Altered reward network responses to social touch in major depression.

BACKGROUND: Social touch is an integral part of social relationships and has been associated with reward. Major depressive disorder (MDD) is characterized by severe impairments in reward processing, but the neural effects of social touch in MDD are still elusive. In this study, we aimed to determine whether the neural processing of social touch is altered in MDD and to assess the impact of antidepressant therapy. METHODS: Before and after antidepressant treatment, 53 MDD patients and 41 healthy controls underwent functional magnetic resonance imaging (fMRI) while receiving social touch. We compared neural responses to social touch in the reward network, behavioral ratings of touch comfort and general aversion to interpersonal touch in patients to controls. Additionally, we examined the effect of treatment response on those measures. RESULTS: Clinical symptoms decreased after treatment and 43.4% of patients were classified as responders. Patients reported higher aversion to interpersonal touch and lower comfort ratings during the fMRI paradigm than controls. Patients showed reduced responses to social touch in the nucleus accumbens, caudate nucleus and putamen than controls, both before and after treatment. Contrary to our hypotheses, these effects were independent of touch velocity. Non-responders exhibited blunted response in the caudate nucleus and the insula compared to responders, again irrespective of time. CONCLUSIONS: These findings suggest altered striatal processing of social touch in MDD. Persistent dysfunctional processing of social touch despite clinical improvements may constitute a latent risk factor for social withdrawal and isolation.

Common and dissociable effects of oxytocin and lorazepam on the neurocircuitry of fear.

Benzodiazepines (BZDs) represent the gold standard of anxiolytic pharmacotherapy; however, their clinical benefit is limited by side effects and addictive potential. Consequently, there is an urgent need to develop novel and safe anxiolytics. The peptide hormone oxytocin (OXT) exhibits anxiolytic-like properties in animals and humans, but whether OXT and BZDs share similar effects on the neural circuitry of fear is unclear. Therefore, the rationale of this ultra-high-field functional MRI (fMRI) study was to test OXT against the clinical comparator lorazepam (LZP) with regard to their neuromodulatory effects on local and network responses to fear-related stimuli. One hundred twenty-eight healthy male participants volunteered in this randomized double-blind, placebo-controlled, between-group study. Before scanning using an emotional face-matching paradigm, participants were randomly administered a single dose of OXT (24 IU), LZP (1 mg), or placebo. On the behavioral level, LZP, but not OXT, caused mild sedation, as evidenced by a 19% increase in reaction times. On the neural level, both OXT and LZP inhibited responses to fearful faces vs. neutral faces within the centromedial amygdala (cmA). In contrast, they had different effects on intra-amygdalar connectivity; OXT strengthened the coupling between the cmA and basolateral amygdala, whereas LZP increased the interplay between the cmA and superficial amygdala. Furthermore, OXT, but not LZP, enhanced the coupling between the cmA and the precuneus and dorsomedial prefrontal cortex. These data implicate inhibition of the cmA as a common denominator of anxiolytic action, with only OXT inducing large-scale connectivity changes of potential therapeutic relevance.

Dissociating the Neural Correlates of Consciousness and Task Relevance in Face Perception Using Simultaneous EEG-fMRI.

