university trial, individuals diagnosed with at least two (one target, one control) animal subtype-specific phobias were randomly assigned (1:1:1) to receive one, three, or five sessions of multivoxel neuroreinforcement in which they were rewarded for implicit activation of a target animal representation. Amygdala response to phobic stimuli was assessed by study staff blind to target and control animal assignments. Pretreatment to posttreatment differences were analyzed with a two-way repeated-measures anova., Results: A total of 23 participants (69.6% female) were randomized to receive one (n = 8), three (n = 7), or five (n = 7) sessions of multivoxel neuroreinforcement. Eighteen (n = 6 each group) participants were analyzed for our primary outcome. After neuroreinforcement, we observed an interaction indicating a significant decrease in amygdala response for the target phobia but not the control phobia. No adverse events or dropouts were reported as a result of the intervention., Conclusion: Results suggest that multivoxel neuroreinforcement can specifically reduce threat signatures in specific phobia. Consequently, this intervention may complement conventional psychotherapy approaches with a nondistressing experience for patients seeking treatment. This trial sets the stage for a larger randomized clinical trial to replicate these results and examine the effects on real-life exposure., Clinical Trial Registration: The now-closed trial was prospectively registered at ClinicalTrials.gov with ID NCT03655262., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

It has been reported that threatening and non-threatening visual stimuli can be distinguished based on the multi-voxel patterns of haemodynamic activity in the human ventral visual stream. Do these findings mean that there may be evolutionarily hardwired mechanisms within early perception, for the fast and automatic detection of threat, and maybe even for the generation of the subjective experience of fear? In this human neuroimaging study, we presented participants ('fear' group: N = 30; 'no fear' group: N = 30) with 2700 images of animals that could trigger subjective fear or not as a function of the individual's idiosyncratic 'fear profiles' (i.e. fear ratings of animals reported by a given participant). We provide evidence that the ventral visual stream may represent affectively neutral visual features that are statistically associated with fear ratings of participants, without representing the subjective experience of fear itself. More specifically, we show that patterns of haemodynamic activity predictive of a specific 'fear profile' can be observed in the ventral visual stream whether a participant reports being afraid of the stimuli or not. Further, we found that the multivariate information synchronization between ventral visual areas and prefrontal regions distinguished participants who reported being subjectively afraid of the stimuli from those who did not. Together, these findings support the view that the subjective experience of fear may depend on the relevant visual information triggering implicit metacognitive mechanisms in the prefrontal cortex. This article is part of the theme issue 'Sensing and feeling: an integrative approach to sensory processing and emotional experience'.

When patients seek professional help for mental disorders, they often do so because of troubling subjective affective experiences. While these subjective states are at the center of the patient's symptomatology, scientific tools for studying them and their cognitive antecedents are limited. Here, we explore the use of concepts and analytic tools from the science of consciousness, a field of research that has faced similar challenges in having to develop robust empirical methods for addressing a phenomenon that has been considered difficult to pin down experimentally. One important strand is the operationalization of some relevant processes in terms of metacognition and confidence ratings, which can be rigorously studied in both humans and animals. By assessing subjective experience with similar approaches, we hope to develop new scientific approaches for studying affective processes and promoting psychological resilience in the face of debilitating emotional experiences., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

