The translocator protein 18kDa ligand etifoxine in the treatment of depressive disorders-a double-blind, randomized, placebo-controlled proof-of-concept study.

BACKGROUND: Recent developments suggest that neurosteroids may achieve rapid antidepressant effects. As such, neurosteroidogenesis mediated by the translocator protein 18 kDa (TSPO) might constitute a promising option for the treatment of depression. Therefore, the current clinical trial aims to get the first evidence of whether TPSO ligands promote rapid antidepressant effects. Furthermore, we study which mechanisms of action, e.g., modulation of distinct neuronal networks, neurosteroidogenesis, endocrinological mechanisms, TSPO expression or microbiome composition, contribute to their putative antidepressant effects. METHODS: This is a randomized, placebo-controlled, double-blind single-center trial of 2-week treatment with the TSPO ligand etifoxine versus placebo in depressive patients. Main eligibility criteria: male or female individuals aged 18 to 65 years with unipolar/bipolar depressive disorder with no other psychiatric main diagnosis or acute neurological/somatic disorder or drug/alcohol dependence during their lifetime. The primary endpoint is the time point at which 50% of the maximal effect has occurred (ET50) estimated by the scores of the Hamilton Depression Scale (HAMD-21). A total of 20 patients per group are needed to detect changes of therapeutic efficacy about 5% and changes of ET50 about 10% with a power of 70%. Assuming a drop-out rate of 10-20%, 50 patients will be randomized in total. The study will be conducted at the Department of Psychiatry and Psychotherapy of the University of Regensburg. DISCUSSION: This study will provide a first proof-of-concept on the potential of the TSPO ligand etifoxine in the treatment of depressive disorders. TRIAL REGISTRATION: Clinical Trials Register (EudraCT number: 2021-006773-38 , registration date: 14 September 2022) and German Register of Clinical Studies (DRKS number: DRKS00031099 , registration date: 23 January 2023).

Short-term effects of etifoxine on human gut microbiome in healthy men.

Background: Neurosteroids have recently gained in interest as a treatment strategy for affective disorders. Etifoxine is known for its dual mode of action, one of which is to stimulate endogenous neurosteroid synthesis. The gut microbiome has been studied in affective disorders, but it has not been investigated in the context of human etifoxine or neurosteroid interventions. Methods: We performed a crossover study with 36 healthy male volunteers who received etifoxine versus alprazolam and placebo in a balanced Williams design. Participants were randomized into six sequences and went through three 5-day treatments followed by wash-out phases of 9 days. Bacterial compositions in stool samples were determined by high-throughput 16S rRNA amplicon sequencing. Results: Gut microbiome analyses revealed no relevant effects between treatments with respect to alpha and beta diversity. Differential abundance analyses yielded etifoxine treatment as the only effect related to changes in microbial features with reductions of Faecalibacterium duncaniae, Roseburia hominis and Lactobacillus rogosae (i.e., Bacteroides galacturonicus). Conclusion: Here we report on the first human investigation of the gut microbiome with short-term etifoxine intervention. Differences in diversity and compositional structure of the microbiome were more likely due to between- subject effects rather than medication. However, five-day treatment with etifoxine reduced the abundance of a few bacterial species. These species are currently seen as beneficial components of a healthy intestinal microbiome. This reduction in abundances may be related to elevated endogenous neurosteroids.

Inhalation-modulated detection of olfactory BOLD responses in the human brain.

Introduction: In contrast to other sensory domains, detection of primary olfactory processes using functional magnetic resonance imaging has proven to be notably challenging with conventional block designs. This difficulty arises from significant habituation and hemodynamic responses in olfactory areas that do not appear to align with extended boxcar functions convolved with a generic hemodynamic response model. Consequently, some researchers have advocated for a transition to event-related designs, despite their known lower detection power compared to block designs. Methods: Here, we conducted a block design experiment with 16s of continuous odorant stimulation alternating with 16s of continuous odorless air stimulation in 33 healthy participants. We compared four statistical analyses that relied either on standard block designs (SBD1-2) or on block designs that were modulated by the participants' individual breathing patterns (MBD1-2). Results: We found that such modulated block designs were comparatively more powerful than standard block designs, despite having a substantially lower design efficiency. Using whole-brain effect size maps, we observed that the right insular and medial aspects of the left piriform cortex exhibited a preference for a breathing-modulated analysis approach. Discussion: Research in olfaction that necessitates designs with longer-lasting blocks, such as those employed in the investigation of state-dependent processing, will benefit from the breathing-modulated analyses outlined in this study.