Current theories of visual consciousness disagree about whether it emerges during early stages of processing in sensory brain regions or later when a widespread frontoparietal network becomes involved. Moreover, disentangling conscious perception from task-related postperceptual processes (e.g., report) and integrating results across different neuroscientific methods remain ongoing challenges. The present study addressed these problems using simultaneous EEG-fMRI and a specific inattentional blindness paradigm with three physically identical phases in female and male human participants. In phase 1, participants performed a distractor task during which line drawings of faces and control stimuli were presented centrally. While some participants spontaneously noticed the faces in phase 1, others remained inattentionally blind. In phase 2, all participants were made aware of the task-irrelevant faces but continued the distractor task. In phase 3, the faces became task-relevant. Bayesian analysis of brain responses demonstrated that conscious face perception was most strongly associated with activation in fusiform gyrus (fMRI) as well as the N170 and visual awareness negativity (EEG). Smaller awareness effects were revealed in the occipital and prefrontal cortex (fMRI). Task-relevant face processing, on the other hand, led to strong, extensive activation of occipitotemporal, frontoparietal, and attentional networks (fMRI). In EEG, it enhanced early negativities and elicited a pronounced P3b component. Overall, we provide evidence that conscious visual perception is linked with early processing in stimulus-specific sensory brain areas but may additionally involve prefrontal cortex. In contrast, the strong activation of widespread brain networks and the P3b are more likely associated with task-related processes.SIGNIFICANCE STATEMENT How does our brain generate visual consciousness-the subjective experience of what it is like to see, for example, a face? To date, it is hotly debated whether it emerges early in sensory brain regions or later when a widespread frontoparietal network is activated. Here, we use simultaneous fMRI and EEG for high spatial and temporal resolution and demonstrate that conscious face perception is predominantly linked to early and occipitotemporal processes, but also prefrontal activity. Task-related processes (e.g., decision-making), on the other hand, elicit brain-wide activations including late and strong frontoparietal activity. These findings challenge numerous previous studies and highlight the importance of investigating the neural correlates of consciousness in the absence of task relevance.

Neural correlates of consciousness in an attentional blink paradigm with uncertain target relevance.

Several event-related potentials (ERPs) have been proposed as neural correlates of consciousness (NCC), most prominently the early visual awareness negativity (VAN) and the late P3b component. Highly influential support for the P3b comes from studies utilizing the attentional blink (AB), where conscious perception of a first visual target (T1) impairs reporting a second target (T2) presented shortly afterwards. Recent no-report studies using other paradigms suggest that the P3b component may reflect post-perceptual processes associated with decision-making rather than awareness. However, no-report studies are limited in their awareness assessment, and their conclusions have not been tested in an AB paradigm. The present study (N = 38) addressed these issues using a novel AB paradigm, which reduced decision-making processes by omitting a discrimination task on T2 stimuli and rendering their relevance uncertain. Nevertheless, awareness was assessed trial by trial. Comparing ERPs in response to seen versus unseen T2 stimuli revealed a VAN but no enhanced P3b regardless of whether they were marked as distinct from distractor stimuli or not. Our results corroborate the VAN and challenge the P3b as NCC despite rigorous trial-by-trial assessment of conscious perception. Thus, they support the idea that awareness emerges during early sensory processing.

Differential effects of prediction error and adaptation along the auditory cortical hierarchy during deviance processing.

Neural mismatch responses have been proposed to rely on different mechanisms, including prediction error-related activity and adaptation to frequent stimuli. However, the hierarchical cortical structure of these mechanisms is unknown. To investigate this question, we recorded hemodynamic responses while participants (N = 54) listened to an auditory oddball sequence as well as a suited control condition. In addition to effects in sensory processing areas (Heschl's gyrus, superior temporal gyrus (STG)), we found several distinct clusters that indexed deviance processing in frontal and parietal regions (anterior cingulate cortex/supplementary motor area (ACC/SMA), inferior parietal lobule (IPL), anterior insula (AI), inferior frontal junction (IFJ)). Comparing responses to the control stimulus with the deviant and standard enabled us to delineate the contributions of prediction error- or adaptation-related brain activation, respectively. We observed significant effects of adaptation in Heschl's gyrus, STG and ACC/SMA, while prediction error-related activity was observed in STG, IPL, AI and IFJ. Additional dynamic causal modeling confirmed the superiority of a hierarchical processing structure compared to a flat structure. Thus, we found that while prediction-error related processes increased with the hierarchical level of the brain area, adaptation declined. This suggests that the relative contribution of different mechanisms in deviance processing varies across the cortical hierarchy.