The Signature Biobank is a longitudinal repository of biospecimen, psychological, sociodemographic, and diagnostic data that was created in 2012. The Signature Consortium represents a group of approximately one hundred Quebec-based transdisciplinary clinicians and research scientists with various expertise in the field of psychiatry. The objective of the Signature Biobank is to investigate the multi-faceted underpinnings of psychiatric disorders among patients in crisis. The Signature Consortium is expanding and includes new active members that seek to highlight the contributions made by Signature Biobank since its inception. This article details our research protocol, directions, and summarizes contributions. To date, we have collected biological samples (n = 1,986), and questionnaire data (n = 2,085) from psychiatric emergency patients of the Institut universitaire en santé mentale de Montréal (Quebec, Canada), with a large proportion from whom both data types were collected (n = 1,926). In addition to this, a subsample of patients was followed-up at hospital discharge, and two additional outpatient clinic appointments (n = 958 with at least one follow-up). In addition, a socio-demographically matched comparison group of individuals who were not hospitalized for psychiatric disorders (n = 149) was recruited from the surrounding catchment area. To summarize, a systematic review of the literature shows that the Signature Biobank has contributed to better characterizing psychiatric comorbidities, biological profiles, and psychosocial functioning across some of the most common psychiatric disorders, including psychosis, mood, anxiety, and substance use disorders. The Signature Biobank is now one of the world's largest repositories of data collected from patients receiving care at a psychiatric emergency unit., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Pavlovian learning processes are central to the etiology and treatment of anxiety disorders. Anhedonia and related perturbations in reward processes have been implicated in Pavlovian learning. Associations between anhedonia symptoms and neural indices of Pavlovian learning can inform transdiagnostic associations among depressive and anxiety disorders., Methods: Participants ages 18 to 19 years (67% female) completed a fear extinction (n = 254) and recall (n = 249) paradigm during functional magnetic resonance imaging. Symptom dimensions of general distress (common to anxiety and depression), fears (more specific to anxiety), and anhedonia-apprehension (more specific to depression) were evaluated. We trained whole-brain multivoxel pattern decoders for anhedonia-apprehension during extinction and extinction recall and tested the decoders' ability to predict anhedonia-apprehension in an external validation sample. Specificity analyses examined effects covarying for general distress and fears. Decoding was repeated within canonical brain networks to highlight candidate neurocircuitry underlying whole-brain effects., Results: Whole-brain decoder training succeeded during both tasks. Prediction of anhedonia-apprehension in the external validation sample was successful for extinction (R 2  = 0.047; r = 0.276, p = .002) but not extinction recall (R 2 < 0.001, r = -0.063, p = .492). The extinction decoder remained significantly associated with anhedonia-apprehension covarying for fears and general distress (t 121  = 3.209, p = .002). Exploratory results highlighted activity in the cognitive control, default mode, limbic, salience, and visual networks related to these effects., Conclusions: Results suggest that patterns of brain activity during extinction, particularly in the cognitive control, default mode, limbic, salience, and visual networks, can be predictive of anhedonia symptoms. Future research should examine associations between anhedonia and extinction, including studies of exposure therapy or positive affect treatments among anhedonic individuals., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The mechanisms underlying the subjective experiences of mental disorders remain poorly understood. This is partly due to long-standing over-emphasis on behavioral and physiological symptoms and a de-emphasis of the patient's subjective experiences when searching for treatments. Here, we provide a new perspective on the subjective experience of mental disorders based on findings in neuroscience and artificial intelligence (AI). Specifically, we propose the subjective experience that occurs in visual imagination depends on mechanisms similar to generative adversarial networks that have recently been developed in AI. The basic idea is that a generator network fabricates a prediction of the world, and a discriminator network determines whether it is likely real or not. Given that similar adversarial interactions occur in the two major visual pathways of perception in people, we explored whether we could leverage this AI-inspired approach to better understand the intrusive imagery experiences of patients suffering from mental illnesses such as post-traumatic stress disorder (PTSD) and acute stress disorder. In our model, a nonconscious visual pathway generates predictions of the environment that influence the parallel but interacting conscious pathway. We propose that in some patients, an imbalance in these adversarial interactions leads to an overrepresentation of disturbing content relative to current reality, and results in debilitating flashbacks. By situating the subjective experience of intrusive visual imagery in the adversarial interaction of these visual pathways, we propose testable hypotheses on novel mechanisms and clinical applications for controlling and possibly preventing symptoms resulting from intrusive imagery., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)