An automated pipeline for obtaining labeled ICA-templates corresponding to functional brain systems.

The complexity of our actions and thinking is likely reflected in functional brain networks. Independent component analysis (ICA) is a popular data-driven method to compute group differences between such networks. A common way to investigate network differences is based on ICA maps which are generated from study-specific samples. However, this approach limits the generalizability and reproducibility of the results. Alternatively, network ICA templates can be used, but up to date, few such templates exist and are limited in terms of the functional systems they cover. Here, we propose a simple two-step procedure to obtain ICA-templates corresponding to functional brain systems of the researcher's choice: In step 1, the functional system of interest needs to be defined by means of a statistical parameter map (input), which one can generate with open-source software such as NeuroSynth or BrainMap. In step 2, that map is correlated to group-ICA maps provided by the Human Connectome Project (HCP), which is based on a large sample size and uses high quality and standardized acquisition procedures. The HCP-provided ICA-map with the highest correlation to the input map is then used as an ICA template representing the functional system of interest, for example, for subsequent analyses such as dual regression. We provide a toolbox to complete step 2 of the suggested procedure and demonstrate the usage of our pipeline by producing an ICA templates that corresponds to "motor function" and nine additional brain functional systems resulting in an ICA maps with excellent alignment with the gray matter/white matter boundaries of the brain. Our toolbox generates data in two different file formats: volumetric-based (NIFTI) and combined surface/volumetric files (CIFTI). Compared to 10 existing templates, our procedure output component maps with systematically stronger contribution of gray matter to the ICA z-values compared to white matter voxels in 9/10 cases by at least a factor of 2. The toolbox allows users to investigate functional networks of interest, which will enhance interpretability, reproducibility, and standardization of research investigating functional brain networks.

GABAergic Effects of Etifoxine and Alprazolam Assessed by Double Pulse TMS.

INTRODUCTION: There is a need for novel anxiolytics with improved side effect profiles compared to benzodiazepines. A promising candidate with alternative pharmacodynamics is the translocator protein ligand, etifoxine. METHODS: To get further insight into its mechanisms of action and side effects compared to the benzodiazepine alprazolam, we performed a double-blind, placebo-controlled, repeated-measures study in 36 healthy male subjects. Participants were examined for trait anxiety and side effects and underwent repeated transcranial magnetic stimulation (TMS) assessments, including motor evoked potentials (MEP), short intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). RESULTS: We observed attenuation of MEPs by alprazolam but not by etifoxine. SICI was not significantly affected by alprazolam or etifoxine. However, the response pattern indicated a lowered SICI threshold after the administration of etifoxine and alprazolam compared to the placebo. ICF and CSP were influenced by neither medication. Alprazolam led to higher sedation and subjective impairment of concentration compared to etifoxine. Individual anxiety trait scores did not affect TMS parameters. DISCUSSION: This study indicated a favorable side effect profile of etifoxine in healthy volunteers. Moreover, it revealed differential GABA-related effects on neuromuscular function by means of TMS. The side effects and TMS profile of etifoxine are compatible with the involvement of neurosteroidogenesis and a predominant α3 subunit modulation compared to alprazolam.

Neurosteroids and translocator protein 18 kDa (TSPO) in depression: implications for synaptic plasticity, cognition, and treatment options.

There is need for novel fast acting treatment options in affective disorders. 3α-reduced neurosteroids such as allopregnanolone are powerful positive allosteric modulators of GABAA receptors and target also extrasynaptic receptors. Their synthesis is mediated by the translocator protein 18 kDa (TSPO). TSPO ligands not only promote endogenous neurosteroidogenesis, but also exert a broad spectrum of functions involving modulation of mitochondrial activity and acting as anti-inflammatory and neuroregenerative agents. Besides affective symptoms, in depression cognitive impairment can be frequently observed, which may be ameliorated through targeting of extrasynaptic GABAA receptors either via TSPO ligands or exogenously administered 3α-reduced neurosteroids. Interestingly, recent findings indicate an enhanced activation of the complement system, e.g., enhanced expression of C1q, both in depression and dementia. It is of note that benzodiazepines have been shown to reduce long-term potentiation and to cause cognitive decline. Intriguingly, TSPO may be crucial in mediating the effects of benzodiazepines on synaptic pruning. Here, we discuss how benzodiazepines and TSPO may interfere with synaptic pruning. Moreover, we highlight recent developments of TSPO ligands and 3α-reduced neurosteroids as therapeutic agents. Etifoxine is the only clinically available TSPO ligand so far and has been studied in anxiety disorders. Regarding 3α-reduced neurosteroids, brexanolone, an intravenous formulation of allopregnanolone, has been approved for the treatment of postpartum depression and zuranolone, an orally available 3α-reduced neurosteroid, is currently being studied in major depressive disorder and postpartum depression. As such, 3α-reduced neurosteroids and TSPO ligands may constitute promising treatment approaches for affective disorders.