Differential Effects of Awareness and Task Relevance on Early and Late ERPs in a No-Report Visual Oddball Paradigm.

To date it is poorly understood how and when deviance processing interacts with awareness and task relevance. Furthermore, an important issue in the study of consciousness is the prevalent confound of conscious perception with the requirement of reporting it. This study addresses these topics using a no-report inattentional blindness paradigm with a visual oddball sequence of geometrical shapes presented to male and female human participants. Electrophysiological responses were obtained in three physically identical Phases A-C that differed only with respect to the instructions: (A) participants were uninformed about the shapes and attended an unrelated foreground task (inattentional blind), (B) were informed about the shapes but still attended the foreground task, and (C) attended the shapes. Conscious processing of shapes was indexed by the visual awareness negativity but not a P3. Deviance processing was associated with the visual mismatch negativity independently of consciousness and task relevance. The oddball P3, however, only emerged when the stimuli were task relevant, and was absent for consciously perceived but task irrelevant stimuli. The P3 thus does not represent a reliable marker of stimulus awareness. This result pattern supports the view of hierarchical predictive processing, where lower levels display automatic deviance processing, whereas higher levels require attention and task relevance.SIGNIFICANCE STATEMENT To react to potentially important changes in our environment it is fundamental to detect deviations from regularities of sensory input. It has yet to be understood how awareness and task relevance of this input interact with deviance processing. We investigated the role of awareness in deviance detection while at the same time circumventing the confound of awareness and report by means of a no-report paradigm. Our results suggest that early processes are elicited automatically, whereas, contrary to prominent theories, late processes do not depend on awareness but on task-based attention.

Dissociating neural correlates of consciousness and task relevance during auditory processing.

In recent years, several ERP components have been identified as potential neural correlates of consciousness (NCC), including early negativities and late positivities. Based on experiments in the visual modality, it has recently been shown that awareness is often confounded with reporting it, possibly overestimating the NCC. It is unknown whether similar constraints also exist in the auditory modality. In order to address this gap, we presented spoken words in a sustained inattentional deafness paradigm. Electrophysiological responses were obtained in three physically identical experimental conditions that differed only with respect to the participants' instructions. Participants were either left uninformed or informed about the presence of spoken words while confronted with an auditory distractor task (U/I condition), informed about the words while exposed to the same task as before (I condition), or requested to respond to the now task-relevant speech stimuli (TR condition). After completion of the U/I condition, only informed participants reported awareness of the words. In ERPs, awareness of words in the U/I and I condition was accompanied by an anterior auditory awareness negativity (AAN). Only when stimuli were task-relevant, i.e., during the TR condition, late positivities emerged. Taken together, these results indicate that early negativities but not late positivities index awareness across sensory modalities. Thus, they provide evidence for a recurrent processing framework, which highlights the importance of early sensory processing in conscious perception.

The causal role of prefrontal hemispheric asymmetry in valence processing of words - Insights from a combined cTBS-MEG study.

Hemispheric asymmetries play an important role in multiple cerebral functions. Asymmetries in prefrontal cortex (PFC) function have been suggested to regulate emotional processing in that right-hemispheric dominance biases towards negative affect, whereas left PFC dominance favors positive affect. This study used transcranial magnetic stimulation to test the causal role of prefrontal asymmetries in the processing of emotional stimuli. To experimentally induce hemispheric asymmetries, 21 healthy volunteers underwent two separate sessions of inhibitory continuous theta burst stimulation (cTBS) to the left versus right dorsolateral prefrontal cortex. Each stimulation was followed by magnetoencephalographic (MEG) recordings of event-related fields elicited by visually presented emotional words in a silent reading task and a subsequent behavioral emotion categorization task. The asymmetry manipulation influenced valence processing of words in early, mid-latency and late time intervals in right occipitotemporal and parietal brain regions. Left-sided cTBS (inducing right-hemispheric dominance) consistently resulted in enhanced brain responses to negative words, while right-sided cTBS (inducing left-hemispheric dominance) enhanced responses to positive words. On a behavioral level, right-hemispheric dominance resulted in more categorization matches of negative compared to positive words, while left-hemispheric dominance resulted in reverse effects. These results provide direct evidence that bottom-up valence processing is influenced by prefrontal hemispheric asymmetry.