Multiple mental disorders have been associated with dysregulation of precise brain processes. However, few therapeutic approaches can correct such specific patterns of brain activity. Since the late 1960s and early 1970s, many researchers have hoped that this feat could be achieved by closed-loop brain imaging approaches, such as neurofeedback, that aim to modulate brain activity directly. However, neurofeedback never gained mainstream acceptance in mental health, in part due to methodological considerations. In this review, we argue that, when contemporary methodological guidelines are followed, neurofeedback is one of the few intervention methods in psychology that can be assessed in double-blind placebo-controlled trials. Furthermore, using new advances in machine learning and statistics, it is now possible to target very precise patterns of brain activity for therapeutic purposes. We review the recent literature in functional magnetic resonance imaging neurofeedback and discuss current and future applications to mental health.

Mental health problems often involve clusters of symptoms that include subjective (conscious) experiences as well as behavioral and/or physiological responses. Because the bodily responses are readily measured objectively, these have come to be emphasized when developing treatments and assessing their effectiveness. On the other hand, the subjective experience of the patient reported during a clinical interview is often viewed as a weak correlate of psychopathology. To the extent that subjective symptoms are related to the underlying problem, it is often assumed that they will be taken care of if the more objective behavioral and physiological symptoms are properly treated. Decades of research on anxiety disorders, however, show that behavioral and physiological symptoms do not correlate as strongly with subjective experiences as is typically assumed. Further, the treatments developed using more objective symptoms as a marker of psychopathology have mostly been disappointing in effectiveness. Given that "mental" disorders are named for, and defined by, their subjective mental qualities, it is perhaps not surprising, in retrospect, that treatments that have sidelined mental qualities have not been especially effective. These negative attitudes about subjective experience took root in psychiatry and allied fields decades ago when there were few avenues for scientifically studying subjective experience. Today, however, cognitive neuroscience research on consciousness is thriving, and offers a viable and novel scientific approach that could help achieve a deeper understanding of mental disorders and their treatment., (© 2021. The Author(s).)

CACNA1A deletions cause epilepsy, ataxia, and a range of neurocognitive deficits, including inattention, impulsivity, intellectual deficiency and autism. To investigate the underlying mechanisms, we generated mice carrying a targeted Cacna1a deletion restricted to parvalbumin-expressing (PV) neurons (PV Cre ;Cacna1a c/+ ) or to cortical pyramidal cells (PC) (Emx1 Cre ;Cacna1a c/+ ). GABA release from PV-expressing GABAergic interneurons (PV-INs) is reduced in PV Cre ;Cacna1a c/+ mutants, resulting in impulsivity, cognitive rigidity and inattention. By contrast, the deletion of Cacna1a in PCs does not impact cortical excitability or behaviour in Emx1 Cre ;Cacna1a c/+ mutants. A targeted Cacna1a deletion in the orbitofrontal cortex (OFC) results in reversal learning deficits while a medial prefrontal cortex (mPFC) deletion impairs selective attention. These deficits can be rescued by the selective chemogenetic activation of cortical PV-INs in the OFC or mPFC of PV Cre ;Cacna1a c/+ mutants. Thus, Cacna1a haploinsufficiency disrupts perisomatic inhibition in frontal cortical circuits, leading to a range of potentially reversible neurocognitive deficits., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Closed-loop neurofeedback has sparked great interest since its inception in the late 1960s. However, the field has historically faced various methodological challenges. Decoded fMRI neurofeedback may provide solutions to some of these problems. Notably, thanks to the recent advancements of machine learning approaches, it is now possible to target unconscious occurrences of specific multivoxel representations. In this tools of the trade paper, we discuss how to implement these interventions in rigorous double-blind placebo-controlled experiments. We aim to provide a step-by-step guide to address some of the most common methodological and analytical considerations. We also discuss tools that can be used to facilitate the implementation of new experiments. We hope that this will encourage more researchers to try out this powerful new intervention method., (© The Author(s) 2020. Published by Oxford University Press.)

