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BACKGROUND: Public speaking is one of the most commonly feared situations reported in both community and university samples. Despite extensive theoretical models and empirical studies aimed at delineating the underlying factors of Public Speaking Anxiety (PSA), the specific variables contributing to its onset remain incompletely characterised. METHODS: The research involved 297 participants from an AmazonTurk survey, engaging with virtual public speaking scenarios differentiated by audience size, engagement levels, and room spatial dimensions. Participants' anticipated anxiety levels were quantitatively assessed across these scenarios, enabling a comprehensive exploration of the interaction between situational variables and PSA, thereby providing a framework to explore the influence of audience size, engagement, and spatial dimensions on PSA. RESULTS: The mixed-effect model revealed a significant interaction among audience size, audience engagement, and room spatial dimensions. Further analyses using principal axis factoring and multiple regression identified three main factors: F1 (Engagement in a Large Audience), F2 (Confinement or Evaluation Anxiety), and F3 (Audience Disengagement). These factors significantly predict PSA scores. CONCLUSIONS: This study reveals that PSA is influenced by a complex interplay of audience size, room dimensions, and audience engagement. The finding underscores the viable way to incorporate these situational variables in both empirical investigations and therapeutic interventions. Specifically, it introduces a novel framework for standardising audience size relative to room capacity.

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Low-threshold mechanosensory C-fibres, C-tactile afferents (CTs), respond optimally to sensations associated with a human caress. Additionally, CT-stimulation activates brain regions associated with processing affective states. This evidence has led to the social touch hypothesis, that CTs have a key role in encoding the affective properties of social touch. Thus, to date, the affective touch literature has focussed on gentle stroking touch. However, social touch interactions involve many touch types, including static, higher force touch such as hugging and holding. This study aimed to broaden our understanding of the social touch hypothesis by investigating relative preference for static vs dynamic touch and the influence of force on these preferences. Additionally, as recent literature has highlighted individual differences in CT-touch sensitivity, this study investigated the influence of affective touch experiences and attitudes, autistic traits, depressive symptomology and perceived stress on CT-touch sensitivity. Directly experienced, robotic touch responses were obtained through a lab-based study and vicarious touch responses through an online study where participants rated affective touch videos. Individual differences were determined by self-report questionnaire measures. In general, static touch was preferred over CT-non-optimal stroking touch, however, consistent with previous reports, CT-optimal stroking (velocity 1-10 cm/s) was rated most pleasant. However, static and CT-optimal vicarious touch were rated comparably for dorsal hand touch. For all velocities, 0.4N was preferred over 0.05N and 1.5N robotic touch. Participant dynamic touch quadratic terms were calculated for robotic and vicarious touch as a proxy CT-sensitivity measure. Attitudes to intimate touch significantly predict robotic and vicarious quadratic terms, as well as vicarious static dorsal hand touch ratings. Perceived stress negatively predicted robotic static touch ratings. This study has identified individual difference predictors of CT-touch sensitivity. Additionally, it has highlighted the context dependence of affective touch responses and the need to consider static, as well as dynamic affective touch.

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Background: Psoriasis is a chronic systemic inflammatory skin disease, coexisting with depression in up to 25% of patients. Little is known about the drivers of comorbidity, including shared neurobiology and depression brain imaging patterns in patients. An immune-mediated crosstalk between the brain and skin has been hypothesized in psoriasis. With the aim of investigating brain structure and connectivity in psoriasis in relation to depression comorbidity, we conducted a brain imaging study including the largest psoriasis patient sample to date (to our knowledge) and the first to investigate the role of depression and systemic inflammation in brain measures. Effects of coexisting psoriatic arthritis (PsA), which represents joint involvement in psoriasis and a higher putative inflammatory state, were further explored. Methods: Brain magnetic resonance imaging (MRI) data of 1,048 UK Biobank participants were used (131 comorbid patients with psoriasis and depression, age-and sex-matched to: 131 non-depressed psoriasis patients; 393 depressed controls; and 393 non-depressed controls). Interaction effects of psoriasis and depression on volume, thickness and surface of a-priori defined regions of interest (ROIs), white matter tracts and 55x55 partial correlation resting-state connectivity matrices were investigated using general linear models. Linear regression was employed to test associations of brain measures with C-reactive protein (CRP) and neutrophil counts. Results: No differences in regional or global brain volumes or white matter integrity were found in patients with psoriasis compared to controls without psoriasis or PsA. Thickness in right precuneus was increased in psoriasis patients compared to controls, only when depression was present (ß = 0.26, 95% CI [Confidence Intervals] 0.08, 0.44; p = 0.02). In further analysis, psoriasis patients who had PsA exhibited fronto-occipital decoupling in resting-state connectivity compared to patients without joint involvement (ß = 0.39, 95% CI 0.13, 0.64; p = 0.005) and controls (ß = 0.49, 95% CI 0.25, 0.74; p < 0.001), which was unrelated to depression comorbidity. Precuneus thickness and fronto-occipital connectivity were not predicted by CRP or neutrophil counts. Precuneus thickening among depressed psoriasis patients showed a marginal correlation with recurrent lifetime suicidality. Conclusions: Our findings provide evidence for a combined effect of psoriasis and depression on the precuneus, which is not directly linked to systemic inflammation, and may relate to suicidality or altered somatosensory processing. The use of the UK Biobank may limit generalizability of results in populations with severe disease.