Electrophysiological correlates of sustained conscious perception.

Previous research on the neural correlates of consciousness (NCC) in visual perception revealed an early event-related potential (ERP), the visual awareness negativity (VAN), to be associated with stimulus awareness. However, due to the use of brief stimulus presentations in previous studies, it remains unclear whether awareness-related negativities represent a transient onset-related response or correspond to the duration of a conscious percept. Studies are required that allow prolonged stimulus presentation under aware and unaware conditions. The present ERP study aimed to tackle this challenge by using a novel stimulation design. Male and female human participants (n = 62) performed a visual task while task-irrelevant line stimuli were presented in the background for either 500 or 1000 ms. The line stimuli sometimes contained a face, which needed so-called visual one-shot learning to be seen. Half of the participants were informed about the presence of the face, resulting in faces being perceived by the informed but not by the uninformed participants. Comparing ERPs between the informed and uninformed group revealed an enhanced negativity over occipitotemporal electrodes that persisted for the entire duration of stimulus presentation. Our results suggest that sustained visual awareness negativities (SVAN) are associated with the duration of stimulus presentation.

Stimulus awareness is associated with secondary somatosensory cortex activation in an inattentional numbness paradigm.

While inattentional blindness and deafness studies have revealed neural correlates of consciousness (NCC) without the confound of task relevance in the visual and auditory modality, comparable studies for the somatosensory modality are lacking. Here, we investigated NCC using functional magnetic resonance imaging (fMRI) in an inattentional numbness paradigm. Participants (N = 44) received weak electrical stimulation on the left hand while solving a demanding visual task. Half of the participants were informed that task-irrelevant weak tactile stimuli above the detection threshold would be applied during the experiment, while the other half expected stimuli below the detection threshold. Unexpected awareness assessments after the experiment revealed that altogether 10 participants did not consciously perceive the somatosensory stimuli during the visual task. Awareness was not significantly modulated by prior information. The fMRI data show that awareness of stimuli led to increased activation in the contralateral secondary somatosensory cortex. We found no significant effects of stimulus awareness in the primary somatosensory cortex or frontoparietal areas. Thus, our results support the hypothesis that somatosensory stimulus awareness is mainly based on activation in higher areas of the somatosensory cortex and does not require strong activation in extended anterior or posterior networks, which is usually seen when perceived stimuli are task-relevant.

Visual perceptual load and processing of somatosensory stimuli in primary and secondary somatosensory cortices.

Load theory assumes that neural activation to distractors in early sensory cortices is modulated by the perceptual load of a main task, regardless of whether task and distractor share the same sensory modality or not. While several studies have investigated the question of load effects on distractor processing in early sensory areas, there is no functional magnetic resonance imaging (fMRI) study regarding load effects on somatosensory stimuli. Here, we used fMRI to investigate effects of visual perceptual load on neural responses to somatosensory stimuli applied to the wrist in a study with 44 participants. Perceptual load was manipulated by an established sustained visual detection task, which avoided simultaneous target and distractor presentations. Load was operationalized by detection difficulty of subtle or clear color changes of one of 12 rotating dots. While all somatosensory stimuli led to activation in somatosensory areas SI and SII, we found no statistically significant difference in brain activation to these stimuli under high compared to low sustained visual load. Moreover, exploratory Bayesian analyses supported the absence of differences. Thus, our findings suggest a resistance of somatosensory processing to at least some forms of visual perceptual load, possibly due to behavioural relevance of discrete somatosensory stimuli and separable attentional resources for the somatosensory and visual modality.