Decoded neurofeedback (DecNef) is a form of closed-loop functional magnetic resonance imaging (fMRI) combined with machine learning approaches, which holds some promises for clinical applications. Yet, currently only a few research groups have had the opportunity to run such experiments; furthermore, there is no existing public dataset for scientists to analyse and investigate some of the factors enabling the manipulation of brain dynamics. We release here the data from published DecNef studies, consisting of 5 separate fMRI datasets, each with multiple sessions recorded per participant. For each participant the data consists of a session that was used in the main experiment to train the machine learning decoder, and several (from 3 to 10) closed-loop fMRI neural reinforcement sessions. The large dataset, currently comprising more than 60 participants, will be useful to the fMRI community at large and to researchers trying to understand the mechanisms underlying non-invasive modulation of brain dynamics. Finally, the data collection size will increase over time as data from newly run DecNef studies will be added.

In a recent experiment, Zhang and colleagues designed a closed-loop brain-machine interface that learned to reduce participants' pain by decoding pain-related brain activity. In doing so, they also highlighted some of the challenges associated with coadaptive processes in brain-machine communication., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In studies of anxiety and other affective disorders, objectively measured physiological responses have commonly been used as a proxy for measuring subjective experiences associated with pathology. However, this commonly adopted "biosignal" approach has recently been called into question on the grounds that subjective experiences and objective physiological responses may dissociate. We performed machine-learning-based analyses on functional magnetic resonance imaging (fMRI) data to assess this issue in the case of fear. Although subjective fear and objective physiological responses were correlated in general, the respective whole-brain multivoxel decoders for the two measures were different. Some key brain regions such as the amygdala and insula appear to be primarily involved in the prediction of physiological reactivity, whereas some regions previously associated with metacognition and conscious perception, including some areas in the prefrontal cortex, appear to be primarily predictive of the subjective experience of fear. The present findings are in support of the recent call for caution in assuming a one-to-one mapping between subjective sufferings and their putative biosignals, despite the clear advantages in the latter's being objectively and continuously measurable in physiological terms.

The idea of targeting unconscious or implicit processes in psychological treatments is not new, but until recently it has not been easy to manipulate these processes without also engaging consciousness. Here we review how this is possible, using various modern cognitive neuroscience methods including a technique known as Decoded Neural-Reinforcement. We discuss the general advantages of this approach, such as how it can facilitate double-blind placebo-controlled studies, and minimize premature patient dropouts in the treatment of fear. We also speculate how this may generalize to other similar physiological survival processes.

Can "hardwired" physiological fear responses (e.g., for spiders and snakes) be reprogramed unconsciously in the human brain? Currently, exposure therapy is among the most effective treatments for anxiety disorders, but this intervention is subjectively aversive to patients, causing many to drop out of treatment prematurely. Here we introduce a method to bypass the subjective unpleasantness in conscious exposure, by directly pairing monetary reward with unconscious occurrences of decoded representations of naturally feared animals in the brain. To decode physiological fear representations without triggering excessively aversive reactions, we capitalize on recent advancements in functional magnetic resonance imaging decoding techniques, and use a method called hyperalignment to infer the relevant representations of feared animals for a designated participant based on data from other "surrogate" participants. In this way, the procedure completely bypasses the need for a conscious encounter with feared animals. We demonstrate that our method can lead to reliable reductions in physiological fear responses, as measured by skin conductance as well as amygdala hemodynamic activity. Not only do these results raise the intriguing possibility that naturally occurring fear responses can be "reprogrammed" outside of conscious awareness, importantly, they also create the rare opportunity to rigorously test a psychological intervention of this nature in a double-blind, placebo-controlled fashion. This may pave the way for a new approach combining the appealing rationale and proven efficacy of conventional psychotherapy with the rigor and leverage of clinical neuroscience., Competing Interests: Conflict of interest statement: M.K. is the inventor of patents related to the DecNef method used in this study, and the original assignee of the patents is Advanced Telecommunications Research Institute International, with which the authors are affiliated., (Copyright © 2018 the Author(s). Published by PNAS.)