Early remission in multiple sclerosis is linked to altered coherence of the Cerebellar Network.

BACKGROUND: The development of permanent disability in multiple sclerosis (MS) is highly variable among patients, and the exact mechanisms that contribute to this disability remain unknown. METHODS: Following the idea that the brain has intrinsic network organization, we investigated changes of functional networks in MS patients to identify possible links between network reorganization and remission from clinical episodes in MS. Eighteen relapsing-remitting MS patients (RRMS) in their first clinical manifestation underwent resting-state functional MRI and again during remission. We used ten template networks, identified from independent component analysis, to compare changes in network coherence for each patient compared to those of 44 healthy controls from the Human Connectome Project test-retest dataset (two-sample t-test of pre-post differences). Combining a binomial test with Monte Carlo procedures, we tested four models of how functional coherence might change between the first clinical episode and remission: a network can change its coherence (a) with itself ("one-with-self"), (b) with another network ("one-with-other"), or (c) with a set of other networks ("one-with-many"), or (d) multiple networks can change their coherence with respect to one common network ("many-with-one"). RESULTS: We found evidence supporting two of these hypotheses: coherence decreased between the Executive Control Network and several other networks ("one-with-many" hypothesis), and a set of networks altered their coherence with the Cerebellar Network ("many-with-one" hypothesis). CONCLUSION: Given the unexpected commonality of the Cerebellar Network's altered coherence with other networks (a finding present in more than 70% of the patients, despite their clinical heterogeneity), we conclude that remission in MS may result from learning processes mediated by the Cerebellar Network.

Translocator protein (18kDa) TSPO: a new diagnostic or therapeutic target for stress-related disorders?

Efficient treatment of stress-related disorders, such as depression, is still a major challenge. The onset of antidepressant drug action is generally quite slow, while the anxiolytic action of benzodiazepines is considerably faster. However, their long-term use is impaired by tolerance development, abuse liability and cognitive impairment. Benzodiazepines act as positive allosteric modulators of É£-aminobutyric acid type A (GABAA) receptors. 3α-reduced neurosteroids such as allopregnanolone also are positive allosteric GABAA receptor modulators, however, through a site different from that targeted by benzodiazepines. Recently, the administration of neurosteroids such as brexanolone or zuranolone has been shown to rapidly ameliorate symptoms in post-partum depression or major depressive disorder. An attractive alternative to the administration of exogenous neurosteroids is promoting endogenous neurosteroidogenesis via the translocator protein 18k Da (TSPO). TSPO is a transmembrane protein located primarily in mitochondria, which mediates numerous biological functions, e.g., steroidogenesis and mitochondrial bioenergetics. TSPO ligands have been used in positron emission tomography (PET) studies as putative markers of microglia activation and neuroinflammation in stress-related disorders. Moreover, TSPO ligands have been shown to modulate neuroplasticity and to elicit antidepressant and anxiolytic therapeutic effects in animals and humans. As such, TSPO may open new avenues for understanding the pathophysiology of stress-related disorders and for the development of novel treatment options.

Individualizing Representational Similarity Analysis.

Representational similarity analysis (RSA) is a popular multivariate analysis technique in cognitive neuroscience that uses functional neuroimaging to investigate the informational content encoded in brain activity. As RSA is increasingly being used to investigate more clinically-geared questions, the focus of such translational studies turns toward the importance of individual differences and their optimization within the experimental design. In this perspective, we focus on two design aspects: applying individual vs. averaged behavioral dissimilarity matrices to multiple participants' neuroimaging data and ensuring the congruency between tasks when measuring behavioral and neural representational spaces. Incorporating these methods permits the detection of individual differences in representational spaces and yields a better-defined transfer of information from representational spaces onto multivoxel patterns. Such design adaptations are prerequisites for optimal translation of RSA to the field of precision psychiatry.

Interindividual variability of functional connectome in schizophrenia.