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RATIONALE: Affiliative tactile interactions help regulate physiological arousal and confer resilience to acute and chronic stress. C-tactile afferents (CTs) are a population of unmyelinated, low threshold mechanosensitive cutaneous nerve fibres which respond optimally to a low force stimulus, moving at between 1 and 10 cm/s. As CT firing frequencies correlate positively with subjective ratings of touch pleasantness, they are hypothesised to form the first stage of encoding affiliative tactile interactions. Serotonin is a key modulator of social responses with known effects on bonding. OBJECTIVES: The aim of the present study was to determine the effect of acutely lowering central serotonin levels on perceptions of CT-targeted affective touch. METHODS: In a double blind, placebo-controlled design, the effect of acute tryptophan depletion (ATD) on 25 female participants' ratings of directly and vicariously experienced touch was investigated. Psychophysical techniques were used to deliver dynamic tactile stimuli; some velocities were targeted to optimally activate CTs (1-10 cm/s), whereas other, faster and slower strokes fell outside the CT optimal range. Discriminative tactile function, cold pain threshold and tolerance were also measured. RESULTS: ATD significantly increased pleasantness ratings of both directly and vicariously experienced affective touch, increasing discrimination of the specific hedonic value of CT targeted velocities. While ATD had no effect on either tactile or cold pain thresholds, there was a trend for reduced tolerance to cold pain. CONCLUSIONS: These findings are consistent with previous reports that depletion of central serotonin levels modulates neural and behavioural responsiveness to appetitive sensory signals.

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Emotional memories are preferentially consolidated during sleep, through the process of memory reactivation. Targeted memory reactivation (TMR) has been shown to boost memory consolidation during sleep, but its neural correlates remain unclear, particularly for emotional memories. Here, we aimed to examine how TMR of emotional material during slow wave sleep (SWS) impacts upon neural processing during a subsequent arousal rating task. Participants were trained on a spatial memory task including negative and neutral pictures paired with semantically matching sounds. The picture-sound pairs were rated for emotional arousal before and after the spatial memory task. Then, half of the sounds from each emotional category (negative and neutral) were cued during SWS. The next day, participants were retested on both the arousal rating and the spatial memory task inside an MRI scanner, followed by another retest session a week later. Memory consolidation and arousal processing did not differ between cued and non-cued items of either emotional category. We found increased responses to emotional stimuli in the amygdala and orbitofrontal cortex (OFC), and a cueing versus emotion interaction in the OFC, whereby cueing neutral stimuli led to an increase in OFC activity, while cueing negative stimuli led to decreased OFC activation. Interestingly, the effect of cueing on amygdala activation was modulated by time spent in REM sleep. We conclude that SWS TMR impacts OFC activity, while REM sleep plays a role in mediating the effect of such cueing on amygdala.

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Healthy individuals display systematic inaccuracies when allocating attention to perceptual space. Under many conditions, optimized spatial attention processing of the right hemisphere's frontoparietal attention network directs more attention to the left side of perceptual space than the right. This is the pseudoneglect effect. We present evidence reshaping our fundamental understanding of this neural mechanism. We describe a previously unrecognized, but reliable, attention bias to the right side of perceptual space that is associated with semantic object processing. Using an object bisection task, we revealed a significant rightward bias distinct from the leftward bias elicited by the traditional line bisection task. In Experiment 2, object-like shapes that were not easily recognizable exhibited an attention bias between that of horizontal lines and objects. Our results support our proposal that the rightward attention bias is a product of semantic processing and its lateralization in the left hemisphere. In Experiment 3, our novel object-based adaptation of the landmark task further supported this proposition and revealed temporal dynamics of the effect. This research provides novel and crucial insight into the systems supporting intricate and complex attention allocation and provides impetus for a shift toward studying attention in ways that increasingly reflect our complex environments. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