A recent fMRI study by Webb et al. (Cortical networks involved in visual awareness independent of visual attention, Proc Natl Acad Sci U S A 2016; 113 :13923-28) proposes a new method for finding the neural correlates of awareness by matching attention across awareness conditions. The experimental design, however, seems at odds with known features of attention. We highlight logical and methodological points that are critical when trying to disentangle attention and awareness.

Motor representations in the human mirror neuron system are tuned to respond to specific observed actions. This ability is widely believed to be influenced by genetic factors, but no study has reported a genetic variant affecting this system so far. One possibility is that genetic variants might interact with visuomotor associative learning to configure the system to respond to novel observed actions. In this perspective, we conducted a candidate gene study on the Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, a genetic variant linked to motor learning in regions of the mirror neuron system, and tested the effect of this polymorphism on motor facilitation and visuomotor associative learning. In a single-pulse TMS study carried on 16 Met (Val/Met and Met/Met) and 16 Val/Val participants selected from a large pool of healthy volunteers, Met participants showed significantly less muscle-specific corticospinal sensitivity during action observation, as well as reduced visuomotor associative learning, compared to Val homozygotes. These results are the first evidence of a genetic variant tuning sensitivity to action observation and bring to light the importance of considering the intricate relation between genetics and associative learning in order to further understand the origin and function of the human mirror neuron system.

Transcranial magnetic stimulation (TMS) studies have shown that observing an action induces muscle-specific changes in corticospinal excitability. From a signal detection theory standpoint, this pattern can be related to sensitivity, which here would measure the capacity to distinguish between two action observation conditions. In parallel to these TMS studies, action observation has also been linked to behavioral effects such as motor priming and interference. It has been hypothesized that behavioral markers of action observation could be related to TMS markers and thus represent a potentially cost-effective mean of assessing the functioning of the action-perception system. However, very few studies have looked at possible relationships between these two measures. The aim of this study was to investigate if individual differences in sensitivity to action observation could be related to the behavioral motor priming and interference effects produced by action observation. To this end, 14 healthy participants observed index and little finger movements during a TMS task and a stimulus-response compatibility task. Index muscle displayed sensitivity to action observation, and action observation resulted in significant motor priming+interference, while no significant effect was observed for the little finger in both task. Nevertheless, our results indicate that the sensitivity measured in TMS was not related to the behavioral changes measured in the stimulus-response compatibility task. Contrary to a widespread assumption, the current results indicate that individual differences in physiological and behavioral markers of action observation may be unrelated. This could have important impacts on the potential use of behavioral markers in place of more costly physiological markers of action observation in clinical settings.

Empathy is an important driver of human social behaviors and presents genetic roots that have been studied in neuroimaging using the intermediate phenotype approach. Notably, the Val66Met polymorphism of the Brain-derived neurotrophic factor (BDNF) gene has been identified as a potential target in neuroimaging studies based on its influence on emotion perception and social cognition, but its impact on self-reported empathy has never been documented. Using a neurogenetic approach, we investigated the association between the BDNF Val66Met polymorphism and self-reported empathy (Davis' Interpersonal Reactivity Index; IRI) in a sample of 110 young adults. Our results indicate that the BDNF genotype is significantly associated with the linear combination of the four facets of the IRI, one of the most widely used self-reported empathy questionnaire. Crucially, the effect of BDNF Val66Met goes beyond the variance explained by two polymorphisms of the oxytocin transporter gene previously associated with empathy and its neural underpinnings (OXTR rs53576 and rs2254298). These results represent the first evidence suggesting a link between the BDNF gene and self-reported empathy and warrant further studies of this polymorphism due to its potential clinical significance.