Schizophrenia is a complex psychiatric disorder that displays an outstanding interindividual variability in clinical manifestation and neurobiological substrates. A better characterization and quantification of this heterogeneity could guide the search for both common abnormalities (linked to lower intersubject variability) and the presence of biological subtypes (leading to a greater heterogeneity across subjects). In the current study, we address interindividual variability in functional connectome by means of resting-state fMRI in a large sample of patients with schizophrenia and healthy controls. Among the different metrics of distance/dissimilarity used to assess variability, geodesic distance showed robust results to head motion. The main findings of the current study point to (i) a higher between subject heterogeneity in the functional connectome of patients, (ii) variable levels of heterogeneity throughout the cortex, with greater variability in frontoparietal and default mode networks, and lower variability in the salience network, and (iii) an association of whole-brain variability with levels of clinical symptom severity and with topological properties of brain networks, suggesting that the average functional connectome overrepresents those patients with lower functional integration and with more severe clinical symptoms. Moreover, after performing a graph theoretical analysis of brain networks, we found that patients with more severe clinical symptoms had decreased connectivity at both whole-brain level and within the salience network, and that patients with higher negative symptoms had large-scale functional integration deficits.

Supracategorical fear information revealed by aversively conditioning multiple categories.

Fear-generalization is a critical function for survival, in which an organism extracts information from a specific instantiation of a threat (e.g., the western diamondback rattlesnake in my front yard on Sunday) and learns to fear - and accordingly respond to - pertinent higher-order information (e.g., snakes live in my yard). Previous work investigating fear-conditioning in humans has used functional magnetic resonance imaging (fMRI) to demonstrate that activity patterns representing stimuli from an aversively-conditioned category (CS+) are more similar to each other than those of a neutral category (CS-). Here we used fMRI and multiple aversively-conditioned categories to ask whether we would find only similarity increases within the CS+ categories or also similarity increases between the CS+ categories. Using representational similarity analysis, we correlated several models to activity patterns underlying different brain regions and found that, following fear-conditioning, between-category and within-category similarity increased for the CS+ categories in the insula, superior frontal gyrus (SFG), and the right temporal pole. When specifically investigating fear-generalization, these between- and within-category effects were detected in the SFG. These results advance prior pattern-based neuroimaging work by exploring the effect of aversively-conditioning multiple categories and indicate an extended role for such regions in potentially representing supracategorical information during fear-learning.

Linking Personality Traits to Individual Differences in Affective Spaces.

Different individuals respond differently to emotional stimuli in their environment. Therefore, to understand how emotions are represented mentally will ultimately require investigations into individual-level information. Here we tasked participants with freely arranging emotionally charged images on a computer screen according to their subjective emotional similarity (yielding a unique affective space for each participant) and subsequently sought external validity of the layout of the individuals' affective spaces through the five-factor personality model (Neuroticism, Extraversion, Openness to Experience, Agreeableness, Conscientiousness) assessed via the NEO Five-Factor Inventory. Applying agglomerative hierarchical clustering to the group-level affective space revealed a set of underlying affective clusters whose within-cluster dissimilarity, per individual, was then correlated with individuals' personality scores. These cluster-based analyses predominantly revealed that the dispersion of the negative cluster showed a positive relationship with Neuroticism and a negative relationship with Conscientiousness, a finding that would be predicted by prior work. Such results demonstrate the non-spurious structure of individualized emotion information revealed by data-driven analyses of a behavioral task (and validated by incorporating psychological measures of personality) and corroborate prior knowledge of the interaction between affect and personality. Future investigations can similarly combine hypothesis- and data-driven methods to extend such findings, potentially yielding new perspectives on underlying cognitive processes, disease susceptibility, or even diagnostic/prognostic markers for mental disorders involving emotion dysregulation.

Temporal Signal-to-Noise Changes in Combined Multislice- and In-Plane-Accelerated Echo-Planar Imaging with a 20- and 64-Channel Coil.