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In the United Kingdom, the most common reasons for a child to come under the care of social services are neglect and abuse. Such early childhood adversity is a risk factor for social-isolation and poor mental health in adulthood. Touch is a key channel for nurturing interactions, and previous studies have shown links between early somatosensory input, experience dependent neural plasticity, and later life emotional functioning. The aim of the present study was to test the relationship between childhood neglect/abuse and later life experiences, attitudes, and hedonic ratings of affective touch. Here, affective touch is defined as low force, dynamic touch which C-Tactile afferents (CTs) respond optimally to. We hypothesized that a childhood lacking in early nurturing tactile stimulation would be associated with reduced sensitivity to socially relevant affective touch in adulthood. To test this, 19 care leavers (average 9.32 ± 3.70 years in foster care) and 32 non-care leavers were recruited through opportunity sampling (mean age = 21.25 ± 1.74 years). Participants completed a range of psychophysical somatosensory tests. First, they rated the pleasantness of CT-optimal (3 cm/s) and non-CT-optimal (0.3 and 30 cm/s) stroking touch applied to their forearm, both robotically and by an experimenter. They also made vicarious ratings of the anticipated pleasantness of social tactile interactions depicted in a series of videos. Finally, they filled in the Childhood Trauma Questionnaire (CTQ) and the Touch Experiences and Attitudes Questionnaire (TEAQ). As expected, care leavers reported significantly higher levels of childhood trauma than the control group. They also reported significantly lower levels of positive childhood touch compared to non-care leavers, but their attitudes and experiences of current intimate and affiliative touch did not differ. Across all psychophysical tests, care leavers showed specific reduction in sensitivity to the affective value of CT targeted 3 cm/s touch. The results of this study support the hypothesis that a lack of nurturing touch in early developmental periods leads to blunted sensitivity to the specific social value of affective touch. Future research should investigate the neural and physiological mechanisms underlying the observed effect.

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BACKGROUND: The initial effects of selective serotonin reuptake inhibitors (SSRIs) in the human living brain are poorly understood. We carried out a 3T resting state fMRI study with pharmacological challenge to determine the brain activation changes over time following different dosages of citalopram. METHODS: During the study, 7.5 mg i.v. citalopram was administered to 32 healthy subjects. In addition, 11.25 mg citalopram was administered to a subset of 9 subjects to investigate the dose-response. Associations with neuroticism (assessed by the NEO PI-R) of the emerging brain activation to citalopram was also investigated. RESULTS: Citalopram challenge evoked significant activation in brain regions that are part of the default mode network, the visual network and the sensorimotor network, extending to the thalamus, and midbrain. Most effects appeared to be dose-dependent and this was statistically significant in the middle cingulate gyrus. Individual citalopram-induced brain responses were positively correlated with neuroticism scores and its subscales in specific brain areas; anxiety subscale scores in thalamus and midbrain and self-consciousness scores in middle cingulate gyrus. There were no sex differences. LIMITATIONS: We investigated only healthy subjects and we used a relatively low sample size in the 11.25 mg citalopram analysis. DISCUSSION: Our results suggest that SSRIs acutely induce an increased arousal-like state of distributed cortical and subcortical systems that is mediated by enhanced serotonin neurotransmission according to levels of neuroticism and underpins trait sensitivity to environmental stimuli and stressors. Studies in depression are needed to determine how therapeutic effects eventually emerge. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.

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Group-level repeated measurements are common in neuroimaging, yet their analysis remains complex. Although a variety of specialized tools now exist, it is surprising that to-date there has been no clear discussion of how repeated-measurements can be analyzed appropriately using the standard general linear model approach, as implemented in software such as SPM and FSL. This is particularly surprising given that these implementations necessitate the use of multiple models, even for seemingly conventional analyses, and that without care it is very easy to specify contrasts that do not correctly test the effects of interest. Despite this, interest in fitting these types of models using conventional tools has been growing in the neuroimaging community. As such it has become even more important to elucidate the correct means of doing so. To begin, this paper will discuss the key concept of the expected mean squares (EMS) for defining suitable F-ratios for testing hypotheses. Once this is understood, the logic of specifying correct repeated measurements models in the GLM should be clear. The ancillary issue of specifying suitable contrast weights in these designs will also be discussed, providing a complimentary perspective on the EMS. A set of steps will then be given alongside an example of specifying a 3-way repeated-measures ANOVA in SPM. Equivalency of the results compared to other statistical software will be demonstrated. Additional issues, such as the inclusion of continuous covariates and the assumption of sphericity, will also be discussed. The hope is that this paper will provide some clarity on this confusing topic, giving researchers the confidence to correctly specify these forms of models within traditional neuroimaging analysis tools.