Emotion perception has been extensively studied in cognitive neurosciences and stands as a promising intermediate phenotype of social cognitive processes and psychopathologies. Exciting imaging genetic studies have recently identified genetic and epigenetic variants affecting brain responses during emotion perception tasks, but characterizing how these variants interact and relate to higher-order cognitive processes remains a challenge. Here, we integrate works in parallel fields and propose a new psychophysical conceptualization to address this issue. This approach proposes to consider genetic variants as 'filters' of perceptual information that can interact to shape different perceptual profiles. Importantly, these perceptual profiles can be precisely described and compared between multivariate genetic groups using a new psychophysical method. Crucially, this approach represents a potentially powerful novel tool to address gene-by-gene and gene-by-environment interactions, and provides a new cognitive perspective to link social perceptive and social cognitive processes in the context of psychiatric disorders.

Unlabelled: Vicarious pain has been shown to enhance observers' nociceptive reactivity and pain perception. We exposed healthy participants to specific parts of facial pain expressions in order to investigate which components are required to induce this modulation. We created 2 classes of stimuli: one containing the most useful information for identification of pain expressions (diagnostic) and one containing the least useful information (antidiagnostic). Twenty-eight normal volunteers received electrical stimulation of the sural nerve immediately after they viewed these stimuli. Subjective ratings (intensity and unpleasantness) as well as the nociceptive flexion reflex (NFR) evoked by the shock were recorded. Results show that diagnostic stimuli lead to higher subjective ratings of shock pain than the antidiagnostic stimuli, but the stimuli classes had no significant impact on the NFR. A control experiment showed that our facial stimuli were given very low valence and arousal ratings compared to stimuli previously used to demonstrate the effect of emotional pictures on pain. Thus, the results are unlikely to be explained by emotions felt by the observer and suggest a vicarious facilitation of supraspinal pain processing induced by key features underlying pain expressions recognition. Results provide further support to the perception-action model of empathy., Perspective: This study demonstrates that visual features that are efficiently used for the recognition of pain expressions are sufficient to induce a vicarious facilitation of self-pain. Supraspinal pain responses were modulated by the informativeness of the areas of the pain expressions that participants viewed prior to the painful stimulations., (Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Empathy is a multi-dimensional concept allowing humans to understand the emotions of others and respond adaptively from a social perspective. This mental process, essential to social interactions, has attracted the attention of many scholars from different fields of study but the blooming interest for empathy in cognitive neurosciences has rekindled this interest. This paper reviews the growing literature stemming from studies using brain stimulation techniques that have investigated directly or indirectly the different components of empathy, including resonance, self-other discrimination, and mentalizing. Some studies have also ventured toward the modulation of this complex process and toward the investigation of different components in populations that show reduced empathic skills. We argue that brain stimulation techniques have the potential to make a unique contribution to the field of empathy research with their exclusive capacity, compared to other brain imaging techniques, to modulate the neural systems involved in the distinct components of this process. Provided the development of innovative ecological paradigms that will put people in actual social interactions as well as comprehensive and adaptive models that can integrate research from different domains, the ultimate goal of this research domain is to devise protocols that can modulate empathy in people with developmental, neurological and psychiatric disorders., (Copyright © 2012 Elsevier Inc. All rights reserved.)

According to an influential view, based on studies of development and of the face inversion effect, human face recognition relies mainly on the treatment of the distances among internal facial features. However, there is surprisingly little evidence supporting this claim. Here, we first use a sample of 515 face photographs to estimate the face recognition information available in interattribute distances. We demonstrate that previous studies of interattribute distances generated faces that exaggerated by 376% this information compared to real-world faces. When human observers are required to recognize faces solely on the basis of real-world interattribute distances, they perform poorly across a broad range of viewing distances (equivalent to 2 to more than 16 m in the real-world). In contrast, recognition is almost perfect when observers recognize faces on the basis of real-world information other than interattribute distances such as attribute shapes and skin properties. We conclude that facial cues other than interattribute distances such as attribute shapes and skin properties are the dominant information of face recognition mechanisms.