Echo-planar imaging (EPI) is the most common method of functional MRI for acquiring the blood oxygenation level-dependent (BOLD) contrast, allowing the acquisition of an entire brain volume within seconds. However, because imaging protocols are limited by hardware (e.g., fast gradient switching), researchers must compromise between spatial resolution, temporal resolution, or whole-brain coverage. Earlier attempts to circumvent this problem included developing protocols in which slices of a volume were acquired faster (i.e., in-plane acceleration (S)) or simultaneously (i.e., multislice acceleration (M)). However, applying acceleration methods can lead to a reduction in the temporal signal-to-noise ratio (tSNR): a critical measure of signal stability over time. Using a 20- and 64-channel receiver coil, we show that enabling S-acceleration consistently yielded a substantial decrease in tSNR, regardless of the receiver coil, whereas M-acceleration yielded less pronounced tSNR decrease. Moreover, tSNR losses tended to occur in temporal, insular, and medial brain regions and were more noticeable with the 20-channel coil, while with the 64-channel coil, the tSNR in lateral frontoparietal regions remained relatively stable up to six-fold M-acceleration producing comparable tSNR to that of no acceleration. Such methodological explorations can guide researchers and clinicians in optimizing imaging protocols depending on the brain regions under investigation.

Reliable local dynamics in the brain across sessions are revealed by whole-brain modeling of resting state activity.

Resting state fMRI is a tool for studying the functional organization of the human brain. Ongoing brain activity at "rest" is highly dynamic, but procedures such as correlation or independent component analysis treat functional connectivity (FC) as if, theoretically, it is stationary and therefore the fluctuations observed in FC are thought as noise. Consequently, FC is not usually used as a single-subject level marker and it is limited to group studies. Here we develop an imaging-based technique capable of reliably portraying information of local dynamics at a single-subject level by using a whole-brain model of ongoing dynamics that estimates a local parameter, which reflects if each brain region presents stable, asynchronous or transitory oscillations. Using 50 longitudinal resting-state sessions of one single subject and single resting-state sessions from a group of 50 participants we demonstrate that brain dynamics can be quantified consistently with respect to group dynamics using a scanning time of 20 min. We show that brain hubs are closer to a transition point between synchronous and asynchronous oscillatory dynamics and that dynamics in frontal areas have larger heterogeneity in its values compared to other lobules. Nevertheless, frontal regions and hubs showed higher consistency within the same subject while the inter-session variability found in primary visual and motor areas was only as high as the one found across subjects. The framework presented here can be used to study functional brain dynamics at group and, more importantly, at individual level, opening new avenues for possible clinical applications.

A Comprehensive Review of Dorsomedial Prefrontal Cortex rTMS Utilizing a Double Cone Coil.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has become increasingly popular during the last decades mainly driven by the antidepressant effects of dorsolateral prefrontal cortex stimulation with "butterfly" coils. Only recently, alternative targets such as the dorsomedial prefrontal cortex (dmPFC) have been brought into focus and innovative coil designs such as the angled geometry of the double cone coil (DCC) have raised hope to reach even deeper located targets. OBJECTIVE: To provide a systematic and comprehensive review on the application of rTMS stimulation of the dmPFC using the DCC in neuropathological and healthy samples. METHODS: We systematically searched the MEDLINE® database (http://www.ncbi.nlm.nih.gov/pubmed/). Due to the heterogeneous naming of DCC stimulation over the dmPFC a variety of search terms was applied resulting in a numeral quantity of 340 hits. RESULTS: DCC stimulation over the dmPFC has been proven to be safe and feasible in various neuropsychiatric disorders and in healthy subjects. Clinical results are encouraging, but have to be considered as preliminary as data from sham-controlled clinical trials and knowledge about the neurobiological underpinnings are still scarce. CONCLUSION: DCC stimulation over the dmPFC represents a promising approach in the fast evolving noninvasive brain stimulation techniques aiming at the functional modulation of brain areas vitally involved in affect, sensory autonomic, cognitive, and salience regulation. This may hold potential for both neuroscientific research and clinical applications in the treatment of psychiatric disorders.

Functional Connectivity in Multiple Sclerosis: Recent Findings and Future Directions.

Multiple sclerosis is a debilitating disorder resulting from scattered lesions in the central nervous system. Because of the high variability of the lesion patterns between patients, it is difficult to relate existing biomarkers to symptoms and their progression. The scattered nature of lesions in multiple sclerosis offers itself to be studied through the lens of network analyses. Recent research into multiple sclerosis has taken such a network approach by making use of functional connectivity. In this review, we briefly introduce measures of functional connectivity and how to compute them. We then identify several common observations resulting from this approach: (a) high likelihood of altered connectivity in deep-gray matter regions, (b) decrease of brain modularity, (c) hemispheric asymmetries in connectivity alterations, and (d) correspondence of behavioral symptoms with task-related and task-unrelated networks. We propose incorporating such connectivity analyses into longitudinal studies in order to improve our understanding of the underlying mechanisms affected by multiple sclerosis, which can consequently offer a promising route to individualizing imaging-related biomarkers for multiple sclerosis.