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Unbalanced group-level models are common in neuroimaging. Typically, data for these models come from factorial experiments. As such, analyses typically take the form of an analysis of variance (ANOVA) within the framework of the general linear model (GLM). Although ANOVA theory is well established for the balanced case, in unbalanced designs there are multiple ways of decomposing the sums-of-squares of the data. This leads to several methods of forming test statistics when the model contains multiple factors and interactions. Although the Type I-III sums of squares have a long history of debate in the statistical literature, there has seemingly been no consideration of this aspect of the GLM in neuroimaging. In this paper we present an exposition of these different forms of hypotheses for the neuroimaging researcher, discussing their derivation as estimable functions of ANOVA models, and discussing the relative merits of each. Finally, we demonstrate how the different hypothesis tests can be implemented using contrasts in analysis software, presenting examples in SPM and FSL.

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C-tactile afferents (CTs) are slowly conducting nerve fibres, present only in hairy skin. They are optimally activated by slow, gentle stroking touch, such as those experienced during a caress. CT stimulation activates affective processing brain regions, alluding to their role in affective touch perception. We tested a theory that CT-activating touch engages the pro-social functions of serotonin, by determining whether reducing serotonin, through acute tryptophan depletion, diminishes subjective pleasantness and affective brain responses to gentle touch. A tryptophan depleting amino acid drink was administered to 16 healthy females, with a further 14 receiving a control drink. After 4 h, participants underwent an fMRI scan, during which time CT-innervated forearm skin and CT non-innervated finger skin was stroked with three brushes of differing texture, at CT-optimal force and velocity. Pleasantness ratings were obtained post scanning. The control group showed a greater response in ipsilateral orbitofrontal cortex to CT-activating forearm touch compared to touch to the finger where CTs are absent. This differential response was not present in the tryptophan depleted group. This interaction effect was significant. In addition, control participants showed a differential primary somatosensory cortex response to brush texture applied to the finger, a purely discriminatory touch response, which was not observed in the tryptophan depleted group. This interaction effect was also significant. Pleasantness ratings were similar across treatment groups. These results implicate serotonin in the differentiation between CT-activating and purely discriminatory touch responses. Such effects could contribute to some of the social abnormalities seen in psychiatric disorders associated with abnormal serotonin function.

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Repeated measurements and multimodal data are common in neuroimaging research. Despite this, conventional approaches to group level analysis ignore these repeated measurements in favour of multiple between-subject models using contrasts of interest. This approach has a number of drawbacks as certain designs and comparisons of interest are either not possible or complex to implement. Unfortunately, even when attempting to analyse group level data within a repeated-measures framework, the methods implemented in popular software packages make potentially unrealistic assumptions about the covariance structure across the brain. In this paper, we describe how this issue can be addressed in a simple and efficient manner using the multivariate form of the familiar general linear model (GLM), as implemented in a new MATLAB toolbox. This multivariate framework is discussed, paying particular attention to methods of inference by permutation. Comparisons with existing approaches and software packages for dependent group-level neuroimaging data are made. We also demonstrate how this method is easily adapted for dependency at the group level when multiple modalities of imaging are collected from the same individuals. Follow-up of these multimodal models using linear discriminant functions (LDA) is also discussed, with applications to future studies wishing to integrate multiple scanning techniques into investigating populations of interest.

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Evidence suggests that depression is a risk factor for dementia; however, the relationship between the two conditions is not fully understood. A novel gene (TOMM40) has been consistently associated with Alzheimer's disease (AD), but has received no attention in depression. We conducted a three-level cross-sectional study to investigate the association of the TOMM40 rs2075650 SNP with depression. We recruited a community sample of 1220 participants (571 controls, 649 lifetime depression) to complete a psychiatric background questionnaire, the Brief Symptom Inventory, and Big Five Inventory at Level-1, 243 (102 controls, 97 remitted, 44 currently depressed) to complete a face-to-face clinical interview and neuropsychological testing at Level-2 and 58 (33 controls, 25 remitted) to complete an emotional face-processing task during fMRI at Level-3. Our results indicated that the TOMM40 rs2075650 G allele was a significant risk factor for lifetime depression (p = 0.00006) and, in depressed subjects, was a significant predictor of low extraversion (p = 0.009). Currently depressed risk allele carriers showed subtle executive dysfunction (p = 0.004) and decreased positive memory bias (p = 0.021) together with reduced activity in the posterior (p(FWE) = 0.045) and anterior (p(FWE) = 0.041) cingulate during sad face emotion processing. Our results suggest that TOMM40 rs2075650 may be a risk factor for the development of depression characterized by reduced extraversion, impaired executive function, and decreased positive emotional recall, and reduced top-down cortical control during sad emotion processing.

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