The neural representation of an individualized relational affective space.

Humans experience emotions every day. Traditionally, psychology has described emotions through discrete labels (e.g. happy, afraid) or standardized affective dimensions (e.g. valence, arousal), and neuroscience has more recently sought the neurobiological basis of emotions via functional neuroimaging. However, by treating emotions similarly among everyone, we neglect that emotions are individualized; thus the overall relational structure of an individual's emotion information may be vital in understanding how the brain represents emotions. Combining behavioral and functional MRI experiments with similarity analyses, we demonstrate that neural activity patterns in the left insula correspond to the multi-dimensional arrangement of individuals' affective spaces, despite interindividual differences, better than to a group-averaged model of affective space, a standardized valence-arousal space, a semantic category space, and a visual similarity space. This finding suggests that the insula may underlie individual-level affective information processing that is specific to one's own affective states, which offers new opportunities for functional neuroimaging to inform clinical approaches of disorders involving emotion dysregulation.

Cross-decoding supramodal information in the human brain.

Perceptual decision making is the cognitive process wherein the brain classifies stimuli into abstract categories for more efficient downstream processing. A system that, during categorization, can process information regardless of the information's original sensory modality (i.e., a supramodal system) would have a substantial advantage over a system with dedicated processes for specific sensory modalities. While many studies have probed decision processes through the lens of one sensory modality, it remains unclear whether there are such supramodal brain areas that can flexibly process task-relevant information regardless of the original "format" of the information. To investigate supramodality, one must ensure that supramodal information exists somewhere within the functional architecture by rendering information from multiple sensory systems necessary but insufficient for categorization. To this aim, we tasked participants with categorizing auditory and tactile frequency-modulated sweeps according to learned, supramodal categories in a delayed match-to-category paradigm while we measured their blood-oxygen-level dependent signal with functional MRI. To detect supramodal information, we implemented a set of cross-modality pattern classification analyses, which demonstrated that the left caudate nucleus encodes category-level information but not stimulus-specific information (such as spatial directions and stimulus modalities), while the right inferior frontal gyrus, showing the opposite pattern, encodes stimulus-specific information but not category-level information. Given our paradigm, these results reveal abstract representations in the brain that are independent of motor, semantic, and sensory-specific processing, instead reflecting supramodal, categorical information, which points to the caudate nucleus as a locus of cognitive processes involved in complex behavior.

Relating experimentally-induced fear to pre-existing phobic fear in the human brain.

While prior work has demonstrated that fear-conditioning changes the neural representation of previously neutral stimuli, it remains unknown to what extent this new representation abstracts away from specific fears and which brain areas are involved therein. To investigate this question, we sought commonalities between experimentally-induced fear via electric shocks and pre-existing phobia. Using functional MRI, we tested the effect of fear-conditioning pictures of dogs in 21 spider-fearful participants across three phases: baseline, post-conditioning, and extinction. Considering phobic stimuli as a reference point for the state of fear allowed us to examine whether fear-conditioning renders information patterns of previously neutral stimuli more similar to those of phobic stimuli. We trained a classification algorithm to discriminate information patterns of neutral stimuli (rats) and phobic stimuli and then tested the algorithm on information patterns from the conditioned stimuli (dogs). Performing this cross-decoding analysis at each experimental phase revealed brain regions in which dogs were classified as rats during baseline, as spiders following conditioning, and again as rats after extinction. A follow-up analysis showed that changes in visual perception information cannot explain the changing classification performance. These results demonstrate a common neural representation for processing fear-eliciting information, either pre-existing or acquired by classical conditioning.

Decoding of auditory and tactile perceptual decisions in parietal cortex.

Perceptual decision making is the process in which stimuli of a rich environment are reduced to a single choice. Parietal cortex is involved in many tasks that require perceptual decisions such as attentional focusing, categorization, and eventually response selection. While much work in both the human and monkey domains has investigated processes related to visual decision making, relatively little research has explored auditory and tactile perceptual decisions. As such, we wanted to know whether these regions also play a role in auditory and tactile decision making. Using functional magnetic resonance imaging on humans and a paradigm specifically designed to avoid motor confounds, we found that one area in the right intraparietal sulcus, contained high-level abstract representations of auditory and tactile category-specific information. Our findings advance the idea that parietal cortex represents information that abstracts away from both the input and output domains.